gebhart/patrepeval huggingface dataset:
Cytokinin Oxidase from Wheat (1989)

As part of the study of the possible role(s) of CBF-1, a cytokinin-binding protein abundant in wheat embryo, a cytokinin oxidase was found in wheat (Triticum aestivum L.) germ and partially purified by conventional purification techniques and high performance chromatofocusing. This preparation catalyzes conversion of N(6)-(Delta(2)-isopentenyl)adenosine to adenosine at a V(max) of 0.4 nanomol per milligram protein per minute at 30 degrees C and pH 7.5, the K(m) being 0.3 micromolar. This high affinity and the apparent molecular weight of 40,000 estimated by high performance gel permeation on a Spherogel TSK-3000 SW column indicate that this enzyme is different from other cytokinin oxidases previously reported. Oxygen is required for the reaction, as for other cytokinin oxidases already described. N(6)-(Delta(2)-isopentenyl)adenine and zeatin riboside are also degraded, but N(6)-(Delta(2)-isopentenyl)adenosine-5'-monophosphate is apparently not a substrate. Benzyladenine is degraded, but to a small extent, and it inhibits slightly the degradation of N(6)-(Delta(2)-isopentenyl)adenosine. The degradation of N(6)-(Delta(2)-isopentenyl)adenosine is strongly inhibited by diphenylurea and its highly active derivative N-(2-chloro-4-pyridyl)-N'-phenylurea.
Congestion control in networks with no congestion drops (2006)

Congestion is intrinsic to the operation of networks and is usually handled by a combination of algorithms at the link and network/transport layers. Link level algorithms alleviate “transient congestion” caused by the temporary oversubscription of a link due to a burst of packets arriving at a switch or router buffer. Network or transport level algorithms alleviate “sustained congestion” which occurs when the longterm arrival rate at a link exceeds its capacity. Algorithms at the two levels interact to provide a scalable, stable and fair bandwidth allocation to the flows passing through the network. Link level algorithms are typically very simple: drop or mark packets with increasing probability as buffer congestion increases; moreover, if a packet arrives at a full buffer, drop it. These dropped or marked packets are used by the transport algorithms to adjust the transmission rate of sources. In this paper we are concerned with networks in which packets cannot be dropped when there is congestion. In such networks a back-pressure mechanism “pauses” the link or links feeding a congested buffer, thus preventing further packets from arriving at the buffer. The links are later unpaused when the buffer becomes uncongested. This paper is a theoretical study of the stability and fairness properties of network level congestion control when pause mechanisms operate at the link level to prevent packet drops. Our focus is on the Backward Congestion Notification (BCN) algorithm which is being considered by the IEEE 802.1 standards body for deployment in switched Ethernet networks.
Graphene based low insertion loss electro-absorption modulator on SOI waveguide (2014)

Graphene is considered a promising material for broadband opto-electronics because of its linear and gapless band structure. Its optical conductivity can be significantly tuned electrostatically by shifting the Fermi level. Using mentioned property, we experimentally demonstrate a graphene based electro-absorption modulator with very low insertion loss. The device is realized on a silicon on insulator (SOI) waveguide operating at 1550 nm wavelength. The modulator shows a modulation depth of 16 dB and an insertion loss of 3.3 dB, surpassing GeSi and previous graphene based absorption modulators and being comparable to silicon Mach-Zehnder interferometer based modulators.
Molecular cloning of the Golgi apparatus uridine diphosphate-N-acetylglucosamine transporter from Kluyveromyces lactis. (1996)

