gebhart/patrepeval huggingface dataset:
A Novel Bifunctional Wax Ester Synthase/Acyl-CoA:Diacylglycerol Acyltransferase Mediates Wax Ester and Triacylglycerol Biosynthesis inAcinetobacter calcoaceticus ADP1 (2003)

Triacylglycerols (TAGs) and wax esters are neutral lipids with considerable importance for dietetic, technical, cosmetic, and pharmaceutical applications. Acinetobacter calcoaceticus ADP1 accumulates wax esters and TAGs as intracellular storage lipids. We describe here the identification of a bifunctional enzyme from this bacterium exhibiting acyl-CoA:fatty alcohol acyltransferase (wax ester synthase, WS) as well as acyl-CoA:diacylglycerol acyltransferase (DGAT) activity. Experiments with a knock-out mutant demonstrated the key role of the bifunctional WS/DGAT for biosynthesis of both storage lipids in A. calcoaceticus. This novel type of long-chain acyl-CoA acyltransferase is not related to known acyltransferases including the WS from jojoba (Simmondsia chinensis), the DGAT1 or DGAT2 families present in yeast, plants, and animals, and the phospholipid:diacylglycerol acyltransferase catalyzing TAG formation in yeast and plants. A large number of WS/DGAT-related proteins were identified in Mycobacterium and Arabidopsis thaliana indicating an important function of these proteins. WS and DGAT activity was demonstrated for the translational product of one WS/DGAT homologous gene from M. smegmatis mc(2)155. The potential of WS/DGAT to establish novel processes for biotechnological production of jojoba-like wax esters was demonstrated by heterologous expression in recombinant Pseudomonas citronellolis. The potential of WS/DGAT as a selective therapeutic target of mycobacterial infections is discussed.
Intrinsic anion channel activity of the recombinant first nucleotide binding fold domain of the cystic fibrosis transmembrane regulator protein. (1992)

The first nucleotide binding fold (NBF-1) from the cystic fibrosis transmembrane regulator (CFTR) has been expressed in bacteria and found to bind ATP and to express anion channel activity when reconstituted onto a planar lipid bilayer. This evidence suggests that the NBF forms the anion-selective portion of the CFTR channel. We also found that the recombinant NBF-1 anion channel is blocked by ATP (1 mM), under which condition it appears to have a minimal conductance of approximately 9 pS and an ohmic current-voltage relationship. We further found that the recombinant NBF-1 bearing the delta F508 mutation has nearly identical anion channel activity to that of the wild-type protein but can be distinguished from wild type under bianionic conditions with chloride and gluconate. We conclude from these data that the anion channel activity of the recombinant NBF-1 could represent all or part of the anion conductance mechanism of CFTR and that the role of the ATP binding by the NBF could be to modulate this anion channel activity.
Specific and Potent RNA Interference in Terminally Differentiated Myotubes (2003)

Double-stranded RNA (dsRNA) interference is a potent mechanism for sequence-specific silencing of gene expression and represents an invaluable approach for investigating gene function in normal and diseased states as well as for drug target validation. Here, we report that skeletal muscle myoblasts and terminally differentiated myotubes are susceptible to RNA interference. We employed an approach in which dsRNA is generated by cellular transcription from plasmids containing long (1 kilobase) inverted DNA repeats of the target gene rather than using dsRNA synthesized in vitro. We show that gene silencing by this method is effective for endogenously expressed genes as well as for exogenous reporter genes. An analysis of the expression of several endogenous genes and exogenous reporters demonstrates that the silencing effect is specific for the target gene containing sequences within the inverted repeat. Our method eliminates the need to chemically synthesize dsRNA and is not accompanied by global repression of gene expression. Furthermore, we show for the first time that sequence-specific dsRNA-mediated gene silencing is possible in differentiated, multinucleated skeletal muscle myotubes. These findings provide an important molecular tool for the examination of protein function in terminally differentiated muscle cells and provide alternative approaches for generating disease models.
The HLA System: Genetics, Immunology, Clinical Testing, and Clinical Implications (2007)

