gebhart/patrepeval huggingface dataset:
The catalytic triad of the influenza C virus glycoprotein HEF esterase: characterization by site-directed mutagenesis and functional analysis (1995)

Influenza C virus is able to inactivate its own cellular receptors by virtue of a sialate 9-O-acetylesterase that releases the acetyl residue at position C-9 of N-acetyl-9-O-acetylneuraminic acid (Neu5,9Ac2). The receptor-destroying enzyme activity is a function of the surface glycoprotein HEF and this esterase belongs to the class of serine hydrolases. In their active site, these enzymes contain a catalytic triad made up of a serine, a histidine and an aspartic acid residue. Sequence comparison with other serine esterases has indicated that, in addition to serine-71 (S71), the amino acids histidine-368 or -369 (H368/369) and aspartic acid 261 (D261) are the most likely candidates to form the catalytic triad of the influenza C virus glycoprotein. By site-directed mutagenesis, mutants were generated in which alanine substituted for either of these amino acids. Using a phagemid expression vector, pSP1D-HEF the HEF gene was expressed in both COS 7 and MDCK I cells. The glycoprotein was obtained in a functional form only in the latter cells, as indicated by its transport to the cell surface and measurable enzyme activity. The low level of expression could be increased by stimulating the NF-KB-binding activity of the cytomegalovirus immediate-early promoter/enhancer element of the vector. The esterase activity of the mutant proteins was compared with that of the wild-type glycoprotein. With Neu5,9Ac2 as the substrate, the esterase specific activities of the S71/A mutant and the H368,369/A mutant were reduced by more than 90%. In the case of the D261/A mutant the specific activity was reduced by 64%. From this data we conclude that S71, H368/369 and D261 are likely to represent the catalytic triad of the influenza C virus glycoprotein HEF. In addition, N280 is proposed to stabilize the oxyanion of the presumptive transition state intermediate formed by the enzyme-substrate complex.
Chemical modification of the reducing chain end in dextrans and trimethylsilylation of its hydroxyl groups (1991)

Abstract The reducing ends of dextrans, of which number‐average molecular weights were 3600 and 16000, were almost quantitatively converted to lactone, amine, and acyllactam groups, successively, by iodine oxidation followed by lactonization, aminolysis with 1,4‐diaminobutane, and finally reaction with terephthaloylbis (ϵ‐caprolactam). Hydroxyl groups in dextrans were also trimethylsilylated for protection with a mixture of 1,1,1,3,3,3‐hexamethyldisilazane and trimethylchlorosilane. In advance of every run, the adequate reaction conditions were search by using D ‐maltose as a low molecular weight model compound for dextrans.
Reversible photochromism of polynorbornenes bearing spiropyran side groups (2012)

In this paper, the synthesis and characterization of poly(norbornene) homo- and copolymers bearing spiropyran side groups are described. Difficulties in the homopolymerization of spiropyrans due to the opened merocyanine form were observed leading to low polymerization yields for homopolymers while copolymers with 10 mol% spiropyran content were prepared in good yield. Spiropyrans are characterized by their reversible photochromism, which was conserved in the polymers as shown by UV–Vis spectroscopy and FT-IR spectroscopy. The switching between the apolar spiropyran form and the zwitterionic merocyanine form also leads to switchable wettability as evidenced by contact angle measurements.
Physical Mapping of a Translocation Breakpoint in Neurofibromatosis (1989)

The gene for von Recklinghausen neurofibromatosis (NF1), one of the most common autosomal-dominant disorders of humans, was recently mapped to chromosome 17 by linkage analysis. The identification of two NF1 patients with balanced translocations that involved chromosome 17q11.2 suggests that the disease can arise by gross rearrangement of the NF1 locus, and that the NF1 gene might be identified by cloning the region around these translocation breakpoints. To further define the region of these translocations, a series of chromosome 17 Not I-linking clones has been mapped to proximal 17q and studied by pulsed-field gel electrophoresis. One clone, 17L1 (D17S133), clearly identifies the breakpoint in an NF1 patient with a t(1;17) translocation. A 2.3-megabase pulsed-field map of this region was constructed and indicates that the NF1 breakpoint is only 10 to 240 kilobases away from 17L1. This finding prepares the way for the cloning of NF1.
Minireview: The OPG/RANKL/RANK System (2001)

