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2025 at 12:26 PM EDTBookmarkSaveGold is on pace to record its first back-to-back weekly loss this year as haven appeal eased on strong US jobs data and progress in international trade talks
Economic data released Friday showed buoyant hiring in April
providing evidence of resilience in an American economy increasingly beset by trade pressures
The strong numbers may keep the Federal Reserve on hold longer
with traders pulling back on bets for Fed rate cuts and pricing in the next reduction in July
itb.ac.id - Institut Teknologi Bandung (ITB) once again hosted the annual PARE Spring School 2024 event
This activity is part of a joint collaboration among the countries in the PARE (Populations
and Environments) consortium for sustainable resource management
include Hokkaido University (Japan); Kasetsart University
and Sirindhorn International Institute of Technology (Thailand); as well as Institut Pertanian Bogor
There were various discussions held at both ITB Jatinangor Campus as well as ITB Ganesha Campus covering topics such as integrated water resource management
sustainability concepts and sustainable development goals
geographical information systems and spatial analysis
and geological factors in water management
Speakers for this event included lecturers from ITB
participants visited various locations for field study visits
The opening of PARE Spring School 2024 took place at KOICA Multipurpose Hall
ITB’s Vice Rector for Academic and Student Affairs
delivered a welcoming speech to the participants
He said that international cooperation is important in maintaining resource sustainability and expressed appreciation for the organizing committee's dedication to run the event
PARE Spring School 2024 at ITB is not merely an exchange of knowledge but also a significant step in strengthening cross-country collaboration networks
It is hoped that this collaboration will have a positive impact on efforts in managing sustainable resources in the upcoming future
Reporter: Ayesha Lativa Mafaza (Post Harvest Technology
2021)Translator: Kezia HosanaEditor: Sherina Wijaya (Geological Engineering
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a European market leader in vehicle glass repair and replacement (VGRR) services
has signed an agreement to acquire 51% of the French company 123 Pare-Brise
a leading independent VGRR specialist in France
Founded in 2020 and headquartered in Marquette-lez-Lille and Bourgoin-Jallieu
123 Pare-Brise operates a network of 129 owned workshops across France
The acquisition provides Cary Group with a strategic entry into the French VGRR market
which has significant size and growth potential
123 Pare-Brise operates with a fully integrated network of workshops and a business model that is focused on direct-to-consumer sales
The company employs just under 900 employees with total sales of approximately 100 MEUR
"The acquisition of 123 Pare-Brise is a significant milestone for Cary Group as we continue to expand our presence in Europe
replacement and calibration of vehicle glass is an important part of the European market. The acquisition of 123 Pare-Brise is a natural step in our consolidation journey and strengthens Cary Group’s position in Europe
We are impressed by the strong growth of the company
the exceptional quality of their services and workshop network and we look forward to working closely with their talented team"
"We are excited to join forces with Cary Group
a company that shares our commitment to quality and customer satisfaction
This partnership will enable us to leverage Cary Group's resources and expertise to further enhance our services and expand our reach in the French market"
The current management team of 123 Pare-Brise
will remain in place to ensure continuity and drive the company's growth post-acquisition
123 Pare-Brise is a French brand specializing in the repair and replacement of all types of auto glass
it has established itself as a benchmark player in France
123 Pare-Brise is based in the Hauts-de-France and Auvergne Rhône Alpe regions of France and relies on a branch network to guarantee consistent quality of service in all its centres
the company will have 130 centres by early 2025 and has a clear ambition: to become the leading independent integrated network in France
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Precious MetalsAll Metal Quotes
Still, futures contracts that settle to the Fed's policy rate continued to point to a start to Fed rate cuts in June, with a total of four quarter-point reductions likely, bringing the rate to the 3.25%-3.5% range by year-end.Reporting by Ann Saphir; Editing by Andrew Heavens
but slipped within the central bank's target range
The S&P/ASX 200 index XJO gained 0.2%
The key trimmed mean measure of core inflation increased by 0.7% in the quarter
taking it back into the Reserve Bank of Australia's 2% to 3% target band for the first time since late 2021
Swaps imply that the chances of a quarter point cut from the RBA in May are over 96%
Rate-sensitive financials XFJ led the gains
adding 0.5% and rising for the tenth straight session
Three of the "Big Four" banks advanced between 0.5% and 1.2%
Technology stocks XXIJ rose 0.8%
tracking Wall Street's overnight gains
On the other hand, energy stocks XEJ dipped 0.9%
President Donald Trump's erratic tariffs raised concerns about weakening global economic growth and fuel demand
Origin Energy ORG
Australia's second-largest power producer
fell 1.6% after reporting a 10% sequential drop in revenue in the third quarter from its stake in the Australia Pacific LNG project (APLNG)
Among individual stocks, Coles Group COL
fell 1% despite posting a 3.4% rise in third-quarter revenue
New Zealand's benchmark S&P/NZX 50 index NZ50G was down 0.3% at 11,987.82 points.
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2025 at 5:22 AM EDTBookmarkSaveTakeaways NEWIndonesian stocks trimmed losses after the country’s new sovereign wealth fund said two former presidents will be advisors
easing market concerns over its leadership
The benchmark Jakarta Composite Index closed 1.6% lower Monday
The rupiah lost about 0.3% against the dollar
putting the currency closer to its weakest level since 1998
Metrics details
Multidrug-resistant Neisseria gonorrhoeae is a pathogenic bacterium that poses a public health concern
we aimed to elucidate the mode of action of the conventional antibiotic novobiocin
which has been selected as a leading compound for novel antigonococcal drugs
Unlike other previously studied bacteria strains
gonorrhoeae strains have a mutation in the parE gene encoding DNA topoisomerase IV
strongly implying that the primary target of novobiocin is DNA topoisomerase IV and not DNA gyrase
The construction of genetically modified strains and structural biology analysis in silico suggest that this target discrepancy is from variations in the amino acid sequences in GyrB (Ile 78 in Escherichia coli
This finding contributes to the development of drugs that target both GyrB and ParE enzymes to a similar extent
Prices may be subject to local taxes which are calculated during checkout
World Health Organization (WHO). Global health sector strategy on sexually transmitted infections 2016–2021: toward ending STIs. Geneva: WHO; 2016. Available from: https://www.who.int/publications/i/item/WHO-RHR-16.09
Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century: past
WHO Guidelines for the Treatment of Neisseria gonorrhoeae. 2016; https://apps.who.int/iris/bitstream/handle/10665/246114/9789241549691-eng.pdf
WHO global antimicrobial resistance surveillance for Neisseria gonorrhoeae 2017–18: a retrospective observational study
Gonorrhoea treatment failure caused by a Neisseria gonorrhoeae strain with combined ceftriaxone and high-level azithromycin resistance
Determination that ALBAMYCIN (novobiocin sodium) capsule
was withdrawn from sale for reasons of safety or effectiveness
The interaction between coumarin drugs and DNA gyrase
DNA uptake sequence-mediated enhancement of transformation in Neisseria gonorrhoeae is strain dependent
Molecular engineering of a PheS counterselection marker for improved operating efficiency in Escherichia coli
Counterselection employing mutated pheS for markerless genetic deletion in Bacteroides species
Highly effective markerless genetic manipulation of Streptococcus suis using a mutated PheS-based counterselectable marker
GNINA 1.0: molecular docking with deep learning
Autodock vina: improving the speed and accuracy of docking with a new scoring function
Lessons learned in empirical scoring with smina from the csar 2011 benchmarking exercise
Active-site residues of Escherichia coli DNA gyrase required in coupling ATP hydrolysis to DNA supercoiling and amino acid substitutions leading to novobiocin resistance
Accumulation of mutations in both gyrB and parE genes is associated with high-level resistance to novobiocin in Staphylococcus aureus
Evaluation of gyrase B as a drug target in Mycobacterium tuberculosis
Multidrug resistance in Neisseria gonorrhoeae: identification of functionally important residues in the MtrD Efflux Protein
Crystal structures of Escherichia coli topoisomerase IV ParE subunit (24 and 43 kilodaltons): a single residue dictates differences in novobiocin potency against topoisomerase IV and DNA gyrase
Novel dual-targeting benzimidazole urea inhibitors of DNA gyrase and topoisomerase IV possessing potent antibacterial activity: intelligent design and evolution through the judicious use of structure-guided design and structure-activity relationships
Download references
We thank Ms. Yuko Shibuya and Ms. Sayaka Takahashi for their technical support for genetic modification study. We also thank Anahid Pinchis from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript
Institute of Microbial Chemistry (BIKAKEN)
The authors declare no competing interests
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations
a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law
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DOI: https://doi.org/10.1038/s41429-024-00797-1
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Mumbai-based premium ceiling, wall, and facade panel manufacturer, PARÉ Innovations, has raised USD 8.5 million (INR 72.9 crore) in its first funding round from Advenza Global Limited, reaching a post-money valuation of INR 540 crore. The capital will be used to drive aggressive expansion in domestic and international markets, as the company aims for an INR 1,000 crore turnover in the next four years.
"This funding marks a significant step towards realising our vision of making PARÉ a global leader in the interior products space," said Bipin Parmar, Managing Director of PARÉ Innovations. "We're excited to accelerate our growth and expansion plans, and look forward to creating exceptional spaces."
