gebhart/patrepeval huggingface dataset:
Topology of cell adhesion molecules. (1989)

The neural cell adhesion molecule (N-CAM) exists in two major forms [ld (large cytoplasmic domain) peptide and sd (small cytoplasmic domain) peptide] that contain transmembrane segments and different cytoplasmic domains and in a third form [ssd (small surface domain) peptide] that lacks transmembrane and cytoplasmic regions. All forms have the same extracellular region of more than 600 amino acid residues, a region also found in a fragment (Fr2) that can be released from cells by proteolysis. The liver cell adhesion molecule (L-CAM) is expressed as a single species that is distinct from N-CAM, but its extracellular region can also be obtained as a proteolytic fragment (Ft1). Examination of the various forms of N-CAM and the Ft1 fragment of L-CAM by electron microscopy of rotary shadowed molecules indicated that they all have rod-shaped structures that contain a hinge region which is apparently flexible. Both the ssd chain and the Fr2 fragment of N-CAM are single rods bent into arms approximately 18 and 10 nm long. The ld and sd chains are longer bent rods that form rosettes comprising two to six branches; detergent treatment disrupts these rosettes into single rods. Specific antibodies that block homophilic N-CAM binding labeled the distal ends of the branches of the ld/sd rosettes and the ends of the longer arm of both the ssd chain and the Fr2 fragment. Antibodies that bind to the sialic acid-rich region of N-CAM bound near the hinge. These data indicate that the N-CAM rosettes are formed by interaction between their transmembrane or cytoplasmic domains and not by interactions involving their homophilic binding sites. The L-CAM Ft1 fragment is also a bent rod with an apparently flexible hinge; like the ssd chain and the Fr2 fragment of N-CAM, it does not form aggregates. The similarities between L-CAM and N-CAM, despite their differences in amino acid sequence, suggest that their general configuration and the presence of a flexible hinge are important elements in assuring effective and specific cell-cell adhesion.
Interferon-gamma drives programmed death-ligand 1 expression on islet β cells to limit T cell function during autoimmune diabetes (2018)

Abstract Type 1 diabetes is caused by autoreactive T cell-mediated β cell destruction. Even though co-inhibitory receptor programmed death-1 (PD-1) restrains autoimmunity, the expression and regulation of its cognate ligands on β cell remains unknown. Here, we interrogated β cell-intrinsic programmed death ligand-1 (PD-L1) expression in mouse and human islets. We measured a significant increase in the level of PD-L1 surface expression and the frequency of PD-L1 + β cells as non-obese diabetic (NOD) mice aged and developed diabetes. Increased β cell PD-L1 expression was dependent on T cell infiltration, as β cells from Rag1-deficient mice lacked PD-L1. Using Rag1-deficient NOD mouse islets, we determined that IFN-γ promotes β cell PD-L1 expression. We performed analogous experiments using human samples, and found a significant increase in β cell PD-L1 expression in type 1 diabetic samples compared to type 2 diabetic, autoantibody positive, and non-diabetic samples. Among type 1 diabetic samples, β cell PD-L1 expression correlated with insulitis. In vitro experiments with human islets from non-diabetic individuals showed that IFN-γ promoted β cell PD-L1 expression. These results suggest that insulin-producing β cells respond to pancreatic inflammation and IFN-γ production by upregulating PD-L1 expression to limit self-reactive T cells.
Effect of tetravalent bispecific CD19×CD3 recombinant antibody construct and CD28 costimulation on lysis of malignant B cells from patients with chronic lymphocytic leukemia by autologous T cells (2004)