The identification of the OPG/RANKL/RANK system as the dominant, final mediator of osteoclastogenesis represents a major advance in bone biology. It ended a long-standing search for the specific factor produced by preosteoblastic/stromal cells that was both necessary and sufficient for osteoclast development. The initial cloning and characterization of OPG as a soluble, decoy receptor belonging to the TNF receptor superfamily was the first step that eventually led to an unraveling of this system. Soon thereafter, the molecule blocked by OPG, initially called OPG-ligand/osteoclast differentiating factor (ODF) and subsequently RANKL, was identified as the key mediator of osteoclastogenesis in both a membrane-bound form expressed on preosteoblastic/stromal cells as well as a soluble form. RANKL, in turn, was shown to bind its receptor, RANK, on osteoclast lineage cells. The decisive role played by these factors in regulating bone metabolism was demonstrated by the findings of extremes of skeletal phenotypes (osteoporosis vs. osteopetrosis) in mice with altered expression of these molecules. Over the past several years, work has focused on identifying the factors regulating this system, the signaling mechanisms involved in the RANKL/RANK pathway, and finally, potential alterations in this system in metabolic bone disorders, from the extremely common (i.e. postmenopausal osteoporosis) to the rare (i.e. familial expansile osteolysis).
Development of a Mouse-Adapted Live Attenuated Influenza Virus That PermitsIn VivoAnalysis of Enhancements to the Safety of Live Attenuated Influenza Virus Vaccine (2015)

The live attenuated influenza virus vaccine (LAIV) is preferentially recommended for use in persons 2 through 49 years of age but has not been approved for children under 2 or asthmatics due to safety concerns. Therefore, increasing safety is desirable. Here we describe a murine LAIV with reduced pathogenicity that retains lethality at high doses and further demonstrate that we can enhance safety in vivo through mutations within NS1. This model may permit preliminary safety analysis of improved LAIVs.
Chlamydia trachomatis60 kDa cysteine rich outer membrane protein: sequence homology between trachoma and LGV biovars (1989)

An 820 bp AccI-PstI fragment of the 60 kDa cysteine rich outer membrane protein (CrP) gene from C. trachomatis serovar L1 was used as a probe to locate the 60 kDa CrP gene of a recent serovar B trachoma isolate (Jali 20/OT). The probe hybridized to a single 1.8 kb SpeI fragment in Southern blot analyses of different restriction endonuclease digests of C. trachomatis serovar B DNA. This fragment was ligated into Lambda Zap II arms and Bluescript SK(-) recombinants, released by infection with the helper phage R408, were used as template for DNA sequence determination. Sequence analysis demonstrated a very high level of homology between the Jali 20/OT 60 kDa CrP and the previously published serovar L1 60 kDa CrP with only 8 out of 507 amino acid substitutions between the two proteins.
Functional human CFTR produced by stable Chinese hamster ovary cell lines derived using yeast artificial chromosomes (1997)

The cystic fibrosis transmembrane conductance regulator gene (CFTR) encodes a transmembrane protein (CFTR) which functions in part as a cyclic adenosine monophosphate (cAMP)-regulated chloride channel. CFTR expression is controlled temporally and cell specifically by mechanisms that are poorly understood. Insight into CFTR regulation could be facilitated by the successful introduction of the entire 230 kb human CFTR and adjacent sequences into mammalian cells. To this end, we have introduced two different CFTR-containing yeast artificial chromosomes (YACs) (320 and 620 kb) into Chinese hamster ovary-K1 (CHO) cells. Clonal cell lines containing human CFTR were identified by PCR, and the genetic and functional analyses of one clone containing each YAC are described. Integration of the human CFTR-containing YACs into the CHO genome at a unique site in each cell line was demonstrated by fluorescence in situ hybridization (FISH). Southern blot analysis suggested that on the order of one copy of human CFTR was integrated per CHO cell genome. Fiber-FISH and restriction analysis suggested that CFTR remained grossly intact. Northern analysis showed full-length, human CFTR mRNA. Immunoprecipitation followed by phosphorylation with protein kinase demonstrated mature, glycosylated CFTR. Finally, chloride secretion in response to cAMP indicated the functional nature of the human CFTR. This study provides several novel results including: (i) functional human CFTR can be expressed from these YACs; (ii) CHO cells are a permissive environment for expression of human CFTR; (iii) the level of human CFTR expression in CHO cells is unexpectedly high given the lack of endogenous CFTR production; and (iv) the suggestion by Fiber-FISH of CFTR integrity correlates with functional gene expression. These YACs and the cell lines derived from them should be useful tools for the study of CFTR expression.
Copper-67-labeled monoclonal antibody Lym-1, a potential radiopharmaceutical for cancer therapy: labeling and biodistribution in RAJI tumored mice. (1988)

