gebhart/patrepeval huggingface dataset:
Anti‐tumor effect in an in vivo model by human‐derived pancreatic RNase with basic fibroblast growth factor insertional fusion protein through antiangiogenic properties (2006)

It is thought that the export of angiogenic fibroblast growth factors (FGF) from tumors may be involved in the onset of tumor angiogenesis. To create a new active targeting drug that inhibits the tumor angiogenic process without toxicities to normal cells, human basic FGF (h-bFGF) was inserted genetically into the Gly89 position of cross-linked RNase1 (the ribonuclease inhibitor protein [RI] binding site of cross-linked human pancreatic RNase) to prevent stereospecific binding to RI. The resultant insertional-fusion protein (CL-RFN89) was active both as h-bFGF and as RNase1. Furthermore, it acquired an additional ability of evading RI through steric blockade of RI binding caused by the fused h-bFGF domain. In the present study, the effect of the resultant protein, CL-RFN89, on the antitumor response though its antiangiogenic properties was investigated in an in vivo model. Continuous systemic treatment with CL-RFN89 significantly inhibited the growth of human A431 squamous cell carcinomas in vivo. Seven days of treatment with CL-RFN89 resulted in a 58.2% inhibition of tumor growth compared with control mice (P < 0.0001). Furthermore, immunohistochemistry using a rat antimouse CD31 antibody showed that treatment with CL-RFN89 reduced tumor vascularization. These findings identify CL-RFN89 as a potent systemic inhibitor of tumor growth as a result of its antiangiogenic properties. This protein appears to be a new systemic antitumor agent.
Aging and Atherosclerosis (2012)

Atherosclerosis is classed as a disease of aging, such that increasing age is an independent risk factor for the development of atherosclerosis. Atherosclerosis is also associated with premature biological aging, as atherosclerotic plaques show evidence of cellular senescence characterized by reduced cell proliferation, irreversible growth arrest and apoptosis, elevated DNA damage, epigenetic modifications, and telomere shortening and dysfunction. Not only is cellular senescence associated with atherosclerosis, there is growing evidence that cellular senescence promotes atherosclerosis. This review examines the pathology of normal vascular aging, the evidence for cellular senescence in atherosclerosis, the mechanisms underlying cellular senescence including reactive oxygen species, replication exhaustion and DNA damage, the functional consequences of vascular cell senescence, and the possibility that preventing accelerated cellular senescence is a therapeutic target in atherosclerosis.
Genetics of gastric cancer. (1996)

Although the death rate from gastric carcinoma in the US and other western communities has decreased in recent times, a similar trend has not been noted in other countries, especially S.E. Asia. Upto 95% of all malignant gastric neoplasms are adenocarcinomata, but other types of gastric cancer have evoked considerable interest in the literature. Genetic factors have been suspected of playing a pivotal role in the etiology of gastric cancer but no clear inheritance pattern has emerged and environmental influences remain the focus of many current theories of pathogenesis. Current evidence implicates the non-random involvement of certain chromosomes and related oncogenes especially Ras and p53. Genes that may predispose to gastric cancer have not been clearly implicated but some studies indicate a familial aggregation of gastric cancer. The objective of this review is to reappraise the role of genetics in the etiology of gastric cancer with special reference to relevant information for practicing clinicians.
NYVAC-Pf7: a poxvirus-vectored, multiantigen, multistage vaccine candidate for Plasmodium falciparum malaria (1996)

The highly attenuated NYVAC vaccinia virus strain has been utilized to develop a multiantigen, multistage vaccine candidate for malaria, a disease that remains a serious global health problem and for which no highly effective vaccine exists. Genes encoding seven Plasmodium falciparum antigens derived from the sporozoite (circumsporozoite protein and sporozoite surface protein 2), liver (liver stage antigen 1), blood (merozoite surface protein 1, serine repeat antigen, and apical membrane antigen 1), and sexual (25-kDa sexual-stage antigen) stages of the parasite life cycle were inserted into a single NYVAC genome to generate NYVAC-Pf7. Each of the seven antigens was expressed in NYVAC-Pf7-infected culture cells, and the genotypic and phenotypic stability of the recombinant virus was demonstrated. When inoculated into rhesus monkeys, NYVAC-Pf7 was safe and well tolerated. Antibodies that recognize sporozoites, liver, blood, and sexual stages of P. falciparum were elicited. Specific antibody responses against four of the P.falciparum antigens (circumsporozoite protein, sporozoite surface protein 2, merozoite surface protein 1, and 25-kDa sexual-stage antigen) were characterized. The results demonstrate that NYVAC-Pf7 is an appropriate candidate vaccine for further evaluation in human clinical trials.
Inhibition of phosphoinositide 3‐kinase δ attenuates allergic airway inflammation and hyperresponsiveness in murine asthma model (2006)

