gebhart/patrepeval huggingface dataset:
Testosterone treatment comes of age: new options for hypogonadal men (2006)

Male hypogonadism is one of the most frequent, but also most underdiagnosed, endocrinopathies. However, the required testosterone treatment is simple and very effective if properly administered. Although testosterone has been available for clinical use for seven decades, until quite recently the treatment modalities were far from ideal. Subdermal testosterone pellets require minor surgery for insertion and often cause local problems. The injectable testosterone enanthate, for a long period the most frequently used mode of administration, lasts for two to four weeks, but produces supraphysiological levels initially and low levels before the next injection. The oral testosterone undecanoate has to be taken three times daily, has an uncertain absorption pattern and results in peaks and valleys of serum testosterone levels throughout the day. With the advent of transdermal testosterone preparations, the desired physiological serum levels could be achieved for the first time. Scrotal testosterone patches were the first to fulfil this requirement. These were followed by nonscrotal skin patches, which, however, cause considerable skin reactions including erythema and blisters. Recently introduced, invisible transdermal testosterone gels increased the intervals of application and are now slowly replacing other modalities. A mucoadhesive buccal testosterone tablet with sustained release is also a recent competing modality. Finally, injectable testosterone undecanoate in castor oil was made into a real depot preparation requiring only four injections per year for replacement therapy. These new preparations with a desired pharmacokinetic testosterone profile give the patient a real choice and make treatment easier. Based on pharmacogenetic considerations taking the androgen receptor polymorphism into account, treatment may be individualized for each patient in the future.
CD2 expression acts as a quantitative checkpoint for immunological synapse structure and T-cell activation (2019)

Abstract The CD2 receptor has been described as an adhesion and costimulatory receptor on T cells. Here, transcriptional profiling of colorectal cancers (CRC) revealed a negative correlation between CD2 expression and “exhausted CD8 + T-cells” gene signatures. Furthermore, we detected reduced surface CD2 levels in exhausted CD127 low PD-1 hi CD3 + CD8 + tumour infiltrating lymphocytes (TILs) in CRC. We describe a CD2 expression-level-dependent switch in CD2-CD58 localization between central and peripheral domains in the immunological synapse (IS). A peripheral “CD2 corolla” formed when CD2 surface expression was sufficiently high and its cytoplasmic domain intact. The corolla recruited other ligated receptors like CD28, boosted recruitment of activated Src-family kinases (pSrc), LAT and PLC-γ in the IS and consequently T-cell activation in response to a tumour antigen. Corolla formation and pSrc in the IS increased linearly with CD2 expression, whereas pSrc signals were reduced by high, “exhausted-like” levels of PD-1, which invaded the corolla. These results suggest two levels of inhibition of Src-family kinases in CD3 + CD8 + TILs: reduced CD2 expression and high PD-1 expression.
Step and flash imprint lithography template characterization, from an etch perspective (2003)

As a means of studying process windows with short turnaround time while avoiding substrate-to-substrate repeatability issues, Step and Flash Imprint Lithography templates were fabricated with physical masking of quadrants during dry etching used to introduce process perturbations. For every 20 s of descum (Ar/O2 etch) time, critical dimensions (CD) were observed to change approximately 2.6 nm on sub-100 nm features. Similarly, increasing Cr overetch time by 20% resulted in a positive CD change of 3.8 nm. Line edge roughness decreased with increasing descum and Cr overetch times. Best overall performance was observed for a 20 s descum used in conjunction with a 110% Cr overetch. Of four tip types studied, sharpened silicon atomic force microscopy tips were able to accurately measure etch depth of 80 nm trenches, but geometrical considerations limited sidewall angle determination to greater than 100°. Cross-sectioning of features on 6×6×0.25 in. quartz plates was successfully accomplished using a focused ion beam technique with typical sidewall angles of about 95° observed on 150 nm features. Finally, minimal microloading was observed for the ICP-based quartz etch process. Feature sizes ranging from 70 nm up to 8 μm possessed an average etch depth of 88.8 nm with a 1.2 nm (1 sigma) variation.
Functionalization of Oligonucleotides by the Incorporation of Thio-Specific Reporter Groups (1994)

