gebhart/patrepeval huggingface dataset:
Rational design of a trispecific antibody targeting the HIV-1 Env with elevated anti-viral activity (2018)

HIV-1 broadly neutralizing antibodies (bNAbs) are being explored as passively administered therapeutic and preventative agents. However, the extensively diversified HIV-1 envelope glycoproteins (Env) rapidly acquire mutations to evade individual bNAbs in monotherapy regimens. The use of a "single" agent to simultaneously target distinct Env epitopes is desirable to overcome viral diversity. Here, we report the use of tandem single-chain variable fragment (ScFv) domains of two bNAbs, specific for the CD4-binding site and V3 glycan patch, to form anti-HIV-1 bispecific ScFvs (Bi-ScFvs). The optimal Bi-ScFv crosslinks adjacent protomers within one HIV-1 Env spike and has greater neutralization breadth than its parental bNAbs. Furthermore, the combination of this Bi-ScFv with a third bNAb recognizing the Env membrane proximal external region (MPER) results in a trispecific bNAb, which has nearly pan-isolate neutralization breadth and high potency. Thus, multispecific antibodies combining functional moieties of bNAbs could achieve outstanding neutralization capacity with augmented avidity.
Abortive intussusceptive angiogenesis causes multi-cavernous vascular malformations (2021)

Mosaic inactivation of <i>CCM2</i> in humans causes cerebral cavernous malformations (CCMs) containing adjacent dilated blood-filled multi-cavernous lesions. We used CRISPR-Cas9 mutagenesis to induce mosaic inactivation of zebrafish <i>ccm2</i> resulting in a novel lethal multi-cavernous lesion in the embryonic caudal venous plexus (CVP) caused by obstruction of blood flow by intraluminal pillars. These pillars mimic those that mediate intussusceptive angiogenesis; however, in contrast to the normal process, the pillars failed to fuse to split the pre-existing vessel in two. Abortive intussusceptive angiogenesis stemmed from mosaic inactivation of <i>ccm2</i> leading to patchy <i>klf2a</i> overexpression and resultant aberrant flow signaling. Surviving adult fish manifested histologically typical hemorrhagic CCM. Formation of mammalian CCM requires the flow-regulated transcription factor KLF2; fish CCM and the embryonic CVP lesion failed to form in <i>klf2a</i> null fish indicating a common pathogenesis with the mammalian lesion. These studies describe a zebrafish CCM model and establish a mechanism that can explain the formation of characteristic multi-cavernous lesions.
High-speed radio-resource scheduler with hardware accelerator for fifth generation mobile communications systems (2017)

This paper presents a high-speed radio-resource scheduler that accelerates the scheduling process of fifth-generation mobile communications systems (5G). A scheduler for 5G systems will have to decide the optimal combination of an antenna and user equipment for efficient communications from a huge number of possible combinations. The reported scheduler with a hardware accelerator performs several high-speed searches to find the optimal combination. Experimental results show that it executes several search methods 40 times faster than a scheduler without acceleration. It improves the system throughput and will enable a practical 5G system to be developed.
Achieving Cinematic Motion with High Dynamic Range (2020)

This paper will explore how the appearance of cinematic motion (the characteristic balance of smoothness and realism of motion commonly used in cinema) is affected by high dynamic range (HDR) presentation. We will report on a psychovisual experiment that investigated how observers rated the smoothness of motion between scenes of different motion types (pans, action, slow movement), frame rates, and luminance levels. We found that in order to match the level of cinematic motion in todays' non-HDR presentation, the frame rate may need to either remain at 24 frames per second (fps) or be increased to 30fps, depending on the type of motion and the luminance level of the scene. We conclude that by selecting the appropriate frame rate depending on the motion type in each scene, content creators will be able to achieve the desired cinematic motion without compromising their use of the HDR color palette.
A critical role for mTORC1 in erythropoiesis and anemia (2014)

