gebhart/patrepeval huggingface dataset:
ER stress-induced mediator C/EBP homologous protein thwarts effector T cell activity in tumors through T-bet repression (2019)

Understanding the intrinsic mediators that render CD8<sup>+</sup> T cells dysfunctional in the tumor microenvironment is a requirement to develop more effective cancer immunotherapies. Here, we report that C/EBP homologous protein (Chop), a downstream sensor of severe endoplasmic reticulum (ER) stress, is a major negative regulator of the effector function of tumor-reactive CD8<sup>+</sup> T cells. Chop expression is increased in tumor-infiltrating CD8<sup>+</sup> T cells, which correlates with poor clinical outcome in ovarian cancer patients. Deletion of Chop in T cells improves spontaneous antitumor CD8<sup>+</sup> T cell immunity and boosts the efficacy of T cell-based immunotherapy. Mechanistically, Chop in CD8<sup>+</sup> T cells is elevated primarily through the ER stress-associated kinase Perk and a subsequent induction of Atf4; and directly represses the expression of T-bet, a master regulator of effector T cell function. These findings demonstrate the primary role of Chop in tumor-induced CD8<sup>+</sup> T cell dysfunction and the therapeutic potential of blocking Chop or ER stress to unleash T cell-mediated antitumor immunity.
Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC- and MAP kinase-dependent mechanism (2008)

Probiotics promote intestinal epithelial integrity and reduce infection and diarrhea. We evaluated the effect of Lactobacillus rhamnosus GG-produced soluble proteins (p40 and p75) on the hydrogen peroxide-induced disruption of tight junctions and barrier function in Caco-2 cell monolayers. Pretreatment of cell monolayers with p40 or p75 attenuated the hydrogen peroxide-induced decrease in transepithelial resistance and increase in inulin permeability in a time- and dose-dependent manner. p40 and p75 also prevented hydrogen peroxide-induced redistribution of occludin, ZO-1, E-cadherin, and beta-catenin from the intercellular junctions and their dissociation from the detergent-insoluble fractions. Both p40 and p75 induced a rapid increase in the membrane translocation of PKCbetaI and PKCepsilon. The attenuation of hydrogen peroxide-induced inulin permeability and redistribution of tight junction proteins by p40 and p75 was abrogated by Ro-32-0432, a PKC inhibitor. p40 and p75 also rapidly increased the levels of phospho-ERK1/2 in the detergent-insoluble fractions. U0126 (a MAP kinase inhibitor) attenuated the p40- and p75-mediated reduction of hydrogen peroxide-induced tight junction disruption and inulin permeability. These studies demonstrate that probiotic-secretory proteins protect the intestinal epithelial tight junctions and the barrier function from hydrogen peroxide-induced insult by a PKC- and MAP kinase-dependent mechanism.
Gene disruption and replacement as a feasible approach for mutagenesis of Campylobacter jejuni (1988)

Campylobacter jejuni and Campylobacter coli are important causes of human enteric infections. Several determinants of pathogenicity have been proposed based on the clinical features of diarrheal disease and on the phenotypic properties of Campylobacter strains. To facilitate an understanding of the genetic determinants of Campylobacter virulence, we have developed a method for constructing C. jejuni mutants by shuttle mutagenesis. In the example described here, a kanamycin resistance gene was inserted into Campylobacter DNA fragments encoding 16S rRNA cloned in Escherichia coli. These disrupted, modified sequences were returned to C. jejuni via conjugation. Through the apparent process of homologous recombination, the kanamycin resistance-encoding sequences were rescued by chromosomal integration, resulting in the simultaneous gene replacement of one of the 16S sequences of C. jejuni and the loss of the vector. We propose that Campylobacter isogenic mutants could be developed by using this system of shuttle mutagenesis.
Histological Assessment of PAXgene Tissue Fixation and Stabilization Reagents (2011)