Copper-67 (67Cu) is one of the most promising radiometals for radioimmunotherapy because of its 61.5 hr physical half-life, abundant beta particles, and gamma emissions suitable for imaging. However, 67Cu is readily transferred from the usual chelates of EDTA or DTPA to albumen. We developed a new macrocycle (6-p-nitrobenzyl-TETA) to chelate copper. Bifunctional chelating agent p-bromoacetamidobenzyl-TETA was conjugated to Lym-1, a monoclonal antibody against human B cell lymphoma, without significantly altering its immunoreactivity. This conjugate was stably labeled with 67Cu under conditions chosen to optimize the yield of a high specific activity radiopharmaceutical. The biodistribution in RAJI tumor bearing mice demonstrated significant tumor uptake (14.7% ID per gram) and extended residence time (120 hr) in contrast to normal organs. After 24 hr, radioactivity was continuously cleared from all tissues except the tumor. This study suggests 67Cu labeled Lym-1 to be a promising radiopharmaceutical for potential use for radioimmunotherapy of B cell lymphoma.
Seven‐Year Surveillance of North American Pediatric Group A Streptococcal Pharyngitis Isolates (2009)

Although overall US and Canadian emm type distribution was consistent and relatively few types dominated nationally, striking intersite and temporal variations within individual sites in prevalent emm types of GAS occurred. These results have important implications for the development and formulation of type-specific GAS vaccines.
Identification of antigenic sites on three hepatitis C virus proteins using phage-displayed peptide libraries (1998)

A novel approach to screening phage-displayed peptide libraries has been used to identify hepatitis C virus (HCV) core, NS4 and NS5 sequences, which are antigenic in humans. Two random peptide libraries were used for screening using a mixture of HCV-positive sera or individual antibodies to core, NS3, NS4, and NS5 HCV proteins affinity-purified from this mixture. Sequencing of 56 selected phage clones resulted in 28 different peptide sequences and identification of seven antigenic regions, three in the core protein (19-26, 34-49, and 73-83), three in the NS4 (1681-1693, 1712-1718, and 1726-1736) and one in the NS5 protein (2251-2260). No NS3-specific peptides were identified. The immune response to core, NS4 and NS5 proteins includes a variety of linear determinants whereas epitopes on the investigated part of NS3 protein appear to be conformation-dependent.
Towards the prioritization of system test cases (2013)

SUMMARY During software development, companies are frequently faced with lack of time and resources, which limits their ability to effectively complete testing efforts. This paper presents a system‐level, value‐driven approach to test case prioritization called the Prioritization of Requirements for Test (PORT). PORT involves analysing and assigning value to each requirement using the following four factors: requirements volatility, customer priority, implementation complexity, and fault proneness. System test cases are prioritized such that the test cases for requirements with higher priority are executed earlier during system test. PORT was applied to four student team projects as well as an industrial case study. The results show that PORT improves the rate of detection of severe failures over random prioritization. Additionally, the results indicate that customer priority was the most important contributor towards improved rate of failure detection. Copyright © 2013 John Wiley &amp; Sons, Ltd.
Developmental Neurocircuitry of Motivation in Adolescence: A Critical Period of Addiction Vulnerability (2003)

An exploration of developmental changes in neurocircuitry involved in impulse control has significant implications for understanding adolescent behavior, addiction vulnerability, and the prevention of addiction in adolescence and adulthood.
Planning sensing strategies in a robot work cell with multi-sensor capabilities (1989)

