gebhart/patrepeval huggingface dataset:
Biosynthesis of the v-sis gene product: signal sequence cleavage, glycosylation, and proteolytic processing. (1986)

The v-sis oncogene and its cellular homolog c-sis encode chain B of platelet-derived growth factor. Cells transformed by v-sis produce a platelet-derived growth factor-related molecule which is able to stimulate the platelet-derived growth factor receptor in an autocrine fashion. Site-directed mutagenesis was used to construct several mutations which substitute charged residues for hydrophobic residues in the proposed signal sequence of the v-sis gene product. Two of these mutations resulted in the synthesis of altered v-sis gene products with an unexpected nuclear location and a loss of biological activity. We also report here the intracellular localization of the v-sis gene product to the endoplasmic reticulum-Golgi compartment, where signal sequence cleavage and N-linked glycosylation occur. The v-sis gene product contains no transmembrane regions, as it is completely protected within isolated microsomes from trypsin proteolysis. Site-directed mutagenesis was also used to alter a proposed proteolytic processing site in the v-sis gene product. This mutant v-sis gene, which encodes Asn-Ser in place of Lys-Arg at residues 110 to 111, was found to retain full biological activity.
Smart clocks have a hand in the smart grid (2011)

Clock synchronization is becoming an increasingly important characteristic of modern wide area monitoring and control systems such as the power grid. It provides an opportunity to coordinate control actions and measurement instants across hundreds of miles and numerous network topologies. Devices and networks have advanced to a point where synchronization across a wide area can be achieved within 1 μs of UTC (Coordinated Universal Time). Along with these advances in clock synchronization must come a shift in the way analysis is performed. Modeling techniques must incorporate the effects of a clock synchronized device, and control techniques can leverage the knowledge of ”time” to achieve unique results. This paper discusses various ways in which clock synchronization affects analysis and performance of the power grid, and presents a few projects related to the technology. Preliminary work has demonstrated the ability of various commercially available devices to provide reliable 1 μs synchronization of clocks, and large variation across devices in terms of clock performance under transient events.
Migration of Mesenchymal Stem Cells Through Cerebrospinal Fluid into Injured Spinal Cord Tissue (2004)

Transplanted MSCs injected into the subarachnoid space of the lumbar spine can migrate to injured thoracic spinal cord tissue. The ratio of MSCs observed at the injury site was significantly higher than in the intact spinal cord, and also infiltrated into the deeper spinal cord parenchyma by the perivascular spaces. Lastly, some MSCs differentiated into Nestin-positive, immature neurons or glial cells.
Adjuvant 5FU plus levamisole in colonic or rectal cancer: improved survival in stage II and III (2001)

Based on the first favourable results of adjuvant therapy of 5FU plus levamisole in Dukes C colonic cancer in 1990, we conducted a prospective trial. 1029 patients were randomised to receive one year 5FU plus levamisole or no further treatment following curative surgery for stage II or III colon (n = 730) or rectal cancer (n = 299). 45% were in stage II and 55% in stage III. With a median follow-up of 4 years and 9 months a significant reduction in odds of death (25%, SD 9%, P = 0.007) was observed for those with adjuvant treatment (65% at 5 year) compared to the observation group (55%). Improved relative survival was present in stage III (56% vs 44%), and in stage II patients (78% vs 70%). In rectal cancer a non-significant difference in disease-free or overall survival was observed. Distant metastases developed in 76%, while local recurrence alone occurred in 14%. An early start of adjuvant treatment (< 4 weeks) did not affect results. Compliance to 5FU plus levamisole was 69%. Severe toxicity did not occur. In conclusion, one year 5FU plus levamisole was of benefit in stage II and III colonic cancer; in rectal cancer a significant positive effect could not be demonstrated.
Potentiation of MyoD1 activity by 5-aza-2'-deoxycytidine. (1990)

