gebhart/patrepeval huggingface dataset:
The C-terminus of complement regulator Factor H mediates target recognition: evidence for a compact conformation of the native protein (2006)

The complement inhibitor Factor H has three distinct binding sites for C3b and for heparin, but in solution uses specifically the most C-terminal domain, i.e. short consensus repeats (SCR) 20 for ligand interaction. Two novel monoclonal antibodies (mABs C14 and C18) that bind to the most C-terminal domain SCR 20 completely blocked interaction of Factor H with the ligands C3b, C3d, heparin and binding to endothelial cells. In contrast, several mAbs that bind to the N-terminus and to the middle regions of the molecule showed no or minor inhibitory effects when assayed by enzyme-linked immunosorbent assay (ELISA) and ligand interaction assays. This paradox between a single functional binding site identified for native Factor H versus multiple interaction sites reported for deletion constructs is explained by a compact conformation of the fluid phase protein with one accessible binding site. On zymosan particles mAbs C14 and C18 blocked alternative pathway activation completely. Thus demonstrating that native Factor H makes the first and initial contact with the C terminus, which is followed by N terminally mediated complement regulation. These results are explained by a conformational hypothetical model: the native Factor H protein has a compact structure and only one binding site accessible. Upon the first contact the protein unfolds and exposes the additional binding sites. This model does explain how Factor H mediates recognition functions during complement control and the clustering of disease associated mutations in patients with haemolytic uraemic syndrome that have been reported in the C-terminal recognition domain of Factor H.
Centering: A Parametric Theory and Its Instantiations (2004)

Centering theory is the best-known framework for theorizing about local coherence and salience; however, its claims are articulated in terms of notions which are only partially specified, such as “utterance,” “realization,” or “ranking.” A great deal of research has attempted to arrive at more detailed specifications of these parameters of the theory; as a result, the claims of centering can be instantiated in many different ways. We investigated in a systematic fashion the effect on the theory's claims of these different ways of setting the parameters. Doing this required, first of all, clarifying what the theory's claims are (one of our conclusions being that what has become known as “Constraint 1” is actually a central claim of the theory). Secondly, we had to clearly identify these parametric aspects: For example, we argue that the notion of “pronoun” used in Rule 1 should be considered a parameter. Thirdly, we had to find appropriate methods for evaluating these claims. We found that while the theory's main claim about salience and pronominalization, Rule 1—a preference for pronominalizing the backward-looking center (CB)—is verified with most instantiations, Constraint 1–a claim about (entity) coherence and CB uniqueness—is much more instantiation-dependent: It is not verified if the parameters are instantiated according to very mainstream views (“vanilla instantiation”), it holds only if indirect realization is allowed, and is violated by between 20% and 25% of utterances in our corpus even with the most favorable instantiations. We also found a trade-off between Rule 1, on the one hand, and Constraint 1 and Rule 2, on the other: Setting the parameters to minimize the violations of local coherence leads to increased violations of salience, and vice versa. Our results suggest that “entity” coherence—continuous reference to the same entities—must be supplemented at least by an account of relational coherence.
Functional assembly of two membrane-binding domains in listeriolysin O, the cytolysin of Listeria monocytogenes (2001)

Listeriolysin O (LLO) is a major virulence factor secreted by the pathogenic Listeria monocytogenes and acts as pore-forming cytolysin. Based on sequence similarities between LLO and perfringolysin (PFO), the cytolysin from Clostridium perfringens of known crystallographic structure, two truncated LLO proteins were produced: LLO-d123, comprising the first three predicted domains, and LLO-d4, the last C-terminal domain. The two proteins were efficiently secreted into the culture supernatant of L. monocytogenes and were able to bind to cell membranes. Strikingly, when expressed simultaneously, the two secreted domains LLO-d123 and LLO-d4 reassembled into a haemolytically active form. Two in-frame linker insertions were generated in the hinge region between the d123 and d4 domains. In both cases, the insertion created a major cleavage site for proteolytic degradation and abolished cytolytic activity, which might suggest that the region connecting d123 and d4 participates in the interaction between the two portions of the monomer.
Fast and secure distributed read-only file system (2000)

Internet users increasingly rely on publicly available data for everything from software installation to investment decisions. Unfortunately, the vast majority of public content on the Internet comes with no integrity or authenticity guarantees. This paper presents the self-certifying read-only file system, a content distribution system providing secure, scalable access to public, read-only data.The read-only file system makes the security of published content independent from that of the distribution infrastructure. In a secure area (perhaps off-line), a publisher creates a digitally-signed database out of a file system's contents. The publisher then replicates the database on untrusted content-distribution servers, allowing for high availability. The read-only file system protocol furthermore pushes the cryptographic cost of content verification entirely onto clients, allowing servers to scale to a large number of clients. Measurements of an implementation show that an individual server running on a 550 Mhz Pentium III with FreeBSD can support 1,012 connections per second and 300 concurrent clients compiling a large software package.
Mutant canine oral papillomavirus L1 capsid proteins which form virus-like particles but lack native conformational epitopes. (1998)