The attachment of reporter groups, drug derivatives, or chemically reactive species to DNA in a sequence-specific manner has the potential to provide new materials for detailed spectroscopic and structural analyses as well as new classes of DNA therapeutics and diagnostics. Sequence specific labeling of a nucleic acid sequence can be achieved by a number of procedures that employ either the nucleobase, the carbohydrate or the phosphate residue as a site for attachment (for a recent review see ref. ). Specific functional groups (such as terminal phosphomonoesters, see Chapter 3) or the enhanced reactivity of selected sites on the purine or pyrimidine building blocks (such as the C5-position of pyrimidines, see Chapter 2) are often used in order to covalently attach an appropriate linker or the desired reporter group. The manner in which the nucleic acid is labeled may be dictated by the specific study involved, but in general the principles of simplicity and versatility are best employed to guide the choice of labeling procedure.
Production of Borreliacidal Antibody to Outer Surface Protein A In Vitro and Modulation by Interleukin-4 (2000)

Borreliacidal antibody production is one of several parameters for establishing the effectiveness of Borrelia burgdorferi vaccines. The production of borreliacidal antibody was studied in vitro by culturing immune lymph node cells with macrophages and B. burgdorferi. We showed that borreliacidal antibody, directed primarily against outer surface protein A (OspA), was readily produced by lymph node cells obtained from C3H/HeJ mice vaccinated with formalin-inactivated B. burgdorferi in aluminum hydroxide, but not recombinant OspA. Anti-OspA borreliacidal antibody was detected in supernatants of cultures of lymph node cells obtained on day 7 after vaccination, peaked on day 17, and rapidly declined. The borreliacidal activity was attributable to immunoglobulin G1 (IgG1), IgG2a, and IgG2b antibodies. When lymph node cells were treated with interleukin-4 (IL-4), production of borreliacidal antibody was inhibited but was unaffected by treatment with anti-IL-4 antibodies. These results suggest that other cytokines, but not IL-4, are mainly responsible for production of the secondary borreliacidal antibody response.
Unsupervised deduplication using cross-field dependencies (2008)

Recent work in deduplication has shown that collective deduplication of different attribute types can improve performance. But although these techniques cluster the attributes collectively, they do not model them collectively. For example, in citations in the research literature, canonical venue strings and title strings are dependent -- because venues tend to focus on a few research areas -- but this dependence is not modeled by current unsupervised techniques. We call this dependence between fields in a record a cross-field dependence. In this paper, we present an unsupervised generative model for the deduplication problem that explicitly models cross-field dependence. Our model uses a single set of latent variables to control two disparate clustering models: a Dirichlet-multinomial model over titles, and a non-exchangeable string-edit model over venues. We show that modeling cross-field dependence yields a substantial improvement in performance -- a 58% reduction in error over a standard Dirichlet process mixture.
Bioorthogonal Click Chemistry: Covalent Labeling in Living Systems (2007)

Abstract The term “click chemistry” defines a powerful set of chemical reactions that are rapid, selective, and high‐yielding. These reactions, some of which are less than 10 years old, have been applied in diverse areas, including drug discovery, materials science, and chemical biology. In chemical biology, click chemistry has been used in the selective labeling of biomolecules within living systems, allowing proteins, glycans, and other important biomolecules to be monitored in a physiologically relevant environment rather than in an in vitro setting. This demanding application requires not only the aforementioned characteristics of click chemistry but, additionally, that the reactions are bioorthogonal – that is, non‐interacting with biological functionality while proceeding under physiological conditions – and that the reagents are non‐toxic. Of the many extant click reactions, only a select few possess this unique combination of attributes, notably the Staudinger ligation of azides and triarylphosphines and [3+2] dipolar cycloadditions of azides with strained alkynes. This minireview describes the characteristics of bioorthogonal click reactions as well as recent applications toward labeling biomolecules in cells and living organisms.
Salmonella Pathogenesis and Processing of Secreted Effectors by Caspase-3 (2010)

