Colorful variety is what the most famous chocolate bar in the 100g format from Ritter Sport stands for. Its dimensions are just as varied as the many different types of chocolate offered.

Awards were presented in the categories of Design, Functionality & Convenience, Logistics & Material Flow, Sustainability, and more. The awards are a precursor to the Gold Awards that will be announced in September.

Michael Kundinger of Kundinger Inc. elaborates on several of the technologies that the company showcased at its booth at the recent Converters Expo.

More than 800 people have been thrown out of work by the abrupt closure of audio-video equipment manufacturer Funai (Thailand) Co in Nakhon Ratchasima.

Requirements of distributed ledger systems for secure human factor services

Client to authenticator protocol/Universal 2-factor framework

New Appendix V - Provisional planning values for the fullband equipment impairment factor and the fullband packet loss robustness factor

Sodium-ion batteries are cheaper than lithium-ion batteries — and they're also more environmentally friendly. And "In the past few years, sodium-ion battery production has increased in the United States," reports the Washington Post, with a new factory planned to manufacture them "in the same way as lithium-ion batteries, just with different ingredients. Instead of using expensive materials like lithium, nickel and cobalt, these will be made of sodium, iron and manganese..." Last month, sodium-ion battery manufacturer Natron Energy announced it would open a "gigafactory" in North Carolina that would produce 24 gigawatt hours of batteries annually, enough energy to charge 24,000 electric vehicles. But sodium-ion batteries are still early in their development compared with lithium-ion, and they have yet to hit the market on a massive scale. "It's unlikely sodium-ion could displace lithium-ion anytime soon," said Keith Beers, polymer science and materials chemistry principal engineer at technical consultancy firm Exponent... The biggest limitation of sodium-ion batteries is their weight. Sodium weighs nearly three times as much as lithium, and it cannot store the same amount of energy. As a result, sodium-ion batteries tend to be larger. Jens Peters, an economics professor at the University of Alcalá in Madrid, said the energy density could be improved over time in sodium-ion batteries. But, he added, "what we found out so far in our assessments is that it is not a game changer." Sodium-ion batteries are touted to be the environmentally friendly alternative to their lithium-ion counterparts, thanks to their raw materials. Sodium, iron and manganese are all abundant elements on the planet, so they require less energy to extract and cost less... Sodium-ion batteries also last longer than lithium-ion ones because they can withstand more charge cycles, said Wendell Brooks, co-CEO of Natron Energy. "Our product can have millions of cycles," said Brooks, "where lithium-ion would have three to five thousand cycles and wear out a lot faster...." Sodium-ion batteries aren't the best fit for smartphones or electric vehicles, which need to store lots of energy. However, one advantage is their low cost. And they could be a good candidate in situations where the size of the battery isn't a concern, like energy storage. "When something is built out to support grid or backup storage, it doesn't need to be very dense. It's staying put," Beers said. Natron will invest nearly $1.4 billion in the factory "to meet the rapidly expanding demand for critical power, industrial and grid energy storage solutions," according to their announcement. "Natron's high-performance sodium-ion batteries outperform lithium-ion batteries in power density and recharging speed, do not require lithium, cobalt, copper, or nickel, and are non-flammable... Natron's batteries are the only UL-listed sodium-ion batteries on the market today, and will be delivered to a wide range of customer end markets in the industrial power space, including data centers, mobility, EV fast charging, microgrids, and telecom, among others."

Read more of this story at Slashdot.

Portnox, provider of cloud-native, zero trust access control solutions, today unveiled the results of its latest survey, ‘CISO Perspectives for 2025’, revealing critical insights into the challenges faced by Chief Information Security Officers (CISOs) at large enterprises.

In June 2024, manufacturing accounted for 8.8% of the UK’s total economic output and employed 2.6 million people – representing 7.0% of the workforce.

Confidence in the sector is rising, with a 1.2% output increase in the first quarter of 2024 compared to the previous quarter, its highest level since 2022.

Boeing factory workers to vote on deal that could end seven-week strike

Boeing factory workers bring an end to turbulence as they vote to return to work

The risk factors include smoking, excessive alcohol use and high LDL cholesterol.

Sara Tenney talks about how ACS creates digital primers to bridge the gap between undergraduate-level depth and scholarly articles. 