Recently, the L1 capsid protein of canine oral papillomavirus (COPV) has been used as an effective systemic vaccine that prevents viral infections of the oral mucosa. The efficacy of this vaccine is critically dependent upon native L1 conformation and, when purified from Sf9 insect cells, the L1 protein not only displays type-specific, conformation-dependent epitopes but it also assembles spontaneously into virus-like particles (VLPs). To determine whether VLP formation was coupled to the expression of conformation-dependent epitopes, we generated a series of N- and C-terminal L1 deletion mutants and evaluated their ability to form VLPs (by electron microscopy) and to react with conformation-dependent antibodies (by immunofluorescence microscopy). We found that (a) deletion of the 26 C-terminal residues generated a mutant protein which formed VLPs efficiently and folded correctly both in the cytoplasm and in the nucleus; (b) further truncation of the L1 C terminus (67 amino acids) resulted in a capsid protein which formed VLPs but which failed to express conformational epitopes; (c) deletion of the first 25 N-terminal amino acids also abolished expression of conformational epitopes (without altering VLP formation) but the native conformation of this deletion mutant could be restored by the addition of the human papillomavirus type 11 N terminus. These results demonstrate that VLP formation and conformational epitope expression can be dissociated and that the L1 N terminus has a critical role in protein folding. In addition, it appears that correct L1 protein folding is not dependent upon the nucleoplasmic environment.
The Utrophin A 5′-Untranslated Region Confers Internal Ribosome Entry Site-mediated Translational Control during Regeneration of Skeletal Muscle Fibers (2005)

Utrophin up-regulation in muscle fibers of Duchenne muscular dystrophy patients represents a potential therapeutic strategy. It is thus important to delineate the regulatory events presiding over utrophin in muscle in attempts to develop pharmacological interventions aimed at increasing utrophin expression. A number of studies have now shown that under several experimental conditions, the abundance of utrophin is increased without a corresponding elevation in its mRNA. Here, we examine whether utrophin expression is regulated at the translational level in regenerating muscle fibers. Treatment of mouse tibialis anterior muscles with cardiotoxin to induce muscle degeneration/regeneration led to a large (approximately 14-fold) increase in the levels of utrophin A with a modest change in expression of its transcript (40%). Isolation of the mouse utrophin A 5'-untranslated region (UTR) revealed that it is relatively long with a predicted high degree of secondary structure. In control muscles, the 5'-UTR of utrophin A caused an inhibition upon translation of a reporter protein. Strikingly, this inhibition was removed during regeneration, indicating that expression of utrophin A in regenerating muscles is translationally regulated via its 5'-UTR. Using bicistronic reporter vectors, we observed that this translational effect involves an internal ribosome entry site in the utrophin A 5'-UTR. Thus, internal ribosome entry site-mediated translation of utrophin A can, at least partially, account for the discordant expression of utrophin A protein and transcript in regenerating muscle. These findings provide a novel target for up-regulating levels of utrophin A in Duchenne muscular dystrophy muscle fibers via pharmacological interventions.
Regioselective and enantioselective epoxidation catalyzed by metalloporphyrins (1993)

Recent progress in regioselective and enantioselective epoxidations catalyzed by metalloporphyrins is discussed here, with an explanation of the biomimetic antecedents of this area and its relevance to synthetic applications. Classification of the catalysts that have been studied allows useful conclusions to be drawn about the development of this field. In particular, both the most promising biomimetic and practical catalysts have arisen from systems that can be systematically modified by convenient synthetic methodology.
Efficient expression of the Saccharomyces cerevisiae PGK gene depends on an upstream activation sequence but does not require TATA sequences. (1986)

The Saccharomyces cerevisiae PGK (phosphoglycerate kinase) gene encodes one of the most abundant mRNA and protein species in the cell. To identify the promoter sequences required for the efficient expression of PGK, we undertook a detailed internal deletion analysis of the 5' noncoding region of the gene. Our analysis revealed that PGK has an upstream activation sequence (UASPGK) located between 402 and 479 nucleotides upstream from the initiating ATG sequence which is required for full transcriptional activity. Deletion of this sequence caused a marked reduction in the levels of PGK transcription. We showed that PGK has no requirement for TATA sequences; deletion of one or both potential TATA sequences had no effect on either the levels of PGK expression or the accuracy of transcription initiation. We also showed that the UASPGK functions as efficiently when in the inverted orientation and that it can enhance transcription when placed upstream of a TRP1-IFN fusion gene comprising the promoter of TRP1 fused to the coding region of human interferon alpha-2.
Incorporation of Wild-Type and C-Terminally Truncated Human Epidermal Growth Factor Receptor into Human Immunodeficiency Virus-Like Particles: Insight into the Processes Governing Glycoprotein Incorporation into Retroviral Particles (1999)

