gebhart/patrepeval huggingface dataset:
Consensus in the presence of partial synchrony (1988)

The concept of partial synchrony in a distributed system is introduced. Partial synchrony lies between the cases of a synchronous system and an asynchronous system. In a synchronous system, there is a known fixed upper bound Δ on the time required for a message to be sent from one processor to another and a known fixed upper bound Φ on the relative speeds of different processors. In an asynchronous system no fixed upper bounds Δ and Φ exist. In one version of partial synchrony, fixed bounds Δ and Φ exist, but they are not known a priori. The problem is to design protocols that work correctly in the partially synchronous system regardless of the actual values of the bounds Δ and Φ. In another version of partial synchrony, the bounds are known, but are only guaranteed to hold starting at some unknown time T , and protocols must be designed to work correctly regardless of when time T occurs. Fault-tolerant consensus protocols are given for various cases of partial synchrony and various fault models. Lower bounds that show in most cases that our protocols are optimal with respect to the number of faults tolerated are also given. Our consensus protocols for partially synchronous processors use new protocols for fault-tolerant “distributed clocks” that allow partially synchronous processors to reach some approximately common notion of time.
The Crystal Structure of Tetanus Toxin Hc Fragment Complexed with a Synthetic GT1b Analogue Suggests Cross-linking between Ganglioside Receptors and the Toxin (2001)

Tetanus toxin, a member of the family of Clostridial neurotoxins, is one of the most potent toxins known. The crystal structure of the complex of the COOH-terminal fragment of the heavy chain with an analogue of its ganglioside receptor, GT1b, provides the first direct identification and characterization of the ganglioside-binding sites. The ganglioside induces cross-linking by binding to two distinct sites on the Hc molecule. The structure sheds new light on the binding of Clostridial neurotoxins to receptors on neuronal cells and provides important information relevant to the design of anti-tetanus and anti-botulism therapeutic agents.
Organic or not organic – that is the question: How the knowledge about the origin of chlorinated compounds can help to reduce formation of 3‐MCPD esters (2012)

Organic or not organic – That is the question: How the knowledge about the origin of the chlorinated compounds can help to reduce formation of 3‐MCPD esters
Gut Microbiota-Dependent Trimethylamine N -Oxide (TMAO) Pathway Contributes to Both Development of Renal Insufficiency and Mortality Risk in Chronic Kidney Disease (2014)

Plasma TMAO levels are both elevated in patients with CKD and portend poorer long-term survival. Chronic dietary exposures that increase TMAO directly contributes to progressive renal fibrosis and dysfunction in animal models.
Molecular Targeting of Intracellular Compartments Specifically in Cancer Cells (2010)

We have implemented a strategy in which a genetically engineered, single-chain protein specifically recognizes cancer cells and is trafficked to a targeted subcellular compartment, such as the nucleus. The recombinant protein termed IL-13.E13K-D2-NLS has a triple functional property: (1) it binds a cancer-associated receptor, interleukin 13 receptor alpha 2 (IL-13Rα2), using modified IL-13 ligand, IL-13.E13K; (2) it exports its C-terminal portion out of the endosomal compartment using Pseudomonas aeruginosa exotoxin A (PE) translocation domain (D2); and (3) it travels to and accumulates in the nucleus guided by the nuclear localization signal (NLS). Here, we have demonstrated that this protein is transported into the brain tumor cells' nucleus, using 3 different methods of protein conjugation to dyes for the purpose of direct visualization of the protein's intracellular trafficking. IL-13.E13K-D2-NLS, and not the controls such as IL-13.E13K-D2, IL-13.E13K-NLS, or IL-13.E13K, accumulated in nuclei very efficiently, which increased with the time the cells were exposed to the protein. Also, IL-13.E13K-D2-NLS did not exhibit nuclear transport in cells with low expression levels of IL-13Rα2. Thus, it is possible to recognize cancer cells through their specific receptors and deliver a conjugated protein that travels specifically to the nucleus. Hence, our molecular targeting strategy succeeded in generating a single-chain proteinaceous agent capable of delivering drugs/labels needed to be localized to the cells' nuclei or potentially any other subcellular compartment, for their optimal efficacy or ability to exert their specific action.
Murine immune response to HIV-1 p24 core protein following subcutaneous, intraperitoneal and intravenous immunization. (1991)

