Nonplanar integrability at two loops

In this article we compute the action of the two loop dilatation operator on restricted Schur polynomials that belong to the su(2) sector, in the displaced corners approximation. In this non-planar large N limit, operators that diagonalize the one loop dilatation operator are not corrected at two loops. The resulting spectrum of anomalous dimensions is related to a set of decoupled harmonic oscillators, indicating integrability in this sector of the theory at two loops. The anomalous dimensions are a non-trivial function of the 't Hooft coupling, with a spectrum that is continuous and starting at zero at large N, but discrete at finite N.Comment: version to appear in JHE

H-1 Nuclear Magnetic Resonance Spin-Lattice Relaxation, C-13 Magic-Angle-Spinning Nuclear Magnetic Resonance Spectroscopy, Differential Scanning Calorimetry, and X-Ray Diffraction of Two Polymorphs of 2,6-Di-Tert-Butylnaphthalene

Polymorphism, the presence of structurally distinct solid phases of the same chemical species, affords a unique opportunity to evaluate the structural consequences of intermolecular forces. The study of two polymorphs of 2,6-di-tert-butylnaphthalene by single-crystal x-ray diffraction, differential scanning calorimetry (DSC), C-13 magic-angle-spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy, and H-1 NMR spin-lattice relaxation provides a picture of the differences in structure and dynamics in these materials. The subtle differences in structure, observed with x-ray diffraction and chemical shifts, strikingly affect the dynamics, as reflected in the relaxation measurements. We analyze the dynamics in terms of both discrete sums and continuous distributions of Poisson processes

Emergency Department visits due to intoxications in a Dutch university hospital: Occurrence, characteristics and health care costs

Background: Intoxications with alcohol and drugs are common in the Emergency Department. This study aimed to describe the occurrence and characteristics of intoxications (alcohol, Drugs of Abuse (DOA), pharmaceutical and chemical) presented to the Emergency Department and the health care costs of these intoxications. Methods: This was a retrospective medical record study of all patients (≥ 16 years) who presented to the Emergency Department of an inner-city academic hospital in the Netherlands due to single or multiple intoxication(s) as the primary or secondary reason in the year 2016. An intoxication was reported as present if the attending physician described the intoxication in the patient's medical record. Results: A total of 783 patients were included, accounting for 3.2% of the adult Emergency Department population (age ≥ 16 year). In 30% more than one substance was used. Intoxications with alcohol, Drugs of Abuse and pharmaceuticals was reported in respectively 62%, 29% and 21% of the intoxicated patients. The mean costs per patient presenting with an intoxication to the Emergency Department was € 1,490. The mean costs per patient were highest for pharmaceutical intoxications (€ 2,980), followed by Drugs of Abuse (€ 1,140) and alcohol (€ 1,070). Conclusions: Intoxications among patients aged 16 years and older are frequently seen at the Emergency Department and are frequently caused by multiple substances. Alcohol is the most common intoxication. Substantial healthcare costs are involved. Therefore, this study suggests that further research into hazardous alcohol consumption and DOA abuse is warranted. Copyright

International nonproprietary names for monoclonal antibodies: an evolving nomenclature system

Appropriate nomenclature for all pharmaceutical substances is important for clinical development, licensing, prescribing, pharmacovigilance, and identification of counterfeits. Nonproprietary names that are unique and globally recognized for all pharmaceutical substances are assigned by the International Nonproprietary Names (INN) Programme of the World Health Organization (WHO). In 1991, the INN Programme implemented the first nomenclature scheme for monoclonal antibodies. To accompany biotechnological development, this nomenclature scheme has evolved over the years; however, since the scheme was introduced, all pharmacological substances that contained an immunoglobulin variable domain were coined with the stem -mab. To date, there are 879 INN with the stem -mab. Owing to this high number of names ending in -mab, devising new and distinguishable INN has become a challenge. The WHO INN Expert Group therefore decided to revise the system to ease this situation. The revised system was approved and adopted by the WHO at the 73rd INN Consultation held in October 2021, and the radical decision was made to discontinue the use of the well-known stem -mab in naming new antibody-based drugs and going forward, to replace it with four new stems: -tug, -bart, -mig, and -ment

