gebhart/patrepeval huggingface dataset:
Chemical Rescue of a Mutant Protein-tyrosine Kinase (2000)

Protein-tyrosine kinases contain a catalytic loop Arg residue located either two or four positions downstream of a highly conserved Asp residue. In this study, the role of this Arg (Arg-318) in the protein-tyrosine kinase C-terminal Src kinase (Csk) was investigated. The observed k(cat) for phosphorylation of the random copolymer poly(Glu,Tyr) substrate by Csk R318A is approximately 3000-fold smaller compared with that of wild type Csk, whereas the K(m) values for ATP and poly(Glu,Tyr) are only mildly affected. The k(cat) value for poly(Glu,Tyr) phosphorylation by the Csk double mutant A316R,R318A is 100-fold greater than the k(cat) value for the single R318A mutant, suggesting that an Arg positioned at the alternative location fulfills a similar function as in wild type. Csk R318A kinase activity can also be partially recovered by several exogenous small molecules including guanidinium and imidazole. These molecules contain key features whose roles in catalysis can be rationalized from a known x-ray structure of the insulin receptor tyrosine kinase. Imidazole is the best of these activators, enhancing phosphorylation rates by Csk R318A up to 100-fold for poly(Glu,Tyr) and significantly stimulating Csk R318A phosphorylation of the physiologic substrate Src. This chemical rescue of mutant protein kinase activity might find applications in cell signal transduction experiments.
Dipeptidyl Peptidase-4 Inhibition and the Treatment of Type 2 Diabetes (2007)

Dipeptidyl peptidase (DPP)-4 is a complex enzyme that exists as a membrane-anchored cell surface peptidase that transmits intracellular signals via a short intracellular tail and as a second smaller soluble form present in the circulation. DPP-4 cleaves a large number of chemokines and peptide hormones in vitro, but comparatively fewer peptides have been identified as endogenous physiological substrates for DPP-4 in vivo. Both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are endogenous physiological substrates for DPP-4, and chemical inhibition of DPP-4 activity, or genetic inactivation of DPP-4 in rodents, results in increased levels of intact bioactive GIP and GLP-1. Furthermore, mice and rats with genetic inactivation or inhibition of DPP-4 exhibit improved glucose tolerance, elevated levels of GLP-1 and GIP, and resistance to diet-induced obesity and hyperglycemia. Sustained DPP-4 inhibition lowers blood glucose via stimulation of insulin and inhibition of glucagon secretion and is associated with preservation of β-cell mass in preclinical studies. Although DPP-4 cleaves dozens of regulatory peptides and chemokines in vitro, studies of mice with genetic inactivation of incretin receptors demonstrate that GIP and GLP-1 receptor–dependent pathways represent the dominant mechanisms transducing the glucoregulatory actions of DPP-4 inhibitors in vivo. The available preclinical data suggests that highly selective DPP-4 inhibition represents an effective and safe strategy for the therapy of type 2 diabetes.

DPP-4 is a widely expressed cell surface peptidase that exhibits a complex biology encompassing cell membrane–associated activation of intracellular signal transduction pathways, cell-cell interaction, and enzymatic activity exhibited by both the membrane-anchored and soluble forms of the enzyme (1). DPP-4, also originally known as the lymphocyte cell surface marker CD26, or as the adenosine deaminase (ADA)-binding protein, is a 766–amino acid serine protease that preferentially cleaves peptide hormones containing a position two alanine or proline. The human gene encoding DPP has been localized …
Transport Layer Security (TLS) Session Resumption without Server-Side State (2006)

This document describes a mechanism that enables the Transport Layer
Security (TLS) server to resume sessions and avoid keeping per-client
session state. The TLS server encapsulates the session state into a
ticket and forwards it to the client. The client can subsequently
resume a session using the obtained ticket. This document obsoletes
RFC 4507. [STANDARDS-TRACK]
Separation of Drug Stereoisomers by the Formation of β-Cyclodextrin Inclusion Complexes (1986)

