gebhart/patrepeval huggingface dataset:
Pattern of Expression of HtrA1 During Mouse Development (2004)

The human HtrA family of proteases consists of four members: HtrA1, HtrA2, HtrA3, and HtrA4. In humans the four HtrA homologues appear to be involved in several important functions such as cell growth, apoptosis, and inflammatory reactions, and they control cell fate via regulated protein metabolism. In previous studies it was shown that the expression of HtrA1 was ubiquitous in normal adult human tissues. Here we examined the expression of HtrA1 protein and its corresponding mRNA during mouse embryogenesis using Northern blotting hybridization, RT-PCR, and immunohistochemical staining analyses. Our results indicate that HtrA1 is expressed in a variety of tissues in mouse embryos. Furthermore, this expression is regulated in a spatial and temporal manner. Relatively low levels of HtrA1 mRNA are detected in embryos at the beginning of organogenesis (E8), and the levels of expression increase during late organogenesis (E14-E19). Our results show that HtrA1 was expressed during embryonic development in specific areas where signaling by TGFbeta family proteins plays important regulatory roles. The expression of HtrA1, documented both at mRNA and protein levels by RT-PCR and immunohistochemistry in the developing nervous system, is consistent with a possible role of this protein both in dividing and postmitotic neurons, possibly via its documented inhibitory effects on TGFbeta proteins. An exhaustive knowledge of the different cell- and tissue-specific patterns of expression of HtrA1 in normal mouse embryos is essential for a critical evaluation of the exact role played by this protein during development.
Role of individual gamma-carboxyglutamic acid residues of activated human protein C in defining its in vitro anticoagulant activity (1992)

To evaluate the contributions of individual gamma-carboxyglutamic acid (gla) residues to the overall Ca(2+)-dependent anticoagulant activity of activated human protein C (APC), we used recombinant (r) DNA technology to generate protein C (PC) variants in which each of the gla precursor glutamic acid (E) residues (positions 6, 7, 14, 16, 19, 20, 25, 26, and 29) was separately altered to aspartic acid (D). In one case, a gla26V mutation ([gla26V]r-PC) was constructed because a patient with this particular substitution in coagulation factor IX had been previously identified. Two additional r-PC mutants were generated, viz, an r-PC variant containing a substitution at arginine (R) 15 ([R15]r-PC), because this particular R residue is conserved in all gla- containing blood coagulation proteins, as well as a variant r-PC with substitution of an E at position 32 ([F31L, Q32E]r-PC), because gla residues are found in other proteins at this sequence location. This latter protein did undergo gamma-carboxylation at the newly inserted E32 position. For each of the 11 recombinant variants, a subpopulation of PC molecules that were gamma-carboxylated at all nonmutated gla- precursor E residues has been purified by anion exchange chromatography and, where necessary, affinity chromatography on an antihuman PC column. The r-PC muteins were converted to their respective r-APC forms and assayed for their amidolytic activities and Ca(2+)-dependent anticoagulant properties. While no significant differences were found between wild-type (wt) r-APC and r-APC mutants in the amidolytic assays, lack of a single gla residue at any of the following locations, viz, 7, 16, 20, or 26, led to virtual complete disappearance of the Ca(2+)-dependent anticoagulant activity of the relevant r-APC mutant, as compared with its wt counterpart. On the other hand, single eliminations of any of the gla residues located at positions 6, 14, or 19 of r-APC resulted in variant recombinant molecules with substantial anticoagulant activity (80% to 92%), relative to wtr-APC. Mutation of gla residues at positions 25 and 29 resulted in r-APC variants with significant but low (24% and 9% of wtr-APC, respectively) levels of anticoagulant activity. The variant, [R15L]r-APC, possessed only 19% of the anticoagulant activity of wrt-APC, while inclusion of gla at position 32 in the variant, [F31L, Q32gla]r-APC, resulted in a recombinant enzyme with an anticoagulant activity equivalent to that of wtr-APC.
New Strategy for Prenatal Diagnosis of X-Linked Disorders (2002)