Founded in 2020 by Bipin Parmar and his son, Parth Parmar, PARÉ Innovations has quickly emerged as a prominent player in the building materials sector. The company specialises in durable, waterproof, maintenance-free ceiling, wall, and facade panels that offer a real wood feel and customisable designs—serving applications in homes, offices, and commercial establishments.
Currently present in 13 countries, PARÉ is now targeting expansion to over 50 global markets. Domestically, the company is focusing on deepening its reach in India's B and C-class cities, tapping into the country's booming real estate and interior décor demand.
With a keen eye on innovation, quality, and craftsmanship, PARÉ is also exploring strategic growth options, including a potential IPO, to further accelerate its upward trajectory. Backed by over three decades of promoter experience, the company claims to have completed numerous world-class projects globally.
By blending Indian manufacturing excellence with global design trends, PARÉ Innovations continues to redefine interior solutions, setting new benchmarks in both aesthetics and performance.
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Article contentConsumers companies are seeing early signs of demand pick up among the 400-million strong group of urban shoppers in India
providing a buffer to any volatility that might be unleashed by the country’s trade negotiations with the US
1 consumer goods maker that’s considered a bellwether for the sector
expects demand conditions to gradually improve boosted by macroeconomic tailwinds
with growth in April to September period exceeding the levels in the preceding six months
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The Indian unit of Unilever Plc also saw lesser “downtrading” this quarter — a practice when buyers start pivoting to cheaper or low-value packs — signaling a recovery in purchasing patterns, its Chief Financial Officer Ritesh Tiwari told reporters last week.
A day later, Reliance Retail, part of Mukesh Ambani’s energy-to-entertainment conglomerate, posted a 29% jump in quarterly profit, boosted in part by Maha Kumbh Mela, world’s largest religious gathering earlier this year.
The green shoots being flagged in India’s consumption story signal a yearlong malaise could be lifting. A strong domestic market will provide some respite to Indian firms as US President Donald Trump’s tariffs threaten global recession. China too is encouraging its firms to focus on the massive home market amid headwinds overseas.
“The worst of the domestic cyclical slowdown seems behind,” said Teresa John, an economist with Nirmal Bang Institutional Equities. Indian government and central bank-led growth boosters “could shield the economy from tariffs,” she said.
About $12 billion of tax sops announced in February, a rate cut this month with signs of more to come, subdued inflation and forecast of an ample monsoon are expected to perk up India’s buyers.
Broader economic factors “should augur well for discretionary income” in both rural and urban regions, Hindustan Unilever’s Tiwari said. He doesn’t expect any new headwinds impacting demand.
Macrotech Developers Ltd.’s Managing Director Abhishek Lodha said last week that he expects a lift to purchasing power for the mid-income housing segment, while Shriram Finance Ltd. — which lends for purchases of cars and bikes — sees demand for loans in urban India to recover in the coming quarters.
Urban demand is showing steady improvement, supported by rising discretionary spending, the finance ministry said in its monthly economic review Tuesday. But risks from ongoing global trade disruptions “warrant close monitoring,” it added.
UltraTech Cement Ltd., India’s biggest maker of this key construction material, expects a strong volumes growth on back of housing and infrastructure demand.
Realtor DLF Ltd. is expecting sales in its high-end shopping complexes to grow as much as 10% in the year ending March 2026 after slightly underwhelming sales a year earlier, Pushpa Bector, senior executive director and business head at DLF Retail, said in an interview this month.
The coming quarter will be “critical” for India’s consumption story, said Satish Meena, founder of consumer data firm, Datum Intelligence. “There is expected to be more money with customers” over the next couple months, he said.
While India’s central bank maintains optimism about domestic growth, a top finance ministry official has warned of the ripple effects of US tariffs.
The “first order” hit from US reciprocal tariffs on India, if imposed, could shave off up to 0.5 percentage point off its economic growth, which is “not a huge impact,” India’s Economic Affairs Secretary Ajay Seth said in Washington last week. “But the second order would be important” if the global economy grows less, he said.
“Given global headwinds, exports and private investments are likely to be more impacted relative to consumption,” Nomura’s Sonal Varma told Bloomberg News. “Labor market signals are also mixed, so consumption itself is not out of the woods.”
Some companies also remain cautious. Tata Consumer Products Ltd., the local partner for Starbucks Corp., said on April 23 it slowed the opening of outlets “a bit” due to softness in the economy.
India’s largest carmaker, Maruti Suzuki India Ltd. has forecast a modest 2% growth for the sector in the year through March 2026.
Others, however, are accelerating their growth initiatives anticipating that the trickle down effect of tax sops, rate cuts and bountiful monsoon — it boosts rural purchasing power — will culminate into a shopping spree.
Reliance Retail, after streaming its operations and closing underperforming stores, plans to make a marketing and advertising splash for Shein in India after a low-key relaunch in February.
Ambani’s unit will also further develop its 30-minute delivery format JioMart to muscle into India’s booming quick commerce segment.
Unilever’s India unit is also stepping up investments.
“On macro, the triggers are tending biasing toward positive now,” Rohit Jawa, chief executive officer at Hindustan Unilever, told analysts on Thursday. “We feel this is the time for us to lean in.”
(Updates with India’s finance ministry commentary in the 10-th paragraph.)
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The Republican co-chair of the state Legislature’s committee on audits said new reports tracking diversity
and inclusion efforts in Wisconsin make lawmakers better equipped to pare down that spending
but he admits doing that will be complicated
Republican-ordered audits published last week found that at state agencies and the Universities of Wisconsin
spending on some DEI activities is tied up with other work
The reports are the latest step in pushback from Republicans over programs they see as wasteful
the state’s university system agreed to a freeze on positions related to DEI and has since eliminated some of those jobs
The audits are performed by the nonpartisan Legislative Audit Bureau. Reports on financial monitoring in the K-12 school system, the unemployment insurance program and other areas of state government are also slated to publish this year
Republican state Sen. Eric Wimberger of Oconto is co-chair of the Joint Legislative Audit Committee and serves on the Joint Finance Committee. He joined WPR’s “Wisconsin Today” for a discussion about the DEI audit and his priorities in the biennial budget writing process
This interview was edited for length and clarity
Kate Archer Kent: Republican state lawmakers have pushed for years to end DEI programs
What does this new audit tell you about DEI activities in Wisconsin higher education
Eric Wimberger: No one has really defined it in a holistic manner
a lot of money has been shoved into these activities with no clear purpose
And obviously that’s separate from whether they philosophically should be done to begin with
KAK: What about this audit is actionable to you as a state senator?
EW: It’s really difficult. They’ll hide it in their normal affirmative action policies that have been around since the 70s. So you’ll have people who do those things, but then for a quarter of the time [they] are supposed to do DEI. At least on the non-UW side, this is related to Executive Order 59
The UW system has their own DEI policies with the Board of Regents
But it’s really hard to pin this down because it’s commingled
KAK: UW system President Jay Rothman said the audit numbers are “old and cold,” and that for more than a year
the UW has been taking action to reduce and reorient DEI positions toward individual student success
Is this audit evaluating a previous version of the UW that is not reflective of today
EW: I don’t know if it’s “old and cold,” but the audit does a snapshot in time. Obviously, it’s not a continuing report. So if you recall a couple years back, [there] was the whole debate over the engineering building and the DEI positions there
So I wouldn’t be totally surprised if there’s some inaccuracy because of a continuing effort to comply with that agreement
nor is it easily separated from other human resources best practices
So what does this particular audit illuminate to you
EW: I don’t think that it can’t be separated or figured out
There’s been a deliberate act to commingle it
in that [if] there is no particular DEI plan for a department
but they are sending people on trips and trainings elsewhere
you can figure out how much those things [cost]
they’re taking their normal non-discrimination people — which is great — but then having them work a quarter time on something that isn’t related to non-discrimination
It’s actually a discriminatory policy
“If you work a quarter of your time on that
then we’re just going to count a quarter of your salary as what the value of that is.” But obviously we’re not going to necessarily terminate that person because they’re doing things that you do want them to do
So how you figure that out by reduction of staff naturally
or just having them do the tasks that they used to do prior to this Executive Order 59 is going to be the way to go
KAK: A couple of the audits in progress involve the Department of Public Instruction
One set to release this spring examines how the state education department monitors the financial information of schools
What do you want to learn from this investigation
EW: This one is really crucial to the largest budgetary expense we have
We spend $15 billion — roughly 15 percent of our entire budget — on K-12 education
The catalyst to this is that for two years
Milwaukee Public Schools were not doing their annual required auditing in order to come up with accurate numbers to plug into the school funding formula
So it got to the point where DPI decided to yank $80 million from them
which was 10 percent of their budget.