For many drugs, only racemic mixtures are available for clinical use. Because different stereoisomers of drugs often cause different physiological responses, the use of pure isomers could elicit more exact therapeutic effects. Differential complexation of a variety of drug stereoisomers by immobilized beta-cyclodextrin was investigated. Chiral recognition and racemic resolution were observed with a number of compounds from such clinically useful classes as beta-blockers, calcium-channel blockers, sedative hypnotics, antihistamines, anticonvulsants, diuretics, and synthetic opiates. Separation of the diastereomers of the cardioactive and antimalarial cinchona alkaloids and of two antiestrogens was demonstrated as well. Three dimensional projections of beta-cyclodextrin complexes of propanolol, which is resolved by this technique, and warfarin, which is not, are compared. These studies have improved the understanding and application of the chiral interactions of beta-cyclodextrin, and they have demonstrated a means to measure optical purity and to isolate or produce pure enantiomers of drugs. In addition, this highly specific technique could also be used in the pharmacological evaluation of enantiomeric drugs.
ULBP2 and RAET1E NKG2D ligands are independent predictors of poor prognosis in ovarian cancer patients (2010)

The human activating immune receptor, NKG2D, binds to a diverse array of cellular ligands of the MIC and unique long 16 (UL16)-binding protein (ULBP)/retinoic acid early transcript (RAET) family. NKG2D is thought to participate in anticancer immune responses. By using tissue microarrays representing over 300 patients with defined clinicopathological factors, we present the first comprehensive screen of the expression of all NKG2D ligands in primary ovarian cancers. NKG2D ligands were expressed by the majority of tumors; however, the level of expression varied considerably. By categorizing each tumor as having negative, low or high expression, it was shown that high expression of several NKG2D ligands is inversely correlated with disease survival. Patients whose tumors had high expression of RAET1E (p = 0.037), ULBP1 (p = 0.036) and ULBP3 (p = 0.004) surviving a median of 11, 14 and 11 months, respectively, compared with disease-specific survival of 29, 30 and 25 months in patients whose tumors showed no expression of these ligands. These results contrast with previous findings showing that high level NKG2D ligand expression is associated with good prognosis in colorectal cancer and suggest a fundamental difference in the involvement of NKG2D-mediated immunity in these two types of cancer. By using multivariate analysis, the factors retaining independent prognostic significance were International Federation of Gynecologists and Obstetricians stage (p < 0.001), presence of residual disease (p = 0.003), ULBP2 (p = 0.042) and RAET1E (p = 0.030).
Carotid body tumors (1993)

A retrospective study of 20 patients treated at the Tata Memorial Hospital over a period of 50 years, 1941-1991, is presented. Seventy-five percent (15/20) of the patients presented before their fifth decade with a male-to-female ratio of 2:1. The commonest presenting symptom was a painless lump in the neck. Twenty-five percent (5/20) had an incisional biopsy done elsewhere prior to referral to our institute. We performed a subadventitial excision of the tumor in 17 patients, 3 of whom were given postoperative radiation therapy. Three patients underwent complete excision of the carotid system without a vascular replacement, one of whom developed hemiparesis secondary to a cerebral infarct. There was no operative/postoperative mortality. Cranial nerve palsy was seen in 45% (9/20) of patients; the hypoglossal nerve was most commonly affected. One patient had a recurrence, 6 years after surgery, whereas 60% of patients operated on before 1987 have completed a 5-year disease free survival. Forty percent of patients have yet to have a 5-year follow-up period. Reports of newer diagnostic and therapeutic modalities are discussed.
224. Polyamides containing carbohydrate residues (1963)

T. P. Bird, W. A. P. Black, E. T. Dewar and J. B. Hare, J. Chem. Soc., 1963, 1208 DOI: 10.1039/JR9630001208
Einleitung (2000)

Bei hoher Kapitalmobilität, geringer Mobilität der Arbeitskräfte sowie gleichzeitiger Inflexibilität der (Nominal-)Löhne droht nach negativen asymmetrischen Schocks steigende Arbeitslosigkeit in den betroffenen Ländern oder Regionen einer Währungsunion. Den Mitgliedstaaten stehen Geldpolitik und flexible Wechselkurse als Anpassungsmechanismen an asymmetrische Schocks nicht zur Verfügung. Fiskalpolitik ist das einzige Instrument, das nationalen Regierungen eingebunden in eine Währungsunion bleibt, auf asymmetrische Schocks zu reagieren, Nachfrageschwankungen zu glätten, und so eine drohende Zunahme der Arbeitslosigkeit abzuwenden.
Enhancement of memory window in short channel non-volatile memory devices using double layer tungsten nanocrystals (2006)

