gebhart/patrepeval huggingface dataset:
Structural Characterization and Biological Functions of Fibroblast Growth Factor (1987)

BASIC AND acidic fibroblast growth factors (FGFs) are closely related molecules that show a similar range of biological activities. They differ, however, in some of their physical and chemical properties and in their tissue distribution (1). Basic FGF [bFGF isoelectric point (pi) 9.6] was first identified by its ability to cause the proliferation and phenotypic transformation of BALB/c 3T3 fibroblasts (2, 3). Acidic FGF (aFGF, pi 5.6) was first identified by its ability to cause proliferation and delayed differentiation of myoblasts (4); it was later rediscovered on the basis of its ability to stimulate endothelial cell proliferation (5, 6). As expected from their structural relationship, both FGF and aFGF interact with the same receptor (7), thereby having similar, if not identical, properties. In contrast to aFGF, which has a cellular distribution more restricted than bFGF, many different cells synthesize bFGF, and essentially all have a specific high affinity receptor for this peptide. bFGF is thus a fundamental regulatory molecule, acting by both autocrine and paracrine mechanisms. Recent studies indicate an important role for both bFGF and aFGF in cells of vascular, nervous, and connective tissue. bFGF and aFGF are multifunctional, since they can either stimulate proliferation and induce or delay differentiation (8). They stimulate other critical processes in cell function as well. As is true for most peptide growth factors, the basic molecular mechanism of action of FGFs is at present unknown. Nevertheless, so many new and varied functions have now been described for bFGF and could be extrapolated to aFGF that, at present, one must consider these two closely related peptides to be general mediators of regulation in the cell, and one of special importance for positive control of cell growth and differentiation.
Collagen-induced arthritis--characteristics of the animal model and implications for the treatment of autoimmune disease. (1991)

Collagen-induced arthritis (CIA) is a chronic polyarthritis induced in mice and rats by immunization with homologous or heterologous type II collagen (CII). In this study, we report on a variety of experiments designed to elucidate the characteristics of CIA and its potential application in the treatment of human disease. The notable results were as follows: Both mouse anti-human-CII monoclonal antibody and a mouse T cell clone reactive to human CII were able to provoke arthritis when i.v. injected into naive mice. When injected together, a synergistic enhancement of the incidence and severity of passive arthritis was seen. However, inoculation with irradiated T cells reactive to human CII could suppress the development of active CIA. Given these results and the fact that CIA closely resembles rheumatoid arthritis both clinically and histologically, we suggest that the CIA animal model provides a good tool for studying the potential of T cell vaccination as a means of treating or preventing human autoimmune diseases.
Low temperature bonding of heterogeneous materials using Al2O3 as an intermediate layer (2018)

Direct wafer bonding is a key enabling technology for many current and emerging photonic devices. Most prior work on direct wafer bonding has, however, focused on the Si platform for fabrication of silicon-on-insulator (SOI) and micro-electromechanical systems (MEMS). As a result, a universal bonding solution for heterogeneous material systems has not yet been developed. This has been a roadblock in the realization of novel devices which need the integration of new semiconductor platforms such as III-V on Si, Ge on Sapphire, LiNbO<sub>3</sub> on GaAs etc. The large thermal expansion coefficient mismatch in the hetero-material systems limits the annealing to low temperatures to avoid stressed films. This work explores the use of Al<sub>2</sub>O<sub>3</sub> as an intermediate layer for bonding heterogeneous materials. The key to achieve a stronger bond is to maximize the hydroxyl group density of the bonding interfaces. The use of Al<sub>2</sub>O<sub>3</sub> helps achieve that, since it has a high hydroxyl group density (around 18 OH/nm<sup>2</sup> at RT) which is approximately 4 times that of a Si surface. This work optimizes the bonding process using Al<sub>2</sub>O<sub>3</sub> by studying the contribution of Al<sub>2</sub>O<sub>3</sub> deposition parameters. An optimized process is presented and applied to bond GaAs on Sapphire and InP on SiO<sub>2</sub>/Si.
Milk Products, Insulin Resistance Syndrome and Type 2 Diabetes (2009)