I think that’s astonishing — a 10 percent cut in their budget and no one bats an eye in the public here
Milwaukee was induced to pass a $200 million referendum on claims that the schools needed the extra money
So they pass the referendum a month later [and] yank the funding for failure to comply with the method that we use to find out what they need
So we’ve got to figure out what DPI is up to in coordinating with or holding school districts to account
to make sure that they’re getting accurate data
and we’re actually giving money to schools in a method that they need
KAK: We’re in the thick of budget writing season
Given the level of uncertainty in the federal government and the cuts to agencies and programs by President Donald Trump and DOGE
how will that affect the next budget of Wisconsin
it’s just going to be block grants administered by the state
We administer a whole lot of federal programming
If there’s some problem that happens — people talk about Medicaid cuts and all that — if that were to actually happen
I think we would certainly take action to make sure nothing bad happens to people in Wisconsin
The biggest problem with the budgeting is the fact that the state Supreme Court changed the rules on how we budget
We would be very content with giving the executive branch $100 million for this or that program
with a caveat that you have to come back to the finance committee with a discernible plan
The Supreme Court said that was a non-delegation issue in the Constitution
and we want to put something specific into the budget
Global law firm White & Case LLP has advised Cary Group
on the acquisition of the French group 123 Pare-Brise
a leading independent vehicle glass repair and replacement specialist in France
The transaction marks Cary Group's entry into the French market
The current management team of 123 Pare-Brise will remain in place to ensure continuity and drive the company's growth post-acquisition
Cary Group is a European market leader in sustainable solutions for the repair and replacement of vehicle glass with a complementary offering in vehicle damage repair
The White & Case team which advised on the transaction was led by partners Guillaume Vitrich (Paris) and Johan Thiman (Stockholm) and included partners Estelle Philippi
Kami Haeri and Jérémie Marthan (all Paris) and associates Nicolas Alfonsi
Camille Coulon and Minh Tu Vu Ngoc (all Paris)
Prior results do not guarantee a similar outcome
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UGM hosted Population-Activities-Resources-Environment (PARE) Spring School 2019 from 15-25 February
As many as 29 students came from five universities in Japan
and Indonesia which are Hokkaido University
For 11 days they attended workshops to learn and discuss crucial issues related to environment
in his remarks appreciated the students joining the PARE Spring School 2019
Panut said it was an honour for UGM to host PARE Spring School 2019
PARE Spring School is an educational programme funded by Japanese Education Ministry
It is run by Hokkaido University in cooperation with 6 ASEAN universities
“There are 29 graduate students from 10 countries learning in Japanese
and Indonesian universities that join PARE Spring School at UGM,” he said when opening the event on Friday (15/2) at University Club UGM
Panut hoped with this programme the students could share ideas and find solutions to resolving existing problems
The students would take part in public lectures given by experts from Hokkaido University
They would also learn on the field and collect data from Progo and Gajah Wong rivers to observe the river water quality
Next the participants would visit Bribin Cave to see firsthand how to elevate water from the underground river
Please contact us for any problem with SIMASTER
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dan Lingkungan Office of Workplace and Environmental Security and Safety and Emergencies)
E: info@ugm.ac.id | P: +62(274)588688 | F: +62(274)565223 | WA: +628112869988
A tanker collects LNG at a storage and distribution facility in Barcelona
(Bloomberg) -- European natural gas pared gains in another roller-coaster day driven by geopolitics
amid news that Russia is willing to discuss a temporary truce in Ukraine
though still ended the week down almost 10% to cap a fourth straight weekly decline
There’s rising speculation that some Russian gas may return to the continent
which is struggling with high energy bills
gas hit a five-month low before US President Donald Trump said he is strongly considering banking sanctions and tariffs on Russia until a cease fire and final peace agreement is reached
That briefly pushed prices almost 9% higher
Speculators closing bullish bets on European gas have also added to the recent selloff
High levels of algorithmic trading and rapid political shifts “don’t make nice bedfellows for a calm orderly market,” said Nick Campbell
“Given the ever-changing narrative regarding the start of peace talks
Russia is ready for talks on a truce if there’s progress toward a final peace settlement
according to people familiar with the matter in Moscow
The US and Ukraine plan to meet in Saudi Arabia next week for their first direct talks since Trump’s Oval Office bust-up with President Volodymyr Zelenskiy last week
the situation on the front line remains intense
An overnight Russian barrage damaged private company DTEK’s gas production facilities in central Ukraine
has been turning to the European markets for fuel imports
It may be difficult for Russian pipeline gas to make a comeback after the European Union went to great lengths to diversify supplies
Yet the bloc still imports large quantities of liquefied natural gas from Russia and appears less intent on phasing those out for now as it focuses on defense priorities
Read Also: EU Leaders Call for Ukraine Gas Solution on Slovakia’s Push
the continent looks well supplied and milder weather has eased pressure on the market
But some LNG vessels have been diverting away from Europe after the recent price drop
while price-sensitive buyers in India are looking to make spot market purchases
Europe’s reliance on volatile LNG cargoes has increased after higher-than-expected gas consumption this winter caused a rapid depletion of the region’s fuel stockpiles
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In the next episode of the Energy Connects podcast
Chiranjib Sengupta sat down with Gauri Singh
Deputy Director-General of International Renewable Energy Agency (IRENA)
In an exclusive Energy Connects studio discussion
Chiranjib Sengupta sat down with Nobuo Tanaka
Executive Director Emeritus of the International Energy Agency (IEA) and the…
In the next episode of the Energy Connects podcast ahead of Japan Energy Summit & Exhibition
Metrics details
In view of the complex environments and varying object scales in drone-captured imagery
a novel PARE-YOLO algorithm based on YOLOv8 for small object detection is proposed
This model enhances feature extraction and fusion across multiple scales through a restructured neck network
it incorporates a lightweight detection head that is optimized for small objects
thereby significantly improving detection performance in cluttered and intricate backgrounds
To further enhance the extraction of small object features
the conventional C2f is replaced with a novel architecture
the EMA-GIoU loss function is proposed to mitigate class imbalance and enhance robustness
particularly in scenarios characterized by skewed class distributions
Evaluation on the VisDrone2019 dataset indicates that PARE-YOLO achieves a 5.9% improvement in mean Average Precision (mAP) at a threshold of 0.5
the PARE-YOLO model exhibits significant robustness
achieving a mean Average Precision (mAP) at a threshold of 0.5 values on the HIT-UAV dataset that are 0.8%
These results underscore the effectiveness of PARE-YOLO in addressing the challenges inherent in aerial scenarios
The code will be available online (https://github.com/Sunnyxiao69/PARE-YOLO)
significantly improving detection performance
the high computational cost of Transformer models limits their application in real-time UAV-based detection and tracking tasks
Deep learning methods significantly outperform traditional machine learning techniques in object classification and localization tasks
This advantage mainly stems from the powerful feature extraction capability of deep learning
its complex network structure can effectively interact and fuse features at different scales to capture multi-scale semantic information and contextual relationships in the data
basic deep learning models often struggle to accurately identify and localize small objects in aerial images
as these objects usually occupy only a small pixel area and are frequently confused with the background
further increases the difficulty of detection
These factors lead to problems such as missed detection and false alarms in small target detection tasks in aerial images
the computational intensity and processing delay of the complex model can also affect the overall detection performance and practicality
most existing real-time detectors rely on Convolutional Neural Networks (CNNs)
they struggle with detecting small objects in complex backgrounds
the PARE-YOLO algorithm is designed to improve the accuracy of small object detection while minimizing computational complexity
The main contributions of this paper are as follows:
The neck network of YOLOv8 is reconstructed: We effectively fuse spatial and multi-scale features
reducing model complexity while better preserving edge and detail information
thereby significantly enhancing detection performance
Efficient detection head is proposed: By adding a small-object detection layer (P2) within high-resolution feature maps and incorporating a Transformer-based RT-DETR detection head
the performance in complex environments is improved
The proposed method notably reduces missed detections
The EMA-GIoU Loss Function is proposed: This novel loss function balances the weights of positive and negative samples using the Exponential Moving Average (EMA)
It also adjusts the focus parameter to control the importance of positive and negative samples
