gebhart/patrepeval huggingface dataset:
Optimal designs for space-time linear precoders and decoders (2002)

We introduce a new paradigm for the design of transmitter space-time coding that we refer to as linear precoding. It leads to simple closed-form solutions for transmission over frequency-selective multiple-input multiple-output (MIMO) channels, which are scalable with respect to the number of antennas, size of the coding block, and transmit average/peak power. The scheme operates as a block transmission system in which vectors of symbols are encoded and modulated through a linear mapping operating jointly in the space and time dimension. The specific designs target minimization of the symbol mean square error and the approximate maximization of the minimum distance between symbol hypotheses, under average and peak power constraints. The solutions are shown to convert the MIMO channel with memory into a set of parallel flat fading subchannels, regardless of the design criterion, while appropriate power/bits loading on the subchannels is the specific signature of the different designs. The proposed designs are compared in terms of various performance measures such as information rate, BER, and symbol mean square error.
Association Between Patatin-Like Phospholipase Domain Containing 3 Gene (PNPLA3) Polymorphisms and Nonalcoholic Fatty Liver Disease: A HuGE Review and Meta-Analysis (2015)

We conducted a meta-analysis to assess the association between patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism and nonalcoholic fatty liver disease (NAFLD) and its subtypes simple steatosis(SS) and nonalcoholic steatohepatitis (NASH). The study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models, with assessment for heterogeneity and publication bias. Twenty-three case-control studies involving 6071 NAFLD patients and 10366 controls were identified. The combined results showed a significant association between NAFLD risk and the rs738409 polymorphism in all genetic models (additive model: OR = 3.41, 95% CI = 2.57-4.52; P < 0.00001). In addition, evidence indicated that the rs738409 polymorphism was significantly associated with NASH in all genetic models (additive model: OR = 4.44, 95% CI = 3.39-5.82; P < 0.00001). The subgroup and sensitivity analyses showed that these changes were not influenced by the ethnicities and ages of subjects or by the source of controls. The rs738409 polymorphism was only significantly associated with risk of simple steatosis in the allele contrast and had no effect in the other genetic models. These findings suggest that the rs738409 polymorphism in PNPLA3 gene confers high cross-ethnicity risk for NAFLD and NASH development.
Zero-shot object recognition by semantic manifold distance (2015)

Object recognition by zero-shot learning (ZSL) aims to recognise objects without seeing any visual examples by learning knowledge transfer between seen and unseen object classes. This is typically achieved by exploring a semantic embedding space such as attribute space or semantic word vector space. In such a space, both seen and unseen class labels, as well as image features can be embedded (projected), and the similarity between them can thus be measured directly. Existing works differ in what embedding space is used and how to project the visual data into the semantic embedding space. Yet, they all measure the similarity in the space using a conventional distance metric (e.g. cosine) that does not consider the rich intrinsic structure, i.e. semantic manifold, of the semantic categories in the embedding space. In this paper we propose to model the semantic manifold in an embedding space using a semantic class label graph. The semantic manifold structure is used to redefine the distance metric in the semantic embedding space for more effective ZSL. The proposed semantic manifold distance is computed using a novel absorbing Markov chain process (AMP), which has a very efficient closed-form solution. The proposed new model improves upon and seamlessly unifies various existing ZSL algorithms. Extensive experiments on both the large scale ImageNet dataset and the widely used Animal with Attribute (AwA) dataset show that our model outperforms significantly the state-of-the-arts.
AZD5438, a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, leads to pharmacodynamic changes and potent antitumor effects in human tumor xenografts (2009)

