gebhart/patrepeval huggingface dataset:
Synthesis of 2‐amino‐5,6‐dihydro‐4H‐1,3‐thiazines and related compounds by acid catalyzed cyclization of allylic isothiuronium salts (1977)

Abstract Several allylic isothiuronium salts 6 have been shown to yield 4‐substituted 2‐amino‐5,6‐dihydro‐4 H ‐1,3‐thiazines ( 2 ; R 3 = H) and the 2‐phenylimino compound 10 on exposure to trifluoroacetic acid or trifluoroacetic acid‐stannic chloride. The overall process constitutes a convenient transformation of readily available ketones or aldehydes 3 into the target hetero‐cycles. The scope and limitations of this approach are discussed in terms of carbenium ion intermediates ( 7 ). Whereas this method successfully led to the imidazo[2,l‐ b ][1,3]thiazine 13 (93% from 12 ), its application to the synthesis of 2‐amino‐2‐thiazolines (eg. 14 → 15 ) or imidazo‐[2,1‐ b ]thiazoles ( eg. 16 → 17 ) was unsuccessful. The 2‐acetylimino derivatives 9 were found to be useful for purification of the 2‐aminothiazines.
c-Kit and c-kit mutations in mastocytosis and other hematological diseases (2000)

Mast cells (MC) are tissue elements derived from hematopoietic stem cells. Their differentiation and proliferation processes are under the influence of cytokines, including one of utmost importance known as stem cell factor (SCF). SCF receptor is encoded by the protooncogene c-kit, belongs to the type III receptor tyrosine kinase subfamily, and is also expressed on other hematopoietic or non-hematopoietic cells. Ligation of c-kit receptor by SCF induces its dimerization, followed by induction of multiple intracellular signaling pathways leading to cell proliferation and activation. Mastocytosis, a relatively rare group of diseases characterized by accumulation of MC in various tissues, are found isolated or sometimes associated with other hematological malignancies in humans. Although the initial events leading to mastocytosis are not yet unraveled, alterations of the c-kit gene have been described. Particularly interesting are acquired mutations resulting in a constitutively activated receptor, possibly involved in the increased numbers of MC in tissues. For this reason, future strategies might be envisaged to target specifically the mutated c-kit and/or its intracellular signaling.
Type II protein secretion and its relationship to bacterial type IV pili and archaeal flagella (2003)

Homologues of the protein constituents of the Klebsiella pneumoniae (Klebsiella oxytoca) type II secreton (T2S), the Pseudomonas aeruginosa type IV pilus/fimbrium biogenesis machinery (T4P) and the Methanococcus voltae flagellum biogenesis machinery (Fla) have been identified. Known constituents of these systems include (1). a major prepilin (preflagellin), (2). several minor prepilins (preflagellins), (3). a prepilin (preflagellin) peptidase/methylase, (4). an ATPase, (5). a multispanning transmembrane (TM) protein, (6). an outer-membrane secretin (lacking in Fla) and (7). several functionally uncharacterized envelope proteins. Sequence and phylogenetic analyses led to the conclusion that, although many of the protein constituents are probably homologous, extensive sequence divergence during evolution clouds this homology so that a common ancestry can be established for all three types of systems for only two constituents, the ATPase and the TM protein. Sequence divergence of the individual T2S constituents has occurred at characteristic rates, apparently without shuffling of constituents between systems. The same is probably also true for the T4P and Fla systems. The family of ATPases is much larger than the family of TM proteins, and many ATPase homologues function in capacities unrelated to those considered here. Many phylogenetic clusters of the ATPases probably exhibit uniform function. Some of these have a corresponding TM protein homologue although others probably function without one. It is further shown that proteins that compose the different phylogenetic clusters in both the ATPase and the TM protein families exhibit unique structural characteristics that are of probable functional significance. The TM proteins are shown to have arisen by at least two dissimilar intragenic duplication events, one in the bacterial kingdom and one in the archaeal kingdom. The archaeal TM proteins are twice as large as the bacterial TM proteins, suggesting an oligomeric structure for the latter.
A Novel Definition and Measurement Method of Group Delay and Its Application (2008)

