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the new tour of the historic park of Miradolo Castle (San Secondo di Pinerolo
after a long process of research and restoration
now rediscovers the original landscape identity desired in 1824 by Marquise Maria Elisabetta Ferrero della Marmora and entrusted to the vision of the famous Prussian landscape architect Xavier Kurten (Brühl
Exactly two hundred years after the commission
the park is presented to the public completely renovated
the result of a meticulous restoration that restored centrality to the compositional and plant elements conceived in the early 19th century.The appointment includes a special guided tour led by the property
during which it will be possible to explore the main interventions carried out in recent years
The tour will offer a close look at the transformation from a formal Italian-style garden to a romantic English-style park
a transition that reflects the cultural changes of the period and the establishment of a new relationship between man and landscape
The work carried out made it possible to recover not only the original structure
but also the deep connection between the park and its historical memory
The recovery project has placed sustainability and accessibility at the center
developed in collaboration with the Institute of the Deaf in Turin
offer both botanical and historical insights
enriching the visit with content accessible to all
it will be possible to participate in the Herbs on a Plate experience: a convivial moment that combines tasting and nature
with a glass of bubbly and a themed tasting
The long process of the park’s rebirth was also possible thanks to a rigorous archival research conducted in 2023 and 2024 by the Parks and Gardens Group of DISAFA - Department of Agricultural
Forestry and Food Sciences of the University of Turin
under the guidance of Professor Marco Devecchi
looked in particular at the historical plant component
the neo-Gothic greenhouse and the surrounding territorial context
Federica Larcher and Enrico Pomatto allowed for the clear identification of historical permanences
landscape design evolutions and the original physiognomy of the park through descriptive sources
iconographic documents and plans preserved in Piedmontese archives
significant funds were spent on the creation of the New Miradolo Garden
Many of the tree species planted during that period are still visible today and form the vegetal framework of the park
are officially recognized by the Piedmont Region: the Ginkgo biloba that greets visitors at the entrance to the castle
The recent history of the park is linked to the arrival of the Cosso Foundation
which crossed the threshold of Miradolo Castle for the first time in 2007 after a long period of deterioration
once the residence of the Bricherasio family
had suffered decades of neglect and renovations that did not respect its original identity
and the park design reduced to a shadow of Kurten’s nineteenth-century vision
through more than fifteen years of self-funded construction sites and enhancement projects
the Foundation has led a patient process of recovery and restoration
A new impetus came in 2022 thanks to two PNRR - NextGenerationEU calls for proposals
which awarded the project The Miradolo Castle Park
ranking it first in Piedmont and eighth nationally
The funds enabled the consolidation of services for the public
restoration of secondary architecture and extraordinary maintenance of historic trees
Particularly relevant was the involvement of architect Paolo Pejrone
one of Italy’s most influential landscape architects
who redesigned the courtly courtyard and the Garden area
enriching the botanical collection with new essences
and recovering historical elements such as the ancient potteries
The park’s lighting was also rethought in harmony with its romantic soul
were designed to offer different lighting scenarios according to the seasons
creating atmospheres that are intimate and respectful of nocturnal wildlife
The carefully metered light accompanies the evening visit without encroaching on the space
allowing the details of the landscape to be captured even as the sun sets
bike friendly area and restoration of the old barn
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A SERIAL killer known as the "The Dusseldorf Vampire" mercilessly slaughtered nine victims and tried to drink their blood
Peter Kurten began his killing spree at the age of nine after a disturbing childhood that saw him mutilate animals for sexual pleasure
or bludgeoning them with a hammer to achieve a heightened sexual state
He would then drink blood from their wounds sparking fear and panic among locals that a real-life vampire was on the loose
The killer took pleasure in his depraved acts - visiting their graves to carry out sex acts
Even talking to police at the scene of the crime wasn’t a step too far for Kurten
had attempted to murder seven more and had a total of nearly 100 crimes when he was eventually caught in 1930
After realising German cops were closing in and that a reward had been issued, he told his oblivious wife to turn him in and claim the money.
He expressed no remorse for his killing spree - instead blaming his abusive childhood and his time in prison for other petty crimes.
Speaking in court, Kurten said: “I had to kill. I did not kill either people I hated, or people I loved. I killed whoever crossed my path at the moment my urge for murder took hold of me."
it took the jury just 90 minutes to reach a guilty verdict and he was handed nine death sentences and ordered to be executed by guillotine
the sound of my own blood gushing from the stump of my neck
“That would be the pleasure to end all pleasures.”
Kurten’s head was dissected and taken away for forensic analysis
But scientists found no abnormalities in his brain - and it’s now on display in the Ripley’s Believe it or Not Museum in Wisconsin
The Dusseldorf Monster was born into a poverty-stricken family with an abusive and alcoholic father who often carried out horrendous beatings on his children
He would order his wife to strip naked and have sex with him while forcing the 13 siblings to watch
He was later jailed for raping his eldest daughter
his mother was able to escape and move the family to Dusseldorf where she later remarried
Having been exposed to violence at a young age
Kurten resorted to bestiality and torturing and killing animals after working with a local dog warden
He later claimed to have killed his first victim at the age of nine after pushing a young boy who couldn’t swim off a raft and holding another boy under the water
He was never convicted for the deaths and they were ruled accidents by authorities
After running away from home at age 16 and living a life of crime in and out of prison
Kurten murdered his first victim as an adult in May 1913
he came across nine-year-old Christine Klein as she slept
slashing her throat and allegedly engaging in sex acts as she lay dying
He returned to the scene of the crime the next day to drink in the tavern - and told cops he took great pleasure in hearing people’s horror reaction to the murder
He then attempted to murder 17-year-old Gertrud Franken by strangling her before fleeing the scene
Kurten was unable to carry on his crime streak after being drafted into the German army in 1914 before he was arrested for desertion and sent back to prison
a candy shop owner and sex worker who herself had been jailed for murdering her ex-fiance - but she had no idea of her new husband’s hidden desires
But it was in 1929 that his killing spree reached a high
as he carried out sick sex acts and drank blood from the wounds
Apollonia Kuhn was stabbed 24 times with a pair of scissors but survived
was stabbed to death with scissors before her body was molested and five days later he killed 45-year-old mechanic Rudolf Scheer
strangled and then stabbed Maria Hahn and told cops he had contemplated nailing her corpse to a tree to shock the public before burying the body
he killed foster sisters Luise Lenzen and Gertrude Hamacher
as they walked home from a fairground strangling
He then switched his murder weapon and used a hammer to kill Elizabeth Dorrier
raping her and leaving her to die days later in hospital
five-year-old Gertrude Albermann whom he stabbed 34 times after luring her into an allotment
The bloodthirsty manic was eventually caught after a victim who survived wrote a letter to a friend about the horrific attack - however
It was passed on to the police who were closing in on Kurten and the sick murderer encouraged his wife to hand him in and pocket the reward money
he confessed to 79 crimes including nine killings
claiming they had been revenge attacks for the horrors inflicted on him in prison and throughout his childhood
He pleaded not guilty by reason of insanity to each charge and he was surrounded by an iron cage to stop the families of his victims from attacking him
After the jury found him guilty of all nine murders he was sentenced to death by guillotine at Klingelputz Prison in Cologne before his head was taken away to be studied
It was later mummified and after the Second World War it was transported and displayed at Ripley’s Believe It or Not Museum
Our journalists strive for accuracy but on occasion we make mistakes. For further details of our complaints policy and to make a complaint please click this link: thesun.co.uk/editorial-complaints/
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Texas — The day after a fire engulfed two buildings at Feather Crest Farms in Kurten
officials confirmed the fire has been fully contained
I was showing you the plant behind me as it was completely engulfed in flames
as you can see it's a much quieter scene – I've confirmed with fire officials the fire is 100% contained and crews are periodically monitoring the site to make sure nothing rekindles
Quiet – that's how many residents describe the city of Kurten
“We kind of like it like that," Kurten resident Clay Greenwelge said
evacuate the building," emergency radios ordered
“Can you confirm that the fire started in the new construction building?" I asked
“It did appear that way," Fire Chief Matthew Drennan said
Fire Chief Drennan said they can't confirm the cause or the location yet – but it does seem that the fire started in the new construction building
