gebhart/patrepeval huggingface dataset:
Metal‐chelating affinity hydrogels for sustained protein release (2007)

Affinity hydrogels based on poly(ethylene glycol) diacrylate and a metal-ion-chelating ligand, glycidyl methacrylate-iminodiacetic acid, have been developed to systematically decrease protein release rates from hydrophilic tissue engineering scaffolds formed in situ. In the current work, tunable and sustained release of a model protein, hexa-histidine tagged green fluorescence protein (hisGFP), is accomplished by judiciously increasing ligand:protein ratio or replacing low-affinity nickel ions with high-affinity copper ions. Agreement between theoretical predictions of a reaction-diffusion model and experimental measurements confirm metal- ion-mediated sustained protein release from these affinity hydrogels is governed by equilibrium protein-ligand binding affinity (dissociation constant, Kd) as well as protein-ligand dissociation kinetics (protein debinding rate constant, k off). The former dictates the release rate in the early period of protein release while the latter determines the long-term sustained release effect. While metal-ion affinity binding has been widely used for various purposes including protein purification and surface patterning, this is the first report describing its application in systematically controlling protein release from hydrophilic PEG networks suitable for cell encapsulation. By using ligands with proper binding kinetic constants (Kd and k off), localized protein delivery can be sustained over clinically relevant timescales while maintaining a favorable environment for cell encapsulation and viability.
The Thiolase Reaction Mechanism: The Importance of Asn316 and His348 for Stabilizing the Enolate Intermediate of the Claisen Condensation (2009)

The biosynthetic thiolase catalyzes a Claisen condensation reaction between acetyl-CoA and the enzyme acetylated at Cys89. Two oxyanion holes facilitate this catalysis: oxyanion hole I stabilizes the enolate intermediate generated from acetyl-CoA, whereas oxyanion hole II stabilizes the tetrahedral intermediate of the acetylated enzyme. The latter intermediate is formed when the alpha-carbanion of acetyl-CoA enolate reacts with the carbonyl carbon of acetyl-Cys89, after which C-C bond formation is completed. Oxyanion hole II is made of two main chain peptide NH groups, whereas oxyanion hole I is formed by a water molecule (Wat82) and NE2(His348). Wat82 is anchored in the active site by an optimal set of hydrogen bonding interactions, including a hydrogen bond to ND2(Asn316). Here, the importance of Asn316 and His348 for catalysis has been studied; in particular, the properties of the N316D, N316A, N316H, H348A, and H348N variants have been determined. For the N316D variant, no activity could be detected. For each of the remaining variants, the k(cat)/K(m) value for the Claisen condensation catalysis is reduced by a factor of several hundred, whereas the thiolytic degradation catalysis is much less affected. The crystal structures of the variants show that the structural changes in the active site are minimal. Our studies confirm that oxyanion hole I is critically important for the condensation catalysis. Removing either one of the hydrogen bond donors causes the loss of at least 3.4 kcal/mol of transition state stabilization. It appears that in the thiolytic degradation direction, oxyanion hole I is not involved in stabilizing the transition state of its rate limiting step. However, His348 has a dual role in the catalytic cycle, contributing to oxyanion hole I and activating Cys89. The analysis of the hydrogen bonding interactions in the very polar catalytic cavity shows the importance of two conserved water molecules, Wat82 and Wat49, for the formation of oxyanion hole I and for influencing the reactivity of the catalytic base, Cys378, respectively. Cys89, Asn316, and His348 form the CNH-catalytic triad of the thiolase superfamily. Our findings are also discussed in the context of the importance of this triad for the catalytic mechanism of other enzymes of the thiolase superfamily.
A study of the dopamine D2 receptor gene in pathological gambling (1996)

