gebhart/patrepeval huggingface dataset:
Expression of Vascular Endothelial Growth Factors and Their Receptors during Osteoblast Differentiation (2000)

Endochondral bone formation is regulated by systemically and locally acting growth factors. A role for vascular endothelial growth factor (VEGF) in this process has recently been proposed, because inactivation of VEGF inhibits endochondral bone formation via inhibition of angiogenesis. Despite the known effect of VEGF as specific endothelial growth factor, its effects on osteoblast differentiation have not been studied. We, therefore, examined the expression of VEGF-A, -B, -C, and -D and their receptors in a model of osteoblast differentiation using the mouse preosteoblast-like cell line KS483. Early in differentiation, KS483 cells express low levels VEGF-A, -B, and -D messenger RNA, whereas during mineralization, KS483 cells express high levels. In addition, expression of the VEGF receptors, VEGFR1, VEGFR2, and VEGF165R/neuropilin, coincided with expression of their ligands, being maximally expressed during mineralization. VEGF-A production during osteoblast differentiation was stimulated by insulin-like growth factor I that enhances osteoblast differentiation and was inhibited by PTH-related peptide that inhibits osteoblast differentiation. Furthermore, continuous treatment of KS483 cells with recombinant human VEGF-A stimulated nodule formation. Although treatment of KS483 cells with soluble FLT1, an agent that blocks binding of VEGF-A and -B to VEGFR1, did not inhibit nodule formation, this observation does not exclude involvement of VEGFR2 in the regulation of osteoblast differentiation. As it is known that VEGF-A, -C, and -D can act through activation of VEGFR2, other isoforms might compensate for VEGF-A loss. The expression pattern of VEGFs and their receptors shown here suggests that VEGFs play an important role in the regulation of bone remodeling by attracting endothelial cells and osteoclasts and by stimulating osteoblast differentiation.
Clinical and imaging correlates of response to treatment with infliximab in patients with ankylosing spondylitis. (2001)

Infliximab was an effective treatment for AS in a short term trial. Longterm control of symptoms and potential alteration in clinical course of disease will require longterm assessment.
Palladium-Catalyzed Borylation of Aryl Halides or Triflates with Dialkoxyborane:  A Novel and Facile Synthetic Route to Arylboronates (1999)

A direct borylation of aryl halides or triflates with dialkoxyborane was investigated. The coupling reaction of pinacolborane with aryl halides or triflates in the presence of a catalytic amount of PdCl(2)(dppf) together with a base provided arylboronates in high yields. The product distributions were strongly dependent on the base employed, and the tertiary amine, especially Et(3)N, was effective for the selective formation of the boron-carbon bond. The reaction conditions were so mild that arylboronates having a variety of functional groups such as carbonyl, cyano, and nitro groups were readily prepared.
Multi-Frequency High-Field EPR Study of Iron Centers in Malarial Pigments (2006)

The multi-frequency high-field electron paramagnetic resonance (HFEPR) was used to study the magnetic properties of malarial pigment hemozoin and its synthetic analogue, beta-hematin. (FeIII-protoporphyrin-IX)2 dimers containing five-coordinate high-spin FeIII, S = 5/2, are the building blocks of these pigments. The fit of EPR spectra that were acquired in an unprecedented wide range of microwave frequencies of 34 and 94 GHz for hemozoin and 27-500 GHz for beta-hematin yielded a complete set of intrinsic spin Hamiltonian parameters: D = +5.85(1) cm-1, E = 0, g perpendicular = 1.95(1), g parallel = 2.00(1). These results point to the existence of largely axial symmetry of the iron environment in the bulk phase of hemozoin and beta-hematin.
Inhibition of “self” engulfment through deactivation of myosin-II at the phagocytic synapse between human cells (2008)

