gebhart/patrepeval huggingface dataset:
Homology modeling study of the human interleukin-7 receptor complex (1996)

Following a recent model of human interleukin-7 (IL-7), we present here a modeling study of the extracellular part of the human IL-7 receptor complex, including the IL-7 specific (IL-7R) and the common gamma (gamma c) chains. The investigation is based on structural homology to the complex of human growth hormone (hGH) bound to its receptor (hGHR). For domain 1 of IL-7R two different models are presented which differ in the alignment to hGHR in three regions. However, these differences affect binding to IL-7 in only one region, at the interface between loop EF of domain 1 of IL-7R and helix C of IL-7. The disulfide pattern in domain 1 of IL-7R is predicted to deviate from that observed in hGHR in that the C'-E disulfide (hGHR) is replaced by a C-C' cross-link. The prediction for the gamma c chain is compared with two previous studies. The models of the complex provide insight into the binding of IL-7 to its receptor and have implications for the suggestion of mutagenesis experiments and the design of (ant)agonists.
Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit (2012)

These guidelines provide a roadmap for developing integrated, evidence-based, and patient-centered protocols for preventing and treating pain, agitation, and delirium in critically ill patients.
An Integrated Mass Spectrometry-based Proteomic Approach (2005)

We developed an integrated proteomic approach to decipher in vivo protein-protein interactions and applied this strategy to globally map the 26 S proteasome interaction network in yeast. We termed this approach QTAX for quantitative analysis of tandem affinity purified in vivo cross-linked (X) protein complexes. For this work, in vivo formaldehyde cross-linking was used to freeze both stable and transient interactions occurring in intact cells prior to lysis. To isolate cross-linked protein complexes with high purification efficiency under fully denaturing conditions, a new tandem affinity tag consisting of a hexahistidine sequence and an in vivo biotinylation signal was adopted for affinity-based purification. Tandem affinity purification after in vivo cross-linking was combined with tandem mass spectrometry coupled with a quantitative SILAC (stable isotope labeling of amino acids in cell culture) strategy to carry out unambiguous protein identification and quantification of specific protein interactions. Using this method, we captured and identified the full composition of yeast 26 S proteasome complex as well as the two known ubiquitin receptors, Rad23 and Dsk2. Quantitative mass spectrometry analysis allowed us to distinguish specific proteasome-interacting proteins (PIPs) from background proteins and led to the identification of a total of 64 potential PIPs of which 42 are novel interactions. Among the 64 putative specific PIPs, there are ubiquitin pathway components, ubiquitinated substrates, chaperones, and transcription and translation regulators, demonstrating the efficacy of the developed approach in capturing in vivo protein interactions. The method offers an advanced technical approach to elucidate the dynamic protein interaction networks of the proteasome and can find a wide range of applications in the studies of other macromolecular protein complex interaction networks.
BIOCHEMISTRY OF ACETATE CATABOLISM IN ANAEROBIC CHEMOTROPHIC BACTERIA (1989)

Oxydation de l'acetate par le cycle de l'acide citrique, et par la voie a la carbone monoxide dehydrogenase, dismutation de l'acetate en dioxyde de carbone et methane chez les bacteries chimiotrophes anaerobies
Potential Role of Tetrahydrobiopterin in the Treatment of Maternal Phenylketonuria (2003)

BH4 supplementation seems to be a promising alternative treatment in some patients with mild PKU. Because blood Phe levels in maternal PKU should be maintained at 120 to 360 micromol/L, clinical relevance may be even greater than for treatment of children with PKU/HPA. BH4 supplementation may also be combined with a Phe-restricted diet, allowing higher Phe intake and protecting mothers from high Phe blood peaks. However, additional studies are necessary to prove the safety and economy of such an alternative treatment in patients with PKU/HPA, especially during pregnancy.
Induction Welding of Hybrid Thermoplastic-thermoset Composite Parts (2015)

