gebhart/patrepeval huggingface dataset:
Prevention of C5 activation ameliorates spontaneous and experimental glomerulonephritis in factor H-deficient mice (2006)

Membranoproliferative glomerulonephritis (MPGN) type II (dense deposit disease) is an inflammatory renal disease characterized by electron-dense deposits and complement C3 on the glomerular basement membrane. There is no effective therapy. We investigated the role of C5 activation in a model of MPGN that develops spontaneously in complement factor H-deficient mice (Cfh(-/-)). At 12 months there was a significant reduction in mortality, glomerular cellularity, neutrophil numbers, and serum creatinine levels in Cfh(-/-) mice deficient in C5. Excessive glomerular neutrophil numbers, frequently seen in patients with MPGN during disease flares, were also observed in Cfh(-/-) mice after the administration of an antiglomerular basement membrane antibody. This exaggerated injurious phenotype was absent in Cfh(-/-) mice deficient in C5 but not in Cfh(-/-) mice deficient in C6, indicating a key role for C5 activation in the induction of renal lesions. Importantly, the renal injury was completely reversed in Cfh(-/-) mice pretreated with an anti-murine C5 antibody. These results demonstrate an important role for C5 in both spontaneous MPGN and experimentally induced nephritis in factor H-deficient mice and provide preliminary evidence that C5 inhibition therapy might be useful in human MPGN type II.
Adenylosuccinate Lyase Deficiency—First British Case (2004)

A deficiency of adenylosuccinate lyase (ASDL) is characterised by the accumulation of SAICAriboside (SAICAr) and succinyladenosine (S-Ado) in body fluids. The severity of the clinical presentation correlates with a low S-Ado/SAICAr ratio in body fluids. We report the first British case of ADSL deficiency. The patient presented at 14 days with a progressive neonatal encephalopathy and seizures. There was marked axial and peripheral hypotonia. Brain MRI showed widespread white matter changes. She died at 4 weeks of age. Concentrations of SAICAr and SAdo were markedly elevated in urine, plasma and CSF and the SAdo/SAICAr ratio was low, consistent with the severe phenotype. The patient was compound heterozygous for 2 novel ADSL mutations; c.9 G>C (A3P) and c.572 C>T (R190X).
Identification of novel conserved functional motifs across most Influenza A viral strains (2011)

The influenza virus has evolved to adapt to its host through variations in the GC content and conservation percentage of the conserved regions. Nineteen universal conserved functional motifs were discovered, of which some were accessible regions with interesting biological functions. These regions will serve as a foundation for universal drug targets as well as universal vaccine design.
Lack of myocardial perfusion immediately after successful thrombolysis. A predictor of poor recovery of left ventricular function in anterior myocardial infarction. (1992)

MCE demonstrates that angiographically successful reflow cannot be used as an indicator of successful myocardial reperfusion in AMI patients. The residual contrast defect in the risk area demonstrated immediately after reflow is a predictor of poor functional recovery of the postischemic myocardium.
Laryngotracheitis in Chickens: The Length of the Preinfectious and Infectious Periods (1989)

Transmission studies to measure the length of the infectious period and the interval between virus inoculation and infectiousness were conducted using the standard National Veterinary Services Laboratory laryngotracheitis (LT) challenge virus (Log 10(6.7) EID50 per ml). Previously unexposed sentinel chickens were placed in contact with chickens inoculated intratracheally with LT virus. Transmission of virus to the sentinel birds was assessed by studying clinical signs and results of virus isolation and challenge. Chickens began to shed infective quantities of virus 2-4 days postinoculation and continued until day 6.
The CRISPR tool kit for genome editing and beyond (2018)

CRISPR is becoming an indispensable tool in biological research. Once known as the bacterial immune system against invading viruses, the programmable capacity of the Cas9 enzyme is now revolutionizing diverse fields of medical research, biotechnology, and agriculture. CRISPR-Cas9 is no longer just a gene-editing tool; the application areas of catalytically impaired inactive Cas9, including gene regulation, epigenetic editing, chromatin engineering, and imaging, now exceed the gene-editing functionality of WT Cas9. Here, we will present a brief history of gene-editing tools and describe the wide range of CRISPR-based genome-targeting tools. We will conclude with future directions and the broader impact of CRISPR technologies.
Small bowel bacterial overgrowth is a common cause of chronic diarrhea (2004)

