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Chief Cataloguer of the National Museum in Krakow
was one of the most outstanding artists working in Albrecht Dürer's circle – a renowned painter
illuminator and stained glass window designer
or whether or not he visited the Royal Town while executing commissions for Krakow
or whether or not he visited the Royal Town while executing commissions for Krakow.The principal subject of this exhibition
the cycle of Saint Catherine of Alexandria designed between the years 1514–1515 for St
originated a little less than two decades after the monumental altar by Veit Stoss (1477–1489) created for the same church; the two works of art
Kulmbach created his works under the influence of both Italian and South German art
revealing his delight over untamed nature which provides the background to human tragedies
He daringly arranged people with individualised features
dressed in elaborated costumes and shown with convincing foreshortening
The master’s works preserved in Krakow are scattered
they have become all but forgotten.In 2016
a several-years long conservation effort was completed on one of the most seminal works by the artist: a cycle of the life of Saint Catherine of Alexandria on eight oblong paintings
The work was specifically designated for St
Mary’s Church in Krakow for one of two altars
and most probably commissioned by the Boner family
The cycle is exhibited for the first time after conservation treatment
within the framework of an exhibition held in the Portrait Room of Bishop Erazm Ciołek Palace – a branch of the National Museum in Krakow
The exposition provides an opportunity to present techniques used by art restorers and the successive stages of conservation treatment
and is illustrated by photographs in the various techniques which correspond to Kulmbach's study drawings brought from foreign collections
The exhibition's highlight is a drawing for the panel Martyrdom of Philosophers from the cycle of Catherine of Alexandria from the Louvre collection
and a precious Polonicum: The Martyrdom of St
Stanislaus – the projection of a panel in the shape of a tondo for a stained glass window from the Kunsthalle in Bremen
opportunity to admire these works of art in Poland.The above-mentioned cycle is surrounded by fragments of other
works by Kulmbach which the artist created for Krakow
including the remains of a Saint Mary triptych in the monastery of the Order of Saint Paul the First Hermit at Skałka (The Flight into Egypt) and in the Princes Czartoryski Museum (the image of Saint Catherine of Alexandria)
as well as fragments of a reredos illustrating the history of John the Evangelist (predella with Descent into the Tomb of Saint John Evangelist
Mary’s Church).The works constituting the core of the exhibition are supplemented with selected paintings by other German artists working on commission in Krakow at the beginning of the 16th century
Also included are goldsmiths' artworks imported from Nuremberg
of which a few are connected with the founding activity of the Boner family
All highlight the ties between Krakow and Nuremberg at the beginning of the 16th century and shows the prosperity of the Kingdom of Poland at the time of King Sigismund I the Old
Krakow was one of the leading artistic and cultural centres in Central Europe.The memory of the master’s greatness and his Krakow painting cycles gradually re-emerged in the 19th century
when Wojciech Korneli Stattler (1800–1875) and Józef Kremer (1806–1875) “pondered over them”
a cycle of watercolours by Maksymilian Cercha from 1849 appeared
documenting the view of the panels from the reredos wings depicting St
and costume studies of the panels from the cycle of Saint Catherine (around 1856–1857) by Jan Matejko.In 1874
Władysław Łuszczkiewicz (1828–1900) popularised Kulmbach's heritage with a lecture at the Polish Academy of Arts and Sciences
which was published together with “contour” drawings
Waldemar Kryciński (1852–1929) made an almost completely preserved copy of the cycle of Saint Catherine; some of his drawings were used as patterns for lithographic pictures printed in the same year at the workshop of Marcin Salb.In 1878
Marian Sokołowski delivered a lecture on Kulmbach's works
subsequently publishing in 1884 a substantial article
his Paintings in Krakow and his Master Jacopo dei Barbari
The author indicated the preserved Kulmbach cycle from the Boners’ Chapel in St
Mary’s Church as the perfect expression of the artist’s mastery
Sokołowski’s inspiration can be found in the juvenile sketchbook of Stanisław Wyspiański from the years 1885–1889 in the collection of the National Museum in Krakow
was inspired by “a different ornament in the late Gothic style
composed of stems and plant braids on which
lizards crawl”.Supplementing the fascination with the work of the Nuremberg artist in the second half of the 19th century are cycles of photographs taken by many Warsaw photographers (including Karol Beyer
mainly known from sources and by Krakow photographers
of whom the best known was Ignacy Krieger (1817/1820–1889).Curators: Mirosław P
Marek Walczak (Instytut Historii Sztuki Uniwersytetu Jagiellońskiego
Aleksandra Hola (Akademia Sztuk Pięknych w Krakowie)Arranger: Łukasz SarnatCoordinator: Aleksandra Kłaput
The central sewage treatment plant in Kulmbach Germany upgraded its inlet lifting pump station for enhanced energy efficiency and optimal operation
Replacing the older variable speed drive (VSD) with an ABB ACQ580 water and wastewater drive
paired with an ABB IE5 synchronous reluctance (SynRM) motor
the town of Kulmbach operates a municipal wastewater utility servicing 8,000 households
the total volume of wastewater amounted to around 11.6 million cubic meters
The city's central sewage treatment plant has the capacity to handle wastewater for a population of 270,000 persons
The inlet lift pump station at the Kulmbach central sewage treatment plant is the end station of the local sewer network
It is also the first station of the sewage treatment plant
the incoming wastewater is elevated up to around six meters with the aid of two alternately operating Archimedes screws
The wastewater then passes through all treatment stages using gravity
In the event of a high inflow of mixed water after e.g
a maximum of 1,400 liters of wastewater per second can be pumped using both Archimedes screw pumps
one of the two pumps has been driven by an ABB IE5 Ultra-premium energy efficient SynRM motor
who is the responsible electrician for the wastewater disposal division at Stadtwerke Kulmbach
explains how the replacement in the utility came about: "The old variable speed drive from another manufacturer that controlled the pump motor
had been tripping sporadically at full load
We decided to replace the entire drivetrain.”
Energy efficiency and cost-effectiveness of ABB IE5 SynRM motors were decisive factors
According to Enrico Porzelt " With energy costs on the rise and resources growing scarcer
it's crucial to safeguard the public and municipal interests in wastewater disposal
energy efficiency and cost-effectiveness are of essential importance
Whether it's designing new buildings or renovating systems
our priority always concern sustainable and energy-efficient solutions"
Another factor that led Enrico Porzelt to choose ABB was their advanced drive technology
ABB’s industry manager and ABB channel partner Max Lamb were able to support Porzelt in a timely manner concerning an incident at a sewage pumping station
Two of the variable speed drives from a third-party manufacturer broke down within a week for dry-installed wastewater pumps
While the third-party manufacturer had a delivery time of over six months
ABB was able to deliver and commission two ACQ580 variable speed drives in a very short time
The ACQ580 drive has embedded functions for water and wastewater applications
which together with the intuitive control panel
It replaced the pump's old variable speed drive
which was still equipped with a passive filter
The 90-kilowatt IE5 SynRM motor replaced the old
this motor is characterized by its higher reliability and lower maintenance requirements
"The fact that we now get the variable speed drive and motor from a single supplier makes it easier for us to design the system that simplifies project planning," explains Enrico Porzelt
The ACQ580 water and wastewater drive regulates the speed of the motor within a speed range of 15 to 50 Hertz
This corresponds to a pump capacity of zero to 100 percent
The amount of wastewater to be pumped depends on the level of wastewater in the upstream basin of the screw pumps
If the water level in the feed shaft rises
If the maximum speed is reached and the level continues to rise
the second Archimedes screw is switched on
Continuous operation offers savings potential
The Archimedes screw pumps are switched on during alternating weeks so that the load and operating hours are roughly the same
"The Archimedes screw pumps run around the clock and are only switched off for maintenance
we expect an energy saving potential that results in lower energy consumption," says Enrico Porzelt
"As the energy measurement of the inlet screws and the inlet pumps are carried out on the same line
the real energy savings from the new ABB motor-drive solution cannot yet be conclusively determined
we expect energy savings to be around from 7 to 10 percent," says Enrico Porzelt
The information is attained from the assessment of evaluated operating data and the engine data provided by the ACQ580
The motor monitoring function in the drive is utilized to surveil the temperature of the windings
the availability of a second control circuit for on-site manual operation
allowing for zero to 100 percent setpoint specification via a potentiometer
Another advantage is the straightforward operation of the ACQ580 water and wastewater drive that is easy to use
The motor-drive train for the second Archimedes pump is scheduled for an upgrade during 2024
An ABB package consisting of an IE5 SynRM motor and an ACQ580 drive for water and wastewater is already waiting to be installed at the central sewage treatment plant in Kulmbach
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GERMANY: The University of Bayreuth has handed over a CO2-powered air conditioning system to the Kulmbach Vocational School Centre (BSZ) for use in its operations and teaching.
