gebhart/patrepeval huggingface dataset:
Prebiotics and Synbiotics in Clinical Medicine (2005)

Pharmaceutical medicine has thus far been unable to stop the increasing global morbidity and mortality both in acute and chronic diseases. Typically, medical practice has focused on reducing the aggressor with treatments such as antibiotics; little interest has been given to efforts to increase the individual's resistance to disease. The increased morbidity has occurred in parallel to a deviation from a large consumption of fresh fruits, vegetables, and tubers rich in live lactic acid bacteria (LAB), plant fibers, and natural antioxidants to an industry-produced diet rich in fat and refined sugar but containing little fiber, antioxidants, and LAB. Plant fiber/prebiotics, plant-derived antioxidants, and LAB/probiotics are known to have the potential to reinforce the immune system of the body and increase resistance to disease. However, this depends on the type of fiber, antioxidant, and strain or combination of strain used. At this stage, only about 10% of the LAB studied have proven strong immunosupportive effects. Similarly, only a few plants contain what has been called superantioxidants, antioxidants 10 or more times stronger than vitamin C and E. Increasing evidence suggests that combining several probiotic bacteria into multistrain probiotics will achieve stronger effects than single-strain probiotics. And combining probiotics and prebiotics into "synbiotics" will further enhance the immunosupportive effects. There is little evidence that a single-strain-based "superprobiotic"/magic LAB will ever be found. Instead, combining several specific and defined probiotics and several key plant fibers into multistrain/multifiber synbiotics appears to be the most promising alternative. Some edge-cutting effects from using multistrain and multifiber compositions are reported both from animal and controlled clinical studies.
A fluorophore ligase for site-specific protein labeling inside living cells (2010)

Biological microscopy would benefit from smaller alternatives to green fluorescent protein for imaging specific proteins in living cells. Here we introduce PRIME (PRobe Incorporation Mediated by Enzymes), a method for fluorescent labeling of peptide-fused recombinant proteins in living cells with high specificity. PRIME uses an engineered fluorophore ligase, which is derived from the natural Escherichia coli enzyme lipoic acid ligase (LplA). Through structure-guided mutagenesis, we created a mutant ligase capable of recognizing a 7-hydroxycoumarin substrate and catalyzing its covalent conjugation to a transposable 13-amino acid peptide called LAP (LplA Acceptor Peptide). We showed that this fluorophore ligation occurs in cells in 10 min and that it is highly specific for LAP fusion proteins over all endogenous mammalian proteins. By genetically targeting the PRIME ligase to specific subcellular compartments, we were able to selectively label spatially distinct subsets of proteins, such as the surface pool of neurexin and the nuclear pool of actin.
Phase I/II Trial of Tremelimumab in Patients With Metastatic Melanoma (2009)

Multiple infusions of tremelimumab were generally tolerable and demonstrated single-agent antitumor activity. Both phase II regimens generated durable tumor responses. Based on its more favorable safety profile, 15 mg/kg every 3 months was selected for further clinical testing.
Rapid Improvement of Acute Schizophrenia Symptoms After Intravenous Sodium Nitroprusside (2013)

clinicaltrials.gov Identifier: NCT01548612.
Cytokine Levels Correlate with Immune Cell Infiltration after Anti-VEGF Therapy in Preclinical Mouse Models of Breast Cancer (2009)

The effect of blocking VEGF activity in solid tumors extends beyond inhibition of angiogenesis. However, no studies have compared the effectiveness of mechanistically different anti-VEGF inhibitors with respect to changes in tumor growth and alterations in the tumor microenvironment. In this study we use three distinct breast cancer models, a MDA-MB-231 xenograft model, a 4T1 syngenic model, and a transgenic model using MMTV-PyMT mice, to explore the effects of various anti-VEGF therapies on tumor vasculature, immune cell infiltration, and cytokine levels. Tumor vasculature and immune cell infiltration were evaluated using immunohistochemistry. Cytokine levels were evaluated using ELISA and electrochemiluminescence. We found that blocking the activation of VEGF receptor resulted in changes in intra-tumoral cytokine levels, specifically IL-1beta, IL-6 and CXCL1. Modulation of the level these cytokines is important for controlling immune cell infiltration and ultimately tumor growth. Furthermore, we demonstrate that selective inhibition of VEGF binding to VEGFR2 with r84 is more effective at controlling tumor growth and inhibiting the infiltration of suppressive immune cells (MDSC, Treg, macrophages) while increasing the mature dendritic cell fraction than other anti-VEGF strategies. In addition, we found that changes in serum IL-1beta and IL-6 levels correlated with response to therapy, identifying two possible biomarkers for assessing the effectiveness of anti-VEGF therapy in breast cancer patients.
A Linear CB Synthesizer (1977)