Red blood cells (RBC) must coordinate their rate of growth and proliferation with the availability of nutrients, such as iron, but the signaling mechanisms that link the nutritional state to RBC growth are incompletely understood. We performed a screen for cell types that have high levels of signaling through mTORC1, a protein kinase that couples nutrient availability to cell growth. This screen revealed that reticulocytes show high levels of phosphorylated ribosomal protein S6, a downstream target of mTORC1. We found that mTORC1 activity in RBCs is regulated by dietary iron and that genetic activation or inhibition of mTORC1 results in macrocytic or microcytic anemia, respectively. Finally, ATP competitive mTOR inhibitors reduced RBC proliferation and were lethal after treatment with phenylhydrazine, an inducer of hemolysis. These results identify the mTORC1 pathway as a critical regulator of RBC growth and proliferation and establish that perturbations in this pathway result in anemia.
Unraveling the Mechanism of Extreme (More than 30 Sigma) Precipitation during August 2018 and 2019 over Kerala, India (2021)

Abstract During August 2018 and 2019 the southern state of India, Kerala, received unprecedented heavy rainfall, which led to widespread flooding. We aim to characterize the convective nature of these events and the large-scale atmospheric forcing, while exploring their predictability by three state-of-the-art global prediction systems: the National Centers for Environmental Prediction (NCEP)-based India Meteorological Department (IMD) operational Global Forecast System (GFS), the European Centre for Medium-Range Weather Forecasts (ECMWF) Integrated Forecast System (IFS), and the Unified Model–based NCUM being run at the National Centre for Medium Range Weather Forecasting (NCMRWF). Satellite, radar, and lightning observations suggest that these rain events were dominated by cumulus congestus and shallow convection with strong zonal flow leading to orographically enhanced rainfall over the Ghats mountain range; sporadic deep convection was also present during the 2019 event. A moisture budget analyses using the fifth major global reanalysis produced by ECMWF (ERA5) and forecast output revealed significantly increased moisture convergence below 800 hPa during the main rain events compared to August climatology. The total column-integrated precipitable water tendency, however, is found to be small throughout the month of August, indicating a balance between moisture convergence and drying by precipitation. By applying a Rossby wave filter to the rainfall anomalies it is shown that the large-scale moisture convergence is associated with westward-propagating barotropic Rossby waves over Kerala, leading to increased predictability of these events, especially for 2019. Evaluation of the deterministic and ensemble rainfall predictions revealed systematic rainfall differences over the Ghats mountains and the coastline. The ensemble predictions were more skillful than the deterministic forecasts, as they were able to predict rainfall anomalies (greater than three standard deviations from climatology) beyond day 5 for August 2019 and up to day 3 for 2018.
Self versus maternal reports of emotional and behavioral difficulties in suicidal and non-suicidal adolescents: An Israeli nationwide survey (2012)

The mental examination of the adolescent patient should be maintained as the central and most reliable source of information regarding the suicidal adolescent. Mental health services planning of national suicide prevention programs should take into account these poor mother-adolescent agreement findings.
Integrated optical label read and payload envelope detection circuit for optical label swapping (2006)

We demonstrate the first integrated 10 Gbps optical label recovery and 40 Gbps optical payload envelope detector circuit. Error free optical label recovery, nanosecond payload envelope detection, and optical label swapping are demonstrated.
Synthesis of dl-α-Tocopherol by Cross Coupling Reaction of Ene-type Chloride with the C10-Grignard Reagent (1995)

Ene-type chloride (5 a) was prepared with trichloroisocyanuric acid as a chlorination reagent from pentenylchromanol (3), obtained from myrcene and 2, 3, 5-trimethylhydroquinone in 3 steps. Chloride (5 a) reacted with 3, 7-dimethyloctylmagnesium bromide in the presence of CuCl (I) as the catalyst in THE to afford mixture consisting of SN2' type cross coupling products (7 a) and (8 a) with high regioselectivity. Compounds (5 b-e) reacted with the Grignard reagent in the presence of CuCl (I) to give SN2' type cross coupling products (7) and (8) with high regioselectivity Table-1. dl-α-Tocopherol was prepared in good yields by the hydrogenation of compounds (7 a) and (8 a).
Nanoelectronic Devices: Microwave Admittance of Gold‐Palladium Nanowires with Proximity‐Induced Superconductivity (Adv. Electron. Mater. 6/2017) (2017)

In article number 1600227, Russell E. Lake and co-workers report a combined experimental and theoretical study of superconducting quantum interference devices. They show that unexpected dissipative effects can disturb the delicate quantum phenomena that govern the electrical impedance of metal nanowires. The results highlight the importance of specific materials properties in quantum technology. Inside cover illustration by Katri Tikkanen.
Molecular and Biological Properties of Insulin Icodec, a New Insulin Analog Designed to Give a Long Half-Life Suitable for Once-Weekly Dosing (2022)