P110delta phosphoinositide 3-kinase (PI3K) plays a pivotal role in the recruitment and activation of certain inflammatory cells. Recent findings revealed that the activity of p110delta also contributes to allergen-IgE-induced mast cell activation and vascular permeability. We investigated the role of p110delta in allergic airway inflammation and hyperresponsiveness using IC87114, a selective p110delta inhibitor, in a mouse asthma model. BALB/c mice were sensitized with OVA and, upon OVA aerosol challenge, developed airway eosinophilia, mucus hypersecretion, elevation in cytokine and chemokine levels, up-regulation of ICAM-1 and VCAM-1 expression, and airway hyperresponsiveness. Intratracheal administration of IC87114 significantly (P<0.05) attenuated OVA-induced influx into lungs of total leukocytes, eosinophils, neutrophils, and lymphocytes, as well as levels of IL-4, IL-5, IL-13, and RANTES in a dose-dependent manner. IC87114 also significantly (P<0.05) reduced the serum levels of total IgE and OVA-specific IgE and LTC(4) release into the airspace. Histological studies show that IC87114 inhibited OVA-induced lung tissue eosinophilia, airway mucus production, and inflammation score. In addition, IC87114 significantly (P<0.05) suppressed OVA-induced airway hyperresponsiveness to inhaled methacholine. Western blot analyses of whole lung tissue lysates shows that IC87114 markedly attenuated the OVA-induced increase in expression of IL-4, IL-5, IL-13, ICAM-1, VCAM-1, RANTES, and eotaxin. Furthermore, IC87114 treatment markedly attenuated OVA-induced serine phosphorylation of Akt, a downstream effector of PI3K signaling. Taken together, our findings implicate that inhibition of p110delta signaling pathway may have therapeutic potential for the treatment of allergic airway inflammation.
HTLV-III in Saliva of People with AIDS-Related Complex and Healthy Homosexual Men at Risk for AIDS (1984)

Peripheral blood leukocytes and saliva from 20 individuals, including four with the acquired immune deficiency syndrome (AIDS), ten with AIDS-related complex (ARC), and six healthy homosexual males at risk for AIDS, were compared as sources of transmissible human T-cell leukemia (lymphotropic) virus type III (HTLV-III), the virus found to be the etiologic agent of AIDS. All of the AIDS and ARC patients and four of the six healthy homosexuals had evidence of prior exposure to HTLV-III as indicated by seropositivity for antibody to HTLV-III structural proteins. Infectious virus was isolated from the peripheral blood of one of the AIDS patients, four of the ARC patients, and two of the healthy homosexual males, consistent with previous reports. HTLV-III was also isolated from the saliva of four of the ARC patients and four of the healthy homosexuals. Virus was also observed by electron microscopy in material prepared by centrifugation of the saliva of one AIDS patient. Although AIDS does not appear to be transmitted by casual contact, the possibility that HTLV-III can be transmitted by saliva should be considered.
Receptors for Dopamine and Somatostatin: Formation of Hetero-Oligomers with Enhanced Functional Activity (2000)

Somatostatin and dopamine are two major neurotransmitter systems that share a number of structural and functional characteristics. Somatostatin receptors and dopamine receptors are colocalized in neuronal subgroups, and somatostatin is involved in modulating dopamine-mediated control of motor activity. However, the molecular basis for such interaction between the two systems is unclear. Here, we show that dopamine receptor D2R and somatostatin receptor SSTR5 interact physically through hetero-oligomerization to create a novel receptor with enhanced functional activity. Our results provide evidence that receptors from different G protein (heterotrimeric guanine nucleotide binding protein)-coupled receptor families interact through oligomerization. Such direct intramembrane association defines a new level of molecular crosstalk between related G protein-coupled receptor subfamilies.
A Hierarchical Network of Interreceptor Interactions Determines Signal Transduction by Neu Differentiation Factor/Neuregulin and Epidermal Growth Factor (1996)