Small bowel bacterial overgrowth is a common (33-67%) cause of chronic diarrhea.
Folate and Cancer Prevention: A New Medical Application of Folate Beyond Hyperhomocysteinemia and Neural Tube Defects (2009)

Folate is an important cofactor in the transfer of one-carbon moieties and plays a key role in DNA synthesis, repair, and methylation. The role of folate has greatly evolved from the prevention of macrocytic anemia to the prevention of cardiovascular disease and neural tube defects. More recently, epidemiologic, animal, and clinical evidence suggests that folate may also play a role in cancer prevention. Two recently published large, prospective epidemiologic studies suggest that maintaining adequate levels of serum folate or moderately increasing folate intakes from dietary sources and vitamin supplements can significantly reduce the risk of pancreatic and breast cancer, respectively. This protective effect of folate appears to be operative in subjects at risk for developing these cancers, namely, male smokers for pancreatic cancer and women regularly consuming a moderate amount of alcohol for breast cancer. Because the expanding role of folate nutrition in cancer prevention has major public health implications, research is required to clearly elucidate the effect of folate on carcinogenesis.
Expression of the Pseudomonas putida OCT Plasmid Alkane Degradation Pathway Is Modulated by Two Different Global Control Signals: Evidence from Continuous Cultures (2003)

Expression of the genes of the alkane degradation pathway encoded in the Pseudomonas putida OCT plasmid are subject to negative and dominant global control depending on the carbon source used and on the physiological status of the cell. We investigated the signals responsible for this control in chemostat cultures under conditions of nutrient or oxygen limitation. Our results show that this global control is not related to the growth rate and responds to two different signals. One signal is the concentration of the carbon source that generates the repressing effect (true catabolite repression control). The second signal is influenced by the level of expression of the cytochome o ubiquinol oxidase, which in turn depends on factors such as oxygen availability or the carbon source used. Since under carbon limitation conditions the first signal is relieved but the second signal is not, we propose that modulation mediated by the cytochrome o ubiquinol oxidase is not classical catabolite repression control but rather a more general physiological control mechanism. The two signals have an additive, but independent, effect, inhibiting induction of the alkane degradation pathway.
Turker-Assisted Paraphrasing for English-Arabic Machine Translation (2010)

This paper describes a semi-automatic paraphrasing task for English-Arabic machine translation conducted using Amazon Mechanical Turk. The method for automatically extracting paraphrases is described, as are several human judgment tasks completed by Turkers. An ideal task type, revised specifically to address feedback from Turkers, is shown to be sophisticated enough to identify and filter problem Turkers while remaining simple enough for non-experts to complete. The results of this task are discussed along with the viability of using this data to combat data sparsity in MT. 1
Nonhematopoietic cells selected for resistance to tumor necrosis factor produce tumor necrosis factor. (1986)

TNF-resistant lines of L cells can be derived from TNF-sensitive populations by repeated exposure to TNF, and these resistant L cells, in contrast to sensitive L cells and other types of cells, lack demonstrable cell surface receptors for TNF. We have now found that TNF-resistant L cells produce a factor that is cytotoxic for L cells and has the following distinguishing characteristics of mouse TNF: it is a protein of 43 kD, composed of 16 kD subunits, that competes with TNF for receptor binding, induces hemorrhagic necrosis of the TNF-sensitive mouse sarcoma Meth A, has synergistic cytotoxic action with interferon, and its activity is neutralized by antibody to TNF. The two conclusions of this study are that cells selected for TNF resistance spontaneously produce a molecule resembling macrophage TNF, and that cells of nonhematopoietic origin are capable of producing TNF.
Artificial Placenta: Two Days of Total Extrauterine Support of the Isolated Premature Lamb Fetus (1969)

A premature lamb fetus was totally sustained by extracorporeal perfusion with the use of a silicone-membrane blood oxygenator and parenteral nutritional support. The fetus remained in a metabolically stable state lasting several days.
Inactivation of Cytochrome P450 3A4 by Bergamottin, a Component of Grapefruit Juice (1998)