which was developed by the university’s Centre for Energy Technology (ZET)
It includes a Bitzer Ecoline transcritical reciprocating compressor with frequency converter and SWEP plate heat exchangers
it will serve vocational training in the field of air conditioning and refrigeration technology in Kulmbach
The project was funded by the Bavarian State Ministry for the Environment and Consumer Protection
“The air conditioning system installed today gives pupils at BSZ access to the most up-to-date know-how research has to offer
they can use this system to develop an understanding of important energy technology issues that need to be solved while complying with strict ecological requirements,” said BSZ director Alexander Battistella
“A first test run recently met with great interest among the students of BSZ
they learned about the ecological advantages of CO2 as a refrigerant and learned about current changes in EU law aimed at increasing climate protection.”
part of the project – FutureClimate – Development of Sustainable Air Conditioning Concepts – was funded by the Bavarian State Ministry for the Environment and Consumer Protection to the tune of approximately €240,000 for three years
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The forerunner of the iconic MP 40 sub-machine gun is back in a collector's grade
made-as-new semi-automatic closed-bolt version that would be civilian-legal in many jurisdictions – if you can afford it
Sport Systeme Dittrich out of Kulmbach (Germany) manufactures the BD 38
a civilian-grade version of the MP 38 sub-machine gun
Sport Systeme Dittrich first introduced the BD 38 in 2005
The MP 38 sub-machine gun was first engineered in the second half of the 1930s by Heinrich Vollmer
Based upon the MP 36 design by Berthold Geipel – ERMA's founder and owner – the MP 38 also integrated some features from Vollmer's signature projects such as the EMP machine-carbine and the prototype VPM 1930
The MP 38 and MP 40 were often incorrectly refered to as the "Schmeisser" by Allied forces
neither Hugo nor Louis Schmeisser had anything to do with the development of either variants
although Schmeisser's patented magazine was used
A close-up of the Bakelite grip and frame wrap
In modern times, the MP 38 has become one of the many historical firearms made available to civilian shooters, collectors and re-enactors thanks to Sport Systeme Dittrich
a gunmaker headquartered in the German town of Kulmbach
Among those historical replicas is the BD 38 – a civilian-grade
semi-automatic version of the original MP 38 sub-machine gun that has been made available in 9mm Luger for international commercial sales and in 9x21 IMI for those Countries where 9x19mm is forbidden or restricted to civilians
the Sport Systeme Dittrich BD 38 can be classified as a handgun or as a long gun
Configuration may thus vary depending from local provisions concerning the features of handguns
and short-barrel rifles: it may feature a fully extensible underfolding stock
or it could be locked permanently in the unfolded or folded position
or totally removed; or it could feature a permanent barrel extension
the Sport Systeme Dittrich BD 38 is a semi-automatic
The original working system was tinkered with to adapt the design for civilian sales
and that was pretty much the only design change that tells the BD 38 apart from the MP 38
Sport Systeme Dittrich still manufactures the new closed-bolt version basing on the original blueprints and largely using original techniques and materials
The entire upper receiver – which hosts the magazine well
and the barrel – is entirely machined out of steel and entirely brunished
The frame is instead manufactured out of aluminum
and features a reddish bakelite shell; the same material is used for the grip panels
The 24,8 cm (9.76") barrel features six right-handed grooves
as well as a hooded blade front sight and the quintessential frontal support for firing from a fixed position
The rear leaf sight is instead mounted on the upper portion and can be set to engage targets within 100 or 200 metres
adjustable for shooting at 100 or 200 metres
field-stripped: the BD 38 strips basically in the same way
The Sport Systeme Dittrich BD 38 field-strips just like the MP 38 and MP 40 sub-machine guns – just as one would expect from a live-firing replica that has been designed and manufactured with the intent to stick as much as possible to the original design
Following is a visual guide highlighting the six steps required to field-strip this absolutely perfect modern replica of a firearm that wrote history
Once the magazine has been removed and the chamber has been checked clear
make sure that the bolt is well forward in a fully locked position
As soon as the disassembly nut has been unscrewed
the top portion can be twisted clockwise and separated from the frame
This provides access to the bolt carrier group for cleaning and maintenance
All the BCG components are machined out of steel
The components are separated; the return spring also dubs as a recoil buffer
The magazine release catch is located on the left side
A nut under the frame can be unscrewed to field-strip the BD 38
The underfolding stock design of the MP 38 / MP 40 would go on to inspire that of the AKMS assault rifle
Just like the original MP 38 and MP 40 sub-machine guns
the BD 38 comes with an underfolding steel stock that's locked and unlocked through a prominent button located on the right side of the frame
and coupled with the robust return spring that dubs as a recoil buffer
it provides stability and accuracy in aimed rapid fire
Firing the BD 38 will be a pleasurable shooting experience
and results on target will be more than satisfying
Sport Systeme Dittrich manufactures several types of double-stack magazines for the BD 38
as two shots is the maximum legal capacity for semi-automatic firearms owned under a hunting license in Germany
if you live in a Country where World War II militaria is readily available and not too expensive
you will be pleased to know that the gun does fit the original MP 38 and MP 40 magazines
great at the range: enthusiasts and collectors
Just like all other historical replicas offered by Sport Systeme Dittrich
we stress: this is not a demilitarized firearms (a former full-auto converted to semi); it's not a cheap reproduction and it's not a replica rebuilt partially from stock components
and the company spent an awful lot of time
gearing up for the production of a reproduction that would be just as faithful to the original as it could ever get
And that's where the two disadvantages of the BD 38 stem from
The first is availability: the BD 38 may be very hard to get in several jurisdictions
it may have been imported in a very small amount
only a handful of samples were ever distributed
The second is price: all those studies to come out with a perfect replica
And that price can be as high as 4000 Euros in some European Countries
That's definitely not something for everybody
Sport-Systeme Dittrich, GmbH
Semi-automatic pistol or semi-automatic carbine
Cocking handle safety blocks the movement of the bolt carrier group
See your dealer for local availability and price
VIDEO / Sport Systeme Dittrich - SSD BD 38 (replica of the MP 38 sub-machine gun)
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Knowledge to understand better and to a responsible approach to the gun world and its rules.