This paper for the first time, reports the memory enhancement characteristics and good retention with feasibility of two-bit operation of small scale devices with gate length down to 100 nm, using double layer W nanocrystals embedded in HfAlO for the next generation memory application. Double layer device shows increasing memory window with scaling which will be extremely beneficial
Immunohistochemical expression of human chorionic gonadotropin and P-glycoprotein in human pituitary glands and craniopharyngiomas (1994)

In order to clarify the cellular origin of craniopharyngiomas, the authors examined the distribution of P-glycoprotein (PGP) and human chorionic gonadotropin (HCG) in five normal adenohypophyses and in 23 craniopharyngiomas using peroxidase immunohistochemistry. The correlation between the expression of PGP in craniopharyngiomas and the recurrence of these tumors was also investigated. A number of pars intermedia cyst-lining cells immunostained positively for anti-PGP antibodies. A small number of adenohypophysial cells were also positive for PGP, but squamous epithelial nests were negative in all samples. However, HCG-beta was consistently demonstrated in adenohypophysial cells, pars intermedia cyst-lining cells, and squamous epithelial nests. In 11 craniopharyngiomas, the apical portion of cuboidal cells and some polygonal cells immunostained positively with anti-PGP antibodies. In four HCG-producing craniopharyngiomas, a large number of tumor cells were immunostained with anti-PGP antibodies, three of which showed a recurrence of cystic tumors. By double labeling, the coexpression of HCG-beta and PGP was demonstrated in these recurrent tumors. Accordingly, it is suggested that craniopharyngiomas produce HCG-like peptides and that craniopharyngiomas are unique squamous neoplasms arising in the sellar region from progenitor cells of a neuroendocrine lineage.
Polymerized Ionic Liquid Block and Random Copolymers: Effect of Weak Microphase Separation on Ion Transport (2012)

A series of polymerized ionic liquid (PIL) block and random copolymers were synthesized from an ionic liquid monomer, 1-[(2-methacryloyloxy)ethyl]-3-butylimidazolium bis(trifluoromethanesulfonyl)imide (MEBIm-TFSI), and a nonionic monomer, methyl methacrylate (MMA), at various PIL compositions with the goal of understanding the influence of morphology on ion transport. For the diblock copolymers, the partial affinity between the PIL and PMMA blocks resulted in a weakly microphase-separated morphology with no evident long-range periodic structure across the PIL composition range studied, while the random copolymers revealed no microphase separation. These morphologies were identified with a combination of techniques, including differential scanning calorimetry, small-angle X-ray scattering, and transmission electron microscopy. Surprisingly, at similar PIL compositions, the ionic conductivity of the block copolymers were ca. 2 orders of magnitude higher than the random copolymers despite the weak microphase-separated morphology evidenced in the block copolymers. We attribute the higher conductivity in the block copolymers to its microphase-separated morphology, since significant differences in conductivity are still observed even when differences in glass transition temperature are considered. This work demonstrates that local confinement and connectivity of conducting ions in nanoscale ionic domains in PIL block copolymers can accelerate ion transport significantly.
De novo-engineered transcription activator-like effector (TALE) hybrid nuclease with novel DNA binding specificity creates double-strand breaks (2011)

Site-specific and rare cutting nucleases are valuable tools for genome engineering. The generation of double-strand DNA breaks (DSBs) promotes homologous recombination in eukaryotes and can facilitate gene targeting, additions, deletions, and inactivation. Zinc finger nucleases have been used to generate DSBs and subsequently, for genome editing but with low efficiency and reproducibility. The transcription activator-like family of type III effectors (TALEs) contains a central domain of tandem repeats that could be engineered to bind specific DNA targets. Here, we report the generation of a Hax3-based hybrid TALE nuclease with a user-selected DNA binding specificity. We show that the engineered TALE nuclease can bind to its target sequence in vitro and that the homodimeric TALE nuclease can cleave double-stranded DNA in vitro if the DNA binding sites have the proper spacing and orientation. Transient expression assays in tobacco leaves suggest that the hybrid nuclease creates DSB in its target sequence, which is subsequently repaired by nonhomologous end-joining repair. Taken together, our data show the feasibility of engineering TALE-based hybrid nucleases capable of generating site-specific DSBs and the great potential for site-specific genome modification in plants and eukaryotes in general.
Safety of Ferric Carboxymaltose Immediately after Infliximab Administration, in a Single Session, in Inflammatory Bowel Disease Patients with Iron Deficiency: A Pilot Study (2015)