Pathological gambling has been termed both the 'pure' and the 'hidden' addiction. 'Pure' because it is not associated with the intake of any addicting substance, and 'hidden' because it is an extension of a common, socially accepted behaviour. The Taq Al variant of the human DRD2 gene has been associated with drug addiction, some forms of severe alcoholism, and other impulsive, addictive behaviours. We have sought to determine if there is a similar association with pathological gambling. A total of 222 non-Hispanic Caucasian pathological gamblers from multiple sites across the US participated in the study. Of these 171 donated a sample of blood, 127 filled out several questionnaires, and 102 did both. Of the 171 pathological gamblers 50.9% carried the D2Al allele versus 25.9% of the 714 known non-Hispanic Caucasian controls screened to exclude drug and alcohol abuse, p<0.00000001, odds ratio (OR)=2.96. For the 102 gamblers who filled out the questionnaires, 63.8% of those in the upper half of the Pathological Gambling Score (more severe) carried the D2A1 allele (OR versus controls=5.03), compared to 40.9% in the lower half (less severe). Of those who had no comorbid substance abuse, 44.1% carried the D2A1 allele, compared to 60.5% of those who had comorbid substance abuse. Forty-eight controls and 102 gamblers completed a shorter version of the Pathological Gambling Score. Of the 45 controls with a score of zero, 17.8% carried the D2A1 allele. Of the 99 gamblers with a score of 5 or more, 52.5% carried the D2A1 allele (X2=15.36, p=0.00009). These results suggest that genetic variants at the DRD2 gene play a role in pathological gambling, and support the concept that variants of this gene are a risk factor for impulsive and addictive behaviours.
Characterization and Evaluation of Detoxification Functions of a Nontumorigenic Immortalized Porcine Hepatocyte Cell Line (HepLiu) (1999)

Primary porcine hepatocytes (PPH) are currently used in research and therapeutic applications as the biological component of extracorporeal liver assist devices to overcome the shortage of human hepatocytes. However, their finite life span and typically rapid loss of functions limit their utility. An immortalized, nontumorigenic, highly differentiated porcine hepatocyte cell line was developed in our laboratory to resolve these disadvantages. PPH were transfected with simian virus 40 (SV40) T antigen under the control of the SV40 early promoter. From the established 69 clones, 23 clones displaying hepatocyte-like morphology were screened for diazepam metabolism. One clone, HepLiu D63, has been maintained in culture for > 2 years, through more than 60 passages and 240 divisions. Albumin protein, present in early passages, was lost at later passages, but albumin transcript still was detectable in later passages. Carbamoyl phosphate synthetase, a gateway enzyme of the urea cycle, was consistently detectable in HepLiu cells. Cytokeratin 18, a characteristic marker of primary hepatocytes, was detected by both immunofluorescent staining and Western blot in HepLiu cells. Furthermore, maintenance of P450 functions in HepLiu cells was evidenced by diazepam and 7-ethoxycoumarin metabolites measured by HPLC. Phase II conjugative function was measured as acetaminophen glucuronidation. P450 dealkylase was demonstrated microscopically by the conversion of a nonfluorescent substrate to a fluorescent product. Both Northern blot analysis and immunofluorescent staining showed SV40 T antigen expression in the nuclei of HepLiu cells. No tumor formation occurred when HepLiu cells were injected into severe combined immunodeficient (SCID) mice nor was the TAI (a tumor marker) mRNA expressed, even in later passages. This immortalized, nontumorigenic, highly functional cell line may provide a valuable tool for drug/toxicological studies, liver biologic regulation studies, and artificial liver support systems.
Thymidine uptake, thymidine incorporation, and thymidine kinase activity in marine bacterium isolates (1990)