I spoke with some workers who were working at the plant yesterday – one of them was a construction worker in that new building
but he did show me these videos of the fire Monday night – and said everything they've built so far – burned to the ground
Other plant workers I spoke with say they returned to work today
Returning somewhere between the quiet of Kurten and the noise of Monday night
I also spoke with the farm CEO – Sam Krouse – he tells me one of the buildings that burned down did have chickens in it at the time and they were all lost
Fire officials at the scene of Feather Crest Farms say the fire is contained to two buildings as of 8:22 p.m
Fire containment is expected to last multiple days
There have been no injuries or deaths reported
Workers were confirmed to be on site at the start of the fire
The cause of the fire hasn't been determined
Officials urge the public to steer clear of the area
Traffic buildup along State Highway 21 earlier in the day slowed firefighters' response to the incident
25 News will provide more information as it becomes available
Multiple fire agencies are responding to a large fire at a Brazos County chicken farm
Authorities have released little information on what caused the blaze at Feathercrest Farms in Kurten or if there are any injuries
25 News is in route to the fire and will have updates to this story as they become available
Metrics details
Head and neck squamous cell carcinoma (HNSCC) is characterized by complex relations between stromal
and immune cells within the tumor microenvironment (TME)
To enable the development of more efficacious therapies
and cell-cell interactions of non-immune and immune cell populations in 6 human papillomavirus (HPV)+ and 12 HPV– HNSCC patient tumor and matched peripheral blood specimens using single-cell RNA sequencing
we show cell type-specific signatures associated with inflammation and HPV status
describe the negative prognostic value of fibroblasts with elastic differentiation specifically in the HPV+ TME
predict therapeutically targetable checkpoint receptor-ligand interactions
and show that tumor-associated macrophages are dominant contributors of PD-L1 and other immune checkpoint ligands in the TME
We present a comprehensive single-cell view of cell-intrinsic mechanisms and cell-cell communication shaping the HNSCC microenvironment
These dynamics warrant a more holistic interrogation of the complex cancer–immune–stroma interaction in the tumor microenvironment (TME)
we aim to overcome these limitations and concomitantly interrogate the HNSCC TME of both HPV+ and carcinogen-induced (HPV–) etiologies
HPV encoded gene heterogeneity within tumor cells provides insights into differential pathways and microenvironmental impact
A Fresh tumor and blood samples from HNSCC patients (n = 18 patients) were collected
Patient image was created using BioRender.com B UMAP dimensionality reduction of the total cohort of 134,606 cells was performed
based on visualization of relevant characteristics: patient contribution (HN01–HN18)
C UMAP plot showing identified cell types [B cells
D Inflammation scores were determined by quantifying the total leukocyte infiltrate in each tumor based on H&E staining (n = 17 patients)
Tertiles were used to segregate patients into three groups based on their inflammation score: low (n = 6 patients)
Patients with HPV+ and HPV– etiologies are indicated
Center lines represent median values for each cohort
Inflammation scores were evaluated using a one-way ANOVA test
E UMAP plot showing cell contributions based on inflammation scores
A Sub-clustering of 27,013 CD8+ T cells (n = 18 patients; cluster 0–13) and visualization of relevant characteristics: patient contribution (HN01–HN18)
as well as all cells from HN03 were excluded) and CD8+ T cell sub-states (cycling
B Hallmark gene sets enriched (using the Computer Overlaps tool from MSigDB) in the top 100 DEGs between CD8+ T cells from high vs
p-values for enrichment were extrapolated from hypergeometric distribution
Examples of genes that were shared by the apoptosis or the hypoxia gene set were GADD45B (encodes Growth arrest and DNA-damage-inducible
BTG2 (encodes BTG anti-proliferation factor 2)
These genes were also enriched in the TNF-signaling pathway
This suggests a qualitative difference of CD8+ T cells depending on the inflammation status of the TME
with cells from tumors with high inflammation scores being more activated and effector-like
while cells from tumors with low inflammation score are stressed by the surrounding TME and may become (pre)-apoptotic
A Sub-clustering of 14,920 epithelial cells (n = 15 patients; cluster 0–16) and visualization of relevant characteristics: patient contribution (HN01
B Hallmark gene sets enriched (using the Computer Overlaps tool from MSigDB) in epithelial cells derived from tumors with low vs
C UMAP visualization of transcripts of HPV16 genes (E1
D HPV+ patient-specific intensity and prevalence of HPV16 gene expression
Color bar indicates normalized gene expression
We confirmed that only a subset of malignant cells expresses E6/E7
we observed a stratified arrangement of E6/E7 expression
with these oncogenes being most expressed by cells of the basal epithelial layer and decreasing towards the cystic lumen
A Sub-clustering of 12,179 stromal cells (non-immune
non-epithelial cells; n = 15 patients; cluster 0–10) and visualization of relevant characteristics: patient contribution (HN01
B Heatmap showing top 10 genes characterizing each cluster (color scale depicts scaled gene expression)
C Sub-clustering of pericytes (cluster 0–4) and visualization of relevant characteristics: patient contribution (HN01–HN18)
A Sub-clustering of 4034 fibroblasts (n = 15 patients; cluster 0–7) and visualization of relevant sample characteristics: patient contribution (HN01
and sub-states (cancer-associated fibroblasts
and fibroblasts with elastic differentiation)
B Heatmap showing top 25 genes characterizing each cluster (color scale depicts scaled gene expression)
C Enriched hallmark gene sets between clusters based on results of gene set enrichment analysis (“singleseqgset” package)
D Overall survival analysis of HPV+ patients from the TCGA HNSCC bulk RNAseq cohort based on gene signature scores of fibroblasts with elastic differentiation and cancer-associated fibroblasts (log rank test p = 0.0013)
where 199/500 patient samples were predicted to have non-zero fractions of fibroblasts with elastic differentiation
A Sub-clustering of 7431 endothelial cells (n = 15 patients; cluster 0–7) and visualization of relevant sample characteristics: patient contribution (HN01
high) and types of endothelial cells (lymphatic and vascular)
Enriched hallmark gene sets between C lymphatic and D vascular endothelial cell clusters based on results of gene set enrichment analysis (“singleseqgset” package) are shown
A Average expression of immune checkpoint receptors and corresponding ligands on all cell types identified in tumors with low
and high inflammation scores is summarized (n = 17 patients)
CellPhoneDB package was used to predict patient-specific ICR–ICL interactions between CD8+ T cells and B CD45− endothelial cells (Endo)
and monocytes) in tumors with low and high inflammation scores
The colored scale represents the log2 mean expression of receptor–ligand pairs
CD274–PDCD1 interactions appeared to be primarily mediated by macrophages and were observed in 8/12 patients regardless of their inflammation status
this interaction was predicted between CD8+ T cells and epithelial cells
HAVCR2–LGALS9 interactions were predicted to be primarily mediated by macrophages (10/12 patients) and endothelial cells (9/10 patients)
TIGIT–NECTIN2 interactions were most common and were projected to be facilitated by non-immune cells
Three or more high-resolution images of regions of interest (ROIs) that contained a balance of tumoral (tumor bed) and peritumoral/stromal regions were acquired from each tumor section
ROIs were selected based on H&E staining in addition to mIF whole slide scans
B A representative ROI selected from patient HN12 is shown
Tumor bed is depicted by the cyan-colored border line in the composite image
C Intensity of PD-L1 expression on CD68+PD-L1+ macrophages and pan-CK+ PD-L1+ tumor cells pooled from all patient-associated ROIs is shown (n = 5 patients)
Datapoints represent 41 individual ROIs colored by patient id
D Patient-specific pooled PD-L1 expression levels are shown
43,517 cells from the 41 ROIs in C were included in the analysis
E Measured distance to CD3+CD8+CD68− T cells from CD68+PD-L1+ macrophages or pan-CK+PD-L1+ tumor cells pooled from all patient-associated ROIs is shown
Dashed lines represent the 35 μm distance used as the cutoff to measure cell-to-cell interactions between evaluated cell types
This distance represents 1–2 cell diameter distance between macrophages (20–30 μm in diameter) and lymphocytes (5–7 μm in diameter)
Calculated median distances across all patients and between evaluated cell types are shown
box limits represent upper and lower quartiles and whiskers represent 1.5× interquartile range
Linear mixed-effects models were used in C and D
with cell group as a fixed effect and individual patient as a random effect
BH-FDR method was used for multiple comparison adjustment
confirming our flow cytometric observations
Close associations between PD-L1+ tumor cells and various T cell subsets within the tumor are due to the ubiquitous presence of tumor cells while macrophages are more heterogeneously distributed within the TME
Such studies demonstrate how other potentially relevant receptor:ligand pairs can be identified to guide targeted therapeutic approaches using scRNAseq datasets
In order to develop more successful therapies
it is necessary to decipher these complex intercellular interactions
Novel technologies such as scRNAseq allow for a multi-dimensional analysis of tumor heterogeneity
Our goal was to generate the most comprehensive scRNAseq data set and profiling of immune and non-immune cells in the TME of HPV+ and HPV– HNSCC to date
Our study leverages the breadth and depth of a large data set for a detailed analysis that permits identification and sub-clustering of major cell subsets of the TME
inflammation- and etiology-specific gene signatures and prediction of putative cell–cell interactions