The enteric pathogen Salmonella enterica serovar Typhimurium causes food poisoning resulting in gastroenteritis. The S. Typhimurium effector Salmonella invasion protein A (SipA) promotes gastroenteritis by functional motifs that trigger either mechanisms of inflammation or bacterial entry. During infection of intestinal epithelial cells, SipA was found to be responsible for the early activation of caspase-3, an enzyme that is required for SipA cleavage at a specific recognition motif that divided the protein into its two functional domains and activated SipA in a manner necessary for pathogenicity. Other caspase-3 cleavage sites identified in S. Typhimurium appeared to be restricted to secreted effector proteins, which indicates that this may be a general strategy used by this pathogen for processing of its secreted effectors.
Type VII collagen is a major structural component of anchoring fibrils. (1986)

Anchoring fibrils are specialized fibrous structures found in the subbasal lamina underlying epithelia of several external tissues. Based upon their sensitivity to collagenase and the similarity in banding pattern to artificially created segment-long spacing crystallites (SLS) of collagens, several authors have suggested that anchoring fibrils are lateral aggregates of collagenous macromolecules. We recently reported the similarity in length and banding pattern of anchoring fibrils to type VII collagen SLS crystallites. We now report the construction and characterization of a murine monoclonal antibody specific for type VII collagen. The epitope identified by this antibody has been mapped to the carboxyl terminus of the major helical domain of this molecule. The presence of type VII collagen as detected by indirect immunofluorescence in a variety of tissues corresponds exactly with ultrastructural observations of anchoring fibrils. Ultrastructural immunolocalization of type VII collagen using a 5-nm colloidal gold-conjugated second antibody demonstrates metal deposition upon anchoring fibrils at both ends of these structures, as predicted by the location of the epitope on type VII collagen. Type VII collagen is synthesized by primary cultures of amniotic epithelial cells. It is also produced by KB cells (an epidermoid carcinoma cell line) and WISH (a transformed amniotic cell line).
Fracture mechanisms in carbon fibres derived from pan in the temperature range 1000-2800 degrees C (1975)

Structural parameters derived from absolute intensity small-angle X-ray scattering experiments have been combined with strength and failure strain data for pan carbon fibres in an elastic/plastic theory of fracture. Good quantitative agreement with the theory is obtained throughout the heat treatment temperature range of 1000-2800 degrees C. The application of a modified griffiths theory, including a plastic work term, gives more qualitative agreement. The influence of the microstructure, in the form of crystalline ribbons, elongated micropores, and non-organized carbon and nitrogen, is discussed in relation to the fibre failure strain. The influence of grosser internal flaws on mechanical properties is also considered.
Absorption of beta-carotene and other carotenoids in humans and animal models. (1996)

Humans appear to absorb various carotenoids in a relatively non-specific fashion, but absorption kinetics and plasma transport seem to differ among carotenoids, possibly because of differences in polarity. Absorbed beta-carotene for the most part is converted, mainly into retinyl esters, but several details with respect to the cleavage reaction remain to be elucidated. Although interactions among carotenoids do exist, their importance and the mechanisms involved are still unclear. No animal model reflects the human situation for beta-carotene metabolism entirely. Thus, for every research question, the optimal model needs to be selected. Methods available for studying beta-carotene metabolism in man are limited. The most promising methods are the single dose-response in chylomicrons, and plasma responses after dosing with stable isotopes.
Characterization of human loricrin. Structure and function of a new class of epidermal cell envelope proteins. (1991)