Grapefruit juice has been found to significantly increase oral bioavailability of several drugs metabolized by cytochrome P450 3A4 (P450 3A4) through inhibiting the enzymatic activity and decreasing the content of intestinal P450 3A4. HPLC/MS/MS and HPLC/UV analyses of ethyl acetate extracts from grapefruit juice revealed the presence of several furanocoumarins of which bergamottin (BG) is the major one. BG was shown to inactivate P450 3A4 in a reconstituted system consisting of purified P450 3A4, NADPH-cytochrome P450 reductase, cytochrome b5, and phospholipids. Inactivation was time- and concentration-dependent and required metabolism of BG. The loss of catalytic activity exhibited pseudo-first-order kinetics. The values of kinactivation and KI calculated from the inactivation studies were 0.3 min-1 and 7.7 microM, respectively. While approximately 70% of the erythromycin N-demethylation activity was lost during incubation with BG in the reconstituted system, P450 3A4 retained more than 90% of the heme as determined either by UV-visible spectroscopy or by HPLC. However, approximately 50% of the apoP450 in the BG-inactivated P450 3A4 incubation mixture could not be recovered from a reverse-phase HPLC column when compared with the -NADPH control. The mechanism of the inactivation appears to involve modification of the apoP450 in the active site of the enzyme instead of heme adduct formation or heme fragmentation. These results indicate that BG, the primary furanocoumarin extracted from grapefruit juice, is a mechanism-based inactivator of P450 3A4. BG was also found to inhibit the activities of P450s 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4 in human liver microsomes.
Peptides Targeting Protein Kinases: Strategies and Implications (2006)

Protein kinases are important key regulators in most, if not all, biological processes and are linked with many human diseases. Protein kinases thus became attractive targets for drug design. Intracellularly active peptides that selectively interfere with kinase function and or kinase-mediated signaling pathways are potential drug compounds with therapeutic implications.
A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV (2020)

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has now become a pandemic, but there is currently very little understanding of the antigenicity of the virus. We therefore determined the crystal structure of CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient, in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein at 3.1-angstrom resolution. CR3022 targets a highly conserved epitope, distal from the receptor binding site, that enables cross-reactive binding between SARS-CoV-2 and SARS-CoV. Structural modeling further demonstrates that the binding epitope can only be accessed by CR3022 when at least two RBDs on the trimeric S protein are in the "up" conformation and slightly rotated. These results provide molecular insights into antibody recognition of SARS-CoV-2.
Application of the Ribonuclease P (RNase P) RNA Gene Sequence for Phylogenetic Analysis of the Genus Saccharomonospora (1998)

Sequences of the RNase P RNA gene were investigated for the phylogenetic analysis of the genus Saccharomonospora. Aligned nucleotide sequences, determined from the PCR-amplified RNase P RNA gene of representative strains of the genus Saccharomonospora, displayed 94.2 +/- 1.3% interspecific variances. The intraspecific similarity value was 99.7-100% in all species tested. Saccharomonospora azurea K161T and 'Saccharomonospora caesia' K76T displayed identical RNase P RNA gene sequences in the region that was determined and Saccharomonospora sp. K180 showed sequences distinct from validly described species with a similarity value of 94.6 +/- 1.0%. The phylogenetic trees constructed by aligning the sequences either within the genus Saccharomonospora or with other Gram-positive bacteria were similar to the ones derived using sequences of the 16S rDNA gene. Advantageous features of this gene for application as a molecular phyletic marker are discussed.
Propofol modulates activation and desensitization of GABAA receptors in cultured murine hippocampal neurons (1994)