for future translational applications and subsequent correlation with on-treatment specimen analyses
which we were able to confirm transcriptionally here
Our observation that fibroblasts with elastic type differentiation have a negative prognostic value specifically for HPV+ patients stresses the importance of seeing HPV+ and HPV– disease as two different diseases that require tailored
specific biomarkers and treatment approaches
LAG3-targeting therapies may be better suited for the treatment of patients with inflamed lesions
The research presented here complies with all relevant local
informed written consent was obtained prior to donation
The University of Pittsburgh Cancer Institute Review Board (Protocol 99-069) approved the study
All transcriptomic analyses of non-immune cell types and their interactions with immune cells
as well as PBL and TIL from HN16-18 are also unpublished
A red blood lysis step was performed on both tumor single-cell suspensions and PBMCs using the 1× solution of RBC lysis buffer (ThermoFisher Scientific; Waltham
viability staining was performed using eBioscience Fixable Viability Dye eFluor 780 (ThermoFisher Scientific) per manufacturer’s protocol
This was followed by a wash and staining with anti-CD45 PE (BioLegend; San Diego
CA) for 30 min in sorting buffer (0.1% BSA in PBS) at 4 °C
viable CD45+ and CD45− cells were sorted using the Beckman Coulter MoFlo Astrios
the cells were washed twice and re-suspended in a sorting buffer
A cell number and viability count were performed on a Cellometer Auto 2000 using the ViaStain™ AOPI Staining Solution (Nexcelom Bioscience LLC
Ready-to sequence Illumina single-cell cDNA libraries were generated using the Chromium Single Cell 3′ Reagent Kit (v2 Chemistry; 10× Genomics; Pleasanton
Single Cell Chip was loaded to retrieve 2000 PBMCs and 4000 cells for CD45+ and CD45– tumor-derived cells
Sequencing libraries (2 nM) were pooled as PBMC and TIL from the same patient and CD45– cells from two different patients
The resulting pooled libraries were diluted to 2 pM
NextSeq 500/550 High Output v2 kits (150 cycles) was used with the following parameters: Read 1: 26 cycles; i7 Index 8 cycles; Read 2: 98 cycles
as specified by the 10× Genomics guidelines
The CellRanger (v.3.0.0; 10× Genomics) pipeline provided was used to process the data. Initially, samples in each pool were demultiplexed using the sample index, and FASTQ files were created for each sample. From these FASTQ files, a counts matrix was generated for each sample by mapping the FASTQ files to a hybrid reference made of the human GrCh38 and the HPV16 genome (https://www.ncbi.nlm.nih.gov/nuccore/NC_001526.4)
The counts matrix comprises gene expression by barcode for each cell present in the sample
all these count matrices were aggregated into a single gene-barcode matrix
cells with less than 200 genes expressed were filtered out
and more than ten percent mitochondrial genes were also removed to ensure only the high quality of cells used in the downstream analyses
Genes expressed in less than 3 cells were also filtered out of the analysis
First, a neighborhood graph was constructed to identify related groups of cells. Next, Leiden clustering was performed on the neighborhood graph. The cluster assignments were then visualized on UMAP plots. Using a combination of top expressed genes in each cluster and a list of known marker genes (Supplementary Fig. 1A)
InferCNV (v.1.2.1) was used to distinguish between the malignant and normal epithelial cells
Cells derived from the PBL were annotated as “Normal” to establish the baseline signal for gene expression
The epithelial cells were annotated as being “Tumor” and each cluster was annotated separately
Patterns between the baseline signal seen in the PBL cells were compared to epithelial cell clusters to determine if the cells in each cluster were malignant or normal epithelial cells
Due to file size limitations on the CIBERSORTx web server
5000 annotated cells were randomly sampled from the TME
Expression profiles of these cells were used to create the single-cell reference matrix
The “Impute Cell Fractions” module was used to infer proportions of all the cell types identified by our scRNA-Seq in HNSCC TCGA samples
A gene signature was created using the top 100 DEGs based on the score generated by the rank_genes_groups() function in Scanpy from fibroblasts with elastic differentiation as well as CAF
A GSVA score was computer per sample using TCGA HNSCC RNAseq data
All normal samples from the TCGA cohort were excluded from the analysis
the samples were divided into 2 groups: High (above the median) or Low (below the median)
Kaplan-Meier plots were generated to compare the overall survival in groups of interest using the survfit() function from the “survival” R package (v.3.2-11)
To segregate inflamed tumors, H&E staining was utilized as a simple, unbiased, and comprehensive measure of the lymphocyte content of each tumor (Supplementary Fig. 1C)
Immune/inflammatory cells per 10 high-power fields were quantified by a trained pathologist unbiased to clinical-pathological information and values averaged
The sum of the average counts in the tumor edge
tumor and stroma was calculated as all-component total immune cell score
Samples above the median inflammation score were categorized as inflamed and samples below the inflammation score were non-inflamed
One patient’s slides (HN03) had no viable tumor cells (only necrosis and stroma) after its use for fresh digestion and scRNAseq
so it was excluded from analysis of inflammation status
all UMAP plots showing inflammation scores do not include PBL cells and all cells from HN03
Three clinical cases of metastatic squamous cell carcinomas with unknown primary tested were reviewed with Advanced Cell Diagnostics (RNAscope® HPV-HR
All slides were handled based on the manufacturer’s guidelines
Images were acquired using an Olympus BX45 (Olympus K.K.
qPCR analysis was performed using the SsoAd-vanced Universal SYBR Green Supermix Kit (Bio-Rad
The relative expression levels of target genes were normalized to the expression level of HPV16 E6 or E7
which yielded 2–ΔΔCt cycle threshold (Ct) values
The primers used for gene expression were as follows: 5′-CAGGAGCGACCCAGAAAGTT-3′ (forward) and 5′-GCAGTAACTGTTGCTTGCAGT-3′ (reverse) for HPV16 E6; 5′-CCGGACAGAGCCCATTACAA-3′ (forward) and 5′-GCTTTGTACGCACAACCGAA-3′ (reverse) for HPV16 E7; 5′-GGTGTTGAGGTAGGTCGTGG-3′ (forward) and 5′-CACACCTGCATTTGCTGCAT-3′ (reverse) for HPV16 L1; 5′-GAATTGGAACAGGGTCGGGT-3′ (forward) and 5′-AAGGGCCCACAGGATCTACT-3′ (reverse) for HPV16 L2
5uM thick formalin-fixed paraffin-embedded (FFPE) tissue sections for selected patient tumor samples were mounted on slides
Sections were deparaffinized at 60 °C for 30 min
and rehydrated using a standard histology protocol
Antigen retrieval was performed using an EDTA buffer (Cell Signaling
MA) in Decloaking chamber at 120 °C for 2 min
The slides were stained using an Autostainer Plus (Agilent Dako) platform with TBST rinse buffer (Cell Signaling)
The IHC slides were treated with 3% hydrogen peroxide for 5 min
MFAP4 (Rabbit Polyclonal IgG; cat.# NBP2-30439
The slides were then incubated in Denature solution (Biocare Medical)
The slides were then counterstained with Hematoxylin (Agilent Dako)
Single-cell tumor suspensions were stained with Zombie NIR (Biolegend) labeling per the manufacturer’s protocol. Samples were washed with FACS buffer (0.2% BSA, 0.02% NaN3, PBS) and labeled for 20 min at 4 °C using the anti-human antibodies detailed in Supplementary Table 3
Data were acquired using LSR Fortessa cytometer (BD Biosciences) and analyzed using FlowJo version 10.6.1 software
Imaging was performed at ×20 on the Vectra Polaris 3.0
pan-CK+PD-L1+) as the fixed effect and individual patient as the random effect
Contrasts of cell subsets were performed using t-tests with the Benjamini–Hochberg FDR adjustment for multiple comparisons
Marker intensities were log-transformed before statistical testing
All tests are two-sided unless otherwise noted
Further information on research design is available in the Nature Research Reporting Summary linked to this article
Intratumor heterogeneity reflects clinical disease course
a novel measure of intratumor genetic heterogeneity
is high in poor-outcome classes of head and neck squamous cell carcinoma
Nivolumab for recurrent squamous-cell carcinoma of the head and neck
Nivolumab vs investigator’s choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long-term survival update of CheckMate 141 with analyses by tumor PD-L1 expression
and acquired resistance to cancer immunotherapy
Single-cell RNA sequencing in cancer: lessons learned and emerging challenges
Immune landscape of viral- and carcinogen-driven head and neck cancer
Single-cell transcriptomic analysis of primary and metastatic tumor ecosystems in head and neck cancer
Phenotype molding of stromal cells in the lung tumor microenvironment
Longitudinal single-cell RNA sequencing of patient-derived primary cells reveals drug-induced infidelity in stem cell hierarchy
Massively parallel digital transcriptional profiling of single cells
Single-cell genomic approaches for developing the next generation of immunotherapies
Dimensionality reduction for visualizing single-cell data using UMAP
Uniform manifold approximation and projection for dimension reduction
SCANPY: large-scale single-cell gene expression data analysis
From Louvain to Leiden: guaranteeing well-connected communities
PD-1 status in CD8(+) T cells associates with survival and anti-PD-1 therapeutic outcomes in head and neck cancer
CD8+ T cell states in human cancer: insights from single-cell analysis
Utility of CD8 score by automated quantitative image analysis in head and neck squamous cell carcinoma
TILs in head and neck cancer: ready for clinical implementation and why (not)
Human papillomavirus and survival of patients with oropharyngeal cancer
Association of estrogen receptor alpha expression with survival in oropharyngeal cancer following chemoradiation therapy
Detection of human papillomavirus-16 in fine-needle aspirates to determine tumor origin in patients with metastatic squamous cell carcinoma of the head and neck
Microenvironmental regulation of tumour angiogenesis
