gebhart/patrepeval huggingface dataset:
Why do cannabinoid receptors have more than one endogenous ligand? (2012)

The endocannabinoid system was revealed following the understanding of the mechanism of action of marijuana's major psychotropic principle, Δ(9)-tetrahydrocannabinol, and includes two G-protein-coupled receptors (GPCRs; the cannabinoid CB1 and CB2 receptors), their endogenous ligands (the endocannabinoids, the best studied of which are anandamide and 2-arachidonoylglycerol (2-AG)), and the proteins that regulate the levels and activity of these receptors and ligands. However, other minor lipid metabolites different from, but chemically similar to, anandamide and 2-AG have also been suggested to act as endocannabinoids. Thus, unlike most other GPCRs, cannabinoid receptors appear to have more than one endogenous agonist, and it has been often wondered what could be the physiological meaning of this peculiarity. In 1999, it was proposed that anandamide might also activate other targets, and in particular the transient receptor potential of vanilloid type-1 (TRPV1) channels. Over the last decade, this interaction has been shown to occur both in peripheral tissues and brain, during both physiological and pathological conditions. TRPV1 channels can be activated also by another less abundant endocannabinoid, N-arachidonoyldopamine, but not by 2-AG, and have been proposed by some authors to act as ionotropic endocannabinoid receptors. This article will discuss the latest discoveries on this subject, and discuss, among others, how anandamide and 2-AG differential actions at TRPV1 and cannabinoid receptors contribute to making this signalling system a versatile tool available to organisms to fine-tune homeostasis.
Rational design of a split-Cas9 enzyme complex (2015)

Cas9, an RNA-guided DNA endonuclease found in clustered regularly interspaced short palindromic repeats (CRISPR) bacterial immune systems, is a versatile tool for genome editing, transcriptional regulation, and cellular imaging applications. Structures of Streptococcus pyogenes Cas9 alone or bound to single-guide RNA (sgRNA) and target DNA revealed a bilobed protein architecture that undergoes major conformational changes upon guide RNA and DNA binding. To investigate the molecular determinants and relevance of the interlobe rearrangement for target recognition and cleavage, we designed a split-Cas9 enzyme in which the nuclease lobe and α-helical lobe are expressed as separate polypeptides. Although the lobes do not interact on their own, the sgRNA recruits them into a ternary complex that recapitulates the activity of full-length Cas9 and catalyzes site-specific DNA cleavage. The use of a modified sgRNA abrogates split-Cas9 activity by preventing dimerization, allowing for the development of an inducible dimerization system. We propose that split-Cas9 can act as a highly regulatable platform for genome-engineering applications.
Presenilin 1 Regulates Pharmacologically Distinct γ-Secretase Activities (2000)

Presenilins (PSs) are polytopic membrane proteins that have been implicated as potential therapeutic targets in Alzheimer's disease because of their role in regulating the gamma-secretase cleavage that generates the amyloid beta protein (Abeta). It is not clear how PSs regulate gamma-secretase cleavage, but there is evidence that PSs could be either essential cofactors in the gamma-secretase cleavage, gamma-secretase themselves, or regulators of intracellular trafficking that indirectly influence gamma-secretase cleavage. Using presenilin 1 (PS1) mutants that inhibit Abeta production in conjunction with transmembrane domain mutants of the amyloid protein precursor that are cleaved by pharmacologically distinct gamma-secretases, we show that PS1 regulates multiple pharmacologically distinct gamma-secretase activities as well as inducible alpha-secretase activity. It is likely that PS1 acts indirectly to regulate these activities (as in a trafficking or chaperone role), because these data indicate that for PS1 to be gamma-secretase it must either have multiple active sites or exist in a variety of catalytically active forms that are altered to an equivalent extent by the mutations we have studied.
Effects of a New Blending Agent on Ethanol−Gasoline Fuels (1996)

