gebhart/patrepeval huggingface dataset:
Sequence and immunological characterization of a serine-rich antigen from Mycobacterium leprae (1993)

Sera from lepromatous leprosy patients were used to screen a Mycobacterium leprae lambda gt11 library. Three positive plaques were picked, and lysogens were constructed. Immunoblot analysis showed that all of the lysogens expressed an apparently identical beta-galactosidase fusion protein which reacted strongly with the sera. The 1.7-kbp insert from one clone was subcloned into the lacZ gene in pUR290; sequence analysis of the end fused to lacZ revealed an open reading frame with no significant homology to previously published sequences. The insert was used to screen an M. leprae cosmid library, and five clones were isolated. The insert was also found to hybridize to clones expressing the M. leprae antigen which had previously been designated class III and 25L. A 1.8-kbp HindIII fragment was subcloned from one of the cosmids and sequenced. The sequence revealed a 1,227-bp open reading frame, encoding a 408-amino-acid protein with a predicted molecular mass of 42,466 Da. The protein contains amino- and carboxy-terminal hydrophobic domains and a hydrophilic central domain; the amino-terminal domain shows some homology to a 51-kDa hypothetical antigen of Mycobacterium tuberculosis, while the hydrophilic region contains a high proportion of serine residues, and we have therefore designated the protein serine-rich antigen (Sra). Some repeated motifs are present in the protein, but their significance is unknown. Seventy-eight percent of serum samples from multibacillary leprosy patients and 68% of serum samples from paucibacillary leprosy patients recognized the fusion protein, showing that this is a major M. leprae antigen. In contrast, all serum samples from endemic controls were negative, while 26% of serum samples from tuberculosis patients were weakly positive.
Actinomycin Resistance and Actinomycin Excretion in a Mutant of Escherichia coli (1970)

A mutant of Escherichia coli resembles its parent in taking up actinomycin after treatment with ethylenediaminetetraacetic acid but differs in that it survives this uptake and excretes actinomycin at an increased rate.
THERAPEUTIC APPROACHES TARGETED AT THE AMYLOID PROTEINS IN ALZHEIMERʼS DISEASE (1992)

CAPUTO, C. B.*; SCOTT, C. W.*; SOBEL, I. R.E.*; SYGOWSKI, L. A.*; WISCHIK, C. M.**; BRUNNER, W. F.* Author Information
Fluorogenic Azidofluoresceins for Biological Imaging (2012)

Fluorogenic probes activated by bioorthogonal chemical reactions can enable biomolecule imaging in situations where it is not possible to wash away unbound probe. One challenge for the development of such probes is the a priori identification of structures that will undergo a dramatic fluorescence enhancement by virtue of the chemical transformation. With the aid of density functional theory calculations reported previously by Nagano and co-workers, we identified azidofluorescein derivatives that were predicted to undergo an increase in fluorescence quantum yield upon Cu-catalyzed or Cu-free cycloaddition with linear or cyclic alkynes, respectively. Four derivatives were experimentally verified in model reactions, and one, a 4-azidonaphthylfluorescein analogue, was further shown to label alkyne-functionalized proteins in vitro and glycoproteins on cells with excellent selectivity. The azidofluorescein derivative also enabled cell imaging under no-wash conditions with good signal above background. This work establishes a platform for the rational design of fluorogenic azide probes with spectral properties tailored for biological imaging.
Safety and Pharmacokinetics of Abacavir (1592U89) following Oral Administration of Escalating Single Doses in Human Immunodeficiency Virus Type 1-Infected Adults (1999)