Determining cell type abundance and expression from bulk tissues with digital cytometry
The biology and function of fibroblasts in cancer
Characterization of microfibrillar-associated protein 4 (MFAP4) as a tropoelastin- and fibrillin-binding protein involved in elastic fiber formation
Host tissue determinants of tumour immunity
Differential DARC/ACKR1 expression distinguishes venular from non-venular endothelial cells in murine tissues
TIM-3 as a target for cancer immunotherapy and mechanisms of action
Fibrinogen-like protein 1 is a major immune inhibitory ligand of LAG-3
The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells
TIGIT and CD96: new checkpoint receptor targets for cancer immunotherapy
Targeted deletion of PD-1 in myeloid cells induces antitumor immunity
Single-cell reconstruction of the early maternal–fetal interface in humans
A phase Ia/Ib study of an anti-TIM-3 antibody (LY3321367) monotherapy or in combination with an anti-PD-L1 antibody (LY3300054): interim safety
and pharmacokinetic findings in advanced cancers
Clinical blockade of PD1 and LAG3 — potential mechanisms of action
Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing
Dysfunctional CD8 T cells form a proliferative
dynamically regulated compartment within human melanoma
Defining T cell states associated with response to checkpoint immunotherapy in melanoma
Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis
CXCL13-producing TFH cells link immune suppression and adaptive memory in human breast cancer
Characterisation and prognostic value of tertiary lymphoid structures in oral squamous cell carcinoma
The immune contexture in cancer prognosis and treatment
altered and cold tumours with combination immunotherapies
Human papillomavirus and rising oropharyngeal cancer incidence in the United States
The biology and life-cycle of human papillomaviruses
a novel HPV16 E7-pHLA-IL-2-Fc fusion protein
enhances tumor antigen specific T cell activation for the treatment of HPV16-driven malignancies
T-cell receptor gene therapy for human papillomavirus-associated epithelial cancers: a first-in-human
The role of retinoid deficiency and estrogens as cofactors in cervical cancer
Stromal fibers in oral squamous cell carcinoma: a possible new prognostic indicator
PD-1 expression in head and neck squamous cell carcinomas derives primarily from functionally anergic CD4+ TILs in the presence of PD-L1+ TAMs
or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised
Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients
The role of the PD-L1:PD-1 pathway in squamous cell carcinoma of the head and neck
Endogenous Galectin-9 suppresses apoptosis in human rheumatoid arthritis synovial fibroblasts
The prognostic role of PD-L1 expression for survival in head and neck squamous cell carcinoma: a systematic review and meta-analysis
Galectin-1–driven T cell exclusion in the tumor endothelium promotes immunotherapy resistance
TIM-3 and VISTA expression on tumor-infiltrating lymphocytes in oropharyngeal squamous cell carcinoma-potential biomarkers for targeted therapy concepts
Phase Ib study of immune biomarker modulation with neoadjuvant cetuximab and TLR8 stimulation in head and neck cancer to overcome suppressive myeloid signals
A mycoplasma peptide elicits heteroclitic CD4+ T cell responses against tumor antigen MAGE-A6
Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles
Kaposi sarcoma–associated herpesvirus miRNAs suppress CASTOR1-mediated mTORC1 inhibition to promote tumorigenesis
QuPath: open source software for digital pathology image analysis
Fitting linear mixed-effects models using lme4
Download references
This research was supported in part by the University of Pittsburgh Center for Research Computing through the resources provided
This research utilized the Hillman Cancer Center Flow Cytometry Core Facility
supported in part by award P30 CA047904 (RLF)
Mosites Initiative for Personalized Head and Neck Cancer Therapy
was supported by the CITP T32 CA082084 and a Hillman Postdoctoral Fellowship for Innovative Cancer Research
was supported by the Programm zur internen Forschungsförderung Essen (IFORES) and the UMEA Junior Clinician Scientist Stipendium
These authors contributed equally: Cornelius H
Graduate Program of Microbiology and Immunology
University of Pittsburgh School of Medicine
Division of Rheumatology and Clinical Immunology
Department of Microbiology and Molecular Genetics
analyzed and interpreted data and wrote the manuscript
provided expertise in experimental design and data analysis
performed multicolor immunofluorescence staining
performed the H&E and IHC slide review and inflammation scoring
analyzed the multispectral immunofluorescence images
performed RNA isolation and RT-PCR for HPV genes; X.C.
provided input on data analysis and computational approaches
identified patients and collected specimens
performed the library preparation for scRNA-seq
provided input for scRNA-seq library preparation and data interpretation
All authors reviewed and contributed to the manuscript
Inc.; Numab Therapeutics AG; Pfizer; Sanofi Tesaro; Zymeworks
Inc (honoraria); Astra-Zeneca/MedImmune (clinical trial
research funding); Bristol-Myers Squibb (honoraria
Novasenta; Patents licensed and Royalties: Astellas
The remaining authors declare no competing interests
Nature Communications thanks Nidal Muhanna and the other
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“It is not about me and my sporting career anymore; now it is about my students and their horses – and my position is to use all my knowledge
experience and passion to help others in the sport,” Ireland’s Jessica Kürten tells World of Showjumping.
“Working with horses is something where you need to gain experience and you never stop learning,” Jessica says
understanding and feeling – why do they react in this way
what am I doing right and what can I do better
There is no written law as to how to communicate with horses – and I think there are more and more people who are hungry for knowledge.”
a European team champion, as well as a winner of the 2008 Global Champions Tour Final and one of only two female riders to ever have won the IJRC Top 10 Final – back in 2007 – was for years a mainstay on the Irish team
Kürten has transitioned from an active international competitor to a sought-after trainer – and, in an attempt to share her knowledge, she has taken on other unexpected roles too
such as being a much-loved commentator on FEI TV
as well as more recently being appointed Chair of the FEI Athletes’ Committee.
“If I could communicate only one word to the equestrian community
but it can pay off in the long run,” Jessica says
You could say that Jessica was born to it; her mother went hunting when she was eight months pregnant
so Jessica was jumping before she was even born
“My first memories are with a donkey,” Jessica recalls
“My parents Rosemary and George had a lovely old donkey and what I did was take him from the stable to the garden
and I would get on the donkey from the bucket and then the donkey would walk back to the stable – and apparently
we had a large pony club community – which I think is a great thing for kids
The decision to take riding seriously was one that Jessica made when she was twelve – and she still remembers the conversation
my father asked if we wanted to take riding seriously
My brother Marcus was then too old to his 1.38m ponies
and I was to take them on and dad thought we should sell my show pony – but mum and I had another plan
We kept all three and for those two years that I was in that age group
I had so much fun with these ponies.”
One of the most memorable moments Jessica has from early on in her career
is not one of winning but rather falling off
I had two horses; one racehorse and one big footed Irish horse that my dad had bought,” Jessica recalls
“I had been teaching this big horse to turn very sharp
because I got the chance to ride at two international shows
was with top riders – it was an important event for me and I had been training a lot
I remember riding to number one and unfortunately over that fence
my horse turned quicker than me and I fell off
because all the top riders were watching at the entrance of the arena
I was extremely embarrassed and by the time I got up and got out of the ring
I don’t need to keep him,’ my dad told me and the horse went on to Italy
but in a very positive way; the rider has to be as good as the horse
and he had a very strong principle of having respect for your horse
which I am so lucky to have learned early on.”
“My list of other memorable moments is long and mixed
and there are many reasons as to why particular achievements were important,” Jessica continues
stands out – and it was with my wonderful Diamond Exchange
My father had sold my horses when I was doing my A-levels because he wanted me to concentrate on school – he thought it was a good idea
He told me that if I got accepted to a university
my father already had a horse in mind; we went and tried this huge horse that was completely out of control
but the feeling on him was amazing,” Jessica tells of Diamond Exchange – the horse that put her on the international showjumping map
“I took him from a five-year-old up to top level
and I won my first World Cup in Millstreet with him
It was just amazing; we were staying in the truck with my parents
To have a World Cup at Millstreet in Ireland was a huge thing
and at that stage we had only watched it on TV
and back then there was a Volvo-car for the winner
for my parents and such a big moment for Ireland
I can remember everything to this day; every detail about the whole competition.”
Jessica was lucky to have amazing horses as her partners
and both she and her husband Eckard created very emotional connections to them
the bond grows closer the more you do together,” Jessica tells
“It is when you go through these big ups and downs
all my horses taught me lessons; they all seemed to demand an individual way of reaching them
All my horses told me how they wanted to have it
and I was continuously adapting to each horse to find the key to be successful in sport – that was my goal
We spent the time to produce and improve our horses
we were always working to make them better
That was always our goal in the stable; not to just take a horse at face value
but to find a way to work with them to make them better.”