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Volume 8 - 2020 | https://doi.org/10.3389/feart.2020.00332
This article is part of the Research TopicSmart Approaches to Predict Urban Flooding: Current Advances and ChallengesView all 13 articles
A correction has been applied to this article in:
Corrigendum: Prediction of Maximum Flood Inundation Extents with Resilient Backpropagation Neural Network: Case Study of Kulmbach
floods are the leading natural disaster in terms of damage and losses per year
Early prediction of such events can help prevent some of those losses
Artificial neural networks (ANN) show a strong ability to deal quickly with large amounts of measured data
we develop an ANN for outputting flood inundation maps based on multiple discharge inputs with a high grid resolution (4 m × 4 m)
After testing different neural network training algorithms and network structures
we found resilience backpropagation to perform best
by introducing clustering for preprocessing discharge curves before training
the quality of the prediction could be improved
Synthetic flood events are used for the training and validation of the ANN
Historical events were additionally used for further validation with real data
The results show that the developed ANN is capable of predicting the maximum flood inundation extents
The mean squared error in more than 98 and 86% of the total area is smaller than 0.2 m2 in the prediction of synthetic events and historical events
Flood is one of the most damaging natural hazards hitting settlements which threatens the safety of civilians and the integrity of infrastructures (Berz, 2001). Flooding is the leading cause of damage and losses in many countries in the world (Kron, 2005). Furthermore, as a result of climate and land-use changes, the flood vulnerability of some regions is expected to rise (Vogel et al., 2011)
Accurate prediction of floods in urban areas can contribute to the development of essential tools to minimize the risks of flooding
Although these scalability techniques reduce the simulation time greatly
it is still unacceptably high in many cases for real-time early warning systems
we develop a method for predicting the maximum flood inundation in an urban area by backpropagation networks based on multiple inflow data for a grid resolution of 4 m × 4 m
this work focuses on applying ANN in an urbanized area for producing high-resolution flood inundation maps from river flooding
For the prediction of maximum flood inundation
only the real-time discharges of the upstream catchments are needed
we introduce the backpropagation artificial neural network
fuzzy c-means clustering methods (FCM) and our criteria for model evaluation
Study Area and Dataset provides basic background information about our study area as well as the synthetic event database for our model training
Results shows the results of our model tuning
the simulation results for synthetic and historical events
To improve the model training behavior by a limited database
we introduce two FCM for the preprocessing of the training dataset
Last sections are the discussion and conclusion of this work
The ANN applied in this work for modeling the study area is a forward-feed neural network (FNN) (Nawi et al., 2007)
producing and transmitting the data in a network structure
The basic element of the neural network is the neuron
Each neuron collects values from the previous layer by summing up the results from the previous neuron values multiplying the weight on each input arc and storing the results on itself
information is proceeded by the weights and transferred over the network
The input layer of all ANNs is given by seven inflows upstream contributing to the urban area of Kulmbach from the event database (further details can be found in “HEC-RAS and Synthetic Event Database” section)
The output layer is set from the raster flood inundation map from the event database
Backpropagation is an algorithm widely applied in neural network studies, for optimizing the weights in forward-feed neural networks (Nawi et al., 2007)
The procession consists of two phases: the training phase collects a part of data from the existing database
tuning the model by changing the weights on input arcs to minimize the bias on the output layer; the recalling phase produces the new outputs for the testing inputs
The rest individuals in the training dataset are used for evaluating the behavior of the network
The total bias between the output of ANN and the observed values is defined as the error function
In order to reduce the error function in each iteration
the weights are modified automatically as described below
The chain rule is applied for minimizing the biases
Wij is weight from i’th neuron to j’th neuron
neti is weighted sum of the inputs of neuron i
ϵ is learning rate taken as 0.01 in our training
The learning rate is used for scaling the gradient in each iteration of the weight update. It is critical to pick up the correct value. A large learning rate will miss the optimal point, while a small learning rate would slow the training process. Herein, we apply the gradient descent algorithm to calculate the update of the weights. To speed up the convergence of the iteration formula (2), resilient backpropagation as defined in Saini (2008) is applied
which treats the update of weights differently depending on the derivative of the error function
Larger alternative learning rate η+ could be set for speeding up the iterations if the error gradient remains in the same direction in neighboring time-steps and smaller alternative learning rate η− when approaching the optimal weights
In which 0 < η− < 1 < η+
In our study these were set constant and equal to η-=0.5,η=+1.2
The study area is divided in 50 × 50 raster each simulated by its own ANN
Output layer: flood inundation extent in each grid
every single event is given a membership u
which indicates the relation between the event and a certain cluster
it means that the event has nothing in common to a specific cluster; if the membership is one
the event is located at the center of the cluster
the membership u can be calculated by the following equations
and based on the event and the distances between the events
the membership uij is to quantify distances between events and cluster centers
dij is Euclidean distance between event j and its corresponding centroid
the total sum of distances between events and the cluster centroids have to be the minimum possible
Therefore the following objective function needs to be optimized:
Two approaches are applied for deciding the clustering parameters: (a) conventional clustering (by pre-selected hydrograph characteristic parameters); (b) dimension reduction methods
the clustering variables chosen were P (peak discharge value)
These can be applied individually or combined
The latter clustering method is based on principal component analysis among the hydrographs
The data are projected to the first several principal eigenvectors for dimensionality reduction via PCA
To determine the optimal number of clustering c
we define the clustering performance index L(c)
The optimal cluster number c can be determined by the maximum of L(c)
To evaluate the performance of the ANN prediction of maximum flood inundation in the study area is based on the mean squared error (MSE) of each grid. It is assumed that the inundation maps from the synthetic events produced using a dynamic model (HEC-RAS) are the observed values. The synthetic events have been produced using the FloodEvac-Tool (Bhola et al., 2018). The model has been validated (Bhola et al., 2019)
As each grid has its own independent training network
the MSE is evaluated using all the pixels in each grid
To evaluate the overall behavior of the model across the training and validation data sets
the average of MSE and the standard deviation of MSE are evaluated
indicating the average accuracy and the spread of the ANN predictions
Since the ANNs are trained on the same data
the inundation maps across the different ANNs are consistent
It shows the location of Kulmbach in Germany
The blue curves represent the river network
The shaded region is the study area with its topography represented
the red points represent the seven inflow boundary conditions (three rivers and four smaller streams)
Comparison of average MSE by the two training algorithms in the testing dataset (Event #121 to Event #180)
(A) Average (among events) MSE by resilient backpropagation (RP)
(B) Average (among events) MSE by conjugate gradient (CGF)
Difference of average MSE by the two training algorithms in the training dataset (Event #1 to Event #120)
Negative values indicate that RP performs better than CGF (i.e.