Abacavir (1592U89) is a nucleoside analog reverse transcriptase inhibitor that has been demonstrated to have selective activity against human immunodeficiency virus (HIV) in vitro and favorable safety profiles in mice and monkeys. A phase I study was conducted to evaluate the safety and pharmacokinetics of abacavir following oral administration of single escalating doses (100, 300, 600, 900, and 1,200 mg) to HIV-infected adults. In this double-blind, placebo-controlled study, subjects with baseline CD4+ cell counts ranging from < 50 to 713 cells per mm3 (median, 315 cells per mm3) were randomly assigned to receive abacavir (n = 12) or placebo (n = 6). The bioavailability of the caplet formulation relative to that of the oral solution was also assessed with the 300-mg dose. Abacavir was well tolerated by all subjects; mild to moderate asthenia, abdominal pain, headache, diarrhea, and dyspepsia were the most frequently reported adverse events, and these were not dose related. No significant clinical or laboratory abnormalities were observed throughout the study. All doses resulted in mean abacavir concentrations in plasma that exceeded the mean 50% inhibitory concentration (IC50) for clinical HIV isolates in vitro (0.07 microgram/ml) for almost 3 h. Abacavir was rapidly absorbed following oral administration, with the time to the peak concentration in plasma occurring at 1.0 to 1.7 h postdosing. Mean maximum concentrations in plasma (Cmax) and the area under the plasma concentration-time curve from time zero to infinity (AUC0-infinity) increased slightly more than proportionally from 100 to 600 mg (from 0.6 to 4.7 micrograms/ml for Cmax; from 1.0 to 15.7 micrograms.h/ml for AUC0-infinity) but increased proportionally from 600 to 1,200 mg (from 4.7 to 9.6 micrograms/ml for Cmax; from 15.7 to 32.8 micrograms.h/ml for AUC0-infinity. The elimination of abacavir from plasma was rapid, with an apparent elimination half-life of 0.9 to 1.7 h. Abacavir was well absorbed, with a relative bioavailability of the caplet formulation of 96% versus that of an oral solution (drug substance in water). In conclusion, this study showed that abacavir is safe and is well tolerated by HIV-infected subjects and demonstrated predictable pharmacokinetic characteristics when it was administered as single oral doses ranging from 100 to 1,200 mg.
Isoprenoid biosynthesis in bacteria: a novel pathway for the early steps leading to isopentenyl diphosphate (1993)

Incorporation of 13C-labelled glucose, acetate, pyruvate or erythrose allowed the determination of the origin of the carbon atoms of triterpenoids of the hopane series and/or of the ubiquinones from several bacteria (Zymomonas mobilis, Methylobacterium fujisawaense, Escherichia coli and Alicyclobacillus acidoterrestris) confirmed our earlier results obtained by incorporation of 13C-labelled acetate into the hopanoids of other bacteria and led to the identification of a novel biosynthetic route for the early steps of isoprenoid biosynthesis. The C5 framework of isoprenic units results most probably (i) from the condensation of a C2 unit derived from pyruvate decarboxylation (e.g. thiamine-activated acetaldehyde) on the C-2 carbonyl group of a triose phosphate derivative issued probably from dihydroxyacetone phosphate and not from pyruvate and (ii) from a transposition step. Although this hypothetical biosynthetic pathway resembles that of L-valine biosynthesis, this amino acid or its C5 precursors could be excluded as intermediates in the formation of isoprenic units.
Microbiological safety of porcine islets: comparison with source pig (2011)

These data fit with spread through the herd by horizontal transmission, not in utero infection. PCMV has to be excluded from the herd to ensure that islets for transplantation are negative for PCMV.
Recent progress in high resolution lithography (2006)

Abstract The nanotechnology revolution of the past decade owes much to the science of lithography, an umbrella term which encompasses everything from conventional photolithography to “unconventional” soft lithography and the self‐assembly of block polymers. In this review, some of the recent advances in lithography are summarized with special reference to the microelectronics industry. The next generation photolithography, two‐photon lithography, step‐and‐flash imprint lithography and nanofabrication using block copolymers are covered, in an attempt to describe more recent work in this vibrant and active field of research. Copyright © 2006 John Wiley &amp; Sons, Ltd.
A new compact representation of morphological profiles: report on first massive VHR image processing at the JRC (2012)

A new compact representation of dierential morphological prole (DMP) vector elds is presented. It is referred to as the CSL model and is conceived to radically reduce the dimensionality of the DMP descriptors. The model maps three characteristic parameters, namely scale, saliency and level, into the RGB space through a HSV transform. The result is a a medium abstraction semantic layer used for visual exploration, image information mining and pattern classication. Fused with the PANTEX built-up presence index, the CSL model converges to an approximate building footprint representation layer in which color represents building class labels. This process is demonstrated on the rst high resolution (HR) global human settlement layer (GHSL) computed from multi-modal HR and VHR satellite images. Results of the rst massive processing exercise involving several thousands of scenes around the globe are reported along with validation gures.
<title>Avidin-biotin system for targeting delivery of photosensitizers and other cytotoxic agents into malignant tissues</title> (1997)