All my horses taught me lessons; they all seemed to demand an individual way of reaching them
“There were so many things that each horse taught me
and I felt a strong connection to most of them,” Jessica tells
Arezzo was one of the last horses I rode and giving him back was a really difficult day for me
there were many tears… It is a joy for me now
as we have bred from some of the stallions I rode
to work with their offspring and I laugh when I see their father’s traits in them
Such wonderful horses I was lucky to have under my saddle and many of them went way beyond expectations
Libertina is one that everyone probably remembers
and she was me – basically the two of us were one
We have unbelievably similar personalities; we are both ambitious
I am a person who always likes to think forward
the memories from my career are really beautiful – and all because of our horses.”
that feeling – it is really difficult to put into words
“I think sometimes a horse and rider meet each other and they absolutely bond from the first second they meet,” Jessica continues
“Like with people; sometimes you meet someone
and there is a bond there – you just start talking and there is an understanding
it takes time to understand why a horse is reacting the way it is but when you do figure it out
I love being with the horses on the ground
but my biggest connection comes from sitting on the back of a horse
I think it is one of the reasons you see people drawn to horses even from families that are not familiar with the sport: Sitting on a horse feels like entering another world
I was very shy when I was young – now I have learned not to be
but I used to say that as soon as I was on a horse
When you have a good relationship with a horse
you become a person you are not when you are on the ground – and that is so special
the feeling sitting on a horse that I have a bond with
The decision to stop riding in 2014 was a long process for the two-time Olympian and European team champion
“It started to be in our thoughts to move in a different direction,” Jessica explains
“My husband and I had been doing the sport very intensely on a high level for many years
having a lot of success and an awful lot of fun
I have to say we enjoyed every moment of it – the ups
everything – and it just started to be that we were getting a bit tired
it was a slow process and it took two years to really decide
I remember driving the truck back from the show in Paris and my husband was in the car in front of me
I rang him up and said: ‘this is the moment
I must say the decision was made with no idea of what I was going to do afterwards
the support from my husband was amazing: He told me that if it took a year for me to know what I wanted to do
that life will take its path – and that is exactly what happened.”
You have to be so egoistic with your time when you want to be at the very top
I wanted to give myself a five-year period – I was 45 when I stopped
because everything in this sport is a very slow process
It did not take two days for me to start training and at one stage I was training a lot; basically
I felt it needed to change; the concept had to be modified
Having less students and more time with their horses
is a concept I am very happy with right now
There are lots of facets in training and I like to think that when I work with my people
a lot of respect for the horses – that is the number one – and great planning
I really like to be involved with the grooms and the horse owners as well
to look for the best way to manage each horse.”
to have that freedom that it was no longer about me – it felt like a relief
but I was very egoistic about my sport,” Jessica explains about her transition from riding to training
“I was lucky to have a team around me – led by my husband who managed me – who followed my egoistic attitude
but at the same time we had one goal and it was for me to succeed with my horses in the sport – and when you have that mindset
You have to be so egoistic with your time when you want to be at the very top that there isn’t really much room for training others
the transition for me was easy – and even enjoyable; I was able to have a free mind and not think about myself anymore
We are very happy to have been brave enough to take this step.”
Jessica was appointed as the Chair of the FEI Athletes’ Committee
a committee which plays a vital role and provides a voice to the athletes’ community within the global FEI decision-making process
“This is all very new,” Jessica says about her role
“I was asked to take on this role at exactly the right moment
as I was in a phase in my life where it would work
The more that we can be there – close to the FEI – and bring the athletes’ voices to them
they have been keen to get information from me
to hear the athletes’ points of view and get feedback on whether they are on the right track or not
I feel like we have had a very open conversation
There are many important points that have come up and important things that need to be decided
and it is imperative for the athletes to have a voice within the executive board of the FEI.”
The majority of the riders are not getting involved
“The majority of the riders are not getting involved
for various reasons; they don’t want to rock the boat
and… this makes it even more important that some do think about the future of our sport
it is about the athletes’ voices within the FEI Executive Board and that means it is my job to communicate as much as possible to the FEI for the athletes
I am thankful when athletes have come to me and shared what they are dealing with; together we are stronger.”
“Complaining is a much-used word in our sport,” Jessica continues to speak about the riders’ involvement when it comes to politics
“I think people should really think twice before complaining; constructive discussion is always better
We have all been under pressure in this sport; under pressure to be successful
to make it all go around financially – we have all been there
you need to keep cool and look for the discussion rather than complain
Everyone has their reasons for doing things
I was really impressed with the latest FEI Sports Forum when we had the discussion between show organizers
sat down and I think that was the first step of trying to find solutions for various difficulties around costs
Complaining is a much-used word in our sport
“We should sometimes just take a breath and look back; the sport is now full of young people
and this is probably why others in my age group are all very keen to voice their opinions and experiences
We see the young people only looking at what is now
and forgetting the work already done to improve equestrian sports
such a wide community as ours can only work with rules and regulations
These rules and regulations over the last years have really helped the sport
and you can only know that if you look back and see how it was before.”
We should sometimes just take a breath and look back
but look at the improvements; the size of the stables
the facilities that need to be available for grooms – and I know we are still working on that
but it has already come far – and we keep improving
The riding hat; we used to ride without a helmet in the warm-up not so long ago
There are so many issues that have been dealt with
I am witnessing a very different situation as to what I thought it would be with the FEI; a very open
There are some smart people within the Executive Board – maybe not all from the equestrian world but in their own right
they are concerned about the good of our sport
I am pleased to be able to take part in these talks and see that there are people who really want our sport to move forward
there are people who are not on the field as I would be and that is where I need to then step in during the meetings; I need to share the viewpoint of the athletes and make sure where we come from is understood.”
one of the biggest challenges the sport is facing is combining business with actual sport
and then we have the riders who are in the sport for commercial reasons – not really to compete but to take home a video
They are looking to use competition as a window to sell their product
And then we have riders who want to win; win the 1.35
the 1.50m and the Olympics – riders who are absolutely passionate about the sport and put the sport first.”
our sport is very demanding financially – it has always been this way – but I think it is harder in this sense now than it has ever been,” Jessica says
riders have to sell horses to survive and that is why we do see top riders losing horses; you have to pay for your staff
pay your stable and put your kids to school – there are so many costs involved
I think this is our biggest challenge; having all this under one hat
should we consider splitting things slightly
I am not sure – and there are not many people who are interested to have this discussion
I search for those who are curious to talk about the direction our sport is taking and what we should be actively doing in our community to push it in the right way
to allow the industry while at the same time save the sport for those – to whom I belong – who are passionate sports people
I understand the industry – we all sell horses – but the other side of me is saying that we have to keep our sport a sport; stay passionate
admire and look up to those who are wanting to win
“We would not have welfare committees if it was all perfect,” Jessica moves on to speak about another challenge the sport is facing – the social license to operate
“I am a great believer that the boundaries should be set from us within and not from people from the outside
we have to take responsibility – everyone has to do it
we ALL have to do it: Take responsibility for your horse and make sure that your horse has it good
we should also communicate when we see things that maybe aren’t correct
Not every conversation is going to be an easy one
“We need to look within ourselves as to where we stand in our relationship with our sport partner
why do we do this sport with horses when we could all be doing something else
at some point we found our way to these incredible animals and we enjoy being with them – we enjoy grooming
if you only want to sit on a horse and have a lesson
then maybe you should take a look in the mirror and ask if this is really the right sport for you?”
If you only want to sit on a horse and have a lesson
then maybe you should take a look in the mirror and ask if this is really the right sport for you
not golf – instead of a bicycle or a racket
our partner in this sport is a living being,” Jessica says
the grooms are there for the horses and are doing a great job
but the riders have to be interested in their horses and be involved as well
There should be a play between the groom and the rider
and take their horse out to the paddock themselves
These things are part of the education young people in our sport should get
You won’t know how to do it right if no one tells you and teaches you
We have to go back to the very beginning and that is where these skills should be taught.”
“A lesson for us all is to not take ourselves too seriously,” Jessica continues
We should not take our life with horses for granted
and keep our togetherness with these amazing animals as the number one priority
As long as we keep our respect and love for the horse and the fact that the horse is a 50% partner with us as our foundation
we will be able to make the boundaries for our sport ourselves and they will not be pushed upon us from the outside
That is my message for everyone in the sport
horse dealer or top rider; we make the boundaries ourselves
we have to touch the imagination of the wider public as well and we need to keep ourselves exciting.”
Seeing beautiful horse-and-rider communication and a beautiful round in good rhythm is what Jessica herself enjoys the most
and myself I loved to ride a fast jump-off,” she says
“I am a passionate competitor and when I was in the ring
I wanted to win and I love seeing that mentality in other riders
A good Nations Cup – there isn’t anything much better
It is an amazing feeling to compete together as a team
you go into this world where you just wish that your colleagues are better than you
it takes a team that has melted together and become one – it’s a phenomenon which can often be seen as an example with the Dutch team
they have been one of the best teams in the world to show how they do it for each other: They always seem to be together
wanting the other one to be better; they are very good in coming together and making it work
This is essential in team competitions and what makes team competition so beautiful – and so important for our sport
And this team spirit is something I wish we had more of.”
We should keep our togetherness with these amazing animals as the number one priority
we have so many different top events in our sport that riders can aim for; there is enough room for everybody and we have to wake up to this,” Jessica says
“We shouldn’t be too aggressive against each other
embrace what we have and be happy that we have it
I believe everyone should pick their place and let others do the same
we need this strength of competition we have right now; we need these sponsorships to allow enough room for our horses and riders to compete at top level.”
that means we are not robots,” Jessica concludes
“If everyone closely involved in equestrian sport would just look in the mirror before going to bed
and think: ‘Am I doing the best for my horse
and is my position in the sport a passionate one?’ – take this thought to bed and sleep on it
The beauty of our sport is our connection with a horse
an ambition to win together – you can only win in this sport when a horse is your true partner
when you come from a place of extreme love of the horse.”