149 grids have positive values and 335 grids have negative values
Number of grids in each combination (number layers and neurons) which outperform all the others
The grid resolution comparison aims to verify if a finer grid improves the prediction performances. Two grid sizes are tested, namely one with 50 × 50 (each grid has 1400 pixels) and another with 100 × 100 (each grid as 350 pixels) grids (Figure 5). The former has 2500 ANN networks that need to be trained, while the latter has 10000. Since the 50 × 50 performed better (see Table 2) and is computationally more efficient
Comparison of average MSE by two grid-size (numbers of ANNs) in the testing dataset (Event 121 to Event #180)
(A) Average (among events) MSE in 50 × 50 grids by RP
(B) Average (among events) MSE in 100 × 100 grids by RP
The impact of grid size on the ANN training
Determine cluster numbers and numbers of principal components
(A) Conventional FCM criteria and their corresponding L(c) values: P (peak discharge value)
(B) Data preserving rate in relation to the numbers of principal components
A minimum data-preserving rate of 97.5% was selected as a good representation of the training database
Table 3. Integral of the bandwidth (90% confidence interval shown in Figure 9) by conventional FCM and PCA-FCM assuming a cluster number equal to 4
Clustering of all the discharge curves in the training dataset of Stream Red Main (biggest inflow) grouped into four clusters by conventional FCM
(A–D) The curves are clustered into the above four clusters
The clustering is based on the combination of P (peak discharge value)
Asterisks represent the 90% confidence intervals of the four clusters (A–D)
Clustering of all the discharge curves in training dataset of Stream Red Main (biggest inflow) into four clusters by PCA-FCM
Sign of MSE difference between PCA-FCM clustered 100 events
only 1.21% (seven out of 580) of total grids have their MSE over 0.2 m2
Example of flood inundation prediction in testing dataset (Event #180)
(B) Inundation prediction from the database
The historical discharges from the historical events are taken from Bavarian Hydrological Services (Bhola et al., 2018)
two representative events are selected to validate the ANN
The February 2005 is an example of an advective precipitation with lower peaks and longer duration
The May 2013 is an example of a convective precipitation with higher peaks and shorter duration
Figures 10, 11 show the MSE obtained for the prediction of the historical event in February2005 and May 2013. In Figure 10, the large MSE occurs mainly in the ponding area to the southwest. Figure 11 shows larger MSE in the southwest than that in February 2005
Average MSE difference between the ANN and the hydrodynamic model of the historical event in February 2005
Comparison of average MSE to observed inundation depth (historical event in February 2005)
Average MSE difference between the ANN and the hydrodynamic model of the historical event in May 2013
a grid is “optimal,” once the error function reaches the minimum
it is possible to conclude that the majority of grids (70%) behave better with two or three hidden layers
no general trend observed between the number of neurons and the number of hidden layers
The “optimal” occurs over all the combinations of the number of hidden layers and the number of neurons
it is possible to find a widespread “optimal” number of neurons
it is seen that the network with fewer neurons behaves better with only two hidden layers
though the network with more neurons behaves better with three hidden layers
the complex dependency between hidden layers and neurons reflects the complexity in the input training datasets
we used two hidden layers with 10 neurons per layer
The results show the capability of the ANN to perform predictions with small MSE (Figure 5)
the 100 × 100 (finer grids) takes 2 h more only for the initialization of the network
the 100 × 100 grid tends to have a larger MSE during the testing phases
which indicates more overfitting than the solution with 50 × 50
it is obvious that a decrease in the number of grids produces less precise results
giving more weight to the training efficiency with less overfitting
it was decided to proceed with the 50 × 50 grid in our study
we choose the first seven principal components for clustering into four groups
we observe five out of seven streams have smaller clustering spread (except Upper Schorgast and White Main)
while the rest two are only slightly larger
It is important to verify that the clustering strategy is efficient
we compare it with three other strategies using the MSE: (a) the original training dataset
consisting of the original 120 events in the training dataset from the synthetic database (RP120) (b) randomly select the 100 events from the 120 events (RP100)
and (c) randomly select 100 events from the four clusters (RP100C)
The results show that the RP100C behaves slightly better than RP120
which means that we can achieve similar good predictions even when with a clustered dataset with a smaller size
The RP100C behaves much better than RP100; this shows that
clustered individuals perform better than random individuals
Validation of the results in the synthetic events using the whole testing datasets is shown in Figure 9
The majority of the predictions are accurate with MSE around 0.1 m2
there are still more than 1.21% of grids with MSE larger than 0.2 m2
Since the terrain elevation is relatively flat (city center) the impact of a highly variable terrain in the ANN predictions is reduced
This could also add to the good agreement found in our results
the results show clearly that the ANN prediction is bounded by the local topography
displaying a very similar inundation extent as the hydraulic model
larger error can occur in the water depths particularly in the southwest of our study area
This is the farthest away area from all the seven inflows (model inputs)
it could be anticipated that this area would be more difficult to predict by the ANN model
As the distance to the inflows (model inputs) increases
the growing uncertainty causes the water depths prediction to deviate from the observed data
It should be noted that the inundation extent is always well predicted
As in the results for the synthetic events
the ANN is able to accommodate the flooded volume within very similar topographic limits as the hydraulic model
This study focuses on using artificial neural networks trained with synthetic events to replace the 2D hydraulic model for flood prediction
A forward-feed network structure was applied and set up with a training dataset with 120 synthetic events and a testing dataset of 60 events
namely resilient backpropagation and conjugate gradient
with their MSE in the whole domain evaluated
Resilient backpropagation performed better than the conjugate gradient with a smaller MSE on average
An investigation of the number of hidden layers and the number of neurons per layer set this to 2 and 10
Complex dependencies from the interaction of these two parameters were observed
It was not possible to find a clear trend over all the ANN with a simple set of network layers and neurons
It was nevertheless noticed that 70% of our networks performed better
once two or three hidden layers have been used
This indicates that the prediction of flood inundation extents by inflow hydrographs is more likely to be precise at a low hidden layer number
The impact of the network size 50 × 50 and 100 × 100 over the studied area was also investigated
the 50 × 50 grids have slightly smaller MSE with much less model tuning time
Conventional FCM and PCA-FCM were investigated in this study
Both clustering methods capture the characteristics in each cluster (by the trend of curves and of confidence intervals)
By checking the 90% confidence interval over all the clusters
we could infer that the cluster spread of PCA-FCM was smaller than the spread with the conventional FCM clustering
The MSE difference map of the clustering strategy showed that this strategy is efficient in reducing the size of the training set
clustering is helpful as the preprocessing of the training dataset
the network could cover a wider range of inputs and avoid overfitting by similar training data
clustering enhanced the performance of the ANN training by reducing the size of the training set and slightly improved the prediction of maximum flood inundation
The prediction results on the testing dataset are very good
The prediction of maximum flood inundation shows no visible difference from the synthetic events in terms of flood extent and water depth
only 1.21% of the wet grids have values larger than 0.2 m2
suggesting that the prediction is successful over 98% ANN
Tests on real events showed that the prediction results of the flood inundation are still very good but with some localize disagreements in the maximum water depths
91.03% in 2005 and 86.38% in 2013 events were good
It was also seen that the model prediction quality decreased as the area of the forecast was further away from the inputs
this work proved that resilient backpropagation networks can be used for replacing the 2D hydraulic model for prediction of flood inundation
requiring only the discharge inflows as inputs
The datasets generated for this study are available on request to the corresponding author
QL and WW set up the prediction model in this work
QL wrote the first version of the manuscript
JL and MD proofread the manuscript and improved it
All authors contributed to manuscript revision
The research presented in this manuscript has been carried out as part of the HiOS project (Hinweiskarte Oberflächenabfluss und Sturzflut) funded by the Bavarian State Ministry of the Environment and Consumer Protection (StMUV) and supervised by the Bavarian Environment Agency (LfU)
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest
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Bhola P and Disse M (2020) Prediction of Maximum Flood Inundation Extents With Resilient Backpropagation Neural Network: Case Study of Kulmbach
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*Correspondence: Qing Lin, dHNjaGluZy5saW5AdHVtLmRl
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Located in Kulmbach, Germany, Töpfer Kulmbach has specialized in the production of labels and packaging for the international beverage industry for 100 years
The company has more than 300 employees and uses offset
flexo and rotogravure for high volume production of labels and packaging
The company exports about 45% of its production
“Sustainability is a primary strategic pillar for our company
and has been for many years,” said Mark Töpfer
“With our certifications and competency with ink and paper
we can deliver the right sustainable solution for our customers.”
has been a satisfied Töpfer customer for 30 years
“When Carlsberg came to us with a project to print with Cradle to Cradle inks,” Töpfer added
“we already had a Cradle to Cradle ink system in place along with all the competencies needed to meet these requirements
Although Carlsberg was using another ink supplier
we convinced them to switch to inks from hubergroup
because our experience has proven that these inks are not only Cradle to Cradle certified
but they comply with other technical requirements within the lifecycle of returnable labels
We had already successfully tested all these things with the hubergroup inks and had established a stable process.”
as opposed to the more commonly known Cradle-to-Grave
waste materials in an old product become the ‘food’ for a new product
It creates a circular economy that goes beyond conventional sustainability efforts
in which products are created according to the principles of an ideal circular economy
This differentiates Cradle to Cradle from conventional recycling (cradle to grave) and the concept of eco-efficiency
It is about eco-effectiveness and goes beyond conventional sustainability tools and approaches
which primarily show the negative influence of humans on the environment
hubergroup was the first manufacturer to receive the EPEA Cradle to Cradle certification for conventional sheetfed products
and its Gecko Green Line Premium for flexible packaging
were also awarded the Cradle to Cradle Products Innovation Institute’s Silver Level Material Health Certificate
its Cradle to Cradle certified inks are somewhat of a specialty offering
“We have a new-launched brand ‘NatureLine’,” he says
“under which we produce with Cradle to Cradle inks
recycled paper and completely renewable energy across the entire production process
who want to have a sustainable labeling solution
we have already 10 customers taking advantage of this brand –new innovative solution
But simply specializing in this area is not enough
Our goal is to switch 100% of our inks to Cradle to Cradle
I personally believe that the Cradle-to-Cradle principle is definitely a system which scales to industrial volumes
and we are working to educate our customers about the benefits.”