The human major histocompatibility complex HLA is located on the short arm of chromosome 6. It is known to be the most polymorphic genetic system in humans. The biological role of the HLA class I and class II molecules is to present processed peptide antigens. The HLA system is clinically important as transplantation antigens. Molecular HLA allele typing is routinely performed to provide HLA class I and class II allele matching in unrelated donor hematopoietic stem cell transplantation. Prospective lymphocyte crossmatching is critical in solid organ transplantation to prevent allograft rejection. HLA alloimmunization causes various problems in transfusion therapy. The HLA system is associated with certain diseases, but its underlying mechanisms are not yet fully explained.
High power air-clad photonic crystal fibre laser (2003)

An Ytterbium-doped photonic crystal fibre laser is demonstrated with a 100 microm2 core area and single transverse mode with an output efficiency of 30 %. Double-clad PCF laser structures are demonstrated with pump cladding NA greater than 0.8 and output power up to 3.9 W. Such lasers are potentially scalable to high power.
Selection in vitro of an HIV-1 variant resistant to both lamivudine (3TC) and zidovudine (1996)

Goulden, M. G.; Cammack, N.; Hopewell, P. L.; Penn, C. R.; Cameron, J. M. Author Information
The Arabidopsis mutant dct is deficient in the plastidic glutamate/malate translocator DiT2 (2003)

The Arabidopsis mutant dicarboxylate transport (dct) is one of the classic mutants in the photorespiratory pathway. It requires high CO2 levels for survival. Physiologic and biochemical characterization of dct indicated that dct is deficient in the transport of dicarboxylates across the chloroplast envelope membrane. Hence, re-assimilation of ammonia generated by the photorespiratory cycle is blocked. However, the defective gene in dct has not been identified at the molecular level. Here, we report on the molecular characterization of the defective gene in dct, on the complementation of the mutant phenotype with a wild-type cDNA, and on the functional characterization of the gene product, DiT2, in a recombinant reconstituted system. Furthermore, we provide the kinetic constants of recombinant DiT1 and DiT2, and we discuss these data with respect to their functions in ammonia assimilation. Moreover, an analysis of the transcript levels of DiT1 and DiT2 in different C3- and C4-type plant species is presented, and we demonstrate that the substrate specificity of DiT2 from the C4-plant Flaveria bidentis is similar to its counterpart from C3 plants.
A phase I dose escalation pharmacokinetic (PK) and pharmacodynamic (PD) study of weekly and twice weekly erlotinib in advanced stage solid malignancies (2007)

3594 Background: Erlotinib is a potent oral TKI of the epidermal growth factor receptor (EGFR). At the current recommended daily dose of 150 mg/day there is activity in advanced stage NSCLC, but with frequent grade 1/2 rash and diarrhea. We performed a phase I dose escalation study of erlotinib with a once and twice weekly schedule to assess the PKs, PDs, and to determine if toxicities would be less on an intermittent but high dose schedule. Methods: A standard dose escalation schedule starting at 1,400 mg once/week and 600 mg twice/week with increments of 200 mg to 4 dose cohorts/schedule was utilized with three patients per cohort. A cycle consisted of 3 weeks of therapy. PKs were performed on cycle 1 and 2. PDs on normal skin punch biopsies were performed at baseline and after cycle 1. Tumour evaluation was done following every 2 nd cycle. Subjects were treated until progression or unacceptable toxicity. Results: 32 patients were enrolled from Oct 2004-April 2006. Median age 58 years (28–74 years); median PS 1 (0–2); and median prior palliative systemic regimens 2 (0–6). In the once weekly schedule the maximum tolerated dose (MTD) was not reached with the top dose of 2,000 mg/week. A median of 2 cycles were delivered (1–14), with 3/13 patients achieving stable disease = 3 months. 4/13 patients had G1 rash and 6/13 patients G1 diarrhea during the first 2 cycles. In the twice weekly schedule the MTD was reached at 1,200 mg twice/week with 2/6 subjects experiencing G3 rash. The recommended dose level is 1,000 mg twice/week. A median of 4 cycles were delivered (1–28) with 2 partial responses, 1 minor response and 6 stable disease = 3 months out of 19 patients in total. G1/2 rash or diarrhea occurred in 13 and 9 patients respectively. No corneal toxicity was seen. The PK data demonstrated a variable but linear pattern. At 1,000 mg twice/week the median C max , T max and AUC 0–24 hr was 6.28 μg/ml, 2 hours and 135 μg.h/ml respectively. PD analysis is ongoing. Conclusions: A once weekly and twice weekly high dose schedule of erlotinib is feasible, with MTD not reached in the once weekly schedule. A recommended dose of 1,000 mg twice/week has clinical activity, is generally well tolerated, and results in significantly higher systemic exposure than the 150 mg once daily dose. No significant financial relationships to disclose.
Monitoring of herbal mixtures potentially containing synthetic cannabinoids as psychoactive compounds (2010)

