gebhart/patrepeval huggingface dataset:
Direct Cell Adhesion to the Angiopoietins Mediated by Integrins (2001)

Genetic ablation of angiopoietin-1 (Ang-1) or of its cognate receptor, Tie2, disrupts angiogenesis in mouse embryos. The endothelial cells in growing blood vessels of Ang-1 knockout mice have a rounded appearance and are poorly associated with one another and their underlying basement membranes (Dumont, D. J., Gradwohl, G., Fong, G. H., Puri, M. C., Gertsenstein, M., Auerbach, A., and Breitman, M. L. (1994) Genes Dev. 8, 1897--1909; Sato, T. N., Tozawa, Y., Deutsch, U., Wolburg-Buchholz, K., Fujiwara, Y., Gendron-Maguire, M., Gridley, T., Wolburg, H., Risau, W., and Qin, Y. (1995) Nature 376, 70--74; Suri, C., Jones, P. F., Patan, S., Bartunkova, S., Maisonpierre, P. C., Davis, S., Sato, T. N., and Yancopoulos, G. D. (1996) Cell 87, 1171--1180). It is therefore possible that Ang-1 regulates endothelial cell adhesion. In this study we asked whether Ang-1 might act as a direct substrate for cell adhesion. Human umbilical vein endothelial cells (HUVECs) plated for a brief period on different substrates were found to adhere and spread well on Ang-1. Similar results were seen on angiopoietin-2 (Ang-2)-coated surfaces, although cells did not spread well on Ang-2. Ang-1, but not Ang-2, supported HUVEC migration, and this was independent of growth factor activity. When the same experiments were done with fibroblasts that either lacked, or stably expressed, Tie2, results similar to those with HUVECs were seen, suggesting that adhesion to the angiopoietins was independent of Tie2 and not limited to endothelial cells. Interestingly, when integrin-blocking agents were included in these assays, adhesion to either angiopoietin was significantly reduced. Moreover, Chinese hamster ovary-B2 cells lacking the alpha(5) integrin subunit did not adhere to Ang-1, but they did adhere to Ang-2. Stable expression of the human alpha(5) integrin subunit in these cells rescued adhesion to Ang-1 and promoted an increase in adhesion to Ang-2. We also found that Ang-1 and Ang-2 bind rather selectively to vitronectin. These results suggest that, beyond their role in modulating Tie2 signaling, Ang-1 and Ang-2 can directly support cell adhesion mediated by integrins.
Regulatory regions of rat insulin I gene necessary for expression in transgenic mice (1991)

Ten transgenic mouse lines harboring the -346/-103 fragment of the rat insulin I enhancer linked to a heterologous promoter and a reporter gene (Eins-Ptk-CAT construct) were produced. Expression of the hybrid transgene was essentially observed in pancreas and to a lesser extent in brain. These results indicate that the rat insulin I promoter is dispensable for pancreatic expression. This insulin gene sequence is the shortest fragment described as conferring tissue-specific expression in transgenic mice. Two short homologous sequences in the rat insulin I enhancer fragment used, IEB2 and IEB1, have been described as playing a dominant role in the regulation of HIT hamster insulinoma cell-specific transcription of the insulin gene (1). We investigated whether the combination of IEB2 and IEB1 sequences is sufficient to confer specific expression in transgenic mice to a IEB2-IEB1-Ptk-CAT gene construct. No CAT activity was observed neither in pancreas nor in any other organ examined in 19 different transgenic mice. Moreover in transient expression experiments in RIN2A rat insulinoma cells, the IEB sequences had a very weak or no enhancer activity. These observations contribute to the conclusion that DNA regulatory elements other than the IEB sequences are necessary for gene expression in vivo.
The role of microorganisms in atopic dermatitis (2006)

Atopic dermatitis (AD) is a common, fluctuating skin disease that is often associated with atopic conditions such as asthma and IgE-mediated food allergy and whose skin lesions are characterized by a Th-2 cell-mediated response to environmental antigens. The increasing prevalence and severity of atopic diseases including AD over the last three decades has been attributed to decreased exposure to microorganisms during early life, which may result in an altered Th-1/Th-2-balance and/or reduced T cell regulation of the immune response. Patients with AD exhibit defects in innate and acquired immune responses resulting in a heightened susceptibility to bacterial, fungal and viral infections, most notably colonization by S. aureus. Toxins produced by S. aureus exacerbate disease activity by both the induction of toxin-specific IgE and the activation of various cell types including Th-2 cells, eosinophils and keratinocytes. Allergens expressed by the yeast Malazessia furfur, a component of normal skin flora, have also been implicated in disease pathogenesis in a subset of AD patients. Microorganisms play an influential role in AD pathogenesis, interacting with disease susceptibility genes to cause initiation and/or exacerbation of disease activity.
Identification of a Critical Motif for the Human Immunodeficiency Virus Type 1 (HIV-1) gp41 Core Structure: Implications for Designing Novel Anti-HIV Fusion Inhibitors (2008)