To the Editor: An invasive approach is still the gold standard for prenatal diagnosis of genetic disorders. Chorionic-villus sampling, the current procedure of choice, allows an early diagnosis, bu...
Computer Simulation of Controlled Radical Polymerization: Effect of Chain Confinement Due to Initiator Grafting Density and Solvent Quality in “Grafting From” Method (2010)

We use stochastic Monte Carlo simulation following the bond fluctuation model to study the effects of grafting density of surface-anchored initiators and solvent quality on controlled radical polymerization (CRP) from flat impenetrable substrates under good and poor solvent conditions. Our CRP model includes a mechanism for activation/deactivation of the chains and neglects termination and chain transfer reactions. The system is, thus, “truly living”. We find that under these conditions, surface-initiated polymerizations at low grafting densities resemble those in the bulk. In contrast, at high initiator grafting densities, these surface-initiated polymerizations result in gradients of the free monomer and chain-end concentrations, which lead to an uneven growth of the chains and ultimately yield polymers with broad molecular weight distributions. Poor solvent conditions exacerbate this problem by collapsing the chains and in some cases forming chain aggregates, which further restrict the access of free monomers by the active polymer chain ends and contribute to their uneven growth and ultimately broader length distributions relative to good solvent conditions. While at low grafting densities the molecular weight distributions can be described by the conventional Schulz-Zimm distribution function, at high grafting densities this approach fails to describe accurately the dispersity in chain lengths.
Alterations in the Spinal Cord T Cell Repertoire During Relapsing Experimental Autoimmune Encephalomyelitis (2000)

The CNS T cell repertoire was analyzed by RT-PCR, spectratyping, and nucleotide sequencing of the amplified products at different times following adoptive transfer of a CD4+, Th1, VB2+ encephalitogenic SJL/J proteolipid protein peptide 139-151-specific T cell clone. The third complementarity-determining region of TCR B chains in the spinal cord was used as an indicator of T cell heterogeneity. Spectratypic analysis revealed that a single peak corresponding to the third complementarity-determining region of the initiating T cell clone predominated during the acute phase. During recovery and relapse the complexity of the spectratype increased. DNA sequence analysis revealed that the donor clone predominated at the acute phase. By the first relapse the donor clone, although represented most frequently, was a minority of the total. Spectratypic analysis of the same samples for several other VB families revealed their presence during acute disease or relapses but, with the exception of VB17, their absence during the recovery stage.
Evaluation of an oral transmucosal administration of dexmedetomidine-butorphanol and dexmedetomidine-methadone in dogs. (2017)

Oral transmucosal (OTM) delivery is a simple and painless method for sedative administration in veterinary medicine and allows a rapid absorption without a first-pass metabolism by the liver (Porters et al. 2014.). OTM is particularly useful in aggressive animals (Santos et al. 2010). The aim of this study is to evaluate the efficacy of the OTM route in dogs for sedative administration in comparison with intramuscular (IM) injection. 24 mix-bread dogs undergoing soft tissue surgery or diagnostic procedures were randomly divided in 4 groups (n = 6): two groups received OTM administration of dexmedetomidine (10 µg/kg-1) together with butorphanol (0.2 mg/kg-1, BTF-OTM group) or methadone (0.2mg/kg-1, MTD-OTM group); two groups received intramuscular (IM) administration of dexmedetomidine (5 µg/kg-1) together with butorphanol (0.2 m/kg-1, BTF-IM group) or methadone (0.2 mg/kg-1, MTD-IM). Heart rate (HR), respiratory rate (RR), sedation score (Gruney et al. 2009) and side effects were recorded 10 (T10), 20 (T20) and 30 (T30) minutes after premedication. Induction was performed at T30 with titrate-to-effect propofol administration and the dosage required was recorded. At each time point BTF-IM group showed a statistically lower HR compared to BTF-OTM; RR was statistically lower at T10 in MTD-OTM group (21.33 ± 8.64 pm) compared to BTF-OTM (46.16 ± 17.98); Dogs in group MTD-IM reached a higher sedation scores at each time point compared to MTD-OTM. The induction dose of propofol appears comparable among groups. Marked vasoconstriction was observed after OTM administration, as probably related to α2-agonists use. Emesis and sialorrhea occurred in two subjects of MTD-OTM group while only one dog presented sialorrhea in BTF-OTM group. In conclusion, OTM administration appears effective and easy to perform; it takes a longer time to achieve a good sedation score, probably related to a gradual absorption of drugs that also leads to a more gradual hemodynamic effects.
Vascular Endothelial Cell Growth Factors Promote the In Vitro Development of Rat Photoreceptor Cells (2000)

