gebhart/patrepeval huggingface dataset:
Wnt 3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cells (2004)

Multipotential adult mesenchymal stem cells (MSCs) are able to differentiate along several known lineages, and lineage commitment is tightly regulated through specific cellular mediators and interactions. Recent observations of a low/high bone-mass phenotype in patients expressing a loss-/gain-of-function mutation in LRP5, a coreceptor of the Wnt family of signaling molecules, suggest the importance of Wnt signaling in bone formation, possibly involving MSCs. To analyze the role of Wnt signaling in mesenchymal osteogenesis, we have profiled the expression of WNTs and their receptors, FRIZZLEDs (FZDs), and several secreted Wnt inhibitors, such as SFRPs, and examined the effect of Wnt 3a, as a representative canonical Wnt member, during MSC osteogenesis in vitro. WNT11, FZD6, SFRP2, and SFRP3 are upregulated during MSC osteogenesis, while WNT9A and FZD7 are downregulated. MSCs also respond to exogenous Wnt 3a, based on increased beta-catenin nuclearization and activation of a Wnt-responsive promoter, and the magnitude of this response depends on the MSC differentiation state. Wnt 3a exposure inhibits MSC osteogenic differentiation, with decreased matrix mineralization and reduced alkaline phosphatase mRNA and activity. Wnt 3a treatment of fully osteogenically differentiated MSCs also suppresses osteoblastic marker gene expression. The Wnt 3a effect is accompanied by increased cell number, resulting from both increased proliferation and decreased apoptosis, particularly during expansion of undifferentiated MSCs. The osteo-suppressive effects of Wnt 3a are fully reversible, i.e., treatment prior to osteogenic induction does not compromise subsequent MSC osteogenesis. The results also showed that sFRP3 treatment attenuates some of the observed Wnt 3a effects on MSCs, and that inhibition of canonical Wnt signaling using a dominant negative TCF1 enhances MSC osteogenesis. Interestingly, expression of Wnt 5a, a non-canonical Wnt member, appeared to promote osteogenesis. Taken together, these findings suggest that canonical Wnt signaling functions in maintaining an undifferentiated, proliferating progenitor MSC population, whereas non-canonical Wnts facilitate osteogenic differentiation. Release from canonical Wnt regulation is a prerequisite for MSC differentiation. Thus, loss-/gain-of-function mutations of LRP5 would perturb Wnt signaling and depress/promote bone formation by affecting the progenitor cell pool. Elucidating Wnt regulation of MSC differentiation is important for their potential application in tissue regeneration.
Measurement and Clinical Monitoring of Human Lymphocyte Clonality by Massively Parallel V-D-J Pyrosequencing (2009)

The complex repertoire of immune receptors generated by B and T cells enables recognition of diverse threats to the host organism. In this work, we show that massively parallel DNA sequencing of rearranged immune receptor loci can provide direct detection and tracking of immune diversity and expanded clonal lymphocyte populations in physiological and pathological contexts. DNA was isolated from blood and tissue samples, a series of redundant primers was used to amplify diverse DNA rearrangements, and the resulting mixtures of barcoded amplicons were sequenced using long-read ultra deep sequencing. Individual DNA molecules were then characterized on the basis of DNA segments that had been joined to make a functional (or nonfunctional) immune effector. Current experimental designs can accommodate up to 150 samples in a single sequence run, with the depth of sequencing sufficient to identify stable and dynamic aspects of the immune repertoire in both normal and diseased circumstances. These data provide a high-resolution picture of immune spectra in normal individuals and in patients with hematological malignancies, illuminating, in the latter case, both the initial behavior of clonal tumor populations and the later suppression or re-emergence of such populations after treatment.
Therapeutic levels of FVIII following a single peripheral vein administration of rAAV vector encoding a novel human factor VIII variant (2013)