The time synchronization accuracy demanded in satellite navigation systems, deep space exploration, and spread spectrum radar has reached the subnanosecond range. The phase distortion induced by RF cables, amplifiers, and mixers affects the spread spectrum signal delay and causes dominant error in time synchronization. To measure and calibrate the influence of phase distortion, it is necessary to devise a high-accuracy group delay measurement method and study its relationship with signal delay. The traditional definition and measurement formula of group delay is based on the derivative, which has some inherent faults such as inconsistency of resolution and accuracy, incapacity to describe the global phase character of signal bandwidth, and difficulty in establishing a relationship with spread spectrum signal delay. To overcome such shortcomings, a novel group delay definition and measurement formula has been put forward based on Taylor series expansion, which has been used in Global Positioning System timing receiver RF cable group delay measurement. The experiment showed that the accuracy of the new group delay measurement was better than 0.01 ns and was very consistent with the signal delay. The maximum bias between the signal delay and the zeroth-order group delay was less than 0.3 ns.
Insulin and Leptin Resistance With Hyperleptinemia in Mice Lacking Androgen Receptor (2005)

Epidemiological evidence suggests that sex differences exist in type 2 diabetes. Men seem to be more susceptible than women to the consequences of obesity and sedentary lifestyle, possibly because of differences in insulin sensitivity and regional body fat deposition. Thus, lacking androgen receptor (AR) in male individuals may promote insulin resistance. To determine whether lacking AR in male individuals contributes to in vivo insulin resistance, an AR knockout model (AR(-/y)) was used to study the correlation between AR and insulin resistance. Progressive reduced insulin sensitivity and impaired glucose tolerance were seen in AR(-/y) mice with advancing age. Aging AR(-/y) mice displayed accelerated weight gain, hyperinsulinemia, and hyperglycemia, and loss of AR contributes to increased triglyceride content in skeletal muscle and liver. Leptin is higher in serum of AR(-/y) mice. Treatment with exogenous leptin fails to stimulate weight loss in AR(-/y) mice in advanced age, suggesting leptin resistance in the AR(-/y/) mice. Exogenous dihydrotestosterone replacement fails to reverse the metabolic abnormalities and insulin resistance in AR(-/y) mice. Our in vivo studies demonstrate that androgen-AR plays key roles in the development of insulin and leptin resistance, which may contribute to the development of type 2 diabetes and cardiovascular disease.
Thrombospondin in Renal Disease (2009)

Thrombospondins (TSPs) are multifunctional matricellular glycoproteins which are involved in the regulation of angiogenesis, proliferation, apoptosis, the NO-cGMP-dependent protein kinase pathway and transforming growth factor (TGF) beta activation. The TSP family consists of 5 members, but currently only data on effects of TSP-1 and TSP-2 in renal disease are available. Both TSPs are hardly expressed within the healthy renal cortex and can be upregulated during renal disease. Using different animal models for renal disease, TSP-1 and -2 were found to be important regulators of pathophysiological changes during renal disease with similar and contrary effects. TSP-1 is a major activator for TGF-beta resulting in profibrotic effects in the injured kidney. In contrast, TSP-2 lacks the ability for its activation. Proapoptotic actions of TSP-1 were found during renal ischemia/reperfusion injury. While TSP-1 exerts proinflammatory actions, the currently available data for TSP-2 propose anti-inflammatory effects for this molecule. Both TSPs are known angiogenesis inhibitors, which could be proved for TSP-2, but antiangiogenic effects for TSP-1 were only evident by treatment with TSP-1 peptides in renal disease. In addition, TSP-2 can inhibit cell proliferation and matrix metalloproteinase 2 activity.
Structure of nisin (1971)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure of nisinErhard Gross and John L. MorellCite this: J. Am. Chem. Soc. 1971, 93, 18, 4634–4635Publication Date (Print):September 1, 1971Publication History Published online1 May 2002Published inissue 1 September 1971https://pubs.acs.org/doi/10.1021/ja00747a073https://doi.org/10.1021/ja00747a073research-articleACS PublicationsRequest reuse permissionsArticle Views1836Altmetric-Citations485LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Bispecific small molecule–antibody conjugate targeting prostate cancer (2013)