The Biden administration announced a $162 million investment in microchip technology on Thursday in an attempt to boost domestic production of computer chips.

The Agency is every online community member's worst fears come to life: a real honest-to-goodness troll/noise factory where dozens of employees using hundreds of accounts post thousands of highly targeted and coordinated attacks as awful comments on Twitter, Facebook, and forums in order to sway public opinion about geopolitics. From a nondescript office building in St. Petersburg, Russia, an army of well-paid “trolls” has tried to wreak havoc all around the Internet — and in real-life American communities...

Panelistas analizaron los motivos del triunfo del candidato republicano, los errores del partido Demócrata y los efectos en la política internacional con el regreso de Trump a la presidencia.

Tipos, factores y causas de la trombosis.

Connor Bedard's former coach says the World Junior hockey phenom is something special; how Buffalo is rallying together after Damar Hamlin's near death on the football field; how the bid to keep Prince Harry's memoir from leaking plays into the hype; seriously though, what exactly is Ozempic?; Toronto bartender mixes alcohol-free cocktails for Dry January and beyond; why BioNTech's plan to ship prefabricated mRNA vaccine factories to Rwanda is controversial; and more.

By Georgia Leybourne, Chief Marketing Officer, Linnworks.

Success in ecommerce and retail today hinges on consumer convenience. It is fast becoming a powerful tool in the e-commerce industry, transforming the way businesses engage with their customers and increasing sales through social commerce.

OMG. I can't believe October is over already. I blame Satisfactory which, okay, I do get it now, and it did destroy my body and mind. I am inches from being done now; I just want to make sure that I finish it with enough force that I do actually put it away, as I could imagine tinkering with my saddest factory forever.

The game isn't without flaw, but I think most of those flaws are not interesting to talk about. I do have one petty but important criticism, which is mildly spoilerful and anyway will only be interesting if you played the game. There is an object called the Somersloop ("cool S") which allows you to double the output of a machine. Canonically this item is some kind of "loop" and the flavor text talks about how it is able to create more energy than you put into it. So when I'm out hunting for Korok seeds I have this thought that maybe I could create a loop of factories whereby it would create infinite resources by repeatedly doubling. And I'm thinking about it but the crafting tree doesn't have any notable loops in it, but I remember the "packager" which allows you to put a fluid in a container or the converse, and I'm like: Yes, that's great! So I get back to base and I am doing this, just for fun to create an infinite fuel factory or whatever, and I realize that the packager just doesn't have a slot for a Somersloop. They must just hate fun, elegant twists. It would not break the game to allow this (you can always get infinite resources lots of other ways) or cause any other problem I can think of. Hmph!

The thing about constructing a factory and watching it churn is that it's basically the same thing as a programming project that you invented for yourself, and it's probably better to do the programming project. Here's progress on my mysterious rectangle:

"...while I’m writing I need total silence, but even so, the music shares such a similar landscape with the text it’s hard to believe it wasn’t present from the beginning."

Ford is getting its workers in Cologne, Germany, to work fewer hours. The carmaker said a "lower than expected demand for electric vehicles" brought on the shift. The carmaker has more than 4,000 employees at its Cologne plant. Ford is slashing the work hours of its manufacturing plant workers in…

Google's cloud division has announced that it will enforce mandatory multi-factor authentication (MFA) for all users by the end of 2025 as part of its efforts to improve account security. "We will be implementing mandatory MFA for Google Cloud in a phased approach that will roll out to all users worldwide during 2025," Mayank Upadhyay, vice president of engineering and distinguished engineer at

The post Ulyanovsky Cartridge Manufacturing Factory appeared first on English Russia.

The carmaker has more than 4,000 employees at its Cologne plant. It also has another plant in Saarlouis, in southwestern Germany.

2FA, the common abbreviation for two-factor authentication is a word often spoken about when one is setting up a website or account where security is vital. With more and more confidential information being uploaded on the net, it makes sense to add additional measures to prevent hackers from gaining access to an account. In terms […]

The post Enabling Two-Factor Authentication (2FA) for a PayPal Account appeared first on Tips and Tricks HQ.