Insulin icodec is a novel insulin analog in clinical development with a terminal elimination half-life of ~196 hours, designed to cover a full week’s basal insulin requirements with a single subcutaneous injection. The insulin molecule was modified to achieve an albumin-bound circulating depot of icodec which acts just as human insulin (HI) but is more slowly cleared.Addition of a C20 fatty diacid containing side chain at B29K via a hydrophilic linker imparts strong but reversible albumin binding. Three amino acid substitutions (A14E, B16H and B25H) ensure reduced enzymatic degradation and contribute to attenuating insulin receptor (IR) binding and clearance, further prolonging the half-life. In vitro studies demonstrated that icodec is a specific and full agonist of human IR, that displays the same dose-dependent mode of action as HI, exemplified by its ability to phosphorylate the IR and stimulate intracellular signaling pathways (phospho-AKT and -ERK). Functional assays have demonstrated that icodec elicits the same pattern of metabolic effects as HI. The affinity of icodec for the IGF-1 receptor was found to be proportionately lower than its binding to the IR. In vitro mitogenic effect of icodec in primary human mammary cells (HMEC), as well as in mammary and colon carcinoma cells (MCF-7 and COLO 205) was found to be low relative to that of HI. Conclusion: icodec is a new insulin analog designed to achieve a slowly cleared, albumin-bound circulating depot which results in a long half-life suited for once weekly injections, covering the basal insulin requirements for a full week.
Integration issues in step and repeat UV nanoimprint lithography (2008)

Nanoimprint Lithography appears to be a competitive candidate for Next Generation Lithography in semiconductor
industry due to its advantages concerning resolution and cost effectiveness. Moreover, UV-Nanoimprint Lithography
(UV-NIL) should enable to reach good overlay values, which is also a major criterion for integration.
In this paper, we present first integration results which were obtained on lines and contact holes. A specific template was
designed for this purpose in collaboration with CEA-LETI, IMS and Molecular Imprints. This template was
characterized by using various techniques (optical and SEM techniques) and showed quite a good quality of the
template; in particular, 50 nm holes were defined.
Molecular Imprints process was then tested by using Imprio55® at MESA+ Research Institute, University of Twente
(Netherlands). In these experiments, 37 4.8 cm 2 fields were imprinted on Double Side Polished wafers. For each field, 52
droplets were dispensed with various volumes. Resolution and non-uniformity were evaluated after imprinting. Then
etching tests were performed.
Synergies in learning words and their referents (2010)

This paper presents Bayesian non-parametric models that simultaneously learn to segment words from phoneme strings and learn the referents of some of those words, and shows that there is a synergistic interaction in the acquisition of these two kinds of linguistic information. The models themselves are novel kinds of Adaptor Grammars that are an extension of an embedding of topic models into PCFGs. These models simultaneously segment phoneme sequences into words and learn the relationship between non-linguistic objects to the words that refer to them. We show (i) that modelling inter-word dependencies not only improves the accuracy of the word segmentation but also of word-object relationships, and (ii) that a model that simultaneously learns word-object relationships and word segmentation segments more accurately than one that just learns word segmentation on its own. We argue that these results support an interactive view of language acquisition that can take advantage of synergies such as these. 1
Scanning X-ray nanodiffraction from ferroelectric domains in strained K0.75Na0.25NbO3 epitaxial films grown on (110) TbScO3 (2017)

Scanning X-ray nanodiffraction on a highly periodic ferroelectric domain pattern of a strained K<sub>0.75</sub>Na<sub>0.25</sub>NbO<sub>3</sub> epitaxial layer has been performed by using a focused X-ray beam of about 100 nm probe size. A 90°-rotated domain variant which is aligned along [1[Formula: see text]2]<sub>TSO</sub> has been found in addition to the predominant domain variant where the domains are aligned along the [[Formula: see text]12]<sub>TSO</sub> direction of the underlying (110) TbScO<sub>3</sub> (TSO) orthorhombic substrate. Owing to the larger elastic strain energy density, the 90°-rotated domains appear with significantly reduced probability. Furthermore, the 90°-rotated variant shows a larger vertical lattice spacing than the 0°-rotated domain variant. Calculations based on linear elasticity theory substantiate that this difference is caused by the elastic anisotropy of the K<sub>0.75</sub>Na<sub>0.25</sub>NbO<sub>3</sub> epitaxial layer.
Total Synthesis of Brevetoxin A: Part 4: Final Stages and Completion (1999)