A growing body of evidence suggests an inverse relationship between calcium and vitamin D status and dairy food intake and the development of the insulin resistance syndrome (IRS) and type 2 diabetes mellitus (t2DM). Observational studies show a consistent inverse association between dairy intake and the prevalence of IRS and t2DM. In a systematic review of the observational evidence, the odds for developing the IRS was 0.71 (95% CI, 0,57-0.89) for the highest dairy intake (3-4 servings/d) vs. the lowest intake (0.9-1.7 servings/d). Few interventional studies have been conducted to evaluate the effects of dairy food intake on the management of prevention of IRS or t2DM. Intervention studies that have examined the independent effects of dairy intake on specific metabolic components of the IRS including blood pressure and obesigenic parameters have shown favorable effects that support the observational findings albeit the results have been less consistent. Many metabolic and dietary factors appear to influence the degree to which dairy affects IRS metabolic parameters including calcium and vitamin D intake status, BMI, ethnicity and age. Overall, the intake of low-fat dairy products is a feature of a healthy dietary pattern which has been shown to contribute to a significant extent to the prevention of IRS.
Enhancement or inhibition of HIV-1 replication by intracellular expression of sense or antisense RNA targeted at different intermediates of reverse transcription (1997)

Plus-strand strong-stop DNA as an intermediate in the early process of viral reverse transcription can be explored as an additional target for anti-HIV gene therapy.
Electrostatic actuation of surface/bulk micromachined single-crystal silicon microresonators (2003)

In fabricating microelectromechanical systems (MEMS), bulk micromachining using [100] and [110] single crystal silicon and surface micromachining using polycrystalline silicon are used. However, both micromachining methods have drawbacks, and micromachining actuating or sensing MEMS using single crystal silicon has been an active research topic in resent years. This paper presents electrostatic actuation of a resonator fabricated by the SBM (surface/bulk micromachining) process. The SBM process allows fabricating released structures in single crystal silicon. To fabricate electrodes and to electrically isolate them, a junction isolation method using reverse-biased diodes is developed. The breakdown voltage of this isolation method is measured to be larger than 150 volts. A SBM processed microresonator is actuated at 36 kHz. A displacement of several /spl mu/m is achieved in atmosphere with a 20 volts peak-to-peak supply.
Graft copolymers from thiolated starch and vinyl monomers (1977)

Abstract Thiol starches of degree of substitution (D.S.) 0.005–0.162 were prepared by displacing starch tosyloxy groups with xanthate and treating the resulting xanthate esters with either sodium hydroxide or sodium borohydride. Acrylonitrile, styrene, acrylamide, acrylic acid, and dimethylaminoethyl methacrylate were grafted onto the thiol starches with hydrogen peroxide as initiator. The peroxide caused both grafting of monomer and coupling of thiol groups to disulfide. Treating graft copolymers with sodium borohydride regenerated thiol groups from disulfide groups so that the grafting sequence could be repeated. By regenerating the thiol groups and repeating the grafting steps, high add‐on and high‐frequency starch graft copolymers were prepared. During four grafting sequences, acrylonitrile reacted with D.S. 0.162 thiol starch to give graft copolymers that contained increasing amounts of polyacrylonitrile (46.0–66.5%). Grafting frequency increased from 183 to 71 anhydroglucose units (AGU)/graft, while molecular weights of the grafted chains ranged between 20,000 and 25,200. The final product was hydrolyzed with potassium hydroxide solution to a copolymer, which absorbed up to 400 ml water per gram. Styrene was grafted onto thiol starch to give products containing 34.4–69.5% polystyrene with 986–3520 AGU/graft and having molecular weights of grafted chains between 276,000 and 364,000. Graft copolymers containing 48.9% polyacrylamide, 21.2% poly(acrylic acid), and 77.7% poly(2‐methacryloyloxyethyldimethylammonium acetate) were obtained under similar conditions.
A homozygous deletion within the carbonic anhydrase-like domain of the Ptprg gene in murine L-cells. (1993)

