gebhart/patrepeval huggingface dataset:
A nitric oxide processing defect of red blood cells created by hypoxia: Deficiency of S-nitrosohemoglobin in pulmonary hypertension (2005)

The mechanism by which hypoxia [low partial pressure of O(2) (pO(2))] elicits signaling to regulate pulmonary arterial pressure is incompletely understood. We considered the possibility that, in addition to its effects on smooth muscle, hypoxia may influence pulmonary vascular tone through an effect on RBCs. We report that exposure of native RBCs to sustained hypoxia is accompanied by a buildup of heme iron-nitrosyl (FeNO) species that are deficient in pO(2-)governed intramolecular transfer of NO to cysteine thiol, yielding a deficiency in the vasodilator S-nitrosohemoglobin (SNO-Hb). S-nitrosothiol (SNO)-deficient RBCs produce impaired vasodilator responses in vitro and exaggerated pulmonary vasoconstrictor responses in vivo and are defective in oxygenating the blood. RBCs from hypoxemic patients with elevated pulmonary arterial pressure (PAP) exhibit a similar FeNO/SNO imbalance and are thus deficient in pO(2)-coupled vasoregulation. Chemical restoration of SNO-Hb levels in both animals and patients restores the vasodilator activity of RBCs, and this activity is associated with improved oxygenation and lower PAPs.
Photosensitized oxygenation of vinylic sulphides (1972)

Rose bengal sensitized photo-oxygenation of vinylic sulphides gave SS-dialkyl dithio-oxalate, SS-dialkyl thiocarbonate, and (alkylthio)aldehyde with elimination of alkyl disulphides from a 1,2-dioxetan intermediate.
β-Catenin Shows an Overlapping Sequence Requirement but Distinct Molecular Interactions for Its Bidirectional Passage through Nuclear Pores (2004)

beta-Catenin is an example of a typical molecule that can be translocated bidirectionally through nuclear pore complexes (NPCs) on its own in a facilitated manner. In this work the nuclear import and export of beta-catenin were examined to compare the sequence requirement of this molecule and to determine whether molecular interactions required for its bidirectional NPC passage are distinct or not. Deletion analysis of beta-catenin revealed that armadillo repeats 10-12 and the C terminus comprise the minimum region necessary for nuclear migration activity. Further dissection of this fragment showed that the C terminus tail plays an essential role in nuclear migration. The region of beta-catenin required for export substantially overlapped the region required for import. Therefore, the NPC translocation of beta-catenin is apparently reversible, which is consistent with findings reported previously. However, different translocating molecules blocked nuclear import and export of beta-catenin differentially. The data herein indicate that beta-catenin shows an overlapping sequence requirement for its import and export but that bidirectional movement through the NPC proceeds through distinct molecular interactions.
General syntheses of 1-alkyltoxoflavin and 8-alkylfervenulin derivatives of biological significance by the regioselective alkylation of reumycin derivatives and the rates of transalkylation from 1-alkyltoxoflavins into nucleophiles (2001)

Regioselective alkylations of reumycin derivatives under alkaline conditions with a dialkyl sulfate or alkyl halide in 1,4-dioxane or DMF to provide 1-alkyltoxoflavin or 8-alkylfervenulin derivatives of biological significance, are described. Namely, the primary and secondary alkylations of reumycin derivatives with appropriate dialkyl sulfates or alkyl bromides under alkaline conditions in 1,4-dioxane gave predominantly 1-alkyltoxoflavin derivatives, while the same alkylations in DMF instead of 1,4-dioxane gave predominantly 8-alkylfervenulin derivatives. In the case of tertiary alkylation, the reumycin derivative with 2-bromo-2-methylpropane in both solvents under the same conditions yielded only the 1-alkyltoxoflavin derivative. Moreover, the rates of transalkylation from 1-alkyltoxoflavin derivatives into nucleophiles, e.g. DMF and n-butylamine, are also described. That is, the toxoflavin derivatives possessing a primary alkyl group at the 1-position were easily dealkylated from the 1-position by heating with DMF, whereupon reumycin (i.e., 1-dealkyltoxoflavin, 8-dealkylfervenulin) derivatives were formed. In other words, transalkylation from the toxoflavin derivatives into DMF took place. However, the transalkylation of 1-alkyltoxoflavin derivatives possessing a secondary or tertiary alkyl group at the 1-position was not observed under such conditions. On the other hand, when heating 1-alkyltoxoflavin derivatives with n-butylamine in 1,4-dioxane, the transalkylations were more easily observed even in the case of 1-alkyltoxoflavin derivatives substituted by a tertiary alkyl group.
Induction of ErbB-3 Expression by α6β4 Integrin Contributes to Tamoxifen Resistance in ERβ1-Negative Breast Carcinomas (2008)