This approach better addresses class imbalance
improving the performance and robustness of the object detection model
The New C2f-PPA structure is presented: By combining pyramid pooling and attention mechanisms
this structure significantly enhances the multi-scale representation capabilities of feature maps
It is particularly effective for detecting small object detection and target detection in complex scenarios
deep learning-based detection methods have become the standard in the field of image object detection
With the rapid advancement of deep learning
convolutional neural network-based object detection techniques have achieved remarkable success
the YOLO (You Only Look Once) network has garnered increasing attention
To effectively utilize the YOLO network for small object detection in UAV imagery
researchers have conducted extensive studies and provided a comprehensive overview of relevant work
This design merges multi-scale feature information and enriches the semantic representation of features
This network adaptively enhances distinguishing features between UAV targets and complex backgrounds
They also propose a spatial-channel-aware attention mechanism to optimize infrared UAV target detection
Based on the limitations of previous studies
this paper presents an improved small object detection algorithm built upon YOLOv8
The aim is to improve the detection of small objects in UAV images
Network architecture of the PARE-YOLO model
The C2f module begins by splitting the input feature map \(X\in R^{C\times H\times W}\) into two parts
\(X_{1}\in R^{C1\times H\times W}\) and \(X_{2}\in R^{C2\times H\times W}\)
where \(X_{1}\) retains the original information and \(X_{2}\) requires further processing
Unlike traditional deep convolution operations
C2f only applies a \({1\times 1}\) convolution on \(X_{2}\) for dimensionality reduction
thereby reducing redundant computation while preserving essential features
where \(W_{i}\) is the convolution kernel, \(k_{i}\) is the kernel size, and \(b_{i}\) is the bias term. Different kernel sizes capture context information at varying scales, adapting to changes in object size within the image. These multi-scale features are fused through the attention mechanism, with the weight coefficient \(\alpha _{i}\) determined by a channel attention mechanism:
Finally, the features from each branch are weighted and summed to obtain the aggregated feature representation Y:
The final output of the C2f-PPA module is produced by concatenating the C2f-processed \(X_{1}\) with the PPA-aggregated multi-scale features Y , resulting in the complete output feature map:
Dynamic sequence feature fusion module
the input feature map that \(F_{s}\in R^{C_{s}\times H_{s}\times W_{s}}\) of different scales are convolution transformed
and the channel dimension is unified to C:
\(W_{s}\) are the height and width of the feature maps
These feature maps are then weighted and fused using a scale-sequence attention mechanism
and the fused feature map is expressed as:
The attention weights \(\alpha _{s}\) are computed using Global Average Pooling and a Multi-Layer Perceptron:
the updated feature fusion formula becomes:
The P2 layer provides higher spatial resolution
significantly enhancing the detection accuracy for small objects
this module is further optimized by introducing residual connections
which help mitigate the vanishing gradient problem
the DSFF module incorporates a weighted EMA-GIoU loss function to stabilize the accuracy of object regression
The EMA-GIoU loss function is expressed as:
where \(B_{pred}\) and \(B_{true}\) are the predicted and ground truth boxes
By introducing the exponential moving average (EMA) method
the gradient updating is further stabilized and the robustness of the network to the scale variation of the object is enhanced
a Transformer-based encoder-decoder architecture is utilized
The encoder executes self-attention operations on the input features to capture global contextual information
The self-attention mechanism is defined by the following formula:
To further enhance the detection of small objects
which combines the global features from the encoder with the detailed features of the P2 layer
The cross-attention mechanism is defined as:
positional encoding is incorporated to retain spatial information
and \(d_{\textrm{mod}el}\) is the model dimension
The decoder output is then passed through a linear layer to predict object classes and bounding box regression parameters
The loss function is a combination of classification loss and bounding box regression loss
By deeply integrating global features with local details
the combination of the RT-DETR detection head and the P2 feature layer significantly improves both the precision and robustness of small object detection
To improve the detection ability of dense small targets in UAV images, the concept of EMASlideVarifocalLoss inspired by Yu et al.39 is introduced
EMA-GIoU is an optimization method that integrates Generalized IoU loss with the Exponential Moving Average strategy
This approach aims to mitigate instability issues in object detection models
particularly in complex scenes and tasks involving small object detection
GIoU extends the traditional IoU loss by introducing the non-overlapping area of the smallest enclosing convex hull
the gradient becomes zero if there is no overlap between the predicted and ground truth boxes
The core idea is to generate an additional penalty by calculating the non-overlapping part of the smallest convex hull
to improve the optimization capability of the model without overlapping between the boundary boxes
where \(A_{C}\) is the minimum closure area and U is the concatenation of the predicted and true frames
GIoU effectively avoids the gradient vanishing problem when there is no overlap
leading to significant improvements in detection accuracy
To further stabilize gradient variations during the training process
EMA smooths the loss function by applying a weighted average of historical losses
especially in complex scenes and small object detection tasks
determining the sensitivity to past losses
EMA-GIoU more effectively smooths out fluctuations in loss values
This reduces oscillations during the training process
it enhances robustness in small object detection tasks and improves generalization in complex backgrounds
The innovation of EMA-GIoU lies in its ability to dynamically adjust the weight of historical losses
This allows the model to perform more stably when managing multi-scale objects
It also prevents the adverse effects of sudden and substantial changes in loss during individual training steps
highlighting its consistency with other small object detection datasets centered around drones
Object types and size distribution in the VisDrone2019 dataset
The following ablation experiments are conducted to evaluate the contribution of each enhanced module to the model detection performance. The results of ablation experiments are summarized in Table 2 by sequentially merging each module into the baseline YOLOv8s model
the YOLOv8s model is used as the baseline model
Ex2 introduces a special small object detector into high-resolution feature mapping
The results show that mAP@0.5 and mAP@0.5:0.95 increased by 5.5% and 3.6% respectively
integrating a Transformer-based RT-DETR detection head enhances performance in complex scenarios
Ex4 combines the P2 detection layer with the RT-DETR head
adding a dynamic sequence feature fusion module with the RT-DETR head increases P by 9.3%
Ex6 combines the EMASlideVarifocalLoss function with the RT-DETR head
Ex7 incorporates the C2f-PPA structure with the RT-DETR head
boosting performance with increases of 10.2% in P
and both mAP metrics improving by 8.9% and 5.8%
demonstrating significant gains over the original YOLOv8s model
To evaluate the impact of different loss functions on model performance, comparative experiments with the following methods: VarifocalLoss, SlideLoss, EMASlideLoss, SlideVarifocalLoss, and EMASlideVarifocalLoss, which are abbreviated as vfl, sl, emasl, svfl, and emasvfl in Table 3
As can be seen from Table 3
replacing the original loss function with emasvfl improves the model performance
The experimental results show that the emasvfl performs best in improving the model detection accuracy
Accuracy comparison and convergence curves for different loss functions on the VisDrone2019 val dataset
To verify the effectiveness of the PARE-YOLO algorithm, the experiments with several advanced algorithms published in recent years on the same dataset are compared. The results are shown in Fig. 7.
Comparison of advanced models on the VisDrone2019 val dataset
As shown in Table 4
PARE-YOLO demonstrates superior performance across a wide range of object detection tasks
which significantly outperforms traditional models such as Faster R-CNN (21.7%) and SSD (25.3%)
It excels in detecting pedestrians (38.5%) and persons (26.0%)
with the highest accuracy in detecting cars (77.6%)
While it shows competitive results for Vans (35.9%) and Trucks (40.3%)
it outperforms alternatives such as YOLOv8s in most categories
PARE-YOLO excels in detecting motorbikes (38.1%)
surpassing methods such as YOLOv9-c and MPE-YOLO
Its strength lies in its robust generalization across diverse object categories and consistent performance
with a better balance between precision and recall
Compared to other algorithms (YOLOv9-c and RT-DETR-r18)that perform well in some categories but poorly in others
PARE-YOLO maintains competitive or superior results across all key categories
This makes it an efficient solution for small object detection in challenging environments such as drone imagery and autonomous driving
Due to different experimental parameters and equipment
the mAP50 of MPE-YOLO is 37.0% which is slightly higher than that of PARE-YOLO at 36.2%
but the mAP50 of PARE-YOLO is 5.9% higher than the original model
while MPE -YOLO has seen an improvement of 5.7%
Performance metrics of PARE-YOLO on the VisDrone2019 val dataset
Comparison of visualization analysis between YOLOv8 and ours across different scenarios (a) uneven lighting scene, (b) occluded scene, (c) dark road scene, (d) crowded scene.