A mouse myogenic determination gene, MyoD1, was transfected into the human osteogenic sarcoma cell line TE85. Several stably transfected clones were isolated which, at low frequencies, formed multinucleated cells with the appearance of skeletal myotubes. Southern blot analysis confirmed the integration of multiple copies of the mouse MyoD1 gene, and Northern analysis and immunofluorescence confirmed its expression in the transfectants. Characterization of the transfectants showed that they expressed immunologically detectable myosin, desmin, mRNA for myogenin, and the delta subunit of the acetylcholine receptor. The cells assembled a functional contractile apparatus since they contracted in response to acetylcholine added to the culture medium. The presence of MyoD1 protein did not abrogate the expression of two genes active in bone cells but not in muscle cells. The transfected cells therefore displayed a chimeric phenotype by expressing simultaneously bone and muscle genes. Interestingly, treatment of the MyoD1 transfected cells with 5-aza-2'-deoxycytidine resulted in a substantial increase in the frequency of myogenic conversion. Thus, the methylation inhibitor increased the ability of MyoD1 to function as a trans-acting factor and activate the muscle phenotype.
Introduction (1993)

Because the Elizabethan Renaissance served as a period where an interest in history was revived and amplified, some of William Shakespeare's writings during that time, including The Life of Henry the Fifth which he wrote in 1599, complies with the themes of that time. This book, which is one of Shakespeare's written histories, presents a patriotic representation of the Hundred Years War between France and England. Compared to the other histories that Shakespeare wrote where the key theme often demonstrated struggles for internal power, Henry V portrays the campaign efforts made by a virtuous king where those few who possessed a just cause were able to defeat the many — a conflict concerning an enemy from without. Shakespeare's play about King Henry V begins by showing what happened in 1415 during the Hundred Years War when Henry's army arrived near Harfleur and ends in 1420 at the Treaty of Troyes.
Lamin B Phosphorylation by Protein Kinase Cα and Proteolysis during Apoptosis in Human Leukemia HL60 Cells (1998)

Protein phosphorylation plays an important role in signal transduction, but its involvement in apoptosis still remains unclear. In this report, the p53-null human leukemia HL60 cells were used to investigate phosphorylation and degradation of lamin B during apoptosis. We found that lamin B was phosphorylated within 1 h after addition of the DNA topoisomerase I inhibitor, camptothecin, and that lamin B phosphorylation preceded lamin B degradation and DNA fragmentation. Using a cell-free system we also found that cytosol from camptothecin-treated cells induced lamin B phosphorylation and degradation in isolated nuclei from untreated HL60 cells. Lamin B phosphorylation was prevented by the protein kinase C (PKC) inhibitor 7-hydroxystaurosporine (UCN-01) but not by the Cdc2 inhibitor, flavopiridol. Phosphorylation of lamin B was inhibited by immunodepletion of PKCalpha from activated cytosol and was restored by addition of purified PKCalpha. PKCalpha activity also increased rapidly as lamin B was phosphorylated after initiation of the apoptotic response in HL60 cells. These data suggest that lamin B is phosphorylated by PKCalpha and proteolyzed before DNA fragmentation in HL60 cells undergoing apoptosis.
PI3K p110δ regulates T-cell cytokine production during primary and secondary immune responses in mice and humans (2010)

We have previously described critical and nonredundant roles for the phosphoinositide 3-kinase p110delta during the activation and differentiation of naive T cells, and p110delta inhibitors are currently being developed for clinical use. However, to effectively treat established inflammatory or autoimmune diseases, it is important to be able to inhibit previously activated or memory T cells. In this study, using the isoform-selective inhibitor IC87114, we show that sustained p110delta activity is required for interferon-gamma production. Moreover, acute inhibition of p110delta inhibits cytokine production and reduces hypersensitivity responses in mice. Whether p110delta played a similar role in human T cells was unknown. Here we show that IC87114 potently blocked T-cell receptor-induced phosphoinositide 3-kinase signaling by both naive and effector/memory human T cells. Importantly, IC87114 reduced cytokine production by memory T cells from healthy and allergic donors and from inflammatory arthritis patients. These studies establish that previously activated memory T cells are at least as sensitive to p110delta inhibition as naive T cells and show that mouse models accurately predict p110delta function in human T cells. There is therefore a strong rationale for p110delta inhibitors to be considered for therapeutic use in T-cell-mediated autoimmune and inflammatory diseases.
Effects of Elevated Carbon Dioxide, Elevated Temperature, and Rice Growth Stage on the Community Structure of Rice Root–Associated Bacteria (2014)

