gebhart/patrepeval huggingface dataset:
Optimizing communication in HPF programs on fine-grain distributed shared memory (1997)

Unlike compiler-generated message-passing code, the coherence mechanisms in shared-memory systems work equally well for regular and irregular programs. In many programs, however compile-time information about data accesses would permit data to be transferred more efficiently---if the underlying shared-memory system offered suitable primitives. This paper demonstrates that cooperation between a compiler and a memory coherence protocol can improve the performance of High Performance Fortran (HPF) programs running on fine-grain distributed shared memory system up to a factor of 2, while retaining the versatility and portability of shared memory. As a consequence, shared memory's performance becomes competitive with message passing for regular applications, while not affecting (or in some cases, even improving) its large advantage for irregular codes. This paper describes the design of our implementation and reports experimental results.
Novel de novo SHANK3 mutation in autistic patients (2008)

A number of studies have confirmed that genetic factors play an important role in autism spectrum disorder (ASD). More recently de novo mutations in the SHANK3 gene, a synaptic scaffolding protein, have been associated with the ASD phenotype. As part of our gene discovery strategy, we sequenced the SHANK3 gene in a cohort of 427 ASD subjects and 190 controls. Here, we report the identification of two putative causative mutations: one being a de novo deletion at an intronic donor splice site and one missense transmitted from an epileptic father. We were able to confirm the deleterious effect of the splice site deletion by RT-PCR using mRNA extracted from cultured lymphoblastoid cells. The missense mutation, a leucine to proline at amino acid position 68, is perfectly conserved across all species examined, and would be predicted to disrupt an alpha-helical domain. These results further support the role of SHANK3 gene disruption in the etiology of ASD.
A large domain common to sperm receptors (Zp2 and Zp3) and TGF‐β type III receptor (1992)

A new family of mosaic proteins is defined by sequence analysis. The family is characterized by a 260 residue domain common to proteins of apparently diverse function and tissue specificity: sperm receptors Zp2 and Zp3, betaglycan (also called TGF-beta type III receptor), uromodulin, as well as the major zymogen granule membrane protein (GP-2). The location of the common domain is similar with respect to putative transmembrane regions. The results lead to the hypothesis that this type of domain has a common tertiary structure and that there is a functional similarity in the recognition mechanism of the sperm receptor system and the TGF-beta receptor complex.
Flagellar Phase Variation inSalmonella entericaIs Mediated by a Posttranscriptional Control Mechanism (2003)

Salmonella enterica has two antigenically distinct flagellin genes, fliC and fljB, that are alternatively expressed. The fljA gene is cotranscribed with fljB and encodes a protein that has been characterized as a transcriptional repressor of the unlinked fliC gene when FljB is expressed. In this study we report genetic evidence that FljA prevents the production of FliC protein through an interaction with the 5'-untranslated region of the fliC mRNA transcript. Studies with operon and gene fusions, Western analyses, and T(2) RNase protection assays were performed for strains with the fljBA promoter locked in either the on or the off orientation. beta-Galactosidase assays of fliC transcriptional and translational fusions to the lac operon demonstrated that while FljA inhibits fliC transcription fivefold in the fljBA(ON) orientation, it has a 200-fold effect on both fliC transcription and translation, indicating that the FljA inhibitor might act at both the transcriptional and translational level. T(2) RNase protection assays also demonstrated a fivefold decrease in fliC transcript levels for cells locked in the fljBA(ON) orientation compared to those in the fljBA(OFF) orientation, and an eightfold decrease in FliC protein levels was observed by Western analysis. This reduction in FliC protein levels is greater than the decrease observed for the transcript. These results are consistent with a new model whereby FljA inhibits FliC expression by an attenuation or translational control mechanism.
Corneal and Conjunctival/Scleral Penetration of p-Aminoclonidine, AGN 190342, and Clonidine in Rabbit Eyes (1990)