Comparison of visualization analysis between YOLOv8 and ours across different scenarios (a) occluded scene
Figure 9 compares the detection heatmaps between YOLOv8s and PARE-YOLO in various scenarios
Light-colored areas represent regions with lower confidence in the feature map
while darker areas indicate higher confidence
The PARE-YOLO detection heatmap aligns more closely with actual target regions
YOLOv8s struggles with attention and sensitivity toward small and distant objects
as shown by the lighter colors in the heatmap
indicating a higher risk of missing small targets
PARE-YOLO shows significantly deeper colors in small object regions
indicating improved attention and feature extraction capabilities for small targets
Through optimized feature fusion and attention mechanisms
PARE-YOLO detects and locates small objects more accurately and ensures higher confidence even in complex scenes
YOLOv8s performs poorly in suppressing background noise
while PARE-YOLO focuses more on small and distant targets and demonstrates superior noise suppression capabilities
PARE-YOLO concentrates attention on the core areas of the targets
further improving the accuracy of predicted bounding boxes
thus enhancing overall detection performance
These results demonstrate that PARE-YOLO has significant advantages in robustness and detection effectiveness
To further observe the detection performance of the proposed algorithm in different scenarios, we also conducted visual analysis and comparative experiments in complex environments. The detection results of the baseline and improved algorithms on the original images are shown in Fig. 10
the improved algorithm effectively identifies occluded targets
the baseline model often misses detections in similar situations
the baseline model fails to detect pedestrians in dark corners
the improved algorithm accurately identifies these low-light targets
showcasing its adaptability in complex lighting conditions
the baseline model experiences false positives and missed detections due to background noise
The improved algorithm effectively utilizes multi-scale feature information to isolate beneficial features for UAV image target detection
This significantly enhances its ability to resist interference in complex backgrounds
Group (d) presents results for aerial scenes
Despite the targets being far away and small
the improved algorithm still accurately detects cars
This highlights its advantage in detecting small-scale objects
the improved algorithm demonstrates remarkable robustness and stability
While the baseline algorithm misdetects overlapping targets
the improved model effectively suppresses noise and successfully identifies each small target
the visualization analysis results confirm that the improved algorithm excels in detecting small objects under various challenging conditions
The enhancements in PARE-YOLO boost its robustness and improve its ability to detect small
It can be seen from Table 5
the PARE-YOLO emerges as a highly advanced and efficient object detection algorithm
demonstrating exceptional performance across a spectrum of key metrics
which not only surpasses YOLOv8(84.9%) but also exhibits competitive results compared to YOLOv9(90.1% ) and YOLOv10(91.5%)
highlights its capability to minimize false positives
outperforming both YOLOv8 (80.5%) and RT-DETR (80.1%)
which further confirms its effectiveness in complex detection scenarios
particularly in scenes with dense and overlapping object distributions
the algorithm excels in the mAP50:95 metric with a score of 52.7%
which indicates its ability to maintain good generalization across different Intersections over Union (IoU) thresholds
PARE-YOLO demonstrates a good balance between precision and recall
with a computational complexity of 45.1G FLOPs
which is significantly lower than models such as YOLOv7 (103.2G) and YOLOv9 (102.3G)
making it highly suitable for resource-constrained environments
The algorithm boasts an impressive inference speed of 123.5 FPS
surpassing YOLOv9 (70.8 FPS) and YOLOv10 (112.7 FPS)
making it an optimal choice for real-time applications
To further compare the proposed model with the baseline model, the comparative experiments on the HIT-UAV test dataset in each category are performed. The detection results are shown in Table 6
As shown in Table 6
the accuracy of the Person and DontCare categories is improved by more than 3 points
indicating that the PARE-YOLO model has a strong detail capture ability for small-scale targets
the classes for the large categories of Car and OtherVehice are slightly lower than those of YOLOv8s
the average accuracy of the PARE-YOLO model (mAP50) reached 81.3%
PARE-YOLO shows a significant improvement in detection accuracy across most categories compared to the baseline model
Visual comparison of detection outcomes across various models on the HIT-UAV dataset
As shown in Fig. 11
PARE-YOLO successfully detects the DontCare and bottom right corner cars in the field
while YOLOv10 fails to detect the bottom right corner cars
both YOLOv10 and RT-DETR fail to detect the pedestrian in the bottom right corner
only PARE-YOLO detects bicycles in the bottom left corner
only PARE-YOLO detects pedestrians in the bottom left corner
PARE-YOLO shows excellent detection accuracy and robustness in infrared scenes
significantly outperforming the YOLOv10 and RT-DETR models
which is a novel aerial small object detection algorithm based on dynamic sequential feature fusion
The approach addresses the unique challenges of aerial imagery
Key innovations include enhanced feature extraction
The model also incorporates a dynamic sequential feature fusion mechanism
This mechanism reorganizes the neck network to capture richer contextual information
We enhance the detection head by incorporating the multi-attention mechanism from the RT-DETR head
This allows the model to better capture scale and spatial features
we utilize the EMA-GIoU loss function for better class balance in crowded scenes
Experimental results show that the mean Average Precision (mAP@0.5) increases by 9.1%
and the mAP@0.5:0.95 improves by 6.2% compared to the baseline model in the VisDrone dataset
visualization comparison experiments in the HIT-UAV dataset demonstrated the strong robustness of the PARE-YOLO
Compared to the advanced YOLOv10 and RT-DETR models
PARE-YOLO demonstrates superior capability in accurately identifying multi-scale targets across various challenging environments
challenges such as occasional omissions of small objects and misclassifications remain
Future research will focus on optimizing performance in lightweight configurations
All the images and experimental test images in this paper were from the open source VisDrone and HIT-UAV datasets. These datasets analyzed during the current research period can be found on the following website. Visdrone: (https://github.com/VisDrone/VisDrone-Dataset), HIT-UAV : (https://github.com/suojiashun/HIT-UAV-Infrared-Thermal-Dataset)
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This work is supported by Science and Technology Development Plan of Jilin Provincial Department of Science and Technology (20220508145RC)
Huiying Zhang and Pan Xiao contributed equally to this work
College of Information and Control Engineering
H.Z: The main contribution to this study is the construction of a comprehensive research plan including theoretical framework
I undertook a large number of experimental operations and data analysis work
and was responsible for writing the methods and results in the paper writing
F.Y: Made important contributions in data analysis and interpretation of experimental results
as well as in the improvement and revision of the paper
Q.Z: Responsible for proving the applicability of the theoretical model and writing this part of the paper
which provided theoretical support for this research
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DOI: https://doi.org/10.1038/s41598-025-88857-w
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LAKEWOOD – With many cuts across all departments, village trustees have carefully pared down their tentative 2025-2026 spending plan.
A public outcry at the April 14 meeting, and receiving incorrect numbers from the town of Busti assessor led to the board’s cuts. Three people from the public attended Thursday’s budget work session, and the board discussed line by line ways to reduce the spending plan.
Trustees said they had listened to village residents, and being totally transparent, held a budget workshop session Thursday.
“We are kind of at a bare bones budget (right now),” Trustee Ellen Barnes said. “We need revenue.”
Both Barnes and Trustee Ben Troche said the most budget cuts came from the Lakewood-Busti Police Department, and the Department of Public Works.
Mayor Randy Holcomb said April 14 that at the next trustees meeting, there will be a reduced version of the budget.
The tentative 2025-2026 spending plan is now $5,579,515 from $5,762,081, and the tax levy or the amount to be raised by taxes is now $2,403,074 from $2,587,640.
Now trustees will vote whether to adopt or not, the tentative budget at their next meeting, Monday, April 28.
I’m really attracted to the tiny house scene. I’m not sure why, but maybe it’s because when I was a little ...
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HOLYOKE, MA — Pare Corporation, a multi-disciplinary engineering firm, has announced the promotion of David L. Loring, P.E., LEED AP, ENV SP, to Senior Vice President of its Western Massachusetts Division.
With over 34 years of engineering design and management experience across New England, Loring has played a pivotal role in Pare’s expansion in the region. He spearheaded the opening of the firm’s Holyoke, MA office and currently leads a range of transportation, municipal, educational, and infrastructure projects—including managing a $15 million contract for intersection upgrades in Springfield, MA.
“David has proven himself through managing our Holyoke office for the past four years,” said Pare CEO John Shevlin. “His leadership has directly contributed to the firm’s growth in Western Massachusetts. We’re proud to recognize his efforts with this well-deserved promotion.”
Beyond his project work, Loring remains active in the professional community. He serves as Treasurer of the Massachusetts Tri-County Highway Superintendents’ Association, Co-Chair of the ACEC-MA QBS Committee, and sits on Western New England University’s College of Engineering Industry Advisory Council.
Founded in 1970, Pare Corporation offers a full range of engineering services across the Eastern U.S., with offices in Rhode Island and Massachusetts.
Volume 9 - 2021 | https://doi.org/10.3389/fbioe.2021.669728
Antibacterial resistance (ABR) is a major life-threatening problem worldwide
Rampant dissemination of ABR always exemplified the need for the discovery of novel compounds
which will lead to the death of the bacteria when acted upon by a compound
One group of enzymes that have proved to be an effective target for druggable candidates is bacterial DNA topoisomerases (DNA gyrase and ParE)