Human immunodeficiency virus type 1 (HIV-1) entry into the host cell involves a cascade of events and currently represents one of most attractive targets in the search for new antiviral drugs. The fusion-active gp41 core structure is a stable six-helix bundle (6-HB) folded by its trimeric N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR). Peptides derived from the CHR region of HIV-1 gp41 are potent fusion inhibitors that target the NHR to block viral and cellular membrane fusion in a dominant negative fashion. However, all CHR peptides reported to date are derived primarily from residues 628 to 673 of gp41; little attention has been paid to the upstream sequence of the pocket binding domain (PBD) in the CHR. Here, we have identified a motif ((621)QIWNNMT(627)) located at the upstream region of the gp41 CHR, immediately adjacent to the PBD ((628)WMEWEREI(635)). Biophysical characterization demonstrated that this motif is critical for the stabilization of the gp41 6-HB core. The peptide CP621-652, containing the (621)QIWNNMT(627) motif, was able to interact with T21, a counterpart peptide derived from the NHR, to form a typical 6-HB structure with a high thermostability (thermal unfolding transition [T(m)] value of 82 degrees C). In contrast, the 6-HB formed by the peptides N36 and C34, which has been considered to be a core structure of the fusion-active gp41, had a T(m) of 64 degrees C. Different from T-20 (brand name Fuseon), which is the first and only HIV-1 fusion inhibitor approved for clinical use, CP621-652 could efficiently block 6-HB formation in a dose-dependent manner. Significantly, CP621-652 had potent inhibitory activity against HIV-1-mediated cell-cell fusion and infection, especially against T-20- and C34-resistant virus. Therefore, our works provide important information for understanding the core structure of the fusion-active gp41 and for designing novel anti-HIV peptides.
Evaluation of Grid Pattern Photocoagulation for Macular Edema in Central Vein Occlusion (1995)

The results of this study do not support a recommendation for macular grid photocoagulation for the population meeting the Central Vein Occlusion Study macular edema group eligibility criteria.
Coronavirus Disease 2019 &ndash; COVID-19 (2020)

In the past decades, several new diseases have emerged in new geographical areas, with pathogens including Ebola, Zika, Nipah, and coronaviruses (CoVs). Recently, a new type of viral infection has emerged in Wuhan City, China, and initial genomic sequencing data of this virus does not match with previously sequenced CoVs, suggesting a novel CoV strain (2019-nCoV), which has now been termed as severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Although Coronavirus disease 2019 (COVID-19) is suspected to originate from an animal host (zoonotic origin) followed by human-to-human transmission, the possibility of other routes such as food-borne transmission should not be ruled out. Compared to diseases caused by previously known human CoVs, COVID-19 shows less severe pathogenesis but higher transmission competence, as is evident from the continuously increasing number of confirmed cases globally. Compared to other emerging viruses such as Ebola virus, avian H7N9, SARS-CoV, or MERS-CoV, SARS-CoV-2 has shown relatively low pathogenicity and moderate transmissibility. Codon usage studies suggest that this novel virus may have been transferred from an animal source such as bats. Early diagnosis by real-time PCR and next-generation sequencing has facilitated the identification of the pathogen at an early stage. Since, no antiviral drug or vaccine exists to treat or prevent SARS-CoV-2, potential therapeutic strategies that are currently being evaluated predominantly stem from previous experience with treating SARS-CoV, MERS-CoV, and other emerging viral diseases. In this review, we address epidemiological, diagnostic, clinical, and therapeutic aspects, including perspectives of vaccines and preventive measures that have already been globally recommended.
Releasing the Brakes on Cancer Immunotherapy (2015)

James Allison, winner of this year's Lasker–DeBakey Clinical Medical Research Award, did seminal work that has led to checkpoint-blockade immunotherapy, arguably the most exciting advance made in cancer treatment in recent years.
Binding of phenol to R6 insulin hexamers* (1999)