A ten-year campaign was successfully completed by the first total synthesis of brevetoxin A (1). A Horner–Wittig type coupling of suitably functionalized BCDE and GHIJ ring systems proved to be the last key step in the total synthesis of this architecturally beautiful molecule.
Mildronate treatment altersγ-butyrobetaine andl-carnitine concentrations in healthy volunteers (2011)

Long-term administration of mildronate significantly lowers l-carnitine plasma concentrations in non-vegetarian, healthy volunteers.
Error Probability of Bit-Interleaved Coded Modulation in Wireless Environments (2006)

The bit-interleaved coded modulation (BICM) method is efficient in mitigating multipath fading by providing time diversity. In this paper, union bounds on the bit and packet error probabilities of the BICM are derived. In the derivation, the authors assume the uniform interleaving of coded bits prior to mapping them onto the signal constellation. This results in a random distribution of the error bits in a codeword over the transmitted symbols. This distribution is evaluated, and the corresponding pairwise error probability is derived. Union bounds are functions of the distance spectrum of the channel code and the signal constellation used in the BICM system. The authors consider BICM systems operating over additive white Gaussian noise (AWGN), Rayleigh, Rician, and Nakagami fading channels. Results show that the new bounds are tight to simulation curves for different channel models. The proposed bounds are general for any coding scheme with a known distance spectrum.
Interaction between the N-terminal domain of human DNA topoisomerase I and the arginine-serine domain of its substrate determines phosphorylation of SF2/ASF splicing factor (1998)

Human DNA topoisomerase I, known for its DNA-relaxing activity, is possibly one of the kinases phosphorylating members of the SR protein family of splicing factors, in vivo. Little is known about the mechanism of action of this novel kinase. Using the prototypical SR protein SF2/ASF (SRp30a) as model substrate, we demonstrate that serine residues phosphorylated by topo I/kinase exclusively located within the most extended arginine-serine repeats of the SF2/ASF RS domain. Unlike other kinases such as cdc2 and SRPK1, which also phosphorylated serines at the RS domain, topo I/kinase required several SR dipeptide repeats. These repeats possibly contribute to a versatile structure in the RS domain thereby facilitating phosphorylation. Furthermore, far-western, fluorescence spectroscopy and kinase assays using the SF2/ASF mutants, demonstrated that kinase activity and binding were tightly coupled. Since the deletion of N-terminal 174 amino acids of Topo I destroys SF2/ASF binding and kinase activity but not ATP binding, we conclude that at least two distinct domains of Topo I are necessary for kinase activity: one in the C-terminal region contributing to the ATP binding site and the other one in the N-terminal region that allows binding of SF2/ASF.
The Relationship between Methionine Uptake and Demethiolation in a Methionine-utilizing Mutant of Pseudomonas fluorescens UK1 (1976)

Microbiology Society journals contain high-quality research papers and topical review articles. We are a not-for-profit publisher and we support and invest in the microbiology community, to the benefit of everyone. This supports our principal goal to develop, expand and strengthen the networks available to our members so that they can generate new knowledge about microbes and ensure that it is shared with other communities.
A New Form of Flat Optics Enabled by Electrowetting Microprisms (2006)

An excellent candidate technology for next-generation beam steering and flat optics is electrowetting microprisms (EMP). EMPs with continuous beam steering through an angle of 14deg (plusmn7deg) have been demonstrated. Projections for EMPs are promising for good switching rate (~10's kHz), polarization independent operation, modulation of field of view, and wide angle steering (>30deg)
High-throughput microscopy reveals the impact of multifactorial environmental perturbations on colorectal cancer cell growth (2021)

Our data indicate that the growth of highly aggressive HCT116 cells is affected by oxygen, substrate stiffness, and liver extracellular matrix. In addition, hypoxia has a protective effect against oxaliplatin-induced cytotoxicity on plastic and liver extracellular matrix. This expansive dataset of CRC cell growth measurements under in situ relevant environmental perturbations provides insights into critical tumor microenvironment features contributing to metastatic seeding and tumor growth. Such insights are essential to dynamical modeling and understanding the multicellular tumor-stroma dynamics that contribute to metastatic colonization. It also establishes a benchmark dataset for training and testing data-driven dynamical models of cancer cell lines and therapeutic response in a variety of microenvironmental conditions.
Systematic review: the effectiveness of budesonide therapy for Crohn's disease (2002)