phenylacetamide and benzohydrazides derivatives were screened for their antibacterial activity against a selected panel of pathogens
The tested compounds displayed significant antibacterial activity with MIC values ranging from 0.64 to 5.65 μg/mL
compounds 5 and 21 exhibited more potent and selective inhibitory activity against Escherichia coli with MIC values at 0.64 and 0.67 μg/mL
compounds exhibited a post-antibiotic effect of 2 h at 1× MIC in comparison to ciprofloxacin and gentamicin
These compounds also demonstrated the concentration-dependent bactericidal activity against E
coli and synergized with FDA-approved drugs
The compounds are screened for their enzyme inhibitory activity against E
whose IC50 values range from 0.27 to 2.80 μg/mL
namely 8 and 25 belonging to the phenylacetamide series
were found to inhibit ParE enzyme with IC50 values of 0.27 and 0.28 μg/mL
compounds were benign to Vero cells and displayed a promising selectivity index (169.0629–951.7240)
and 25 (IC50: <1 and Selectivity index: >200) exhibited potent activity in reducing the E
coli biofilm in comparison with ciprofloxacin
These astonishing results suggest the potential utilization of phenylacetamide and benzohydrazides derivatives as promising ParE inhibitors for treating bacterial infections
GyrB and Topo IV (ParE), bacterial enzymes possess structural similarities in conserved regions, quinolones and coumarins sensitivity and, subunit organization. However, the most considerable difference between these enzyme structures is the long α-helices of each monomer’s C-terminus (Tourova et al., 2010)
it is clear that fluoroquinolones preferentially bind to ParE enzyme than GyrB
ParE is an unexplored target and could not establish any type of drug resistance
we concentrated on exploring the efficiency of small molecule inhibitors targeting ParE enzyme
These interactions are homologous to the donor/acceptor motif
explored in drug design and development of kinase inhibitors
quinazolidinediones series exploit these donor/acceptor interactions with the ParE protein
In our earlier work, we reported the synthesis, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), time-kill kinetics of phenylacetamide and benzohydrazides derivatives (1–29) (Supplementary Table 1) (Yele et al., 2020, 2021)
we report in vitro MIC and MBC against Escherichia coli (NCIM 2065) (E
methicillin-resistant Staphylococcus aureus (MRSA) (NCIM 5021 and ATCC 43300)
post-antibiotic effect (PAE) and anti-biofilm studies were performed against E
we determined the IC50 values of title compounds (1–29) against E
The panel of bacteria selected for the current study are Escherichia coli (NCIM 2065) (E
These strains were retrieved from the National Collection of Industrial Microorganisms (NCIM)
and American Type Culture Collection repositories
All the strains were cultured using Mueller-Hinton broth before the study
The checkerboard method was used to determine the synergy between the test sample and the antibiotics (ciprofloxacin, gentamicin, rifampicin and doxycycline) against a panel of bacteria (Pandey et al., 2017)
Serial twofold dilutions of each antibiotic to at least double the MIC were freshly prepared before testing
the test compounds were serially diluted along the ordinate ranged from 0.625 to 20 μg/mL
the antibiotics were serially diluted as shown along the abscissa ranged from 0.625 to 5 μg/mL/ml in 96 well microtiter plate
An inoculum ∼106 CFU/mL of specific bacterial strain was prepared
and 100 μL was inoculated in each microtiter well
and the plates were incubated at 37°C for 24 h under aerobic conditions
The ΣFICs (fractional inhibitory concentrations) were calculated as follows:
To determine the PAE, young culture of E. coli was diluted in MHBII ∼106 CFU/mL and exposed to 0.5× and 1× MIC of ciprofloxacin, gentamicin, and compounds 5 and 21 incubated at 37°C for 1 h (Suller and Lloyd, 2002)
The culture was centrifuged and washed twice with MHBII to remove the traces of antibiotics used
The cells obtained were resuspended in antibiotic or sample free MHBII and incubated at 37°C
Samples collected for every 1 h were inoculated on the agar plate followed by the enumeration of CFU
PAE can be calculated using the following equation:
T refers to difference in time required for 1 Log 10 increase in CFU vs
CFU observed immediately after removing the test sample or antibiotic
C refers to similarly treated sample free control
the inhibitory assay was performed for the synthesized compounds 1–29 using a commercial ParE assay kit (ProFoldin
The assay was performed as per the standard protocol provided by the ProFoldin
The title compounds were screened at six concentrations ranging from 0.1 to 3.2 μg/mL
ParE hydrolyzes ATP as the source of molecular energy to perform decatenation reactions
Fluoroquinolones and aminocoumarins usually block ATPase activity to hinder the biological activities of topoisomerase II
the topoisomerase ATPase assay can be used for high-throughput screening of topoisomerase inhibitors
coli ParE enzyme was based on the detection of inorganic phosphate produced by the hydrolysis of ATP in the presence of DNA
The phosphate is detected using a microplate reader at an absorbance wavelength of 650 nm
The selected compounds were tested for the inhibition of ATPase activity of ParE enzyme
The total volume of ATPase assay reaction mixture consists of 18 μL of H2O
coli ParE and different concentrations of the test sample were dissolved in DMSO
The reaction mixture was incubated for 1 h at 37°C and then quenched with 45 μL of Dye
The IC50 values were determined from the absorbance readings using no enzyme and no compound controls
They were calculated using the non-linear regression curve fit method
Vero cells were centrifuged, and cell count was adjusted to ∼105 cells/mL using Hi-media, Dulbecco’s Modified Eagle Medium (DMEM) containing 10% FBS. 100 μL (approximately 10,000 cells/well) of the diluted cell suspension was added to each well of a 96-well plate and incubated 24 h (Patel et al., 2009)
obtained pellets were resuspended with 100 μL of different concentrations of test samples prepared in maintenance media and incubated at 37°C for 48 h in a 5% CO2 atmosphere
Microscopic examination of plates was carried out
20 μL of 3-(4,5 dimethyl thiazole-2-yl)- 2,5-diphenyl tetrazolium bromide (MTT
and plates were gently shaken and incubated for 2 h at 37°C in 5% CO2 atmosphere
To solubilize the formed formazan crystals
100 μL of DMSO was added and gently shaken
The absorbance was measured using a microplate reader at a wavelength of 540 nm
and the concentration of drug or test samples required to inhibit the cell growth by 50% was generated from the dose-response curves
The absorbance was recorded at 600 nm of wavelength using Tecan-i-control
The best-docked poses of ligands were selected based on the Glide emodel
The BFG of synthesized ligands were computed using molecular mechanics-generalized born surface area (MM-GBSA)/Prime approach with OPLS3e forcefield (Roos et al., 2019). Energy minimization of protein-ligand complexes and simulation were carried out using Prime and VSGB 2.0 energy model (Li et al., 2011)
Optimized implicit solvation model and physics-based corrections included in this energy model for all types of interactions (Hydrogen bonding
Mean absorbances and their standard deviations (SDs) were computed for tested strains and controls
determined in triplicate and repeated three times
A two-way analysis of variance was used to determine the statistical significance
Statistical analysis was performed in GraphPad Prism v5.01 software (San Diego
A p-value ≤ 0.01 or lower was considered as statistically significant
Minimum inhibitory concentration (MIC) of synthesized compounds (1–29) against the selected bacterial strains
All compounds exhibited good antibacterial activity with MIC values ranging from 0.64 to 5.65 μg/mL
it should be noticed that the sensitivity of bacterial strains toward title compounds was in general different
The compounds 5 and 21 appeared to be most active against E
coli with an MIC of 0.64 and 0.67 μg/mL followed by compound 1 (MIC
24 (0.78 μg/mL) and 25 (0.72 μg/mL)
compounds 8 (0.66 μg/mL) and 21 (0.68 μg/mL) showed significant antibacterial activity against MRSA (NCIM 5021)
While MRSA (ATCC 43300) appeared to be sensitive against compound 5 with MIC at 0.68 μg/mL
Minimum bactericidal concentration (MBC) (μg/mL)¶ and MBC/MIC ratio of benzohydrazides and phenylacetamide derivatives (1–29) against a panel of organisms
Compounds 5 and 21 exhibited significant MIC (0.64 and 0.67 μg/mL), and MBC values at onefold MIC against E. coli are considered for further evaluation. Time-kill kinetics demonstrated the bactericidal property of compounds 5 (Figure 1A) and 21 (Figure 1B) against E
coli bacterial culture was serially diluted to attain ∼105 CFU/mL concentration and treated with test samples and ciprofloxacin at concentrations of 0.5× and 1.0× MIC
The 50 μL was collected and sub-cultured on an agar plate at regular time intervals of 0
The cultured agar plates were incubated at 37°C
CFU was calculated from the colonies formed on the agar plate at each time interval
Time-kill curves were plotted using the CFU/mL of surviving bacteria at each time point in the compound’s absence or presence
Tested samples exhibited significant bactericidal property against E
Time-kill kinetics of compound (A) 5 and (B) 21
The checkerboard method was employed to determine the synergy between compounds 5, 21, and antibiotics ciprofloxacin, gentamicin, rifampicin and doxycycline. The results have shown that compounds 5 (Table 3) and 21 (Table 4) synergized with the FDA-approved antibiotics
demonstrating significant potential to be a part of a multi-drug regimen
Determination of synergy of compound 5 with approved antibiotics
Determination of synergy of compound 21 with approved antibiotics
PAE of compounds 5 and 21 were evaluated with ciprofloxacin and gentamicin as controls. The results demonstrated that compounds 5 and 21 exhibited a PAE of ∼2 h at 10× MIC compared to ciprofloxacin and gentamicin (Table 5)
Post-antibiotic effect of compound 5 and 21
E. coli ParE enzyme inhibition assay was performed for the synthesized compounds 1–29 using commercial ParE assay kit (ProFoldin, Hudson, United States). The compounds displayed IC50 values (Figure 2) in the range of 0.27–2.80 μg/mL. Among, the assayed molecules, the two compounds namely 8 and 25 belonging to the phenylacetamide series were found to inhibit ParE enzyme with IC50 values of 0.27 and 0.28 μg/mL, respectively (Figure 3)
14 (0.36 μg/mL) 17 (0.86 μg/mL)
and 24 (0.48 μg/mL) belonging to both phenylacetamide and benzohydrazides series displayed significant inhibitory activity against ParE enzyme with IC50 values less than <1 μg/mL
10 (1.84 μg/mL) 11 (1.81 μg/mL)
and 28 (1.93 μg/mL) exhibited variable activity against E
coliParE enzyme with IC50 values ranging from 1 to 2 μg/mL
and 29 (2.77 μg/mL) displayed partial significant inhibition against ParE enzyme with IC50 values in the range of 2–2.80 μg/mL
Data are expressed as mean ± SD (n = 3)