An approach is presented for planning sensing strategies dynamically on the basis of the system's current best information about the world. The approach is for the system to propose a sensing operation automatically and then to determine the maximum ambiguity which might remain in the world description if that sensing operation were applied. The system then applies that sensing operation which minimizes this ambiguity. To do this, the system formulates object hypotheses and assesses its relative belief in those hypotheses to predict what features might be observed by a proposed sensing operation. Furthermore, since the number of sensing operations available to the system can be arbitrarily large, equivalent sensing operations are grouped together using a data structure that is based on the aspect graph. In order to measure the ambiguity in a set of hypotheses, the authors apply the concept of entropy from information theory. This allows them to determine the ambiguity in a hypothesis set in terms of the number of hypotheses and the system's distribution of belief among those hypotheses.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Paediatric burns anaesthesia : the things that make a difference : review (2014)

Anaesthesia and pain management for paediatric burns continues to challenge and frustrate healthcare professionals in this field of medicine. This review aims to provide some practical management strategies to enable the improved care of burned children. The pathophysiology of burns, toxic shock syndrome, inhalational injuries and perioperative care of paediatric burns is addressed.
Extracellular Signal–Regulated Kinase 1/2 Mitogen-Activated Protein Kinase Pathway Is Involved in Myostatin-Regulated Differentiation Repression (2006)

The cytokines of transforming growth factor beta (TGF-beta) and its superfamily members are potent regulators of tumorigenesis and multiple cellular events. Myostatin is a member of TGF-beta superfamily and plays a negative role in the control of cell proliferation and differentiation. We now show that myostatin rapidly activated the extracellular signal-regulated kinase 1/2 (Erk1/2) cascade in C2C12 myoblasts. A more remarkable Erk1/2 activation stimulated by myostatin was observed in differentiating cells than proliferating cells. The results also showed that Ras was the upstream regulator and participated in myostatin-induced Erk1/2 activation because the expression of a dominant-negative Ras prevented myostatin-mediated inhibition of Erk1/2 activation and proliferation. Importantly, the myostatin-suppressed myotube fusion and differentiation marker gene expression were attenuated by blockade of Erk1/2 mitogen-activated protein kinase (MAPK) pathway through pretreatment with MAPK/Erk kinase 1 (MEK1) inhibitor PD98059, indicating that myostatin-stimulated activation of Erk1/2 negatively regulates myogenic differentiation. Activin receptor type IIb (ActRIIb) was previously suggested as the only type II membrane receptor triggering myostatin signaling. In this study, by using synthesized small interfering RNAs and dominant-negative ActRIIb, we show that myostatin failed to stimulate Erk1/2 phosphorylation and could not inhibit myoblast differentiation in ActRIIb-knockdown C2C12 cells, indicating that ActRIIb was required for myostatin-stimulated differentiation suppression. Altogether, our findings in this report provide the first evidence to reveal functional role of the Erk1/2 MAPK pathway in myostatin action as a negative regulator of muscle cell growth.
Generator-produced copper-62-PTSM as a myocardial PET perfusion tracer compared with nitrogen-13-ammonia. (1996)

These results suggest that the MBF estimates using 62Cu-PTSM in a low flow range may be as accurate as those with 13NH3. In a high flow range, however, the extraction fraction of 62Cu-PTSM is considered to be lower than that of 13NH3, and this may limit the estimation of MBF with 62Cu-PTSM after pharmacological vasodilatation.
Propene Polymerization with the Isospecific, Highly Regioselective rac-Me2C(3-t-Bu-1-Ind)2ZrCl2/MAO Catalyst. 2. Combined DFT/MM Analysis of Chain Propagation and Chain Release Reactions (2001)