The ErbB family includes four homologous transmembrane tyrosine kinases. Whereas ErbB-1 binds to the epidermal growth factor (EGF), both ErbB-3 and ErbB-4 bind to the Neu differentiation factors (NDFs, or neuregulins), and ErbB-2, the most oncogenic family member, is an orphan receptor whose function is still unknown. Because previous lines of evidence indicated the existence of interreceptor interactions, we used ectopic expression of individual ErbB proteins and their combinations to analyze the details of receptor cross talks. We show that 8 of 10 possible homo-and heterodimeric complexes of ErbB proteins can be hierarchically induced by ligand binding. Although ErbB-2 binds neither ligand, even in a heterodimeric receptor complex, it is the preferred heterodimer partner of the three other members, and it favors interaction with ErbB-3. Selective receptor overexpression in human tumor cells appears to bias the hierarchical relationships. The ordered network is reflected in receptor transphosphorylation, ErbB-2-mediated enhancement of ligand affinities, and remarkable potentiation of mitogenesis by a coexpressed ErbB-2. The observed superior ability of ErbB-2 to form heterodimers, in conjunction with its uniquely high basal tyrosine kinase activity, may explain why ErbB-2 overexpression is associated with poor prognosis.
Transforming growth factor-β and breast cancer: Cell cycle arrest by transforming growth factor-β and its disruption in cancer (2000)

Altered responsiveness to extracellular signals and cell cycle dysregulation are hallmarks of cancer. The cell cycle is governed by cyclin-dependent kinases (cdks) that integrate mitogenic and growth inhibitory signals. Transforming growth factor (TGF)-beta mediates G1 cell cycle arrest by inducing or activating cdk inhibitors, and by inhibiting factors required for cdk activation. Mechanisms that lead to cell cycle arrest by TGF-beta are reviewed. Loss of growth inhibition by TGF-beta occurs early in breast cell transformation, and may contribute to breast cancer progression. Dysregulation of cell cycle effectors at many different levels may contribute to loss of G1 arrest by TGF-beta. Elucidation of these pathways in breast cancer may ultimately lead to novel and more effective treatments for this disease.
Relationship between solute transport properties and tissue morphology in human annulus fibrosus (2009)

Poor nutritional supply to the intervertebral disc is believed to be an important factor leading to disc degeneration. However, little is known regarding nutritional transport in human annulus fibrosus (AF) and its relation to tissue morphology. We hypothesized that solute diffusivity in human AF is anisotropic and inhomogeneous, and that transport behaviors are associated with tissue composition and structure. To test these hypotheses, we measured the direction-dependent diffusivity of a fluorescent molecule (fluorescein, 332 Da) in three regions of AF using a fluorescence recovery after photobleaching (FRAP) technique, and associated transport results to the regional variation in water content and collagen architecture in the tissue. Diffusivity in AF was anisotropic, with higher values in the axial direction than in the radial direction for all regions investigated. The values of the diffusion coefficient ranged from 0.38 +/- 0.25 x 10(-6) cm(2)/s (radial diffusivity in outer AF) to 2.68 +/- 0.84 x 10(-6) cm(2)/s (axial diffusivity in inner AF). In both directions, diffusivity decreased moving from inner to outer AF. Tissue structure was investigated using both scanning electron microscopy and environmental scanning electron microscopy. A unique arrangement of microtubes was found in human AF. Furthermore, we also found that the density of these microtubes varied moving from inner to outer AF. A similar trend of regional variation was found for water content, with the highest value also measured in inner AF. Therefore, we concluded that a relationship exists among the anisotropic and inhomogeneous diffusion in human AF and the structure and composition of the tissue.
Isoenzymes of pyruvate kinase (1990)