Deregulation of the cell cycle has long been recognized as an essential driver of tumorigenesis, and agents that selectively target key cell cycle components continue to hold promise as potential therapeutics. We have developed AZD5438, a 4-(1-isopropyl-2-methylimidazol-5-yl)-2-(4-methylsulphonylanilino) pyrimidine, as a potent inhibitor of cyclin-dependent kinase (cdk) 1, 2, and 9 (IC(50), 16, 6, and 20 nmol/L, respectively). In vitro, AZD5438 showed significant antiproliferative activity in human tumor cell lines (IC(50) range, 0.2-1.7 micromol/L), causing inhibition of the phosphorylation of cdk substrates pRb, nucleolin, protein phosphatase 1a, and RNA polymerase II COOH-terminal domain and blocking cell cycling at G(2)-M, S, and G(1) phases. In vivo, when orally administered at either 50 mg/kg twice daily or 75 mg/kg once daily, AZD5438 inhibited human tumor xenograft growth (maximum percentage tumor growth inhibition, range, 38-153; P < 0.05). In vivo, AZD5438 reduced the proportion of actively cycling cells. Further pharmacodynamic analysis of AZD5438-treated SW620 xenografts showed that efficacious doses of AZD5438 (>40% tumor growth inhibition) maintained suppression of biomarkers, such as phospho-pRbSer(249)/Thr(252), for up to 16 hours following a single oral dose. A comparison of different schedules indicated that chronic daily oral dosing provided optimal cover to ensure antitumor efficacy. These data indicate that broad cdk inhibition may provide an effective method to impair the dysregulated cell cycle that drives tumorigenesis and AZD5438 has the pharmacologic profile that provides an ideal probe to test this premise.
Production of axial skeletal malformations with the nitric oxide synthesis inhibitor NG‐nitro‐L‐arginine methyl ester (L‐NAME) in the mouse (2007)

This study provides evidence that in utero exposure to L-NAME can affect organogenesis of the axial skeleton.
In situ molecular NMR picture of bioavailable calcium stabilized as amorphous CaCO3biomineral in crayfish gastroliths (2011)

Bioavailable calcium is maintained by some crustaceans, in particular freshwater crayfish, by stabilizing amorphous calcium carbonate (ACC) within reservoir organs--gastroliths, readily providing the Ca(2+) needed to build a new exoskeleton. Despite the key scientific and biomedical importance of the in situ molecular-level picture of biogenic ACC and its stabilization in a bioavailable form, its description has eluded efforts to date. Herein, using multinuclear NMR, we accomplish in situ molecular-level characterization of ACC within intact gastroliths of the crayfish Cherax quadricarinatus. In addition to the known CaCO(3), chitin scaffold and inorganic phosphate (Pi), we identify within the gastrolith two primary metabolites, citrate and phosphoenolpyruvate (PEP) and quantify their abundance by applying solution NMR techniques to the gastrolith "soluble matrix." The long-standing question on the physico-chemical state of ACC stabilizing, P-bearing moieties within the gastrolith is answered directly by the application of solid state rotational-echo double-resonance (REDOR) and transferred-echo double-resonance (TEDOR) NMR to the intact gastroliths: Pi and PEP are found molecularly dispersed throughout the ACC as a solid solution. Citrate carboxylates are found < 5 Å from a phosphate (intermolecular CP distance), an interaction that must be mediated by Ca(2+). The high abundance and extensive interactions of these molecules with the ACC matrix identify them as the central constituents stabilizing the bioavailable form of calcium. This study further emphasizes that it is imperative to characterize the intact biogenic CaCO(3). Solid state NMR spectroscopy is shown to be a robust and accessible means of determining composition, internal structure, and molecular functionality in situ.
Distributed delayed stochastic optimization (2012)

We analyze the convergence of gradient-based optimization algorithms that base their updates on delayed stochastic gradient information. The main application of our results is to gradient-based distributed optimization algorithms where a master node performs parameter updates while worker nodes compute stochastic gradients based on local information in parallel, which may give rise to delays due to asynchrony. We take motivation from statistical problems where the size of the data is so large that it cannot fit on one computer; with the advent of huge datasets in biology, astronomy, and the internet, such problems are now common. Our main contribution is to show that for smooth stochastic problems, the delays are asymptotically negligible and we can achieve order-optimal convergence results. We show n-node architectures whose optimization error in stochastic problems-in spite of asynchronous delays-scales asymptotically as O(1/√nT) after T iterations. This rate is known to be optimal for a distributed system with n nodes even in the absence of delays. We additionally complement our theoretical results with numerical experiments on a logistic regression task.
A DESIGN OF A ROTATING GANTRY WITH EASY STEERING FOR PROTON THERAPY (2002)