Herbal mixtures like 'Spice' with potentially bioactive ingredients were available in many European countries since 2004 and are still widely used as a substitute for cannabis, although merchandized as 'herbal incense'. After gaining a high degree of popularity in 2008, big quantities of these drugs were sold. In December 2008, synthetic cannabinoids were identified in the mixtures which were not declared as ingredients: the C(8) homolog of the non-classical cannabinoid CP-47,497 (CP-47,497-C8) and a cannabimimetic aminoalkylindole called JWH-018. In February 2009, a few weeks after the German legislation put these compounds and further pharmacologically active homologs of CP-47,497 under control, another cannabinoid appeared in 'incense' products: the aminoalkylindole JWH-073. In this paper, the results of monitoring of commercially available 'incense' products from June 2008 to September 2009 are presented. In this period of time, more than 140 samples of herbal mixtures were analyzed for bioactive ingredients and synthetic cannabimimetic substances in particular. The results show that the composition of many products changed repeatedly over time as a reaction to prohibition and prosecution of resellers. Therefore neither the reseller nor the consumer of these mixtures can predict the actual content of the 'incense' products. As long as there is no possibility of generic definitions in the controlled substances legislation, further designer cannabinoids will appear on the market as soon as the next legal step has been taken. This is affirmed by the recent identification of the aminoalkylindoles JWH-250 and JWH-398. As further cannabinoids can be expected to occur in the near future, a continuous monitoring of these herbal mixtures is required. The identification of the synthetic opioid O-desmethyltramadol in a herbal mixture declared to contain 'kratom' proves that the concept of selling apparently natural products spiked with potentially dangerous synthetic chemicals/pharmaceuticals is a continuing trend on the market of 'legal highs'.
A high slew-rate CMOS amplifier for analog signal processing (1990)

The performances of several types of analog VLSI circuits are limited by the setting behavior of CMOS amplifiers. An amplifier with a nonsaturated input stage which achieves a high slew-rate response is presented. The impact of this slew-rate amplifier on switched-capacitor circuits is described. Prototyping amplifier circuits were fabricated by the MOSIS service using a 2- mu m scalable CMOS technology. When biased at a DC power dissipation of 1 mW, the two-stage amplifier achieves a slew rate of 80 V/ mu s, a positive-supply rejection ratio of 73 dB, and a negative-supply rejection ratio of 57 dB and 50 kHz.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A mutant p53 tumor suppressor protein is a target for peptide-induced CD8+ cytotoxic T-cells. (1993)

Cytotoxic T-lymphocytes (CTL) recognize processed peptide fragments of any endogenous protein, after these peptides are carried to the cell surface by class I major histocompatibility molecules. Thus, a tumor antigen does not have to be expressed as an intact protein on the cell surface to be recognizable by CTL. However, mutant oncogene products have not yet been shown to be targets of CD8+ CTL. Here, we generate p53-specific CD8+ CTL by immunizing BALB/c mice with spleen cells pulsed with a peptide, corresponding to a 21-amino acid sequence encompassing a point mutation (135 Cys to Tyr) in the mutant p53 gene product from a human lung carcinoma. The mutation created a new Kd class I molecule binding motif sequence, and the determinant recognized was mapped to this motif and presented by the Kd class I molecule. The wild type peptide, without the mutation, was not recognized. Importantly, the CTL killed specifically BALB/c fibroblasts transfected with the mutant p53 gene and endogenously expressing the mutant protein, but not control fibroblasts or ones transfected with a different human mutant p53 gene. Thus, endogenously synthesized mutant p53, at levels found in tumors, can render cells targets for specific CTL, and these CTL can be generated by peptide immunization. These findings point the way toward an approach to selective immunotherapy against tumors.
Strategies to generate high-titer, high-potency recombinant AAV3 serotype vectors (2016)