We have isolated and characterized a full-length cDNA clone encoding human loricrin. Curiously, this protein displays major differences from the recently described mouse loricrin (Mehrel, T., Hohl, D., Nakazawa, H., Rothnagel, J.A., Longley, M.A., Bundman, D., Cheng, C.K., Lichti, U., Bisher, M.E., Steven, A. C., Steinert, P.M., Yuspa, S.H., and Roop, D.R. (1990) Cell 61, 1103-1112). Although both proteins are glycine-serine-cysteine-rich, the sequences have not been conserved. However, analysis of the sequences reveals a common motif of quasi-peptide repeats of an aliphatic or aromatic amino acid residue followed by several glycine and/or serine and cysteine residues. These sequences are interspersed and flanked by short glutamine- or glutamine/lysine-rich peptides. Thus loricrins consist of a family of cell envelope proteins of highly variable sequences that nevertheless retain common structural elements. We show that unlike all other putative protein components of the cell envelope, loricrins are highly insoluble, due at least in part to cross-linking by disulfide bonds. Furthermore, we have isolated four peptides from purified human cell envelopes that contain recognizable loricrin sequences and which are cross-linked by the N epsilon-(gamma-glutamyl)lysine isodipeptide bond. The presence of such bonds thus affords an explanation for the extraordinary insolubility of loricrin by cross-linking to the cell envelope and can also explain the low steady-state levels of monomeric loricrin in cytoskeletal extracts of epidermis. This study represents the first report of this isodipeptide cross-link in a protein component of the cornified cell envelope. We propose a model for the structure of loricrin in which (i) the unusual glycine-serine-rich sequences adopt a flexible loop conformation, indexed on the recurrent aliphatic residues; (ii) inter- or intramolecular isodipeptide and disulfide cross-links induce or stabilize folding of loricrin so as to form a more compact rosette-like structure; and (iii) the presence of the flexible glycine-rich loops necessarily will impact a flexible character to the cell envelope and entire epithelium.
Regulation of T Cell Responsiveness Against Mycobacterial Antigens by HLA Class 2 Immune Response Genes (1989)

Helper T lymphocytes can only recognize mycobacterial antigens when they are presented by HLA class 2 molecules. Thus, these molecules may play an important role in the regulation of the immune response against mycobacteria. In this paper it is demonstrated that the T cells from individuals with different HLA class 2 molecules react to different mycobacterial antigens. These data indicate that HLA class 2 molecules are the products of immune response (Ir) genes for mycobacteria. Such genetically controlled differences in antimycobacterial T cell reactivity may explain the association of certain HLA class 2 alleles with a different course of mycobacterial infections and may have implications for vaccine development.
Mass spectrometry meets chip technology: A new proteomic tool in cancer research? (2001)

DNA chip technologies are the most exiting genomic tools, which were developed within the last few years. It is, however, evident that knowledge of the gene sequence or the quantity of gene expression is not sufficient to predict the biological nature and function of a protein. This can be particularly important in cancer research where post-translational modifications of a protein can specifically contribute to the disease. To address this problem, several proteomic tools have been developed. Currently the most widely used proteomic tool is two-dimensional protein gel electrophoresis (2-DE), which can display protein expression patterns to a high degree of resolution. As an alternative to 2-DE, a preliminary study using a new technique was employed to generate protein expression patterns from whole tissue extracts. Surface-enhanced laser desorption/ionization (SELDI) allows the retention of proteins on a solid-phase chromatographic surface (ProteinChip Array) with direct detection of retained proteins by time of flight-mass spectrometry (TOF-MS). Using this system, we analyzed eight cases of renal cell carcinoma (RCC) including normal, peripheral and central tumor tissue as well as four microdissected cases of cervical intraepithelial neoplasia (CIN) and three microdissected cases of cervix uteri carcinoma. Differentially expressed proteins were found by comparing the protein expression patterns generated using SELDI-based TOF-MS of tumor tissue with normal and neoplastic tissue, respectively. By applying this fast and powerful ProteinChip array technology it becomes possible to investigate complex changes at the protein level in cancer associated with tumor development and progression.
The effect of lipocortin 1 on neutrophil deformability (1996)