The recent boom in Citizens Band radio popularity, coupled with a shortage of crystals, has caused phase locked loop frequency synthesizers to be incorporated into new radio designs. A number of digital integrated circuits have been introduced which contain a reference oscillator, an oscillator divider, a programmable divider, and a phase detector. This paper reviews the requirements for the complete phase locked loop frequency synthesizer and presents a linear integrated circuit to complement the existing digital circuits and complete the system. The new circuit contains a voltage controlled oscillator, a crystal oscillator or buffer, a mixer, and logic circuitry to control the receive or transmit condition with an out-of-lock override switch.
Nursing management issues in hip and knee replacement surgery (2004)

Total hip replacement (THR) and total knee replacement (TKR) are carried out for the relief of pain in hip or knee joints usually caused by osteoarthritis. Such replacements last for 10-15 years and therefore many nurses will care for patients with a THR/TKR even if that is not the primary reason for the patient seeking care. The different types of THR/TKR and how patients can be prepared for surgery are discussed. The major long-term complications of loosening or dislocation of the components of the THR/TKR and of infection are explored and the presenting symptoms are highlighted. The article is intended to be useful not only for orthopaedic nurses but also for nurses generally.
The application of tissue adhesives in small bowel anastomoses (1982)

One layer everted end-to-end anastomosis was performed on the small bowel of mongrel dogs. Cultures of Serratia marcescens were injected into the lumen. Twenty-four hours later the animals were reexplored, and peritoneal cultures were observed. In animals where Fibrin Seal (consisting of fibrinogen, cold insoluble globulin, factor XIII, platelet growth factor, antiplasmin, thrombin, and calcium chloride) was applied to the suture line, negative cultures were found except for two experiments in which dehiscence or contamination from the Serratia injection site occurred.
Heteropolysaccharides from lactic acid bacteria (1999)

Microbial exopolysaccharides are biothickeners that can be added to a wide variety of food products, where they serve as viscosifying, stabilizing, emulsifying or gelling agents. Numerous exopolysaccharides with different composition, size and structure are synthesized by lactic acid bacteria. The heteropolysaccharides from both mesophilic and thermophilic lactic acid bacteria have received renewed interest recently. Structural analysis combined with rheological studies revealed that there is considerable variation among the different exopolysaccharides; some of them exhibit remarkable thickening and shear-thinning properties and display high intrinsic viscosities. Hence, several slime-producing lactic acid bacterium strains and their biopolymers have interesting functional and technological properties, which may be exploited towards different products, in particular, natural fermented milks. However, information on the biosynthesis, molecular organization and fermentation conditions is rather scarce, and the kinetics of exopolysaccharide formation are poorly described. Moreover, the production of exopolysaccharides is low and often unstable, and their downstream processing is difficult. This review particularly deals with microbiological, biochemical and technological aspects of heteropolysaccharides from, and their production by, lactic acid bacteria. The chemical composition and structure, the biosynthesis, genetics and molecular organization, the nutritional and physiological aspects, the process technology, and both food additive and in situ applications (in particular in yogurt) of heterotype exopolysaccharides from lactic acid bacteria are described. Where appropriate, suggestions are made for strain improvement, enhanced productivities and advanced modification and production processes (involving enzyme and/or fermentation technology) that may contribute to the economic soundness of applications with this promising group of biomolecules.
Direct Titration of Epoxy Compounds and Aziridines. (1964)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDirect Titration of Epoxy Compounds and Aziridines.R. R. JayCite this: Anal. Chem. 1964, 36, 3, 667–668Publication Date (Print):March 1, 1964Publication History Published online1 May 2002Published inissue 1 March 1964https://pubs.acs.org/doi/10.1021/ac60209a037https://doi.org/10.1021/ac60209a037research-articleACS PublicationsRequest reuse permissionsArticle Views1270Altmetric-Citations235LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Identification of the nerve terminal targets of botulinum neurotoxin serotypes A, D, and E. (1993)