While the Carlsberg opportunity provided Töpfer with added incentive to accelerate development of its Cradle to Cradle solutions
the company believes that this approach is ultimately the most important driver for growth in what has increasingly become a commodity market for beverage labels
provide us with the ability to diversify our client base and differentiate ourselves in the marketplace,” Töpfer commented
“Particularly in markets like Latin America
are global companies that want to ensure regulatory compliance no matter where their products are sold
Our Cradle to Cradle approach ensures they are using labeling solutions that meet these objectives.”
“We appreciate the partnership approach hubergroup has,” Töpfer noted
“They are the primary ink supplier for our company
and they wouldn’t be in that position if they didn’t offer us exceptional customer service
and they help us with application engineering as we encounter new opportunities
taking only a few weeks to provide them with a Cradle to Cradle solution
a speed that is almost unheard of in the industry
and we look forward to an ongoing partnership as we both strive to address many of the ecological issues facing the world today within our respective spheres of influence.”
In addition to working towards a goal of 100% Cradle to Cradle production of beverage labels using offset printing
Töpfer is also close to being Cradle to Cradle certified for rotogravure
“This makes production of very high volumes feasible in compliance with Cradle to Cradle strategies
and hubergroup has worked with us to ensure our success – and that of our customers – in this arena as well,” Töpfer stated
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Provost Jim Todd and Depute Provost Claire Leitch made a special trip to Germany last weekend to celebrate the 50th anniversary of Kilmarnock being twinned with the town of Kulmbach
They were invited by the Oberburgermeister (Lord Mayor) of Kulmbach
to attend a motorcycle rally over the weekend and were warmly welcomed by councillors and members of the public
The rally involved all of the police forces in Europe who send two motorcycle police from their respective countries to take part in competitions
The event ends with a prize-giving ceremony and a festival of food and music which thousands of people from all over the area attend
The Provost and Depute Provost also signed the Golden Book of Kulmbach that contains the original twinning agreement signed 50 years ago
They then met politicians and residents from the town and were given a tour of the area including a visit to Plassenburg Castle which sits above the town.
Provost Todd said: “We had an incredible weekend in Kulmbach and received the warmest of welcomes from our twin town hosts
It was great to see the original signatures from the twinning agreement in the Golden Book and to remember the special association that Kilmarnock and Kulmbach shares
“Everyone we met in Kulmbach spoke about how they want to keep the twinning connection alive in the future and this special bond of friendship is something that we would certainly wish to continue as well.”
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By Doug Gollan
which specializes in connecting Europe’s many small airports
said it has added three new Cirrus SR22 aircraft to its fleet
the company says the new additions are part of its long-term strategy to provide a wider offering in Europe
“Fly Aeolus offers its regional customers new travel opportunities and lowers the cost of air taxi flights from the region
in this case especially in the Ruhrgebiet area
but also throughout North Rhine-Westphalia.”
Fly Aeolus will service customers in the north of Lower Saxony
it said prices will be reduced there as well as across Schleswig-Holstein and Mecklenburg-Western Pomerania
The new aircraft based in Kulmbach reduces the cost of flights for customers in Northern Bavaria
Fly Aeolus offers three membership options ranging from 10,000 euros for its Pre-paid Personal membership to an Elite membership priced at 50,000 euros
Fly Aeolus has been a leader in taxi flights as a cost-effective way to save travel time
The Cirrus SR22 is a four-seat single-engine aircraft built by Cirrus Aircraft in Duluth
the Cirrus SR22 is equipped with a parachute system for the entire aircraft
This safety system has contributed to the sales success of this aircraft
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▪ The aim of the proceedings is to further strengthen the Group's fundamentally positive positioning in the market and to make the company in question fit for the future - self-administration is also being examined as a suitable restructuring option for other companies; foreign companies not included in the restructuring process
▪ Company draws up restructuring plan - experienced Schultze & Braun team led by restructuring expert Dr
Jürgen Erbe advises and supports management
▪ Business operations and production to be continued in full - wages and salaries of around 520 Gienanth GmbH employees to be secured via employment agency
Eisenberg (Pfalz)/Schwandorf/Kulmbach/Chemnitz
a core company of the Gienanth Foundry Group
filed an application for debtor-in-possession restructuring proceedings with the Kaiserslautern Local Court on November 27
This is Gienanth's response to the recent increase in financial burdens on the entire group of companies
The company is currently examining whether self-administration is also a suitable restructuring option for other companies
This review includes the companies Gienanth Group GmbH
Gienanth Sales GmbH and Gienanth Verwaltungs GmbH (all Eisenberg)
Fronberg Guss GmbH (Schwandorf) and Gienanth Zaigler MBA GmbH (Kulmbach)
Other Group companies in Austria and the Czech Republic are not and will not be part of the restructuring proceedings
The aim of the proceedings at Gienanth is to make the Group fit for the future and to further strengthen its fundamentally positive positioning in the market
Business operations at the headquarters in Eisenberg are to be continued in full following the Kaiserslautern Local Court's decision on the application
"The proceedings should provide us and our business partners with the necessary security and reliability
Our customers know us as a reliable partner at their side who is committed to the highest quality
It is precisely this commitment to ourselves that we want to manifest with the restructuring process of our central operating company," says Torsten Stein
The Group's approximately 1000 employees have already been informed of the proceedings
The wages and salaries of the approximately 520 employees of Gienanth GmbH are to be covered by the employment agency up to and including the end of January 2024
Gienanth will then resume paying the employees' wages and salaries
Despite a very stable foothold in its core markets and positive business development until 2019
the Gienanth Group has suffered financial losses in recent years due to the effects of the geopolitical
The Covid-19 pandemic led to production stoppages worldwide and high absenteeism rates in the workforce
supply chains were severely disrupted and the availability of important individual parts was significantly restricted
"Our customers in the automotive industry in particular had to cut back their production due to the lack of availability of semiconductors and therefore also placed fewer orders with Gienanth," reports Gienanth Managing Director Stephan Vrublovsky
there were considerable additional burdens due to the sharp rise in prices for raw materials and energy
particularly as a result of Russia's war against Ukraine
Gienanth was able to pass these increases on to customers
which put additional pressure on the balance sheet
The sanctions against Russia also meant that the Kulmbach and Schwandorf production sites were no longer able to fulfill larger orders destined for the Russian market
The strategically motivated takeover of the Gienanth site in Chemnitz as part of the transformation from a pure product supplier to a system provider also led to a financial burden for the Group as a whole
"We were well on the way to organizing and integrating the structures and processes in Chemnitz to bring the plant into the black
the major fire in Chemnitz ruined our plans and also brought further burdens for the entire Group due to the loss of production and the loss of company assets
We therefore had to make the difficult decision not to rebuild the site," says Torsten Stein
The restructuring process at the core operating company is intended to give Gienanth the opportunity to respond to the aforementioned challenges in a targeted manner and make the Group fit for the future
"We want to secure the company and as many of our jobs as possible in the long term," says Stephan Vrublovsky
Gienanth will draw up a restructuring plan in the coming months and look for potential investors who are willing and able to provide our group of companies with fresh money and lead it into the future
We will start a targeted search for interested parties in the coming days."