To develop an effective antitumor immunotherapy for B-lineage non-Hodgkin's lymphoma, we constructed a tetravalent tandem diabody (tanDb) specific for both human CD19 (B-cell marker) and CD3 (T-cell antigen). Here, we report the effective killing of malignant primary B cells from patients with B-cell chronic lymphocytic leukemia (B-CLL) by autologous T cells induced by tanDb at very low E:T ratios. Mononuclear cells from patients with B-CLL were cultured with bispecific antibody fragments in either the presence or absence of monospecific anti-CD28 antibody. Use of tetravalent tanDbs caused almost quantitative elimination of malignant B cells from the blood samples of 19 patients and some cytotoxic activity in 3 of 23 analyzed cases. In contrast, the structurally similar but bivalent diabody and single-chain diabody demonstrated nearly no antitumor activity in an autologous system. tanDb-induced activation and proliferation of T cells occurred only in the presence of CD19+ target cells. Expression of the B7-1 (CD80) and B7-2 (CD86) molecules on the surface of leukemia cells made unnecessary the additional CD28-costimulation of T cells. When only a few tanDb molecules were present, the effect of CD28 costimulation on T-cell activation was more pronounced. Depending on the patient sample, we observed a 10- to 1,000-fold decrease of the half-maximal concentrations of tanDb for cell lysis. Upon CD28 crosslinking by agonistic MAb, specific tumor cell lysis was found at tanDb concentrations as low as 0.5 pM. These data demonstrate that the tetravalent CD19xCD3 tanDb might be a promising tool for the immunotherapy of human B-cell leukemias and lymphomas.
Some Properties of Generalized Tensor Bezoutian with Respect to a General Polynomial Basis (2010)

In this note, the authors carry over the tensor Bezoutian for polynomial matrices to the case of a general polynomial basis. Some of important properties, such as the Barnett-type factorization, the expressions in terms of controllability- and observability-type matrices, and some intertwining relations with companion matrices and resultant matrices, are characterized.
Internalizing Versus Non-internalizing Receptors for Targeting L-Methioninase to Cancer Cells (2006)

We reported previously that L-methioninase targeted to the urokinase receptor of MCF-7 breast cancer cells is significantly more effective in inhibiting cell proliferation and migration than free L-methioninase both in vitro and in vivo. L-methioninase was targeted by linking at its amino terminus to an amino-terminal fragment (ATF) of urokinase. The ATF was selected for targeting because is has previously been shown not to internalize within the cells. The present study was designed to determine the effectiveness of targeting L-methioninase to a cancer cell receptor that is internalizing in comparison with ATF-methioninase, which does not internalize. Transforming growth factor-α (TGF-α) was selected for targeting to the epidermal growth factor receptor which is overexpressed in numerous cancer cell lines and is an internalizing receptor. Two fusion proteins, ATF-methioninase and TGF-methioninase (TGF-α linked to the amino terminus of L-methioninase), were produced by recombinant methods and purified. In an in vitro culture wounding assay over 3 days to measure cell proliferation and migration of MCF-7 breast cancer cells and PC-3 prostate cancer cells, both fusion proteins inhibited the proliferation and migration of both cancer cell lines. However, the inhibition was significantly greater for ATF-methioninase compared to TGF-methioninase, especially at treatment days 2 and 3. These results indicate that, for a fixed dosage of the fusion protein, it is more advantageous to have L-methioinase bind to a receptor and remain externalized, rather than to bind to a receptor which leads to internalization of L-methioninase. Further, it may be advantageous to target other anticancer agents to the urokinase receptor on the cancer cell surface by means of the amino-terminal fragment of urokinase.
Expression patterns of transcribed human endogenous retrovirus HERV-K(HML-2) loci in human tissues and the need for a HERV Transcriptome Project (2008)

Our, to date, largest-scale study reveals in greater detail expression patterns of individual HML-2 loci in human tissues of clinical interest. Moreover, large-scale, specialized studies are indicated to better comprehend transcriptional activity and regulation of HERVs. We thus emphasize the need for a specialized HERV Transcriptome Project.
Using character recognition and segmentation to tell computer from humans (2004)

How do you tell a computer from a human? The situation arises often on the Internet, when online polls are conducted, accounts are requested, undesired email is received, and chat-rooms are spammed. The approach we use is to create a visual challenge that is easy for humans but difficult for a computer. More specifically, our challenge is to recognize a string of random distorted characters. To pass the challenge, the subject must type in the correct corresponding ASCII string. From an OCR point of view, this problem is interesting because our goal is to use the vast amount of accumulated knowledge to defeat the state of the art OCR algorithms. This is a role reversal from traditional OCR research. Unlike many other systems, our algorithm is based on the assumption that segmentation is much more difficult than recognition. Our image challenges present hard segmentation problems that humans are particularly apt at solving. The technology is currently being used in MSN's Hotmail registration system, where it has significantly reduced daily registration rate with minimal Consumer Support impact.
Keratinolytic proteinase produced byCandida albicans (1984)