The effects of free-air carbon dioxide enrichment (FACE) and elevated soil and water temperature (warming) on the rice root-associated bacterial community were evaluated by clone library analysis of the 16S ribosomal RNA gene. Roots were sampled at the panicle initiation and ripening stages 41 and 92 days after transplanting (DAT), respectively. The relative abundances of the methanotrophs Methylosinus and Methylocystis were increased by warming and decreased by FACE at 92 DAT, which indicated that microbial methane (CH4) oxidation in rice roots may have been influenced by global warming. The relative abundance of Burkholderia kururiensis was increased by warming at 41 DAT and by FACE or warming at 92 DAT. The abundances of methanotrophs increased during rice growth, which was likely induced by an enhancement in the emission of CH4 from the paddy fields, suggesting that CH4 is one of the predominant factors affecting the structure of the microbial community in rice roots. Marked variations in the community structure were also observed during rice growth in other genera: Bradyrhizobium, Clostridium, and an unknown genus close to Epsilonproteobacteria were abundant at 92 DAT, whereas Achromobacter was abundant at 41 DAT. These results demonstrated that the community structures of rice root-associated bacteria were markedly affected by FACE, temperature, and the rice growth stage.
Covalent Adaptable Networks: Reversible Bond Structures Incorporated in Polymer Networks (2012)

Smart and responsive: Reversible transesterification reactions were recently used within a polymer network to create a covalently crosslinked material that is capable of being processed as well as mended and recycled. This work is highlighted in the context of the covalent adaptable network approach and illustrates the bond cleavage and reformation mechanism that enable the adaptability of these materials (see picture).
Detection of AML1/ETO fusion transcript as a tool for diagnosing t(8;21) positive acute myelogenous leukemia. (1994)

The nonrandom chromosomal translocation t(8;21)(q22;q22) can be found frequently in acute myelogenous leukemia with maturation (AML-M2). The breakpoint of this translocation has been cloned and characterized, and fusion transcript AML1/ETO has been identified. Reverse transcription polymerase chain reaction (RT-PCR) can be used to amplify the breakpoint site of AML1/ETO in t(8;21)-positive AML-M2 patients. The chimeric transcript can be detected in all 16 (100%) t(8;21)-positive AML-M2 patients. In all samples, the size of the amplified DNA fragments and pattern of restriction digest were identical, indicating that the t(8;21) translocation breakpoint occurs within a single intron of the AML1 and ETO genes. Interestingly, this fusion transcript was also detected in one of 13 AML-M2 patients without the t(8;21) translocation, indicating that a masked translocation involving chromosomes 8 and 21, exists in AML. Minimal residual disease was detected by semi-nested RT-PCR in all four patients tested, who had been in complete remission for 12, 15, 34, and 52 months, respectively. These results indicate that RT-PCR amplification of the AML1/ETO fusion transcript is a powerful tool for diagnosing and monitoring minimal residual disease in AML-M2 patients.
Adenosine receptor specificity in preconditioning of isolated rabbit cardiomyocytes: evidence of A3 receptor involvement (1994)

Preconditioning can be induced in isolated myocytes by a 5 min preincubation/30 min postincubation protocol, and a similar protection induced by adenosine agonists with A3, but not A1 selectivity. Preconditioning is blocked by non-selective or selective A1/A3 adenosine antagonists and a specific protein kinase C inhibitor, but not by A1 antagonists with little affinity for A3 receptors. The results suggest that preconditioning in isolated rabbit myocytes requires participation of adenosine receptors with agonist/antagonist binding characteristics of the A3 subtype, and is likely to be mediated by activation of protein kinase C.
The ABRF Edman Sequencing Research Group 2008 Study: investigation into homopolymeric amino acid N-terminal sequence tags and their effects on automated Edman degradation (2009)