With more and more online marketplaces popping up, many individuals prefer to pay for items, whether they be new or second hand using the PayPal Goods and Services option. The PayPal ‘Goods and Services’ option gives buyers further peace of mind with the PayPal guarantee. If the seller does not provide what they have described, […]

The post Factoring In PayPal Fees When Sending Money Using the Goods and Services Option appeared first on Tips and Tricks HQ.

Yi Zhang
Sep 1, 2005; 4:1240-1250
Research

Zika virus (ZIKV) is a neurotropic flavivirus that causes several diseases including birth defects such as microcephaly. Intrinsic immunity is known to be a frontline defense against viruses through host anti-viral restriction factors. Limited knowledge is available on intrinsic immunity against ZIKV in brains. Amyloid precursor protein (APP) is predominantly expressed in brains and implicated in the pathogenesis of Alzheimer's diseases. We have found that ZIKV interacts with APP, and viral infection increases APP expression via enhancing protein stability. Moreover, we identified the viral peptide, HGSQHSGMIVNDTGHETDENRAKVEITPNSPRAEATLGGFGSLGL, which is capable of en-hancing APP expression. We observed that aging brain tissues with APP had protective effects on ZIKV infection by reducing the availability of the viruses. Also, knockdown of APP expression or blocking ZIKV-APP interactions enhanced ZIKV replication in human neural progenitor/stem cells. Finally, intracranial infection of ZIKV in APP-null neonatal mice resulted in higher mortality and viral yields. Taken together, these findings suggest that APP is a restriction factor that protects against ZIKV by serving as a decoy receptor, and plays a protective role in ZIKV-mediated brain injuries.

Hepatocyte nuclear factor-1β (HNF-1β) is a tissue-specific transcription factor that is required for normal kidney development and renal epithelial differentiation. Mutations of HNF-1β produce congenital kidney abnormalities and inherited renal tubulopathies. Here, we show that ablation of HNF-1β in mIMCD3 renal epithelial cells results in activation of β-catenin and increased expression of lymphoid enhancer–binding factor 1 (LEF1), a downstream effector in the canonical Wnt signaling pathway. Increased expression and nuclear localization of LEF1 are also observed in cystic kidneys from Hnf1b mutant mice. Expression of dominant-negative mutant HNF-1β in mIMCD3 cells produces hyperresponsiveness to exogenous Wnt ligands, which is inhibited by siRNA-mediated knockdown of Lef1. WT HNF-1β binds to two evolutionarily conserved sites located 94 and 30 kb from the mouse Lef1 promoter. Ablation of HNF-1β decreases H3K27 trimethylation repressive marks and increases β-catenin occupancy at a site 4 kb upstream to Lef1. Mechanistically, WT HNF-1β recruits the polycomb-repressive complex 2 that catalyzes H3K27 trimethylation. Deletion of the β-catenin–binding domain of LEF1 in HNF-1β–deficient cells abolishes the increase in Lef1 transcription and decreases the expression of downstream Wnt target genes. The canonical Wnt target gene, Axin2, is also a direct transcriptional target of HNF-1β through binding to negative regulatory elements in the gene promoter. These findings demonstrate that HNF-1β regulates canonical Wnt target genes through long-range effects on histone methylation at Wnt enhancers and reveal a new mode of active transcriptional repression by HNF-1β.

Evolving evidence suggests that nicotine may contribute to impaired asthma control by stimulating expression of nerve growth factor (NGF), a neurotrophin associated with airway remodeling and airway hyperresponsiveness. We explored the hypothesis that nicotine increases NGF by reducing lung fibroblast (LF) microRNA-98 (miR-98) and PPARγ levels, thus promoting airway remodeling. Levels of NGF, miR-98, PPARγ, fibronectin 1 (FN1), endothelin-1 (EDN1, herein referred to as ET-1), and collagen (COL1A1 and COL3A1) were measured in human LFs isolated from smoking donors, in mouse primary LFs exposed to nicotine (50 μg/ml), and in whole lung homogenates from mice chronically exposed to nicotine (100 μg/ml) in the drinking water. In selected studies, these pathways were manipulated in LFs with miR-98 inhibitor (anti-miR-98), miR-98 overexpression (miR-98 mimic), or the PPARγ agonist rosiglitazone. Compared with unexposed controls, nicotine increased NGF, FN1, ET-1, COL1A1, and COL3A1 expression in human and mouse LFs and mouse lung homogenates. In contrast, nicotine reduced miR-98 levels in LFs in vitro and in lung homogenates in vivo. Treatment with anti-miR-98 alone was sufficient to recapitulate increases in NGF, FN1, and ET-1, whereas treatment with a miR-98 mimic significantly suppressed luciferase expression in cells transfected with a luciferase reporter linked to the putative seed sequence in the NGF 3'UTR and also abrogated nicotine-induced increases in NGF, FN1, and ET-1 in LFs. Similarly, rosiglitazone increased miR-98 and reversed nicotine-induced increases in NGF, FN1, and ET-1. Taken together, these findings demonstrate that nicotine-induced increases in NGF and other markers of airway remodeling are negatively regulated by miR-98.