Conference Article| April 01 1990 Isoenzymes of pyruvate kinase HILARY MUIRHEAD HILARY MUIRHEAD 1Department of Biochemistry, University of Bristol, Bristol BS8 1TD, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1990) 18 (2): 193–196. https://doi.org/10.1042/bst0180193 Article history Received: October 10 1989 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation HILARY MUIRHEAD; Isoenzymes of pyruvate kinase. Biochem Soc Trans 1 April 1990; 18 (2): 193–196. doi: https://doi.org/10.1042/bst0180193 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: PK, pyruvate kinase This content is only available as a PDF. © 1990 Biochemical Society1990 Article PDF first page preview Close Modal You do not currently have access to this content.
How Proteolysis Drives the Cell Cycle (1996)

Oscillations in the activity of cyclin-dependent kinases (CDKs) promote progression through the eukaryotic cell cycle. This review examines how proteolysis regulates CDK activity-by degrading CDK activators or inhibitors-and also how proteolysis may directly trigger the transition from metaphase to anaphase. Proteolysis during the cell cycle is mediated by two distinct ubiquitin-conjugation pathways. One pathway, requiring CDC34, initiates DNA replication by degrading a CDK inhibitor. The second pathway, involving a large protein complex called the anaphase-promoting complex or cyclosome, initiates chromosome segregation and exit from mitosis by degrading anaphase inhibitors and mitotic cyclins. Proteolysis therefore drives cell cycle progression not only by regulating CDK activity, but by directly influencing chromosome and spindle dynamics.
N‐Heterocyclic Carbenes as Organocatalysts (2007)

Organocatalyzed reactions represent an attractive alternative to metal-catalyzed processes notably because of their lower cost and benign environmental impact in comparison to organometallic catalysis. In this context, N-heterocyclic carbenes (NHCs) have been studied for their ability to promote primarily the benzoin condensation. Lately, dramatic progress in understanding their intrinsic properties and in their synthesis have made them available to organic chemists. This has resulted in a tremendous increase of their scope and in a true explosion of the number of papers reporting NHC-catalyzed reactions. Here, we highlight the ever-increasing number of reactions that can be promoted by N-heterocyclic carbenes.
Isolation of a Paramyxovirus from the Cerebrospinal Fluid of a Dog with Posterior Paresis (1980)

A paramyxovirus was isolated from cerebrospinal fluid of a dog with a history of incoordination and posterior paresis. The virus apparently was not related to canine distemper virus (CDV), considering the lack of virus neutralization with CDV-specific antibody, negative immunofluorescence with CDV-specific conjugate, and avirulence for ferrets. The virus was antigenically related to a prototype strain of canine parainfluenza virus, as determined by positive immunofluorescence with canine parainfluenza virus-specific conjugate and virus neutralization tests.
Heel lancing in term new-born infants: an evaluation of pain by frequency domain analysis of heart rate variability (1999)

The aim of the investigation was to assess pain by frequency domain analysis of heart rate variability (HRV) during a routine heel lancing procedure in term new-born infants. Beat-to-beat heart rate (HR) was recorded in 23 healthy new-born infants on the maternity ward during blood sampling for neonatal screening. A sham heel prick prior to the sharp lancing procedure was performed randomly in half of the infants. Spectral analysis of HRV was assessed for each of the following sequences: (1) baseline (2) sham heel prick (3) sharp heel prick and (4) squeezing the heel for blood sampling. The response to the sham prick did not differ significantly from the sharp prick. Compared with the baseline, sharp lancing gave rise to minor increases in HR and variability in the low frequency band of the spectral analysis. A clear stress response was provoked when the heel was squeezed for blood sampling, indicated by an increased HR and a decreased spectral power in the high frequency band (i.e. lower vagal tone). The different stress responses during the lancing and the squeezing of the heel were clearly illustrated when principal component analysis was applied and the vectors for the changes in HR and spectral pattern were indicated. In conclusion, the squeezing of the heel is the most stressful event during the heel prick procedure.
Adding dynamically-typed language support to a statically-typed language compiler (2012)