Protein tyrosine phosphatases, on purely theoretical grounds, were suggested as possible tumor suppressor genes, and receptor protein tyrosine phosphatase gamma (PTPRG) has been proposed, on the basis of its location at human chromosome region 3p14.2, specifically as a tumor suppressor gene for renal cell carcinoma. We have isolated murine genomic and complementary DNA clones for analysis and mapping of the murine Ptprg locus; interspecific backcross analysis showed that the Ptprg locus maps to the centromeric region of mouse chromosome 14. We also observed a homozygous, intragenic deletion in the Ptprg gene in all clonal derivatives of the original L-cell strain, a methylcholanthrene-treated mouse connective tissue cell line which produces sarcomas in syngeneic mice. The deletion begins in the second intron of the carbonic anhydrase-like domain of the Ptprg gene and ends in the fourth intron of the carbonic anhydrase-like domain. At the genomic level, perhaps several hundred kilobases of DNA are deleted; at the complementary DNA level the 400 base pairs comprising exons 2, 3, and 4 of the carbonic anhydrase-like domain are deleted. By reverse transcription polymerase chain reaction, an amplified fragment is produced from L-cell mRNA which is 400 base pairs shorter than the wild type gene product, suggesting that the deleted gene is transcribed and may produce a protein product. Thus, mouse L-cells have lost one Ptprg allele and sustained an intragenic deletion in the other; such allele loss and mutation frequently occur at tumor suppressor gene loci.
Gaussian Mixture Optimization Based on Efficient Cross-Validation (2010)

A Gaussian mixture optimization method is developed by using the cross-validation (CV) likelihood as an objective function instead of the conventional training set likelihood. The optimization is based on reducing the number of mixture components by selecting and merging pairs of Gaussians step by step according to the objective function so as to remove redundant components and improve the generality of the model. The CV likelihood is more effective for avoiding over-fitting than is the conventional likelihood, and it provides a termination criterion that does not rely on empirical thresholds. While the idea is simple, one problem is its infeasible computational cost. To make such optimization practical, an efficient evaluation algorithm using sufficient statistics is proposed. In addition, aggregated CV (AgCV) is developed to further improve the generalization performance of CV. Large-vocabulary speech recognition experiments on oral presentations show that the proposed methods improve speech recognition performance with automatically determined model complexity. The AgCV-based optimization is computationally more expensive than the CV-based method but gives better recognition performance.
Small carcinoma of the pancreas is curable: New computed tomography finding, pathological study and postoperative results from a single institute (2005)

The presence of s-PC qualifies as early PC and has a good prognosis. The CT black + white sign will be useful in the diagnosis of s-PC accompanying pancreatitis.
Histones induce rapid and profound thrombocytopenia in mice (2011)

Histones are released from dying cells and contribute to antimicrobial defense during infection. However, extracellular histones are a double-edged sword because they also damage host tissue and may cause death. We studied the interactions of histones with platelets. Histones bound to platelets, induced calcium influx, and recruited plasma adhesion proteins such as fibrinogen to induce platelet aggregation. Hereby fibrinogen cross-linked histone-bearing platelets and triggered microaggregation. Fibrinogen interactions with αIIbβ3 integrins were not required for this process but were necessary for the formation of large platelet aggregates. Infused histones associated with platelets in vivo and caused a profound thrombocytopenia within minutes after administration. Mice lacking platelets or αIIbβ3 integrins were protected from histone-induced death but not from histone-induced tissue damage. Heparin, at high concentrations, prevented histone interactions with platelets and protected mice from histone-induced thrombocytopenia, tissue damage, and death. Heparin and histones are evolutionary maintained. Histones may combine microbicidal with prothrombotic properties to fight invading microbes and maintain hemostasis after injury. Heparin may provide an innate counter mechanism to neutralize histones and diminish collateral tissue damage.
Autonomic neural regulation of immunity (2005)