Recombinant adeno-associated virus (rAAV) vectors encoding human factor VIII (hFVIII) were systematically evaluated for hemophilia A (HA) gene therapy. A 5.7-kb rAAV-expression cassette (rAAV-HLP-codop-hFVIII-N6) containing a codon-optimized hFVIII cDNA in which a 226 amino acid (aa) B-domain spacer replaced the entire B domain and a hybrid liver-specific promoter (HLP) mediated 10-fold higher hFVIII levels in mice compared with non-codon-optimized variants. A further twofold improvement in potency was achieved by replacing the 226-aa N6 spacer with a novel 17-aa peptide (V3) in which 6 glycosylation triplets from the B domain were juxtaposed. The resulting 5.2-kb rAAV-HLP-codop-hFVIII-V3 cassette was more efficiently packaged within AAV virions and mediated supraphysiologic hFVIII expression (732 ± 162% of normal) in HA knock-out mice following administration of 2 × 10(12) vector genomes/kg, a vector dose shown to be safe in subjects with hemophilia B. Stable hFVIII expression at 15 ± 4% of normal was observed at this dose in a nonhuman primate. hFVIII expression above 100% was observed in 3 macaques that received a higher dose of either this vector or the N6 variant. These animals developed neutralizing anti-FVIII antibodies that were abrogated with transient immunosuppression. Therefore, rAAV-HLP-codop-hFVIII-V3 substantially improves the prospects of effective HA gene therapy.
A Drosophila Axin homolog, Daxin, inhibits Wnt signaling (1999)

The vertebrate Axin protein, the product of the mouse fused gene, binds to beta-catenin to inhibit Wnt signaling. We have identified a homolog of Axin in Drosophila, Daxin. Using double-stranded RNA interference, we generated loss-of-function phenotypes that are similar to overexpression of the Drosophila Wnt gene wingless (wg). Overexpression of Daxin produces phenotypes similar to loss of wg. In addition, we show that Daxin overexpression can modify phenotypes elicited by wg and another Drosophila Wnt gene, DWnt-2. Using immunoprecipitation of endogenous Daxin protein from embryos we show that Daxin interacts with Armadillo and Zeste-white 3. The loss-of-function and overexpression phenotypes show that Daxin, like its mammalian counterpart, acts as a negative regulator of wg/Wnt signaling.
Deep Generative Dual Memory Network for Continual Learning (2017)

Despite advances in deep learning, neural networks can only learn multiple tasks when trained on them jointly. When tasks arrive sequentially, they lose performance on previously learnt tasks. This phenomenon called catastrophic forgetting is a fundamental challenge to overcome before neural networks can learn continually from incoming data. In this work, we derive inspiration from human memory to develop an architecture capable of learning continuously from sequentially incoming tasks, while averting catastrophic forgetting. Specifically, our contributions are: (i) a dual memory architecture emulating the complementary learning systems (hippocampus and the neocortex) in the human brain, (ii) memory consolidation via generative replay of past experiences, (iii) demonstrating advantages of generative replay and dual memories via experiments, and (iv) improved performance retention on challenging tasks even for low capacity models. Our architecture displays many characteristics of the mammalian memory and provides insights on the connection between sleep and learning.
A Chinese Hamster Mutant Cell Line with a Defect in the Integral Membrane Protein CII-3 of Complex II of the Mitochondrial Electron Transport Chain (1995)

In this study, a respiration-deficient Chinese hamster cell line with a defect in succinate dehydrogenase activity is shown to result from a single base change in a codon in the coding sequence for the membrane anchor protein CII-3 (also referred to as QPs-1). A premature translation stop results in the truncation of 33 amino acids from the C terminus. Bovine cDNA encoding this peptide complements the mutation. There is about 82% identity between these two mammalian proteins. The gene for CII-3 was mapped on human chromosome 1, and because it is also found on minichromosomes characterized by our laboratory, we can localize it on the short arm within 1-2 megabases from the centromere.
Chemically synthesized peptides predicted from the nucleotide sequence of the hepatitis B virus genome elicit antibodies reactive with the native envelope protein of Dane particles. (1981)

Thirteen peptides corresponding to amino acid sequences predicted from the nucleotide sequence of the hepatitis B surface antigen were synthesized chemically. The free or carrier-linked synthetic peptides were injected into rabbits, and 7 of the 13 elicited an antipeptide response. Antisera against four of the six soluble peptides longer than 10 amino acids were reactive with native antigen and specifically precipitated the 23,000- and 28,000-dalton forms from Dane particles. As the hepatitis molecule had not been chosen for study because of any structural feature suggesting unique opportunities for success, these results suggest that the strategy is general and should work for any protein as long as enough domains are studied. Peptides such as these could prove to be ideal vaccines.
Data-Driven Plant-Model Mismatch Quantification in Input-Constrained Linear MPC (2016)