Phagocytosis of foreign cells or particles by macrophages is a rapid process that is inefficient when faced with "self" cells that display CD47-although signaling mechanisms in self-recognition have remained largely unknown. With human macrophages, we show the phagocytic synapse at cell contacts involves a basal level of actin-driven phagocytosis that, in the absence of species-specific CD47 signaling, is made more efficient by phospho-activated myosin. We use "foreign" sheep red blood cells (RBCs) together with CD47-blocked, antibody-opsonized human RBCs in order to visualize synaptic accumulation of phosphotyrosine, paxillin, F-actin, and the major motor isoform, nonmuscle myosin-IIA. When CD47 is functional, the macrophage counter-receptor and phosphatase-activator SIRPalpha localizes to the synapse, suppressing accumulation of phosphotyrosine and myosin without affecting F-actin. On both RBCs and microbeads, human CD47 potently inhibits phagocytosis as does direct inhibition of myosin. CD47-SIRPalpha interaction initiates a dephosphorylation cascade directed in part at phosphotyrosine in myosin. A point mutation turns off this motor's contribution to phagocytosis, suggesting that self-recognition inhibits contractile engulfment.
Rare protein-altering variants in ANGPTL7 lower intraocular pressure and protect against glaucoma (2020)

Protein-altering variants that are protective against human disease provide in vivo validation of therapeutic targets. Here we use genotyping data from UK Biobank (n = 337,151 unrelated White British individuals) and FinnGen (n = 176,899) to conduct a search for protein-altering variants conferring lower intraocular pressure (IOP) and protection against glaucoma. Through rare protein-altering variant association analysis, we find a missense variant in ANGPTL7 in UK Biobank (rs28991009, p.Gln175His, MAF = 0.8%, genotyped in 82,253 individuals with measured IOP and an independent set of 4,238 glaucoma patients and 250,660 controls) that significantly lowers IOP (β = -0.53 and -0.67 mmHg for heterozygotes, -3.40 and -2.37 mmHg for homozygotes, P = 5.96 x 10-9 and 1.07 x 10-13 for corneal compensated and Goldman-correlated IOP, respectively) and is associated with 34% reduced risk of glaucoma (P = 0.0062). In FinnGen, we identify an ANGPTL7 missense variant at a greater than 50-fold increased frequency in Finland compared with other populations (rs147660927, p.Arg220Cys, MAF Finland = 4.3%), which was genotyped in 6,537 glaucoma patients and 170,362 controls and is associated with a 29% lower glaucoma risk (P = 1.9 x 10-12 for all glaucoma types and also protection against its subtypes including exfoliation, primary open-angle, and primary angle-closure). We further find three rarer variants in UK Biobank, including a protein-truncating variant, which confer a strong composite lowering of IOP (P = 0.0012 and 0.24 for Goldman-correlated and corneal compensated IOP, respectively), suggesting the protective mechanism likely resides in the loss of interaction or function. Our results support inhibition or down-regulation of ANGPTL7 as a therapeutic strategy for glaucoma.
Chemopreventive Agents (1998)

Certain protease inhibitors, called the anticarcinogenic protease inhibitors in this review, are capable of preventing carcinogenesis in a wide variety of in vivo and in vitro model systems. The anticarcinogenic protease inhibitors are extremely potent agents with the ability to prevent cancer, with some unique characteristics as anticarcinogenic agents. The anticarcinogenic protease inhibitors have the ability to irreversibly suppress the carcinogenic process. They do not have to be continuously present to suppress carcinogenesis. They can be effective when applied in both in vivo and in vitro carcinogenesis assay systems at long time periods after carcinogen exposure, and are effective as anticarcinogenic agents at extremely low molar concentrations. While several different types of protease inhibitors can prevent the carcinogenic process, the most potent of the anticarcinogenic protease inhibitors on a molar basis are those with the ability to inhibit chymotrypsin or chymotrypsin-like proteases. The soybean-derived protease inhibitor, Bowman-Birk inhibitor (BBI), is a potent chymotrypsin inhibitor that has been extensively studied for its ability to prevent carcinogenesis in many different model systems. Much of this review is focused on the characteristics of BBI as the anticarcinogenic protease inhibitor, as this is the protease inhibitor that has risen to the human trial stage as a human cancer chemopreventive agent. Part of this review hypothesizes that the Bowman-Birk family of protease inhibitors plays a role in plants similar to that of alpha1-antichymotrypsin in people. Both BBI and alpha1-antichymotrypsin are potent inhibitors of chymotrypsin and chymotrypsin-like enzymes, are highly anti-inflammatory, and are thought to play important roles in the defense of their respective organisms. It is believed that BBI will be shown to play a major role in the prevention and/or treatment of several different diseases, in addition to cancer.
An oncogenic point mutation confers high affinity ligand binding to the neu receptor. Implications for the generation of site heterogeneity. (1992)