Successful use of ethanol−gasoline blends as engine fuel alternatives depends on producing a stable homogeneous liquid fuel. It is crucial to avoid the phase separation phenomenon which occurs due to the hydrophilic character of alcohols and the solubility behavior of gasoline−alcohol−water three-component system. In this study an industrial byproduct is introduced as a new blending agent to ethanol−gasoline fuels, and its effects on the phase separation problem were investigated on samples prepared by blending unleaded gasoline with 5, 10, 15, and 20% (v/v) azeotropic ethanol, respectively.
Synthesis of luminescent heterometallic bis-lanthanide complexes via selective, sequential metallation (2006)

A modular synthetic method for the differential incorporation of two lanthanide ions into a single molecular scaffold is reported; the mixed bimetallic Tb/Eu complex displays an interesting solvent polarity-dependent ratiometric luminescence.
Bacterial Membranes: Structure, Domains, and Function (2017)

The bacterial cytoplasmic membrane is composed of roughly equal proportions of lipids and proteins. The main lipid components are phospholipids, which vary in acyl chain length, saturation, and branching and carry head groups that vary in size and charge. Phospholipid variants determine membrane properties such as fluidity and charge that in turn modulate interactions with membrane-associated proteins. We summarize recent advances in understanding bacterial membrane structure and function, focusing particularly on the possible existence and significance of specialized membrane domains. We review the role of membrane curvature as a spatial cue for recruitment and regulation of proteins involved in morphogenic functions, especially elongation and division. Finally, we examine the role of the membrane, especially regulation of synthesis and fluid properties, in the life cycle of cell wall-deficient L-form bacteria.
Variable kappa gene rearrangement in lymphoproliferative disorders: an analysis of V kappa gene usage, VJ joining and somatic mutation. (1994)

We have studied a diverse group of lymphoproliferative disorders (acute lymphoblastic leukaemia (ALL), chronic lymphocytic leukaemia (CLL), non-Hodgkin lymphoma (NHL) and myeloma) to determine if V kappa gene use is random or disease-specific and whether somatic mutations (a late event in B-cell differentiation) can provide additional information on the type of B cell involved in the neoplastic clone. In this group of disorders V kappa gene selection is not random and some members of each V kappa family are preferentially rearranged. V kappa genes from the distal portion of the locus are seldom used, possibly because rearrangement of the proximal locus by deletion is more efficient than rearrangement of the distal locus by inversion. Although pseudogenes account for 46% of the V genes in the kappa locus none were ever rearranged, even in non-functional rearrangements of lambda-producing leukemias, suggesting the existence of a mechanism which down-regulates the rearrangement of pseudogenes. N regions were noted at the VJ junction in 20% of alleles (in six CLL, three NHL, two ALL and one myeloma) possibly the result of kappa-chain recombination during the early period of B-cell maturation in which TdT is expressed. Nucleotide addition or imprecise joining at the VJ junction, resulting in a shift in the reading frame, were the commonest causes of non-functional rearrangement. The occurrence of somatic mutation broadly correlated with the stage of B-cell maturation from which the different disorders are thought to arise. However, there was no strict association and somatic mutations were demonstrated in 'typical CLL' while V kappa genes were germline in some follicular lymphomas; these findings suggest either heterogeneity in the stage of B-cell maturation at which these disorders arise or some variability in the process of somatic mutation.
Physico-Chemical Characteristics of KhesariDhal (Lathyrus sativus): Changes inα-Galactosides, Monosaccharides andDisaccharides during Food Processing (1996)

Lathyrus sativus, also known as Khesari dhal in India, is a good source of protein and also desirable from the agricultural point of view as it is drought-resistant and can be grown with low agriculture inputs of fertiliser, irrigation and pesticide. In common with other legume seeds,Lathyruscontains the flatulence causing α-galactosides. This is a study of the physico-chemical properties of four selectedLathyrus sativuslines (Red flower, a high β-ODAP line; EC-242692, a medium β-ODAP line; L-1276, a low β-ODAP line; and Pusa-24, a very low β-ODAP line) to determine the most effective way of removing the flatulence factors by using simple processes such as soaking, dehusking and germination. Physico-chemical properties like swelling and hydration capacity ofLathyrusseeds were higher than other legumes, which suggests higher consumer preference in terms of cooking time and fuel consumption over other beans. Germination was the most effective procedure for removing α-galatosides (85–92%). Dehusking of pre-soaked seeds also achieved a high α-galactoside reduction (61–80%). Soaking in alkaline medium and thereafter boiling for 9 min brought about a lower reduction (33–74%), but these losses were still higher than those obtained by soaking in drinking water or soaking in boiled water for 2 h (11–49% and 7–44%, respectively).
Non-Abelian Statistics of Half-Quantum Vortices inp-Wave Superconductors (2001)