Although recombinant adeno-associated virus serotype 3 (AAV3) vectors were largely ignored previously, owing to their poor transduction efficiency in most cells and tissues examined, our initial observation of the selective tropism of AAV3 serotype vectors for human liver cancer cell lines and primary human hepatocytes has led to renewed interest in this serotype. AAV3 vectors and their variants have recently proven to be extremely efficient in targeting human and nonhuman primate hepatocytes in vitro as well as in vivo. In the present studies, we wished to evaluate the relative contributions of the cis-acting inverted terminal repeats (ITRs) from AAV3 (ITR3), as well as the trans-acting Rep proteins from AAV3 (Rep3) in the AAV3 vector production and transduction. To this end, we utilized two helper plasmids: pAAVr2c3, which carries rep2 and cap3 genes, and pAAVr3c3, which carries rep3 and cap3 genes. The combined use of AAV3 ITRs, AAV3 Rep proteins, and AAV3 capsids led to the production of recombinant vectors, AAV3-Rep3/ITR3, with up to approximately two to fourfold higher titers than AAV3-Rep2/ITR2 vectors produced using AAV2 ITRs, AAV2 Rep proteins, and AAV3 capsids. We also observed that the transduction efficiency of Rep3/ITR3 AAV3 vectors was approximately fourfold higher than that of Rep2/ITR2 AAV3 vectors in human hepatocellular carcinoma cell lines in vitro. The transduction efficiency of Rep3/ITR3 vectors was increased by ~10-fold, when AAV3 capsids containing mutations in two surface-exposed residues (serine 663 and threonine 492) were used to generate a S663V+T492V double-mutant AAV3 vector. The Rep3/ITR3 AAV3 vectors also transduced human liver tumors in vivo approximately twofold more efficiently than those generated with Rep2/ITR2. Our data suggest that the transduction efficiency of AAV3 vectors can be significantly improved both using homologous Rep proteins and ITRs as well as by capsid optimization. Thus, the combined use of homologous Rep proteins, ITRs, and capsids should also lead to more efficacious other AAV serotype vectors for their optimal use in human gene therapy.
Ligation of synthetic activated DNA substrates by site-specific recombinases and topoisomerase I. (1993)

The FLP protein of the 2-microns plasmid of Saccharomyces cerevisiae is a conservative site-specific recombinase that is involved in the amplification of the plasmid. This recombination reaction proceeds via the covalent attachment of the protein to the 3'-phosphoryl group at the site of the breaks through a phosphotyrosine linkage. We have recently developed an assay that measures FLP-mediated strand ligation independent of FLP-mediated cleavage and covalent attachment to the DNA. The substrate for ligation was produced by FLP-induced cleavage of the FLP recognition site followed by digestion with Pronase and was shown to contain (at least) a tyrosine residue at the 3'-PO4 terminus adjacent to the FLP cleavage sites. We have now synthesized artificial substrates that bear a tyrosine residue on the 3'-PO4 of an appropriate oligonucleotide and find that this substrate is ligated as efficiently as the previous ligation substrates that were isolated after FLP cleavage of the substrate. Analogous substrates for other members of the integrase family of recombinases (lambda integrase protein, P1-Cre protein) as well as for mammalian topoisomerase I are also active as ligation substrates with their cognate protein. This class of activated substrates should be useful in the study of breakage and reunion reactions involving DNA.
Chloroplasts of higher plants synthesize L-phenylalanine via L-arogenate. (1986)

The specific enzymological route of L-phenylalanine biosynthesis has not been established in any higher plant system. The possible pathway routes that have been identified in microorganisms utilize either phenylpyruvate or L-arogenate as a unique intermediate. We now report the presence of arogenate dehydratase (which converts L-arogenate to L-phenylalanine) in cultured-cell populations of Nicotiana silvestris. Prephenate dehydratase (which converts prephenate to phenylpyruvate) was not detected. Arogenate dehydratase was also found in washed spinach chloroplasts, and these data add to emerging evidence in support of the existence in the plastidial compartment of a complete assembly of enzymes comprising aromatic amino acid biosynthesis. Arogenate dehydratase from tobacco and spinach were both specific for L-arogenate, inhibited by L-phenylalanine, and activated by L-tyrosine. Apparent Km values for L-arogenate (0.3 X 10(-3) M), pH optima (pH 8.5-9.5), and temperature optima for catalysis (32-34 degrees C) were also similar.
A NEW TECHNIQUE FOR TRANSURETHRAL RESECTION OF SUPERFICIAL BLADDER TUMOR IN 1 PIECE (2000)

