Bero Roos
Theor. Probability and Math. Statist. 111 (), 137-151.
Abstract, references and article information

Chris A.J. Klaassen
Theor. Probability and Math. Statist. 111 (), 9-19.
Abstract, references and article information

Elisa Vidal
Dec 1, 2020; 61:1733-1746
Research Articles

Spatial changes of FAs in the retina in response to different dietary n-3 formulations have never been explored, although a diet rich in EPA and DHA is recommended to protect the retina against the effects of aging. In this study, Wistar rats were fed for 8 weeks with balanced diet including either EPA-containing phospholipids (PLs), EPA-containing TGs, DHA-containing PLs, or DHA-containing TGs. Qualitative changes in FA composition of plasma, erythrocytes, and retina were evaluated by gas chromatography-flame ionization detector. Following the different dietary intakes, changes to the quantity and spatial organization of PC and PE species in retina were determined by LC coupled to MS/MS and MALDI coupled to MS imaging. The omega-3 content in the lipids of plasma and erythrocytes suggests that PLs as well as TGs are good omega-3 carriers for retina. However, a significant increase in DHA content in retina was observed, especially molecular species as di-DHA-containing PC and PE, as well as an increase in very long chain PUFAs (more than 28 carbons) following PL-EPA and TG-DHA diets only. All supplemented diets triggered spatial organization changes of DHA in the photoreceptor layer around the optic nerve. Taken together, these findings suggest that dietary omega-3 supplementation can modify the content of FAs in the rat retina.

The faithful segregation, or “partition,” of many low-copy number bacterial plasmids is driven by plasmid-encoded ATPases that are represented by the P1 plasmid ParA protein. ParA binds to the bacterial nucleoid via an ATP-dependent nonspecific DNA (nsDNA)-binding activity, which is essential for partition. ParA also has a site-specific DNA-binding activity to the par operator (parOP), which requires either ATP or ADP, and which is essential for it to act as a transcriptional repressor but is dispensable for partition. Here we examine how DNA binding by ParA contributes to the relative distribution of its plasmid partition and repressor activities, using a ParA with an alanine substitution at Arg351, a residue previously predicted to participate in site-specific DNA binding. In vivo, the parAR351A allele is compromised for partition, but its repressor activity is dramatically improved so that it behaves as a “super-repressor.” In vitro, ParAR351A binds and hydrolyzes ATP, and undergoes a specific conformational change required for nsDNA binding, but its nsDNA-binding activity is significantly damaged. This defect in turn significantly reduces the assembly and stability of partition complexes formed by the interaction of ParA with ParB, the centromere-binding protein, and DNA. In contrast, the R351A change shows only a mild defect in site-specific DNA binding. We conclude that the partition defect is due to altered nsDNA binding kinetics and affinity for the bacterial chromosome. Furthermore, the super-repressor phenotype is explained by an increased pool of non-nucleoid bound ParA that is competent to bind parOP and repress transcription.

With hundreds of vessels passing through Windsor's waterways every year, the company that fuels many of them will receive nearly $5 million in new funding to improve their infrastructure for the distribution of lower-carbon fuels — making the shipping industry more sustainable and lower emission. 

The Education Department wants states to re-submit "equity plans" to ensure that effective teachers are matched with disadvantaged and minority students.

Commissioner Navarro to provide Naloxone kits and training at event Insurance Commissioner Trinidad Navarro, in collaboration with Public Health’s Kent County Community Response Team, the First Presbyterian Church of Smyrna, and the Smyrna-Clayton Ministerium will provide free training and opioid rescue kits to residents on Wednesday, October 14 from 2:00 to 5:00PM. The event, taking […]

DOVER, DE (Aug. 29, 2022) – The Delaware Division of Public Health’s (DPH) Office of Health Crisis Response (OHCR) is announcing it will begin including fentanyl test strips in Narcan kits it distributes to the public. The effort is part of a harm-reduction strategy aimed at preventing accidental overdoses due to fentanyl consumption.   Fentanyl is now the leading cause of […]

The Delaware Emergency Management Agency (DEMA) and Delaware Division of Public Health (DPH) will distribute potassium iodide (KI) tablets to Delaware residents living within a 10-mile radius (also known as the Emergency Planning Zone or EPZ) of the Salem/Hope Creek Nuclear Generating Stations.