T. A. Suslina
St. Petersburg Math. J. 35 (), 537-570.
Abstract, references and article information

Carnosine (β-alanyl-l-histidine) and anserine (β-alanyl-3-methyl-l-histidine) are abundant peptides in the nervous system and skeletal muscle of many vertebrates. Many in vitro and in vivo studies demonstrated that exogenously added carnosine can improve muscle contraction, has antioxidant activity, and can quench various reactive aldehydes. Some of these functions likely contribute to the proposed anti-aging activity of carnosine. However, the physiological role of carnosine and related histidine-containing dipeptides (HCDs) is not clear. In this study, we generated a mouse line deficient in carnosine synthase (Carns1). HCDs were undetectable in the primary olfactory system and skeletal muscle of Carns1-deficient mice. Skeletal muscle contraction in these mice, however, was unaltered, and there was no evidence for reduced pH-buffering capacity in the skeletal muscle. Olfactory tests did not reveal any deterioration in 8-month-old mice lacking carnosine. In contrast, aging (18–24-month-old) Carns1-deficient mice exhibited olfactory sensitivity impairments that correlated with an age-dependent reduction in the number of olfactory receptor neurons. Whereas we found no evidence for elevated levels of lipoxidation and glycation end products in the primary olfactory system, protein carbonylation was increased in the olfactory bulb of aged Carns1-deficient mice. Taken together, these results suggest that carnosine in the olfactory system is not essential for information processing in the olfactory signaling pathway but does have a role in the long-term protection of olfactory receptor neurons, possibly through its antioxidant activity.

Cellular energy demands are met by uptake and metabolism of nutrients like glucose. The principal transcriptional regulator for adapting glycolytic flux and downstream pathways like de novo lipogenesis to glucose availability in many cell types is carbohydrate response element–binding protein (ChREBP). ChREBP is activated by glucose metabolites and post-translational modifications, inducing nuclear accumulation and regulation of target genes. Here we report that ChREBP is modified by proline hydroxylation at several residues. Proline hydroxylation targets both ectopically expressed ChREBP in cells and endogenous ChREBP in mouse liver. Functionally, we found that specific hydroxylated prolines were dispensable for protein stability but required for the adequate activation of ChREBP upon exposure to high glucose. Accordingly, ChREBP target gene expression was rescued by re-expressing WT but not ChREBP that lacks hydroxylated prolines in ChREBP-deleted hepatocytes. Thus, proline hydroxylation of ChREBP is a novel post-translational modification that may allow for therapeutic interference in metabolic diseases.

Oxygen regulates hypoxia-inducible factor (HIF) transcription factors to control cell metabolism, erythrogenesis, and angiogenesis. Whereas much has been elucidated about how oxygen regulates HIF, whether lipids affect HIF activity is un-known. Here, using cultured cells and two animal models, we demonstrate that lipoprotein-derived fatty acids are an independent regulator of HIF. Decreasing extracellular lipid supply inhibited HIF prolyl hydroxylation, leading to accumulation of the HIFα subunit of these heterodimeric transcription factors comparable with hypoxia with activation of downstream target genes. The addition of fatty acids to culture medium suppressed this signal, which required an intact mitochondrial respiratory chain. Mechanistically, fatty acids and oxygen are distinct signals integrated to control HIF activity. Finally, we observed lipid signaling to HIF and changes in target gene expression in developing zebrafish and adult mice, and this pathway operates in cancer cells from a range of tissues. This study identifies fatty acids as a physiological modulator of HIF, defining a mechanism for lipoprotein regulation that functions in parallel to oxygen.