Propofol (2,6 di-isopropylphenol) is an alkyphenol recently introduced for use as a general anesthetic. The modulation of GABAA receptor activation and desensitization by propofol was studied using a rapid perfusion system and whole-cell voltage-clamp recordings from mouse hippocampal neurons. The effects of concentrations of propofol used clinically on single-channel and synaptic currents were also examined. Propofol evoked current responses (EC50 = 61 microM) and shifted the dose-response curve of GABA-activated current to the left without altering the maximum of the GABA response. Preincubation with propofol and GABA led to desensitization of the GABA response (EC50 = 454 microM and 23 microM, respectively). Saturating concentrations of GABA (600 microM) evoked currents that peaked and then declined in a biexponential fashion with fast and slow time constants of tau f = 1.0 sec and tau s = 3.5 sec. Propofol (10 microM) did not change the amplitude of the peak response but decreased the rates of decay approximately 1.5-fold and enhanced the steady-state current proportionately. Recovery from desensitization was also biexponential (tau f = 11 sec, tau s = 69 sec) but not influenced by propofol. Single-channel recordings from outside-out patches demonstrated that both propofol and GABA activated channels with a 30 pS and 21 pS open state. Propofol increased the frequency but not the duration or conductance of GABA-activated events. Miniature inhibitory postsynaptic currents (mlPSCs) were evoked by the application of hypertonic sucrose to the cell soma. Propofol (2 microM) prolonged the decay time of mlPSCs to an extent similar to which it increased the open probability of GABA-activated channels (2.3- vs 3-fold). A sequential model, based on a previous scheme of GABA receptor gating (Weiss and Magelby, 1989), is presented to summarize propofol's actions on GABAA receptor function. We show through simulation that the model reliably reproduced the whole-cell tracings. Our results indicate that propofol's neurodepressive actions will be associated with enhancement of inhibitory synaptic transmission.
Nucleotide Sequence of an Arabidopsis cDNA for Geranylgeranyl Pyrophosphate Synthase (1994)

GGPS is an enzyme involved in the early steps of isoprenoid synthesis in plants. The bell pepper (Capsicum annuum) GGPS catalyzes the stepwise addition of isopentenyl PPi, first to dimethylallyl PPi, second to geranyl PPi, and fmally to farnesyl PPi to form geranylgeranyl PPi (Kuntz et al., 1992). Geranylgeranyl PPi is utililized by plants for many compounds such as carotenoids, Chls, and phylloquinones and as a precursor for GA3. A plant GGPS cDNA from
Compstatin, a peptide inhibitor of C3, prolongs survival of ex vivo perfused pig xenografts (1999)

Compstatin, a newly described C3-binding peptide, inhibits complement activation by blocking C3 convertase-mediated cleavage of C3. As the complement activation is an essential part of the rejection reaction, we evaluated the ability of Compstatin to delay or prevent hyperacute rejection in an ex vivo xenograft model. Pig kidneys were perfused with fresh human blood containing either Compstatin (n=6) or a control agent (n=6). Graft survival and activation of complement, leukocytes and platelets both in the fluid-phase and in the tissue were examined. The survival of the Compstatin-perfused kidneys (median, 380 min) was significantly (P=0.0036) longer than that of the controls (median, 90 min). The classical complement pathway (C1rs-C1inhibitor and C4bc) was significantly and equally activated in both groups during the first 60 min. C3 activation products increased fivefold and terminal complement complex eightfold in the control group, but no increase occurred in the Compstatin group during this period. Immunohistochemistry showed less C3 and fibrin deposition and immune electron microscopy showed less terminal SC5b-9 complement complex deposition in the Compstatin group. A significant change in total white cells, neutrophils, myeloperoxidase, and expression of the surface activation markers CD11b (CR3) and CD35 (CR1) and CD62L (L-selectin) was observed in both groups. Leukocyte activation was lower in the Compstatin group but the difference was not statistically significant. There were no differences in platelet counts, thrombospondin, soluble P-selectin or beta-thromboglobulin between the groups. We conclude that Compstatin prolongs graft survival and suggest that it may be a useful agent for attenuating hyperacute rejection by inhibiting C3 and thus terminal complement pathway activation.
Critical role for PAR1 in kallikrein 6‐mediated oligodendrogliopathy (2013)