The ocular penetration pathways of three alpha 2-adrenergic agents (p-aminoclonidine, AGN 190342, and clonidine) were investigated in rabbits both in vitro and in vivo. The corneal permeabilities of the compounds correlated positively with their octanol/water distribution coefficients. The ocular drug absorption via corneal and conjunctival/scleral penetration routes was evaluated separately after drug perfusion in vivo. In most cases, the corneal route was the major pathway for the intraocular drug absorption. However, the conjunctival/scleral penetration pathway was the predominant pathway for the delivery of p-aminoclonidine, the least lipophilic compound among the three drugs, to the ciliary body. The drug concentration in the iris was contributed mainly by the corneal route and correlated well with drug lipophilicity.
VIP and PACAP induce selective neuronal differentiation of mouse embryonic stem cells (2004)

The capacity of embryonic stem cells (ES cells) to differentiate into neuronal cells represents a potential source for neuronal replacement and a model for studying factors controlling early stages of neuronal differentiation. Various molecules have been used to induce such differentiation but so far neuropeptides acting via functional G-protein-coupled receptors (GPCRs) have not been investigated. Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are neuropeptides expressed in early development which affect neuronal precursor proliferation and neuronal differentiation. VIP and PACAP share two common receptors (VPAC1 and VPAC2 receptors) while only PACAP binds with high affinity to PAC1 receptors. The aim of the study was to determine whether VIP and PACAP could produce functional neuronal differentiation of ES cells. Mouse ES cells were allowed to aggregate in embryoid bodies (EBs) in the presence or not of VIP and PACAP for 1 week. VIP and PACAP potently increased the proportion of EB-derived cells expressing specifically a neuronal phenotype shown by immunocytochemistry and neurite outgrowth without altering glial cell number. Binding and RT-PCR analyses demonstrated the presence of VPAC2 and PAC1 receptors on ES cells. Accordingly, both peptides increased cyclic AMP and intracellular calcium. In contrast, EB-derived cells only expressed a functional PAC1 receptor, suggesting a switch in GPCR phenotype during ES cell differentiation. These original data demonstrate that functional GPCRs for VIP and PACAP are present on ES cells and that these neuropeptides may induce their differentiation into a neuronal phenotype. It opens an exciting new field for neuropeptide regulation of tissue ontogenesis.
Aspartate Dehydrogenase, a Novel Enzyme Identified from Structural and Functional Studies of TM1643 (2003)

The open reading frame TM1643 of Thermotoga maritima belongs to a large family of proteins, with homologues in bacteria, archaea, and eukaryotes. TM1643 is found in an operon with two other genes that encode enzymes involved in the biosynthesis of NAD. In several bacteria, the gene in the position occupied by TM1643 encodes an aspartate oxidase (NadB), which synthesizes iminoaspartate as a substrate for NadA, the next enzyme in the pathway. The amino acid sequence of TM1643 does not share any recognizable homology with aspartate oxidase or with other proteins of known functions or structures. To help define the biological functions of TM1643, we determined its crystal structure at 2.6A resolution and performed a series of screens for enzymatic function. The structure reveals the presence of an N-terminal Rossmann fold domain with a bound NAD(+) cofactor and a C-terminal alpha+beta domain. The structural information suggests that TM1643 may be a dehydrogenase and the active site of the enzyme is located at the interface between the two domains. The enzymatic characterization of TM1643 revealed that it possesses NAD or NADP-dependent dehydrogenase activity toward l-aspartate but no aspartate oxidase activity. The product of the aspartate dehydrogenase activity is also iminoaspartate. Therefore, our studies demonstrate that two different enzymes, an oxidase and a dehydrogenase, may have evolved to catalyze the first step of NAD biosynthesis in prokaryotes. TM1643 establishes a new class of amino acid dehydrogenases.
Biosensing with conically shaped nanopores and nanotubes (2006)

In this review we consider recent results from our group that are directed towards developing "smart" synthetic nanopores that can mimic the functions of biological nanopores (transmembrane proteins). We first discuss the preparation and characterization of conical nanopores synthesized using the track-etch process. We then consider the design and function of conical nanopores that can rectify the ionic current that flows through these pores under an applied transmembrane potential. Finally, two types of sensors that we have developed with these conical nanopores are described. The first sensor makes use of molecular recognition elements that are bound to the nanopore mouth to selectively block the nanopore tip, thus detecting the presence of the analyte. The second sensor makes use of conical nanopores in a resistive-pulse type experiment, detecting the analyte via transient blockages in ionic current.
Single-cell optoporation and transfection using femtosecond laser and optical tweezers (2013)

