gebhart/patrepeval huggingface dataset:
A Versatile Route to Functionalized Dilactones as Monomers for the Synthesis of Poly(α‐hydroxy) Acids (2003)

Abstract A synthetic pathway to functionalized six‐membered dilactones structurally analogous to lactide is described. Through the use of orthogonal protecting groups, the synthesis of functionalized dilactones was performed in a straightforward way by cyanuric chloride‐mediated cyclization of the corresponding linear α‐hydroxy acid dimers. The synthesis of three different dilactones − methylglycolide, benzyloxymethylglycolide, and 2‐benzyloxymethyl‐5‐methylglycolide − by the same procedure demonstrated the versatility of this route. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)
A Phase Diagram for the Binary Blends of Nearly Symmetric Diblock Copolymers. 1. Parameter Space of Molecular Weight Ratio and Blend Composition (2001)

A phase diagram as a function of molecular weight ratio and blend composition was constructed for the binary blends of nearly symmetric polystyrene-block-polyisoprene (PS−PI) copolymers. In this study we prepared four series of binary blends, and every blend consists of a copolymer, hereafter designated as α, whose number-average molecular weight (Mn) and volume fraction of PS-block (fPS) are 1.0 × 105 and 0.47, respectively. Four PS−PI copolymers (hereafter designated β), each of which is blended with α, have their Mn and fPS in the range 1.2 × 104−2.1 × 104 and 0.40−0.49, respectively, and therefore the molecular weight ratio of α to β, hereafter designated as r, ranges between 4.8 and 8.3. All the blends showed partial miscibility of the constituent copolymers; that is, at a certain blend composition the macrophase separation between α and β occurred. However, the range of blend compositions where the constituent copolymers phase-separate became small as r decreased. As for the two blend series where r = 4.8 and 6.9, the PS cylindrical morphology was observed over wide blend compositions, although the constituent copolymers have nearly symmetric compositions and by themselves are self-assembled into lamellar morphology.
Didehydroamino Acids (DDAA) and Didehydropeptides (DDP) (1988)

Syntheses, reactions, and spectroscopic investigations in the field of didehydroamino acids published between 1982 and October 1987 are reviewed. A survey of natural compounds containing this subunit is also given. 1. Introduction 2. Syntheses of Didehydroamino Acids and Didehydropeptides 2.1. Syntheses via Elimination Reactions 2.2. Syntheses via C-C Bond Formation 3. Syntheses of Didehydropeptides by Amide Formation 3.1. Merrifield Peptide Synthesis 4. Isolation, Structure Elucidation, and Syntheses of Natural Products Containing Didehydroamino Acids 4.1. Syntheses of Peptide Hormones Containing Didehydroamino Acids 4.2. Didehydropeptides from Bacteria 4.3. Didehydropeptides from Fungi 4.4. Didehydropeptides from Marine Organisms 5. Reactions of Didehydroamino Acids 5.1. Reactions at the α,β-Double Bond 5.2. Reactions at the Carboxyl Function 5.3. Reactions at Nitrogen 6. Spectroscopic and Physical-Chemical Investigations of Didehydroamino Acids and Didehydropeptides
New Insights Concerning the Glucose-dependent Insulin Secretagogue Action of Glucagon-like Peptide-1 in Pancreatic β-Cells (2004)