We provided evidence that a strong relationship occurs between alpha6beta4 and ErbB-3 positivity in ERbeta1-negative breast cancers. We also found that the association between ErbB-3 and P-Akt positivity mainly occurs in ERbeta1-negative breast cancer derived from patients with lower DFS indicating that both receptors are clinically relevant in predicting the response to Tamoxifen.
Treatment of hepatitis C infection (1999)

Editor—We were disappointed that McCarthy and Wilkinson’s review of recent advances in hepatology underplayed important public health issues and treatment options surrounding hepatitis C virus.1 In Western Europe about 5 million people are chronic carriers of hepatitis C virus, and in industrialised countries the virus accounts for 40% of cases of end stage cirrhosis and 30% of liver transplants.2 Hepatitis C is thus an important health problem.

Recent data confirm that combination antiviral treatment with ribavirin and interferon is better than interferon alone, with a 38-43% sustained response rate (polymerase chain reaction negative) with 12 months of combination treatment compared with 13-19% with interferon alone.3,4 Although ribavirin has been supplied for use only in trials in the United Kingdom, it is imminently to be licensed for patients who relapse after interferon alone and is already licensed for this indication in the United States and other European countries.

Moreover, a recent international consensus conference on hepatitis C recommended that interferon and ribavirin be first line treatment for previously untreated (naive) patients without contraindication to ribavirin. Duration of treatment should be tailored to viral load and viral genotype. It was suggested that patients with viral genotype 1 should have a six month course of combination treatment before viral response to treatment is assessed compared with three months for those infected with other viral genotypes. These recommendations (drawn from a panel of experts) have important public health and economic implications.

Lastly, we are not aware of any large trials using ribavirin alone in patients with recurrent hepatitis C infection after transplantation as it has little in vitro activity against the virus. Preliminary data on 122 patients with chronic recurrent infection after transplantation from Italy suggest that sustained response rates of up to 50% (similar to that in chronic non-immunocompromised hepatitis C infection) can be obtained safely in selected groups without precipitating graft rejection.5 Patients with coexistent HIV infection should be considered for antiviral treatment of hepatitis C if HIV disease activity is stable. We must be aware of improvements in treatment options for hepatitis C and the public health issues surrounding these advances, particularly in an environment where health resources are finite.
Biological activities and signaling pathways of the granulin/epithelin precursor. (1999)

Growth-regulated cells, such as 3T3 mouse embryo fibroblasts (MEFs), require more than one growth factor for growth, usually the insulin-like growth factor I (IGF-I) in combination with either platelet-derived growth factor or epidermal growth factor. Singly, these growth factors cannot sustain the growth of 3T3 cells. However, if the IGF-I receptor (IGF-IR) is even modestly overexpressed, then IGF-I, by itself, stimulates the growth of MEFs in monolayer and makes them capable of forming colonies in soft agar. The granulin/epithelin precursor (GEP) has been identified as the only growth factor, thus far, that can stimulate by itself the growth of R- cells, a 3T3-like cell line in which the genes for the IGF-IR have been deleted. We have expressed GEP in R- cells and show that these cells can now grow in serum-free medium. GEP, however, cannot replace other functions of the IGF-IR, such as protection from apoptosis (anoikis) or transforming activity (colony formation in soft agar). GEP activates, in R- cells, the two signaling pathways that are known to be sufficient for IGF-I-mediated mitogenesis in cells overexpressing the IGF-IR, the mitogen-activated protein kinase and the phosphatidylinositol 3-kinase pathways. This may explain why GEP, by itself, can replace the IGF-IR for growth in monolayer cultures. It also confirms that, for transformation, other pathways must be activated besides the two pathways that are sufficient for mitogenesis.
Physicochemical optimisation of plasmid delivery by cationic lipids (2004)