Single-session administration of FCM after IFX was safe and effective in IBD patients and can offer a good cost-benefit ratio and improve treatment adherence. To our knowledge, this study is the first to evaluate FCM and IFX administration in a single treatment session.
Group and phase velocity coupling of colliding pulses in a nanostructure (2011)

It is generally accepted that, in a laser cavity, the group delay--responsible for the round trip time--and the phase delay both have a linear dependence on the cavity length. We show that nanostructures, such as quantum wells, can create a coupling between phase and group velocities, resulting in a periodic dependence of the repetition rate on the laser cavity length.
Photovoltaic Performance of Ultrasmall PbSe Quantum Dots (2011)

We investigated the effect of PbSe quantum dot size on the performance of Schottky solar cells made in an ITO/PEDOT/PbSe/aluminum structure, varying the PbSe nanoparticle diameter from 1 to 3 nm. In this highly confined regime, we find that the larger particle bandgap can lead to higher open-circuit voltages (∼0.6 V), and thus an increase in overall efficiency compared to previously reported devices of this structure. To carry out this study, we modified existing synthesis methods to obtain ultrasmall PbSe nanocrystals with diameters as small as 1 nm, where the nanocrystal size is controlled by adjusting the growth temperature. As expected, we find that photocurrent decreases with size due to reduced absorption and increased recombination, but we also find that the open-circuit voltage begins to decrease for particles with diameters smaller than 2 nm, most likely due to reduced collection efficiency. Owing to this effect, we find peak performance for devices made with PbSe dots with a first exciton energy of ∼1.6 eV (2.3 nm diameter), with a typical efficiency of 3.5%, and a champion device efficiency of 4.57%. Comparing the external quantum efficiency of our devices to an optical model reveals that the photocurrent is also strongly affected by the coherent interference in the thin film due to Fabry-Pérot cavity modes within the PbSe layer. Our results demonstrate that even in this simple device architecture, fine-tuning of the nanoparticle size can lead to substantial improvements in efficiency.
Zoster in Normal Children After Varicella Vaccine (1989)

Journal Article Zoster in Normal Children After Varicella Vaccine Get access Stanley A. Plotkin, Stanley A. Plotkin Division of Infectious Diseases, Children's Hospital of Philadelphia, and Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania Please address requests for reprints to Dr. Stanley A. Plotkin, Division of Infectious Diseases, The Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104. Search for other works by this author on: Oxford Academic PubMed Google Scholar Stuart E. Starr, Stuart E. Starr Division of Infectious Diseases, Children's Hospital of Philadelphia, and Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania Search for other works by this author on: Oxford Academic PubMed Google Scholar Karen Connor, Karen Connor Division of Infectious Diseases, Children's Hospital of Philadelphia, and Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania Search for other works by this author on: Oxford Academic PubMed Google Scholar David Morton David Morton Division of Infectious Diseases, Children's Hospital of Philadelphia, and Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 159, Issue 5, May 1989, Pages 1000–1001, https://doi.org/10.1093/infdis/159.5.1000 Published: 01 May 1989
Single Cell Antimicrobial Susceptibility Testing by Confined Microchannels and Electrokinetic Loading (2013)

Multidrug-resistant pathogens are an emerging global health problem. In addition to the need of developing new antibiotics in the pipeline, the ability to rapidly determine the antibiotic resistance profiles of bacteria represents one of the most crucial steps toward the management of infectious diseases and the prevention of multidrug-resistant pathogens. Here, we report a single cell antimicrobial susceptibility testing (AST) approach for rapid determination of the antibiotic resistance of bacterial pathogens. By confining individual bacteria in gas permeable microchannels with dimensions comparable to a single bacterium, the antibiotic resistance of the bacteria can be monitored in real-time at the single cell level. To facilitate the dynamic loading of the bacteria into the confined microchannels for observation, AC electrokinetics is demonstrated for capturing bacteria to defined locations in high-conductivity AST buffer. The electrokinetic technique achieves a loading efficiency of about 75% with a negligible effect on the bacterial growth rate. To optimize the protocol for single cell AST, the bacterial growth rate of individual bacteria under different antibiotic conditions has been determined systematically. The applicability of single cell AST is demonstrated by the rapid determination of the antimicrobial resistant profiles of uropathogenic clinical isolates in Mueller-Hinton media and in urine. The antibiotic resistance profiles of bacteria can be determined in less than 1 h compared to days in standard culture-based AST techniques.
Trends in Enzyme Therapy for Phenylketonuria (2004)