Sirens will be activated for three to five minutes, followed by a test message of the Emergency Alert System (EAS) on local radio stations. Sirens tested are the same ones used to alert the public in the event of an actual emergency. There are 37 sirens in Delaware located within a 10-mile radius of the Salem-Hope Creek Generating Stations in New Jersey. The sirens cover an area north from Delaware City, west to Middletown, and south to Woodland Beach. This test is part of an ongoing program that continually monitors the integrity of the siren system.

  New Castle, Del. – Del Monte Fresh Produce N.A., Inc. is expected to expand its extensive United States’ logistics network upon the closing set for May 20, 2017 for the site of the former AstroPower building, currently owned by Christina School District, located at 300 Executive Drive, Pencader Industrial Park in New Castle with […]

The Delaware Emergency Management Agency (DEMA) and Delaware Division of Public Health (DPH) will distribute free potassium iodide (KI) tablets to Delaware residents living within a 10-mile radius (also known as the Emergency Planning Zone or EPZ) of the Salem/Hope Creek Nuclear Generating Stations. The free tablets will be distributed on Thursday, October 24, between 11 a.m. and 7 p.m. at the Townsend Fire Company, 107 Main Street, Townsend, 19734. Phone: (302) 378-8111.

Man sentenced to three years imprisonment after admitting to possessing and distributing child pornography

High-throughput sequencing (HTS) technologies have been instrumental in investigating biological questions at the bulk and single-cell levels. Comparative analysis of two HTS data sets often relies on testing the statistical significance for the difference of two negative binomial distributions (DOTNB). Although negative binomial distributions are well studied, the theoretical results for DOTNB remain largely unexplored. Here, we derive basic analytical results for DOTNB and examine its asymptotic properties. As a state-of-the-art application of DOTNB, we introduce DEGage, a computational method for detecting differentially expressed genes (DEGs) in scRNA-seq data. DEGage calculates the mean of the sample-wise differences of gene expression levels as the test statistic and determines significant differential expression by computing the P-value with DOTNB. Extensive validation using simulated and real scRNA-seq data sets demonstrates that DEGage outperforms five popular DEG analysis tools: DEGseq2, DEsingle, edgeR, Monocle3, and scDD. DEGage is robust against high dropout levels and exhibits superior sensitivity when applied to balanced and imbalanced data sets, even with small sample sizes. We utilize DEGage to analyze prostate cancer scRNA-seq data sets and identify marker genes for 17 cell types. Furthermore, we apply DEGage to scRNA-seq data sets of mouse neurons with and without fear memory and reveal eight potential memory-related genes overlooked in previous analyses. The theoretical results and supporting software for DOTNB can be widely applied to comparative analyses of dispersed count data in HTS and broad research questions.

ATP-binding cassette transporter subfamily G member 2 (ABCG2) is a membrane-bound transporter responsible for the efflux of various xenobiotics and endobiotics, including protoporphyrin IX (PPIX), an intermediate in the heme biosynthesis pathway. Certain genetic mutations and chemicals impair the conversion of PPIX to heme and/or increase PPIX production, leading to PPIX accumulation and toxicity. In mice, deficiency of ABCG2 protects against PPIX-mediated phototoxicity and hepatotoxicity by modulating PPIX distribution. In addition, in vitro studies revealed that ABCG2 inhibition increases the efficacy of PPIX-based photodynamic therapy by retaining PPIX inside target cells. In this review, we discuss the roles of ABCG2 in modulating the tissue distribution of PPIX, PPIX-mediated toxicity, and PPIX-based photodynamic therapy.