Botulinum neurotoxins are metalloproteins with one zinc atom bound to the zinc binding motif of zinc endopeptidases. Here we show that botulinum neurotoxin serotypes A, D, and E are zinc endoproteases specific for components of the synaptic vesicle docking and fusion complex. Serotypes A and E cleave SNAP-25, a 25-kDa protein of the synaptic terminal, while serotype D is specific for VAMP/synaptobrevin, a membrane protein of synaptic vesicles. Both rat brain VAMP isoforms are cleaved at a single Lys-Leu peptide bond. The proteolytic activity of these neurotoxins is inhibited by EDTA and captopril.
Cloning mammalian genes by expression selection of genetic suppressor elements: association of kinesin with drug resistance and cell immortalization. (1994)

We describe a general strategy for cloning mammalian genes whose downregulation results in a selectable phenotype. This strategy is based on expression selection of genetic suppressor elements (GSEs), cDNA fragments encoding either specific peptides that act as dominant inhibitors of protein function or antisense RNA segments that efficiently inhibit gene expression. Since GSEs counteract the gene from which they are derived, they can be used as dominant selectable markers for the phenotype associated with downregulation of the corresponding gene. A retroviral library containing random fragments of normalized (uniform abundance) cDNA expressed in mouse NIH 3T3 cells was used to select for GSEs inducing resistance to the anticancer drug etoposide. Three GSEs were isolated, two of which are derived from unknown genes and the third encodes antisense RNA for the heavy chain of a motor protein kinesin. The kinesin-derived GSE induces resistance to several DNA-damaging drugs and immortalizes senescent mouse embryo fibroblasts, indicating that kinesin is involved in the mechanisms of drug sensitivity and in vitro senescence. Expression of the human kinesin heavy-chain gene was decreased in four of four etoposide-resistant HeLa cell lines, derived by conventional drug selection, indicating that downregulation of kinesin represents a natural mechanism of drug resistance in mammalian cells.
Optimal Load Balancing on Sonet Bidirectional Rings (1997)

In this paper we consider the Ring Loading Problem, which arises in the design of SONET bidirectional rings. The issue of demand splitting divides the ring loading problem into the two kinds. One allows a demand to be split and routed in two different directions and the other does not. The former kind becomes a relaxation of the latter. We present an efficient exact solution procedure for the case with demand splitting, and a two-approximation algorithm for the case without demand splitting. Computational results are also shown to prove the efficiency of the proposed procedures.
Novel Variants of Oct-3/4 Gene Expressed in Mouse Somatic Cells (2008)

It has been suggested that Oct-3/4 may regulate self-renewal in somatic stem cells, as it does in embryonic stem cells. However, recent reports raise the possibility that detection of human Oct-3/4 expression by RT-PCR is prone to artifacts generated by pseudogene transcripts and argue against a role for Oct-3/4 in somatic cells. In this study, we clarified Oct-3/4 expression in mouse somatic tissues using designed PCR primers, which can exclude amplification of its pseudogenes. We found that novel alternative transcripts are indeed expressed in somatic tissues, rather than the normal length transcripts in germline and ES cells. The alternative transcripts indicate the expression of two kinds of truncated proteins. Furthermore, we determined novel promoter regions that are sufficient for the expression of Oct-3/4 transcript variants in somatic cells. These findings provide new insights into the postnatal role of Oct-3/4 in somatic tissues.
Optimized hardware and software for fast full-chip simulation (2005)