Within SPIDIA, an EC FP7 project aimed to improve pre analytic procedures, the PAXgene Tissue System (PAXgene), was designed to improve tissue quality for parallel molecular and morphological analysis. Within the SPIDIA project promising results were found in both genomic and proteomic experiments with PAXgene-fixed and paraffin embedded tissue derived biomolecules. But, for this technology to be accepted for use in both clinical and basic research, it is essential that its adequacy for preserving morphology and antigenicity is validated relative to formalin fixation. It is our aim to assess the suitability of PAXgene tissue fixation for (immuno)histological methods. Normal human tissue specimens (n = 70) were collected and divided into equal parts for fixation either with formalin or PAXgene. Sections of the obtained paraffin-embedded tissue were cut and stained. Morphological aspects of PAXgene-fixed tissue were described and also scored relative to formalin-fixed tissue. Performance of PAXgene-fixed tissue in immunohistochemical and in situ hybridization assays was also assessed relative to the corresponding formalin-fixed tissues. Morphology of PAXgene-fixed paraffin embedded tissue was well preserved and deemed adequate for diagnostics in most cases. Some antigens in PAXgene-fixed and paraffin embedded sections were detectable without the need for antigen retrieval, while others were detected using standard, formalin fixation based, immunohistochemistry protocols. Comparable results were obtained with in situ hybridization and histochemical stains. Basically all assessed histological techniques were found to be applicable to PAXgene-fixed and paraffin embedded tissue. In general results obtained with PAXgene-fixed tissue are comparable to those of formalin-fixed tissue. Compromises made in morphology can be called minor compared to the advantages in the molecular pathology possibilities.
Why Do Organic Compounds Crystallise Well or Badly or Ever so Slowly? Why Is Crystallisation Nevertheless Such a Good Purification Technique? (2009)

Observation of the comparative crystallisation behaviour of over 400 related acylanilides has allowed some understanding of the role of conformation and molecular symmetry in determining the time taken by organic compounds to crystallise. This may be related to the number of alternative orientations in which a molecule can attempt to dock at a crystal site. Two- to 3-fold slowing of crystal growth compared with molecules with conformationally symmetric groups would be expected if the process involves simple acceptance of a single molecule at a growth site. The observed reduction in rate is much larger than this. It is suggested that it may be around x3 where x is the number of alternative orientations. An attempt is made to account for the failure of some compounds to form extended domains of crystal perfection, by considering the fitting of impurity molecules or the misfitting of correct molecules in the lattice. As an explanation of the role of crystallisation in purification, a proposal is made as to why an identical molecule is more likely to fit into an existing crystal lattice than any foreign molecule.
A sauvagine/corticotropin-releasing factor receptor expressed in heart and skeletal muscle. (1995)

Corticotropin-releasing factor (CRF) mediates many critical aspects of the physiological response to stress. These effects are elicited by binding to specific high-affinity receptors, which are coupled to guanine nucleotide stimulatory factor (Gs)-response pathways. Recently, a gene encoding a receptor for CRF, expressed in pituitary and the central nervous system (PC-CRF receptor), was isolated and characterized. Here we report the identification and characterization of a second, distinct CRF receptor that is expressed primarily in heart and skeletal muscle and exhibits a specific ligand preference and antagonist sensitivity compared with the PC-CRF receptor. We refer to this second receptor as the heart/muscle (HM)-CRF receptor.
Basolateral protein transport in streptolysin O-permeabilized MDCK cells. (1994)

We have reconstituted polarized protein transport in streptolysin O-permeabilized MDCK cells from the TGN to the basolateral surface and to the apical surface. These transport steps are dependent on temperature, energy and exogenously supplied cytosol. Using this in vitro system we show that a whole tail peptide (WT peptide) corresponding to the cytoplasmic tail of a basolaterally sorted protein, the vesicular stomatitis virus glycoprotein (VSV G) inhibits the TGN to basolateral transport but does not affect any other transport step. Inhibition of VSV G transport to basolateral surface by WT peptide did not result in missorting of the protein to the apical surface. Mutation of the single tyrosine residue in the WT peptide reduced its inhibitory potency four- to fivefold. These results suggest that the VSV G tail physically interacts with a component of the sorting machinery. Using a cross-linking approach, we have identified proteins that associate with the cytoplasmic tail domain of VSV G. One of these polypeptides, Tin-2 (Tail interacting protein-2), associates with VSV G in the TGN, the site of protein sorting, but not in the ER nor at the cell surface. Tin-2 does not associate with apically targeted hemagglutinin. WT peptide that inhibited the basolateral transport of VSV G also inhibited the association of Tin-2 with VSV G. Together, these properties make Tin-2 a candidate basolateral sorter. The results demonstrate the usefulness of the SLO-permeabilized cell system in dissecting the sorting machinery.
Gene isolation by complementation in Candida albicans and applications to physical and genetic mapping (1992)