Non-viral gene therapy is based on the use of plasmid expression vectors and chemical or physical plasmid DNA delivery systems. This review discusses the roles of cationic lipids as vectors for gene transfection, reviews different strategies employed to improve cationic lipids for in vivo use, and provides original results on the physicochemistry of lipoplexes. Cationic lipid/DNA delivery vehicles have evolved considerably since their initial gene transfection experiments. Much work has been carried out to investigate their structure/activity relationships, methods of formulation and physicochemical properties. Further work has also focused on enhancing and prolonging their stability in a physiological environment as well as increasing their site-specific and tissue-specific interactions. Original data presented in this report confirm that cationic lipids associated to DNA form supramolecular lamellar structures, which protect DNA from serum DNAse degradation. The effect of formulation (and hence the size of the particles) on lipoplex in vivo circulation half-life and biodistribution is also discussed. A list of abbreviations can be found at the end of the review.
Using the kinetic Wulff plot to design and control nonpolar and semipolar GaN heteroepitaxy (2012)

For nonpolar and semipolar orientations of GaN heteroepitaxially grown on sapphire substrates, the development of growth procedures to improve surface morphology and microstructure has been driven in a largely empirical way. This work attempts to comprehensively link the intrinsic properties of GaN faceted growth, across orientations, in order to understand, design and control growth methods for nonpolar (1 1 2 0) GaN and semipolar (1 1 2 2) GaN on foreign substrates. This is done by constructing a comprehensive series of kinetic Wulff plots (or v-plots) by monitoring the advances of convex and concave facets in selective area growth. A methodology is developed to apply the experimentally determined v-plots to the interpretation and design of evolution dynamics in nucleation and island coalescence. This methodology offers a cohesive and rational model for GaN heteroepitaxy along polar, nonpolar and semipolar orientations, and is broadly extensible to the heteroepitaxy of other materials. We demonstrate furthermore that the control of morphological evolution, based on invoking a detailed knowledge of the v-plots, holds a key to the reduction of microstructural defects through effective bending of dislocations and blocking of stacking faults. The status and outlook of semipolar and nonpolar GaN growth on sapphire substrates will be presented.
Effect of choline esters and oleic acid on the penetration of acyclovir, estradiol, hydrocortisone, nitroglycerin, retinoic acid and trifluorothymidine across hairless mouse skin in vitro. (1989)

Five choline esters, lauroylcholine, myristoylcholine, palmitoylcholine, stearoylcholine and oleoylcholine, were evaluated as skin penetration enhancers by testing their effects on the penetration of six drugs, acyclovir, 17 beta-estradiol, hydrocortisone, nitroglycerin, all-trans-retinoic acid and trifluorothymidine, across hairless mouse skin in vitro and comparing the results to those obtained with oleic acid. The results show that the transdermal delivery of the drugs tested from propylene glycol vehicle systems, can be significantly increased by adding small amounts of choline esters and/or oleic acid to the vehicle. Lauroylcholine was a better enhancer than oleic acid for the transdermal delivery of 17 beta-estradiol and, in mixtures, lauroylcholine and oleic acid acted as synergists giving larger enhancement of the transdermal delivery of nitroglycerin and acyclovir than when used separately.
High-resolution analysis of the human T-cell receptor repertoire (2015)

Unbiased dissection of T-cell receptor (TCR) repertoire diversity at the nucleotide level could provide important insights into human immunity. Here we show that TCR ligation-anchored-magnetically captured PCR (TCR-LA-MC PCR) identifies TCR α- and β-chain diversity without sequence-associated or quantitative restrictions in healthy and diseased conditions. TCR-LA-MC PCR identifies convergent recombination events, classifies different stages of cutaneous T-cell lymphoma in vivo and demonstrates TCR reactivation after in vitro cytomegalovirus stimulation. TCR-LA-MC PCR allows ultra-deep data access to both physiological TCR diversity and mechanisms influencing clonality in all clinical settings with restricted or distorted TCR repertoires.
Ein neuer Katalysator für selektive Hydrierungen (1952)

Abstract Es wird die Darstellung eines Palladium‐Blei‐Katalysators und seine Anwendung für einige Partialhydrierungen unter Erhaltung aliphatischer Doppelbindungen beschrieben.
Antichemokine immunotherapy for allergic diseases (2001)