We propose a rotating gantry with easy trajectory correction which is needed when we change the gantry rotational angle for proton therapy. The gantry is a standard type with 5.0 m rotating radius, and delivers proton beam with maximum energy of 250 MeV. The beam from the transport course is deflected by an upsream bending magnet BM1 and finally deflected by two bending magnets BM2 and BM3 to the irradiation nozzle. The radii and maximum field strengths of these bending magnets are 1.5 m and 1.6 T. Five quadrupole magnets are installed between BM1 and BM2. The dispersion function at the irradiation nozzle can be tuned to be zero by two steering magnets used in the gantry and two beam position monitor in the nozzle. The beam trajectory in the nozzle is easily and quickly corrected by using two beam position monitors in the nozzle. This present trajectory correction keeps higher treatment efficiency when it is necessary to correct the trajectory differently for each rotating angle. 1
On-Wire Lithography (2005)

We report a high-throughput procedure for lithographically processing one-dimensional nanowires. This procedure, termed on-wire lithography, combines advances in template-directed synthesis of nanowires with electrochemical deposition and wet-chemical etching and allows routine fabrication of face-to-face disk arrays and gap structures in the range of five to several hundred nanometers. We studied the transport properties of 13-nanometer gaps with and without nanoscopic amounts of conducting polymers deposited within by dip-pen nanolithography.
Substratum-growth factor collaborations are required for the mitogenic activities of activin and FGF on embryonal carcinoma cells. (1991)

When P19 mouse embryonal carcinoma cells are grown in a serum-free N2 medium on surfaces of tissue culture plastic, they die within two days. The death of these P19 cells is prevented by activin A and basic FGF (bFGF). The cells do not divide under these conditions. However, when P19 cells are cultured on substrata of extracellular matrix proteins such as laminin and fibronectin, activin A and bFGF are potent mitogens. These data show that the substratum to which cells are exposed can regulate their mitogenic response to growth factors.
CRISPR/Cas9‐mediated genome engineering: An adeno‐associated viral (AAV) vector toolbox (2014)

Its remarkable ease and efficiency make the CRISPR (clustered regularly interspaced short palindromic repeats) DNA editing machinery highly attractive as a new tool for experimental gene annotation and therapeutic genome engineering in eukaryotes. Here, we report a versatile set of plasmids and vectors derived from adeno-associated virus (AAV) that allow robust and specific delivery of the two essential CRISPR components - Cas9 and chimeric g(uide)RNA - either alone or in combination. All our constructs share a modular design that enables simple and stringent guide RNA (gRNA) cloning as well as rapid exchange of promoters driving Cas9 or gRNA. Packaging into potent synthetic AAV capsids permits CRISPR delivery even into hard-to-transfect targets, as shown for human T-cells. Moreover, we demonstrate the feasibility to direct Cas9 expression to or away from hepatocytes, using a liver-specific promoter or a hepatic miRNA binding site, respectively. We also report a streamlined and economical protocol for detection of CRISPR-induced mutations in less than 3 h. Finally, we provide original evidence that AAV/CRISPR vectors can be exploited for gene engineering in vivo, as exemplified in the liver of adult mice. Our new tools and protocols should foster the broad application of CRISPR technology in eukaryotic cells and organisms, and accelerate its clinical translation into humans.
CD25+CD4+ Regulatory T Cells from the Peripheral Blood of Asymptomatic HIV-infected Individuals Regulate CD4+ and CD8+ HIV-specific T Cell Immune Responses In Vitro and Are Associated with Favorable Clinical Markers of Disease Status (2004)