Lithography simulation is an increasingly important part of semiconductor manufacturing due to the decreasing k1 value. It is not only required in lithography process development, but also in RET design, RET verification, and process latitude analysis, from library cells to full-chip. As the design complexity grows exponentially, pure software based simulation tools running on general-purpose computer clusters are facing increasing challenges in meeting today’s requirements for cycle time, coverage, and modeling accuracy. We have developed a new lithography simulation platform (Tachyon<sup>TM</sup>) which achieves orders of magnitude speedup as compared to traditional pure software simulation tools. The platform combines innovations in all levels of the system: algorithm, software architecture, cluster-level architecture, and proprietary acceleration hardware using application specific integrated circuits. The algorithm approach is based on image processing, fundamentally different from conventional edge-based analysis. The system achieves superior model accuracy than conventional full-chip simulation methods, owing to its ability to handle hundreds of TCC kernels, using either vector or scalar optical model, without impacting throughput. Thus first-principle aerial image simulation at the full-chip level can be carried out within minutes. We will describe the hardware, algorithms and models used in the system and demonstrate its applications of the full chip verification purposes.
Unusual Metal Ion Catalysis in an Acyl-Transferase Ribozyme (1998)

Most studies of the roles of catalytic metal ions in ribozymes have focused on inner-sphere coordination of the divalent metal ions to the substrate or ribozyme. However, divalent metal ions are strongly hydrated in water, and some proteinenzymes, such as Escherichia coli RNase H and exonuclease III, are known to use metal cofactors in their fully hydrated form [Duffy, T. H., and Nowak, T. (1985) Biochemistry 24, 1152-1160; Jou, R., and Cowan, J. A. (1991) J. Am. Chem. Soc. 113, 6685-6686]. It is therefore important to consider the possibility of outer-sphere coordination of catalytic metal ions in ribozymes. We have used an exchange-inert metal complex, cobalt hexaammine, to show that the catalytic metal ion in an acyl-transferase ribozyme acts through outer-sphere coordination. Our studies provide an example of a fully hydrated Mg2+ ion that plays an essential role in ribozyme catalysis. Kinetic studies of wild-type and mutant ribozymes suggest that a pair of tandem G:U wobble base pairs adjacent to the reactive center constitute the metal-binding site. This result is consistent with recent crystallographic studies [Cate, J. H., and Doudna, J. A. (1996) Structure 4, 1221-1229; Cate, J. H., Gooding, A. R., Podell, E., Zhou, K., Golden, B. L., Kundrot, C. E., Cech, T. R., and Doudna, J. A. (1996) Science 273, 1678-1685; Cate, J. H., Hanna, R. L., and Doudna, J. A. (1997) Nat. Struct. Biol. 4, 553-558] showing that tandem wobble base pairs are good binding sites for metal hexaammines. We propose a model in which the catalytic metal ion is bound in the major groove of the tandem wobble base pairs, is precisely positioned by the ribozyme within the active site, and stabilizes the developing oxyanion in the transition state. Our results may have significant implications for understanding the mechanism of protein synthesis [Noller, H. F., Hoffarth, V., and Zimniak, L. (1992) Science 256, 1416-1419].
Antigen‐antibody interactions: Elucidation of the epitope and strain‐specificity of a monoclonal antibody directed against the pilin protein adherence binding domain of Pseudomonas aeruginosa strain K (1992)