The Edman Sequence Research Group (ESRG) of the Association of Biomolecular Resource designs and executes interlaboratory studies investigating the use of automated Edman degradation for protein and peptide analysis. In 2008, the ESRG enlisted the help of core sequencing facilities to investigate the effects of a repeating amino acid tag at the N-terminus of a protein. Commonly, to facilitate protein purification, an affinity tag containing a polyhistidine sequence is conjugated to the N-terminus of the protein. After expression, polyhistidine-tagged protein is readily purified via chelation with an immobilized metal affinity resin. The addition of the polyhistidine tag presents unique challenges for the determination of protein identity using Edman degradation chemistry. Participating laboratories were asked to sequence one protein engineered in three configurations: with an N-terminal polyhistidine tag; with an N-terminal polyalanine tag; or with no tag. Study participants were asked to return a data file containing the uncorrected amino acid picomole yields for the first 17 cycles. Initial and repetitive yield (R.Y.) information and the amount of lag were evaluated. Information about instrumentation and sample treatment was also collected as part of the study. For this study, the majority of participating laboratories successfully called the amino acid sequence for 17 cycles for all three test proteins. In general, laboratories found it more difficult to call the sequence containing the polyhistidine tag. Lag was observed earlier and more consistently with the polyhistidine-tagged protein than the polyalanine-tagged protein. Histidine yields were significantly less than the alanine yields in the tag portion of each analysis. The polyhistidine and polyalanine protein-R.Y. calculations were found to be equivalent. These calculations showed that the nontagged portion from each protein was equivalent. The terminal histidines from the tagged portion of the protein were demonstrated to be responsible for the high lag during N-terminal sequence analysis.
Histopathological Image Analysis: A Review (2009)

Over the past decade, dramatic increases in computational power and improvement in image analysis algorithms have allowed the development of powerful computer-assisted analytical approaches to radiological data. With the recent advent of whole slide digital scanners, tissue histopathology slides can now be digitized and stored in digital image form. Consequently, digitized tissue histopathology has now become amenable to the application of computerized image analysis and machine learning techniques. Analogous to the role of computer-assisted diagnosis (CAD) algorithms in medical imaging to complement the opinion of a radiologist, CAD algorithms have begun to be developed for disease detection, diagnosis, and prognosis prediction to complement the opinion of the pathologist. In this paper, we review the recent state of the art CAD technology for digitized histopathology. This paper also briefly describes the development and application of novel image analysis technology for a few specific histopathology related problems being pursued in the United States and Europe.
Influence of electrolyte composition on the effective electric field strength in capillary zone electrophoresis (1995)

In capillary zone electrophoresis the electrophoretic velocity of an ion decreases as the concentration of the background electrolyte solution is increased. This is caused by changes in the electrophoretic mobility of the ion (muep) as well as by changes in the net force affecting it, namely the effective electric field strength (Eeff). The electrophoretic mobility of an ion is altered through changes in absolute viscosity of the electrolyte solution and changes in the solvated size of the ion. Eeff is altered mainly by changes in the magnitude of the charge asymmetry effect and the electrophoretic effect, both of which retard the motion of ions. In this study, the three-marker technique was used to study the effect of background electrolyte concentration (0.02-0.08M 3-[cyclohexylamino]-1-propanesulfonic acid and counter ion (Li, Na, K, and Cs) on Eeff. It was found that the concentration of the background electrolyte markedly affects Eeff and that Eeff approaches E as the concentration of the background electrolyte approaches zero. The counter ion had a minor effect on Eeff: as the size of the hydrated radius of the counter ion increased, Eeff decreased. The three-marker technique proved to be efficient for such determinations.
HNH proteins are a widespread component of phage DNA packaging machines (2014)

The genome packaging reactions of tailed bacteriophages and herpes viruses require the activity of a terminase enzyme, which is comprised of large and small subunits. Phage genomes are replicated as linear concatemers composed of multiple copies of the genome joined end to end. As the terminase enzyme packages the genome into the phage capsid, it cleaves the DNA into single genome-length units. In this work, we show that the phage HK97 HNH protein, gp74, is required for the specific endonuclease activity of HK97 terminase and is essential for phage head morphogenesis. HNH proteins are a very common family of proteins generally associated with nuclease activity that are found in all kingdoms of life. We show that the activity of gp74 in terminase-mediated cleavage of the phage cos site relies on the presence of an HNH motif active-site residue, and that the large subunit of HK97 terminase physically interacts with gp74. Bioinformatic analysis reveals that the role of HNH proteins in terminase function is widespread among long-tailed phages and is uniquely required for the activity of the Terminase_1 family of large terminase proteins.
Detecting bacteria and determining their susceptibility to antibiotics by stochastic confinement in nanoliter droplets using plug-based microfluidics (2008)