Kallikrein 6 (KLK6) is a secreted serine protease preferentially expressed by oligodendroglia in CNS white matter. Elevated levels of KLK6 occur in actively demyelinating multiple sclerosis (MS) lesions and in cases of spinal cord injury (SCI), stroke, and glioblastoma. Taken with recent evidence establishing KLK6 as a CNS-endogenous activator of protease-activated receptors (PARs), we hypothesized that KLK6 activates a subset of PARs to regulate oligodendrocyte physiology and potentially pathophysiology. Here, primary oligodendrocyte cultures derived from wild type or PAR1-deficient mice and the murine oligodendrocyte cell line, Oli-neu, were used to demonstrate that Klk6 (rodent form) mediates loss of oligodendrocyte processes and impedes morphological differentiation of oligodendrocyte progenitor cells (OPCs) in a PAR1-dependent fashion. Comparable gliopathy was also elicited by the canonical PAR1 agonist, thrombin, as well as PAR1-activating peptides (PAR1-APs). Klk6 also exacerbated ATP-mediated oligodendrogliopathy in vitro, pointing to a potential role in augmenting excitotoxicity. In addition, Klk6 suppressed the expression of proteolipid protein (PLP) RNA in cultured oligodendrocytes by a mechanism involving PAR1-mediated Erk1/2 signaling. Microinjection of PAR1 agonists, including Klk6 or PAR1-APs, into the dorsal column white matter of PAR1(+/+) but not PAR1(-/-) mice promoted vacuolating myelopathy and a loss of immunoreactivity for myelin basic protein (MBP) and CC-1(+) oligodendrocytes. These results demonstrate a functional role for Klk6-PAR1 signaling in oligodendroglial pathophysiology and suggest that antagonists of PAR1 or its protease agonists may represent new modalities to moderate demyelination and to promote myelin regeneration in cases of CNS white matter injury or disease.
Proteasome inhibition-induces endoplasmic reticulum dysfunction and cell death of human cholangiocarcinoma cells (2007)

Proteasome inhibition induces ER dysfunction and caspase-independent cell death selectively in human cholangiocarcinoma cells. Proteasome inhibitors warrant evaluation as anticancer agents for the treatment of human cholangiocarcinoma.
Noise and the Kelvin method (1991)

The Kelvin probe, used to measure changes in work function (wf), has proved particularly useful as a UHV surface analysis technique, having applications in the study of thin films, adsorption kinetics, surface photovoltage spectroscopy, surface topographies, etc. However the Kelvin circuit is plagued by noise problems, which are considerably enhanced by long connecting wires and the nonideal UHV environment. Careful shielding is essential in order to improve the signal-to-noise (S/N) ratio, especially at backing potentials close to the null condition. Although lock-in-amplifier (LIA) based automatic compensation systems are available they operate on low signal levels and are prone to electromagnetic pickup from the driving element and mechanical instabilities of the vibrating capacitor. We discuss the general noise spectrum and describe an alternative ‘‘off-null’’ approach utilizing a data-acquisition-system (DAS) based measuring system that features an active suspension system (ASS), automatic set-up, and software elimination of driver talkover. This system has applications where very high resolution (&amp;lt;0.1 meV) is required, or if low S/N ratios caused by reduced probe dimensions or a high noise background would otherwise prejudice the measurement.
Detection of Chlamydia trachomatis in Clinical Specimens by Nucleic Acid (1985)

A nucleic acid spot hybridization assay was used to detect Chlamydia trachomatis DNA. The hybridization probes included DNA isolated from elementary bodies of lymphogranuloma venereum (LGV) strains and cloned fragments of both chromosomal and plasmid DNA. The sensitivity of the test was in the range 10 to 100 pg homologous DNA and 10 in vitro infected cells. Cross-reactivity with bacterial DNA was avoided when purified chlamydia-specific DNA fragments were used as probes. C. trachomatis was detectable in most of the clinical specimens with large amounts of infectious particles. Also some isolation-negative specimens gave a positive signal in the test.
Proofs that yield nothing but their validity and a methodology of cryptographic protocol design (1986)

In this paper we demonstrate the generality and wide applicability of zero-knowledge proofs, a notion introduced by Goldwasser, Micali and Rackoff. These are probabilistic and interactive proofs that, for the members x of a language L, efficiently demonstrate membership in the language without conveying any additional knowledge. So far, zero-knowledge proofs were known only for some number theoretic languages in NP ∩ Co-NP.