We have identified and characterized a novel trophic effect of vascular endothelial cell growth factor (VEGF) on photoreceptor cells. Treatment of retinal cultures, derived from postnatal day 1 (P1) rats, with VEGF-2 resulted in a dose- and time-dependent increase in the level of rhodopsin protein, as determined by ELISA assay. After 7-9 d of treatment the VEGF-1 or VEGF-2, at a concentration of 10 ng/ml, induced a 200-300% increase in rhodopsin protein and a 220% increase in the number of rhodopsin-immunopositive cells. Treatment with VEGF-2 induced a 250% increase in the number of syntaxin-immunopositive cells and a 67% increase in high-affinity GABA uptake, both markers for amacrine cells. In contrast, there was no increase in the non-neuronal cell populations. VEGF-2 induced an approximately 300% increase in the number of bromodeoxyuridine-labeled (BrdU) retinal cells within 48 hr of treatment. After 3 d in culture both the basal and stimulated levels of BrdU incorporation were reduced, suggesting that the proliferative effect of VEGF was restricted developmentally. Furthermore, there was a developmentally dependent increase in the mitogenic response to VEGF-2, with retinal cultures derived from E15, E20, or P1 animals demonstrating a 50, 100, and 300% increase in thymidine incorporation, respectively. However, VEGF treatment resulted in an increase in the number of rhodopsin-immunopositive cells only when the cultures were derived from P1 animals. Therefore, retinal progenitor cells appear to be targets for VEGF, and thus VEGF may be involved in the regulation of the early developmental program of retinal neurogenesis.
Extensive genomic copy number variation in embryonic stem cells (2008)

Recent analysis of the human and mouse genomes has revealed that highly identical duplicated elements account for >5% of the sequence content. These elements vary in copy number between individuals. Copy number variations (CNVs) contribute significantly to genetic differences among individuals and are increasingly recognized as a causal factor in human diseases with different etiologies. In inbred mouse strains, CNVs have been fixed by inbreeding, but they are highly variable among strains. Within strains, de novo germ-line CNVs can occur, leading to interindividual variation. By analyzing the genome of clonal isolates of mouse ES cells derived from common parental lines, we have uncovered extensive and recurrent CNVs. This variation arises during mitosis and can be cotransmitted into the mouse germ line along with engineered alleles, contributing to genetic variability. The frequency and extent of these genomic changes in ES cells suggests that all somatic tissues in individuals will be mosaics composed of variants of the zygotic genome. Human ES (hES) cells and derived somatic lineages may be similarly affected, challenging the concept of a stable somatic genome.
New approach of the extrapolation procedure in the determination of acid-base constants of poorly soluble pharmaceuticals. (1979)

A new approach to the graphic extrapolation procedure is proposed for the determination of pK-value of pharmaceuticals poorly soluble in water. It is based on a direct potentiometric method for the determination of acid-base constants in non-aqueous and mixed solvents in which no preliminary calibration of the galvanic cell is needed (glass and calomel electrodes). In this way the applicability of the graphic extrapolation procedure is enlarged for a great number of organic solvents miscible with water for which no buffer pH-standards are available.
RNA interference: from model organisms towards therapy for neural and neuromuscular disorders (2004)

Experimental RNA interference (RNAi) leading to the selective knockdown of gene function is induced by introducing into cells either double stranded RNA (dsRNA), or short interfering RNA (siRNA) fragments into which dsRNA is cut. The siRNA triggers degradation of homologous messenger RNA (mRNA). Widely used as a research tool in the genetic model organisms Caenorhabditis elegans, Drosophila melanogaster and mouse to investigate the function of individual genes, RNAi has also been deployed in genome-wide, specific gene-knockdown screens. Recent rapid progress in the application of RNAi to mammalian cells, including neurons and muscle cells, offers new approaches to drug target identification and validation. Advances in targeted delivery of RNAi-inducing molecules has raised the possibility of using RNAi directly as a therapy for a variety of human genetic and other neural and neuromuscular disorders. Here, we review examples of the application of RNAi to worm, fly and mouse models of such diseases aimed at understanding their pathophysiology and we address problems to be solved in developing RNAi-based therapies.
JASMONATE-INSENSITIVE1 Encodes a MYC Transcription Factor Essential to Discriminate between Different Jasmonate-Regulated Defense Responses in Arabidopsis[W] (2004)