One assumption made in bacterial production estimates from [3H]thymidine incorporation is that all heterotrophic bacteria can incorporate exogenous thymidine into DNA. Heterotrophic marine bacterium isolates from Tampa Bay, Fla., Chesapeake Bay, Md., and a coral surface microlayer were examined for thymidine uptake (transport), thymidine incorporation, the presence of thymidine kinase genes, and thymidine kinase enzyme activity. Of the 41 isolates tested, 37 were capable of thymidine incorporation into DNA. The four organisms that could not incorporate thymidine also transported thymidine poorly and lacked thymidine kinase activity. Attempts to detect thymidine kinase genes in the marine isolates by molecular probing with gene probes made from Escherichia coli and herpes simplex virus thymidine kinase genes proved unsuccessful. To determine if the inability to incorporate thymidine was due to the lack of thymidine kinase, one organism, Vibrio sp. strain D19, was transformed with a plasmid (pGQ3) that contained an E. coli thymidine kinase gene. Although enzyme assays indicated high levels of thymidine kinase activity in transformants, these cells still failed to incorporate exogenous thymidine into DNA or to transport thymidine into the cells. These results indicate that the inability of certain marine bacteria to incorporate thymidine may not be solely due to the lack of thymidine kinase activity but may also be due to the absence of thymidine transport systems.
Aminohaloborane in organic synthesis. 1. Specific ortho substitution reaction of anilines (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAminohaloborane in organic synthesis. 1. Specific ortho substitution reaction of anilinesTsutomu Sugasawa, Tatsuo Toyoda, Makoto Adachi, and Kazuyuki SasakuraCite this: J. Am. Chem. Soc. 1978, 100, 15, 4842–4852Publication Date (Print):July 1, 1978Publication History Published online1 May 2002Published inissue 1 July 1978https://pubs.acs.org/doi/10.1021/ja00483a034https://doi.org/10.1021/ja00483a034research-articleACS PublicationsRequest reuse permissionsArticle Views2991Altmetric-Citations119LEARN 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
The pancreas in human type 1 diabetes (2010)

Type 1 diabetes (T1D) is considered a disorder whose pathogenesis is autoimmune in origin, a notion drawn in large part from studies of human pancreata performed as far back as the 1960s. While studies of the genetics, epidemiology, and peripheral immunity in T1D have been subject to widespread analysis over the ensuing decades, efforts to understand the disorder through analysis of human pancreata have been far more limited. We have reviewed the published literature pertaining to the pathology of the human pancreas throughout all stages in the natural history of T1D. This effort uncovered a series of findings that challenge many dogmas ascribed to T1D and revealed data suggesting the marked heterogeneity in terms of its pathology. An improved understanding and appreciation for pancreatic pathology in T1D could lead to improved disease classification, an understanding of why the disorder occurs, and better therapies for disease prevention and management.
AGGLUTININS IN CHILDREN VACCINATED WITH THE DPT VACCINES USED IN FINLAND, SEROTYPES OF BORDETELLA PERTUSSIS STRAINS ISOLATED DURING WHOOPING COUGH EPIDEMICS IN 1976–1977 AND WHOOPING COUGH ATTACK RATE IN CHILDREN IN THE EPIDEMIC AREAS. (1982)

The purpose of this study was to find an answer to the question of why whooping cough cases occur in Finland in spite of the high acceptance rate of DPT vaccine. To this end agglutinins 1,2 and 3 were determined in children vaccinated in 1962–1976 with vaccine A, manufactured by the National Public Health Institute, Helsinki. The amount of agglutinins 1 and 2 was unmeasurable, while an agglutinin 3 titre of±40 was obtained in 9/14(64%). This vaccine contains strain no. 18 530, which is serotype 1.2.3. Vaccine B from the same manufacturer contains strains 18 530 and 1 772, both of which are serotype 1.2.3. In children vaccinated with vaccine B since 1976 the agglutinin 1 titre was±20 in 14/18 (78%) cases. A similar titre of agglutinin 2 was obtained in 14/19 (74%) of cases and of agglutinin 3 in 5/19 (26%). A titre of±40 was obtained for agglutinin 1 in 4/18(22%) cases, for agglutinin 2 in 5/19 (26%) cases and for agglutinin 3 in 14/19 (74%) cases. Of the Bordetella pertussis strains isolated during two whooping cough epidemics in 1976–1977, 83 were serotyped. All these strains were serotype 1.2. The whooping cough attack rate was estimated in 242 incompletely and 44 completely vaccinated children during the epidemics in question. Of the incompletely vaccinated children 188/242(78%) contracted whooping cough and 54/242(22%) remained healthy. Of the completely vaccinated children 17/44(38%) contracted whooping cough and 27/44(62%) remained healthy.
Mucosal barrier mechanisms. Interplay between secretory IgA (SIgA), IgG and mucins on the surface properties and association of salmonellae with intestine and granulocytes. (1982)