In this paper, we present a novel data-driven approach for estimating plant-model mismatch for linear MIMO systems operating under constrained MPC. We begin with analyzing the closed-loop plant data; under the assumption that changes in the active set of constraints of the controller are due to (low frequency) setpoint changes, we separate the data into a finite number of fixed active set (FAS) subsets, each of which features a time-invariant active set of MPC constraints. We establish an explicit relationship relating the magnitude of plant-model mismatch to the autocovariance of the system output in the FAS case, while accounting for changes in the setpoint value. The mismatch estimation problem is then formulated as a global optimization calculation, aimed at minimizing the discrepancy between the autocovariance estimated using this theoretical tool, and the autocovariance of plant outputs computed from operating data for each FAS subset. A chemical process case study is presented to illustrate the effectiveness of the approach.
Alterations in cadherin and catenin expression during the biological progression of melanocytic tumours. (1999)

The most important alterations in membranous cadherin and catenin expression are seen late in the biological progression of melanocytic tumours at the stage of "in transit" or regional lymph node metastasis, with implications for tumour growth, invasion, and dissemination.
Secretion of human insulin by a transformed yeast cell (1987)

A yeast expression plasmid encoding a mini-proinsulin molecule was constructed and transformed into Saccharomyces cerevisiae. The plasmid encoded the sequence: B-Arg-Arg-Leu-Gln-Lys-Arg-A in which B represents the B-chain (30 amino acid residues) and A represents the A-chain (21 amino acid residues) of human insulin. The secreted peptides were shown to be a mixture of human insulin and des(B-30)human insulin. Thus, correct disulphide bridges can be established in proinsulin-like molecules devoid of a normal C-peptide region. Furthermore, the specificity of the yeast processing enzymes is so similar to the proinsulin converting enzymes in the human pancreatic beta-cell that it allows the processing of the mini-proinsulin to insulin.
Transplantation 50 Years Later — Progress, Challenges, and Promises (2004)

A half-century has elapsed since the first transplantation, and this procedure is now accepted as the treatment of choice for end-stage organ failure. This article reviews the many developments since that historic moment. Although tremendous progress has contributed to the success of this form of therapy, several challenges remain if transplantation is to be widely available with minimal risks and optimal outcomes.
Automatic category generation for text documents by self-organizing maps (2000)

One important task for text data mining is automatic text categorization, which assigns a text document to some predefined category according to their correlations. Traditionally, these categories as well as the correlations among them are determined bp human experts. In this paper, we devised a novel approach to automatically generate categories. The self-organizing map model is used to generate two maps, namely the word cluster map and the document cluster map, in which a neuron represents a cluster of words and documents respectively. Our approach is to analyze the document cluster map to find centroids of some super-clusters. We also devised a method to select the category term from the word cluster map. The hierarchical structure of categories may be generated by recursively applying the same method. Text categorization is the natural consequence of such automatic category generation process.
A Microfabricated Planar Electrospray Array Ionic Liquid Ion Source With Integrated Extractor (2009)

This paper reports the design, fabrication, and experimental characterization of a fully microfabricated planar array of externally fed electrospray emitters that produces heavy molecular ions from the ionic liquids EMI-BF <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> and EMI-Im. The microelectromechanical systems (MEMS) electrospray array is composed of the following two microfabricated parts: 1) an emitter die with as many as 502 emitters in 1.13 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> and 2) an extractor component that provides assembly alignment, electrical insulation, and a common bias voltage to the emitter array. The devices were created using Pyrex and silicon substrates, as well as microfabrication techniques such as deep reactive ion etching, low-temperature fusion bonding, and anodic bonding. The emitters are coated with black silicon, which acts as a wicking material for transporting the liquid to the emitter tips. The extractor electrode uses a 3-D MEMS packaging technology that allows hand assembly of the two components with micrometer-level precision. Experimental characterization of the MEMS electrospray array includes current-voltage characteristics, time-of-flight mass spectrometry, beam divergence, and imprints on a collector. The data show that with both ionic liquids and in both polarities, the electrospray array works in the pure ionic regime, emitting ions with as little as 500 V of bias voltage. The data suggest that the MEMS electrospray array ion source could be used in applications such as coating, printing, etching, and nanosatellite propulsion.
Key Residues in Mycobacterium tuberculosis Protein Kinase G Play a Role in Regulating Kinase Activity and Survival in the Host (2009)