The neu protooncogene encodes a receptor tyrosine kinase homologous to the receptor for the epidermal growth factor. The oncogenic potential of neu is released upon chemical carcinogenesis, which replaces a glutamic acid for a valine residue, within the single transmembrane domain. This results in constitutive receptor dimerization and activation of the intrinsic catalytic function. To study the implications of the oncogenic mutation and the consequent receptor dimerization on the interaction with the yet incompletely characterized ligand of p185neu, we constructed chimeric proteins between the ligand binding domain of the epidermal growth factor receptor and the transmembrane and cytoplasmic domains of the normal or the transforming Neu proteins. The chimeric receptors displayed cellular and biochemical differences characteristic of the normal and the transforming Neu proteins and therefore may reliably represent the ligand binding functions of the two receptor forms. Analyses of ligand binding revealed qualitative and quantitative differences that were a result of the single mutation; whereas the normal chimera (valine version) displayed two populations of binding sites with approximately 90% of the receptors in the low affinity state, the transforming receptor (glutamic acid version) showed a single population of binding sites with relatively high affinity. Kinetics measurements indicated that the difference in affinities was because of slower rates of both ligand association and ligand dissociation from the constitutively dimerized mutant receptor. It therefore appears that the oncogenic mutation, by permanently dimerizing the receptor, establishes a high affinity ligand binding state which is functionally equivalent to the ligand-occupied normal receptor. Our conclusion is further supported by the rates of endocytosis of the wild-type and the mutant receptor. Hence, these results provide the first experimental evidence from living cells which supports a model that attributes the heterogeneity of ligand binding sites to the state of oligomerization of receptor tyrosine kinases.
Optical burst switching for service differentiation in the next-generation optical Internet (2001)

In an effort to eliminate the electronic bottleneck, new optical switches/routers (hardware) are being built for the next-generation optical Internet where IP runs over an all-optical WDM layer. However, important issues yet to be addressed in terms of protocols (software) are how to develop a new paradigm that does not require any buffer at the WDM layer, as in circuit switching, and elimination of any layers between which exist mainly due to historical reasons. At the same time, such a paradigm should also efficiently support bursty traffic with high resource utilization as in packet switching. This article surveys design issues related to a new switching paradigm called optical burst switching, which achieves a balance between circuit and packet switching while avoiding their shortcomings. We describe how OBS can be applied to the next-generation optical Internet, and in particular how offset times and delayed reservation can help avoid the use of buffer, and support quality of service at the WDM layer.
Expression of ERp29, an Endoplasmic Reticulum Secretion Factor in Basal-Cell Carcinoma (2006)

The role of endoplasmic reticulum (ER)-stress proteins in the pathogenesis of neoplasia remains obscure. ERp29 encodes for an ER protein that is thought to facilitate the transport of secretory proteins in the early secretory pathway. ERp29 is expressed at varying levels in virtually every tissue tested, yet its precise role remains obscure. To test if ERp29 is associated with the pathogenesis of skin cancer, in the present study we have assessed the expression of ERp29 in basal-cell carcinoma of the skin. A bank of 104 basal skin carcinoma, including 50 nodular, 29 infiltrating, 15 superficial, 7 sclerosing, 2 fibroepithelial, and 1 pigmented cell carcinoma, were assessed by immunohistochemistry for ERp29 expression. Thirty-nine (37.5%) of the samples tested expressed ERp29 with the infiltrating carcinomas displaying more intense (++,+++) immunoreactivity (6/29, P < 0.05) and the superficial carcinomas exhibiting the less intense anti-ERp29 staining (1/15, P < 0.05). Collectively our results suggest that ERp29 is expressed in a subset of basal-cell carcinoma of the skin with the infiltrating carcinomas exhibiting the highest incidence of immunopositivity. The role of ERp29 in the pathogenesis of the disease and its potential diagnostic value should be explored in future investigations.
Bringing the Excitement of Biological Research into the Chemistry Classroom at MIT (2007)