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Share on FacebookShare on X (formerly Twitter)Share on PinterestShare on LinkedInBobby Kurten has deep roots in the Brazos Valley and an absolute passion for agriculture
But if you don't know him personally you probably at least recognize his last name
"The city of Kurten is named for my family," Kurten said
My great granddaddy came over here from Germany in 1850."
And it was all those years ago that the Kurten family began it's legacy of agriculture in the Brazos Valley
Kurten now shares his passion with agriculture with the next generation
"I have gone to elementary schools and talked to them about the cattle business
They'll have a cowboy day in some of those classes," he said
"That's more swinging a rope and cracking a whip more than anything else."
Bobby says the future of agriculture is bright if we keep embracing the latest technology
"Here in the United States we have the most healthy
most abundant food supply of any place in the world
Texas — The CEO of Feather Crest Farms responded to 25 News with a statement in the wake of a large fire at the chicken farm Monday night
at least 100 firefighters were still on scene
For more on our coverage of the fire, click here.
Share on FacebookShare on X (formerly Twitter)Share on PinterestShare on LinkedInBRYAN
Texas (KBTX) - Multiple fire departments are still battling a large fire burning at a chicken farm in a rural part of Northeast Brazos County
at Feather Crest Farms near Fickey Road east of Kurten and officials Monday night said it could be days before it’s fully extinguished
“Monday evening a fire occurred at Feather Crest farm in Kurten
“The fire affected two chicken houses on site
and we are very sad to say one house had chickens in it at the time that have been lost
We are thankful for the swift actions of our entire team and that they are all safe
We also deeply appreciate the first responders who reached the farm quickly and helped to prevent any further damage.”
Feather Crest Farms in Kurten owned by MPS Eggs is one of six facilities the company owns nationwide
They are the sixth largest egg producer in the country
providing eggs for brands in major stores like Kroger
Footage shared by photographer James Nowak with KBTX shows that the fire at Feather Crest Farms is burning on the south end near Democrat Road. Still no word on what started it. 🔴DETAILS --> https://t.co/yVA74bzp08 pic.twitter.com/DSzeXXxrQm
Black plumes of smoke could be seen as far away as Limestone County as two buildings burned on the property but it’s unclear what exactly started it
There is no public threat or hazmat concerns linked to the blaze
authorities said in a news conference Monday evening
According to Brazos County Sheriff Wayne Dicky
Democrat Road is closed and all lanes of Highway 21 are back open
but authorities are urging people to stay away from the area and not stop on the side of the road to take photos
Ground footage shared by Jim Suydam with KBTX shows that the fire at Feather Crest Farms continues to burn into the night. Firefighters have come from other counties nearby to help out.🔴DETAILS --> https://t.co/yVA74bzWPG pic.twitter.com/BMRMuASrZT
The fire is contained to the two buildings but it’ll be later this evening before firefighters have progression stopped on the flames
Part of the challenge in this fire is a tall
metal building is engulfed and walls are beginning to collapse
It’s also too dangerous to send firefighters into the structure
Authorities say the mission now is to contain the flames and calm winds are helping
and Madison Counties have responded to provide mutual assistance and firefighters are having to shuttle in water to the property from other areas
leaving some residents in the Kurten area with low water pressure
@KBTXNews @KBTXRusty pic.twitter.com/zCKyMi3m1N
Brazos County District 2 Volunteer Fire Department is in command at the fire scene
no injuries have been reported and we’re told a company spokesperson should be sharing more information on Tuesday
Drivers are being asked to stay out of the area so emergency crews can continue to come in and out of the property
BTU posted that system operators must take about 140 customers out of service so firefighters can safely respond to the fire
The facility is in a rural part of the county with few homes nearby
Footage shared by photographer James Nowak with KBTX shows that the fire at Feather Crest Farms is burning on the south end near Democrat Road. Still no word on what started it. 🔴DETAILS --> https://t.co/yVA74bzp08 pic.twitter.com/DSzeXXxrQm
Ground footage shared by Jim Suydam with KBTX shows that the fire at Feather Crest Farms continues to burn into the night. Firefighters have come from other counties nearby to help out.🔴DETAILS --> https://t.co/yVA74bzWPG pic.twitter.com/BMRMuASrZT
@KBTXNews @KBTXRusty pic.twitter.com/zCKyMi3m1N
has selected Stefan Kürten as their CEO for the Organising Committee of the Rhine-Ruhr 2025 FISU World University Games
The decision was made in close consultation with its institutional partners: the Federal Ministry of the Interior
Building and Community as well as the State Chancellery of the State of North Rhine-Westphalia
Kürten is positive about the upcoming task: “I would like to contribute to hosting major sporting events in Germany
This has always been a matter close to my heart
as I see sport as part of our German and European culture
it is important to me to have an impact on society through the Rhine-Ruhr 2025 FISU World University Games and to develop an innovative and sustainable format of a major sporting event
When this challenge is implemented in close cooperation with students and universities
It is a particular pleasure for me to take responsibility for a leading multi-sport event at several locations in my home state of North Rhine-Westphalia and to shape the process together with the institutional partners at international
adh chairman of the board Jörg Förster adds: “With Stefan Kürten
we were able to win an experienced leader from the field of national and international media sports exploitation as CEO of the Organising Committee of the Rhine-Ruhr 2025 FISU Games
we have the best prerequisites for the successful conception
implementation and perception of the Rhine-Ruhr 2025 FISU World University Games in Germany
adh and its institutional partners are looking forward to the cooperation.”
Stefan Kürten took his seat as CEO of the Organising Committee on 1 November, the day after the chairman of the board Jörg Förster presented the Organisers’ general plans for the Rhine-Ruhr 2025 FISU Games during the 37th FISU General Assembly.
© International University Sports Federation
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Sam KurtenThis content was written and submitted by the supplier
It has only been modified to comply with this publication’s space and style
Kurten, who is entering his senior year at Cedarburg High School in Cedarburg, Wis., is learning hands-on technical skills through his apprenticeship at Matrix Packaging Machinery
and it has helped steer him toward his future goals
He has been interested in learning how things work from the time he was young
The aquatic array of components piqued his interest in tinkering with things
and his passion for hands-on skills was born
his interests have become more sophisticated
he is drawn to machining and engineering and has even built a small workshop at home with welders
and grinders just so he can learn how things work
When Kurten heard that Matrix was participating in the Ozaukee Youth Apprenticeship Program
he knew it would be the perfect way to learn more about his interests
He has been a Matrix apprentice for about a year and has learned machining skills through hands-on activities and projects
He is using critical thinking to solve problems and has a helpful team to mentor him throughout the educational process
"We have some really great machinists at Matrix that are absolutely at the top of their profession,” he said
they always know what I’m trying to figure out and are there to help me with problems."
Giving high school students like Kurten an experiential education is something that Matrix believes positively impacts lives
Eric Walker, Mechanical Engineering Manager at Matrix
has seen how Kurten’s exposure to different aspects of the business has shown him how different departments work together and how they interact
Sam wouldn’t truly understand what goes on in machining and engineering,” Walker said
Sam sees machining and engineering working together.”
Kurten has proven that he’s the right intern for the job
“He is a very bright young man – that was evident even during his interview
It was obvious to me that he was going to be a very strong candidate
He has been ideal for this apprenticeship program.”
students like Kurten benefit from interactive learning and on-the-job training
That exposure helps create future industrial workers and leaders
something that is important as the current workforce starts to age
It also gives Matrix the opportunity to engage with and guide younger individuals into the world of manufacturing
Walker is proud of Matrix’s commitment to the community and its desire to introduce future apprentices to possible careers
"Matrix has a vested interest in serving the community,” Walker said
“We have access to these young individuals through a program like this
it’s an outreach tool for us and allows us to engage in the excitement of younger individuals
and that gives them a bright outlook for their future.”
the hands-on work environment and guidance provided by his apprenticeship allow him to work in an area he sees in his future – which is leaning toward engineering
The knowledge and skills he is gaining at Matrix will give him an advantage over other students entering the career
He is learning how specific tools can be used to create new packaging machine parts
while also learning how engineering can utilize those components for better system performance
“My apprenticeship with Matrix has really opened my eyes to all the possibilities within packaging and manufacturing,” Kurten said
it’s been a really great experience to be able to do something that’s going to help me long-term.”
The Rhine-Ruhr 2025 FISU World University Games Summer will be held in the North Rhine Westphalia region of Germany from 16-27 July 2025
and officials from up to 170 countries are expected in the region
for one of the world’s largest multi-sport events after the Olympic and Paralympic Games
The athletes will compete in 18 sports over 12 days in Bochum
The work towards getting all the pieces together to host the event are in full swing
and Germany’s vision goes far beyond the stadium
The Rhine-Ruhr 2025 promises an innovative and sustainable celebration of sport that will inspire the population and inspire the youth to take advantage of the region’s diverse offerings in sports
as Rhine-Ruhr 2025 CEO Stefan Kürten explains
“We want to present Games that are there for everyone
that take into account the wishes of the youth and also presents North Rhine-Westphalia in its diversity with all its possibilities,” he said
it is of course particularly important for us to anchor the Rhine-Ruhr 2025 World University Games in the public’s consciousness
An active participation process of the population and also the universities and students is therefore planned,” he added
“We want students from all over the world to come to the Rhine-Ruhr region
experience the event and get to know the region – a metropolitan region that is looking to the future and developing into a centre for research
technology and sustainable projects.”