Protein kinase G (PknG) in Mycobacterium tuberculosis has been shown to modulate phagosome-lysosome fusion. The protein has three distinct domains, an N-terminal Trx domain, a kinase domain, and a C-terminal TPR domain. The present study extensively analyzes the roles of these domains in regulating PknG kinase activity and function. We find that the kinase domain of PknG by itself is inactive, signifying the importance of the flanking domains. Although the deletion of the Trx domain severely impacts the activity of the protein, the C-terminal region also contributes significantly in regulating the activity of the kinase. Apart from this, PknG kinase activity is dependent on the presence of threonine 309 in the p + 1 loop of the activation segment. Mutating the conserved cysteine residues in the Trx motifs makes PknG refractory to changes in the redox environment. In vitro experiments identify threonine 63 as the major phosphorylation site of the protein. Importantly, we find that this is the only site in the protein that is phosphorylated in vivo. Macrophage infection studies reveal that the first 73 residues, the Trx motifs, and the threonine 63 residue are independently essential for modulating PknG-mediated survival of mycobacteria in its host. We have extended these studies to investigate the role of PknG and PknG mutants in the pathogenesis of mycobacteria in mice. Our results reinforce the findings from the macrophage infection experiments, and for the first time demonstrate that the expression of PknG in non-pathogenic mycobacteria allows the continued existence of these bacteria in host tissues.
The Art of Multiprocessor Programming : 並行プログラミングの原理から実践まで (2009)

原理（相互排他；並行オブジェクト；共有メモリの基礎；プリミティブな同期操作の相対能力 ほか） 実践（スピンロックと競合；モニタとブロッキング同期；リンクリスト：ロックの役割；並行キューとＡＢＡ問題 ほか）
Mechanisms of oxidant-mediated cell injury. The glycolytic and mitochondrial pathways of ADP phosphorylation are major intracellular targets inactivated by hydrogen peroxide. (1988)

Inhibition of ADP phosphorylation by both glycolysis and mitochondria in P388D1 cells exposed to H2O2 is described. Net glucose uptake and lactate production were inhibited by oxidant exposure (ED50 = 50-100 microM). Glycolysis was specifically inactivated at the glyceraldehyde-3-phosphate dehydrogenase step by three independent mechanisms: (a) direct inactivation of the intracellular enzyme (ED50 approximately equal to 100 microM); (b) reduction of the intracellular concentration and redox potential of its nicotinamide cofactors; and (c) a cytosolic pH shift further from the enzyme optima. Consistent with inhibition of glycolysis at the glyceraldehyde-3-phosphate dehydrogenase step, a rise in the intracellular concentration of glyceraldehyde 3-phosphate, dihydroxyacetone phosphate, and fructose 1,6-bisphosphate was observed. The calculated combined inhibition of glyceraldehyde-3-phosphate dehydrogenase activity could be reasonably correlated with the depression in glycolytic flux rate with the appropriate modeling. The steady-state contribution by mitochondria to the total intracellular ATP pool was indirectly determined by the use of various metabolic inhibitors and was found to rapidly decline following exposure to 300-800 microM H2O2. The inhibition of ADP phosphorylation appeared to be related more to the direct inhibition of the ATPase-synthase complex rather than to the diminished capacity of the respiratory chain for coupled electron transport. Both the estimated rates of ADP phosphorylation by glycolysis and mitochondria and the estimated rate of ATP hydrolysis by ongoing metabolism were utilized to model the approximate decline in intracellular ATP expected at 15-min exposure to various H2O2 concentrations. Theoretical calculations and the measured intracellular ATP status were in good agreement. Oxidant exposure for 15 min resulted in dose-dependent killing of the cells (ED50 = 500 microM), indicating a close correlation between H2O2-mediated loss of intracellular ATP and cell viability. The possible contribution of impaired energy homeostasis during oxidant-mediated injury to the process of cell dysfunction and death is discussed.
Oral inoculation with herpes simplex virus type 1 infects enteric neuron and mucosal nerve fibers within the gastrointestinal tract in mice (1996)