The murine immune response to baculovirus-produced human immunodeficiency virus type-1 (HIV-1)p24 was examined after injection by three different routes: subcutaneously (s.c.), intraperitoneally (i.p.) and intravenously (i.v.). Both antigen-specific T-cell proliferation and serum antibody were induced by i.p. injection. In contrast, s.c. and i.v. injection of antigen resulted in specific antibody generation alone. Lympho-proliferative responses seen after i.p. injection were confined to splenocytes, and were greater after a low dose of antigen than after a high dose. p24-specific proliferation was not detected in lymph node cells. CD4:CD8 ratios were normal in lymph nodes and spleen at all times, irrespective of the dose or route of administration. p24-specific serum IgG antibodies were detected in all animals after the second injection of antigen. After s.c. and i.v. administration of high doses of antigen, the median antibody titres continued to rise after a third injection, but plateaued in animals injected by the i.p. route. In contrast, low doses of antigen given i.p. increased the median titre during and after the course of four injections. A low antigen dose given s.c. resulted in a plateau of median titre between the third and fourth injections. In i.v.-injected animals the median titre decreased between the third and fourth injections. IgG1 p24-specific antibodies were detected in all immunized mice, whereas IgM antibodies were detectable only following i.p. injection of antigen.
Genetic polymorphisms that predict outcome and need for treatment in cardiovascular disease (2006)

A familial risk of cardiovascular disease is well known. The specific genotypes at risk are increasingly being discovered. The science has progressed to the point that genotype-specific interventions are increasingly feasible.
Murine susceptibility to radiation-induced pulmonary fibrosis is influenced by a genetic factor implicated in susceptibility to bleomycin-induced pulmonary fibrosis. (1997)

From evidence of interpatient variability in normal tissue sensitivity to radiotherapy and from radiation studies using inbred mouse strains, it is hypothesized that individual variation in susceptibility to radiation-induced pulmonary fibrosis is genetically controlled. A genetic model has been developed from the fibrosis-prone C57BL/6J and the fibrosis-resistant C3Hf/Kam mouse strains. Inheritance of the fibrotic phenotype was characterized in F1 and F2 (F1 intercross) generations derived from the parental strains. Genetic mapping was used to determine whether the quantitative trait loci (QTL), which influence susceptibility to bleomycin-induced lung fibrosis in these progenitor strains, could be implicated in susceptibility to radiation-induced lung fibrosis. Mice were treated with 14 or 16 Gy (60Co) to the whole thorax. The doses were selected to investigate the response at the LD50 and LD100 of C3Hf/Kam mice. The animals were sacrificed 33 weeks after treatment or when moribund. The percentage of lung with fibrosis for each mouse was quantified with image analysis of a histological section of the lung. For both the 14- and 16-Gy data sets, heritability was estimated at 38 +/- 11%, and the number of genetic factors influencing susceptibility to pulmonary fibrosis was estimated to be one or two. Two hundred fifty-five F2 intercross mice were genotyped with markers at the bleomycin loci on chromosomes 11 and 17 (chromosome 17 marker is at the major histocompatibility complex). Genetic linkage was established for the marker on chromosome 17 (P = 3.0 x 10(-6)), which accounts for 6.6% of the F2 phenotypic variance but not for the markers surrounding the QTL on chromosome 11 (P = 0.37). The inheritance data suggested that susceptibility to radiation-induced pulmonary fibrosis is a heritable trait controlled by two genetic loci, and through genomic mapping, a QTL on chromosome 17 was identified as one of the loci.
Mutagenesis of the Signal Sequence of Yellow Fever Virus prM Protein: Enhancement of Signalase Cleavage In Vitro Is Lethal for Virus Production (2000)