It is well established that the selectivity of accumulation of photosensitizer in malignant tissues determines largely the efficiency of photodynamic therapy. Existing photosensitizers have insufficient selectivity. Thus the conjugates of photosensitizers with different carriers are promising for targeting delivery into tumor. Recently the potential of the antibody-avidin-biotin system is well studied for in vivo diagnostics. In this work we suggest to use this system for targeted delivery of the polybiotinylated compounds into cancer cells. The avidin-biotin system is highly flexible from the point of view of the pharmacokinetics of uptake of photosensitizers and the pharmacodynamics of their action. This makes it possible to select optimal conditions for phototoxic action of polybiotinylated photosensitizers and some other drugs, which are derivatives of 'Photosens' and 'Teraphthal.'
The Current Status of Camptothecin Analogues as Antitumor Agents (1993)

The nuclear enzyme topoisomerase I (topo I) has been recently recognized as the target for the anticancer drug camptothecin (CPT) and its derivatives. Two of the agents that target this enzyme--topotecan (TPT) and CPT-11--appear to be active against a broad range of human tumors. In the following presentation, we review 1) the role of topo I in normal cells, 2) the chemistry and proposed mechanism of action of CPT and its analogues, 3) the results of preclinical and clinical testing of TPT and CPT-11, and 4) mechanisms of resistance to these agents. In normal cells, topo I is thought to be involved in gene transcription and DNA replication. During the course of its normal catalytic cycle, topo I transiently forms a covalent bond with DNA. CPT and its derivatives slow the religation step of the enzyme and stabilize the covalent adduct between topo I and DNA. In S-phase cells, advancing replication forks convert these topo I-DNA adducts into double-strand breaks that appear to be responsible for the cytotoxicity of these agents. Preclinical studies demonstrate antineoplastic activity for TPT and CPT-11 in a variety of tumor models. Phase I studies have identified neutropenia as the dose-limiting toxicity for both drugs. Gastrointestinal effects might also be dose-limiting for CPT-11 administered on some schedules. CPT-11 has shown antitumor activity in phase II trials for patients with carcinomas of lung, cervix, ovary, colon, and rectum and for patients with non-Hodgkin's lymphoma. Phase II studies of TPT are in progress. Resistance to the cytotoxic effects of these agents might result from decreased production of topo I or from production of a mutated form of topo I. In addition, decreased metabolic activation of CPT-11 (which is a pro-drug) and active efflux of TPT by P-glycoprotein-mediated transport might contribute to resistance. As agents with a novel mechanism of action, tolerable toxicity, and encouraging antitumor activity in early clinical trials, TPT and CPT-11 are undergoing further clinical development. If these agents can be successfully combined with other active chemotherapy agents, the topo I-directed agents offer the potential for significant advances in the treatment of patients with a variety of malignancies.
Characterization of the DNA-binding protein antigen Ku recognized by autoantibodies from patients with rheumatic disorders. (1986)

We have characterized the biochemical nature of the Ku protein, the antigen recognized by autoantibodies from certain patients with scleroderma-polymyositis overlap syndrome. From extracts of HeLa cells labeled with [32P]orthophosphate, anti-Ku antibodies precipitated a high molecular weight nucleic acid identified as DNA because of sensitivity to DNase I and resistance to RNase. From extracts of cells labeled with [35S] methionine, these antibodies precipitated two polypeptides of 70,000 and 80,000 Da. These proteins were purified using immunoaffinity column chromatography. In immunoblots most sera containing anti-Ku antibodies recognized both Ku proteins but one serum bound only to the 70,000-Da subunit. When nucleosomal segments of chromatin were used as antigen, anti-Ku antibodies precipitated dinucleosomes and larger forms of chromatin but not mononucleosomes. Thus, the Ku antigen is a novel DNA-binding protein that is at least partially exposed on nucleosomal segments of chromatin.
Wiskott-Aldrich Syndrome Protein Physically Associates with Nck through Src Homology 3 Domains (1995)