ADVERTISEMENT RETURN TO ISSUEPREVIn FocusNEXTBringing the Excitement of Biological Research into the Chemistry Classroom at MITElizabeth Vogel Taylor, * and Catherine L. Drennan, View Author Information Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139* Corresponding author, [email protected]Cite this: ACS Chem. Biol. 2007, 2, 8, 515–517Publication Date (Web):August 17, 2007Publication History Received26 July 2007Accepted26 July 2007Published online17 August 2007Published inissue 1 August 2007https://pubs.acs.org/doi/10.1021/cb700156nhttps://doi.org/10.1021/cb700156nnewsACS PublicationsCopyright © 2007 American Chemical SocietyRequest reuse permissionsArticle Views268Altmetric-Citations3LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Biology,Peptides and proteins,Students,Teaching and learning methods,Undergraduates Get e-Alerts
Cytotoxicity of 2,2‘:6‘,2‘ ‘-Terpyridineplatinum(II) Complexes against Human Ovarian Carcinoma (1999)

2,2':6',2''-Terpyridineplatinum(II) complexes are shown to possess cytotoxicity against a number of human ovarian tumor cell lines. Many of the complexes show similar activity against cisplatin- and doxorubicin-resistant cell lines as the parental cells suggesting that there is little or no cross-resistance with cisplatin or doxorubicin. The cytotoxicity of bis[2,2':6',2''-terpyridineplatinum(II)] complexes is strongly dependent on the nature of the linker. Bis[2,2':6',2''-terpyridineplatinum(II)] complexes with a flexible linker at the 4'-position show poor cytotoxicity; by contrast bis[2,2':6',2''- terpyridineplatinum(II)] complexes with rigid and short linkers at platinum(II) are strikingly effective. Several of the compounds show greater cytotoxicity against human ovarian cell lines than carboplatin, the therapeutic agent currently advocated for the treatment of human ovarian cancers.
Manipulating Degradation Time in a N-isopropylacrylamide-Based Co-polymer with Hydrolysis-Dependent LCST (2010)

A thermosensitive, bioresorbable and in situ gelling co-polymer, poly(N-isopropylacrylamide-co-dimethyl-gamma-butyrolactone acrylate-co-acrylic acid), was synthesized by radical co-polymerization with varying dimethyl-gamma-butyrolactone acrylate (DBA) content. The materials properties were characterized using differential scanning calorimetry, gel-permeation chromatography in conjunction with static light scattering, Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR) and acid titration. The initial lower critical solution temperature (LCST) of the synthesized co-polymer is between room temperature and body temperature. With the increase of DBA content, the LCST decreases, but then increases after the ring-opening hydrolysis of the DBA side-group. The FT-IR and NMR spectra show the co-polymerization of three monomers, as well as the hydrolysis-dependent ring-opening of the DBA side-group. The addition of acrylic acid increases the initial LCST and accelerates the degradation rate of the co-polymer. An indirect cytotoxicity test indicated that this co-polymer has relatively low cytotoxicity as seen with 3T3 fibroblast cells.
Towards a theory of software protection and simulation by oblivious RAMs (1987)