The mannan chains of Kluyveromyces lactis mannoproteins are similar to those of Saccharomyces cerevisiae except that they lack mannose phosphate and have terminal alpha1-->2-linked N-acetylglucosamine. The biosynthesis of these chains probably occurs in the lumen of the Golgi apparatus, by analogy to S. cerevisiae. The sugar donors, GDP-mannose and UDP-GlcNAc, must first be transported from the cytosol, their site of synthesis, via specific Golgi membrane transporters into the lumen where they are substrates in the biosynthesis of these mannoproteins. A mutant of K. lactis, mnn2-2, that lacks terminal N-acetylglucosamine in its mannan chains in vivo, has recently been characterized and shown to have a specific defect in transport of UDP-GlcNAc into the lumen of Golgi vesicles in vitro. We have now cloned the gene encoding the K. lactis Golgi membrane UDP-GlcNAc transporter by complementation of the mnn2-2 mutation. The mnn2-2 mutant was transformed with a genomic library from wild-type K. lactis in a pKD1-derived vector; transformants were isolated and phenotypic correction was monitored following cell surface labeling with fluorescein isothiocyanate conjugated to Griffonia simplicifolia II lectin, which binds terminal N-acetylglucosamine, and a fluorescent activated cell sorter. A 2.4-kb DNA fragment was found to restore the wild-type lectin binding phenotype. Upon loss of the plasmid containing this fragment, reversion to the mutant phenotype occurred. The above fragment contained an open reading frame for a multitransmembrane spanning protein of 328 amino acids. The protein contains a leucine zipper motif and has high homology to predicted proteins from S. cerevisiae and C. elegans. In an assay in vitro, Golgi vesicles isolated from the transformant had regained their ability to transport UDP-GlcNAc. Taken together, the above results strongly suggest that the cloned gene encodes the Golgi UDP-GlcNAc transporter of K. lactis.
Oncolytic activity of the E1B-55 kDa-deleted adenovirus ONYX-015 is independent of cellular p53 status in human malignant glioma xenografts. (2002)

Treatment of malignant gliomas remains a major challenge in adults and children because of high treatment failure. The E1B 55 kDa-gene deleted adenovirus, ONYX-015 (ONYX Pharmaceuticals), was demonstrated to replicate selectively in and lyse tumor cells. Currently ongoing clinical trials of ONYX-015 in head and neck tumors are promising. Here, we demonstrate ONYX-015-mediated cell lysis and antitumor activity in three of four s.c. human malignant glioma xenografts deriving from primary tumors. Intratumoral injections of ONYX-015, 1 x 10(8) plaque-forming units daily for 5 consecutive days, yielded significant tumor growth delay in the p53 mutant xenografts IGRG88 and the p53 wild-type IGRG93 and IGRG121 treated at an advanced tumor stage. The p53 wild-type tumors IGRG93 and IGRG121 experienced 45% and 82% complete tumor regressions. Four and 8 of 11 animals, respectively, survived tumor free 4 months after treatment. Widespread intratumoral adenoviral replication was observed in tumor cells of these two xenografts compared with only scattered replication in the p53-mutant tumors. In addition to a fast tumor growth rate, wild-type p53 status was associated with increased antitumor activity of the E1B-attenuated virus, and induction of functional p53 may therefore determine adenoviral cytolysis in tumor cells. In conclusion, ONYX-015 displayed a major antitumor activity in human xenografts derived from primary malignant glioma supporting its development in the treatment of these highly malignant tumors.
Anti-proliferative effects of GW441756, a novel inhibitor of NGFreceptor tyrosine kinase a (TRKA), in human sarcoma (2010)

Several experimental data have shown a relevant involvement of Nerve Growth Factor (NGF) in neoplastic proliferation and survival. NGF acts through two receptors and two distinct transduction pathways: high affinity TrKA receptor connected to proliferation via AKT, and low-affinity p75 receptor connected to apoptosis via caspases. Our previous studies have shown that TrKA inhibitors have a relevant anti-proliferative effects in neoplasia. GW441756 is a novel TrKA-inhibitor (IC50 = 2nM) that displays an higher selectivity on TrKA respect to previous inhibitors and a 100-fold selectivity over a range of other kinases. However, its biological effects in cancer cells is still unknown. The aim of our study was to investigate in vitro the biological effects of this new inhibitor in human muscle sarcoma cancer cell line HTB114, at basal condition and following GW441756 administration. As revealed by thymidine incorporation, GW441756 induced a dose-dependent decrease in neoplastic proliferation. Contemporaneously, Annexin V assay demonstrated a dramatic dose-dependent increase in apoptosis. To further characterize these results, we studied AKT and caspases activation by cytofluorimetric analysis. In agreement to its anti-proliferative-pro-apoptotic effects, GW441756 did not induce AKT activation, but produced a relevant increase of caspase-3 that, in turn, leads to apoptosis. In conclusion, GW441756 has a comparable anti-neoplastic effect respect to previous TrKA inhibitors, but with a lower effective dosage (10 μM vs 50 μM of other TrKAinhibitors). Our data have a preclinical relevance to achieve anti-proliferative effects in muscular sarcomas by TrKA-inhibitors administration.
RR Interval Variability Is Inversely Related to Inflammatory Markers: The CARDIA Study (2007)