Candida albicans was cultivated in various media that contained human stratum corneum, human scalp hair or keratin powder (cow's hoof) as a nitrogen source. Production of a keratinolytic proteinase (KPase) was observed when C. albicans was incubated in the medium containing stratum corneum. However, there was no production of a KPase that could digest human stratum corneum in the medium containing hair or keratin powder. alpha-fibrous protein extracted from human stratum corneum was digested by the KPase. The pH optimum of the enzyme was 4.0 and enzyme activity was inhibited by pepstatin A and chymostatin. The KPase, a kind of carboxyl proteinase, may be important for C. albicans to enable it to play a pathogenic role in vivo.
Contribution de la toponymie à l’histoire du Poitou gallo-romain (1998)

Gauthier Pierre. Contribution de la toponymie à l’histoire du Poitou gallo-romain. In: Onomastique et histoire - Onomastique littéraire. Actes du Colloque d’onomastique d’Aix-en-Provence (octobre 1994) Paris : Société française d'onomastique, 1998. pp. 121-131. (Actes des colloques de la Société française d'onomastique, 8)
Sustained FVIII Expression and Phenotypic Correction of Hemophilia A in Neonatal Mice Using an Endothelial-Targeted Sleeping Beauty Transposon (2006)

Hemophilia A, deficiency of coagulation factor VIII (FVIII), is an attractive candidate for gene therapy as expression of modest amounts of FVIII can provide therapeutic benefit. Most gene transfer approaches for hemophilia have focused on the liver, as this is the major source of endogenous FVIII; however, increasing evidence suggests that endothelial cells are capable of synthesis and release of FVIII. Here the Sleeping Beauty (SB) transposon is employed to target long-term expression of the human B-domain-depleted FVIII gene (approved gene symbol F8) within lung endothelia of hemophilic mice. As the formation of inhibitory antibodies to FVIII has been a significant impediment toward achieving therapeutic plasma levels after gene or protein therapy, we chose to perform gene transfer in neonatal mice, which are more likely to be immune tolerant. Using this approach, low therapeutic levels of FVIII ( approximately 10%), as well as phenotypic correction of the bleeding disorder, were achieved in all animals that received the FVIII transposon and functional transposase throughout the duration of the study (24 weeks). Rechallenge of these animals with additional gene transfer did not result in significant increases in FVIII levels, due mainly to increases in inhibitory antibodies. These studies demonstrate the feasibility of using endothelial-targeted SB transposons for the treatment of hemophilia A.
Program transformation and runtime support for threaded MPI execution on shared-memory machines (2000)

Parallel programs written in MPI have been widely used for developing high-performance applications on various platforms. Because of a restriction of the MPI computation model, conventional MPI implementations on shared-memory machines map each MPI node to an OS process, which can suffer serious performance degradation in the presence of multiprogramming. This paper studies compile-time and runtime techniques for enhancing performance portability of MPI code running on multiprogrammed shared-memory machines. The proposed techniques allow MPI nodes to be executed safety and efficiently as threads. Compile-time transformation eliminates global and static variables in C code using node-specific data. The runtime support includes an efficient and provably correct communication protocol that uses lock-free data structure and takes advantage of address space sharing among threads. The experiments on SGI Origin 2000 show that our MPI prototype called TMPI using the proposed techniques is competitive with SGI's native MPI implementation in a dedicated environment, and that it has significant performance advantages in a multiprogrammed environment.
Hepatic disease associated with ground-glass inclusions in hepatocytes after cyanamide therapy. (1986)

In a retrospective review of 2400 consecutive liver biopsy specimens, 60 cases with ground-glass hepatocytes were identified, 41 specimens gave a positive reaction to orcein stain and 19 a negative staining. These 19 specimens were obtained from chronic alcoholics who had been admitted to a detoxication program that used aversive drugs and who were hepatitis B surface antigen negative. The use of cyanamide (Colme), an inhibitor of aldehyde dehydrogenase could be documented in 11 instances. In addition to ground-glass hepatocytes, which were periodic acid-Schiff positive and had a periportal or paraseptal distribution, these liver specimens showed a variety of hepatic lesions: cirrhosis in five cases, portal and periportal inflammation in six, triaditis in five, portal fibrosis in two, and minimal changes in one. Patients with shorter courses of cyanamide were those who had less severe histologic lesions. In three patients who had a liver biopsy carried out before the cyanamide treatment ground-glass hepatocytes were not found. These data indicate that ground-glass hepatocytes that stain with periodic acid-Schiff may develop after cyanamide treatment. They are associated with structural hepatic damage of varied severity in patients submitted to a long-term treatment.
Stochastic mechanisms in gene expression (1997)