In this paper, we demonstrate a new single-cell optoporation and transfection technique using a femtosecond Gaussian laser beam and optical tweezers. Tightly focused near-infrared (NIR) femtosecond laser pulse was employed to transiently perforate the cellular membrane at a single point in MCF-7 cancer cells. A distinct technique was developed by trapping the microparticle using optical tweezers to focus the femtosecond laser precisely on the cell membrane to puncture it. Subsequently, an external gene was introduced in the cell by trapping and inserting the same plasmid-coated microparticle into the optoporated cell using optical tweezers. Various experimental parameters such as femtosecond laser exposure power, exposure time, puncture hole size, exact focusing of the femtosecond laser on the cell membrane, and cell healing time were closely analyzed to create the optimal conditions for cell viability. Following the insertion of plasmid-coated microparticles in the cell, the targeted cells exhibited green fluorescent protein (GFP) under the fluorescent microscope, hence confirming successful transfection into the cell. This new optoporation and transfection technique maximizes the level of selectivity and control over the targeted cell, and this may be a breakthrough method through which to induce controllable genetic changes in the cell.
Modulation of factor VII levels by intron 7 polymorphisms: population and in vitro studies (2000)

Previous studies have established that factor VII gene (F7) polymorphisms (5′F7 and R353Q) contribute about one-third of factor VII (FVII) level variation in plasma. However, F7 genotyping in patients with cardiovascular disease has produced conflicting results. Population and expression studies were used to investigate the role of intron 7 (IVS7 ) polymorphisms, including repeat and sequence variations, in controlling activated FVII (FVIIa) and antigen (FVIIag) levels. Genotype–phenotype studies performed in 438 Italian subjects suggested a positive relation between the IVS7 repeat number and FVII levels. The lowest values were associated with theIVS7 + 7G allele. The screening of 52 patients with mild FVII deficiency showed an 8-fold increase in frequency (8%) of this allele, and among heterozygotes for identical mutations, lower FVII levels were observed in the IVS7 + 7G carriers. This frequent genetic component participates in the phenotypic heterogeneity of FVII deficiency. The evaluation of the individual contribution of polymorphisms was assisted by the expression of each IVS7variant, as a minigene, in eukaryotic cells. The novel quantitative analysis revealed that higher numbers of repeats were associated with higher mRNA expression levels and that the IVS7 + 7Gallele, previously defined as a functionally silent polymorphism, was responsible for the lowest relative mRNA expression. Taken together, these findings indicate that the IVS7 polymorphisms contribute to the plasmatic variance of FVII levels via differential efficiency of mRNA splicing. These studies provide further elements to understand the control of FVII levels, which could be of importance to ensure the hemostatic balance under pathologic conditions.
Discovery of 4-Azaindole Inhibitors of TGFβRI as Immuno-oncology Agents (2018)

The multifunctional cytokine TGFβ plays a central role in regulating antitumor immunity. It has been postulated that inhibition of TGFβ signaling in concert with checkpoint blockade will provide improved and durable immune response against tumors. Herein, we describe a novel series of 4-azaindole TGFβ receptor kinase inhibitors with excellent selectivity for TGFβ receptor 1 kinase. The combination of compound <b>3f</b> and an antimouse-PD-1 antibody demonstrated significantly improved antitumor efficacy compared to either treatment alone in a murine tumor model.
Computer Architecture and Organization (1989)

From the Publisher:
Computer Architecture and Organization, 3rd edition, provides a comprehensive and up-to-date view of the architecture and internal organization of computers from a mainly hardware perspective. With a balanced treatment of qualitative and quantitative issues. Hayes focuses on the understanding of the basic principles while avoiding overemphasis on the arcane aspects of design. This approach best meets the needs of undergraduate or beginning graduate-level students.
Quasi-discrete Hankel transform (1998)

A quasi-discrete Hankel transform (QDHT) is presented as a new and efficient framework for numerical evaluation of the zero-order Hankel transform. A discrete form of Parseval's theorem is obtained for the first time to the authors' knowledge, and the transform matrix is discussed. It is shown that the S factor, defined as the products of a truncated radius, is critical to building the QDHT.
Tumor-stroma interactions in pancreatic ductal adenocarcinoma (2007)