We have isolated three genes, ARG57, SER57, and LYS1, on the basis of their function in Candida albicans. A C. albicans transformation vector containing the C. albicans URA3 gene, a Candida ARS sequence, and a portion of the Saccharomyces cerevisiae 2 microns circle containing the replication origin was constructed. Clones from genomic libraries in this vector were isolated by direct complementation of the auxotrophies in strain 1006 (arg57 ser57 lys1 ura3 MPA1). Transformants typically contain two to four plasmids in a mixed tandem multimer. A scheme to resolve mixed multimers into monomers in vivo by transformation of S. cerevisiae with Candida transformant DNA selecting Ura+ transformants was devised. Monomeric plasmids were then isolated by transformation of Escherichia coli with the S. cerevisiae transformant DNA. These were retested by transformation of strain 1006 to identify the specific plasmid that complemented the auxotrophy. The chromosomal locations of the genes were determined by hybridization to C. albicans chromosomes separated on contour-clamped homogenous electric field gels. We used these locations to assess the stability of individual C. albicans chromosomes in parasexual genetic analysis. The Lys(+)-complementing clone was shown to be LYS1 by complementation of S. cerevisiae lys1 mutants. These cloned genes help to align the Candida physical and genetic maps and provide additional markers for the transformation system.
Safety, tolerability, pharmacokinetics, and efficacy of AMG 403, a human anti-nerve growth factor monoclonal antibody, in two phase I studies with healthy volunteers and knee osteoarthritis subjects (2015)

ClinicalTrials.gov NCT02348879 . Registered 23 December 2014. Clintrials.gov NCT02318407 . Registered 2 December 2014.
Beta-adrenergic neuroeffector abnormalities in the failing human heart are produced by local rather than systemic mechanisms. (1992)

In order to investigate the general cause of beta-adrenergic receptor neuroeffector abnormalities in the failing human heart, we measured ventricular myocardial adrenergic receptors, adrenergic neurotransmitters, and beta-adrenergic receptor-effector responses in nonfailing and failing hearts taken from nonfailing organ donors, subjects with endstage biventricular failure due to idiopathic dilated cardiomyopathy (IDC), and subjects with primary pulmonary hypertension (PPH) who exhibited isolated right ventricular failure. Relative to nonfailing PPH left ventricles, failing PPH right ventricles exhibited (a) markedly decreased beta 1-adrenergic receptor density, (b) marked depletion of tissue norepinephrine and neuropeptide Y, (c) decreased adenylate cyclase stimulation in response to the beta agonists isoproterenol and zinterol, and (d) decreased adenylate cyclase stimulation in response to Gpp(NH)p and forskolin. These abnormalities were directionally similar to, but generally more pronounced than, corresponding findings in failing IDC right ventricles, whereas values for these parameters in nonfailing left ventricles of PPH subjects were similar to values in the nonfailing left ventricles of organ donors. Additionally, relative to paired nonfailing PPH left ventricles and nonfailing right ventricles from organ donors, failing right ventricles from PPH subjects exhibited decreased adenylate cyclase stimulation by MnCl2. These data indicate that: (a) Adrenergic neuroeffector abnormalities present in the failing human heart are due to local mechanisms; systemic processes do not produce beta-adrenergic neuroeffector abnormalities. (b) Pressure-overloaded failing right ventricles of PPH subjects exhibit decreased activity of the catalytic subunit of adenylate cyclase, an abnormality not previously described in the failing human heart.
Blending of brain-machine interface and vision-guided autonomous robotics improves neuroprosthetic arm performance during grasping (2016)

NCT01364480 and NCT01894802 .
TEX101 is shed from the surface of sperm located in the caput epididymidis of the mouse (2005)

It is generally believed that cell-to-cell cross-talk and signal transduction are mediated by cell surface molecules that play diverse and important regulatory roles in spermatogenesis and fertilization. Recently, we identified a novel plasma membrane-associated protein, TES101-reactive protein (TES101RP, or TEX101), on mouse testicular germ cells. In this study, we investigate Tex101 mRNA expression in the adult mouse testis using in situ hybridization, and we examine the fate of TEX101 during sperm transport by immunohistochemical and Western blot analyses. Tex101 mRNA was expressed in a stage-specific manner in spermatocytes and in step 1-9 spermatids of the testis, but not in spermatogonia. Although the TEX101 protein remained on the cell surfaces of step 10-16 spermatids and testicular sperm, it was shed from epididymal sperm located in the caput epididymidis. The results of this study provide additional information on germ cell-specific TEX101 expression during spermatogenesis and post-testicular sperm maturation.
Reaktionen mit Diazoketonen. VI. Synthese einiger 2‐Alkylamino‐ und 2‐Arylamino‐4‐aryl‐thiazole (1968)