Bispecific antibodies, which simultaneously target CD3 on T cells and tumor-associated antigens to recruit cytotoxic T cells to cancer cells, are a promising new approach to the treatment of hormone-refractory prostate cancer. Here we report a site-specific, semisynthetic method for the production of bispecific antibody-like therapeutics in which a derivative of the prostate-specific membrane antigen-binding small molecule DUPA was selectively conjugated to a mutant αCD3 Fab containing the unnatural amino acid, p-acetylphenylalanine, at a defined site. Homogeneous conjugates were generated in excellent yields and had good solubility. The efficacy of the conjugate was optimized by modifying the linker structure, relative binding orientation, and stoichiometry of the ligand. The optimized conjugate showed potent and selective in vitro activity (EC50 ~ 100 pM), good serum half-life, and potent in vivo activity in prophylactic and treatment xenograft mouse models. This semisynthetic approach is likely to be applicable to the generation of additional bispecific agents using drug-like ligands selective for other cell-surface receptors.
Estimation of evolutionary distance between nucleotide sequences. (1984)

A mathematical formula for estimating the average number of nucleotide substitutions per site (delta) between two homologous DNA sequences is developed by taking into account unequal rates of substitution among different nucleotide pairs. Although this formula is obtained for the equal-input model of nucleotide substitution, computer simulations have shown that it gives a reasonably good estimate for a wide range of nucleotide substitution patterns as long as delta is equal to or smaller than 1. Furthermore, the frequency of cases to which the formula is inapplicable is much lower than that for other similar methods recently proposed. This point is illustrated using insulin genes. A statistical method for estimating the number of nucleotide changes due to deletion and insertion is also developed. Application of this method to globin gene data indicates that the number of nucleotide changes per site increases with evolutionary time but the pattern of the increase is quite irregular.
Genetic Susceptibility to Asthma — Bronchial Hyperresponsiveness Coinherited with a Major Gene for Atopy (1995)

Background. Bronchial hyperresponsiveness, a risk factor for asthma, consists of a heightened bronchoconstrictor response to a variety of stimuli. The condition has a heritable component and is closely related to serum IgE levels and airway inflammation. The basis for these relations is unknown, as is the mechanism of genetic susceptibility to bronchial hyperresponsiveness. We attempted to define the interrelation between atopy and bronchial hyperresponsiveness and to investigate the chromosomal location of this component of asthma.
Vitamin K-Dependent Biosynthesis of γ-Carboxyglutamic Acid (1999)

V ITAMIN K, AN ESSENTIAL vitamin, is a cofactor for a single known enzymatic reaction: the conversion of glutamic acid to γ-carboxyglutamic acid in vitamin K-dependent proteins during their biosynthesis. Since the discovery of vitamin K and its association with blood coagulation,[1][1] many
Large-eddy simulations of a turbulent Coanda jet on a circulation control airfoil (2010)

Large-eddy simulations are performed of a turbulent Coanda jet separating from a rounded trailing edge of a simplified circulation control airfoil model. The freestream Reynolds number based on the airfoil chord is 0.49×106, the jet Reynolds number based on the jet slot height is 4470, and the ratio of the peak jet velocity to the freestream velocity is 3.96. Three different grid resolutions are used to show that their effect is very small on the mean surface pressure distribution, which agrees very well with experiments, as well as on the mean velocity profiles over the Coanda surface. It is observed that the Coanda jet becomes fully turbulent just downstream of the jet exit, accompanied by asymmetric alternating vortex shedding behind a thin (but blunt) jet blade splitting the jet and the external flow. A number of “backward-tilted” hairpin vortices (i.e., the head of each hairpin being located upstream of the legs) are observed around the outer edge of the jet over the Coanda surface. These hairpins create strong upwash between the legs and weak downwash around them, contributing to turbulent mixing of the high-momentum jet below the hairpins and the low-momentum external flow above them. The probability density distribution of velocity fluctuations is shown to be highly asymmetric in this region, consistent with the observation that the hairpin vortices create strong upwash and weak downwash. Turbulent structures inside the jet, its spreading rate, and self-similarity are also discussed.
Selective Pressure to Increase Charge in Immunodominant Epitopes of the H3 Hemagglutinin Influenza Protein (2010)