The 'cytokine theory of disease' states that an overproduction of cytokines can cause the clinical manifestations of disease. Much effort has been expended to determine how cytokines are regulated in normal health. Transcriptional, translational and other molecular control mechanisms protect the host from excessive cytokine production. A recent discovery revealed an unexpected pathway that inhibits macrophage cytokine production. The inflammatory reflex is a physiological pathway in which the autonomic nervous system detects the presence of inflammatory stimuli and modulates cytokine production. Afferent signals to the brain are transmitted via the vagus nerve, which activates a reflex response that culminates in efferent vagus nerve signalling. Termed the 'cholinergic anti-inflammatory pathway', efferent activity in the vagus nerve releases acetylcholine (ACh) in the vicinity of macrophages within the reticuloendothelial system. ACh can interact specifically with macrophage alpha7 subunits of nicotinic ACh receptors, leading to cellular deactivation and inhibition of cytokine release. This 'hard-wired' connection between the nervous and immune systems can be harnessed therapeutically in animal models of inflammatory disease, via direct electrical stimulation of the vagus nerve, or through the use of cholinergic agonists that specifically activate the macrophage alpha7 subunit of the ACh receptor. Autonomic dysfunction has been associated with human inflammatory diseases including rheumatoid arthritis, diabetes and sepsis; whether this dysfunction results from the inflammatory component of these diseases, or is actually an underlying cause, is now less clear. The description of the cholinergic anti-inflammatory now brings to the fore several new therapeutic strategies for inflammatory disease, and suggests that many of these diseases may actually be diseases of autonomic dysfunction.
Indirect hemagglutination test for human antibody to typhus and spotted fever group rickettsiae (1975)

An indirect hemagglutination (IHA) test is described that uses glutaraldehyde-stabilized erythrocytes treated with a rickettsial erythrocyte-sensitizing substance obtained from Rickettsia typhi or Rickettsia rickettsii. The serological reagent was stable for at least 3 months at room temperature and 6 months at 4 C. It exhibited group specificity and no group cross-reactivity. At a minimum dilution of 1:40, acute and early convalescent epidemic and murine typhus antisera showed 86% positive reactors, whereas similar spotted fever antisera had 74% positive reactors. In comparison with the indirect fluorescent antibody test, the IHA procedure gave lower titers but showed comparable detection of seroconversion with most paired sera. The IHA test demonstrated significantly higher titers than the complement fixation test and was more sensitive than either the complement fixation or Weil-Felix test in identifying seroconversion. No agglutination was observed when sensitized erythrocytes were tested with rodent sera known to contain rickettsial antibodies.
Correction of Iron Deficiency with an Iron-Fortified Fluid Whole Cowʼs Milk in Children (1997)

The use of IFFWCM alone could be an effective, relatively inexpensive, and well-tolerated treatment of iron deficiency in children.
A review of existing strategies for designing long-acting parenteral formulations: Focus on underlying mechanisms, and future perspectives (2021)

The need for long-term treatments of chronic diseases has motivated the widespread development of long-acting parenteral formulations (LAPFs) with the aim of improving drug pharmacokinetics and therapeutic efficacy. LAPFs have been proven to extend the half-life of therapeutics, as well as to improve patient adherence; consequently, this enhances the outcome of therapy positively. Over past decades, considerable progress has been made in designing effective LAPFs in both preclinical and clinical settings. Here we review the latest advances of LAPFs in preclinical and clinical stages, focusing on the strategies and underlying mechanisms for achieving long acting. Existing strategies are classified into manipulation of <i>in vivo</i> clearance and manipulation of drug release from delivery systems, respectively. And the current challenges and prospects of each strategy are discussed. In addition, we also briefly discuss the design principles of LAPFs and provide future perspectives of the rational design of more effective LAPFs for their further clinical translation.
Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5′ UTR as in the 3′ UTR (2007)

In animals, microRNAs (miRNAs) bind to the 3' UTRs of their target mRNAs and interfere with translation, although the exact mechanism of inhibition of protein synthesis remains unclear. Functional miRNA-binding sites in the coding regions or 5' UTRs of endogenous mRNAs have not been identified. We studied the effect of introducing miRNA target sites into the 5' UTR of luciferase reporter mRNAs containing internal ribosome entry sites (IRESs), so that potential steric hindrance by a microribonucleoprotein complex would not interfere with the initiation of translation. In human HeLa cells, which express endogenous let-7a miRNA, the translational efficiency of these IRES-containing reporters with 5' let-7 complementary sites from the Caenorhabditis elegans lin-41 3' UTR was repressed. Similarly, the IRES-containing reporters were translationally repressed when human Ago2 was tethered to either the 5' or 3' UTR. Interestingly, the method of DNA transfection affected our ability to observe miRNA-mediated repression. Our results suggest that association with any position on a target mRNA is mechanistically sufficient for a microribonucleoprotein to exert repression of translation at some step downstream of initiation.
Melanocyte lineage-specific antigen gp100 is recognized by melanoma-derived tumor-infiltrating lymphocytes. (1994)