Herpes simplex virus type 1 (HSV-1) is commonly encountered first during childhood as an oral infection. After this initial infection resolves, the virus remains in a latent form within innervating sensory ganglia for the life of the host. We have previously shown, using a murine model, that HSV-1 placed within the lumen of the esophagus gains access to nerves within the gut wall and establishes a latent infection in sensory ganglia (nodose ganglia) of the tenth cranial nerve (R. M. Gesser, T. Valyi-Nagy, S. M. Altschuler, and N. W. Fraser, J. Gen. Virol. 75:2379-2386, 1994). Peripheral processes of neurons in these ganglia travel through the vagus nerve and function as primary sensory receptors in most of the gastrointestinal tract, relaying information from the gut wall and mucosal surface to secondary neurons within the brain stem. In the work described here, we further examined the spread of HSV-1 through the enteric nervous system after oral inoculation. By immunohistochemistry, HSV-1 was found to infect myenteric ganglia in Auerbach's plexus between the inner and outer muscle layers of the gut wall, submucosal ganglia (Meisner's plexus), and periglandular ganglion plexuses surrounding submucosal glands. Virus-infected nerve fibers were also seen projecting through the mucosal layer to interact directly with surface epithelial cells. These intramucosal nerve fibers may be a conduit by which intraluminal virus is able to gain access to the enteric nervous system from the gastrointestinal lumen.
Biocompatible Surfaces Prepared by Immobilized Heparin or Hyaluronate (1987)

Artificial surfaces modified with immobilized heparin or hyaluronate were evaluated as possible approaches to improve biocompatibility. The heparin surface was highly thromboresistant in contact with blood, as manifested by minimal cell adhesion and a pronounced capacity to inactivate coagulation enzymes such as thrombin and factor Xa. The hyaluronate coating also reduced cell adhesion, but this coating seemed to be less effective than the heparin surface. Outgrowth of human macrophages was not affected by the hyaluronate coating, nor did it display any capacity to inactivate coagulation enzymes. It is concluded that the heparin surface exhibits a high degree of biocompatibility in contact with blood and cell culture, which should make it an interesting candidate for use in the ear compartment.
Nanocrystals of Cesium Lead Halide Perovskites (CsPbX3, X = Cl, Br, and I): Novel Optoelectronic Materials Showing Bright Emission with Wide Color Gamut (2015)

Metal halides perovskites, such as hybrid organic-inorganic CH3NH3PbI3, are newcomer optoelectronic materials that have attracted enormous attention as solution-deposited absorbing layers in solar cells with power conversion efficiencies reaching 20%. Herein we demonstrate a new avenue for halide perovskites by designing highly luminescent perovskite-based colloidal quantum dot materials. We have synthesized monodisperse colloidal nanocubes (4-15 nm edge lengths) of fully inorganic cesium lead halide perovskites (CsPbX3, X = Cl, Br, and I or mixed halide systems Cl/Br and Br/I) using inexpensive commercial precursors. Through compositional modulations and quantum size-effects, the bandgap energies and emission spectra are readily tunable over the entire visible spectral region of 410-700 nm. The photoluminescence of CsPbX3 nanocrystals is characterized by narrow emission line-widths of 12-42 nm, wide color gamut covering up to 140% of the NTSC color standard, high quantum yields of up to 90%, and radiative lifetimes in the range of 1-29 ns. The compelling combination of enhanced optical properties and chemical robustness makes CsPbX3 nanocrystals appealing for optoelectronic applications, particularly for blue and green spectral regions (410-530 nm), where typical metal chalcogenide-based quantum dots suffer from photodegradation.
Taxanes Alone or in Combination With Anthracyclines As First-Line Therapy of Patients With Metastatic Breast Cancer (2008)

Taxanes were significantly worse than single-agent anthracyclines in terms of PFS, but not in terms of response rates or survival. Taxane-based combinations were significantly better than anthracycline-based combinations in terms of response rates and PFS, but not in terms of survival.