The GLP-1 receptor is a Class B heptahelical G-protein-coupled receptor that stimulates cAMP production in pancreatic beta-cells. GLP-1 utilizes this receptor to activate two distinct classes of cAMP-binding proteins: protein kinase A (PKA) and the Epac family of cAMP-regulated guanine nucleotide exchange factors (cAMPGEFs). Actions of GLP-1 mediated by PKA and Epac include the recruitment and priming of secretory granules, thereby increasing the number of granules available for Ca(2+)-dependent exocytosis. Simultaneously, GLP-1 promotes Ca(2+) influx and mobilizes an intracellular source of Ca(2+). GLP-1 sensitizes intracellular Ca(2+) release channels (ryanodine and IP (3) receptors) to stimulatory effects of Ca(2+), thereby promoting Ca(2+)-induced Ca(2+) release (CICR). In the model presented here, CICR activates mitochondrial dehydrogenases, thereby upregulating glucose-dependent production of ATP. The resultant increase in cytosolic [ATP]/[ADP] concentration ratio leads to closure of ATP-sensitive K(+) channels (K-ATP), membrane depolarization, and influx of Ca(2+) through voltage-dependent Ca(2+) channels (VDCCs). Ca(2+) influx stimulates exocytosis of secretory granules by promoting their fusion with the plasma membrane. Under conditions where Ca(2+) release channels are sensitized by GLP-1, Ca(2+) influx also stimulates CICR, generating an additional round of ATP production and K-ATP channel closure. In the absence of glucose, no "fuel" is available to support ATP production, and GLP-1 fails to stimulate insulin secretion. This new "feed-forward" hypothesis of beta-cell stimulus-secretion coupling may provide a mechanistic explanation as to how GLP-1 exerts a beneficial blood glucose-lowering effect in type 2 diabetic subjects.
STUDIES ON DISPERSED PANCREATIC EXOCRINE CELLS (1974)

The functional characteristics of separated guinea pig pancreatic exocrine cells have been examined following dissociation of the gland by a procedure described in the previous paper (J. Cell Biol. 1974. 63:1037). The ability of isolated cells to incorporate labeled amino acids into secretory proteins was assessed biochemically and by quantitative electron microscope autoradiography. Incorporation remained linear for up to 4-h incubation at levels equivalent to those of pancreatic slices; over 95% of the exocrine cells in the population were viable, and all appeared to be equally active in incorporating amino acids. The capacity of separated cells to transport, concentrate, and store exportable proteins was monitored by electron microscope autoradiography on populations pulse labeled with [(3)H]leucine and chase incubated for 4 h. The same overall pathway previously mapped in pancreatic slices was followed by secretory proteins in separated cells although in quantitative studies a defect was noted in the rate of conversion of condensing vacuoles to zymogen granules. Secretogogue responsiveness was assessed by monitoring discharge of labeled secretory proteins or of amylase in response to carbamylcholine and caerulein to the medium. While the separated cells released secretory proteins linearly for up to 4 h in response to both secretogogues, the net release was approximately 50% less than previously noted for pancreatic slices and required a ten times higher concentration of stimulant. The defect may represent alteration in receptors due to the protease used for dissociation. Our data indicate, however, that separated exocrine cells retain their ability to process secretory proteins stepwise and vectorially which is consistent with preservation of structural polarity.
DNA Demethylating Agents and Chromatin-Remodelling Drugs: Which, How and Why? (2003)

DNA hypermethylation at the CpG dinucleotides clustered in "islands" in the promoter regions of genes causes transcriptional repression through the remodelling of chromatin. Aberrant methylation patterns of tumor suppressor genes and their subsequent silencing constitute a common feature of many cancers. Thus, the search for drugs that interfere in methylation-mediated gene repression has become one of the major goals in the design of cancer therapies. The major actors in the mammalian methylation system are DNA-methyltransferases (DNMTs), and methyl-CpG-binding proteins (MBDs), which recognize methylated cytosine and recruit repressor complexes, including histone deacetylases (HDACs). In this context, two major groups of drugs can be distinguished. The first one is constituted by substances that inhibit the action of DNMTs, either competing with cytosine or with S-adenosylmethionine (SAM, AdoMet) or acting over the DNMTs themselves. The second group involves compounds that inhibit subunits of the repressor complexes, such as HDACs. In this manuscript we review these two different groups of drugs, discussing their properties and the side effects that have been described (that occur by interference with other metabolic pathways). We also propose the logical pharmacological extension of these findings to design more specific and effective drugs for the prevention and treatment of human cancer.
Targeting the BACE1 Active Site Flap Leads to a Potent Inhibitor That Elicits Robust Brain Aβ Reduction in Rodents (2016)

By targeting the flap backbone of the BACE1 active site, we discovered 6-dimethylisoxazole-substituted biaryl aminothiazine 18 with 34-fold improved BACE1 inhibitory activity over the lead compound 1. The cocrystal structure of 18 bound to the active site indicated two hydrogen-bond interactions between the dimethylisoxazole and threonine 72 and glutamine 73 of the flap. Incorporation of the dimethylisoxazole substitution onto the related aminothiazine carboxamide series led to pyrazine-carboxamide 26 as a very potent BACE1 inhibitor (IC50 < 1 nM). This compound demonstrated robust brain Aβ reduction in rat dose-response studies. Thus, compound 26 may be useful in testing the amyloid hypothesis of Alzheimer's disease.
Organic acids - their efficacy and modes of action in pigs (2001)