Recent evidence reveals that the immune system is under the direct control of the vagus nerve via the "cholinergic anti-inflammatory pathway." Stimulation of vagus nerve activity significantly inhibits cytokine levels in animal models, and cholinergic agents inhibit cytokine release by human macrophages. Moreover, when vagus nerve activity is decreased or absent, cytokines are overproduced. Atherosclerosis is an inflammatory disease characterized by elevated levels of CRP and IL-6, but the relationship between cardiac vagal activity and cytokine levels in healthy humans is not well understood. Here we measured RR interval variability, an index of cardiac vagal modulation, and CRP and IL-6 in 757 subjects participating in a subset of the year 15 data collection in the CARDIA study of the evolution of risk factors in young adults. Univariate analysis revealed that all indices of RRV were strongly and inversely related to IL-6 (log pg/mL b=-0.08 and -0.17 for HF and LF power, P<0.001 respectively) and CRP (log mg/L b=-0.14 and -0.26 for HF and LF power, P<0.001 respectively) levels. In the multivariate model including gender, race, age, smoking, physical activity, SBP, BMI, and disease, the inverse relationship between RRV and inflammatory markers, although slightly attenuated, remained significant. These findings are consistent with the hypothesis that diminished descending vagal anti-inflammatory signals can allow cytokine overproduction in humans.
Short Protocols in Immunology: A Compendium of Methods from Current Protocols in Immunology (2005)

Short Protocols in Immunology is an easy-to use companion to Current Protocols in Immunology. Drawn from the most fundamental and widely used methods in the well-known parent volume, this book provides step-by-step protocols in their most easily accessible format for use at the bench. Immunologists in basic science and clinical work alike will find techniques they rely on, including production, purification, and fragmentation of antibodies; assays for lymphocyte function; measurement of cytokines and cytokine receptors; biochemistry of lymphocyte activation; innate immunity, isolation of human immune cell populations, detection and analysis of HIV, and animal models for a variety of autoimmune and infectious diseases.
Design of generic biosensors based on green fluorescent proteins with allosteric sites by directed evolution (1999)

Protein-engineering techniques have been adapted for the molecular design of biosensors that combine a molecular-recognition site with a signal-transduction function. The optical signal-transduction mechanism of green fluorescent protein (GFP) is most attractive, but hard to combine with a ligand-binding site. Here we describe a general method of creating entirely new molecular-recognition sites on GFPs. At the first step, a protein domain containing a desired molecular-binding site is inserted into a surface loop of GFP. Next, the insertional fusion protein is randomly mutated, and new allosteric proteins that undergo changes in fluorescence upon binding of target molecules are selected from the random library. We have tested this methodology by using TEM1 beta-lactamase and its inhibitory protein as our model protein-ligand system. 'Allosteric GFP biosensors' constructed by this method may be used in a wide range of applications including biochemistry and cell biology.
Identification by RNA Profiling and Mutational Analysis of the Novel Copper Resistance Determinants CrdA (HP1326), CrdB (HP1327), and CzcB (HP1328) in Helicobacter pylori (2002)

Mechanisms involved in maintaining cytoplasmic metal ion homeostasis play a central role in the adaptation of Helicobacter pylori to the changing gastric environment. An investigation of the global regulatory responses to copper ions by using RNA profiling with a threshold factor of 4.0 revealed that copper induces transcription of 19 H. pylori genes and that only the ferritin gene pfr is repressed. The 57-fold copper induction identified the HP1326 gene encoding an H. pylori-specific protein as a candidate for a novel copper resistance determinant. The HP1326 gene is expressed as a monocistronic unit, and two small HP1326 mRNAs are copper induced. The HP1326 protein is secreted and is required for copper resistance maintained by cytoplasmic copper homeostasis, as H. pylori HP1326 mutants were copper sensitive and displayed increased copper induction of HP1326 transcription as well as elevated copper repression of ferritin synthesis. The clear copper-sensitive phenotype displayed by H. pylori HP1327 and HP1328 mutants provides strong evidence that the HP1326 protein, together with the signal peptide site of the H. pylori-specific protein HP1327, whose gene is located downstream from that encoding HP1326, and the CzcB and CzcA metal efflux system component homologs HP1328 and HP1329, constitutes a novel type of copper efflux pump, as discussed below. The HP1329 gene could not be inactivated, but the 14-fold transcriptional copper induction determined by RNA profiling points towards a function of the encoded CzcA homolog in copper resistance. In summary, results from RNA profiling identified the novel H. pylori-specific copper resistance determinants CrdA (HP1326) and CrdB (HP1327), which are required for adaptation to copper-rich environmental conditions.
Mutational analysis of the conserved basic domain of human immunodeficiency virus tat protein (1989)