In spite of the importance of jasmonates (JAs) as plant growth and stress regulators, the molecular components of their signaling pathway remain largely unknown. By means of a genetic screen that exploits the cross talk between ethylene (ET) and JAs, we describe the identification of several new loci involved in JA signaling and the characterization and positional cloning of one of them, JASMONATE-INSENSITIVE1 (JAI1/JIN1). JIN1 encodes AtMYC2, a nuclear-localized basic helix-loop-helix-leucine zipper transcription factor, whose expression is rapidly upregulated by JA, in a CORONATINE INSENSITIVE1-dependent manner. Gain-of-function experiments confirmed the relevance of AtMYC2 in the activation of JA signaling. AtMYC2 differentially regulates the expression of two groups of JA-induced genes. The first group includes genes involved in defense responses against pathogens and is repressed by AtMYC2. Consistently, jin1 mutants show increased resistance to necrotrophic pathogens. The second group, integrated by genes involved in JA-mediated systemic responses to wounding, is activated by AtMYC2. Conversely, Ethylene-Response-Factor1 (ERF1) positively regulates the expression of the first group of genes and represses the second. These results highlight the existence of two branches in the JA signaling pathway, antagonistically regulated by AtMYC2 and ERF1, that are coincident with the alternative responses activated by JA and ET to two different sets of stresses, namely pathogen attack and wounding.
Performance evaluation of switched fibre channel I/O system using-FCP for SCSI (2002)

Shows how using the mixed mode protocol of FCP for SCSI it is possible to support over 2000 32Kbyte I/O operations per second and over 5600 8Kbyte I/Os per second. This provides a sustained data transfer rate of 46 to 65 Mbytes/sec using 1.0625 Gbaud FC links. The results presented here are based on simulation of FCP for SCSI on a model which incorporates real switch performance data and thus is an estimate of how this protocol would perform on the Ancor switch.
Quantized generation time in mammalian cells as an expression of the cellular clock. (1976)

The distribution of possible generation times in mammalian cells does not appear to be continous within the limits of range for each cell type; rather, generation time is quantized in multiples of 3-4 hr. Synchronous cultures of Chinese hamster V79 cells were prepared using manual and automated methods to select and stage mitotic cells. Using synchronous cultures and time-lapse video tape microscopy, it was possible to show that generation times within a population of mitotically selected cells normally disperse in a quantized fashion, with intervals of 3-4 hr occurring between bursts in division. In addition, at temperatures above 37 degrees, V79 cells have a 7.5-8.5 hr modal cell cycle, while at temperatures from 36.5 degrees to 33.5 degrees the modal cell cycle is 11-12 hr long. A survey of the synchrony literature reveals that the tendency to preferred generation times holds between cell lines. The distribution of modal generation times from a variety of different cell types forms a series with a similar interval but with a greater range of values than that observed here for V79 cells. To satisfy the published data and the work presented here, I propose a subcycle, Gq, which has a traverse time equal to the period of the clock. The period appears to be fixed at close to the same value in all mammalian somatic cells. The timekeeping mechanism appears to be temperature compensated, since the time required to traverse Gq is constant at temperatures between 34 degrees and 39 degrees. It is suggested that cell cycle time increases at lower temperatures, lower serum concentration, and high cell densitite because the number of rounds of traverse through Gq increases.
Analysis of innate and acquired resistance to anti-CD20 antibodies in malignant and nonmalignant B cells (2013)