In the second of a series of experiments designed to identify p47nck-Src homology 3 (SH3)-binding molecules, we report the cloning of SAKAP II (Src A box Nck-associated protein II) from an HL60 cDNA expression library. This molecule has been identified as a cDNA encoding the protein product of WASP, which is mutated in Wiskott-Aldrich syndrome patients. Studies in vivo and in vitro demonstrated a highly specific interaction between the SH3 domains of p47nck and Wiskott-Aldrich syndrome protein. Furthermore, anti-Wiskott-Aldrich syndrome protein antibodies recognized a protein of 66 kDa by Western blot (immunoblot) analysis. In vitro translation studies identified the 66-kDa protein as the protein product of WASP, and subcellular fractionation experiments showed that p66WASP is mainly present in the cytosol fraction, although significant amounts are also present in membrane and nuclear fractions. The main p47nck region implicated in the association with p66WASP was found to be the carboxy-terminal SH3 domain.
Cloning and Characterization of IL-22 Binding Protein, a Natural Antagonist of IL-10-Related T Cell-Derived Inducible Factor/IL-22 (2001)

The class II cytokine receptor family includes the receptors for IFN-alphabeta, IFN-gamma, IL-10, and IL-10-related T cell-derived inducible factor/IL-22. By screening genomic DNA databases, we identified a gene encoding a protein of 231 aa, showing 33 and 34% amino acid identity with the extracellular domains of the IL-22 receptor and of the IL-20R/cytokine receptor family 2-8, respectively, but lacking the transmembrane and cytoplasmic domains. A lower but significant sequence identity was found with other members of this family such as the IL-10R (29%), cytokine receptor family 2-4/IL-10Rbeta (30%), tissue factor (26%), and the four IFN receptor chains (23-25%). This gene is located on chromosome 6q24, at 35 kb from the IFNGR1 gene, and is expressed in various tissues with maximal expression in breast, lungs, and colon. The recombinant protein was found to bind IL-10-related T cell-derived inducible factor/IL-22, and to inhibit the activity of this cytokine on hepatocytes and intestinal epithelial cells. We propose to name this natural cytokine antagonist IL-22BP for IL-22 binding protein.
C-reactive protein and community-acquired pneumonia in ambulatory care: systematic review of diagnostic accuracy studies (2008)

CRP may be of value in ruling out a diagnosis of CAP in situations where the probability of CAP >10%, typically accident and emergency departments. In primary care, additional diagnostic testing with CRP is unlikely to alter the probability of CAP sufficiently to change subsequent management decisions such as antibiotic prescribing or referral to hospital.
ABC Multidrug Transporters: Target for Modulation of Drug Pharmacokinetics and Drug-Drug Interactions (2011)

Nine proteins of the ABC superfamily (P-glycoprotein, 7 MRPs and BCRP) are involved in multidrug transport. Being localised at the surface of endothelial or epithelial cells, they expel drugs back to the external medium (if located at the apical side [P-glycoprotein, BCRP, MRP2, MRP4 in the kidney]) or to the blood (if located at the basolateral side [MRP1, MRP3, MRP4, MRP5]), modulating thereby their absorption, distribution, and elimination. In the CNS, most transporters are oriented to expel drugs to the blood. Transporters also cooperate with Phase I/Phase II metabolism enzymes by eliminating drug metabolites. Their major features are (i) their capacity to recognize drugs belonging to unrelated pharmacological classes, and (ii) their redundancy, a single molecule being possibly substrate for different transporters. This ensures an efficient protection of the body against invasion by xenobiotics. Competition for transport is now characterized as a mechanism of interaction between co-administered drugs, one molecule limiting the transport of the other, which potentially affects bioavailability, distribution, and/or elimination. Again, this mechanism reinforces drug interactions mediated by cytochrome P450 inhibition, as many substrates of P-glycoprotein and CYP3A4 are common. Induction of the expression of genes coding for MDR transporters is another mechanism of drug interaction, which could affect all drug substrates of the up-regulated transporter. Overexpression of MDR transporters confers resistance to anticancer agents and other therapies. All together, these data justify why studying drug active transport should be part of the evaluation of new drugs, as recently recommended by the FDA. Keywords: P-glycoprotein, BCRP, MRP, ADME properties, drug-drug interactions, multidrug transporter, ABC superfamily, MDR efflux pumps, pharmacokinetic, metabolites
Total Synthesis and Protein Kinase Activity of C(7) Methyl Derivatives of K252a (1999)