Excitation spectrum of a half-quantum vortex in a p-wave superconductor contains a zero-energy Majorana fermion. This results in a degeneracy of the ground state of the system of several vortices. From the properties of the solutions to Bogoliubov-de Gennes equations in the vortex core we derive the non-Abelian statistics of vortices identical to that for the Moore-Read (Pfaffian) quantum Hall state.
Activation of innate immune responses through Toll‐like receptor 3 causes a rapid loss of salivary gland function (2008)

Our results demonstrate that engagement of TLR3 within the salivary glands results in a rapid loss of glandular function. This phenomenon is associated with the production of type I IFN and inflammatory cytokines in the salivary glands. Restoration of glandular function suggests that for viral etiology of SS, a chronic infection of salivary glands might be necessary.
Immunosuppressive factor(s) extracted from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) II. Cellular source and effect on responder and nonresponder mice. (1977)

The synthetic terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) fails to stimulate development of GAT-specific antibody responses in nonresponder strains of mice, but does stimulate the development of GAT-specific suppressor T cells that inhibit the development of normal anti-GAT antibody responses to GAT complexed to methylated bovine serum albumin (GAT-MBSA). Furthermore, extracts prepared from lymphoid cells of GAT-primed, but not control, nonresponder mice inhibit the development of antibody responses to GAT-MBSA by normal nonresponder mice. This suppression is specific, dose-dependent, and can be readily analyzed in vitro. The suppressive factor is a T-cell product. An extract from GAT-primed DBA/1 mice inhibits the response to GAT-MBSA by spleen cells from histoincompatible strains of mice that are nonresponders to GAT, but not strains that are responders to GAT.
Pseudo dynamic logic (SDL): a high-speed and low-power dynamic logic family (2003)

In this paper, a new logic-design style called Pseudo Dynamic Logic (SDL) is introduced. In this logic-design style, the internal nodes of the logic circuits are not precharged to high or low values, rather the initial charges on nodes are shared to yield an intermediate precharge value for faster evaluation. A 32-bit adder has been designed and simulated using HSPICE Level-49 parameters of a 0.6 /spl mu/m CMOS process. Simulated measurements on this adder show that the worst-case delay is 1.56 ns. This demonstrates 2.1 times speed improvement in comparison to a domino dynamic logic design implemented with the same technology.
Acoustic Echo Cancellation for Dynamically Steered Microphone Array Systems (2007)

A new method for integrating dynamically steered beamforming filters and acoustic echo cancellation is presented. The proposed method enables beam steering independent AEC processing without parallel AEC filters for each microphone input (a.k.a. AEC-first configuration). Especially for larger microphone arrays the proposed method can provide significant computational savings with comparable performance to AEC-first configuration.
NK cell-mediated anti-tumor immune response to human prostate cancer cell, PC-3: immunogene therapy using a highly secretable form of interleukin-15 gene transfer (2001)

Interleukin (IL)-15 is a pleiotropic cytokine that is important for innate and adaptive immune cell homeostasis. The expression of IL-15 protein is controlled by posttranscriptional mechanisms. Here, we constructed a human IL-15 expression vector consisting of the human IL-2 signal peptide, the human IL-15 mature peptide-coding sequences, and an out-of-frame human growth hormone gene. Human prostate cancer cells, PC-3, transfected with this highly secretable form of the IL-15 gene, successfully secreted abundant bioactive IL-15 protein. In nude mice, the growth of PC-3 cells producing IL-15 was remarkably retarded. NK cell-depletion using anti-asialo GM1 antibody restored tumorigenicity. Histologically, tumors derived from IL-15-producing PC-3 cells contained necrotic areas with high apoptotic index. Splenocytes incubated with supernatant of transfectants killed target PC-3 cells and expressed a significantly high level of mIFN-gamma mRNA. These observations suggest that NK cell-mediated, anti-tumor effects of IL-15 could provide a potential rationale for gene therapy of prostate cancer.
Electron Transfer Reactions in Pulping Systems (I): Theory and Applicability to Anthraquinone Pulping (1985)