Software protection is one of the most important issues concerning computer practice. There exist many heuristics and ad-hoc methods for protection, but the problem as a whole has not received the theoretical treatment it deserves. In this paper, we make the first steps towards a theoretic treatment of software protection: First, we distill and formulate the key problem of learning about a program from its execution. Second, assuming the existence of one-way permutations, we present an efficient way of executing programs such that it is infeasible to learn anything about the program by monitoring its executions. How can one efficiently execute programs without allowing an adversary, monitoring the execution, to learn anything about the program? Traditional cryptographic techniques can be applied to keep the contents of the memory unknown throughout the execution, but are not applicable to the problem of hiding the access pattern. The problem of hiding the access pattern efficiently corresponds to efficient simulation of Random Access Machines (RAM) on an oblivious RAM. We define an oblivious RAM to be a (probabilistic) RAM for which (the distribution of) the memory access pattern is independent of the input. We present an (on-line) simulation of t steps of an arbitrary RAM with m memory cells, by less than t·me steps of an oblivious RAM with 2m memory cells, where e>0 is an arbitrary constant.
HUMAN FOLLICLE STIMULATING HORMONE: FIRST PROPOSAL FOR THE AMINO ACID SEQUENCE OF THE HORMONE-SPECIFIC, β SUBUNIT (hFSHβ) (1974)

Amino acid sequence of hFSHβ has been derived from the sequences of the tryptic and thermolytic peptides of the reduced and carboxymethylated subunit. hFSHβ consists of 115 residues. Two carbohydrate moieties are linked at positions 7 and 24. Heterogeneity exists at the NH2-terminus and COOH-terminus. hFSHβ exhibits surprisingly greater sequence homology with hTSHβ (49 identical positions) than with hLHβ (39 identical positions).
Técnicas Utilizadas para el Estudio de Tiempos: un Análisis Comparativo (2005)

El estudio de tiempos juega un papel importante en la productividad de cualquier empresa de productos o servicios. Con este se pueden determinar los estandares de tiempo para la planeacion, calcular costos, programar, contratar, evaluar la productividad, establecer planes de pago, entre otras actividades por lo que, cualquier empresa que busque un alto nivel competitivo debe centrar su atencion en las tecnicas de estudio de tiempos, y tener la capacidad de seleccionar la tecnica adecuada para analizar la actividad seleccionada. El presente trabajo se divide en dos secciones. En la primera se discuten algunas de las tecnicas usadas por los expertos para el estudio de tiempos. En la segunda seccion se lleva acabo un analisis comparativo entre tres tecnicas de estudio de tiempos para tres diferentes actividades.
Mitochondria and FOXO3: breath or die (2013)

Forkhead box O (FOXO) transcription factors are regulators of cell-type specific apoptosis and cell cycle arrest but also control longevity and reactive oxygen species (ROS). ROS-control by FOXO is mediated by transcriptional activation of detoxifying enzymes such as Superoxide dismutase 2 (SOD2), Catalase or Sestrins or by the repression of mitochondrial respiratory chain proteins resulting in reduced mitochondrial activity. FOXO3 also regulates the adaptation to hypoxia by reducing mitochondrial mass and oxygen consumption during HIF-1α activation. In neuronal tumor cells, FOXO3 triggers ROS-accumulation as a consequence of transient mitochondrial outer membrane permeabilization, which is essential for FOXO3-induced apoptosis in these cells. Cellular ROS levels are affected by the FOXO-targets Bim, BclxL, and Survivin. All three proteins localize to mitochondria and affect mitochondrial membrane potential, respiration and cellular ROS levels. Bim-activation by FOXO3 causes mitochondrial depolarization resulting in a transitory decrease of respiration and ROS production. Survivin, on the other hand, actively changes mitochondrial architecture, respiration-efficacy and energy metabolism. This ability distinguishes Survivin from other anti-apoptotic proteins such as BclxL, which inhibits ROS by inactivating Bim but does not alter mitochondrial function. Importantly, FOXO3 simultaneously also activates ROS-detoxification via induction of SESN3. In this paper we discuss the hypothesis that the delicate balance between ROS-accumulation by Bim-triggered mitochondrial damage, mitochondrial architecture and ROS-detoxifying proteins determines cell fate. We provide evidence for a FOXO self-reactivating loop and for novel functions of FOXO3 in controlling mitochondrial respiration of neuronal cells, which further supports the current view that FOXO transcription factors are information-integrating sentinels of cellular stress and critical modulators of cell homeostasis.
Decision Curve Analysis: A Novel Method for Evaluating Prediction Models (2006)

Decision curve analysis is a suitable method for evaluating alternative diagnostic and prognostic strategies that has advantages over other commonly used measures and techniques.