Phenylketonuria (PKU) is an inborn error of amino acid metabolism caused by phenylalanine hydroxylase (PAH) deficiency. Dietary treatment has been the cornerstone for controlling systemic phenylalanine (Phe) levels in PKU for the past 4 decades. Over the years, it has become clear that blood Phe concentration needs to be controlled for the life of the patient, a difficult task taking into consideration that the diet becomes very difficult to maintain. Therefore alternative models of therapy are being pursued. This review describes the progress made in enzyme replacement therapy for PKU. Two modalities are discussed, PAH and phenylalanine ammonia-lyase PAH. Developing stable and functional forms of both enzymes has proven difficult, but recent success in producing polyethylene glycol-modified forms of active and stable PAH shows promise.
Loss of CDKN2A and p14ARF expression occurs frequently in human nonmelanoma skin cancers (2007)

In addition to mutations in the p53 gene, loss of expression of CDKN2A via deletion also plays an important role in the pathogenesis of human NMSC. While p53 mutations are induced by UVB, deletions in CDKN2A could arise spontaneously, perhaps during tumour progression.
Sequences Responsible for Transcription Termination on a Gene Segment in Saccharomyces cerevisiae (1984)

We have mapped a signal sequence for mRNA 3'-end formation in Saccharomyces cerevisiae by using a Drosophila melanogaster DNA segment that complements a yeast adenine-8 mutation. That the 3' end of the transcript in S. cerevisiae nearly coincides with that in D. melanogaster is consistent with the possibility that mRNA termini are similarly determined in both organisms. Deletion analysis reveals that the complete signal is no more than 21 base pairs long. Part of the signal is the sequence TTTTTATA, which is seen in the termination region of several yeast genes. TTTTTATA appears to be able to act autonomously as a partial termination signal. The efficiency of the complete signal is affected by substitution of sequences downstream from it. This modulation of the effect of a signal is consistent with termination in S. cerevisiae, resembling rho-dependent termination in bacteria.
SM3 Hash function (2014)

This document discribles a hash function which is invented by Xiaoyun
Wang et al. This algorithm is published by Chinese Commercial
Cryptography Administration Office ([SM3]) for the use of electronic
authentication service system. This document gives IETF standard
description of the algorithm.
A phosphatidic acid-binding protein of the chloroplast inner envelope membrane involved in lipid trafficking (2006)

The biogenesis of the photosynthetic thylakoid membranes inside plant chloroplasts requires enzymes at the plastid envelope and the endoplasmic reticulum (ER). Extensive lipid trafficking is required for thylakoid lipid biosynthesis. Here the trigalactosyldiacylglycerol2 (tgd2) mutant of Arabidopsis is described. To the extent tested, tgd2 showed a complex lipid phenotype identical to the previously described tgd1 mutant. The aberrant accumulation of oligogalactolipids and triacylglycerols and the reduction of molecular species of galactolipids derived from the ER are consistent with a disruption of the import of ER-derived lipids into the plastid. The TGD1 protein is a permease-like component of an ABC transporter located in the chloroplast inner envelope membrane. The TGD2 gene encodes a phosphatidic acid-binding protein with a predicted mycobacterial cell entry domain. It is tethered to the inner chloroplast envelope membrane facing the outer envelope membrane. Presumed bacterial orthologs of TGD1 and TGD2 in Gram-negative bacteria are typically organized in transcriptional units, suggesting their involvement in a common biological process. Expression of the tgd2-1 mutant cDNA caused a dominant-negative effect replicating the tgd2 mutant phenotype. This result is interpreted as the interference of the mutant protein with its native protein complex. It is proposed that TGD2 represents the substrate-binding or regulatory component of a phosphatidic acid/lipid transport complex in the chloroplast inner envelope membrane.