Small amounts of phenolic compounds are being used as preservatives in pharmaceutical insulin preparations. It has been shown previously that these compounds bind to specific sites on the insulin hexamer and act as allosteric effectors, inducing a transformation of the T6 hexamer to the R6 hexamer, via a T3R3 intermediate. In this article, the crystal structures of eight different insulin derivatives, all in the phenol-containing R6 form, are analyzed with respect to their phenol-binding sites. While six phenol molecules are normally bound per insulin hexamer, one of the engineered insulins appears to contain only three phenols but yet exists in an R6 conformation. This observation provides additional evidence for an inherent nonequivalence of the two trimers in the insulin hexamer. The unusual observation of a seventh phenol molecule bound to the hexamer of crystalline A21Gly-B31,B32Arg2 insulin (HOE 901), a long-acting derivative currently undergoing phase III clinical trials, provides a partial explanation for its protracted activity.
Local Venoarterial Pathway for Uterine-Induced Luteolysis in Cows (1976)

The involvement of the main uterine vein and ovarian artery in the local pathway for uterine-induced luteolysis was studied in mature Holstein cows. At surgery on days 8-11 of diestrus, all cows were unilaterally hysterectomized and allocated to one of 4 groups: 1) controls with hysterectomy contralateral to CL, 2) controls with hysterectomy ipsilateral to CL, 3) hysterectomy ipsilateral to CL and surgical anastomosis of the main uterine vein from intact to hysterectomized side, and 4) hysterectomy ipsilateral to CL and surgical anastomosis of ovarian artery from intact to hysterectomized side. At necropsy on day 30, the surgical anastomosis was examined for patency and CL were weighed. Cows with an occluded venous anastomosis were reassigned to group 5. CL weights from 15 cows (3 per group) were analyzed. Mean weight of CL was less (P < 0.05) for group 1 controls (489 mg), group 3 with venous anastomosis (1920 mg), and group 4 with arterial anastomosis (708 mg), than for group 2 controls (4710 mg) or group 5 with occluded venous anastomosis (5142 mg). Mean weight of CL was not significantly different among groups 1,3, and 4 or between groups 2 and 5. Results indicate the involvement of a venoarterial pathway in the local uteroovarian luteolytic effect in cows. The main uterine vein serves as the proximal or uterine component and the ovarian artery serves as the distal or ovarian component of the pathway.
Expression of Notch-1 and Its Ligands, Delta-Like-1 and Jagged-1, Is Critical for Glioma Cell Survival and Proliferation (2005)

The Notch family of proteins plays an integral role in determining cell fates, such as proliferation, differentiation, and apoptosis. We show that Notch-1 and its ligands, Delta-like-1 and Jagged-1, are overexpressed in many glioma cell lines and primary human gliomas. Immunohistochemistry of a primary human glioma tissue array shows the presence in the nucleus of the Notch-1 intracellular domain, indicating Notch-1 activation in situ. Down-regulation of Notch-1, Delta-like-1, or Jagged-1 by RNA interference induces apoptosis and inhibits proliferation in multiple glioma cell lines. In addition, pretreatment of glioma cells with Notch-1 or Delta-like-1 small interfering RNA significantly prolongs survival in a murine orthotopic brain tumor model. These results show, for the first time, the dependence of cancer cells on a single Notch ligand; they also suggest a potential Notch juxtacrine/autocrine loop in gliomas. Notch-1 and its ligands may present novel therapeutic targets in the treatment of glioma.
Ultrastructural Analysis of Indwelling Vascular Catheters: A Quantitative Relationship between Luminal Colonization and Duration of Placement (1993)

To assess the degree of luminal and extraluminal colonization of long-term central venous catheters (CVC), 359 indwelling silicone CVC from 340 consecutive cancer patients were examined. All CVC were cultured by the roll-plate and sonication quantitative culture techniques. Semiquantitative electron microscopy was done on 39 CVC associated with catheter infections and on 26 culture-negative controls. An additional 10 culture-negative CVC obtained after death were also studied by electron microscopy. Ultrastructural colonization and biofilm formation was universal and quantitatively independent of clinical catheter-related infections. Ultrastructural colonization and biofilm formation was predominantly luminal in long-term CVC (> 30 days). Based on a composite definition, the sensitivity of the roll-plate catheter tip culture was 42%-45% compared with 65%-72% for the sonication of the tip. Colonization of indwelling catheters is universal regardless of culture results. For long-term CVC, colonization becomes predominantly luminal and extraluminal quantitative catheter cultures are of limited diagnostic sensitivity.
Bioinformatic design of A-kinase anchoring protein- in silico : A potent and selective peptide antagonist of type II protein kinase A anchoring (2003)