The management of the Gienanth Group will be supported in the restructuring process by an experienced team from the law firm Schultze & Braun
"The planned restructuring procedure under self-administration would enable us to carry out the restructuring within a manageable period of time
Gienanth has already done a lot of the necessary preparatory work in recent months
Gienanth is well established in its markets
has positioned itself strategically in many future-oriented markets and is an essential and indispensable supplier of high-quality castings
This is possible with the right investor," says Dr
About Gienanth: The company headquarters in Eisenberg (Palatinate) was founded in 1795 as a hammer mill
the Gienanth Group is a well-established foundry group that specializes in the production and finishing of high-quality iron castings using machine and hand moulding processes
Gienanth offers its customers ready-to-install product solutions made of cast iron for the mobility and mechanical engineering industries as well as decentralized energy supply with unit weights of up to 15 tons
include cast parts for cars and commercial vehicles
agricultural and construction machinery and railroad technology
as well as cylinder crankcases and add-on parts for large engines and mechanical engineering components
the group of companies generates a turnover of around 300 million euros per year
Self-administration: Restructuring under self-administration is a procedure under insolvency law that the company can carry out under its own management
the management remains fully capable of acting and can act without restriction
It is supervised by a trustee appointed by the court
The aim of self-administration is to restructure the company
The management is advised and supported by a team of recognized restructuring experts
this is a team from Schultze & Braun comprising the lawyers Dr
Jürgen Erbe (general representative for all companies in self-administration)
Dirk Pehl (all restructuring lawyers and also general representatives for individual group companies in self-administration) and Alexander von Saenger (restructuring employment law)
the consulting firm Roland Berger with a team led by Mathias Heller and Marco Horstmann and the law firm Baker McKenzie with the lawyers Joachim Ponseck
Swierczok and Tim Hosgör have already been supporting the group of companies for the past few weeks
I would like to receive the bi-weekly Foundry-Planet newsletter with all latest news
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Metrics details
The hepatitis B virus (HBV) has been described as stealth virus subverting immune responses initially upon infection
Impaired toll-like receptor signaling by the HBV surface antigen (HBsAg) attenuates immune responses to facilitate chronic infection
This implies that HBV replication may trigger host innate immune responses in the absence of HBsAg
using highly replicative transgenic mouse models
An HBV replication-dependent expression of antiviral genes was exclusively induced in HBsAg-deficient mice
These interferon responses attributed to toll-like receptor 3 (TLR3)-activated Kupffer and liver sinusoidal endothelial cells and further controlled the HBV genome replication
activation of TLR3 with exogenous ligands indicated additional HBs-independent immune evasion events
Our data demonstrate that in the absence of HBsAg
hepatic HBV replication leads to Tlr3-dependent interferon responses in non-parenchymal liver cells
We hypothesize that HBsAg is a major HBV-mediated evasion mechanism controlling endogenous antiviral responses in the liver
Eradication of HBsAg as a therapeutic goal might facilitate the induction of endogenous antiviral immune responses in patients chronically infected with HBV
Aim of the present study was to characterize HBV-mediated antiviral innate immune responses in vivo
which were detectable in a highly replicative HBV transgenic mouse model that lacks the small HBsAg
The comparison with an HBsAg-recovered mouse strain should give insights into the role of the HBsAg in immune induction and evasion
One future therapeutic goal might be the complete eradication of HBsAg
thereby facilitating the induction of endogenous antiviral immune responses against HBV
Hepatic interferon responses can be detected in HBV-s-mut but not HBV-s-rec mice
Two-month-old transgenic HBV mice (HBV-s-mut
HBV-s-rec) and wild type littermates (WT) and were put to death
RNA from liver tissue was extracted and changes in gene expression of Ifnb1
Il10 (B) were determined by quantitative RT-PCR
Copy numbers were normalized to 100,000 copies of GAPDH (mean values ± SEM)
Application of HBV-specific siRNA efficiently suppresses HBV replication in vivo.
HBsAg-deficient transgenic HBV mice exhibit HBV replication-dependent interferon responses
Two-month-old transgenic HBV (HBV-s-mut) mice or HBV-negative littermates (WT) were given 200 μl of small interfering RNA (siRNA) (4 μg/g body weight) via tail vein injection
RNA was extracted from liver tissue and changes in gene expression of Ifnb1 (A)
Isg15 (B) and Ifit1 (C) were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR)
Copy numbers were normalized to 100,000 copies Gapdh (mean ± SEM)
which showed basal expression of these genes
PMHs isolated from HBV-s-mut animals did not significantly respond to either HBV replication or the endogenous Ifnb1 expressed by the neighboring NPCs
HBV-induced interferon responses are mediated by F4/80+ cells (KCs) and liver sinusoidal endothelial cells (LSECs)
LSECs and a remaining cell fraction were isolated from two-month-old transgenic HBV (HBV-s-mut) mice and from HBV-negative littermates (WT)
RNA was extracted; gene expression of Ifnb1 (A)
Isg15 (B) and Ifit1 (C) was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR)
Copy numbers were normalized to 100,000 copies of Gapdh (mean ± SEM)
Tlr3 is consistently activated in transgenic HBV-s-mut mice and thereby controls HBV replication
Transgenic HBV (HBV-s-mut) mice were crossbred with Toll-like receptor 3-deficient (Tlr3−/−) mice
Two-month-old HBV-negative littermates (WT)
HBV-s-mut mice and HBV-s-mut/Tlr3−/− mice were put to death
Tlr3 (G) and HBV mRNA expression (D) were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR)
DNA was extracted from liver tissue and changes in HBV DNA were quantified by PCR (E)
HBcAg was detected by western blot analysis and densitometric analysis was performed (F)
n = 4 (E,G) and n = 3 (F) animals; *p < 0.05
Activation of TLR3 by Poly(I:C) in HBV-s-mut mice is suppressed but still effective in vivo
Two-month-old male transgenic HBV (HBV-s-mut) mice and their wild type (WT) littermates were given Toll-like receptor 3 (Tlr3) ligand polyinosinic-polycytidylic acid (Poly[I:C]; 4 μg/g body weight) via tail vein injection
Mice were put to death 6 h or 24 h after injection
RNA was extracted and changes in gene expression of Ifnb1 (A)
Isg15 (B) and HBV (C) were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR)
DNA was extracted from liver tissue and changes in HBV DNA were quantified by PCR (D)
HBcAg was detected by western blot analysis and densitometric analysis was performed (E)
Activation of TLR3 by Poly(I:C) in HBV-s-mut-derived primary hepatocytes is suppressed but still effective
Primary murine hepatocytes (PMHs) were isolated from two-month-old male HBV-s-mut mice and their wild type littermates (WT)
cultured and stimulated with 25 μg/ml of Tlr3 ligand Poly(I:C) for 6 h
however the underling mechanisms remained unclear
abrogation of HBV-induced interferon responses was observed in Tlr3-deficient HBV-s-mut mice
indicating the involvement of Tlr3 in antiviral responses against HBV
the absence of Tlr3 in this system provoked an increase in the hepatic levels of HBV mRNA
indicating an enhanced HBV replication in these mice
Although HBV-s-mut mice-derived PMHs did not show significant induction of Ifnb1 or interferon stimulated gene expression
in liver tissue viral replication was controlled by constitutive Tlr3 activation
The NPCs continuously produced antiviral mediators
These contradictory findings might be explained by either local restrictions of antiviral immune induction and immune tolerance or indirect action of these antiviral mediators
We here conclude that therapeutic suppression of HBsAg in CHB patients may overcome immune evasion by rebooting the antiviral innate immune responses
This hypothesis needs to be proven in future studies
where neutralization of serum HBsAg in the HBV-s-rec model might reactivate endogenous immune responses
This led us to hypothesize that patients might be able to mount an efficient antiviral immune response against HBV once the HBsAg could be eliminated from the blood circulation
Polyinosinic-polycytidylic acid (Poly[I:C]) was obtained from Invivogen (Toulouse