Chemokines have emerged as critical regulators of leukocyte function and as such represent attractive new targets for the therapy of allergic diseases. Recent studies have revealed important roles for the chemokine family in both the afferent and efferent limbs of the immune system, orchestrating and integrating innate and acquired immune responses. A subset of chemokines including eotaxin-1 (also called CCL11), eotaxin-2 (CCL24), eotaxin-3 (CCL26), MCP (monocyte chemoattractant protein)-3 (CCL7), MCP (monocyte chemoattractant protein)-4 (CCL13), TARC (thymus- and activation-regulated chemokine) (CCL17), and MDC (macrophage-derived chemokine) (CCL22) are highly expressed in allergic inflammation and are regulated by T helper type 2 cytokines. Receptors for these chemokines, including CCR3 (CC chemokine receptor 3), CCR4 (CC chemokine receptor 4) and CCR8 (CC chemokine receptor 8) are expressed on key leukocytes associated with allergic inflammation, such as T helper type 2 cells, eosinophils, mast cells and basophils, establishing a subset of chemokine/chemokine receptors potentially important in allergic inflammation. Recent data using inhibitory antibodies and chemokine antagonists support the concept that interfering with this subset of chemokines and their receptors represents a new approach to allergy immunotherapy.
Preparation, characterization, and immunological properties in mice of Escherichia coli O157 O-specific polysaccharide-protein conjugate vaccines (1994)

Escherichia coli O157 causes severe enteritis and the extraintestinal complication of hemolytic-uremic syndrome, with their highest incidence occurring in children. We postulated that serum immunoglobulin G (IgG) antibodies to the O-specific polysaccharide of lipopolysaccharide (LPS) may confer protective immunity to enteric pathogens by inducing bactericidal reactions against the ingested organisms in the jejunum (J. B. Robbins, C. Chu, and R. Schneerson, Clin. Infect. Dis. 15:346-361, 1992; S. C. Szu, R. Gupta, and J. B. Robbins, p. 381-394, in I. K. Wachsmuth, P. A. Blake, and O. Olsvik, ed., Vibrio cholerae, 1994). Because polysaccharide-protein conjugates induce serum IgG antibodies in infants, we bound the O-specific polysaccharide of E. coli O157 to proteins. E. coli O157 LPS, treated with acetic acid or hydrazine, was derivatized with adipic acid dihydrazide and bound to proteins by carbodiimide-mediated condensation. Conjugates of these adipic hydrazide derivative were prepared with bovine serum albumin, formalin-treated exotoxin C of Clostridium welchii (Pig Bel toxoid), or Pseudomonas aeruginosa recombinant exoprotein A. The conjugates had low levels of endotoxin and elicited serum antibodies with bactericidal activity to the O157 LPS. The largest increase in LPS antibodies was of the IgG class. Clinical evaluation of E. coli O157-toxoid conjugates is planned.
NYK/FLK-1: a putative receptor protein tyrosine kinase isolated from E10 embryonic neuroepithelium is expressed in endothelial cells of the developing embryo. (1993)

A protein tyrosine kinase (NYK/FLK-1), bearing all the hallmarks of a growth factor receptor, has been isolated from a cDNA library generated from enriched populations of mouse day 10 embryonic neuroepithelium and from day 18 embryonic colon. Sequence analysis of cDNAs covering the entire coding region of this 5.7 kb mRNA predicted the presence of seven immunoglobulin-like domains in the extracellular region of this molecule. This feature, coupled with the detection of an insert domain bisecting the kinase domain of the predicted protein sequence, places NYK/FLK-1 firmly in the Platelet-derived Growth Factor Receptor-related class of molecules. NYK/FLK-1 is expressed at high levels in adult heart, lung, kidney, brain and skeletal muscle, but is also expressed at lower levels in most other adult tissues. In situ hybridization of day 12.5 embryo sections demonstrated NYK/FLK-1 mRNA expression in endothelial cells lining the dorsal aorta and intervertebral veins. In addition, expression was found in cells lining the capillary plexus which surrounds the developing neuroepithelium, and in the endothelial cells which are found within the embryonic lung, spleen, liver and metanephros.
Efficacy of different hormonal protocols for oestrous induction in postpartum anoestrous and suboestrous cows (2011)