A combined DFT/MM analysis has been carried out on the chain propagation steps and on possible mechanisms for the formation of unsaturations in propene polymerization catalyzed by rac-Me2C(3-t-Bu-1-Ind)2ZrCl2/methylalumoxane (1/MAO). The results are compared to the available experimental data on its polymerization performance. The insertion of the si propene enantioface at the R,R site is favored by 4.0−6.0 kcal/mol, in good agreement with the (slightly underestimated) experimental value of 4.6 kcal/mol. Mechanistic aspects related to highly hindered catalysts are also discussed. The large amount of allyl end groups measured in i-PP produced at any [propene] can be rationalized, especially at the highest monomer concentration, by allylic activation of a coordinated propene; allyl end groups formed by this route add to those formed by the unimolecular β-Me transfer reaction. Chain release mechanisms involving a coordinated propene (allylic activation and β-H transfer) kinetically compete. The relatively high rate of chain-end epimerization observed for this catalyst, as well as the presence of internal vinylidene groups, can be rationalized by the relatively high stability of the product of β-H transfer to the metal due to a H2C−H···Zr agostic interaction. Allylic activation of the growing chain end followed by propene insertion is the source of internal vinylidene unsaturations, but likely not of epimerization. Calculations support the hypothesis that the allylic chain end activation could also occur upon β-H transfer to a coordinated monomer; hence, the formation of internal vinylidenes could also proceed without developing H2. Finally, we conclude that within the single-center, two-state catalyst model developed to account for the nonlinear activity/[M] relationship, the fast propagating site is the Zr−CH2CH(CH3)P, while the Zr−C(CH3)2P (tertiary alkyl) formed during the course of chain epimerization, proposed by Busico, represents a suitable model for the catalyst resting state.
Targeted Liposome‐Loaded Microbubbles for Cell‐Specific Ultrasound‐Triggered Drug Delivery (2013)

One of the main problems in cancer treatment is disease relapse through metastatic colonization, which is caused by circulating tumor cells (CTCs). This work reports on liposome-loaded microbubbles targeted to N-cadherin, a cell-cell adhesion molecule expressed by CTCs. It is shown that such microbubbles can indeed bind to N-cadherin at the surface of HMB2 cells. Interestingly, in a mixture of cells with and without N-cadherin expression, binding of the liposome-loaded microbubbles mainly occurs to the N-cadherin-expressing cells. Importantly, applying ultrasound results in the intracellular delivery of a model drug (loaded in the liposomes) in the N-cadherin-expressing cells only. As described in this paper, such liposome-loaded microbubbles may find application as theranostics and in devices aimed for the specific killing of CTCs in blood.
A Miniaturized Nafion-Based Glucose Sensor: in vitro and in vivo evaluation in dogs (1994)

We have developed an implantable glucose sensor based on a new tri-layer membrane configuration. The needle-type sensor integrates a Pt working electrode and a Ag/AgCl reference electrode. Its size is equivalent to a 25 gauge needle (0.5 mm in diamater). Poly (o-phenylenediamine) was used as an inner coating to reduce interference by small compounds present in the body fluids, and the perfluorinated ionomer, Nafion as a biocompatible, protective, outer coating. Glucose oxidase trapped in an albumin/glutaraldehyde matrix was sandwiched between these coatings. In vitro tests in buffer showed the sensors had a good selectively, a sensitivity of about 25 nA/mM, and a 90% response time of 33 s. Stabilization of the current following polarization required 10 to 30 min in vitro and 30 to 40 in vivo. Although these sensors remained stable for many weeks in saline solution, their implantation in animals resulted in the degradation of the protective Nafion outer coating, which in turn, led to the failure of the incorporated reference electrode. We demonstrated that if unprotected, the AgCl layer of the reference electrode rapidly dissolves in the biological environment. However, we later showed that in vivo degradation of Nafion can be prevented by heat curing. When heat cured sensors were subcutaneously implanted in dogs, the sensors' signal closely followed the plasma glucose level during glucose tolerance tests. The response of the sensors implanted in dogs was retained for 10 days.
Antibiotics and the Placebo Reaction in Acne (1966)

TETRACYCLINE has been widely accepted as a highly effective and reliable agent in the treatment of acne vulgaris. Its effectiveness is attested to by the clinical experience of numerous dermatologists, but is not supported by the majority of double-blind studies. Two well-controlled clinical studies demonstrated that tetracycline was clearly more effective than a placebo, and two similarly controlled studies showed no significant difference.<sup>1-4</sup> For editorial comment, see page 362. The pharmacological effectiveness of tetracycline was questioned for several reasons. First, the dose used in acne therapy is relatively low. Secondly, tetracycline might be expected to induce a high rate of placebo benefit because it is a modern wonder drug, it is expensive, and ideally it might free the patient from the drudgery of constant topical care. In order to determine the effectiveness of antibiotics in the treatment of acne and to delineate the percentage of placebo reactors, we undertook