More accurate histological diagnosis regarding the growth pattern and depth of lamina propria invasion was possible with removal of the tumor and surrounding material in 1 piece compared to conventional transurethral resection.
Ukitsapai: O 'ciúme/inveja' na música e nos rituais Wauja (2006)

Baseando-me em recente trabalho de campo entre os Wauja do alto Xingu2 , pretendo refletir sobre musica, emocoes e relacoes de ge- nero focalizando alguns aspectos dos rituais de iamurikuma, kawoka e do pequi. Para tanto, comeco tracando um breve comentario sobre o significado do universo sonoro para os Wauja, ressaltando um aspecto que creio relevante para esta analise, que vem a ser o jogo estabelecido entre ver/ouvir presente em varios rituais. Comento em seguida o universo conflitivo em que se da a aquisicao do conhecimento musical por parte das mulheres no iamurikuma, bem como apresento brevemente o mito a que este ritual se remete. A seguir, introduzo a questao das emocoes que permeiam a tematica dos cantos destas festas e comento a relacao dialogica que se estabelece entre tais rituais.
Etretinate Therapy for Generalized Pustular Psoriasis in Children (1987)

Two children, 19 months of age, were independently treated with a compassionate protocol of etretinate therapy for recalcitrant, debilitating pustular psoriasis. Laboratory test results, roentgenograms of the spine, and bone age were periodically monitored. Over a 31/2-year period of intermittent treatment with a maximum dosage of 1.5 mg/kg/d, both children showed remarkable improvement with no apparent drug effect on growth and development. Side effects included xerosis, skin fragility and transient, minimal elevations of aspartate aminotransferase, lactic dehydrogenase, and triglyceride levels. Etretinate therapy may prove to be a viable treatment option for the child with intractable pustular psoriasis that seriously impairs quality of life.
Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration (2018)

The thymus is not only extremely sensitive to damage but also has a remarkable ability to repair itself. However, the mechanisms underlying this endogenous regeneration remain poorly understood, and this capacity diminishes considerably with age. We show that thymic endothelial cells (ECs) comprise a critical pathway of regeneration via their production of bone morphogenetic protein 4 (BMP4) ECs increased their production of BMP4 after thymic damage, and abrogating BMP4 signaling or production by either pharmacologic or genetic inhibition impaired thymic repair. EC-derived BMP4 acted on thymic epithelial cells (TECs) to increase their expression of <i>Foxn1</i>, a key transcription factor involved in TEC development, maintenance, and regeneration, and its downstream targets such as <i>Dll4</i>, a key mediator of thymocyte development and regeneration. These studies demonstrate the importance of the BMP4 pathway in endogenous tissue regeneration and offer a potential clinical approach to enhance T cell immunity.
Potent selective nonpeptidic inhibitors of human lung tryptase (1999)

Human lung tryptase, a homotetrameric serine protease unique to mast cell secretory granules, has been implicated in the pathogenesis of asthma. A hypothesis that tethered symmetrical inhibitors might bridge two adjacent active sites was explored via a rationally designed series of bisbenzamidines. These compounds demonstrated a remarkable distanced-defined structure-activity relationship against human tryptase with one series possessing subnanomolar potencies. Additional evidence supporting the concept of active-site bridging is also presented.
How to Use Windows NT 4.0 Workstation (1996)

From the Publisher:
In the highly acclaimed Ziff-Davis tradition, you'll be guided step-by-illustrated-step through a tour of Windows NT 4. You'll start by learning the basics of Windows NT 4 desktop features and navigation. In no time at all you'll be adding hardware seamlessly to your system and taming unmanageable files. You'll also learn to network your machine, surf the internet from your desktop, and access your workstation from afar.