Human immunodeficiency virus (HIV) disease is associated with loss of CD4(+) T cells, chronic immune activation, and progressive immune dysfunction. HIV-specific responses, particularly those of CD4(+) T cells, become impaired early after infection, before the loss of responses directed against other antigens; the basis for this diminution has not been elucidated fully. The potential role of CD25(+)CD4(+) regulatory T cells (T reg cells), previously shown to inhibit immune responses directed against numerous pathogens, as suppressors of HIV-specific T cell responses was investigated. In the majority of healthy HIV-infected individuals, CD25(+)CD4(+) T cells significantly suppressed cellular proliferation and cytokine production by CD4(+) and CD8(+) T cells in response to HIV antigens/peptides in vitro; these effects were cell contact dependent and IL-10 and TGF-beta independent. Individuals with strong HIV-specific CD25(+) T reg cell function in vitro had significantly lower levels of plasma viremia and higher CD4(+): CD8(+) T cell ratios than did those individuals in whom this activity could not be detected. These in vitro data suggest that CD25(+)CD4(+) T reg cells may contribute to the diminution of HIV-specific T cell immune responses in vivo in the early stages of HIV disease.
8-oxoguanine (8-hydroxyguanine) DNA glycosylase and its substrate specificity. (1991)

Substrate specificities of FPG protein (also known as formamidopyrimidine DNA glycosylase) and 8-hydroxyguanine endonuclease were compared by using defined duplex oligodeoxynucleotides containing single residues of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-oxo-7,8-dihydro-2'-deoxyadenosine (8-oxodA), and 2,6-diamino-4-hydroxy-5-(N-methyl)formamidopyrimidine (Me-Fapy). Duplexes containing 8-oxodG positioned opposite dC, dG, or dT were cleaved, whereas single-stranded DNA and duplexes containing 8-oxodG.dA or 8-oxodA positioned opposite any of the four DNA bases were relatively resistant. Both enzymes cut duplexes containing 8-oxoG.dC 3' and 5' to the modified base but failed to cleave duplex DNA containing synthetic abasic sites, mismatches containing dG, or unmodified DNA. 8-Oxoguanine, identified by HPLC-electrochemical detection techniques, was released during the enzymatic reaction. Apparent Km values for FPG protein acting on duplex substrates containing a single Me-Fapy or 8-oxodG residue positioned opposite dC were 41 and 8 nM, respectively, and those for 8-hydroxyguanine endonuclease were 30 and 13 nM, respectively. Comparison of the properties of the two enzyme activities suggest that they are identical. In view of the widespread distribution of 8-oxodG in cellular DNA, the demonstrated miscoding and mutagenic properties of this lesion, and the existence of a bacterial gene coding for FPG protein, we propose that 8-oxodG DNA is the primary physiological substrate for a constituent glycosylase found in bacteria and mammalian cells.
Salmonella typhimurium deletion mutants lacking adenylate cyclase and cyclic AMP receptor protein are avirulent and immunogenic (1987)

Salmonella typhimurium SR-11 mutants with cya::Tn10 or crp::Tn10 mutations were found to be avirulent and immunogenic for BALB/c mice. Fusaric acid-resistant derivatives with deletions of the Tn10 and adjacent DNA sequences were constructed in S. typhimurium SR-11 strains with or without the virulence plasmid pStSR100. These delta cya delta crp strains grew more slowly than wild-type strains. They possessed wild-type ability to attach to, invade, and persist in gut-associated lymphoid tissue for up to a week but exhibited a diminished ability to reach mesenteric lymph nodes and the spleen. Mice 4 to 8 weeks old were resistant to oral infection with 10(9) cells of several different delta cya and delta cya delta crp strains (the equivalent to 10(4) 50% lethal doses of wild-type S. typhimurium SR-11) and 30 days after immunization became resistant to oral challenge with 10(3) to 10(4) 50% lethal doses of wild-type S. typhimurium SR-11.
Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases (2007)