Chemical structure of highly active compounds 8 and 25 in phenylacetamide series
Cytotoxicity profile against Vero cells and Selectivity index (SI) of selected compounds against E
XP-docking and binding free energy (kcal/moL) results of synthesized compounds (1–29) against E
The BFG of compounds with E. coli ParE was computed using MM-GBSA/Prime approach. The ΔGbind values were observed in the range of –34.26 to –55.20 kcal/mol. All the energy terms of Prime calculations were represented in the Table 7
van der Waals energy was found to be in the range of –31.31 to –55.28 kcal/mol
the synthesized phenylacetamide and benzohydrazides derivatives were screened for their ParE inhibitory activity
the compounds displayed potent antibacterial activity against E
Both phenylacetamide and benzohydrazides series exhibited optimal activity against selected strains (Table 1)
most of the compounds shown potential inhibition of E
The compounds which exhibited potency against E
coli were observed to inhibit MRSA (ATCC43300) at MIC <1 μg/mL
The activity in the phenylacetamide series may be attributed to amide linkage (29) or the presence of nitro (1
25) have shown promising inhibition of bacteria because of benzothiazole ring flanked by substituted phenyl ring via an amide linkage
the compounds in the benzohydrazides series also shown prominent inhibitory activity that may be ascribed to the presence of formylformohydrazide (O = C-NH-NH-C = O) (12
which is linked to the substituted phenyl rings through the formylformohydrazide (21
coli compared to the ciprofloxacin and untreated E
After analyzing the activity of these compounds, we performed synergy testing using a checkerboard assay with different approved drugs like ciprofloxacin, gentamicin, rifampicin, and doxycycline. The results obtained were astounding, exemplifying that the selected compounds 5 and 21 were considered the best candidates in multi-drug regimens (Tables 3, 4)
In addition, compounds exhibited significant PAE at 10× MIC in 2 h compared to ciprofloxacin. In contrast, both compounds exhibited more activity at 10× MIC in comparison with gentamicin (Table 5)
compounds 5 and 24 displayed promising activity with IC50 values of 0.35 ± 0.03 and 0.48 ± 0.06 μg/mL
which may be attributed to the presence of electron-withdrawing groups
such as carboxyl and nitro at position four of the phenyl ring
The variation among the activities of both the compounds maybe because of the substituted phenoxy moiety present in compound 5
the replacement of electron-withdrawing groups with chlorine atoms shown detrimental to the inhibitory activity (10
the compounds 14 and 21 shown significant inhibitory activity against E
coli ParE at IC50 of 0.36 ± 0.02 and 0.50 ± 0.06 μg/mL
The potent activity of these compounds may be because of the presence of electron-withdrawing group NO2 at position four of the phenyl ring
the molecules possess different chemical moieties (substituted phenoxy moiety; 14 and 2-mercaptobenzothiazole group; 21) responsible for the variation in the activity
The compounds possessing electron-releasing groups (12
20) have exhibited partial inhibitory activity against E
The binding strength of the compounds 8 (57.427 kcal/mol) and 25 (57.822) indicated higher binding of the ligands in the catalytic pocket of enzyme
The non-polar solvation energy (ΔGsolv: –9.00 to 16.41 kcal/mol) term was moderately favorable while coulombs (ΔGcou: 43.39 to –23.63 kcal/mol) and covalent (ΔGcov: 11.12 to –17.86 kcal/mol) energy terms were unfavorable for the inhibitory activity
it should be noted that van der Waals energy (ΔGvdW: –31.31 to –55.28 kcal/mol) term was found to be favorable and is the key driving forced for the ligand binding
This is in agreement with the Glide Emodel (–29.937 to –46.484 kcal/mol) having significant weighting of the force field
3D-interaction diagrams of (A) compound 8 and (B) compound 25 exposing key interactions with the catalytic residues of E
The broad structural activity relationship was summarized in Figure 6
compounds have shown significant potential inhibition of E
the variation in their inhibitory concentrations might be because of the chemical substitutions at different positions on the aromatic rings
Broad structure-activity relationship of the phenylacetamide and benzohydrazides
it is clear that compounds possessing electron-withdrawing groups
such as nitro and carboxyl moieties (8 and 25) increased the activity toward the E
methoxy groups decreased the inhibitory activity (12
The halogen substitution on the aromatic rings possesses substantial activity of these compounds against E
the replacement of the phenyl ring with fused aromatic system or with anisole markedly decrease the inhibitory activity (28 and 29)
(3) Both amide and hydrazide linker were found to be necessary for the activity as evident by their IC50s and docking results
(4) Potent activity was observed with both the phenylacetamide and benzothiazole ring systems (8 and 25)
We have previously synthesized and tested a series of phenylacetamide and benzohydrazides
which displayed interesting antibacterial activity against selected bacteria strains
we have successfully performed antibacterial screening for E
compounds 5 and 21 exhibited significant MIC and MBC
these compounds showed PAE at 2 h compared to ciprofloxacin and gentamicin and established concentration-dependent bactericidal property
The compounds exhibited synergistic activity with FDA-approved drugs indicating the better potential for the multi-drug regimen
the molecular structures of the compounds 8 and 25 were found to be favorable for E
coli ParE inhibition as evident by their IC50 values IC50 of 0.27 ± 0.02 μg/mL and 0.28 ± 0.03 μg/mL
The significant values of CC50 and selectivity index indicated that drugs were more effective and safer during in vivo treatment
compounds 8 and 25 also exhibited significant antibiofilm activity
as evidenced by their biofilm mass reduction
the phenylacetamide series (compounds 8 and 25) represent one of the most exciting chemical scaffolds in the bacterial armamentarium
As a novel chemical that addressing ABR by targeting unexplored targets like ParE
the representative compounds 8 and 25 can further be investigated to develop potent antibacterial agents for use against nosocomial pathogens
The original contributions presented in the study are included in the article/Supplementary Material
further inquiries can be directed to the corresponding author/s
BS and AW were involved in the in vitro studies
All authors read and approved the final manuscript
The authors acknowledge the All India Council of Technical Education
National Doctoral Fellowship (NDF)—56149
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
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fbioe.2021.669728/full#supplementary-material
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Wadhwani AD and Mohammed AA (2021) Benzohydrazide and Phenylacetamide Scaffolds: New Putative ParE Inhibitors
Copyright © 2021 Yele, Sanapalli, Wadhwani and Mohammed. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY)
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*Correspondence: Afzal Azam Mohammed, YWZ6YWw5YXphbUBob3RtYWlsLmNvbQ==; YWZ6YWxAanNzdW5pLmVkdS5pbg==
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Paré began writing and publishing other books
She also continued to sell her publications in gas stations and grocery stores around the country
cementing them as everyday pieces of knowledge
after three decades of writing over 200 published cookbooks
with over 30 million copies sold worldwide
She was one of the top-selling cookbook authors in the world
In 2004, Paré was inducted into the Order of Canada. She also received many other awards in her lifetime like the Queen Elizabeth II’s Golden and Diamond Jubilee Medals
Paré was inducted into the Alberta Business Hall of Fame and the Taste Canada Hall of Fame
Jean Paré died in Edmonton on 24 December 2022
represented the immense trust that Canadian cooks had in Paré and their almost endless appetite for her recipes
Bloomberg’s Peggy Collins weighs in on President-elect Trump saying he will not pare back his tariff policy and states Trump sees his tariffs as a negotiation tool and revenue raiser
Peggy speaks with Kailey Leinz and Joe Mathieu on Bloomberg’s “Balance of Power.” (Source: Bloomberg)
Luke Kawa4/8/25US stocks swiftly pare gains as White House confirms 104% tariffs on ChinaUS stocks are falling out of bed
with the S&P 500 completely retracing an advance of 4% on confirmation that an escalating trade war is indeed happening
White House Press Secretary Karoline Leavitt said the additional 50% tariffs imposed on China following its retaliatory tariffs on the US are going into effect
*LEAVITT: US TO IMPOSE 104% TARIFFS ON CHINA TOMORROW: FOX BIZ
A Goldman Sachs basket of US stocks with high exposure to China (ex semiconductors) is in the red and lagging the benchmark US stock index
with the underperformance swelling after that headline hit the wires
US stocks opened well in the red amid fresh tariffs floated by President Donald Trump and a disorderly surge in Asian currencies, particularly Taiwan’s
but spent most of the day clawing back those losses before faltering into the close
The S&P 500’s nine-session winning streak was snapped with a 0.6% decline
The Nasdaq 100 gave back 0.7% and the Russell 2000 brought up the rear with a 0.8% drop
Every S&P 500 sector ETF outside of communication services and industrials closed in the red
punctuated by a big drop in energy stocks as OPEC+ agreed to boost production again next month
Shares of Netflix, Paramount, and other media giants slid after Trump claimed he’d slap a 100% tariff on foreign-made films to try to reverse Hollywood’s slowdown
Berkshire Hathaway shares slipped 5% after longtime CEO Warren Buffett said he’d be turning the keys over to his successor
Skechers stock jumped as much as 25% after the ’90s sneaker icon announced a $9.4 billion go-private deal with private equity firm 3G Capital
Hims & Hers popped after the company appointed Nader Kabbani, a longtime Amazon exec
Tyson Foods shares slid nearly 8%
one of the worst performers in the S&P 500
after the company posted mixed Q2 results and beef sales fell for the sixth-straight quarter
Marathon Digital shares fell after the company reported a dip in month-over-month bitcoin production
sending its stock down nearly 9% ahead of its upcoming earnings report
Gains on the day were led in part by Delta Airlines
Hims slips after market despite earnings, revenue beatThe company reported that it has 2.37 million subscribers, up 38% year over year but less than the 2.42 million analysts expected.
Despite a positive report, the stock sunk in after-hours trading.
The company has high short interest and the stock has risen significantly in the past week. Its earnings report could be make or break for short sellers.
You may wonder how someone who grew up near the ocean in Los Angeles and once intended to spend his days as a merchant marine ended up in landlocked middle America.