The tat trans-activators encoded by the known strains of primate immunodeficiency virus share a conserved, highly basic protein domain. Mutagenesis of this sequence in the tat gene of human immunodeficiency virus type 1 is shown here to reduce, but not eliminate, the trans-activation of human immunodeficiency virus type 1-specific gene expression. The degree of inhibition is shown to vary in a dose-dependent manner and is most marked at low levels of tat expression. Multiple mutations of the basic domain of tat were found to impair both the in vivo stability and the nuclear localization of the tat protein. It is proposed that this protein domain serves to efficiently target the tat gene product to its appropriate site or substrate within the nucleus of expressing cells.
On the inclusion of solvent molecules in the crystal structures of organic compounds (2000)

The Cambridge Structural Database has been searched for all crystal structures including organic solvent molecules (solvates) and solvent water molecules (hydrates). Well above 300 different solvent molecules were identified and the frequencies with which they occur in crystal structures, as a function of the year of publication, were established. The crystal structures are classified as `organic' and `metalloorganic'; it is shown that the relative prevalences of various cocrystallized solvents are different in the two groups. Several frequently used organic solvents are also common ligands for metal ions. Special interest has been focused on the existence of heterosolvates, i.e. crystal structures which include more than one type of solvent molecule. Up to five different types of solvent molecules were found in a single crystal structure. It is suggested that the use of solvent mixtures during crystallizations may prove to be a more useful and versatile approach for obtaining crystals of high-molecular-weight organic compounds than has hitherto been recognized.
Sulfonamide-Based Inhibitors of Aminoglycoside Acetyltransferase Eis Abolish Resistance to Kanamycin in Mycobacterium tuberculosis (2016)

A two-drug combination therapy where one drug targets an offending cell and the other targets a resistance mechanism to the first drug is a time-tested, yet underexploited approach to combat or prevent drug resistance. By high-throughput screening, we identified a sulfonamide scaffold that served as a pharmacophore to generate inhibitors of Mycobacterium tuberculosis acetyltransferase Eis, whose upregulation causes resistance to the aminoglycoside (AG) antibiotic kanamycin A (KAN) in Mycobacterium tuberculosis. Rational systematic derivatization of this scaffold to maximize Eis inhibition and abolish the Eis-mediated KAN resistance of M. tuberculosis yielded several highly potent agents. A crystal structure of Eis in complex with one of the most potent inhibitors revealed that the inhibitor bound Eis in the AG-binding pocket held by a conformationally malleable region of Eis (residues 28-37) bearing key hydrophobic residues. These Eis inhibitors are promising leads for preclinical development of innovative AG combination therapies against resistant TB.
Regioselective Aromatic Substitution of 6,8‐Dihydroxy‐4‐ethoxycarbonyl‐2H‐isoquinolin‐1‐one Derivatives Using the Stille Coupling Reaction. (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
Ultrathin Aluminum Oxide Tunnel Barriers (2002)

Ballistic electron emission microscopy is used to study the formation of ultrathin tunnel barriers by the oxidization of aluminum. An O2 exposure, approximately 30 mTorr sec, forms a uniform tunnel barrier with a barrier height straight phi(b) of 1.2 eV. Greater O2 exposure does not alter straight phi(b) or the ballistic transmissivity of the oxide conduction band. Tunneling spectroscopy indicates a broad energy distribution of electronic states in the oxide. With increasing O2 dose the states below 1.2 eV gradually become localized, but until this localization is complete these states can provide low-energy single-electron channels through the oxide.
Mark-release-recapture of sand flies fed on leishmanial dogs: the natural life-cycle of Leishmania infantum in Phlebotomus ariasi. (2002)