Compartmentalization of the cAMP-dependent protein kinase (PKA) is coordinated through association with A-kinase anchoring proteins (AKAPs). A defining characteristic of most AKAPs is a 14- to 18-aa sequence that binds to the regulatory subunits (RI or RII) of the kinase. Cellular delivery of peptides to these regions disrupts PKA anchoring and has been used to delineate a physiological role for AKAPs in the facilitation of certain cAMP-responsive events. Here, we describe a bioinformatic approach that yields an RII-selective peptide, called AKAP-in silico (AKAP-IS), that binds RII with a K(d) of 0.4 nM and binds RI with a K(d) of 277 nM. AKAP-IS associates with the type II PKA holoenzyme inside cells and displaces the kinase from natural anchoring sites. Electrophysiological recordings indicate that perfusion of AKAP-IS evokes a more rapid and complete attenuation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor currents than previously described anchoring inhibitor peptides. Thus, computer-based and peptide array screening approaches have generated a reagent that binds PKA with higher affinity than previously described AKAPs.
β–Amino Ester Polymers Facilitate in Vivo DNA Transfection and Adjuvant Plasmid DNA Immunization (2005)

Increased in vivo expression of intramuscularly delivered plasmid DNA will be essential for clinical success in gene therapy and plasmid DNA vaccination. We screened polymers from a library of beta-amino esters for their ability to augment transgene expression as measured by beta-galactosidase activity and cellular immune responses. Among the candidates identified in this screen, poly[(1,6-di(acryloxyethoxy)hexane)-co-(4-aminobutanol)] enhanced plasmid DNA transgene expression by sevenfold (P=0.0001) and its immunogenicity by 70% (P=0.03). We found that polymers with moderately hydrophobic backbones and terminal alcohol groups facilitated transfection most effectively in vivo. We also observed a log-linear correlation (R2=0.93) between peak cellular immune responses and transgene activity in all evaluated polymer-plasmid DNA formulations, clarifying the relationship between immunogenicity and the quantity of expressed antigen.
Apolipoprotein(B) identifies dyslipidemic phenotypes associated with cardiovascular risk in normocholesterolemic type 2 diabetic patients. (1999)

Hyperapo(B) was found in almost half of the normocholesterolemic type 2 diabetic patients and was frequently associated with low HDLc levels and hypertriglyceridemia. Thus, given its independent association with cardiovascular disease and that it identifies high-risk phenotypes in normocholesterolemic diabetic patients apo(B) should be used to evaluate the lipidic pattern of these patients.
Four-Terminal P-N-P-N Transistors (1952)

The equivalent circuit of a p-n-p-n transistor is obtained. It is demonstrated that a p-n-p transistor and an n-p-n transistor can be connected so that the combination has the same equivalent circuit as the p-n-p-n structure. A simplified circuit is obtained which can be used when the p-n-p-n transistor is connected as a hook-collector transistor. A method of adjusting the current gain of p-n-p-n transistors by external means is given as well as experimental results.
ChemInform Abstract: SYNTHESIS AND MASS SPECTRA OF SOME SUBSTITUTED 2‐(2′‐BENZAZOLYLAMINO)PYRIMIDINES (1983)

Abstract Aus den o‐substituierten Anilinen (I) werden mit Dicyandiamid (II) die Benzazole (III) hergestellt, die mit den β‐Dicarbonylverbindungen (IV), (VI) bzw. (VIII) zu den Pyrimidinen (V), (VII) bzw. (IX) kondensiert werden.
10 Gbps silicon waveguide-integrated infrared avalanche photodiode (2013)

We have fabricated monolithic silicon avalanche photodiodes capable of 10 Gbps operation at a wavelength of 1550 nm. The photodiodes are entirely CMOS process compatible and comprise a p-i-n junction integrated with a silicon-on-insulator (SOI) rib waveguide. Photo-generation is initiated via the presence of deep levels in the silicon bandgap, introduced by ion implantation and modified by subsequent annealing. The devices show a small signal 3 dB bandwidth of 2.0 GHz as well as an open eye pattern at 10 Gbps. A responsivity of 4.7 ± 0.5 A/W is measured for a 600 µm device at a reverse bias of 40 V.
Regulatory Mechanisms Involving Nicotinamide Adenine Nucleotides As Allosteric Effectors (1970)