Abstract Phenyldiazomethylketone reagieren mit Thioharnstoff oder dessen N‐substituierten Derivaten zu 2‐Alkylamino‐ bzw. 2‐Aryl‐4‐thiazolen, deren Bildungsmechanismus diskutiert wird. Substituenteneinflüsse auf die Reaktion werden untersucht.
Technique to compensate waveform distortion in again-saturatedsemiconductor optical amplifier using a semiconductor saturable absorber (1998)

A technique to compensate waveform distortion induced in a gain-saturated semiconductor optical amplifier (SOA) is proposed and demonstrated. A saturable absorber, which is actually an SOA biased below the transparency current, is placed after an SOA. The loss dynamics of the absorber compensate the SOA gain dynamics and a less distorted signal can be output.
Facile Synthesis of Unsymmetrical 9-Phospha- and 9-Arsafluorenes (2006)

Unsymmetrical 9-chloro-9-phosphafluorenes (dibenzophospholes) and 9-chloro-9-arsafluorenes (dibenzoarsoles) have been obtained by simple thermolysis of m-terphenyldichlorophosphines and -arsines in close to quantitative yields. The reaction temperatures are about 200 degrees C for the phosphines and 140 degrees C for the arsine, and the reactions are complete within 5 min. Alternatively, these compounds can be synthesized through an AlCl3-catalyzed Friedel-Crafts type ring-closure reaction at low temperatures, but this method suffers from difficult workup procedures. The P(As)-Cl functionality is readily alkylated. Methylation of m-xylyl derivative 4 afforded 1-(3,5-dimethylphenyl)-6,8,9-trimethyl-9-phosphafluorene, 11. The latter compound formed the complexes 11 x Fe(CO)4, 12, and 11 x RuCl2(eta(6)-p-cymene), 13, indicating its good donor properties. The new compounds have been characterized by 1H, 13C{1H}, and 31P{1H} NMR spectroscopy; mass spectrometry; and single-crystal X-ray crystallography in the case of 11, 12, and 13.
The Minority of Alexander III of Scotland (1971)

KING ALEXANDER II died at the age of fifty-one on 8 July 1249 leaving as his heir his only son, Alexander III, then aged just seven years and ten months. Whatever the comparative maturity of the new boy-king, there clearly followed a period of minority government, which must have raised more serious constitutional and political problems than Scotland had so far had to solve in her known history in connection with the disadvantages of an hereditary monarchy. Malcolm IV had been aged twelve when he succeeded in 1153 and Alexander II aged sixteen in 1214, and there is no evidence that either was regarded as anything but fully adult. Alexander III on the other hand is usually thought to have been under some restraint as a minor for some thirteen years until he was as old as twenty-one in September 1262. 1 These thirteen years were certainly an unsettled period in Scotland worthy of study in detail, and then perhaps it may be more possible than at present to compare the Scottish experience with that of other countries which also survived the strain of minority government in the thirteenth century, such as Sicily, England, Castille, France and Jerusalem. It was indeed a striking feature of the age that monarchy did not require the presence of an adult king; and in Scotland as elsewhere this must have been so because there was general support for the continuing crown authority rather than for the individual monarch. This argument is all the stronger when it is realized that in the case of Scotland little evidence survives of formal arrangements being made at either the beginning or the end of the period of minority.
Relative promoter strengths in four human prostate cancer cell lines evaluated by particle bombardment‐mediated gene transfer* (2002)

The particle bombardment gene-transfer technology can be effectively employed as an efficient method for in vitro gene-transfer into prostate tumor cells. The characterization of relative promoter strength and preference may be useful for future studies of cancer gene therapy approaches.
Interferon Induction by a 2′‐Modified Double‐Helical RNA, Poly(2′‐azido‐2′‐deoxyinosinic acid) · polycytidylic acid (1978)