A proposal to increase penalties for certain traffic violations and crimes was given first-round approval May 1 after lawmakers amended it to include several other bills heard by the Judiciary Committee.
Lawmakers gave first-round approval May 1 to a bill that would change disclaimer requirements for political advertisements.
Lawmakers gave first-round approval May 1 to a bill that would update provisions of law related to pharmacy benefit managers.
Lawmakers gave first-round approval May 1 to a proposal intended to correct an unintended consequence of a recent change in the way community colleges are funded.
Senators advanced the Government, Military and Veterans Affairs annual election cleanup bill from the first round of debate May 1.
Lawmakers gave general file approval May 1 to a bill that would change meeting requirements and duties for the state’s African American Commission.
A bill that would eliminate the state’s lifetime ban on Supplemental Nutrition Assistance Program eligibility for individuals with certain drug-related convictions was advanced from select file April 30 after being amended to include a substance abuse treatment requirement.
A bill that would limit scheduled increases to the state’s minimum wage and establish a separate, lower wage for young Nebraskans was given second-round approval April 30 following a successful cloture motion.
A proposal to combine two state agencies tasked with managing Nebraska’s water resources received final approval from lawmakers May 1.
A measure intended to encourage certain defense contractors to relocate to Nebraska advanced to final reading April 30 after lawmakers amended it to ensure that it rewards the creation of new jobs.
Lawmakers gave final approval April 30 to a bill that rolls back various recently enacted tax incentives.
Senators gave first-round approval April 29 to a package of revenue-related bills, including a proposal under which Nebraska educational savings plan trust accounts could be used to pay for private K-12 education.
Senators gave first-round approval April 29 to a Transportation and Telecommunications Committee omnibus bill that would update state law regulating telecommunications companies and common carriers.
A proposal to cut county inheritance tax rates while also distributing replacement revenue to counties advanced from general file April 29.
Lucille Pare Sayers, 86, entered into eternal rest on March 22, 2025. She was the wife of the late Thomas Sayers and daughter of the late Louis P. and Cecile Rocheleau Pare.
For over 20 years, Lucille worked as the bookkeeper at the Burban Press, a family printing company formerly located at the corner of Brown and Campbell Ave. in West Haven. She retired in 1993. After retirement, she worked for a short time at Fitzgerald's Florist.
Her family includes four children Thomas (Rose) Sayers, Raymond (Patty) Sayers, Theresa (the late Pat) DiMeglio, Michael (Sue) Sayers, two granddaughters Amanda (Carsen) Long and Heather Sayers, two great grandchildren Dale and Mackenzie Long and her sister Cecile Pare. Her siblings Richard, Louis and Theresa Pare predecease her.
A deeply religious communicant of the former Our Lady of Victory Church, Lucille enjoyed spending time with her family. She was an avid reader of mystery and romance books and loved spending time in the garden.
Gov. Josh Stein’s newly released budget recommendations include a plan to increase starting teacher pay above $50,000
with the goal of making it the highest in the Southeast
Stein noted in his State of the State address that Republicans in the N.C. House have already filed a similar teacher pay bill. That proposal is sponsored by Rep
who was recently appointed to a powerful role as a co-chair of the House Appropriations Committee
She spoke about the bill in an interview on this week’s episode of the WUNC Politics Podcast.
This conversation has been lightly edited for brevity and clarity
What's the thought process behind introducing this teacher pay plan now
"I think it's something that needs to happen
and I think there's a lot of support for it in the General Assembly from both sides of the aisle
"A lot of people in the education community
particularly our school boards and our districts
And I think that in my current role as a chair of Appropriations (Committee)
it was appropriate for me to file this bill
and I look forward to fighting for it in those negotiations
"I think that it is important that we are the top in the Southeast
It is very important for us to be creating an environment in North Carolina where we can attract the best and the brightest educators coming out of school and retain those educators."
The revenue landscape this year looks like it could be a little bit more tight
Do you feel like there's going to be the resources to do this kind of teacher pay increase
or is this something that may get scaled back
While we are being very prudent when it comes to budgeting and fiscal strategy and managing our budget responsibly
we also need to meet the needs of North Carolina and prioritize the things that matter."
Stein and other Democrats are calling for is freezing income tax cuts for the corporate and individual level to free up more funding for things like teacher pay
Is that something House budget writers are likely to have to look at
and I think — at least from the House side
obviously — but I think that's part of the discussion
We want to make sure that we have enough runway that we can meet the needs of western North Carolina
I think that we all understand that tax cuts are positive ..
Another education bill you filed this session would require more transparency around school district jobs based in a central office
What's the goal with looking at how much school districts are paying for some of their top administrators
"It's good for the taxpayer to understand whether tax dollars are being invested when it comes to the central office administrative part of public education
or 'we are seeing our property taxes go up so high,' which is a problem
I think that they're wondering where those dollars are going to
So this bill is a common sense bill for taxpayer transparency."
Paré also discussed her bills to create tax exemptions for tipped wages and gambling losses
and a bill addressing extraterritorial jurisdiction powers for Wake County towns
Listen to the full podcast interview here.
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President Trump is poised to address a joint session of Congress on March 4
the first-year equivalent of the annual State of the Union address
Whatever one thinks of this administration’s policies and many executive orders
and reformers from every political party should work to pare it back
If America’s Founders had one overriding principle
it is this: Don’t put too much power in one place
As we approach 2026 and America’s semi-quincentennial (quarter millennial)
celebrating 250 years since the signing of the Declaration of Independence in 1776
it’s an apt time to realize the center of power has long since moved away from the states and toward Washington
power has increasingly centralized in the president at the expense of Congress and the judiciary
For his part, Trump has already usurped Congress’s power of the purse to impose trade tariffs, and he has floated the idea of creating a sovereign wealth fund without Congress
He can cite a precedent as recent as President Joe Biden’s attempt to spend $400 billion on student loans without congressional involvement
Before that, President Barack Obama infamously pledged to use his pen and phone when Congress threatened to block his policies
Bush started two wars without congressional approval
President Woodrow Wilson jailed political opponents during World War I in violation of court orders
Trump’s annual speech itself is arguably an indicator of burgeoning presidential power
Thomas Jefferson transmitted his State of the Union addresses to Congress in written form
partly because he felt that appearing in person before Congress looked too much like a king pressuring the legislature
Jefferson’s tradition of respecting congressional independence continued for more than a century until Woodrow Wilson
whose grand views of presidential power mirror Trump’s
This instability discourages investment and slows innovation and growth
many of Trump’s first-term executive orders on regulation were overturned by Biden on his first day in office
some of those same orders are back in effect
and the odds are the next Democratic president will overturn them again
The Constitution gives all taxing powers to Congress and none to the president
Congress delegated its tariff-making powers to the president for expediency reasons
Trump has used these powers to impose tariffs on hundreds of billions of dollars of goods
often announced on social media with little to no notice and certainly with no congressional input
Congress hasn’t raised tariffs since the 1930 Smoot-Hawley tariffs that worsened the Great Depression — and for good reason
created 1,000 jobs in those industries but cost 75,000 jobs in steel- and aluminum-using industries ranging from autos to beverages
Trump’s speech to Congress will inspire and provoke
There should be one thing everyone can agree on: the presidency has grown too powerful
Congress rightly has sole legislative and spending power
Congress must either codify Trump’s executive orders in legislation or repeal them outright
And the courts must stop unconstitutional behavior from Congress and the president while upholding policies that are constitutional
The state of our union is that America is in good shape
our Founding institutions are undergoing another stress test
the courts and to each of us to see that it passes
Read the full article at DC Journal
The 2025 edition of Wayne Crews’s Ten Thousand Commandments is out now
The economy shrank 0.3 percent in the first quarter of 2025…
Federal regulation costs trillions of dollars each year
and paperwork reshaping the economy without a…
Markets went down when President Trump threatened to fire Fed chair Jerome Powell and went up when he backed off
Agencies issued new regulations ranging…
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The buying started as we got into the early stages of European trade and that's helping with the overall market mood. In Europe, the DAX is leading the charge and is up 1% on the day now with the CAC 40 up 0.5%. Are dip buyers poised to seize back control? The near-term chart below will be one to watch in Wall Street later, should the risk mood hold up.
There's still some distance in reaching the 100-hour moving average (red line). But that'll be the first key near-term test for dip buyers in turning the momentum back on their side.
the compilation will feature tracks from Coffintexts
Colombian label TraTraTrax have announced a new compilation
Due for release on 15th November, the third edition of the label's series features tracks from Coffintexts
Launched in 2022 by label founders DJ Lomalinda, Nyksan and Verraco, the series was designed to bring together heavyweights of the region, friends and fam + Latin diaspora". The first edition featured in DJ Mag's Top Compilations of 2022.
No one can sit on these legendary Rimax chairs
or to stand and dance on those same chairs
“16 bangers with a very diverse sound spectrum
all crossed by sharp and futuristic sound design
Familiar household names and new artists who have been recent favourites make up the vol
Earlier this year, TraTraTrax announced the launch of an ambient sub-label with the 'Ezmerelda' EP. Last month, the label released their first artist album, 'Desde los oídos de un sapo' by Uruguayan DJ
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India may allow lowering the government’s ownership in five state-run banks via stake sales or the lenders themselves selling shares to large investors that will help them meet minimum public holding norms