A meta-analysis of published data shows that dietary organic acids enhance the growth and feed to gain ratio of weaned piglets and fattening pigs. In weaned piglets, the improved growth performance was related to increased feed intake. neither weanind weight, the existing level of performance nor dietary crude protein content influenced the response of weaned piglets to organic acids. In fattening pigs, the growth response increased with dietary crude protein content, whereas the existinf level of performance had no effect. The performance response was greater in the growing than finishing phase. Several modes of action claimed for beneficial effects of organic acids are discussed. Improved nutrient digestibilities result from decreased microbial activity in the gut which spares nutrients from microbes to the animal and reduces microbial protein synthesis. Organic acids may also influence pancreatic excrine secretion and gut morphology. Effects on Escherichia coli counts and the incidence of diarrhoea are generally inconsistent.
Expression of a borage desaturase cDNA containing an N-terminal cytochrome b 5 domain results in the accumulation of high levels of Δ 6 -desaturated fatty acids in transgenic tobacco (1997)

gamma-Linolenic acid (GLA; C18:3 delta(6,9,12)) is a component of the seed oils of evening primrose (Oenothera spp.), borage (Borago officinalis L.), and some other plants. It is widely used as a dietary supplement and for treatment of various medical conditions. GLA is synthesized by a delta6-fatty acid desaturase using linoleic acid (C18:2 delta(9,12)) as a substrate. To enable the production of GLA in conventional oilseeds, we have isolated a cDNA encoding the delta6-fatty acid desaturase from developing seeds of borage and confirmed its function by expression in transgenic tobacco plants. Analysis of leaf lipids from a transformed plant demonstrated the accumulation of GLA and octadecatetraenoic acid (C18:4 delta(6,9,12,15)) to levels of 13.2% and 9.6% of the total fatty acids, respectively. The borage delta6-fatty acid desaturase differs from other desaturase enzymes, characterized from higher plants previously, by the presence of an N-terminal domain related to cytochrome b5.
Ion Gel Gated Polymer Thin-Film Transistors (2007)

We have fabricated polymer semiconductor thin-film transistors using an ion gel (ionic liquid plus triblock copolymer) as the gate dielectric layer. The gate capacitance of the ion gel can be as large as 40 μF/cm2 at 10 Hz and 2 μF/cm2 at 1 kHz. In addition, the polarization response time of the ion gel is much faster than previously tested solid polymer electrolytes, allowing the ion gel gated transistors to operate at higher frequencies (>100 Hz).
A collaborative memory system for high-performance and cost-effective clustered architectures (2011)

With the fast development of highly integrated distributed systems (cluster systems), especially those encapsulated within a single platform [28, 9], designers have to face interesting memory hierarchy design choices that attempt to avoid disk storage swapping. Disk swapping activities slow down application execution drastically. Leveraging remote free memory through Memory Collaboration has demonstrated its cost-effectiveness compared to overprovisioning for peak load requirements. Recent studies propose several ways on accessing the under-utilized remote memory in static system configurations, without detailed exploration on the dynamic memory collaboration. Dynamic collaboration is an important aspect given the run-time memory usage fluctuations in clustered systems.
Targeting DNA with Triplexes (2000)

The formation of intermolecular DNA triple helices offers the possibility of designing compounds with extensive sequence recognition properties which may be useful as antigene agents or tools in molecular biology. In these structures a third strand oligonucleotide binds in the DNA major groove, making specific contacts with substituents on the exposed faces of the base pairs. Although triplexes form with exquisite specificity their use suffers from several drawbacks. Two limitations of this approach, which are considered in this review are, firstly that conditions of low pH are necessary for formation of the C+*GC triplet, and secondly that these structures are often less stable than their duplex counterparts. This review outlines the strategies that have been employed to overcome these drawbacks. The pH problem is addressed by considering the various DNA base analogues that have been used to recognise GC base pairs in a pH independent fashion, and discusses the benefits and limitations of each analogue. Triplex stability can be increased by using novel base analogues, backbone modifications and the use of triplex-specific binding ligands.
Folate, vitamin B12, and homocysteine in major depressive disorder (1997)