A study was conducted on 95 Red Sindhi x Jersey crossbred postpartum anoestrous/Subestrous animals. Sixty animals were divided into three categories depending on presence/absence and category of follicle/CL on the ovary. The animals with smooth ovaries (n=12) were treated with double dose of GnRH at 2 weeks interval. The animals (n=13) having ovaries with small follicle (5 mm) were treated with single dose of GnRH. The animals with medium/large sized follicle (10 mm or more) were either treated with co-synch (GPG, n=12) or modified ov-synch (GPH, n=13) protocol, while the animals having ovaries with CL/RCL (n=10) were treated with double dose of PG at 11 days interval. Thirty five PPA animals irrespective of different ovarian status were either treated with homoeopathic drugs (n=7) or served as untreated control (n=28). Out of the six treatment groups, the groups treated with GPG or GPH protocol resulted in highest response (100%, 100%) in oestrus induction as well as conception rate (58.33% and 76.92) as compared to other groups including control.
High-performance 2-D FPGA DCTs using polynomial transforms (1999)

No abstract available.
Immunoglobulin Fc Heterodimer Platform Technology: From Design to Applications in Therapeutic Antibodies and Proteins (2016)

The monospecific and bivalent characteristics of naturally occurring immunoglobulin G (IgG) antibodies depend on homodimerization of the fragment crystallizable (Fc) regions of two identical heavy chains (HCs) and the subsequent assembly of two identical light chains (LCs) via disulfide linkages between each HC and LC. Immunoglobulin Fc heterodimers have been engineered through modifications to the CH3 domain interface, with different mutations on each domain such that the engineered Fc fragments, carrying the CH3 variant pair, preferentially form heterodimers rather than homodimers. Many research groups have adopted different strategies to generate Fc heterodimers, with the goal of high heterodimerization yield, while retaining biophysical and biological properties of the wild-type Fc. Based on their ability to enforce heterodimerization between the two different HCs, the established Fc heterodimers have been extensively exploited as a scaffold to generate bispecific antibodies (bsAbs) in full-length IgG and IgG-like formats. These have many of the favorable properties of natural IgG antibodies, such as high stability, long serum half-life, low immunogenicity, and immune effector functions. As of July 2016, more than seven heterodimeric Fc-based IgG-format bsAbs are being evaluated in clinical trials. In addition to bsAbs, heterodimeric Fc technology is very promising for the generation of Fc-fused proteins and peptides, as well as cytokines (immunocytokines), which can present the fusion partners in the natural monomeric or heterodimeric form rather than the artificial homodimeric form with wild-type Fc. Here, we present relevant concepts and strategies for the generation of heterodimeric Fc proteins, and their application in the development of bsAbs in diverse formats for optimal biological activity. In addition, we describe wild-type Fc-fused monomeric and heterodimeric proteins, along with the difficulties associated with their preparations, and discuss the use of heterodimeric Fc as an alternative scaffold of wild-type Fc for naturally monomeric or heterodimeric proteins, to create Fc-fusion proteins with novel therapeutic modality.
Photodynamic Photorejuvenation (2002)

BACKGROUND The visible signs of photodamage are characterized by wrinkling, coarse skin texture, pigmentation alterations, telangiectases, and in some case actinic keratosis (AKs). Intense pulsed light (IPL) photorejuvenation has been shown to improve each of the different components of photodamaged skin except AKs. OBJECTIVE To present photodynamic therapy with topical 5-aminolevulinic acid (ALA-PDT) using IPL as a light source for treatment of AK in patients having IPL photorejuvenation. METHODS Seventeen patients with varying degrees of photodamage and AKs (total of 38 AKs) were treated with two treatments with a 1-month interval of ALA-PDT using IPL as a light source. RESULTS Thirty-three of 38 AKs disappeared with two ALA-PDT treatments using IPL. The follow-up period was 3 months. The technique was very well tolerated. Erythema and crusting took 1 week to resolve in the AK area. The cosmetic results were excellent in all patients without pigmentary alterations or scarring. CONCLUSION This study describes a new application of IPL technology. Patients who are candidates for photorejuvenation procedures presenting with AKs can now have AKs treated as part of the photorejuvenation process rather than necessitating separate topical therapy with 5-fluorouracil (5-FU) or cryotherapy. In addition, many patients with AKs may benefit from the combination treatment with 5-ALA and IPL.
Survival and recovery of apheresis platelets stored in a polyolefin container with high oxygen permeability (2008)

The in vitro characteristics of PCs stored in a highly oxygen-permeable container were stable at least 7 days. The in vivo study supports the suitability of PO-80 for 7-day platelet storage.