Rhine-Ruhr will also be collaborating with the other major events lined-up in Germany – European Championships Munich 2022
Berlin 2023 Special Olympics World Games and UEFA Euro 2024
“We have interacted with these high-profile events
We see ourselves as a string of pearls of sporting events
where each event tries to build on the previous one and become better
We also want to present our event in the best possible way and showcase Germany as a beautiful
culturally diverse and sustainable sporting location
Rhine-Ruhr 2025’s success will play a massive role in promoting sports
science and culture in the region,” Kürten said
“The Games will give a new impetus to sport
These Games are about showing the younger generations that the experiences of the athletes and those who are inspired by the event will be of great benefit to their future
spectators and followers can go home with unforgettable memories and a positive impression
Thanking stakeholders and partners for their limitless support
Kürten added: “All stakeholders have shown a great level of interest
we can make our Games special and set a benchmark for generations to follow.”
The Games are held in partnership with FISU
the General German University Sports Association (adh) in close cooperation with the Federal Ministry of the Interior and Community
the State Chancellery of North Rhine-Westphalia
the adh member universities and other partners in organised sports and science
Fraser Yachts has appointed Anders Kurtén as company CEO. The former CEO of Finnish shipyard, Baltic Yachts joins the firm with over a quarter of a decade of management
and product development experience across both the marine and luxury sectors
says the decision to appoint the Finnish executive comes after “one of the most extensive worldwide searches ever” to find a leader with a fitting profile
“I am pleased to say we didn’t need to compromise on any of our core criteria,” he says
“Anders comes with an in-depth and pragmatic understanding of the yachting and luxury sectors
a knowledge and passion for the Internet of Things (IoT) and its application for greater client service and support
and a track record for delivering sustained growth through hands-on team inspiration and drive.”
he helped spearhead and execute the company’s recent strategic turnaround to deliver the respected and much sought-after brand that it is today
With a background in IT solutions-based services and the approaches of the IoT (the collective network of connected devices)
Kurtén has a track record in applying that knowledge to start-ups and mature brands alike throughout his 25 years of management.
“This is a great opportunity to join a company that I have always admired and considered the benchmark of excellence,” says Kurtén
“With so many recent quantum leaps in sustainable technologies
it is a truly exciting time to be a part of this industry
The coming years will bring great things - and I am firmly convinced that our joint future will be forever greener.”
delivered directly from The Superyacht Group's editors and market analysts
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The latest hybrid project from the Australian boatbuilder is the fifth model to be launched from its Silver Series
The Finnish shipyard’s new custom yacht is currently undertaking preliminary trials
with its foils to be fitted for further testing later this year
Two-year build period culminates in the naming and launching of the 33.5m Baltic 110 Zemi
Work has begun at the Jakobstad facility
which Baltic hopes to be fully operational by 2024
Fraser is proud to be among the first to sign the Commitment Charter of the new Monaco Capital of Advanced Yachting initiative
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Credit: FraserFraser appoints Anders Kurtén as CEO 30 August 2023 • by Gabrielle Lazaridis Brokerage firm Fraser has announced Anders Kurtén as its new CEO
As former CEO of Finnish shipyard Baltic Yachts, Kurtén joins the international brokerage firm with over 25 years of experience across both the marine and luxury sectors.
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Share on FacebookShare on X (formerly Twitter)Share on PinterestShare on LinkedInHundreds of people gathered for a special fundraiser in Kurten Sunday
A group of local women are hoping to open a new home for women battling addiction
They say these services in B/CS are desperately needed
"The women's home will be the only free non-medical detox center in our community," said Cassie Corgey
who is the President and Founder of the non-profit
"When it was time for me to go to treatment I had to go two hours away and you know it's really not convenient when you don't have a car and you don't have any family
And it's a little scary to just get up and go two hours away
You know I am a recovering alcoholic and drug addict," she said
Organizers were thankful for the huge show of support
"I think it shows that this community cares about the women and their well being
aunts and I think as a community in Bryan / College Station
I think everybody wants to see this happen," said Amanda Holland
Some of the leaders have struggled with addiction and substance abuse themselves
it's just a lot of work and a lot of learning a new way of living
And it doesn't come naturally to us and we have to be taught
I was taught and that's my job today is to teach other women how to do this thing
It's very doable and it just has to be taught," said Phyllis Babin
She said they will need ongoing donations to offer their services
and with this we're going to be helping a lot of women," said Corgey
The group is still working on finding a location for the halfway house and hope it will be in B/CS
A van was donated to the organization Sunday to assist them with transportation
Jessica Kürten has been appointed as new Chair of the FEI Athletes’ Committee for the term 2022-2026
Maria Gretzer has held the position as Chair since 2013
and will now be replaced by Kürten – herself an accomplished showjumper that for years was a mainstay on the Irish team
and that in 2007 won the IJRC Top 10 Final – one of only two female riders to do so through the history of the final
Although Kürten no longer competes herself
she is today a much sought-after trainer and a familiar face on the international showjumping scene. “The equestrian sport has always been my passion,” Kürten said to World of Showjumping
“My job as trainer and some commentary is very fulfilling
I will do my very best to listen and understand the voices of our athletes.”
The FEI Athletes’ Committee consists of the FEI Athlete Representatives from the different FEI Technical Committees – across the disciplines of dressage
The FEI Athletes’ Committee plays a vital role
and provides a voice to the athlete community
within the global FEI decision-making process
Rodrigo Pessoa was recently elected as the FEI Athlete Representative for the term 2022-2026.
2023 - 1:48AMJohn Wayne GacyResponsible for at least 33 murders and countless rapes of boys
John Wayne Gacy is remembered as one of America's worst serial killers
Before getting the lethal injection in 1994
Gacy had managed three KFC restaurants in his younger life
in addition to volunteering as a clown to entertain children in hospital
Read more: How the world's second worst serial killer walked free from prison
Oklahoma executed 59-year-old death row inmate Phillip Hancock
who was sentenced to death for the 2001 double murder of Robert Jett and James Lynch
Hancock had claimed the killings were done in self-defence
Hancock had one simple request for his final meal
Hancock requested fried chicken with no sides
He was pronounced dead at 11.29am on Thursday (local time)
the state's Department of Corrections said
was executed by lethal injection for the 1996 murder of 21-year-old Juli Busken
and shot in the head near Lake Stanley Draper in far southeastern Oklahoma City
The murder went unsolved for years until new DNA evidence matched Sanchez
sweet iced tea and apple pie with vanilla ice cream
Tennessee's longest waiting death row inmate
David Earl Miller was a 22-year-old drifter living with a church pastor when he brutally murdered 23-year-old Lee Standifer in 1981
The young woman met Miller for a drink before they went back to the pastor's house and Miller smashed her skull with a fire poker and repeatedly stabbed her
The now 61-year-old requested fried chicken as his final meal
He had successfully appealed against death by lethal injection and instead faced the electric chair
His last words were "It beats being on death row."
Timothy McVeigh killed 168 people and injured hundreds more when he detonated a truck bomb underneath a federal government building in Oklahoma City in 1995
McVeigh expressed no regrets over the devastating act of domestic terrorism
He requested two pints of mint chocolate chip ice cream as his last meal before his lethal injection
Congress passed a law that prohibited McVeigh
Friedrich Heinrich Karl Haarmann became known as the Butcher of Hanover after he sexually assaulted
murdered and mutilated at least 24 boys and young men in Germany in the wake of World War I
Haarman was not told of his scheduled execution until the night before
he was granted an expensive cigar and a cup of Brazilian coffee
Read more: How the world's second worst serial killer walked free from prison
Peter Kürten was nicknamed the Vampire of Düsseldorf for a series of gruesome murders committed in the German city in 1929
Before his scheduled execution by guillotine two years later
Kürten was granted a last meal of Wiener Schnitzel
He asked for seconds and his request was granted
Aileen Wuornos killed seven men while working as a prostitute in Florida in 1989 and 1990
She ultimately declined a last meal and instead asked for a cup of black coffee
Her last words reflected an unbalanced mental state
I would just like to say I'm sailing with the rock
stabbed and tortured two college students in Akron
It took nearly 20 years for Cooey to be put to death
with the killer famously arguing that at 125kg
bear claw pastries and a bottle of Mountain Dew
It took him until midnight to finish eating his last meal
White supremacist Lawrence Brewer and two others offered local African-American man James Byrd Jr a lift home in the town of Jasper
They beat Byrd and chained him by the ankles to the back of a ute
dragging him for about 5km until he was decapitated
Brewer requested and was granted a lavish last meal
a bucket of ice cream and a slab of peanut butter fudge
Brewer said he wasn't hungry and didn't eat any
the state of Texas decided to stop granting last meal requests
One of the most notorious serial killers in America
Ted Bundy confessed to murdering 30 young women and girls
but the true number is suspected to be much higher
Bundy did not make a food request on death row
so was given the default last meal in the Florida State Prison – steak
In 1981 Ricky Ray Rector shot three people at a restaurant in Arkansas
then murdered a police officer while pretending to surrender
Rector then shot himself in the head in a suicide attempt
but the injury left him with serious brain damage that rendered him mentally disabled
He was executed in 1992 with the approval of then-Governor Bill Clinton
who was keen to burnish his "tough on crime" credentials during the presidential campaign
fried chicken and cherry Kool-Aid before his execution
but told the prison guard he was saving his slice of pecan pie "for later"
Victor Feguer kidnapped an Iowa doctor he had never met named Edward Bartels and shot him in a cornfield in Illinois
Feguer was hanged three years later in front of a crowd that included politician John Ely
who was so disturbed by the execution that he successfully legislated to ban the death penalty in Iowa
Feguer's last meal was simple and bizarre: a single olive with the pit still in it
His hope was that an olive tree would sprout from his grave as a symbol of peace
Scotty Morrow was executed by lethal injection in Georgia on May 2
for the murders of his ex-partner Barbara Ann Young and her friend Tonya Rochelle Woods on December 29
He requested a huge last meal of a hamburger with mayonnaise
the Georgia Department of Corrections said
Responsible for at least 33 murders and countless rapes of boys
Read more: How the world's second worst serial killer walked free from prison
Oklahoma executed 59-year-old death row inmate Phillip Hancock
His last words were \"It beats being on death row.\"
Read more: How the world's second worst serial killer walked free from prison
who was keen to burnish his \"tough on crime\" credentials during the presidential campaign
but told the prison guard he was saving his slice of pecan pie \"for later\"
going from young rider level all the way to achieving the goal of competing at the Olympic Games in Tokyo
Jessica Kürten and Czech rider Anna Kellnerova have decided to move in different directions in the sport
and I’m proud of what Anna and her horses have achieved,” Kürten comments to World of Showjumping
“These six years have been really outstanding, but now it’s time for me to do something else and take on new challenges.”