A STING (stimulator of interferon genes) agonist GSK3996915 under investigation in early discovery for hepatitis B was orally dosed to a mouse model for understanding the parent drug distribution in liver, the target organ. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) was used to quantify the distribution of GSK3996915 in liver collected from mice administered a single oral dose at 90 mg/kg. GSK3996915 was detected with a zonal distribution localized in the portal triad and highly concentrated in the main bile ducts, indicating clearance through biliary excretion. High spatial resolution imaging showed the distribution of the parent drug localized to the cellular populations in the sinusoids, including the Kupffer cells. Additionally, a series of drug-related metabolites were observed to be localized in the central zones of the liver. These results exemplify the potential of utilizing MALDI IMS for measuring not only quantitative drug distribution and target exposure but also drug metabolism and elimination in a single suite of experiments.

Glioblastoma (GBM) is a disease of the whole brain, with infiltrative tumor cells protected by an intact blood-brain barrier (BBB). GBM has a poor prognosis despite aggressive treatment, in part due to the lack of adequate drug permeability at the BBB. Standard of care GBM therapies include radiation and cytotoxic chemotherapy that lead to DNA damage. Subsequent activation of DNA damage response (DDR) pathways can induce resistance. Various DDR inhibitors, targeting the key regulators of these pathways such as ataxia telangiectasia mutated and Rad3-related (ATR), are being explored as radio- and chemosensitizers. Elimusertib, a novel ATR kinase inhibitor, can prevent repair of damaged DNA, increasing efficacy of DNA-damaging cytotoxic therapies. Robust synergy was observed in vitro when elimusertib was combined with the DNA-damaging agent temozolomide; however, we did not observe improvement with this combination in in vivo efficacy studies in GBM orthotopic tumor-bearing mice. This in vitro–in vivo disconnect was explored to understand factors influencing central nervous system (CNS) distribution of elimusertib and reasons for lack of efficacy. We observed that elimusertib is rapidly cleared from systemic circulation in mice and would not maintain adequate exposure in the CNS for efficacious combination therapy with temozolomide. CNS distribution of elimusertib is partially limited by P-glycoprotein efflux at the BBB, and high binding to CNS tissues leads to low levels of pharmacologically active (unbound) drug in the brain. Acknowledging the potential for interspecies differences in pharmacokinetics, these data suggest that clinical translation of elimusertib in combination with temozolomide for treatment of GBM may be limited.

In nuclear medicine, estimating the number of radioactive decays that occur in a source organ per unit administered activity of a radiopharmaceutical (i.e., the time-integrated activity coefficient [TIAC]) is an essential task within the internal dosimetry workflow. TIAC estimation is commonly derived by least-squares fitting of various exponential models to organ time–activity data (radiopharmaceutical biodistribution). Rarely, however, are methods used to objectively determine the model that best characterizes the data. Additionally, the uncertainty associated with the resultant TIAC is generally not evaluated. As part of the MIRDsoft initiative, MIRDfit has been developed to offer a biodistribution fitting software solution that provides the following essential features and advantages for internal dose assessment: nuclear medicine–appropriate fit functions; objective metrics for guiding best-fit selection; TIAC uncertainty calculation; quality control and data archiving; integration with MIRDcalc software for dose calculation; and a user-friendly Excel-based interface. For demonstration and comparative validation of MIRDfit’s performance, TIACs were derived from serial imaging studies involving ¹⁸F-FDG and ¹⁷⁷Lu-DOTATATE using MIRDfit. These TIACs were then compared with TIAC estimates obtained using other software. In most cases, the TIACs agreed within approximately 10% between MIRDfit and the other software. MIRDfit has been endorsed by the MIRD Committee of the Society of Nuclear Medicine and Molecular Imaging and has been integrated into the MIRDsoft suite of free dosimetry software; it is available for download at no user cost (https://mirdsoft.org/).