Overall, the results are consistent with findings linking low folate levels to poorer response to antidepressant treatment. Folate levels might be considered in the evaluation of depressed patients who do not respond to antidepressant treatment.
Polymers for Biomedical Applications (2008)

Polymers represent the largest and versatile class of biomaterials being extensively applied in multitude of biomedical applications. This versatility is attributed to the relative ease with which polymers can be designed and prepared with a wide variety of structures and appropriate physical, chemical, surface and biomimetic properties. As described in this book a new arsenal of synthetic and applied methodologies are under study that provides an enhanced range of tools to greatly expand the biomedical applications of polymeric materials.
Rescue and expression of human immunoglobulin genes to generate functional human monoclonal antibodies (1992)

Human monoclonal antibody production has been hampered for many years by the instability of cell lines and low levels of expression of the antibodies. We describe here the rescue of human immunoglobulin genes utilizing micro-mRNA preparation from a small number of human hybridoma cells and conventional cDNA cloning. This allows cloning and immediate high-level expression from full-length human heavy and light chain cDNA molecules and provides a mechanism to rescue whole human monoclonal antibodies of proven efficacy.
Naive Monocytes Can Trigger Transendothelial Migration of Peripheral Blood Cells Through the Induction of Endothelial Tumour Necrosis Factor‐α (2000)

In this manuscript we describe a potentially new mechanism by which unstimulated human monocytes activate endothelial cells (EC) through the secondary induction of endothelial tumour necrosis factor alpha (TNF-alpha). Serum free supernatants (SN) of peripheral blood mononuclear cells (PBMC) strongly induce the expression of intercellular adhesion molecule 1 (ICAM-1, CD54), vascular cell adhesion molecule 1 (VCAM-1, CD106), and endothelial-leukocyte adhesion molecule 1 (ELAM-1, CD62E) on human EC 24 and 4 h post treatment, respectively. Further characterization of the responsible subpopulation revealed the CD14+ monocytes and a monocytic cell line (MM6) to produce an endothelial activating factor (EAF). The EAF also triggers an adhesion and a transendothelial migration (TEM) of peripheral blood cells. Using neutralization with an anti TNF-alpha MoAb MAK195, EAF is not identical with TNF-alpha, but induces the expression of endothelial TNF-alpha, since MAK195 blocked TEM only when coincubated with EC, not with monocytes. Furthermore, intracellular TNF-alpha was significantly upregulated in EC after treatment with SN-MM6. Another evidence for a secondary autocrine mechanism was provided by culturing the EC with a conditioned medium of SN-MM6 treated EC. This conditioned medium induces an adhesion molecule expression and TEM in a similar way to SN-MM6 and can completely be inactivated by anti TNF-alpha. Taken together, these data may have an impact for, e.g. transplantational settings that donor monocytes may trigger an inflammatory response in the absence of further activation signals by eliciting an endogenous TNF-alpha response in the host.
TOTAL PARENTERAL NUTRITION (2009)

Parenteral nutrition is a form of therapy in which elemental nutrients (sugars, lipids, amino acids, vitamins and minerals) are given as an intravenous infusion. It is complementary and not competitive to enteral nutrition. While a vast majority of patients can be managed by enteral nutrition, a few patients need parenteral nutrition for survival. Very few patients may need both enteral and parenteral nutrition for short periods. The indications, delivery methods and formulations of parenteral nutrition have been refined in the past 30 years. It is now possible to give parenteral nutrition for prolonged periods at home. Three-in-one parenteral nutrition mixture bags are presently available in India. This article discusses the practical aspects of using parenteral nutrition in everyday practice.
Interleukin-6 Inhibition in Inflammatory Diseases: Results Achieved and Tasks to Accomplish (2017)