The Wnt/β-catenin pathway is one of the major pathways that regulates embryonic development, adult homeostasis, and stem cell self-renewal. In this pathway, transcription factors T-cell factor and lymphoid enhancer factor (TCF/LEF) serve as a key switch to repress or activate Wnt target gene transcription by recruiting repressor molecules or interacting with the β-catenin effector, respectively. It has become evident that the protein stability of the TCF/LEF family members may play a critical role in controlling the activity of the Wnt/β-catenin signaling pathway. However, factors that regulate the stability of TCF/LEFs remain largely unknown. Here, we report that pVHL binding protein 1 (VBP1) regulates the Wnt/β-catenin signaling pathway by controlling the stability of TCF/LEFs. Surprisingly, we found that either overexpression or knockdown of VBP1 decreased Wnt/β-catenin signaling activity in both cultured cells and zebrafish embryos. Mechanistically, VBP1 directly binds to all four TCF/LEF family members and von Hippel-Lindau tumor-suppressor protein (pVHL). Either overexpression or knockdown of VBP1 increases the association between TCF/LEFs and pVHL and then decreases the protein levels of TCF/LEFs via proteasomal degradation. Together, our results provide mechanistic insights into the roles of VBP1 in controlling TCF/LEFs protein stability and regulating Wnt/β-catenin signaling pathway activity.

Acute lung injury (ALI), is a rapidly progressing heterogenous pulmonary disorder that possesses a high risk of mortality. Accumulating evidence has implicated the activation of the p65 subunit of NF-κB [NF-κB(p65)] activation in the pathological process of ALI. microRNAs (miRNAs), a group of small RNA molecules, have emerged as major governors due to their post-transcriptional regulation of gene expression in a wide array of pathological processes, including ALI. The dysregulation of miRNAs and NF-κB activation has been implicated in human diseases. In the current study, we set out to decipher the convergence of miR-99b and p65 NF-κB activation in ALI pathology. We measured the release of pro-inflammatory cytokines (IL-1β, IL-6, and TNFα) in bronchoalveolar lavage fluid using ELISA. MH-S cells were cultured and their viability were detected with cell counting kit 8 (CCK8) assays. The results showed that miR-99b was up-regulated, while PRDM1 was down-regulated in a lipopolysaccharide (LPS)-induced murine model of ALI. Mechanistic investigations showed that NF-κB(p65) was enriched at the miR-99b promoter region, and further promoted its transcriptional activity. Furthermore, miR-99b targeted PRDM1 by binding to its 3'UTR, causing its down-regulation. This in-creased lung injury, as evidenced by increased wet/dry ratio of mouse lung, myeloperoxidase activity and pro-inflammatory cytokine secretion, and enhanced infiltration of inflammatory cells in lung tissues. Together, our findings indicate that NF-κB(p65) promotion of miR-99b can aggravate ALI in mice by down-regulating the expression of PRDM1.

VOLUME 289 (2014) PAGES 6604–6618In Fig. 4G, in the foxi1 panel, the images in Fig. 4G, i and l, corresponding to “smad1 MO” and “smad5 MO + samd1/9 mRNA” samples, respectively, were inadvertently reused during figure preparation. This error has now been corrected using images pertaining to each treatment and sample. This correction does not affect the results or conclusions of the work.jbc;295/52/18650/F4F1F4Figure 4G.