Proteolytic processing at the C-prM junction in the flavivirus polyprotein involves coordinated cleavages at the cytoplasmic and luminal sides of an internal signal sequence. We have introduced at the COOH terminus of the yellow fever virus (YFV) prM signal sequence amino acid substitutions (VPQAQA mutation) which uncoupled efficient signal peptidase cleavage of the prM protein from its dependence on prior cleavage in the cytoplasm of the C protein mediated by the viral NS2B-3 protease. Infectivity assays with full-length YFV RNA transcripts showed that the VPQAQA mutation, which enhanced signal peptidase cleavage in vitro, was lethal for infectious virus production. Revertants or second-site mutants were recovered from cells transfected with VPQAQA RNA. Analysis of these viruses revealed that single amino acid substitutions in different domains of the prM signal sequence could restore viability. These variants had growth properties in vertebrate cells which differed only slightly from those of the parent virus, despite efficient signal peptidase cleavage of prM in cell-free expression assays. However, the neurovirulence in mice of the VPQAQA variants was significantly attenuated. This study demonstrates that substitutions in the prM signal sequence which disrupt coordinated cleavages at the C-prM junction can impinge on the biological properties of the mutant viruses. Factors other than the rate of production of prM are vitally controlled by regulated cleavages at this site.
Detecting changes in aerial views of man-made structures (2002)

Many applications require detecting structural changes in a scene over a period of time. Comparing intensity values of successive images is not effective as such changes don't necessarily reflect actual changes at a site but might be caused by changes in the view point, illumination and seasons. We take the approach of comparing a 3-D model of the site, prepared from previous images, with new images to infer significant changes. This task is difficult as the images and the models have very different levels of abstract representations. Our approach consists of several steps: registering a site model to a new image, model validation to confirm the presence of model objects in the image; structural change detection seeks to resolve matching problems and indicate possibly changed structures; and finally updating models to reflect the changes. Our system is able to detect missing (or mis-modeled) buildings, changes in model dimensions, and new buildings under some conditions.
A Method to Assess Genomic DNA Methylation Using High-Performance Liquid Chromatography/Electrospray Ionization Mass Spectrometry (2002)

Eukaryotic DNA is methylated at some cytosine residues, and this epigenetic feature performs critical functions. We developed a method for quantitative determination of 5-methyl-2'-deoxycytidine in human DNA using liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS). The DNA was enzymatically hydrolyzed by sequential digestion with three enzymes. DNA hydrolyzates were subsequently separated by reversed-phase high-performance liquid chromatography in isocratic mode. The four major DNA bases and 5-methyl-2'-deoxycytidine were resolved and eluted in 13 min. Identification of 2'-deoxycytidine and 5-methyl-2'-deoxycytidine was obtained by combined diode array UV spectra analysis and mass spectra of chromatographic peaks. The isotopomers [15N3]-2'-deoxycytidine and (methyl-d3,ring-6-d1)-5-methyl-2'-deoxycytidine were used as internal standards. Ions of m/z 126 and 130 were used to detect 5-methyl-2'-deoxycytidine and its isotopomer, and ions of m/z 112 and 115 were used to detect 2'-deoxycytidine and its stable isotopomer, respectively. The DNA methylation status was calculated on the basis of the amount of 5-methyl-2'-deoxycytidine per microgram of DNA with percent relative standard deviations (%RSD) for a method precision of 7.1 (within-day) and 5.7 (day-to-day). This method also allows the measurement of 5-methyl-2'-deoxycytidine expressed as a percentage of total deoxycytidine residues in genomic DNA with %RSD for method precision of 1.9 (within-day) and 1.7 (day-to-day). This LC/MS method for quantitative determination of genomic DNA methylation status is rapid, sensitive, selective, and precise.
DUX4 recruits p300/CBP through its C-terminus and induces global H3K27 acetylation changes (2016)

Ectopic expression of the double homeodomain transcription factor DUX4 causes facioscapulohumeral muscular dystrophy (FSHD). Mechanisms of action of DUX4 are currently unknown. Using immortalized human myoblasts with a titratable DUX4 transgene, we identify by mass spectrometry an interaction between the DUX4 C-terminus and the histone acetyltransferases p300/CBP. Chromatin immunoprecipitation shows that DUX4 recruits p300 to its target gene, ZSCAN4, displaces histone H3 from the center of its binding site, and induces H3K27Ac in its vicinity, but C-terminal deleted DUX4 does not. We show that a DUX4 minigene, bearing only the homeodomains and C-terminus, is transcriptionally functional and cytotoxic, and that overexpression of a nuclear targeted C-terminus impairs the ability of WT DUX4 to interact with p300 and to regulate target genes. Genomic profiling of DUX4, histone H3, and H3 modifications reveals that DUX4 binds two classes of loci: DNase accessible H3K27Ac-rich chromatin and inaccessible H3K27Ac-depleted MaLR-enriched chromatin. At this latter class, it acts as a pioneer factor, recruiting H3K27 acetyltransferase activity and opening the locus for transcription. In concert with local increased H3K27Ac, the strong H3K27Ac peaks at distant sites are significantly depleted of H3K27Ac, thus DUX4 uses its C-terminus to induce a global reorganization of H3K27 acetylation.
Poly(A) Tail Length Control Is Caused by Termination of Processive Synthesis (1995)