fed ad libidum and received humane care according to the criteria outlined in the Guide for the Care and Use of Laboratory Animals prepared by the National Academy of Sciences and published by the National Institutes of Health
The animal study design was approved by the local committee (Landesamt für Natur
Primary murine hepatocytes (PMHs), were prepared by liberase perfusion as described previously12
PMHs had been separated by low-speed centrifugation steps (50 × g for 10 min at 4 °C)
The supernatant containing the non-parenchymal liver cells (NPCs) was centrifuged at 300 × g for 10 min at 4 °C
NPCs were either directly lysed for RNA extraction or Kupffer cells (KCs) and liver sinusoidal endothelial cells (LSECs) were further separated using F4/80- and CD146-directed MicroBeads (Miltenyi Biotec
KCs and LSECs were lysed for RNA extraction and quantitative reverse transcription polymerase chain reaction (qRT-PCR)
PMHs were directly lysed or seeded into collagen I–coated culture plates for 24 h and stimulated with Poly(I:C) (25 μg/ml) for additional 6 h
Western blot analysis was performed as previously described43
The following antibodies were used: anti-HBV core (HBcAg) (16)
Signal intensities were measured with FUSION FX7 Advanced system and FUSION-CAPT Advanced software (Vilber Lourmat
Hepatic HBV DNA was quantified by PCR using the Platinum SYBR Green Kit (Invitrogen/Life technologies
Germany) with the sense primer 5′-TGC CTC ATC TTC TTR TTG GTT CT-3′ and the antisense primer 5′-CCC CAA WAC CAK ATC ATC CAT ATA-3′
The primer contained wobble bases (r = purine (A,G)
w = weak binding (A,T) and k = keto (G,T))
Serum analyses of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were performed with the Spotchem™II analyzer and Spotchem™II reagent strips (liver-panel1; Arkray
Japan) according to the manufacturer’s instructions
HBeAg and HBsAg were detected in serum samples of HBV transgenic mice with the chemiluminescent microparticle immunoassay (CMIA) ARCHITECT HBeAg and HBsAG assay with the ARCHITECT immunoassay analyzer (Abbott Diagnostics
according to the manufacturer’s instructions
Murine liver tissue samples were fixed in 4.5% Histofix (Carl-Roth
Sections were cut for immunohistochemistry staining with rabbit polyclonal anti-HBV core antibody (Dako
Histologic findings were visualized with an Axioplan microscope and AxioCam Hrc (Carl Zeiss
Data are expressed as mean ± SEM (standard error of mean)
Differences between two groups were determined with the Wilcoxon test
Statistical significance was set at the level of p < 0.05
Hepatitis B virus genome replication triggers toll-like receptor 3-dependent interferon responses in the absence of hepatitis B surface antigen
Role of Toll-like receptors in liver health and disease
Genomic analysis of the host response to hepatitis B virus infection
Stealth and cunning: hepatitis B and hepatitis C viruses
Impaired TLR3/IFN-beta signaling in monocyte-derived dendritic cells from patients with acute-on-chronic hepatitis B liver failure: relevance to the severity of liver damage
Regulation of Toll-like receptor-2 expression in chronic hepatitis B by the precore protein
HBsAg inhibits TLR9-mediated activation and IFN-alpha production in plasmacytoid dendritic cells
Toll-like receptor signaling inhibits hepatitis B virus replication in vivo
Toll-like receptor-mediated control of HBV replication by nonparenchymal liver cells in mice
Hepatitis B virus polymerase blocks pattern recognition receptor signaling via interaction with DDX3: implications for immune evasion
The hepatitis B virus X protein disrupts innate immunity by downregulating mitochondrial antiviral signaling protein
HBV suppresses toll-like receptor mediated innate immune responses in murine parenchymal and non-parenchymal liver cells
Toll-like receptor-mediated immune responses are attenuated in the presence of high levels of hepatitis B virus surface antigen
Assembly of hepadnaviral virions and subviral particles
Escaping high viral load exhaustion: CD8 cells with altered tetramer binding in chronic hepatitis B virus infection
Chemical modifications on siRNAs avoid Toll-like-receptor-mediated activation of the hepatic immune system in vivo and in vitro
Identification of proteins that mediate the pro-viral functions of the interferon stimulated gene 15 in hepatitis C virus replication
Mouse Models of Hepatitis B Virus Infection Comprising Host-Virus Immunologic Interactions
Temporal analysis of early immune responses in patients with acute hepatitis B virus infection
Circulating hepatitis B virus nucleic acids in chronic infection : representation of differently polyadenylated viral transcripts during progression to nonreplicative stages
Serum hepatitis B virus RNA levels as an early predictor of hepatitis B envelope antigen seroconversion during treatment with polymerase inhibitors
T cells expressing a chimeric antigen receptor that binds hepatitis B virus envelope proteins control virus replication in mice
Noncytolytic control of viral infections by the innate and adaptive immune response
IFNgamma expression inhibits LHBs storage disease and ground glass hepatocyte appearance
but exacerbates inflammation and apoptosis in HBV surface protein-accumulating transgenic livers
Recombinant duck interferon gamma inhibits duck hepatitis B virus replication in primary hepatocytes
Interleukin-18 inhibits hepatitis B virus replication in the livers of transgenic mice
IL-12 promotes HBV-specific central memory CD8+ T cell responses by PBMCs from chronic hepatitis B virus carriers
Interleukin-12 inhibits hepatitis B virus replication in transgenic mice
but interleukin-6 controls early gene expression in hepatitis B virus infection
Tumor necrosis factor activates a conserved innate antiviral response to hepatitis B virus that destabilizes nucleocapsids and reduces nuclear viral DNA
Tumor necrosis factor alpha inhibition of hepatitis B virus replication involves disruption of capsid Integrity through activation of NF-kappaB
New insights into how HBV manipulates the innate immune response to establish acute and persistent infection
Reduced Toll-like receptor 3 expression in chronic hepatitis B patients and its restoration by interferon therapy
TLR3 plays significant roles against hepatitis B virus
Innate immune responses in hepatitis B virus (HBV) infection
Poly(I:C) treatment leads to interferon-dependent clearance of hepatitis B virus in a hydrodynamic injection mouse model
Longitudinal analysis of CD8+ T cells specific for structural and nonstructural hepatitis B virus proteins in patients with chronic hepatitis B: implications for immunotherapy
Chemical modification of siRNAs for in vivo use
Transgenic mice replicating hepatitis B virus but lacking expression of the major HBsAg
Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice
Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3
The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments
Differential responses to IFN-alpha subtypes in human T cells and dendritic cells
TLRs antiviral effect on hepatitis B virus in HepG2 cells
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Sabrina Driftmann and Thekla Kemper for excellent technical support
This work was partially supported by the Deutsche Forschungsgemeinschaft (TRR60)
LMI and MJJ performed this work as employees of Roche Kulmbach GmbH
HV is head of the Axolabs GmbH Kulmbach (MH
Department of Gastroenterology and Hepatology
University Hospital at the University Duisburg-Essen
Joerg Friedrich Schlaak & Ruth Broering
Huazhong University of Science and Technology
Matthias Johannes John & Hans-Peter Vornlocher
Jochen Deckert & Hans-Peter Vornlocher
University Hospital at the University of Ulm
Conceptualization of the study was done by C.I.R.
Methodology and experimental setup was performed by C.I.R.
Resources and materials were produced and provided by M.H.
The authors declare no competing financial interests
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In a draft of the dedication of his Four Books on Human Proportion, Dürer wrote that de’ Barbari was born in Venice. Other sources echo this, but there is no firm evidence. “Walch”, after all, is probably just a variant of “welsch”, which simply meant “Italian”. It seems that Barbari may have been working in Venice from about 1480. He was certainly still there in the late 1490s, as evidenced by his massive woodcut aerial view of the city dated 1500.
De’ Barbari did not simply export Italian styles to Germany. He embellished northern motifs with an Italian idiom. Above all, he arrived in Germany at a time when the both emperor and the leading princes of the Holy Roman Empire were keen to experiment with new forms of cultural politics. De’ Barbari’s true significance, Böckem concludes, lies in the way that he engaged in a genuine two-way dialogue with German artists.