This analysis aimed to identify clinical factors associated with positivity on repeat ⁶⁸Ga-PSMA-11 PET/CT after a negative scan in patients with recurrent prostate cancer (PCa) under observation. Methods: This single-center, retrospective analysis included patients who underwent at least 2 ⁶⁸Ga-PSMA-11 PET/CT scans (PET1 and PET2) at UCLA between October 2016 and June 2021 for recurrent PCa with negative PET1 and no PCa-related treatments between the 2 scans. Using Prostate Cancer Molecular Imaging Standardized Evaluation criteria to define negative and positive scans, the final cohort was divided into PET2-negative (PET2-Neg) and PET2-positive (PET2-Pos). The same PET1 was used twice in the more than 2 PET cases with inclusion criteria fulfilled. Patient characteristics and clinical parameters were compared between the 2 cohorts using Mann–Whitney U test and Fisher exact test. Areas under the curve (AUCs) of the receiver operating characteristic and the Youden index were computed to determine the discrimination ability of statistically significant factors and specific cut points that maximized sensitivity and specificity, respectively. Results: The final analysis included 83 sets of 2 PET/CT scans from 70 patients. Thirty-nine of 83 (47%) sets were PET2-Neg, and 44 of 83 (53%) sets were PET2-Pos. Prostate-specific antigen (PSA) increased from PET1 to PET2 for all 83 (100%) sets of scans. Median PSA at PET1 was 0.4 ng/mL (interquartile range, 0.2–1.0) and at PET2 was 1.6 ng/mL (interquartile range, 0.9–3.8). We found higher serum PSA at PET2 (median, 1.8 vs. 1.1 ng/mL; P = 0.015), absolute PSA difference (median, 1.4 vs. 0.7 ng/mL; P = 0.006), percentage of PSA change (median, +270.4% vs. +150.0%: P = 0.031), and median PSA velocity (0.044 vs. 0.017 ng/mL/wk, P = 0.002) and shorter PSA doubling time (DT; median, 5.1 vs. 8.3 mo; P = 0.006) in the PET2-Pos cohort than in the PET2-Neg cohort. Receiver operating characteristic curves showed cutoffs for PSA at PET2 of 4.80 ng/mL (sensitivity, 34%; specificity, 92%; AUC, 0.66), absolute PSA difference of 0.95 ng/mL (sensitivity, 62%; specificity, 71%; AUC, 0.68), percentage of PSA change of a positive 289.50% (sensitivity, 48%; specificity, 82%; AUC, 0.64), PSA velocity of 0.033 ng/mL/wk (sensitivity, 57%; specificity, 80%; AUC, 0.70), and PSA DT of 7.91 mo (sensitivity, 71%; specificity, 62%; AUC, 0.67). Conclusion: Patients with recurrent PCa under observation after a negative ⁶⁸Ga-PSMA-11 PET/CT scan with markedly elevated serum PSA levels and shorter PSA DT are more likely to have positive findings on repeat ⁶⁸Ga-PSMA-11 PET/CT.

An explosion at a food-coloring factory in Louisville, Ky., hospitalized at least 11, including two in critical condition, on Tuesday afternoon.

An explosion at a food-coloring factory in Louisville, Ky., hospitalized at least 11, including two in critical condition, on Tuesday afternoon.

Holly Oakley
Oct 4, 2006; 26:10129-10140
Neurobiology of Disease

Holly Oakley
Oct 4, 2006; 26:10129-10140
Neurobiology of Disease

Odor information arrives first in the main olfactory bulb and is then broadcasted to the olfactory cortices and striatum. Downstream regions have unique cellular and connectivity architectures that may generate different coding patterns to the same odors. To reveal region-specific response features, tuning and decoding of single-unit populations, we recorded responses to the same odors under the same conditions across regions, namely, the main olfactory bulb (MOB), the anterior olfactory nucleus (AON), the anterior piriform cortex (aPC), and the olfactory tubercle of the ventral striatum (OT), of awake male mice. We focused on chemically closely related aldehydes that still create distinct percepts. The MOB had the highest decoding accuracy for aldehydes and was the only region encoding chemical similarity. The MOB had the highest fraction of inhibited responses and narrowly tuned odor-excited responses in terms of timing and odor selectivity. Downstream, the interconnected AON and aPC differed in their response patterns to the same stimuli. While odor-excited responses dominated the AON, the aPC had a comparably high fraction of odor-inhibited responses. Both cortices share a main output target that is the MOB. This prompted us to test if the two regions convey also different net outputs. Aldehydes activated AON terminals in the MOB as a bulk signal but inhibited those from the aPC. The differential cortical projection responses generalized to complex odors. In summary, olfactory regions reveal specialized features in their encoding with AON and aPC differing in their local computations, thereby generating inverse net centrifugal and intercortical outputs.