In cellular regulatory networks, genetic activity is controlled by molecular signals that determine when and how often a given gene is transcribed. In genetically controlled pathways, the protein product encoded by one gene often regulates expression of other genes. The time delay, after activation of the first promoter, to reach an effective level to control the next promoter depends on the rate of protein accumulation. We have analyzed the chemical reactions controlling transcript initiation and translation termination in a single such "genetically coupled" link as a precursor to modeling networks constructed from many such links. Simulation of the processes of gene expression shows that proteins are produced from an activated promoter in short bursts of variable numbers of proteins that occur at random time intervals. As a result, there can be large differences in the time between successive events in regulatory cascades across a cell population. In addition, the random pattern of expression of competitive effectors can produce probabilistic outcomes in switching mechanisms that select between alternative regulatory paths. The result can be a partitioning of the cell population into different phenotypes as the cells follow different paths. There are numerous unexplained examples of phenotypic variations in isogenic populations of both prokaryotic and eukaryotic cells that may be the result of these stochastic gene expression mechanisms.
Vanadyl‐induced Fenton‐like reaction in RNA (1990)

Vanadyl (VO2+) complexed to RNA reacts with hydrogen peroxide in a Fenton-like manner producing hydroxyl radicals (.OH). The hydroxyl radicals can be spin trapped with 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) forming the DMPO-OH spin adduct. In addition, in the presence of ethanol the formation of the hydroxyethyl radical adduct of DMPO (DMPO-ETOH) confirms the production of hydroxyl radicals by the RNA/VO2+ complex. When the reaction between the RNA/VO2+ complex and H2O2 is carried out in the presence of the spin trap 2-methyl-2-nitrosopropane (MNP), radicals produced in the reaction of .OH with RNA are trapped. Base hydrolysis of the MNP-RNA adducts (pH 12) followed by a reduction in the pH to pH 7 after hydrolysis is complete, yields an MNP adduct with a well-resolved ESR spectrum identical to the ESR spectrum obtained from analogous experiments with poly U. The ESR spectrum consists of a triplet of sextets (aN = 1.48 mT, a beta N = 0.25 mT and a beta H = 0.14 mT), indicating that the unpaired nitroxide electron interacts with the nuclei of a beta-nitrogen and beta-hydrogen. The results suggest that the .OH generated in the RNA/VO2+ reaction with H2O2 add to the C(5) carbon of uracil forming a C(6) carbon centered radical. This radical is subsequently spin trapped by MNP.
Compilation of small RNA sequences (1991)

This is an update containing small RNA sequences published during 1990. Approximately two hundred small RNA sequences are available in this and earlier compilations. The hard copy print out of this set will be available directly from us (inquiries should be addressed to R. Reddy). These files will be available on
Engineering Orthopedic Tissue Interfaces (2009)

While a wide variety of approaches to engineering orthopedic tissues have been proposed, less attention has been paid to the interfaces, the specialized areas that connect two tissues of different biochemical and mechanical properties. The interface tissue plays an important role in transitioning mechanical load between disparate tissues. Thus, the relatively new field of interfacial tissue engineering presents new challenges--to not only consider the regeneration of individual orthopedic tissues, but also to design the biochemical and cellular composition of the linking tissue. Approaches to interfacial tissue engineering may be distinguished based on if the goal is to recreate the interface itself, or generate an entire integrated tissue unit (such as an osteochondral plug). As background for future efforts in engineering orthopedic interfaces, a brief review of the biology and mechanics of each interface (cartilage-bone, ligament-bone, meniscus-bone, and muscle-tendon) is presented, followed by an overview of the state-of-the-art in engineering each tissue, including advances and challenges specific to regenerating the interfaces.
CROSS-TALK BETWEEN BONE MARROW AND TISSUE INJURY: NOVEL REGENERATIVE THERAPY FOR SEVERELY DAMAGED TISSUES BY MOBILIZING BONE MARROW MESENCHYMAL STEM CELLS IN VIVO (2013)