The host stromal response to an invasive epithelial carcinoma is frequently called a desmoplastic reaction (DR) and is a universal feature of pancreatic ductal adenocarcinoma (PDA). This DR is characterized by a complex interplay between the normal host epithelial cells, invading tumor cells, stromal fibroblasts, inflammatory cells, proliferating endothelial cells, an altered extracellular matrix, and growth factors activating oncogenic signaling pathways by autocrine and paracrine mechanisms. Hence, the tumor microenvironment is a dynamic process promoting tumor growth and invasion through mechanisms likely to include anoikis resistance, genomic instability, and drug resistance. Cell coculture models, murine models (xenograft and genetic), and gene expression profiling studies on human PDA biopsies have identified several key molecules, such as collagen type I, fibronectin, laminin, matrix metalloproteinases (MMP) and their inhibitors (tissue inhibitors of MMP), growth factors (transforming growth factor beta, platelet-derived growth factor, connective tissue growth factor, and hepatocyte growth factor), chemokines, and integrins as constituents of the DR. Despite these findings, it is unclear which molecular-cellular events initiate and drive desmoplasia in PDA. Accumulating evidence indicates that pancreatic stellate cells when activated switch to a myofibroblast phenotype that produces components of the extracellular matrix, MMPs, and tissue inhibitors of MMPs by activating the mitogen-activated protein kinase (extracellular signal-regulated kinase 1/2) pathway. Based on current evidence, several therapeutic strategies are been evaluated on identified potential therapeutic targets. This review summarizes our current understanding of the mechanisms that potentially drive the DR in PDA and future possibilities for therapeutic targeting of this critical process.
Comparison of Blue Luminescence Between Spark-processed Photoluminescing Silicon and Ambient Air Aged Anodically Etched Porous Silicon (1996)

Ambient air aged anodically etched porous silicon (PS) and spark-processed silicon (sp-Si) show interesting similarities and dissimilarities in some of their luminescence-related properties. Among these similarities are: (1) the photoluminescence (PL) peak maximum in the blue/violet (410 ㎚); (2) the blue/violet PL peak positions are essentially unchanged with temperature ; (3) PL decay times in the nanosecond region which are independent of the detection wavelength, which is much faster in decay times compared to that of observed decay time in SiO₂. Among the dissimilarities are: (1) the PL intensity of blue/violet luminescence, namely, the PL intensity of sp-Si is at least 2 orders of magnitude larger than that of an ambient air aged PS; (2) the blue/violet PL intensity of sp-Si is more stable than that of ambient air aged PS under UV illuminations; (3) FTIR spectra of sp-Si favor those modes, which involve silicon -oxygen bonds in SiO₂ stoichiometry, whereas ambient air aged PS can be considered as a nonstoichiometric oxide judging from the observed vibrational spectra.
Latent Herpetic Infections Following Experimental Viraemia (1976)

The spectrum of tissues harbouring latent herpes simplex virus following intravenous inoculation of mice was defined by in vitro co-cultivation techniques. The virus could be detected in central and peripheral nervous systems (including adrenal medulla), but could not be found in any non-neural tissues. Spinal ganglia were the organs most commonly involved. The relationship of these findings to the natural history of herpetic infections is discussed.
First Demonstration of a Full C-Band Tunable WDM-PON System with Novel High-Temperature DS-DBR Lasers (2014)

We demonstrate automatic operation of a cooler-less tunable-laser based WDM-PON system. Using a pilot-tone based overhead channel and centralized wavelength locking scheme, 1 Gb/s and 10 Gb/s data transmission is demonstrated in a multi-user set-up.
Endometrial Brush Biopsy (Tao Brush) (2000)

We examined 200 cases of endometrial brush biopsy (EBB) using the Tao brush and correlated findings with histologic findings from subsequent dilatation and curettage (D&C) or hysterectomy specimens. Diagnosis by EBB relied mainly on histologic evaluation of H&E-stained tissue sections and was complemented by additional cytologic smear examination. EBB correctly detected the following cases: endometrioid adenocarcinoma, 3; complex hyperplasia with atypia, 1; simple hyperplasia without atypia (SH), 2; and benign endometrium, 177. In 3 cases the diagnosis of atrophic endometrium was made by EBB; corresponding D&C specimens were nondiagnostic. Five cases of SH were interpreted by EBB as proliferative endometrium, and 13 endometrial polyps were not identified by EBB. Nine samples were nondiagnostic. Sensitivity and specificity were 100% for detecting atypical hyperplasia and carcinoma. However, it was difficult for EBB to distinguish SH from disordered proliferative endometrium or to diagnose endometrial polyps. We found that diagnosis by EBB is reproducible; a second pathologist blinded to histologic follow-up correctly identified all adenocarcinoma/atypical hyperplasia cases. EBB is an accurate, safe, and easy procedure that is well tolerated by patients and should be considered in the initial evaluation of high-risk outpatients.
Prostate‐specific membrane antigen retargeted measles virotherapy for the treatment of prostate cancer (2009)