The evolutionary speed and the consequent immune escape of H3N2 influenza A virus make it an interesting evolutionary system. Charged amino acid residues are often significant contributors to the free energy of binding for protein-protein interactions, including antibody-antigen binding and ligand-receptor binding. We used Markov chain theory and maximum likelihood estimation to model the evolution of the number of charged amino acids on the dominant epitope in the hemagglutinin protein of circulating H3N2 virus strains. The number of charged amino acids increased in the dominant epitope B of the H3N2 virus since introduction in humans in 1968. When epitope A became dominant in 1989, the number of charged amino acids increased in epitope A and decreased in epitope B. Interestingly, the number of charged residues in the dominant epitope of the dominant circulating strain is never fewer than that in the vaccine strain. We propose these results indicate selective pressure for charged amino acids that increase the affinity of the virus epitope for water and decrease the affinity for host antibodies. The standard PAM model of generic protein evolution is unable to capture these trends. The reduced alphabet Markov model (RAMM) model we introduce captures the increased selective pressure for charged amino acids in the dominant epitope of hemagglutinin of H3N2 influenza (R (2) > 0.98 between 1968 and 1988). The RAMM model calibrated to historical H3N2 influenza virus evolution in humans fit well to the H3N2/Wyoming virus evolution data from Guinea pig animal model studies.
Lipopolysaccharide Is in Close Proximity to Each of the Proteins in Its Membrane Receptor Complex (2001)

The structural features of some proteins of the innate immune system involved in mediating responses to microbial pathogens are highly conserved throughout evolution. Examples include members of the Drosophila Toll (dToll) and the mammalian Toll-like receptor (TLR) protein families. Activation of Drosophila Toll is believed to occur via an endogenous peptide rather than through direct binding of microbial products to the Toll protein. In mammals there is a growing consensus that lipopolysaccharide (LPS) initiates its biological activities through a heteromeric receptor complex containing CD14, TLR4, and at least one other protein, MD-2. LPS binds directly to CD14 but whether LPS then binds to TLR4 and/or MD-2 is not known. We have used transient transfection to express human TLRs, MD-2, or CD14 alone or in different combinations in HEK 293 cells. Interactions between LPS and these proteins were studied using a chemically modified, radioiodinated LPS containing a covalently linked, UV light-activated cross-linking group ((125)I-ASD-Re595 LPS). Here we show that LPS is cross-linked specifically to TLR4 and MD-2 only when co-expressed with CD14. These data support the contention that LPS is in close proximity to the three known proteins of its membrane receptor complex. Thus, LPS binds directly to each of the members of the tripartite LPS receptor complex.
Assessment of quality of life in patients with non-operated pancreatic cancer after videothoracoscopic splanchnicectomy. (2011)

Introduction: Pancreatic tumours are a crucial medical issue. The majority of patients report sick in the late stage of carcinoma clinical advancement, which considerably limits the possibility of surgical treatment. Pancreatic cancer patients with no other alternative but palliative treatment constitute a large group. Aim: To assess pain intensity levels and quality of life of pancreatic cancer patients after videothoracoscopic splanchnicectomy. Material and methods: Between 2001 January and 2010 November in the Department of Thorax, General Surgery and Oncology of the Medical University of Lodz 262 patients with pancreatic tumours were hospitalized. In 121 cases grade 3 and grade 4 tumours were observed. Hundred and twenty-one videothoracoscopic procedures of sympathetic trunk and ganglion excision were performed in 89 patients. Results: Before the procedure the pain intensity level according to VAS was 5.66 (3.9-7.2; SD 1.24) in the trial group and 5. SD 1.15) in the control group. The quality of life average assessment in both groups did not differ statistically (p = 1.07) and was SD 0.92) in patients before the operation and in the control group SD 0.75). On the 7 th postoperative day the pain intensity on average was 2.33 (1.2-3.9; SD 0.78) and 4.57 (3.6-5.5; SD 0.69) respectively. One week after the procedure the quality of patients' life was estimated at SD 1.38) and in the control group at SD 0.71); the differences are significant (p < 0.05). Thirty days after the procedure 12 patients did not t ake any painkillers (13.5%), and in the others a considerable decrease of the taken drugs was observed. On average, the pain intensity was estimated at 1. SD 0.68). The quality of life, on the other hand, improved considerably in relation to the state prior to the procedure, but increased insignificantly in relation to the state on the 7 th postoperative day to 70.9 SD 1.14). Conclusions: Splanchnicectomy is a safe method of cancer pain treatment in patients with advanced pancreatic tumours. Videothoracoscopic excision of visceral nerve thoracic section contributes to the statistically significant decrease of cancer pain intensity and considerably improves the quality of patients' lives.
Imidoylketene−Oxoketenimine Interconversion. Rearrangement of a Carbomethoxyketenimine to a Methoxyimidoylketene and 2-Methoxy-4-quinolone (1996)