Poly(A) polymerase synthesizes poly(A) tails rapidly and processively only when the substrate RNA is bound simultaneously by two stimulatory proteins, the cleavage and polyadenylation specificity factor (CPSF) and poly(A)-binding protein II (PAB II). A burst of synthesis terminates after the addition of about 250 nucleotides, a length corresponding to that of newly synthesized poly(A) tails in vivo. Further elongation is slow. Length control can be reproduced with premade poly(A) tails of different lengths and is insensitive to large changes in the elongation rate. Thus, the control mechanism truly measures the length of the poly(A) tail. The stimulatory action of PAB II is similar on long and short tails. Coating of poly(A) with one PAB II molecule for approximately 30 nucleotides is required, such that the number of PAB II molecules in the polyadenylation complex is a direct measure of poly(A) tail length. CPSF also stimulates poly(A) polymerase on long and short tails. Long tails differ from short ones only in that they do not permit the simultaneous stimulation of poly(A) polymerase by CPSF and PAB II. Consequently, elongation of long tails is distributive. Thus, length control is brought about by an interruption of the interactions responsible for rapid and processive elongation of short tails. The 3'-end of the poly(A) tail is not sequestered in the protein-RNA complex when the correct length has been reached. Neither ATP hydrolysis nor turnover of the polymerized AMP is involved in length control.
Chemical Nanolithography with Electron Beams (2001)

A highly focused electron beam as the agent for spatially selective reductionof nitro groups to amino groups in a self-assembled monolayer of aromatics is the key feature of a novel technique in chemical nanolithography presented here. Treatment of the reactive amino groups with different reactants after each e-beam writing step yields a surface with a defined array of chemically diverse structures; for example, see the line pattern in the Figure.
Growth hormone-releasing hormone and growth hormone-releasing peptide as therapeutic agents to enhance growth hormone secretion in disease and aging. (1997)

Growth hormone (GH) secretion is pulsatile and is tightly regulated. In this chapter the effects of aging, nutrition, the feedback effects of IGF-I, and the role of body composition in the decline of GH secretion will be discussed. In GH-deficient adults there is an increase in the amount of intra-abdominal (visceral) fat. Similarly, with increasing age, there is an increase in visceral fat and there is a tight correlation between 24-hour GH release and visceral fat in the elderly. This may have serious metabolic consequences, including insulin resistance and increased cardiovascular risk. There are at least four potential mechanisms for the age-related decline in GH secretion: 1) decreased release of growth hormone releasing-hormone (GHRH); 2) increased release of somatostatin; 3) enhanced sensitivity to IGF-I feedback; and 4) decreased somatotroph mass. The latter two potential mechanisms are discussed. There is little evidence that there is any change in sensitivity to IGF-I feedback with aging and the somatotroph cell mass appears to be preserved in older subjects. The GH axis may be stimulated by either GHRH or by growth hormone-releasing peptide (GHRP) and related compounds. Chronic therapy with GHRH in GH-deficient children restores GH secretion and accelerates linear growth. Mutations of the GHRH receptor lead to GH deficiency and short stature. This indicates the essential role of GHRH in regulation of GH secretion. Growth hormone releasing peptide was discovered in 1981. Recently, the GHRP/GH secretagogue receptor has been cloned and orally active GHRP mimetics have been developed. One such compound, MK-677, stimulates pulsatile GH secretion and its effects persist for 24 hours. Oral administration of MK-677 for a month in the elderly demonstrates that this route stimulates a physiologic pattern of GH secretion. The amplitude of the GH pulses was increased but the number of GH pulses was unchanged. Thus, in older individuals, the amount of GH secreted in 24 hours is restored toward that seen in young adults. This compound also enhances GH secretion in GH-deficient adults who had been GH-deficient during childhood. The development of stable, orally active molecules to stimulate the GHRP/GH secretagogue receptor is a practical reality. These GH secretagogues may have a therapeutic role in short stature and adult GH deficiency. In addition, the use of GH secretagogues in normal aging merits investigation, as growth hormone may regulate body composition in older adults.
Cdk-interacting protein 1 directly binds with proliferating cell nuclear antigen and inhibits DNA replication catalyzed by the DNA polymerase delta holoenzyme. (1994)