BACKGROUND AND PURPOSE:

Physician-industry relationships can be useful for driving innovation and technologic progress, though little is known about the scale or impact of industry involvement in neuroradiology. The purpose of this study was to assess the trends and distributions of industry payments to neuroradiologists.

This week viewers to BBC World News have been watching a series of reports focusing on the Arab uprisings, two years after they first began. Correspondents have been in Damascus, Tunis, Cairo, the Syria-Lebanon border and elsewhere. Their eyewitness TV reporting is accompanied by further explanation and analysis on our website, bbc.com/news. These are expert journalists, with years of experience and knowledge, living the story on behalf of the audience. They demonstrate our commitment to reporting the world, and bringing clarity to complex events.

Until now, however, viewers in the world's biggest TV market, the US, have found it hard to access BBC reporting of this kind. The market is saturated with TV channels, but for the past couple of years we've been very focused on securing widespread carriage on the distribution systems which bring TV into most homes.

So today the BBC is delighted to announce we have agreed to a partnership with the US cable giant - Time Warner Cable - and through this and other deals, a further 10 million homes in the US will have access to BBC World News 24 hours a day, seven days a week.

This means by the end of this year we will be available in 25 million homes, including those in most of the major markets - New York, Washington DC, Los Angeles, Chicago, Boston. There is still some way to go before we can say we have reached everyone - but 2012 has been a year of significant breakthroughs for us in the US.

The BBC is already well-known in America through its partnerships with public radio, through the success of our website BBC.com/news, and because of our nightly broadcast on public television fronted by Katty Kay. We believe our brand of high-quality, intelligent and non-partisan journalism has something to offer US audiences, and we're determined to make access to our services as simple as possible.

The timing could not be better. We're just a few weeks away from the first broadcasts of BBC World News from our brand new headquarters in central London. Three new studios, a big investment in production and journalism, and working more closely with BBC journalists working in English and 27 other languages - it's more than just a new home, it's a new start. We're delighted to share that even more widely.

Richard Porter is controller of English at BBC Global News

ThermoGenesis Announces Global Res-Q Distribution Agreement With GE Healthcare

Collaboration brings SynXis® platform and global GDS/IDS connectivity and alternative distribution channels for up to 1,200 independent hotels and resorts globally with a focus on driving growth in the United Arab Emirates, Turkey, Qatar, and Saudi Arabia

By 2030, direct digital bookings are expected to reshape the landscape of hotel distribution, overtaking online travel agencies (OTAs) as the primary channel for global hotel reservations. Skift Research’s 2024 Hotel Distribution Outlook reveals that while OTAs currently dominate the market, hotels are increasingly focusing on direct digital channels to engage travelers more effectively and reduce dependency on intermediaries. This shift is projected to generate $409 billion in global hotel bookings through direct digital channels by the end of the decade, marking a pivotal transition in how consumers book travel accommodations.

Shahan Taj Mohammed highlights that NDC is reshaping airline retailing, offering unmatched personalization, efficiency, and flexibility.

Cambridge : Cambridge University Press, 2023.

India and the US will become the engines of global growth, says Nirmala Sitharaman

London ; New York : Continuum, 2006.

WIRED takes a tour of the automated world of online grocery shopping at Ocado’s distribution warehouse http://wired.uk/K3eqQO

Dr. Nahid Bhadelia, founding director of the BU Center for Emerging Infectious Diseases Policy and Research (CEID), explores why vaccines haven’t always been getting to where they need to go during the Covid-19 pandemic.

AIADMK secretary A. Anbalagan and former MLA A. Baskar led the demonstration against the govt.’s ‘failure’ to supply free rice and sugar as promised; the former alleged that only beneficiaries in constituencies of those in power received the gift

Creating a safer environment for women and children is a complex issue; punishment alone cannot change society

National Bureau of Economic Research

National Bureau of Economic Research