Interleukin-6 (IL-6) is a prototypical cytokine featuring functional pleiotropy and redundancy. Under situations of stress, such as infection or tissue injury, IL-6 is rapidly synthesized and plays a major role in host defense. However, uncontrolled excessive or persistent production of IL-6 has a pathological effect in various diseases. Thus, IL-6 blockade was expected to become a novel therapeutic strategy for IL-6–mediated inflammatory diseases, and the first-in-class IL-6 inhibitor tocilizumab, which blocks IL-6 activity by inhibiting IL-6 binding to its receptor, was developed. Clinical trials of tocilizumab have verified its efficacy and tolerable safety profile in several diseases, and it has been approved for the treatment of patients with rheumatoid arthritis, Castleman's disease, systemic and polyarticular juvenile idiopathic arthritis, and giant cell arteritis. Off-label use and clinical trials strongly indicate that tocilizumab will be applicable for a wide variety of acute and chronic inflammatory diseases.
Effect of surfactants on the intensity of chemiluminescence emission from acridinium ester labelled proteins (1988)

In order to establish optimum conditions for the chemiluminescent (CL) reaction of two acridinium ester labelled proteins (human albumin and rabbit anti-human albumin IgG), we investigated the effects of the following factors known to influence the CL emission: pH, presence of proteins, relative concentrations of components of CL reaction and presence of surfactants. Under optimal conditions of pH and hydrogen peroxide concentration, hexadecyl trimethyl ammonium chloride (CTAC) increased the intensity of the CL reaction of the acridinium ester labelled albumin by 42-fold. Triton X-100, Tween-20, 23 lauryl ether (Brij 35) and sodium dodecyl sulphate (SDS) exerted a much smaller effect. In the case of the acridinium ester labelled antibody, the greatest increase was obtained with Triton X-100 (15-fold) followed by CTAC, Brij 35 and Tween 20 (SDS decreased the emission intensity).
Exercise and immunology (1994)

The documented effects of physical activity on host defense date to the early 1900s, although the influences of exercise on infectious and neoplastic disease susceptibility in healthy persons have long been subject to widespread disagreement. Even less is known of the effects of exercise in reducing illness predilection for persons already susceptible to, or afflicted by, immune disease or dysfunction. Recently, however, reports suggest that exercise may reduce the incidence and severity of infection. These reports have been bolstered by well-conducted epidemiologic and laboratory studies demonstrating a link between moderate exercise and either heightened immune function or reduced disease incidence, a relationship that is reversed in instances of immoderate exercise. This symposium will present current information addressing beneficial and detrimental influences of exercise on immune function and disease susceptibility. The authors will emphasize direct effects of acute exercise and physical training on immune cells and their neuroendocrine/immune modulators. The relationship among exercise, infection susceptibility, and immune system function will be highlighted, as well as exercise-induced activation of, and illness/disease regulation by, natural killer cells. Consequences of exercise on immune function and disease advancement will be addressed for persons with neoplasia, autonomic dysfunction, aging-related immunosenescence, and AIDS.
Imputation of missing data using machine learning techniques (1996)

A serious problem in mining industrial data bases is that they are often incomplete, and a significant amount of data is missing, or erroneously entered. This paper explores the use of machine-learning based alternatives to standard statistical data completion (data imputation) methods, for dealing with missing data. We have approached the data completion problem using two well-known machine learning techniques. The first is an unsupervised clustering strategy which uses a Bayesian approach to cluster the data into classes. The classes so obtained are then used to predict multiple choices for the attribute of interest. The second technique involves modeling missing variables by supervised induction of a decision tree-based classifier. This predicts the most likely value for the attribute of interest. Empirical tests using extracts from industrial databases maintained by Honeywell customers have been done in order to compare the two techniques. These tests show both approaches are useful and have advantages and disadvantages. We argue that the choice between unsupervised and supervised classification techniques should be influenced by the motivation for solving the missing data problem, and discuss potential applications for the procedures we are developing.
Telomerase activity in thyroid neoplasms evaluated by the expression of human telomerase reverse transcriptase (hTERT). (2005)

These results suggest that: i) telomerase activity contributes to anaplastic transformation of differentiated carcinoma and ii) hTERT measurement may contribute to diagnosing follicular carcinoma, but whether it can be applied to preoperative diagnosis by fine-needle aspiration biopsy specimens remains unclear.