Wild-caught Phlebotomus ariasi Tonnoir permitted to feed on dogs infected with Leishmania infantum Nicolle were marked with fluorescent powder and released into their natural habitat in an uninhabited area of the Cévennes in southern France. Over a period of 29 days after release, 253 females were recaptured with CDC miniature light traps or by active search at night with portable UV lamps. The ovaries and infections in the alimentary tract were then examined. The females oviposited 6 nights after in infecting blood meal. Second blood meals were never taken during the maturation of eggs. During the first ovarian cycle, midgut infections with promastigotes were only moderately heavy. The intensity of infection increased markedly during the second ovarian cycle and, in the third ovarian cycle, the first pharynx infected with paramastigotes was seen (on day 19). From day 19 to day 29, 76% of the flies had pharyngeal infections. Three out of 19 sand flies with pharyngeal infections recaptured during this period had metacyclic promastigotes in their mouthparts. The long time required for parasites to reach the proboscis in completely natural conditions suggests that their presence in the mouthparts is not a prerequisite for transmission by bite. It is more likely that transmission is most commonly by the regurgitation of metacyclic promastigotes from the thoracic midgut following damage to the stomodaeal valve by chitinase produced by the parasite during its development in the gut of the fly. Nevertheless, it is reasonable to assume that the bite of a fly with metacyclic promastigotes in the proboscis (or salivary glands) would also be infective.
Localization of epitopes for monoclonal antibodies at the N‐terminus of the porcine zona pellucida glycoprotein pZPC (1995)

Zona pellucida glycoproteins play an important role in fertilization. In this study, attempts have been made to identify and define epitopes of monoclonal antibodies (mAbs) possessing contraceptive efficacy in vitro. The porcine zona glycoprotein pZPC, a homologue of mouse/human ZP3, was reduced and alkylated and subsequently digested with trypsin. Reverse-phase HPLC of the tryptic digest yielded twenty two peaks (T1-T22). When tested against mAbs reactive against sequential determinants on pZPC, T11 was immunoreactive with two mAbs, mAb-455 and mAb-467, as shown by antigen inhibition ELISA. IC50 values of 3.1 nM and 8.6 nM were recorded versus mAb-455 and mAb-467 respectively, and approximated the IC50 values obtained with intact pZPC. Amino acid analysis, Edman degradation, and FAB-MS identified T11 as the N-blocked decapeptide pyro-Gln-Pro-Val-Trp-Gln-Asp-Glu-Gly-Gln-Arg derived from the N-terminus of pZPC. Synthesis of overlapping octapeptides further identified VWQDE and WQDE as the minimum motifs with antigenic activity for mAb-455 and mAb-467, respectively. Glycine replacement peptides confirmed residues W,Q,E as critical for binding mAb-455 and W,Q,D,E as critical for binding mAb-467. Both mAbs inhibited binding of boar sperm to zona-encased porcine oocytes. These results, the first to define peptide epitopes of porcine zona glycoprotein, will assist in the design of an immunocontraceptive vaccine based on synthetic peptides corresponding to pZPC or its homologues in other species.
ICOS Deficiency Is Associated with a Severe Reduction of CXCR5+CD4 Germinal Center Th Cells (2006)

ICOS is expressed on activated T cells and particularly on CXCR5+ follicular Th cells in germinal centers (GC). Its deletion leads to a profound deficiency in memory B cell formation and switched Ab response in humans. Here, we show that in ICOS-deficient patients the generation of GCs is severely disturbed, and the numbers of circulating CXCR5+CD45RO+ memory CD4 T cells are significantly reduced, indicating an essential role of ICOS in the differentiation of CXCR5+CD4 T cells. The GC-specific CD57+CXCR5+ subpopulation is virtually absent. In ICOS-/- mice, the decrease of circulating CXCR5+CD4 T cells reflects the reduction of CXCR5+ follicular Th cells in lymph nodes and spleen. Therefore, in concurrence with the absence of CXCR5+ T cells in the blood of CD40L-deficient patients, these data support the hypothesis that circulating CD57+CXCR5+ T cells are GC derived and thus may serve as a surrogate marker for the presence of functional GCs in humans.