Recent efforts in these laboratories have resulted in the development of a synthetic approach to C(7) alkyl analogs in the K252a class of indolocarbazole natural products. Synthesis of 7(R)-methyl K252a (3a) and 7-(S)-methyl K252a (3b) will be described along with their activity against protein tyrosine kinases.
Ultrafast integrable and reconfigurable XNOR, AND, NOR, and NOT photonic logic gate (2006)

A novel, simple, compact, and integrable scheme of reconfigurable and ultrafast photonic logic gate is demonstrated, based on a single semiconductor optical amplifier (SOA) and able to process ultrafast signals. XNOR function has been optically implemented exploiting four-wave mixing and cross-gain modulation in an SOA. The same scheme can be easily reconfigured to obtain AND, NOR, and NOT logic gates. Performances in terms of bit error rate for 20-ps return-to-zero signals at 10 Gb/s show a power penalty limited to 0.5 dB for all logic gates but the AND, which experiences regeneration (-2-dB power penalty) due to nonlinear SOA noise compression.
Mitogen activated protein (MAP) kinase signal transduction pathways and novel anti-inflammatory targets (2002)

Over the last decade important advances have been made in our understanding of the molecular events underlying cellular responses to extracellular signals. Increased understanding of signal transduction mechanisms and gene regulation involved in immune responses has created opportunities for the discovery of novel therapeutic compounds useful in treating inflammatory disorders. One of the best studied signalling routes is the mitogen activated protein (MAP) kinase signal transduction pathway which plays a crucial role in many aspects of immune mediated inflammatory responses. Here, our current understanding of the MAP kinase pathway is reviewed, as well as recent advances in the design of novel agents that are able to modulate the activity of these signalling cascades.
Cleavage of membrane-anchored growth factors involves distinct protease activities regulated through common mechanisms. (1992)

The membrane-anchored forms of transforming growth factor-alpha (TGF-alpha) and stem cell growth factors (Kit ligands) KL-1 and KL-2 are converted to soluble growth factor forms by a regulated proteolytic cleavage process. Each of these proteins is cleaved at a distinct site, however their cleavage is activated via a common set of intracellular signaling mechanisms. By using a panel of protease inhibitors, we show here that at least two cell-associated serine protease activities with distinct specificities participate in membrane growth factor cleavage. Two serine protease inhibitors of broad specificity, diisopropylfluorophosphate and 3,4-dichloroisocoumarin, prevent the cleavage of proTGF-alpha and KL-1 but not that of KL-2. Of the agents tested, N-tosyl-L-phenylalanine chloromethyl ketone and various haloenol lactone derivatives are the most potent inhibitors of cleavage of all three membrane growth factors. It is concluded that cleavage of membrane-anchored growth factors involves a proteolytic system with multiple serine protease activities regulated through common mechanisms.
Quantum-key-distribution protocol with pseudorandom bases (2018)

Quantum key distribution (QKD) offers a way for establishing information-theoretical secure communications. An important part of QKD technology is a high-quality random number generator for the quantum-state preparation and for post-processing procedures. In this work, we consider a class of prepare-and-measure QKD protocols, utilizing additional pseudorandomness in the preparation of quantum states. We study one of such protocols and analyze its security against the intercept-resend attack. We demonstrate that, for single-photon sources, the considered protocol gives better secret key rates than the BB84 and the asymmetric BB84 protocols. However, the protocol strongly requires single-photon sources.
DeformWear (2017)

Due to their small surfaces, wearable devices make existing techniques for touch input very challenging. This paper proposes deformation input on a tiny and soft surface as an input modality for wearable computing devices. We introduce DeformWear, tiny wearable devices that leverage single-point deformation input on various body locations. Despite the small input surface, DeformWear enables expressive and precise input using high-resolution pressure, shear, and pinch deformations. We present a first set of interaction techniques for tiny deformation-sensitive wearable devices. They enable fluid interaction in a large input space by combining multiple dimensions of deformation. We demonstrate their use in seven application examples, showing DeformWear as a standalone input device and as a companion device for smartwatches, head-mounted displays, or headphones. Results from a user study demonstrate that these tiny devices allow for precise and expressive interactions on many body locations, in standing and walking conditions.