Rough Salmonella typhimurium 395 MR 10 bacteria sensitized with SIgA were used to assess the effect of secretory IgA (SIgA) on bacterial association with the intestine of rat and with a column of hog gastric mucin, and on IgG-mediated surface properties and interaction with polymorphonuclear leucocytes. It was found that SIgA increased the affinity for mucus belt of the intestine and for the mucin column, but reduced IgG-enhanced phagocytosis and surface hydrophobicity and charge of the bacteria. It is suggested that the ability of SIgA to render bacteria mucophilic and to modify IgG-mediated reactions serve the purpose of secluding bacteria from contact with mucosal membranes and depress inflammatory reactions at the site of infection.
MiR-27a Modulates Radiosensitivity of Triple-Negative Breast Cancer (TNBC) Cells by Targeting CDC27 (2015)

The miR-27a-CDC27 axis might play an important role in modulating response to radiotherapy in TNBC cells. Testing miR-27a expression might be a useful way to identify a subgroup of patients who will benefit from an IR-based therapeutic approach.
Shade: a fast instruction-set simulator for execution profiling (1994)

Tracing tools are used widely to help analyze, design, and tune both hardware and software systems. This paper describes a tool called Shade which combines efficient instruction-set simulation with a flexible, extensible trace generation capability. Efficiency is achieved by dynamically compiling and caching code to simulate and trace the application program. The user may control the extent of tracing in a variety of ways; arbitrarily detailed application state information may be collected during the simulation, but tracing less translates directly into greater efficiency. Current Shade implementations run on SPARC systems and simulate the SPARC (Versions 8 and 9) and MIPS I instruction sets. This paper describes the capabilities, design, implementation, and performance of Shade, and discusses instruction set emulation in general.
High-Resolution Thin-Film Device to Sense Texture by Touch (2006)

Touch (or tactile) sensors are gaining renewed interest as the level of sophistication in the application of minimum invasive surgery and humanoid robots increases. The spatial resolution of current large-area (greater than 1 cm(2)) tactile sensor lags by more than an order of magnitude compared with the human finger. By using metal and semiconducting nanoparticles, a approximately 100-nm-thick, large-area thin-film device is self-assembled such that the change in current density through the film and the electroluminescent light intensity are linearly proportional to the local stress. A stress image is obtained by pressing a copper grid and a United States 1-cent coin on the device and focusing the resulting electroluminescent light directly on the charge-coupled device. Both the lateral and height resolution of texture are comparable to the human finger at similar stress levels of approximately 10 kilopascals.
Animal models of schizophrenia: a critical review. (2001)

Current research into schizophrenia has remained highly fragmented, much like the clinical presentation of the disease itself. Differing theories as to the cause and progression of schizophrenia, as well as the heterogeneity of clinical symptoms, have made it difficult to develop a coherent framework suitable for animal modelling. However, a number of limited animal models have been developed to explore various causative theories and to test specific mechanistic hypotheses. Historically, these models have been based on the manipulation of neurotransmitter systems believed to be involved in schizophrenia. In recent years, the emphasis has shifted to targeting relevant brain regions in an attempt to explore potential etiologic hypotheses. The specific animal models developed within these frameworks are described in this review. Emphasis is placed on the critical evaluation of currently available models because these models help to shape the direction of future research.
[Cytotoxic effect of methionine-gamma-lyase on neoplastic cells in culture]. (1983)

The influence of methionine-gamma-lyase from Pseudomonas putida on DNA synthesis by CaOv and L-8 cell lines has been studied. The agent has been demonstrated to inhibit the incorporation of 3H-thymidine into L-8 cell line and to have no effect on CaOv cells.
Antigen-induced in vitro antibody production in humans: tetanus toxoid-specific antibody synthesis. (1982)