Abstract Glucose 6-phosphate dehydrogenase from Escherichia coli is purified about 170-fold. The purified enzyme has no absolute requirement for divalent metal ions for activity. However, it is activated by Mg++, spermidine, or a number of other polycations. The apparent activation constant for spermidine is approximately 0.2 mm. In the presence of saturating concentrations of spermidine or other polycations, Mg++ ions have no further stimulatory effect. The enzyme is inhibited in an allosteric manner by DPNH and this inhibition is not reversed by DPN+, AMP, or spermidine. Compounds of physiological interest related to DPNH (ATP, GTP, acetyl coenzyme A, and coenzyme A) do not cause any inhibition. The initial velocity plots of the enzyme follow the Michaelis-Menten equation in the absence of DPNH. In its presence, however, the velocity versus substrate plots for TPN+ become sigmoidal (but remain hyperbolic for glucose-6-P as the variable substrate). Inhibition against both of the substrates of the enzyme by DPNH is noncompetitive. In addition, the inhibition curves for DPNH are also sigmoidal, suggesting a multisite binding of the inhibitor on the enzyme surface. A comparison is made between the kinetic characteristics of glucose-6-P dehydrogenase and different enzymes of carbohydrate metabolism in E. coli which have been demonstrated to be inhibited by DPNH, and it is pointed out that they all have one property in common, viz. that the rate-concentration plots for only one of the reactant substrates are sigmoidal in the presence of the inhibitor. The physiological implications of such kinetic behavior are discussed and it is concluded that the oxidative pentose pathway serves primarily to generate reducing power (TPNH) for biosynthetic purposes.
"Spot 14" Protein: A Metabolic Integrator in Normal and Neoplastic Cells (1998)

"Spot 14" (S14) was originally identified as a mRNA from rat liver that responded rapidly to thyroid hormone, and has now been shown to play a key role in the tissue-specific regulation of lipid metabolism. In addition to its responsiveness to thyroid hormone, S14 gene transcription is controlled by dietary substrates, such as glucose and polyunsaturated fatty acids, and by fuel-related hormones including insulin and glucagon. The S14 protein forms homodimers via a carboxyl-terminal "zipper" domain. The protein is located primarily in the cell nucleus, and its expression in liver is limited to the perivenous portion of the hepatic lobule, the site of fatty acid synthesis. S14 protein is critical for the induction of key enzymes involved in the switching of hepatic metabolism from the fasted to the fed state. S14 antisense oligonucleotides inhibit both the intracellular production of lipids and their export as very low-density lipoprotein (VLDL) particles. S14 acts at the level of transcription to regulate expression of genes encoding key metabolic enzymes, including those required for long-chain fatty acid synthesis. The human S14 gene is located at 11q13.5, a region that is amplified in a subset of aggressive breast cancers. S14 mRNA is expressed in most breast cancer-derived cell lines, and the protein is found in the nuclei of two thirds of human breast cancer specimens, but not in normal nonlactating mammary glands. S14 expression in breast tumors is highly concordant with overabundance of a key lipogenic enzyme. This indicates the association of S14 with enhanced tumor lipogenesis, an established marker of poor prognosis. In addition to the utility of S14 as a model system for elucidation of the mechanism of thyroid hormone action, studies of its regulation and function have provided insights into tissue-specific metabolic control by hormones and dietary substrates in both normal and neoplastic tissues.
The genetic basis for the antigenicity of the VP2 protein of the infectious bursal disease virus (1993)

The genomic region coding for the antigenic structure responsible for the induction of neutralizing antibodies was localized in the central variable region of the VP2 gene by comparing the nucleotide sequence of five escape mutants derived from the standard infectious bursal disease virus strain Cu-1. Exchange of a single amino acid at one of the prominent hydrophilic parts of this region proved to be sufficient for altering the neutralizing properties. The reactivity of neutralizing antibodies with peptides expressed in vitro encompassing both hydrophilic areas suggests that the entire variable region is engaged in the formation of this conformation-dependent antigenic site. VP2-specific, non-neutralizing monoclonal antibodies directed against the sequence-dependent epitope of the serotype I strain Cu-1 and the serotype II strain 23/82 cross-reacted with peptides located towards the carboxy terminus of VP2; no reaction occurred with peptides derived from the amino-terminal side adjacent to the variable region.
Predicting the outcome of patients with higher-risk myelodysplastic syndrome treated with hypomethylating agents (2011)

The hypomethylating agents (HMAs) azacitidine (AZA) and decitabine (DAC) improve long-term outcomes of higher-risk (International Prognostic Scoring System [IPSS] intermediate-2 or high) myelodyspl...