FVP of triazole 13 produces the isolable ketenimine 11 together with indole 15. 11 undergoes reversible interconversion with imidoylketene 10 above 380 °C. The latter cyclizes to quinolone 12. Meldrum's acid derivative 16 produces the same ketene 10 above 200 °C, and the latter isomerizes to ketenimine 11 at 200 °C by a 1,3-shift of a MeO group. A competing elimination of MeOH from 16 produces (phenylimino)propadienone 20.
EFFECTS OF CALCIUM ION CONCENTRATION ON THE DEGENERATION OF AMPUTATED AXONS IN TISSUE CULTURE (1973)

Light and electron microscope studies were conducted on the nature of the degenerative changes in amputated nerve fibers of cultured rat sensory ganglia and on the effects of media with differing calcium concentrations upon these changes. With glucose-enriched Eagle's media (MEM) containing 1.6 mM calcium, the amputated myelinated and unmyelinated axons undergo a progressive granular disintegration of their axoplasm with collapse and fragmentation of myelin sheaths between 6 and 24 h after transection. With MEM containing only 25-50 microM calcium, the granular axoplasmic degeneration does not occur in transected fibers and they retain their longitudinal continuity and segmental myelin ensheathment for at least 48 h. Addition of 6 mM EGTA to MEM (reducing the estimated Ca(++) below 0.3 microM) results in the structural preservation of both microtubules and neurofilaments within transected axons. A transient focal swelling of amputated axons occurs, however, in cultures with normal and reduced calcium. These observations suggest that an alteration in the permeability of the axolemma is a crucial initiating event leading to axonal degenerative changes distal to nerve transection. The loss of microtubules and neurofilaments and the associated granular alterations of the axoplasm in transected fibers appears to result from the influx of calcium into the axoplasm.
Daylight and health: A review of the evidence and consequences for the built environment (2013)

Daylight has been associated with multiple health advantages. Some of these claims are associations, hypotheses or beliefs. This review presents an overview of a scientific literature search on the proven effects of daylight exposure on human health. Studies were identified with a search strategy across two main databases. Additionally, a search was performed based on specific health effects. The results are diverse and either physiological or psychological. A rather limited statistically significant and well-documented scientific proof for the association between daylight and its potential health consequences was found. However, the search based on specific health terms made it possible to create a first subdivision of associations with daylight, leading to the first practical implementations for building design.
A public key cryptosystem and a signature scheme based on discrete logarithms (1985)

A new signature scheme is proposed, together with an implementation of the Diffie-Hellman key distribution scheme that achieves a public key cryptosystem. The security of both systems relies on the difficulty of computing discrete logarithms over finite fields.
Defect-free, conformally grown (100) GaAs films (1990)

By using selective epitaxy, submicron-thick (100) GaAs films can be conformally grown between two sandwiching dielectric layers. The defect structure of such GaAs films is investigated using chemical etching and transmission electron microscopy. The conformally grown films exhibit specular surfaces and appear virtually free from defects. A qualitative model for defect trapping is presented which suggests that the dislocations are blocked on the capping dielectric layer when they should thread laterally.