Covalent modifications of histones, such as acetylation and methylation, play important roles in the regulation of gene expression. Histone lysine methylation has been implicated in both gene activation and repression, depending on the specific lysine (K) residue that becomes methylated and the state of methylation (mono-, di-, or trimethylation). Methylation on K4, K9, and K36 of histone H3 has been shown to be reversible and can be removed by site-specific demethylases. However, the enzymes that antagonize methylation on K27 of histone H3 (H3K27), an epigenetic mark important for embryonic stem cell maintenance, Polycomb-mediated gene silencing, and X chromosome inactivation have been elusive. Here we show the JmjC domain-containing protein UTX (ubiquitously transcribed tetratricopeptide repeat, X chromosome), as well as the related JMJD3 (jumonji domain containing 3), specifically removes methyl marks on H3K27 in vitro. Further, the demethylase activity of UTX requires a catalytically active JmjC domain. Finally, overexpression of UTX and JMJD3 leads to reduced di- and trimethylation on H3K27 in cells, suggesting that UTX and JMJD3 may function as H3K27 demethylases in vivo. The identification of UTX and JMJD3 as H3K27-specific demethylases provides direct evidence to indicate that similar to methylation on K4, K9, and K36 of histone H3, methylation on H3K27 is also reversible and can be dynamically regulated by site-specific histone methyltransferases and demethylases.
Complementary series (1961)

A set of complementary series is defined as a pair of equally long, finite sequences of two kinds of elements which have the property that the number of pairs of like elements with any one given separation in one series is equal to the number of pairs of unlike elements with the same given separation in the other series. (For instance the two series, 1001010001 and 1000000110 have, respectively, three pairs of like and three pairs of unlike adjacent elements, four pairs of like and four pairs of unlike alternate elements, and so forth for all possible separations.) These series, which were originally conceived in connection with the optical problem of multislit spectrometry, also have possible applications in communication engineering, for when the two kinds of elements of these series are taken to be +1 and -1, it follows immediately from their definition that the sum of their two respective autocorrelation series is zero everywhere, except for the center term. Several propositions relative to these series, to their permissible number of elements, and to their synthesis are demonstrated.
[Relationship between endothelial cells and extracellular matrix: investigation using the model of angiogenesis in vitro]. (1992)

Using model of angiogenesis in vitro, the relationship between endothelial cells and extracellular matrix was studied. Endothelial cells of bovine brain microvascular vessels (BBECs), carotid artery (BCECs) and aorta (BAECs) were cultured on type I collagen gel and Matrigel. BBECs make tubular structures and BCECs and BAECs grow and make confluent monolayer on type I collagen gel. BCECs and BAECs make tubular structures when second layer of collagen gel was overlaid. BBECs, BCECs and BAECs rapidly make tubular structures on Matrigel. These morphological changes were not affected by basic fibroblast growth factor. The effect of extracellular matrices on the cell kinetics and morphology of cultured bovine carotid artery endothelial cells was studied. Endothelial cells show a cobble stone appearance on plastic and type I collagen gel. They proliferate and make capillary-like structures on reconstituted gels composed of type I collagen and basement membrane substrata. And that endothelial cells forming capillary-like structures were increased with the increase in the concentration of basement membrane substrata. Transmission electromicroscopic examination study revealed endothelial cells forming capillary-like structures have junctional complexes on type I collagen and its mixture with basement membrane substrata. But endothelial cells on basement membrane substrata have no junctional complexes. These results suggest that BBECs have more potent angiogenic ability than BCECs and BAECs. And that proliferation and morphogenesis of endothelial cells are regulated by extracellular matrices.
An Update on the Pathophysiology of Complex Regional Pain Syndrome (2010)

Complex regional pain syndrome (CRPS) is a neuropathic pain disorder with significant autonomic features. Few treatments have proven effective, in part, because of a historically poor understanding of the mechanisms underlying the disorder. CRPS research largely conducted during the past decade has substantially increased knowledge regarding its pathophysiologic mechanisms, indicating that they are multifactorial. Both peripheral and central nervous system mechanisms are involved. These include peripheral and central sensitization, inflammation, altered sympathetic and catecholaminergic function, altered somatosensory representation in the brain, genetic factors, and psychophysiologic interactions. Relative contributions of the mechanisms underlying CRPS may differ across patients and even within a patient over time, particularly in the transition from "warm CRPS" (acute) to "cold CRPS" (chronic). Enhanced knowledge regarding the pathophysiology of CRPS increases the possibility of eventually achieving the goal of mechanism-based CRPS diagnosis and treatment.