The PSMA retargeted virus warrants further investigation as a virotherapy agent.
Interleukin-5 inhibits translocation of Bax to the mitochondria, cytochrome c release, and activation of caspases in human eosinophils (2001)

The apoptosis and subsequent clearance of eosinophils without histotoxic mediator release is thought to be crucial in the resolution of airway inflammation in asthma. Interleukin-5 (IL-5) is a potent suppressor of eosinophil apoptosis. The mechanism by which IL-5 inhibits spontaneous eosinophil apoptosis was investigated. Freshly isolated eosinophils constitutively expressed the conformationally active form of Bax in the cytosol and nucleus. During spontaneous and staurosporine-induced apoptosis, Bax underwent a caspase-independent translocation to the mitochondria, which was inhibited by IL-5. Eosinophil apoptosis was associated with the release of cytochrome c from the mitochondria, which was also inhibited by IL-5. IL-5 and the cell-permeable caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-(OMe) fluoromethyl ketone (z-VAD.fmk), prevented phosphatidylserine (PS) externalization, although only IL-5 inhibited loss of mitochondrial membrane potential (DeltaPsim). Peripheral blood eosinophils endogenously expressed "initiator" caspase-8 and -9, and "effector" caspase-3, -6, and -7. Spontaneous eosinophil apoptosis was associated with processing of caspase-3, -6, -7, -8, and -9. IL-5 and z-VAD.fmk prevented caspase activation in spontaneous apoptosis. The results suggest that spontaneous eosinophil apoptosis involves Bax translocation to the mitochondria, cytochrome c release, caspase-independent perturbation of the mitochondrial membrane, and subsequent activation of caspases. IL-5 inhibits spontaneous eosinophil apoptosis at a site upstream of Bax translocation.
Human and machine dimensions of 3D interfaces for virtual environments (1995)

No abstract available.
Generation of Human-Induced Pluripotent Stem Cells in the Absence of Exogenous Sox2 (2009)

Induced pluripotent stem cell technology has attracted enormous interest for potential application in regenerative medicine. Here, we report that a specific glycogen synthase kinase 3 (GSK-3) inhibitor, CHIR99021, can induce the reprogramming of mouse embryonic fibroblasts transduced by only two factors, Oct4 and Klf4. When combined with Parnate (also named tranylcypromine), an inhibitor of lysine-specific demethylase 1, CHIR99021 can cause the reprogramming of human primary keratinocyte transduced with the two factors, Oct4 and Klf4. To our knowledge, this is the first time that human iPS cells have been generated from somatic cells without exogenous Sox2 expression. Our studies suggest that the GSK-3 inhibitor might have a general application to replace transcription factors in both mouse and human reprogramming.
Conjugated avidin binds to mast cell granules. (1985)

The glycoprotein, avidin, conjugated either to the enzyme horseradish peroxidase, or to the fluorochrome dyes, fluorescein or rhodamine, identifies the granules of mast cells in both tissues and cell suspensions. In the absence of prior fixation, mast cells were not identified with conjugated avidin; however, granules released from these cells were stained with this labeled glycoprotein. The specificity of avidin for mast cells was confirmed by the absence of conjugated avidin-positive cells in the skin of mice (S1/S1d) deficient in mature dermal mast cells. Electron microscopic studies confirmed that avidin binds specifically to individual mast cell granules rather than to other cellular structures. Rodent and human mast cells were readily stained with avidin conjugated to horseradish peroxidase or to either of the fluorochrome dyes. The conjugated avidin staining technique is a reliable and simple method for identifying rodent and human mast cells, one that is useful as both an investigative and a clinical tool.