Abstract A key step in the delignification of wood is the breakage of the β-aryl ether bonds of lignin. Two mechanisms are discussed for how anthrahydroquinone (AHQ) brings about this particular fragmentation. The “adduct” mechanism involves bond formation between lignin quinonemethide (QM) intermediates and AHQ, followed by fragmentation. The other mechanism (“SET” mechanism) involves a single electron transfer between AHQ and a lignin QM followed by fragmentation. The literature concerning adducts and SET reactions is reviewed and analyzed. The SET mechanism must be considered as a viable alternative to one based entirely on adduct formation.
Transient pass-transistor leakage current in SOI MOSFET's (1997)

This paper reports an accurate method of measuring the anomalous leakage current in pass-gate MOSFET's unique to SOI devices. A high-speed measurement setup is used to provide experimental results, and to quantify the magnitude of leakage. Particularly, great care is taken to measure only the device leakage current and not the currents due to parasitic capacitances. Systematic influences of different factors such as temperature, bias, device history, and device structure on this leakage current are experimentally established,.
Distinct patterns and kinetics of chemokine production regulate dendritic cell function (1999)

Dendritic cells (DC) have been showed to both produce and respond to chemokines. To understand how this may impact on DC function, we analyzed the kinetics of chemokine production and responsiveness during DC maturation. After stimulation with LPS, TNF-alpha or CD40 ligand, the inflammatory chemokines MIP-1alpha, MIP-1beta and IL-8 were produced rapidly and at high levels, but only for a few hours, while RANTES and MCP-1 were produced in a sustained fashion. The constitutive chemokines TARC, MDC and PARC were expressed in immature DC and were up-regulated following maturation, while ELC was produced only at late time points. Activated macrophages produced a similar spectrum of chemokines, but did not produce TARC and ELC. In maturing DC chemokine production had different impact on chemokine receptor function. While CCR1 and CCR5 were down-regulated by endogenous or exogenous chemokines, CCR7 levels gradually increased in maturing DC and showed a striking resistance to ligand-induced down-regulation, explaining how DC can sustain the response to SLC and ELC throughout the maturation process. The time-ordered production of inflammatory and constitutive chemokines provides DC with the capacity to self-regulate their migratory behavior as well as to recruit other cells for the afferent and efferent limb of the immune response.
Discriminative language modeling with conditional random fields and the perceptron algorithm (2004)

This paper describes discriminative language modeling for a large vocabulary speech recognition task. We contrast two parameter estimation methods: the perceptron algorithm, and a method based on conditional random fields (CRFs). The models are encoded as deterministic weighted finite state automata, and are applied by intersecting the automata with word-lattices that are the output from a baseline recognizer. The perceptron algorithm has the benefit of automatically selecting a relatively small feature set in just a couple of passes over the training data. However, using the feature set output from the perceptron algorithm (initialized with their weights), CRF training provides an additional 0.5% reduction in word error rate, for a total 1.8% absolute reduction from the baseline of 39.2%.
Machine-independent virtual memory management for paged uniprocessor and multiprocessor architectures (1987)

This paper describes the design and implementation of virtual memory management within the CMU Mach Operating System and the experiences gained by the Mach kernel group in porting that system to a variety of architectures. As of this writing, Mach runs on more than half a dozen uniprocessors and multiprocessors including the VAX family of uniprocessors and multiprocessors, the IBM RT PC, the SUN 3, the Encore MultiMax, the Sequent Balance 21000 and several experimental computers. Although these systems vary considerably in the kind of hardware support for memory management they provide, the machine-dependent portion of Mach virtual memory consists of a single code module and its related header file. This separation of software memory management from hardware support has been accomplished without sacrificing system performance. In addition to improving portability, it makes possible a relatively unbiased examination of the pros and cons of various hardware memory management schemes, especially as they apply to the support of multiprocessors.
Light-emitting diodes as measurement devices for femtosecond laser pulses (1997)