Previous results have indicated that incorporation of surface glycoprotein into retroviral particles is not a specific process and that many heterologous viral and cellular glycoproteins can be incorporated as long as they do not have long cytoplasmic C-terminal regions which were presumed to be sterically inhibitory. In this study, this concept has been directly examined by analyzing the incorporation of the wild-type human epidermal growth factor receptor (Wt-EGFR) and of a C-terminally truncated mutant of Wt-EGFR (Tr-EGFR) into human immunodeficiency virus (HIV)-like particles. Incorporation was directly analyzed at the protein level and by immunogold labelling of enriched HIV-like particles. In agreement with the above concept, Tr-EGFR, with only 7 C-terminal amino acids (aa), was efficiently incorporated into HIV-like particles. Incorporation of the Wt-EGFR species, with 542 C-terminal cytoplasmic aa, was reduced by a factor of about 5 in comparison to that of the Tr-EGFR species. However, the Wt-EGFR species was still very significantly present in the HIV-like particles. A series of control experiments verified that this represents genuine incorporation of Wt-EGFR into the membrane of HIV-like particles. These observations allow further speculation as to the processes governing glycoprotein incorporation into retroviral particles and indicate that the internal virus structure of HIV (in particular the matrix layer [MA]) can accommodate much larger heterologous cytoplasmic domains in incorporated glycoproteins than previously assumed.
Effects of oviductal fluid on sperm penetration and cortical granule exocytosis during fertilization of pig oocytes in vitro (1996)

The effects of oviductal fluid on sperm penetration and cortical granule exocytosis in pigs were examined. Cortical granule exocytosis in oocytes matured in vivo and in vitro was observed by staining with fluorescent-labelled lectin and laser-scanning confocal microscopy. Exocytosis of matured oocytes was classified into three categories after in vitro fertilization: complete cortical granule exocytosis and even distribution of exudate in the entire perivitelline space (type I); complete exocytosis and partial distribution of exudate (type II) and incomplete cortical granule exocytosis (type III). The incidence of oocytes with type I exocytosis was higher in oocytes matured in vivo than in those matured in vitro. The addition of oviductal fluid at a concentration of 1% or 10% to the fertilization medium decreased sperm penetration and the mean number of spermatozoa present in penetrated eggs. The distribution of cortical granule exudate was not different in the presence of 1% oviductal fluid after sperm penetration from that of control groups. When oocytes were cultured for 1.5 h in medium containing 10% or 30% oviductal fluid before insemination, the incidence of monospermy increased without a decrease in sperm penetration. Preculture of oocytes in medium containing 30% oviductal fluid increased type I cortical granule reaction and increased resistance of the zona pellucida to dissolution by 0.1% (w/v) pronase at the time of sperm penetration. These results suggest that a factor(s) from the oviductal secretion is required for the complete cortical granule reaction and in the modification of the zona pellucida.
Identification of a pocket factor that is critical to Zika virus assembly (2020)

Zika virus (ZIKV) is an emerging mosquito borne flavivirus and a major public health concern causing severe disease. Due to the presence of a lipid membrane and structural heterogeneity, attaining an atomic resolution structure is challenging, but important to understand virus assembly and life cycle mechanisms that offer distinct targets for therapeutic intervention. We here use subvolume refinement to achieve a 3.4 Å resolution structure and identify two distinct lipid moieties. The first arises from the inner leaflet and is coordinated by hydrophobic residues of the M and E transmembrane helices that form a binding pocket not previously characterized. The second lipid arises from the outer leaflet coordinate between two E protein helices. Structure-based mutagenesis identifies critical hydrophobic interactions and their effect on the virus life cycle. Results show that lipids play an essential role in the ZIKV assembly pathway revealing a potential target of lipid based antiviral drug development.
Insulin: new roles for an ancient hormone (1999)