This article describes plug-based microfluidic technology that enables rapid detection and drug susceptibility screening of bacteria in samples, including complex biological matrices, without pre-incubation. Unlike conventional bacterial culture and detection methods, which rely on incubation of a sample to increase the concentration of bacteria to detectable levels, this method confines individual bacteria into droplets nanoliters in volume. When single cells are confined into plugs of small volume such that the loading is less than one bacterium per plug, the detection time is proportional to plug volume. Confinement increases cell density and allows released molecules to accumulate around the cell, eliminating the pre-incubation step and reducing the time required to detect the bacteria. We refer to this approach as 'stochastic confinement'. Using the microfluidic hybrid method, this technology was used to determine the antibiogram - or chart of antibiotic sensitivity - of methicillin-resistant Staphylococcus aureus (MRSA) to many antibiotics in a single experiment and to measure the minimal inhibitory concentration (MIC) of the drug cefoxitin (CFX) against this strain. In addition, this technology was used to distinguish between sensitive and resistant strains of S. aureus in samples of human blood plasma. High-throughput microfluidic techniques combined with single-cell measurements also enable multiple tests to be performed simultaneously on a single sample containing bacteria. This technology may provide a method of rapid and effective patient-specific treatment of bacterial infections and could be extended to a variety of applications that require multiple functional tests of bacterial samples on reduced timescales.
Physiologic and plasma hormone correlates of survival in endotoxic dogs: effects of opiate antagonists. (1989)

Two groups of awake dogs were given an iv bolus of endotoxin (3.0 mg/kg from Salmonella typhimurium); one group (n = 9) was pretreated with either naloxone (2.0 mg/kg iv bolus with 1.7 mg/kg.h; n = 6) or naltrexone (2.0 mg/kg iv bolus with repeat bolus of 1.0 mg/kg at 1, 3 and 5 h; n = 3) and the second group (n = 10) received no opiate antagonist. All of nine dogs that were pretreated with an antagonist survived for 24 h, compared to only five of ten dogs that were not pretreated. Survival correlated with improved BP (mean of 91 vs. 61 mm Hg) and cardiac output (3.9 vs. 2.45 L/min) measured during the first 3 h after the infliction of shock. However, both antagonist-treated and nonantagonist-treated survivors had BP and cardiac output which were statistically lower than their baseline values or saline-treated controls at comparable times. Nonsurvivors had significantly higher levels of norepinephrine (peak level: 1149 ng/ml) and epinephrine (peak level: 31.29 ng/ml) than survivors. Opiate antagonists thus appeared to increase survival in a subgroup of dogs that might not otherwise have survived if they had not been so treated; this survival was associated with improved hemodynamics, but not with increased adrenergic activity.
ECDI-fixed allogeneic splenocytes induce donor-specific tolerance for long-term survival of islet transplants via two distinct mechanisms (2008)

A major challenge for human allogeneic islet transplantation is the development of effective methods to induce donor-specific tolerance to obviate the need for life-long immunosuppression that is toxic to the insulin-producing beta cells and detrimental to the host. We developed an efficient donor-specific tolerance therapy that utilizes infusions of ethylene carbodiimide (ECDI)-treated donor splenic antigen-presenting cells that results in indefinite survival of allogeneic islet grafts in the absence of immunosuppression. Furthermore, we show that induction of tolerance is critically dependent on synergistic effects between an intact programmed death 1 receptor-programmed death ligand 1 signaling pathway and CD4(+)CD25(+)Foxp3(+) regulatory T cells. This highly efficient antigen-specific therapy with a complete avoidance of immunosuppression has significant therapeutic potential in human islet cell transplantation.