We present results showing that, when it is used as a photodetector, a light-emitting diode (LED) has a power-dependent response that can be used for sensitive detection and characterization of picosecond and femtosecond laser pulses. A characterization of a typical LED is presented at 800 nm, and we demonstrate how this effect can be used to construct an extremely compact novel autocorrelator based on a Wollaston prism.
Genetic mapping and variability of seven soybean simple sequence repeat loci (1994)

Microsatellites or simple sequence repeats are stretches of short tandemly repeated DNA sequence motifs, dispersed throughout the genomes of most eukaryotes. Simple sequence repeat polymorphisms (SSRPs) have recently been reported in plants. Here we present the genetic map position of seven different soybean (Glycine max (L.) Merr. and Glycine soja Sieb. and Zucc.) SSRPs contained in sequenced genes, four of which represent newly mapped positions for these genes. The other three SSRPs coincided with independently established RFLP map positions for the corresponding genes. When a set of 61 soybean accessions was screened at four of these loci by using agarose gels, the average number of alleles per locus was 7.75, the effective number of alleles (ne) was 2.57, and the level of allele differentiation (delta(t)) was 0.62. Allelic variation decreased sharply with increasing levels of domestication, with the level of differentiation going from 84% in the wild soybean to 43% in the elite germplasm. Variation levels observed on a subset made of 19 of the 61 lines were always higher for SSRPs than for RFLP markers, with the average number of alleles per locus going from 4.25 to 2.15. In comparison with RFLP markers, SSRPs are more informative and are easier to analyse but require more effort to develop.
Enhanced differentiation of human embryonic stem cells to mesenchymal progenitors by inhibition of TGF-β/activin/nodal signaling using SB-431542 (2010)

Directing differentiation of human embryonic stem cells (hESCs) into specific cell types using an easy and reproducible protocol is a prerequisite for the clinical use of hESCs in regenerative-medicine procedures. Here, we report a protocol for directing the differentiation of hESCs into mesenchymal progenitor cells. We demonstrate that inhibition of transforming growth factor beta (TGF-beta)/activin/nodal signaling during embryoid body (EB) formation using SB-431542 (SB) in serum-free medium markedly upregulated paraxial mesodermal markers (TBX6, TBX5) and several myogenic developmental markers, including early myogenic transcriptional factors (Myf5, Pax7), as well as myocyte-committed markers [NCAM, CD34, desmin, MHC (fast), alpha-smooth muscle actin, Nkx2.5, cTNT]. Continuous inhibition of TGF-beta signaling in EB outgrowth cultures (SB-OG) enriched for myocyte progenitor cells; markers were PAX7(+) (25%), MYOD1(+) (52%), and NCAM(+) (CD56) (73%). DNA microarray analysis revealed differential upregulation of 117 genes (>2-fold compared with control cells) annotated to myogenic development and function. Moreover, these cells showed the ability to contract (80% of the population) and formed myofibers when implanted intramuscularly in vivo. Interestingly, SB-OG cells cultured in 10% fetal bovine serum (FBS) developed into a homogeneous population of mesenchymal progenitors that expressed CD markers characteristic of mesenchymal stem cells (MSCs): CD44(+) (100%), CD73(+) (98%), CD146(+) (96%), and CD166(+) (88%) with the ability to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro and in vivo. Furthermore, microarray analysis of these cells revealed downregulation of genes related to myogenesis: MYH3 (-167.9-fold), ACTA1 (-161-fold), MYBPH (-139-fold), ACTC (-100.3-fold), MYH8 (-45.5-fold), and MYOT (-41.8-fold) and marked upregulation of genes related to mesoderm-derived cell lineages. In conclusion, our data provides a simple and versatile protocol for directing the differentiation of hESCs into a myogenic lineage and then further into mesenchymal progenitors by blocking the TGF-beta signaling pathway.