Recent research has greatly expanded the domain of insulin action. The classical action of insulin is the control of glucose metabolism through the dual feedback loop linking plasma insulin with plasma glucose concentrations. This canon has been revised to incorporate the impact of insulin resistance or insulin deficiency, both of which alter glucose homeostasis through maladaptive responses (namely, chronic hyperinsulinaemia and glucose toxicity). A large body of knowledge is available on the physiology, cellular biology and molecular genetics of insulin action on glucose production and uptake. More recently, a number of newer actions of insulin have been delineated from in vitro and in vivo studies. In sensitive individuals, insulin inhibits lipolysis and platelet aggregation. In the presence of insulin resistance, dyslipidaemia, hyper-aggregation and anti-fibrinolysis may create a pro-thrombotic milieu. Preliminary evidence indicates that hyperinsulinaemia per se may be pro-oxidant both in vitro and in vivo. Insulin plays a role in mediating diet-induced thermogenesis, and insulin resistance may therefore be implicated in the defective thermogenesis of diabetes. In the kidney, insulin spares sodium and uric acid from excretion; in chronic hyperinsulinaemic states, these effects may contribute to high blood pressure and hyperuricaemia. Insulin hyperpolarises the plasma membranes of both excitable and non-excitable tissues, with consequences ranging from baroreceptor desensitisation to cardiac refractoriness (prolongation of QT interval). Under some circumstances insulin is vasodilatory-the mechanism involving both the sodium-potassium pump and intracellular calcium transients. Finally, by crossing the blood-brain barrier insulin exerts a host a central effects (sympatho-excitation, vagal withdrawal, stimulation of corticotropin releasing factor), collectively resembling a stress reaction. Description and understanding of these new roles, their interactions, the interplay between insulin resistance and hyperinsulinaemia, and their implications for cardiovascular disease have only begun.
Overview of immunosuppression in liver transplantation (2009)

Continued advances in surgical techniques and immunosuppressive therapy have allowed liver transplantation to become an extremely successful treatment option for patients with end-stage liver disease. Beginning with the revolutionary discovery of cyclosporine in the 1970s, immunosuppressive regimens have evolved greatly and current statistics confirm one-year graft survival rates in excess of 80%. Immunosuppressive regimens include calcineurin inhibitors, anti-metabolites, mTOR inhibitors, steroids and antibody-based therapies. These agents target different sites in the T cell activation cascade, usually by inhibiting T cell activation or via T cell depletion. They are used as induction therapy in the immediate peri- and post-operative period, as long-term maintenance medications to preserve graft function and as salvage therapy for acute rejection in liver transplant recipients. This review will focus on existing immunosuppressive agents for liver transplantation and consider newer medications on the horizon.
Factors Affecting Blood Glucose Monitoring: Sources of Errors in Measurement (2009)

Glucose monitoring has become an integral part of diabetes care but has some limitations in accuracy. Accuracy may be limited due to strip manufacturing variances, strip storage, and aging. They may also be due to limitations on the environment such as temperature or altitude or to patient factors such as improper coding, incorrect hand washing, altered hematocrit, or naturally occurring interfering substances. Finally, exogenous interfering substances may contribute errors to the system evaluation of blood glucose. In this review, I discuss the measurement of error in blood glucose, the sources of error, and their mechanism and potential solutions to improve accuracy in the hands of the patient. I also discuss the clinical measurement of system accuracy and methods of judging the suitability of clinical trials and finally some methods of overcoming the inaccuracies. I have included comments about additional information or education that could be done today by manufacturers in the appropriate sections. Areas that require additional work are discussed in the final section.
Bulk-Type All Solid-State Batteries with 5 V Class LiNi0.5Mn1.5O4 Cathode and Li10GeP2S12 Solid Electrolyte (2016)

All solid-state batteries are of key importance in the development of next-generation energy storage devices with high energy density. Herein, we report the fabrication and operation of bulk-type 5 V-class all solid-state batteries consisting of LiNi0.5Mn1.5O4 cathode, Li10GeP2S12 solid-electrolyte, and Li metal anode. The 1st discharge capacity is about 80 mAh g–1 with an average voltage of 4.3 V. The discharge capacity gradually decreases during the subsequent cycles. X-ray diffraction and electrochemical impedance spectroscopy measurements reveal that the capacity fading results from the growth of a resistive interfacial layer on the cathode composite. The development of suitable conductive additive and sulfide solid electrolyte materials is essential for the development of high-voltage all solid-state batteries.
Chiral metal phosphate catalysis: highly asymmetric hetero-Diels–Alder reactions (2014)

We report a highly enantioselective hetero-Diels-Alder reaction of α-keto esters and isatins catalyzed by chiral calcium BINOL-derived phosphates. The structure of the catalyst is detailed by X-ray crystal structure analysis.
진행성 위암 환자에서의 5년 생존율에 관한 연구 (1985)

The records of 600 patients with diagnosis of advanced stomach cancer were reviewed from Kyung Hee University Hospital over the 6-year period, 1973 to 1979. The 5-year survivors are only 15 patients. The 30 patients died within 5-year after diagnosis were selected randomly as control group. In the 5-year survivors, total gastrectomy or by-pass procedure was performed less frequently Only 13% of the main lesion were located in cardia and high body. Involvements of adjacent organ were none Histologically, the 5-year survivors showed a tendency of less serosal invasion, less lymph node metastasis, and higher grade & more frequency of the stromal reaction.