Cdk-interacting protein 1 (Cip1) is a p53-regulated 21-kDa protein that inhibits several members of the cyclin-dependent kinase (CDK) family. It was initially observed in complexes containing CDK4, cyclin D, and proliferating cell nuclear antigen (PCNA). PCNA, in conjunction with activator 1, acts as a processivity factor for eukaryotic DNA polymerase (pol) delta, and these three proteins constitute the pol delta holoenzyme. In this report, we demonstrate that Cip1 can also directly inhibit DNA synthesis in vitro by binding to PCNA. Cip1 efficiently inhibits simian virus 40 replication dependent upon pol alpha, activator 1, PCNA, and pol delta, and this inhibition can be overcome by additional PCNA. Simian virus 40 DNA replication, catalyzed solely by high levels of pol alpha-primase complex, is unaffected by Cip1. Using the surface plasmon resonance technique, a direct physical interaction of PCNA and Cip1 was detected. We have observed that Cip1 efficiently inhibits synthesis of long (7.2 kb) but not short (10 nt) templates, suggesting that its association with PCNA is likely to impair the processive movement of pol delta during DNA chain elongation, as opposed to blocking assembly of the pol delta holoenzyme. The implications of the Cip1-PCNA interaction with respect to regulation of DNA synthesis, cell cycle checkpoint control, and DNA repair are discussed.
Ventricular Nucleic Acid and Protein Levels with Myocardial Growth and Hypertrophy (1966)

The myocardial DNA, RNA, actomyosin, and total protein concentrations were determined in rat ventricles ranging between 251 and 1635 mg. Three phases of myocardial growth were evident. Phase 1 (ventricular weights less than 550 mg): DNA concentrations remained relatively constant with increasing ventricular weight. The increasing total DNA per ventricle suggests continuing mitotic activity. Phase 2 (ventricular weights between 550 and 1000 mg): total DNA per ventricle remained relatively constant; with ventricular growth there was a progressive decrease in DNA concentrations. This would be the phase of true myocardial hypertrophy. Phase 3: DNA concentrations continued to slowly decrease although the total DNA per ventricle increased. It would appear that this is the result of a renewed synthesis of DNA. In phases 1 and 2, the RNA concentrations progressively decreased, although the RNA/DNA ratio was increasing. This ratio appeared to reach its maximum value by the end of phase 2 and remain relatively constant in phase 3. Thus in phase 3, the concentrations of DNA and RNA simultaneously decreased to maintain this constant ratio. The ventricular total protein and ventricular actomyosin levels did not change over this range of ventricular weights.
Crystallization and preliminary X-ray diffraction studies of recombinantEscherichia coli4-diphosphocytidyl-2-C-methyl-D-erythritol synthetase (2001)

Diphosphocytidyl-methylerythritol (DPCME) synthetase is involved in the mevalonate-independent pathway of isoprenoid biosynthesis, where it catalyses the formation of 4-diphosphocytidyl-2-C-methyl-D-erythritol from 2-C-methyl-D-erythritol 4-phosphate and CTP. The Escherichia coli enzyme has been cloned, expressed in high yield, purified and crystallized. Elongated tetragonal prismatic crystals grown by the hanging-drop vapour-diffusion method using polyethylene glycol (PEG) 4000 as the precipitant belong to space group P4(1)2(1)2 (or P4(3)2(1)2), with unit-cell parameters a = b = 73.60, c = 175.56 A. Diffraction data have been recorded to 2.4 A resolution using synchrotron radiation.