“Working with Jessica has been a great journey and I am grateful for the knowledge and experience I have been able to gain along the way from her,” 24-year-old Kellnerova says
“I thank Anna and everyone who has been involved in the team over the last years for their amazing work and motivation,” Kürten closes off
Stefan Kürten.Save this storySaveSave this storySaveIn a show of new paintings and works on paper at Manhattan’s Alexander and Bonin gallery
Düsseldorf-based artist Stefan Kürten presents imagined modernist homes set in lush gardens
are beautiful and imposing in their strict linear form; they would clash with their idyllic landscapes were it not for the dappled light painted across their surfaces
and marble terraces to blend softly into their surroundings
2015.The quality of light and the color palette differ from scene to scene
placing each in a specific time of day or year
a pink dusk sky glows above a serene reflecting pool
where house and sunset are mirrored so closely they appear like an impossible basement
a midday summer sun set in a green sky sends zebra-stripe shadows across a wood deck; nearby
giant sunflower heads waver in the hazy heat
The tall trees in Undiscovered Soul (2014)
their leaves and needles rendered in many minute brushstrokes
catch the day’s last light against a purple evening sky as splotchy shadows spread across a cement eave below
golden starbursts explode overhead like fireworks in colors to match the rich ochre terrace
four mysterious light sources hang hidden in the leaves above the house
There are no people in Kürten’s visions; though these places seem like homes
their worlds are eerily abandoned and seemingly full of secrets
Through May 30 at Alexander and Bonin, 132 Tenth Avenue, New York; alexanderandbonin.com
The newest member of the Dewey Beach Police Department has worked his first shifts as K-9 Smoke started on patrol with partner and handler Cpl
Kurten said he planned to slowly introduce Smoke to his new surroundings
including his first trip to the police station Oct
Most of his life has been spent in a training environment
Smoke and Kurten just returned from a month-long K-9 training program at Tarheel Canine Training Center in North Carolina
where Smoke learned to be an excellent tracker on hard
soft and mixed surfaces to aid in locating lost people as well as criminal suspects
The canine crime fighter is also trained to detect ecstasy
noting many dogs are not certified in detecting marijuana anymore
Smoke will sit with his nose pointed directly at the drug source
Smoke has learned to bark upon entry when officers enter a building
meaning he will return immediately when called during an encounter
his presence will be a deterrent so we don’t need that,” Kurten said
Smoke is also trained in handler protection and crowd control
and will be working on muzzle work so that he can work crowd control with no bite
his tail is wagging like playing tug of war,” Kurten said
a cross between a Belgian Malinois and Dutch shepherd
“His favorite toy is obviously the ball,” Kurten
and I’m going to give him salmon oil to keep his coat shiny.”
K-9 training will continue daily at the station
and monthly with K-9s from other local municipalities
Kurten said he hopes to do demonstrations with Smoke and with K-9 Jasper
who is currently training with his handler
and have stickers and trading cards of him,” Kurten said
Smoke will be officially sworn in at the next commissioners’ meeting
More than two million people worldwide suffer from multiple sclerosis (MS)
the immune system destroys "by mistake" cells in the brain and the spinal cord
This leads to spots of inflammation that cause more or less severe symptoms
depending on their location and size: the affected persons may feel a tingling sensation in their arms and legs
they trip frequently or have vision problems
they can no longer walk on their own and are confined to a wheelchair
but the available drugs can at least mitigate the symptoms
"We cannot even predict when a patient will have a next flare-up
or whether MS will develop after a first flare-up"
Professor of Anatomy and Cell Biology at the Julius-Maximilians-Universität Würzburg
Although new drugs have been introduced to the market recently
there is no way of telling which of them is best suited for which patients
"Quite often doctors simply try one drug
very frustrating for both patient and doctor – all the more because it is a known fact that MS must be treated efficiently at an early stage to prevent its long-term progress and the loss of brain tissue
Kürten's team has now succeeded for the first time in developing a biomarker for MS: a blood analysis may be able to help decide which of the two "therapy classics" should be used in the early phase of the disease
Patients with autoreactive B cells in their blood would need to be treated with Copaxone
whereas patients without such B cells are likely to benefit more from an IFN-beta therapy
These findings were made in cooperation with TEVA Pharmaceutical Industries and Cellular Technology Limited
"All we need are blood samples from the patients"
Kürten’s colleague Damiano Rovituso
The white blood cells are isolated from the samples and stimulated for four days in a cell culture so that the immune system's memory B cells start producing antibodies
"We then determine whether these antibodies attack the tissue of the central nervous system." This is a highly specific test for multiple sclerosis
because B lymphocytes and their antibodies can contribute directly to nerve fibre damage
The findings of the study have been published in the "Scientific Reports" journal
The scientists have performed tests on a total of 57 MS patients
Contributors to the study were the Departments of Neurology of the University Hospitals of Cologne and Würzburg
the Caritas hospital Bad Mergentheim and the Charité Universitätsmedizin Berlin
Before these new insights may find their way to standard treatment
they have to be confirmed by a clinical study with a larger number of patients
Stefanie Kürten says that such a study is expected to start in 2015
funded by the pharmaceutical company TEVA Pharmaceutical Industries
The study will be performed in cooperation with Stefan Braune
Professor of Neurology at the Technical University of Munich
He will recruit for the study patients from all over Germany through the nationwide network NeuroTransData GmbH
Next step: Explore the effect of antibodies
Stefanie Kürten wants to find out which target structures in the brain are attacked by the antibodies from the memory B cells of individual positive tested patients
By this she expects to gain further insight into the course of the disease
"We may then be able to develop therapies that attack the pathogenic B cells directly."
A new biomarker for multiple sclerosis: the inflammatory cell rim from microglial cells surrounding brain lesions was found to directly correlate with the severity and speed of disease progression
researchers use a very large dataset to identify predictive brain imaging-based biomarkers of mental illness in adolescents
Could a single biomarker detect all types of diseases related to dopamine deficiency in the brain
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View upcoming auction estimates and receive personalized email alerts for the artists you follow
Nye & Company Auctioneers’ two-day Chic and Antique auction slated for Wednesday and Thursday
"The most important themes in my work are flowers
wallpaper-like patterns and domestic architecture
comfort and safety in a complex and sometimes frightening world..
and our attempts to create a 'perfect world' that we can inhabit
Alexander and Bonin is pleased to announce Index
Dewey Beach police officers Carl Kurten and Jack Kane were promoted and honored at the April 21 commissioners meeting
Chief Constance Speake promoted Kurten to corporal
stating the former patrolman first class was a 24-year veteran who has served in Virginia
school resource officer and certified instructor
dedication and abilities made my decision easy to have you take the lead in reestablishing our K-9 unit as its first handler in years,” Speake said
“I am delighted to have a person of your integrity
knowledge and background to step into your new role as a supervisor and K-9 handler.”
The Milton VFW Post 6984 presented Patrolman First Class Jack Kane with the Officer of the Year Award for his actions in saving six people and a dog from an April 2022 fire that damaged three homes in Dewey Beach
a member of Milton VFW Post 6984 and former part-time Dewey Beach police officer
when Kane was on his way home after his shift
he heard a call for a critical medical emergency
noting that Kane joined a Delaware State Police officer in performing CPR on the individual
After Story presented a certificate and $100 check to Kane from Post 6984
he said Kane was also the recipient of the State of Delaware VFW National Law Enforcement Award for his highly professional record of service
and admiration of his peers and the public he serves
“This honor reflects the proud ideals and high standards of the Veterans of Foreign Wars of the United States,” Story said