group box 1 （HMGB1）, which mobilizes a sub-population of non-hematopoietic cells from bone marrow into the circulation to repair skin and restore Col 7 expression. These bone marrow-derived epithelial stem/progenitor cells are derived from a lineage-negative, platelet-derived growth factor alpha-positive mesenchymal stem cell pool in bone marrow, which represents less than 0.3% of the total bone marrow cell population. In addition, systemic administration of HMGB1 to wounded wild-type mice leads to faster wound healing with recruitment of these bone marrow cells to the wounded skin. This study identifies a suitable cell population for cell therapy approaches in individuals with RDEB, but also has broader implications for clinical medicine in identifying a means of mobilizing and recruiting a key population of bone marrow cells germane to tissue repair.
Staphylococcus and biofilms (2002)

The genetic and molecular basis of biofilm formation in staphylococci is multifaceted. The ability to form a biofilm affords at least two properties: the adherence of cells to a surface and accumulation to form multilayered cell clusters. A trademark is the production of the slime substance PIA, a polysaccharide composed of beta-1,6-linked N-acetylglucosamines with partly deacetylated residues, in which the cells are embedded and protected against the host's immune defence and antibiotic treatment. Mutations in the corresponding biosynthesis genes (ica operon) lead to a pleiotropic phenotype; the cells are biofilm and haemagglutination negative, less virulent and less adhesive on hydrophilic surfaces. ica expression is modulated by various environmental conditions, appears to be controlled by SigB and can be turned on and off by insertion sequence (IS) elements. A number of biofilm-negative mutants have been isolated in which polysaccharide intercellular adhesin (PIA) production appears to be unaffected. Two of the characterized mutants are affected in the major autolysin (atlE) and in D-alanine esterification of teichoic acids (dltA). Proteins have been identified that are also involved in biofilm formation, such as the accumulation-associated protein (AAP), the clumping factor A (ClfA), the staphylococcal surface protein (SSP1) and the biofilm-associated protein (Bap). Concepts for the prevention of obstinate polymer-associated infections include the search for new anti-infectives active in biofilms and new biocompatible materials that complicate biofilm formation and the development of vaccines.
Complement deficiency states and infection: epidemiology, pathogenesis and consequences of neisserial and other infections in an immune deficiency. (1984)

Inherited deficiencies of the complement proteins are rare in unselected populations. Examination of patients with the clinical correlates of complement deficiency (autoimmune disease and certain bacterial infections) shows the frequency of inherited complement deficiency to rise enormously (5.9% of patients with systemic lupus erythematosus, 10 to 25% of adults with sporadic meningococcal disease). Autoimmune diseases of all types, but especially systemic lupus erythematosus, discoid lupus and glomerulonephritis, are seen in all categories of complement deficiency, most typically in those of the early classical pathway (C1, C4, C2). Pneumococcal infections are characteristic of deficiencies of the early classical pathway, as well. Deficiencies of C3 are associated with severe disease including autoimmune phenomena, pneumococcal and neisserial infections. C3-deficient patients become ill substantially earlier in life. Infections with N. meningitidis and N. gonorrhoeae are most typical of the late component deficiencies, with over 40% of homozygotes affected. Despite the presence of this deficiency from birth and the peak age-specific incidence of meningococcal disease in the general population at ages 3-8 months, the median age of first infection in the late component-deficient patients is 17 years. Relapse of infection is ten times more common in these patients, and discrete recurrences are seen in 45% of affected individuals. An unusual and unexplained predilection for infection with serogroup Y N. meningitidis exists. Despite an immune deficiency, and problems with ascertainment bias, it appears that persons with late component complement deficiency enjoy less mortality than normals who contract meningococcal disease. Attempts to explain the pathogenesis of neisserial infection in late component deficiencies have focused on the concept that normally non-pathogenic serum-sensitive bacteria are etiologic in the absence of serum bactericidal activity. Data to support this concept remain to be developed and contrary data exist. A separate mechanism may predispose properdin-deficient patients to meningococcal infection, since they appear to develop fulminant infections with high mortality.