• Joachim Whaley is a professor of German history and thought at the University of Cambridge and a fellow of the British Academy. He is the author of Germany and the Holy Roman Empire 1493-1806 (two volumes, Oxford University Press, 2012)
Jacopo de’ Barbari: Künstlerschaft und Hofkultur um 1500
Böhlau Verlag, 515pp., €74.95 (hb). In German only
his remarkable journal and drawings go on show in Aachen before travelling to London
news10 January 2020Possible Dürer discovered above souvenir shop in Vienna's cathedral Experts believe underdrawing in St Stephen’s is first evidence that the master worked in the Austrian capital
Roche’s decision to abandon RNAi drug research as part of extensive cuts across its business has investors worried that enthusiasm for the gene-silencing technique is waning
After investing more than $500 million in less than three years to assemble an RNAi research effort
Roche is shutting down RNAi R&D at sites in Kulmbach
Mass.-based Alnylam was the hardest hit by the news
Roche handed Alnylam $331 million in a broad research pact covering RNAi drugs
The deal included the purchase of the Kulmbach site
which became Roche’s “center of excellence” for RNAi research
Alnylam received a nice chunk of funding each year from Roche
it reported $57 million in research revenues from the collaboration
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Roche’s decision to abandon RNAi drug research as part of extensive cuts across its business has investors worried that enthusiasm for the gene-silencing technique is waning. Shares of Alnylam and Tekmira
After investing more than $500 million in less than three years to assemble an RNAi research effort, Roche is shutting down RNAi R&D at sites in Kulmbach, Germany; Madison, Wis.; and Nutley, N.J. (C&EN, Nov. 22, page 6)
It also would have enjoyed royalties on any drug that reached the market
For Alnylam, the setback comes just weeks after Novartis declined to opt in to a technology licensing clause in a five-year research pact
Novartis’ decision cost Alnylam a $100 million payment
and the biotech firm subsequently said it would cut 25–30% of its employees
loses out on a licensing deal signed just last year
Roche paid $18.4 million to formulate its RNAi products using Tekmira’s lipid nanoparticle delivery technology
Roche expected the pact would enable it to put its first RNAi-based drug into human studies by the end of this year
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industry observers are not convinced that the drug industry has given up on the technology
“We believe this was a move that had mainly to do with internal resource allocation decisions and not a reflection on the progress made by Roche or their confidence in the space,” says Simos Simeonidis
the company made cuts in technology areas where spending was high but commercial products were still years away
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Copyright © 2025 American Chemical Society
The city cycling campaign is once again calling on people to cycle as much as possible in their everyday life and leisure time for three weeks
Tirschenreuth and the city of Hof are continuing their cooperation in the CITY CYCLING campaign
The district of Kulmbach is a new addition to the cooperation in 2025
The joint 21-day campaign period starts on June 29 and ends on July 19
The renewed cooperation is due to the strong response from the population
with some new participation records and impressive mileage in the region
"CITY CYCLING has established itself as a real success story
I am all the more pleased that we are once again sending a strong signal for sustainable mobility together with our neighboring districts and the city of Hof," emphasize the district administrators from Hof
Roland Grillmeier and Peter Berek as well as the mayor of Hof Eva Döhla
"I am sure that we will be able to surpass last year's impressive results and I look forward to everyone taking part again or for the first time."
the CITY CYCLING campaign is once again calling on people to leave their cars at home for three weeks and cycle as many journeys as possible in their everyday life and leisure time
In addition to contributing to climate protection and promoting personal health
the playful competition between teams and municipalities provides additional motivation
High-quality prizes from regional sponsors await the most active participants
Registration is now open. Further information and registration details can be found here: www.stadtradeln.de
If you have any questions, please contactJulia Baumgärtner, tel. 09281 / 815 - 1564, julia.baumgaertner(at)stadt-hof.de.
Firefighters in the German city of Dortmund needed to use a giant water bath to bring this EV blaze under control. — dpa
Supported Characters→ alphanumeric→ space→ dash
Operators→ &→ |→ ( … )
Example→ (hybrid | electric) & suv & perodua to match arictles of perodua suv with either hybrid or electric engine
Bank manager Juergen Schaller never expected to end up getting a trucker’s licence and driving 20,000 kilometres per year.
But as brick-and-mortar branches vanish from the rolling Franconia region of northern Bavaria, the neatly dressed savings bank executive jumps behind the wheel four days a week to bring mobile services -- including cash machine and consultation room -- to tiny countryside villages.
The switch from desk to dashboard has enabled Schaller “to do something else while staying in touch with the customers”, he said.
High-street banks are increasingly being forced to shutter branches, as more and more customers go online, rural populations shrink and low interest rates eat into profits.
As a result, banks such as the public-sector Sparkassen, where Schaller is a branch manager, are having to rethink their business models.
In Schaller’s Kronach-Kulmbach district alone, tucked away in the southeast corner of Germany, six branches sporting the red “S” logo of the widely popular savings banks group closed their doors last year.
A similar trend is seen across the country as a whole: nationwide, the number of physical bank branches has plunged by a quarter over the past 15 years to 35 per 100,000 people, according to a study by public investment bank KfW.
The European average is 37 per 100,000, with Spaniards the most spoiled for choice with 67.
Steffen Haberzettl, the sales director for the Kronach-Kulmbach Sparkasse, said it was primarily local businesses and older people who had not embraced online banking who were taking advantage of the mobile branch, which first set off on its rounds in 2015.
Haberzettl estimated that around 20 people visited the bank at each stop, equivalent to 12,000 customer contacts a year -- a tiny number compared with some 8,800 online banking logins per day.
But “we invested in this service for our clients knowing that it wouldn’t make enough money to pay for itself”, he said. Local politicians who sit on the Sparkasse board were reluctant to plunge their constituents into a bankless wilderness as the number of closures mount.
So, they opted to hit the road instead in one of Germany’s 66 itinerant branches.
In the bank’s trailer, 70-something Maria Neubauer is happy to wait for an appointment with Schaller in his tiny office during his 90-minute stop opposite the church in the slate-tiled village of Tschirn.
“The Sparkasse bus is great for making transfers, or doing anything you need,” she said.
“We’re happy, especially those of us who don’t have a car” to visit a branch further away, another villager Maria Greiner said as she printed an account statement from a nearby machine.
Other customers were busy withdrawing cash on the chilly town square from the ATM embedded in the flank of the trailer.
Schaller makes his rounds to small villages such as this from Monday to Thursday, keeping Fridays free to do maintenance work on the red and white truck and trailer.
He has no access to the cash on board, and so far he’s had no run-ins with would-be bankrobbers.
Banking sector experts predict that the Europe-wide trend towards fewer bank branches will continue apace.
“The speed at which it will happen is hard to predict, and will depend above all on how the banks manage to keep branches relevant as a channel for their customers,” said Thomas Schnarr of consultancy Oliver Wyman.
Nevertheless, “human relationships remain fundamental. Especially complicated questions require personalized advice for retail clients and businesses”, his colleague Alexander Peitsch said.
For his part, Juergen Schaller said he is not qualified to provide such specialist counselling to his clients, many of whom know him by name.
Instead, he passes on individual requests for loans or investments to a colleague sitting in one of the Sparkasse’s brick-and-mortar branches.
+ 2 PhotosDriver fined 75 times the going rate for speed camera offenceThe driver was caught clocked at 81km/h in a 70km/h zone by one of the town’s speed cameras, a low range offence that would normally attract a fine of just €20 (AUD$32).
But, closer inspection of the photo captured by the speed camera soon had Oberfranken Police revising its penalty.
The driver of the BMW can be seen giving the speed camera an internationally recognised gesture of ill-will, aka ‘flipping the bird’.
Revoking his initial €20 penalty notice, the driver was instead summoned to the Kulmbach district court, charged with ‘being insulting in road traffic’.
Not only was the driver handed with a revised €1500 fine, but he’ll also spend time catching public transport after the court suspended his license for one month.
The lesson here? Mind your manners when driving.
Rob Margeit is an award-winning Australian motoring journalist and editor who has been writing about cars and motorsport for over 25 years. A former editor of Australian Auto Action, Rob’s work has also appeared in the Sydney Morning Herald, The Age, Wheels, Motor Magazine, Street Machine and Top Gear Australia. Rob’s current rides include a 1996 Mercedes-Benz E-Class and a 2000 Honda HR-V Sport.
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