The anti-CD20 monoclonal antibody, rituximab, provides a significant therapeutic benefit for patients with B-cell disorders. However, response to therapy varies and relapses are common, so an understanding of both inherited and acquired rituximab resistance is needed. In order to identify mechanisms of inherited resistance, sensitive versus resistant individuals were selected from a survey of 92 immortalized lymphoblastoid B-cell lines from normal individuals. Levels of CD20 protein and surface expression were lower in the resistant group. In contrast, CD20 mRNA levels were not correlated with susceptibility, suggesting regulation at a post-transcriptional level. To examine acquired resistance, resistant sublines were selected from both lymphoblastoid as well as lymphoma cell lines. Confirming previous findings, there was significant down-regulation of CD20 protein expression in all the resistant sublines. CD20 mRNA splice variants are reported to be associated with development of resistance. Three splice variants were observed in our cell lines, each lacking the binding epitope for rituximab, but none were associated with rituximab resistance. The second generation anti-CD20 mAb, ofatumumab, was more active compared with rituximab in vitro in the survey of all B-cell lines, mirroring results that have been reported previously with malignant B-cells. These studies show that normal B-lymphoblastoid cell lines can be used to model both innate and acquired mechanisms of resistance. They validate the important role of CD20 expression and enable future genetic studies to identify additional mediators of anti-CD20 mAb resistance.
Microstructure of poly(vinyl alcohol) hydrogels produced by freeze/thaw cycling (1999)

To understand the reversible gelation and subsequent aging of hydrogels prepared by freeze/thaw processing of poly(vinyl alcohol) (PVOH) solutions, the microstructures of gels prepared by different freeze/thaw protocols and aged to varying extents are studied by cryogenic transmission electron microscopy, solid-state nuclear magnetic resonance, X-ray scattering, and differential scanning calorimetry (DSC). As discussed in the literature, gelation by the freeze/thaw process occurs as a homogeneous aqueous poly(vinyl alcohol) solution is cycled, perhaps multiple times, between temperatures above 0 °C and well below 0 °C. The current investigation has determined that a few percent of chain segments crystallize during the first cycle, organizing themselves into 3–8 nm primary crystallite junctions separated on an irregular mesh by an average spacing of ∼ 30 nm. Aging or imposition of additional freeze/thaw cycles augments the level of crystallinity and transforms the as-formed liquid-like microstructure, characterized in the electron microscope by rounded ∼ 30 nm pores, into a fibrillar network. Observation that the transformation occurs at fixed mesh spacing and approximately constant average crystallite size suggests the formation of secondary crystallites that do not affect network connectivity. Dendritic ice crystallization and possibly spinodal decomposition superimpose on this nanoscale structure a matrix of much larger pores. © 1999 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 37: 3438–3454, 1999
Toward high-level reuse of statechart-based AI in computer games (2011)

Designing an interesting AI for a computer game is a complex undertaking, providing motivation to reuse portions of successful AIs. Here we advocate a layered Statechart-based AI as a modular approach that simplifies reuse. We analyze Statechart interactions and communications with respect to AI design, and propose an interface for Statechart-based AI modules that summarizes interactions.
Theoretical Study of the Electronic Structure of PbS Nanoclusters (1996)

The semiempirical tight-binding method was used to study the electronic structure of spherical PbS nanocrystals. The effects of spin−orbit coupling were included, and the calculated band gaps were found to agree well with previously published experimental values for PbS clusters. The size dependence of the band gaps was studied for clusters containing as many as 912 atoms (35-Å diameter). Direct diagonalization was used for small clusters, and Lanczos recursion was used to determine the band gaps and the eigenfunctions for the larger clusters. Analysis of the eigenfunctions revealed that the HOMO and LUMO states were spread throughout the cluster. Densities of states for the PbS nanoclusters converged to the bulk density of states, and the joint densities of states were computed as an approximation to the absorption spectra of the nanoclusters.
Characteristics of electrode impedance and stimulation efficacy of a chronic cortical implant using novel annulus electrodes in rat motor cortex (2013)

The present results provide support for the use of annulus electrodes in future applications in cortical neural prostheses.
Camera-based model to predict the total difference between effect coatings under directional illumination (2011)

A camera-based model is established to predict the total difference for samples of metallic panels with effect coatings under directional illumination, and the testing results indicate that the model can precisely predict the total difference between samples with metallic coatings with satisfactory consistency to the visual data. Due to the limited amount of testing samples, the model performance should be further developed by increasing the training and testing samples.