International nonproprietary names for monoclonal antibodies: an evolving nomenclature system

Appropriate nomenclature for all pharmaceutical substances is important for clinical development, licensing, prescribing, pharmacovigilance, and identification of counterfeits. Nonproprietary names that are unique and globally recognized for all pharmaceutical substances are assigned by the International Nonproprietary Names (INN) Programme of the World Health Organization (WHO). In 1991, the INN Programme implemented the first nomenclature scheme for monoclonal antibodies. To accompany biotechnological development, this nomenclature scheme has evolved over the years; however, since the scheme was introduced, all pharmacological substances that contained an immunoglobulin variable domain were coined with the stem -mab. To date, there are 879 INN with the stem -mab. Owing to this high number of names ending in -mab, devising new and distinguishable INN has become a challenge. The WHO INN Expert Group therefore decided to revise the system to ease this situation. The revised system was approved and adopted by the WHO at the 73rd INN Consultation held in October 2021, and the radical decision was made to discontinue the use of the well-known stem -mab in naming new antibody-based drugs and going forward, to replace it with four new stems: -tug, -bart, -mig, and -ment. Keywords: International Nonproprietary Name (INN); antibodies; antibody-based drugs; antibody-drug conjugates; biological drugs; biologics; nomenclature scheme; pharmaceuticals; safety; therapeutic antibodies

Correction for Kipkorir et al., "De Novo Cobalamin Biosynthesis, Transport, and Assimilation and Cobalamin-Mediated Regulation of Methionine Biosynthesis in Mycobacterium smegmatis"

Volume 203, no. 7, e00620-20, 2021, https://doi.org/10.1128/JB.00620-20. Page 1: This article was published on 8 March 2021 with Stephanie S. Dawes missing from the byline. The byline was updated in the version posted on 21 January 2022. The following corrections were also made in that version. Page 1, footnote box: The following footnote was added. “§Present address: Stephanie S. Dawes, Laboratory of Structural Biology, School of Biological Sciences and Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand.” Page 14, Acknowledgments, line 3: “and Stephanie Dawes for providing the DmetE cobK::hyg mutant” was deleted. Page 14, Acknowledgments, lines 1 and 2 from bottom: “(to V.M. and D.F.W.)” was changed to “(to S.S.D., V.M., and D.F.W.).

Seismogenic faults, landslides, and associated tsunamis off southern Italy - Cruise No. M86/2, December 27, 2011 - January 17, 2012, Cartagena (Spain) - Brindisi (Italy)

Summary The continental margins of southern Italy are located along converging plate boundaries, which are affected by intense seismicity and volcanic activity. Most of the coastal areas experienced severe earthquakes, landslides, and tsunamis in historical and/or modern times. The most prominent example is the Messina earthquake of Dec. 28, 1908 (Ms=7.3; 80,000 casualties), which was characterized by the worst tsunami Italy experienced in the historical time (~2000 casualties). It is, however, still unclear, whether this tsunami was triggered by a sudden vertical movement along a major fault during the earthquake or as a result of a giant marine slide initiated by the earthquake. The recurrence rates of major landslides and therefore the risk associated with landslides is also unknown. Based on detailed bathymetric data sets collected by Italian colleagues in the frame of the MaGIC Project (Marine Geohazards along the Italian Coast), we collected seismic data (2D and 3D) and gravity cores in three working areas (The Messina Straits, off Eastern Sicily, the Gioia Basin). A dense grid of new 2D-seismic data in the Messina Straits will allow to map fault patterns in great detail. One interesting outcome in this context is the identification of a set of normal faults striking in an EW-direction, which is almost perpendicular to the previously postulated faults. This EW-striking faults seem to be active. The area off eastern Sicily is characterized by numerous landslides and a complex deformation pattern. A 3D-seismic data set has been collected during the cruise using the so called P-cable in order to investigate these deformation patterns in detail. The new data will be the basis for a risk assessment in the working areas

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology