gebhart/patrepeval huggingface dataset:
REGULATION OF B CELL FUNCTION BY THE IMMUNOSUPPRESSIVE AGENT LEFLUNOMIDE1 (1996)

Leflunomide is an immunosuppressive drug capable of inhibiting cellular and humoral mediated responses in vivo. The mechanism responsible for suppression of B cell antibody responses in vivo has not been identified. In this study we demonstrate that leflunomide functions to inhibit murine B cell antibody production by directly acting on the B cell. Experiments performed in vivo showed that both T cell-dependent as well as T cell-independent antigen responses were suppressed by leflunomide. Initial in vitro experiments demonstrated that leflunomide inhibited B cell antibody production by decreasing B cell proliferation. The suppression of B cell proliferation induced by a variety of stimuli that use different signal cascade components suggested that leflunomide was acting on a common component required for B cell proliferation. Kinetic studies with LPS activated B cells revealed that leflunomide retained its inhibitory activity when added as late as 24 hr after stimulation in an 88-hr assay. By analyzing the cell cycle of LPS-stimulated B cells we observed that leflunomide targets two different stages in cell cycle transition: (1) from G1 to S phase and (2) from S phase to G2/M phase. Analysis of one of the cyclin-dependent kinases, Cdk2 protein, by Western blot revealed that Cdk2 levels were decreased, in the presence of leflunomide, 48 hr after stimulation. These data further confirmed that leflunomide inhibited B cell progression through the S phase. We also present evidence that the addition of exogenous uridine reversed the antiproliferative activity of leflunomide. This indicated that leflunomide acted as a pyrimidine synthesis inhibitor, thereby inhibiting B cell proliferation and cell cycle progression.
The policy responses of tourism agencies to emerging digital skills constraints: A critical assessment of six countries (2022)

Abstract This paper analyses policies and practices designed to support digital transformation in the tourism workforce in six OECD countries, namely Germany, Greece, Iceland, New Zealand, Switzerland, and the United Kingdom. Data for the project were gathered via a questionnaire survey, interviews with key informants and examination of various policy documents in 2021. Contrasting practice in relation to digital skills development is revealed. Significant deficiencies are evident in relation to the availability of high‐quality data, evaluation, understanding, leadership, and infrastructure among the six countries. Ways in which effective policy development might emerge are suggested.
A prospective randomized wait list control trial of intravenous iron sucrose in older adults with unexplained anemia and serum ferritin 20–200 ng/mL (2014)

Anemia is common in older persons and is associated with substantial morbidity and mortality. One third of anemic older adults have unexplained anemia of the elderly (UAE). We carried out a randomized, wait list control trial in outpatients with UAE and serum ferritin levels between 20 and 200 ng/mL. Intravenous iron sucrose was given as a 200-mg weekly dose for 5 weeks either immediately after enrollment (immediate intervention group) or following a 12-week wait list period (wait list control group). The primary outcome measure was changed in 6-minute walk test (6MWT) distances from baseline to 12 weeks between the two groups. Hematologic, physical, cognitive, and quality of life parameters were also assessed. The study was terminated early after 19 subjects enrolled. The distance walked in the 6MWT increased a mean 8.05±55.48 m in the immediate intervention group and decreased a mean 11.45±49.46 m in the wait list control group (p=0.443). The hemoglobin increased a mean 0.39±0.46 g/dL in the immediate intervention group and declined a mean 0.39±0.85 g/dL in the wait list control group (p=0.026). Thus, a subgroup of adults with UAE may respond to intravenous iron. Enrollment of subjects into this type of study remains challenging.
Lessons from the Growth Plate: Computational Modelling of Chondrogenic Differentiation (2016)

Introduction: The pathways and genes/proteins orchestrating postnatal fracture repair and those involved in embryonic bone development are deemed to be highly similar. As a result of this similarity, combining insights from the wealth of studies focusing on bone developmental biology may provide useful information on the driving mechanisms of differentiation in fracture repair. In this study, we develop a computational approach that evaluates how the individual interactions between genes/proteins can give rise to behaviour observed in the growth plate and what influence individual perturbations can have on cell fate decisions. Materials and Methods: Through manual literature curation a network consisting of 46 genes/proteins, playing a primary role in endochondral ossification, was developed. The network model focuses on cell fate decisions governed by Sox9 and Runx2, transcription factors that play instrumental roles in both chondro- and osteogenic differentiation. In the context of the growth plate, Sox9 and Runx2 are respectively associated with proliferative and hypertrophic chondrocytes. The dynamics of this network were simulated using a simple additive framework. Through a Monte Carlo canalisation analysis the stability of various attractors, associated with a specific cell fate was assessed. Lastly, a genetic algorithm was employed to generate an ensemble of models that capture expression profiles (based on 27 genes/proteins) observed in proliferative and hypertrophic chondrocytes. Results: By means of perturbations (i.e. loss of function and gain of function of individual genes/proteins) this model can be used to perform an in silico screening to determine the relative contribution of each signal to different cell fates. This in silico screening hence highlights which genes/proteins have a large, positive or negative, impact on determining cell fate. In repeating this screening for the generated ensemble of models, trained to mimic growth plate expression profiles and differing only in parameter values, a measure for the uncertainty of the screening results was obtained. Most effects were consistent throughout the ensemble, though some pathways (e.g. the effects of BMPs on Sox9) showed ambivalent results. Discussion: The development of the network model allows for a more holistic assessment of the effect of individual genes/proteins on cell fate decisions. In addition, ensemble modelling can show where more input is needed to determine the effect of a particular perturbation. For tissue engineering, the analysis provides an overview of possible interventions that decrease or increase the propensity for attaining stable (Sox9) or transient (Runx2) cartilage. Conclusion: In integrating interactions from a wide variety of studies the developed model comprises a compendium of knowledge on growth plate signalling. Through dynamical simulations, this information can be effectively harnessed to instruct tissue engineering approaches.
An assessment of data matrix barcode recognition under scaling, rotation and cylindrical warping (2011)

Data Matrix is a 2D barcode with high information density and wide applicability. When printed in documents or used for labeling products, the barcode may be subject to deformations. This paper looks at the recognition of Data Matrix barcodes is under scaling, rotation and cylindrical warping. The results suggest that the readability of Data Matrix barcodes is immune to rotation transformations and responds well to scaling, while it is more seriously impaired by cylindrical warping.
First-Principles Energy Band Calculation for SrAl2O4 with Monoclinic Structure (2002)

Abstract The electronic structure of strontium aluminate, SrAl2O4, is calculated by using the scalar-relativistic full potential linearized augmented plane wave (FLAPW) method. SrAl2O4 is predicted to be an indirect-gap material, since the valence band maximum locates near Z point and the conduction band minimum at Γ point. The valence band with the width ca. 5.3 eV is mainly constructed from O 2p orbitals, where Al 3s3p and Sr 5s5p slightly hybridize with O 2p, and the lower conduction band from Sr 5s orbitals.
Genome-Wide Association Studies in an Isolated Founder Population from the Pacific Island of Kosrae (2009)

It has been argued that the limited genetic diversity and reduced allelic heterogeneity observed in isolated founder populations facilitates discovery of loci contributing to both Mendelian and complex disease. A strong founder effect, severe isolation, and substantial inbreeding have dramatically reduced genetic diversity in natives from the island of Kosrae, Federated States of Micronesia, who exhibit a high prevalence of obesity and other metabolic disorders. We hypothesized that genetic drift and possibly natural selection on Kosrae might have increased the frequency of previously rare genetic variants with relatively large effects, making these alleles readily detectable in genome-wide association analysis. However, mapping in large, inbred cohorts introduces analytic challenges, as extensive relatedness between subjects violates the assumptions of independence upon which traditional association test statistics are based. We performed genome-wide association analysis for 15 quantitative traits in 2,906 members of the Kosrae population, using novel approaches to manage the extreme relatedness in the sample. As positive controls, we observe association to known loci for plasma cholesterol, triglycerides, and C-reactive protein and to a compelling candidate loci for thyroid stimulating hormone and fasting plasma glucose. We show that our study is well powered to detect common alleles explaining >/=5% phenotypic variance. However, no such large effects were observed with genome-wide significance, arguing that even in such a severely inbred population, common alleles typically have modest effects. Finally, we show that a majority of common variants discovered in Caucasians have indistinguishable effect sizes on Kosrae, despite the major differences in population genetics and environment.
An Asian Perspective of the Management of COVID-19: the Asian National Cancer Centers Alliance Led Regional Comparison (2020)

Objective: To describe how the Asian National Cancer Centers Alliance (ANCCA) members preserve high standards of care for cancer patients while battling the COVID-19 pandemic and to propose new strategies in the Asian Cancer Centers’ preparedness to future pandemics. Methods: A 41-question-based survey was developed using an online survey tool and conducted among 15 major Asian National Cancer Centers, including 13 ANCCA members. Direct interviews of several specialists were conducted subsequently to obtain additional answers to key questions that emerged during the survey analysis. Result: Institution/country-specific results provided a strong insight on the diverse ways of managing the pandemic around Asia, while maintaining well-balanced cancer care. Pragmatic strategies were put in place in each NCC hospital, including zoning and intensive triage depending on the pandemic impact. Distancing strategies and telemedicine were implemented in different capacity depending on the national healthcare system. In addition, there was a diverse impact on the manpower and financial aspect of cancer care across surveyed NCCs relating to magnitude of the pandemic impact on the country. Conclusion: The priorities nevertheless remain on maintaining cancer care delivery while protecting both patients and health care workers from the risk of COVID-19 infection. The role of a think-tank such as ANCCA to help share experiences in a timely manner can enhance preparedness in future pandemic scenarios.
Hepatic leukostasis and hypoxic stress in adhesion molecule-deficient mice after gut ischemia/reperfusion. (1997)

The concept that leukocyte-endothelial cell adhesion (LECA) is a major determinant of the tissue injury elicited by ischemia/reperfusion (I/R) is largely based on studies employing adhesion molecule-specific monoclonal antibodies. The objective of this study was to assess the contribution of LECA to I/R injury using mutant mice (all on a C57B1 background) that are deficient in either intracellular adhesion molecule-1, P-selectin, or CD11/CD18. The accumulation of fluorescently labeled leukocytes and the number of nonperfused sinusoids in livers of control and adhesion molecule-deficient mice were monitored by intravital microscopy for 1 h after release of the occluded (for 15 min) superior mesenteric artery. Autofluorescence of pyridine nucleotide (NADH) was measured as an indicator of mitochondrial O2 consumption and redox status. The number of stationary leukocytes in the liver after gut I/R was significantly elevated compared with baseline values in C57B1 (control) mice. Autofluorescence of NADH was also significantly increased (indicating hypoxia) after I/R in these mice, especially in the pericentral region. Intercellular adhesion molecule-1-, CD11/CD18-, and P-selectin-deficient mice all exhibited a blunted leukosequestration response to I/R and smaller increments in nonperfused sinusoids, relative to C57B1 mice. All adhesion molecule-deficient mice also exhibited an attenuated increment in NADH autofluorescence in the pericentral region, relative to control mice. These results from adhesion molecule-deficient mice provide additional support for the view that LECA is an important determinant of the liver dysfunction induced by gut I/R.
Molecular Determinants of Virulence and Stability of a Reporter-Expressing H5N1 Influenza A Virus (2015)

The ability to visualize influenza viruses has far-reaching benefits in influenza virus research. Previously, we reported that an H5N1 virus bearing the Venus reporter gene became more pathogenic to mice and that its reporter gene was more highly expressed and more stably maintained after mouse adaptation. Here, we investigated the molecular determinants behind this enhanced virulence and reporter stability. We found that mutations in PB2 (V25A) and PA (R443K) play crucial roles in the stable maintenance of a foreign protein as an NS1 fusion protein in influenza A virus and in the virulence of influenza virus in mice. Our findings further our knowledge of the pathogenicity of influenza virus in mammals and will help advance influenza virus-related live-imaging studies in vitro and in vivo.
Phosphorylation of Isocyanates and Aldehydes Mediated by Multifunctional N-Phosphine Oxide-substituted Imidazolylidenes (2017)

Abstract The direct syntheses of imidic-phosphinic mixed anhydrides and phosphinates were accomplished via phosphorylation of isocyanates or aldehydes with N-phosphine oxide-substituted imidazolylidenes (PoxIms) that are equipped with both nucleophilic carbene and electrophilic phosphorus moieties. In addition, the catalytic cyclotrimerization of phenyl isocyanate took place by employing a PoxIm having bis-N-phosphine oxide groups. The results presented in the current study demonstrate that judiciously designed multifunctional carbenes represent a promising potential for the phosphorylation of heterocumulenes and carbonyl compounds.
An overview of FDA-approved vaccines & their innovators (2017)

A survey of FDA-approved biologicals focused upon the development of immunotherapies over time to gain insight on the challenges and trends of vaccine development today. Areas covered: A total of 135 different immune-based therapies were broadly divided into passive or active immunotherapies. Whereas just over half of passive immunotherapies targeted infectious diseases, the vast majority of active immunotherapy products (vaccines) were directed against a handful of viral and bacterial pathogens. We also analyze changes in vaccine strategy, including the use of viable antigens and subunit approaches. Expert commentary: An analysis of vaccine innovators revealed an ever-increasing presence of the private sector and a relatively diminishing role for the public sector . Whereas North American companies have contributed to the approval of two-thirds of vaccines, European companies have regained parity in terms of hosting innovators of vaccine research and development.
ChemInform Abstract: SYNTHESIS AND REACTIONS OF 1,2‐DIHALOALKYLSULFONYL ISOCYANATES (1982)

Abstract Die dihalogenierten Isocyanate (I)‐(Ii) können durch Umsetzung der entsprechenden Alkenylisocyanate (II) mit Br, bzw. C12 erhalten werden, wobei (Ic), (If), (Ig) und (Ii) als erythro/threo‐Gemische anfallen.
Throughput reliability analysis of cloud-radio access networks (2016)

This paper develops a stochastic geometry-based analytical approach for calculating the throughput reliability of a cloud-radio access network (C-RAN) comprising randomly distributed remote radio heads (RRHs) and randomly located users. A tunable distance-based RRH transmit power control mechanism along with cooperative joint transmissions by the RRHs is employed to achieve power savings and high throughput reliability. The analytical result for the throughput reliability serves as input to analysis of per user achievable average rate and C-RAN network-level performance metrics of spectral efficiency and energy efficiency. The analytical results are validated by Monte Carlo simulation results with good agreement, thus confirming the accuracy of the developed analytical approach. The key finding from the analysis is that by carefully tuning the RRH transmit power and cooperation parameter (cluster radius), it is possible to realize a threefold improvement in the energy efficiency along with 108% enhancement in the spectral efficiency of C-RANs. Copyright © 2016 John Wiley & Sons, Ltd.
Smart Radio Environments Empowered by AI Reconfigurable Meta-Surfaces:\n An Idea Whose Time Has Come (2019)

Future wireless networks are expected to constitute a distributed intelligent\nwireless communications, sensing, and computing platform, which will have the\nchallenging requirement of interconnecting the physical and digital worlds in a\nseamless and sustainable manner.\n Currently, two main factors prevent wireless network operators from building\nsuch networks: 1) the lack of control of the wireless environment, whose impact\non the radio waves cannot be customized, and 2) the current operation of\nwireless radios, which consume a lot of power because new signals are generated\nwhenever data has to be transmitted.\n In this paper, we challenge the usual "more data needs more power and\nemission of radio waves" status quo, and motivate that future wireless networks\nnecessitate a smart radio environment: A transformative wireless concept, where\nthe environmental objects are coated with artificial thin films of\nelectromagnetic and reconfigurable material (that are referred to as\nintelligent reconfigurable meta-surfaces), which are capable of sensing the\nenvironment and of applying customized transformations to the radio waves.\nSmart radio environments have the potential to provide future wireless networks\nwith uninterrupted wireless connectivity, and with the capability of\ntransmitting data without generating new signals but recycling existing radio\nwaves.\n This paper overviews the current research efforts on smart radio\nenvironments, the enabling technologies to realize them in practice, the need\nof new communication-theoretic models for their analysis and design, and the\nlong-term and open research issues to be solved towards their massive\ndeployment. In a nutshell, this paper is focused on discussing how the\navailability of intelligent reconfigurable meta-surfaces will allow wireless\nnetwork operators to redesign common and well-known network communication\nparadigms.\n
An Autosomal Dominant Form of Ras-Related C3 Botulinum Toxin Substrate 2 (RAC2) Is Associated with Haematopoiesis Failure (2021)

Abstract Severe combined immunodeficiencies (SCIDs) constitute a heterogeneous group of life-threatening genetic disorders that typically present in the first year of life. Reticular dysgenesis (RD) is an autosomal recessive form of human Severe Combined Immunodeficiency (SCIDs) characterized by the absence of blood neutrophils and T lymphocytes. This pathology is due to biallelic mutations in the adenylate kinase 2 (AK2) gene, encoding for a mitochondrial protein which regulates the homeostasis of adenine nucleotides. In three newborns presenting a RD-like clinical phenotype as frequent infections and a profound leukopenia, we identified an heterozygous dominant missense mutation in the gene coding for Rac Family Small GTPase 2 (RAC2) protein (p.G12R). Hematopoietic stem cell transplantation (HSCT) performed soon after birth was successful in two out of the three patients attesting that the inherited defect was intrinsic and not micro-environmental. RAC2 protein belongs to the Rac subfamily of RHO small GTPases. In the inactive GDP-bound state, RAC2 is located in the cytosol and upon stimulation, the active RAC2-GTP-bound form translocates to the plasma membrane. Unlike the other members of the Rac subfamily (RAC1 and RAC3), RAC2 is mostly expressed on hematopoietic cells and during T cell differentiation. To gain insight into the disease, we transduced human hematopoietic stem and progenitor cells (HSPCs) with a lentiviral construct containing the RAC2 mutated form. The mutation inhibits HSPCs proliferation and differentiation toward the myeloid and lymphoid lineages reproducing the patients' clinical phenotype. In this condition, we also observed high apoptosis level and an alteration of mitochondrial activity and Ros production. In a biochemical model, we demonstrated that the substitution of the glycine (G) amino-acid by a bulky flexible arginine (R) may prevent GTP hydrolysis. Lastly, our findings suggest that RAC2 gene sequencing must be considered in newborn screening programs for SCID detection. To decipher the mechanisms regulating RAC2 functions, we studied the impact of the p.G12R mutation on a human AML cell line expressing RAC2 protein. Our preliminary data highlight that the cell cycle and mitochondrial activity are disrupted by G12R mutation. By holotomography, we also observed morphological changes and accumulation of lipid droplets into the cells. All these data suggest that RAC2 defective signalling pathway is linked to cell metabolism imbalance and further investigations are ongoing to better understand how RAC2 controls cell energy demand, especially during differentiation. Disclosures Cavazzana: Smart Immune: Other: co-founder.
Simulation of the writing and erasing processes of GeSbTe and GeSbTeSn with GeN interlayers in the case of dual level DVR discs (2003)

In current research on optical phase change data storage, it is essential to understand accurately the physics underlying writing and erasing processes. Computer simulation combined with the appropriate physical models and experimental data is the most valuable tool available. We have established optical, thermal and phase transformation (thermodynamics and kinetics) models and constructed a simulation based on them. We use this simulation to reproduce and forecast the writing and erasing processes of GeSbTe and GeSbTeSn with GeN interlayers in the case of dual level DVR (digital video recording) discs.