Applications written in dynamically typed scripting languages are increasingly popular for Web software development. Even on the server side, programmers are using dynamically typed scripting languages such as Ruby and Python to build complex applications quickly. As the number and complexity of dynamically typed scripting language applications grows, optimizing their performance is becoming important. Some of the best performing compilers and optimizers for dynamically typed scripting languages are developed entirely from scratch and target a specific language. This approach is not scalable, given the variety of dynamically typed scripting languages, and the effort involved in developing and maintaining separate infrastructures for each. In this paper, we evaluate the feasibility of adapting and extending an existing production-quality method-based Just-In-Time (JIT) compiler for a language with dynamic types. Our goal is to identify the challenges and shortcomings with the current infrastructure, and to propose and evaluate runtime techniques and optimizations that can be incorporated into a common optimization infrastructure for static and dynamic languages. We discuss three extensions to the compiler to support dynamically typed languages: (1) simplification of control flow graphs, (2) mapping of memory locations to stack-allocated variables, and (3) reduction of runtime overhead using language semantics. We also propose four new optimizations for Python in (2) and (3). These extensions are effective in reduction of compiler working memory and improvement of runtime performance. We present a detailed performance evaluation of our approach for Python, finding an overall improvement of 1.69x on average (up to 2.74x) over our JIT compiler without any optimization for dynamically typed languages and Python.
Sox2-positive dermal papilla cells specify hair follicle type in mammalian epidermis (2009)

The dermal papilla comprises the specialised mesenchymal cells at the base of the hair follicle. Communication between dermal papilla cells and the overlying epithelium is essential for differentiation of the hair follicle lineages. We report that Sox2 is expressed in all dermal papillae at E16.5, but from E18.5 onwards expression is confined to a subset of dermal papillae. In postnatal skin, Sox2 is only expressed in the dermal papillae of guard/awl/auchene follicles, whereas CD133 is expressed both in guard/awl/auchene and in zigzag dermal papillae. Using transgenic mice that express GFP under the control of the Sox2 promoter, we isolated Sox2(+) (GFP(+)) CD133(+) cells and compared them with Sox2(-) (GFP(-)) CD133(+) dermal papilla cells. In addition to the 'core' dermal papilla gene signature, each subpopulation expressed distinct sets of genes. GFP(+) CD133(+) cells had upregulated Wnt, FGF and BMP pathways and expressed neural crest markers. In GFP(-) CD133(+) cells, the hedgehog, IGF, Notch and integrin pathways were prominent. In skin reconstitution assays, hair follicles failed to form when dermis was depleted of both GFP(+) CD133(+) and GFP(-) CD133(+) cells. In the absence of GFP(+) CD133(+) cells, awl/auchene hairs failed to form and only zigzag hairs were found. We have thus demonstrated a previously unrecognised heterogeneity in dermal papilla cells and shown that Sox2-positive cells specify particular hair follicle types.
Silicon-on-insulator 'gate-all-around' MOS device (2002)

The total-dose radiation hardness of MOS devices is roughly inversely proportional to the square of the thickness of the oxide layers in contact with the silicon. In SOI (silicon-on-insulator) devices, the silicon layer sits on an oxide layer of typically 400 nm. It is proposed that a thin, gate-quality oxide can be realized at the front as well as the back of the devices, which should greatly enhance the radiation hardness. Double-gate devices (i.e. the same gate at the front and the back of the device) have been shown to have, at least theoretically, interesting short-channel and high transconductance properties. The only reported realization of such a device used a complicated, highly non-planar process (vertical devices) and left one edge of the device in contact with a thick oxide, which can be detrimental to rad-hard performances. Fabrication processes and device performances are described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Targeting CD4+CD25+FoxP3+ regulatory T-cells for the augmentation of cancer immunotherapy. (2007)

CD4+CD25+FoxP3+ T-regulatory (Treg) cells are vital to the maintenance of peripheral self tolerance and are implicated in tolerance to foreign antigens. Increasing evidence shows that Treg cells may also play an important role in immune evasion mechanisms employed by cancer. Treg cells are actively recruited and induced by tumors to block innate and adaptive immune priming, effector function and memory response, which can inhibit the efficacy of therapeutic cancer vaccines. As such, modulation of Treg cell function in cancer has been studied using various approaches, with encouraging preclinical and clinical findings. However, controlled and effective modulation of Treg cell function for cancer therapeutics will be contingent on a better understanding of the molecular basis of Treg cell interaction with tumor cells and ensuing immunosuppressive mechanisms.