Although the presence of free 2′‐hydroxyl groups in both strands of a double‐stranded RNA complex has been recognized as one of the major requisites for the interferon‐inducing activity of double‐stranded RNAs, we have found a particular analogue of (I) n · (C) n in which the 2′‐hydroxyls of the purine nucleotide strand were replaced by azido groups, (dIn 3 ) n · (C) n , to be highly effective in inducing interferon. Various other 2′‐azido analogues of (I) n · (C) n and (A) n · (U) n , i.e. (dIn 3 ) n · (br 5 C) n , (I) n · (dCn 3 ) n , (dAn 3 ) n · (U) n , (A) n · (dUn 3 ) n , (dAn 3 ) n · (rT) n and (dAn 3 ) n · (dUn 3 ) n , were inactive as inducers of interferon. In human fibroblast cultures, the interferon‐inducing activity of (dIn 3 ) n · (C) n equalled that of (I) n · (C) n . In other interferon‐induction systems (primary rabbit kidney cells, mouse L‐929 cells, intact rabbits), (dIn 3 ) n · (C) n was less active than (I) n · (C) n . As assessed by both radio‐chemical and biological means, (dIn 3 ) n · (C) n was more susceptible to degradation by pancreatic ribonuclease and human serum nucleases than was (I) n · (C) n . The t m of (dIn 3 ) n · (C) n was 52.5 °C, as compared to 62.5 °C for (I) n · (C) n , both determined in 0.15 M Na + , pH 7.0. Under the same conditions, (dIn 3 ) n · (br 5 C) n had a t m of 77 °C and (I) n · (br 5 C) n had a t m of 87 °C. The reactivity of (dIn 3 ) n · (C) n and (dIn 3 ) n · (br 5 C) n towards antibodies to double‐stranded RNA was evaluated by quantitative complement fixation, counterimmunoelectrophoresis and competitive radioimmunoassay. In these tests, (dIn 3 ) n · (C) n and (dIn 3 ) n · (br 5 C) n showed an immunoreactivity pattern comparable to that of (I) n · (C) n and (I) n · (br 5 C) n .
Identification of Sites of Glycosylation (2003)

Glycoproteins typically contain three types of glycans (1), the so-called N-linked glycans which are attached via an amide bond to asparagine in a Asn-Xxx-Ser(Thr) motif where Xxx can be any amino acid except proline; the O-linked glycans that are attached to serine or threonine, and glycosylphosphatidylinositol lipid anchors attached to the carboxy-terminus of some proteins. Glycoproteins containing N-linked glycans typically possess from 1-20 glycosylation sites that may or may not be occupied, usually with a range of carbohydrate structures. Each individual glycoprotein is known as a “glycoform”. All of these N-linked carbohydrate structures contain a trimannosyl-chitobiose [Manα 1→(Manα 1 →6)Manβ 1 →-4GlcNAcβ 1→ 4GlcNAc] pentasaccharide core with one or more glycan chains (antennae) attached to each of the nonreducing mannose residues (see Fig. 1). Glycans containing only mannose in the antennae are termed “high-mannose,” those with galactose and GlcNAc in both antennae are termed “complex” and glycans with both mannose and GlcNAc on different antennae are known as “hybrid” glycans. Fucose, sialic acid, other monosaccharides and sulphate are frequently also present. O-linked glycans are usually smaller, lack a common core structure and are usually found in groups on adjacent or closely spaced amino acids. Several structural types are recognised (see Fig. 1). Unlike the case of N-linked glycans, there is no consensus sequence of amino acids directing O-linked glycosylation.
Design and Implementation of a Micromanipulation System Using a Magnetically Levitated MEMS Robot (2009)

Magnetic levitation of microrobots is presented as a new technology for micromanipulation tasks. The microrobots were fabricated based on microelectromechanical systems technology and weigh less than 1 g. The robots can be positioned in 3-D using magnetic field. It is shown that microrobots can be produced using commercially available magnets or electrodeposited magnetic films. A photothermal microgripper is integrated to the microrobots to perform micromanipulation operations. The microgrippers can be actuated remotely by laser focusing that makes the microrobot free of any wiring. This leads to increased motion range with more functionality in addition to dust-free motion and ability to work in closed environments. The 3-D motion capability of the microrobots is verified experimentally and it was demonstrated that the microgrippers can be operated in a vertical range of 4 mm and a horizontal range of 4 mm times 5 mm. Micromanipulation experiments such as pick-and-place, pushing, and pulling were demonstrated using objects with 100 mum and 1 mm diameter.