Lipocortn 1 (Lc1) is an anti-inflammatory protein, which, given systemically, inhibits polymorphonuclear neutrophil (PMN) emigration from the circulation to sites of inflammation; delivery of Lc1 to the inflamed site is ineffective. We have examined the effect of Lc1 on changes in PMN deformability, and observed a consistent improvement in the deformability of unstimulated PMN; N-formyl-methionyl-leucyl-phenylalanine (fMLP)-activated cell deformability was unaltered. A Lc1-induced increase in cell deformability may reduce PMN sequestration so contributing to the anti-migratory effects of systemic Lc1 previously demonstrated in vivo.
Phenotype and Genotype of Pancreatic Cancer Cell Lines (2010)

The dismal prognosis of pancreatic adenocarcinoma is due in part to a lack of molecular information regarding disease development. Established cell lines remain a useful tool for investigating these molecular events. Here we present a review of available information on commonly used pancreatic adenocarcinoma cell lines as a resource to help investigators select the cell lines most appropriate for their particular research needs. Information on clinical history; in vitro and in vivo growth characteristics; phenotypic characteristics, such as adhesion, invasion, migration, and tumorigenesis; and genotypic status of commonly altered genes (KRAS, p53, p16, and SMAD4) was evaluated. Identification of both consensus and discrepant information in the literature suggests careful evaluation before selection of cell lines and attention be given to cell line authentication.
Fruit juice consumption by infants and children: a review. (1996)

The pattern of fruit juice consumption has changed over time. Fifty years ago, orange juice was the major juice produced and it was consumed primarily to prevent scurvy. Now, apple juice is the juice of choice for the under 5 age group. While fruit juice is a healthy, low-fat, nutritious beverage, there have been some health concerns regarding juice consumption. Nursing bottle caries have long been recognized as a consequence of feeding juice in bottles, using the bottle as a pacifier, and prolonged bottle feeding. Non-specific chronic diarrhea or "toddler's" diarrhea has been associated with juice consumption, especially juices high in sorbitol and those with a high fructose to glucose ratio. This relates to carbohydrate malabsorption, which varies by the type, concentration, and mixture of sugars present in different fruit juices. Fruit juice consumption by preschoolers has recently increased from 3.2 to about 5.5 fl oz/day. Consumption of fruit juice helps fulfill the recommendation to eat more fruits and vegetables, with fruit juice accounting for 50% of all fruit servings consumed by children, aged 2 through 18 years, and 1/3 of all fruits and vegetables consumed by preschoolers. Concomitant with the increase in fruit juice consumption has been a decline in milk intake. This is concerning as milk is the major source of calcium in the diet, and at present, only 50% of children, aged 1 through 5 years, meet the RDA for calcium. Studies of newborn infants and preschool-aged children have demonstrated a preference for sweet-tasting foods and beverages. Thus, it is not surprising that some children, if given the opportunity, might consume more fruit juice than is considered optimal. Eleven percent of healthy preschoolers consumed > or = 12 fl oz/day of fruit juice, which is considered excessive. Excess fruit juice consumption has been reported as a contributing factor in some children with nonorganic failure to thrive and in some children with decreased stature. In other children, excessive fruit juice consumption has been associated with an increased caloric intake and obesity. This paper reviews the role of fruit juice in the diets of infants and children and outlines areas for future research. Recommendations regarding fruit juice consumption based on current data are also given.
The Path Integral Formulation of Gravitational Thermodynamics (1998)

The first objective of this article is to show that the black hole partition function can be placed on a firm logical foundation by enclosing the black hole in a spatially finite "box" or boundary. The presence of the box has the effect of stabilizing the black hole and yields a system with a positive heat capacity. The second objective of this article is to explore the origin of black hole entropy. This is accomplished through the construction of a path integral expression for the density matrix for the gravitational field, and through an analysis of the connection between the density matrix and the black hole density of states. Our results suggest that black hole entropy can be associated with an absence of certain "inner boundary information" for the system. (Based on the talk presented by J.D. Brown at the conference "The Black Hole 25 Years After", Santiago, Chile, January 1994.)