We recently isolated a cDNA clone that encodes the melanocyte lineage-specific antigen glycoprotein (gp)100. Antibodies directed against gp100 are an important tool in the diagnosis of human melanoma. Since the gp100 antigen is highly expressed in melanocytic cells, we investigated whether this antigen might serve as a target for antimelanoma cytotoxic T lymphocytes (CTL). Here, we demonstrate that cytotoxic tumor-infiltrating lymphocytes (TIL) derived from a melanoma patient (TIL 1200) are directed against gp100. HLA-A2.1+ melanoma cells are lysed by TIL from this patient. In addition, murine double transfectants, expressing both HLA-A2.1 and gp100, are lysed by TIL 1200, whereas transfectants expressing only HLA-A2.1 are not susceptible to lysis. Furthermore, the HLA-A2.1+ melanoma cell line BLM, which lacks gp100 expression and is resistant to lysis, becomes susceptible after transfection of gp100 cDNA. Finally, HLA-A2.1+ normal melanocytes are lysed by TIL 1200. These data demonstrate that the melanocyte differentiation antigen gp100 can be recognized in the context of HLA-A2.1 by CTL from a melanoma patient. Gp100 may therefore constitute a useful target for specific immunotherapy against melanoma, provided that no unacceptable cytotoxicity towards normal tissue is observed.
Cytokine release syndrome with novel therapeutics for acute lymphoblastic leukemia (2016)

T-cell-engaging immunotherapies are exciting new approaches to treat patients with acute lymphoblastic leukemia (ALL). These unique agents, which include blinatumomab, a CD3/CD19 bispecific antibody, and chimeric antigen receptor (CAR) modified T cells targeted to CD19 have shown unprecedented remission rates in the relapsed, refractory ALL setting. Cytokine release syndrome (CRS), resulting from the high magnitude of immune activation by these therapies, is the most significant treatment-related toxicity. CRS manifests with fever and malaise and can progress to life-threatening capillary leak with hypoxia and hypotension. The clinical signs of CRS correlate with T-cell activation and high levels of cytokines, including interleukin 6 (IL-6). Tocilizumab, an anti-IL-6 receptor antagonist, is usually effective in the management of severe CRS induced by CAR T cells and has been adopted by most clinical trial programs. With blinatumomab administration, the goal has been to prevent CRS with corticosteroid premedication, disease cytoreduction, and dose adjustments. Collaborative efforts are underway to harmonize the definition and grading system of CRS to allow for better interpretation of toxicities across trials and allow for informed management algorithms.
The Stress Response Factors Yap6, Cin5, Phd1, and Skn7 Direct Targeting of the Conserved Co-Repressor Tup1-Ssn6 in S. cerevisiae (2011)

Maintaining the proper expression of the transcriptome during development or in response to a changing environment requires a delicate balance between transcriptional regulators with activating and repressing functions. The budding yeast transcriptional co-repressor Tup1-Ssn6 is a model for studying similar repressor complexes in multicellular eukaryotes. Tup1-Ssn6 does not bind DNA directly, but is directed to individual promoters by one or more DNA-binding proteins, referred to as Tup1 recruiters. This functional architecture allows the Tup1-Ssn6 to modulate the expression of genes required for the response to a variety of cellular stresses. To understand the targeting or the Tup1-Ssn6 complex, we determined the genomic distribution of Tup1 and Ssn6 by ChIP-chip. We found that most loci bound by Tup1-Ssn6 could not be explained by co-occupancy with a known recruiting cofactor and that deletion of individual known Tup1 recruiters did not significantly alter the Tup1 binding profile. These observations suggest that new Tup1 recruiting proteins remain to be discovered and that Tup1 recruitment typically depends on multiple recruiting cofactors. To identify new recruiting proteins, we computationally screened for factors with binding patterns similar to the observed Tup1-Ssn6 genomic distribution. Four top candidates, Cin5, Skn7, Phd1, and Yap6, all known to be associated with stress response gene regulation, were experimentally confirmed to physically interact with Tup1 and/or Ssn6. Incorporating these new recruitment cofactors with previously characterized cofactors now explains the majority of Tup1 targeting across the genome, and expands our understanding of the mechanism by which Tup1-Ssn6 is directed to its targets.