Abstract The capacity of the immune system to respond to an antigenic stimulus with the production of antigen-specific immunoglobulin (Ig) is one of its fundamental properties. Recently, in vitro models of antigen-induced, antigen-specific antibody production have been developed using human peripheral blood mononuclear cells (PBMNC). In the present study, tetanus toxoid (TT), a soluble antigen to which humans are commonly immunized, was used to trigger in vitro antigen-specific antibody synthesis by peripheral blood lymphocytes from subjects recently boosted in vivo to this recall antigen. A sensitive and specific enzyme-linked immunosorbent assay was developed for detecting anti-TT antibody. TT alone, without exogenous mitogen, induced primarily an IgG anti-TT response in vitro. Optimal responses were obtained at the extremely low antigen concentration of 1 ng/ml, concentrations at which little polyclonal Ig production was observed. In contrast, maximum polyclonal Ig synthesis was seen at concentrations of TT greater than 1 µg, levels at which specific anti-TT production was suppressed. Specific anti-TT responses were dependent on the presence of T lymphocytes. Antigen-inducible responses showed significant differences when compared with responses induced by the polyclonal B cell activator, pokeweed mitogen (PWM). T cell help for the antigen-induced specific response was radiosensitive in contrast to T cell help for the PWM-induced responses that were relatively radioresistent. In addition, antigen-inducible anti-TT-specific B cell responses were present in nylon wool T cell fractions, whereas PWM-inducible responses were not found, suggesting the presence of different subpopulations of antigen-specific B lymphocytes in peripheral blood. When stimulatory concentrations of TT were combined with PWM, unexpected suppression of the PWM-inducible responses occurred in some cases, whereas both specific antibody production against another antigen and polyclonal Ig production remained unchanged. Thus, a TT-induced, TT-specific culture and assay system for anti-TT production by human PBMNC has been developed that provides a sensitive and accessible in vitro model for delineating the precise role of antigen in the activation and immunoregulation of specific antibody responses in man.
Coordination chemistry of cis,cis and trans,trans 1,1′-[1,2-phenylenebis(methylene)]bis(2,2,3,4,4-pentamethylphosphetane) (2010)

The cis,cis (5) and trans,trans (9) forms of the bidentate ligand 1,1'-[1,2-phenylenebis(methylene)]bis(2,2,3,4,4-pentamethylphosphetane) have been prepared from common precursors using two separate synthetic routes. The cis,cis isomer is attained selectively through the direct reaction of two mol equivalents of 2,2,3,4,4-pentamethylphosphetane with alpha,alpha'-dibromo-o-xylene in acetone. Protection of the 2,2,3,4,4-pentamethylphosphetane with BH(3) and conversion to the lithium phosphido-borane prior to adding the alpha,alpha'-dihalo-o-xylene leads to the isolation of the trans,trans isomer of 1,1'-[1,2-phenylenebis(methylene)]bis(2,2,3,4,4-pentamethylphosphetane). Both isomers have been fully characterised by spectroscopic and, in the case of the all-cis isomer, single-crystal X-ray methods. The two isomers have been coordinated to Mo(0) to give complexes of the type cis-Mo(CO)(4)(L). The solid state structures of cis-Mo(CO)(4)(5), 10, and cis-Mo(CO)(4)(9), 12, have been determined by single-crystal X-ray methods and reveal significant differences between the two forms, most notably in the chelate bite angle which is 100.68(18) degrees in 10 compared to 88.12(2) degrees in 12. Ligand 5 has also been coordinated to Pd(II) and Pd(0) and the structure of the complex Pd(5)Cl(2) (11) determined by single-crystal methods. The solid-state structure of Pd(5)Cl(2) reveals a significant tetrahedral distortion from the normal square planar geometry.
II-VI photovoltaic heterojunctions for solar energy conversion (1974)

Several different II-VI heterojunctions show possible promise for photovoltaic conversion of solar energy. Two of these are p-CdTe/n-CdS and p-CdTe/n-Zn0.35Cd0.65S, which have a maximum solar efficiency of 17 and 23%, respectively. We report here specifically on the properties of p-CdTe/n-CdS cells prepared (a) by close-spaced vapor transport of CdTe onto single-crystal CdS, and (b) by two-source vacuum evaporation of CdS onto single-crystal CdTe. Cells with efficiency of 4.0% have been produced without detailed attention to optimization of cell design; these cells have quantum efficiencies as high as 0.85.