Budesonide is significantly more effective than placebo or 5-ASA for inducing remission of active Crohn's disease. Although budesonide is 13% less effective for the induction of remission in active Crohn's disease than conventional corticosteroids, it is less likely to cause corticosteroid-related adverse effects. Budesonide is ineffective in maintaining remission.
A −104dBc/Hz in-band phase noise 3GHz all digital PLL with phase interpolation based hierarchical time to digital convertor (2011)

An ADPLL which uses a time-to-digital convertor with &#60;0.13rad resolution achieves LO generation at 3GHz with −104dBc/Hz in-band phase noise. The fine and stable resolution is derived by known phase interpolation circuits. It is fabricated in a 65nm CMOS process and the active area is 0.18mm2. keywords: ADPLL, TDC, phase interpolator.
Comparative Study of Antennal and Maxillary Palp Olfactory Sensilla of Female Biting Midges (Diptera: Ceratopogonidae:Culicoides) in the Context of Host Preference and Phylogeny (2013)

Culicoides biting midges (Diptera Ceratopogonidae) are vectors of disease, including bluetongue and African horse sickness. Host preference of these insects is primarily regulated by olfactory cues, detected by olfactory sensilla on the antennae and maxillary palps. In this study, we analyzed the sensillum repertoire of biting midge species with known host preferences. Five different morphological sensillum types, sensilla trichodea, s. chaetica, s. ampullacea, s. coeloconica, and grooved peg sensilla, were present on the antennae of all species. In addition sensilla basiconica were present on the maxillary palps. We found that the numbers of short blunt-tipped s. trichodea, s. coeloconica, and s. basiconica are significantly higher in the ornithophilic Culicoides festivipennis (Kieffer) compared with the mammalophilic Culicoides obsoletus (Meigen) and Culicoides chiopterus (Meigen). In contrast, we found that the mammalophilic Culicoides pulicaris (L.) and the opportunistic Culicoides punctatus (Meigen) have intermediate numbers of these sensillum types. Comparison with available data from other species strongly suggests that these differences in the number of specific sensillum types, in general, are a reflection of host preference and not of phylogeny. We discuss the putative function of the individual sensillum types in relation to host volatile detection.
Cholesterol, Atherosclerosis, and APOE in Vascular Contributions to Cognitive Impairment and Dementia (VCID): Potential Mechanisms and Therapy (2021)

Vascular contributions to cognitive impairment and dementia (VCID) are a common cause of cognitive decline, yet limited therapies exist. This cerebrovascular disease results in neurodegeneration <i>via</i> acute, chronic, local, and systemic mechanisms. The etiology of VCID is complex, with a significant impact from atherosclerosis. Risk factors including hypercholesterolemia and hypertension promote intracranial atherosclerotic disease and carotid artery stenosis (CAS), which disrupt cerebral blood flow and trigger ischemic strokes and VCID. Apolipoprotein E (APOE) is a cholesterol and phospholipid carrier present in plasma and various tissues. APOE is implicated in dyslipidemia and Alzheimer disease (AD); however, its connection with VCID is less understood. Few experimental models for VCID exist, so much of the present information has been drawn from clinical studies. Here, we review the literature with a focus on the clinical aspects of atherosclerotic cerebrovascular disease and build a working model for the pathogenesis of VCID. We describe potential intermediate steps in this model, linking cholesterol, atherosclerosis, and APOE with VCID. APOE4 is a minor isoform of APOE that promotes lipid dyshomeostasis in astrocytes and microglia, leading to chronic neuroinflammation. APOE4 disturbs lipid homeostasis in macrophages and smooth muscle cells, thus exacerbating systemic inflammation and promoting atherosclerotic plaque formation. Additionally, APOE4 may contribute to stromal activation of endothelial cells and pericytes that disturb the blood-brain barrier (BBB). These and other risk factors together lead to chronic inflammation, atherosclerosis, VCID, and neurodegeneration. Finally, we discuss potential cholesterol metabolism based approaches for future VCID treatment.