The C-terminal region of Pseudomonas aeruginosa strain K (PAK) pilin comprises both an epitope for the strain-specific monoclonal antibody PK99H, which blocks pilus-mediated adherence, and the adherence binding domain for buccal and tracheal epithelial cells. The PK99H epitope was located in sequence 134-140 (Asp-Glu-Gln-Phe-Ile-Pro-Lys) by using a single alanine replacement analysis on the 17-residue synthetic peptide corresponding to the PAK C-terminal sequence 128-144. Indeed, a 7-residue peptide corresponding to this sequence was shown to have a similar binding affinity to that of the native conformationally constrained (disulfide bridged) 17-residue peptide. This epitope was found to contain two critical residues (Phe137 and Lys140) and one nonessential residue (Gln136). Interestingly, the peptide, Phe-Ile-Pro-Lys, which constitutes the four most important side chains for antibody binding did not bind to PK99H. It was of interest to investigate the structural basis of the strain-specificity of PK99H utilizing naturally occurring pilin sequences. Therefore, all different residues found in the sequence corresponding to the PK99H epitope of the four other strains (PAO, CD4, K122-4, and KB7) were substituted one at a time in the PAK sequence and the changes in binding affinity of these analogs to the antibody PK99H were determined by competitive ELISA. The strain-specificity of PK99H for strains PAO, K122-4, and KB7 can be explained by the accumulated sequence changes in these strains, and at least two amino acid changes were required to explain the strain-specificity of PK99H. Similarly, cross-reactivity of PK99H with CD4 can be explained by the fact that there was only one side chain responsible for decreasing binding affinity compared to the PAK sequence.
First clinical trial of a novel caspase inhibitor: anti-apoptotic caspase inhibitor, IDN-6556, improves liver enzymes (2003)

Following intravenous administration of a novel anti-apoptotic caspase inhibitor, adverse events were mild-to-moderate in severity, resolved in a few days and did not result in any subject terminating treatment prematurely. The effects in hepatic impaired patients appear to be consistent with both the administration and subsequent abrupt withdrawal of an effective hepatoprotective drug that delays cell death in hepatocytes.
Properties and Biological Activities of Thioredoxins (2001)

The mammalian thioredoxins are a family of small (approximately 12 kDa) redox proteins that undergo NADPH-dependent reduction by thioredoxin reductase and in turn reduce oxidized cysteine groups on proteins. The two main thioredoxins are thioredoxin-1, a cytosolic and nuclear form, and thioredoxin-2, a mitochondrial form. Thioredoxin-1 has been studied more. It performs many biological actions including the supply of reducing equivalents to thioredoxin peroxidases and ribonucleotide reductase, the regulation of transcription factor activity, and the regulation of enzyme activity by heterodimer formation. Thioredoxin-1 stimulates cell growth and is an inhibitor of apoptosis. Thioredoxins may play a role in a variety of human diseases including cancer. An increased level of thioredoxin-1 is found in many human tumors, where it is associated with aggressive tumor growth. Drugs are being developed that inhibit thioredoxin and that have antitumor activity.
Ghrelin regulates mitochondrial-lipid metabolism gene expression and tissue fat distribution in liver and skeletal muscle (2004)

Ghrelin is a gastric hormone increased during caloric restriction and fat depletion. A role of ghrelin in the regulation of lipid and energy metabolism is suggested by fat gain independent of changes in food intake during exogenous ghrelin administration in rodents. We investigated the potential effects of peripheral ghrelin administration (two times daily 200-micrograms [DOSAGE ERROR CORRECTED] sc injection for 4 days) on triglyceride content and mitochondrial and lipid metabolism gene expression in rat liver and muscles. Compared with vehicle, ghrelin increased body weight but not food intake and circulating insulin. In liver, ghrelin induced a lipogenic and glucogenic pattern of gene expression and increased triglyceride content while reducing activated (phosphorylated) stimulator of fatty acid oxidation, AMP-activated protein kinase (AMPK, all P < 0.05), with unchanged mitochondrial oxidative enzyme activities. In contrast, triglyceride content was reduced (P < 0.05) after ghrelin administration in mixed (gastrocnemius) and unchanged in oxidative (soleus) muscle. In mixed muscle, ghrelin increased (P < 0.05) mitochondrial oxidative enzyme activities independent of changes in expression of fat metabolism genes and phosphorylated AMPK. Expression of peroxisome proliferator-activated receptor-gamma, the activation of which reduces muscle fat content, was selectively increased in mixed muscle where it paralleled changes in oxidative capacities (P < 0.05). Thus ghrelin induces tissue-specific changes in mitochondrial and lipid metabolism gene expression and favors triglyceride deposition in liver over skeletal muscle. These novel effects of ghrelin in the regulation of lean tissue fat distribution and metabolism could contribute to metabolic adaptation to caloric restriction and loss of body fat.