With the increasing requirements on aircrafts with respect to performance and costs, there is a need for a systematical use of the advantages of different materials and innovative joining technologies. This necessitates inter alia the use of thermoplastic- and thermoset composites. The most promising technology which enables an automated process to join composite parts without rivets is the induction welding. However, the parameters influencing induction welding of thermoplastic with thermoset composites are not yet described in literature. Therefore in this study, the main factors influencing this process the film material, the film thickness and the welding temperature were identified and discussed.
Plasma source atmospheric pressure ionization detection of liquid injection using an ion trap storage/reflectron time-of-flight mass spectrometer (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPlasma source atmospheric pressure ionization detection of liquid injection using an ion trap storage/reflectron time-of-flight mass spectrometerBenjamin M. Chien, Steven M. Michael, and David M. LubmanCite this: Anal. Chem. 1993, 65, 14, 1916–1924Publication Date (Print):July 15, 1993Publication History Published online1 May 2002Published inissue 15 July 1993https://pubs.acs.org/doi/10.1021/ac00062a018https://doi.org/10.1021/ac00062a018research-articleACS PublicationsRequest reuse permissionsArticle Views111Altmetric-Citations25LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Strategies for the management of adverse events associated with mTOR inhibitors (2014)

Mammalian target of rapamycin (mTOR) inhibitors are used as potent immunosuppressive agents in solid-organ transplant recipients (everolimus and sirolimus) and as antineoplastic therapies for various cancers (eg, advanced renal cell carcinoma; everolimus, temsirolimus, ridaforolimus). Relevant literature, obtained from specific PubMed searches, was reviewed to evaluate the incidence and mechanistic features of specific adverse events (AEs) associated with mTOR inhibitor treatment, and to present strategies to effectively manage these events. The AEs examined in this review include stomatitis and other cutaneous AEs, wound-healing complications (eg, lymphocele, incisional hernia), diabetes/hyperglycemia, dyslipidemia, proteinuria, nephrotoxicity, delayed graft function, pneumonitis, anemia, hypertension, gonadal dysfunction, and ovarian toxicity. Strategies for selecting appropriate patients for mTOR inhibitor therapy and minimizing the risks of AEs are discussed, along with best practices for identifying and managing side effects. mTOR inhibitors are promising therapeutic options in immunosuppression and oncology; most AEs can be effectively detected and managed or reversed with careful monitoring and appropriate interventions.
An Optimized microRNA Backbone for Effective Single-Copy RNAi (2013)

Short hairpin RNA (shRNA) technology enables stable and regulated gene repression. For establishing experimentally versatile RNAi tools and minimizing toxicities, synthetic shRNAs can be embedded into endogenous microRNA contexts. However, due to our incomplete understanding of microRNA biogenesis, such "shRNAmirs" often fail to trigger potent knockdown, especially when expressed from a single genomic copy. Following recent advances in design of synthetic shRNAmir stems, here we take a systematic approach to optimize the experimental miR-30 backbone. Among several favorable features, we identify a conserved element 3' of the basal stem as critically required for optimal shRNAmir processing and implement it in an optimized backbone termed "miR-E", which strongly increases mature shRNA levels and knockdown efficacy. Existing miR-30 reagents can be easily converted to miR-E, and its combination with up-to-date design rules establishes a validated and accessible platform for generating effective single-copy shRNA libraries that will facilitate the functional annotation of the genome.
Pathological impact of SMN 2 mis‐splicing in adult SMA mice (2013)

Loss-of-function mutations in SMN1 cause spinal muscular atrophy (SMA), a leading genetic cause of infant mortality. The related SMN2 gene expresses suboptimal levels of functional SMN protein, due to a splicing defect. Many SMA patients reach adulthood, and there is also adult-onset (type IV) SMA. There is currently no animal model for adult-onset SMA, and the tissue-specific pathogenesis of post-developmental SMN deficiency remains elusive. Here, we use an antisense oligonucleotide (ASO) to exacerbate SMN2 mis-splicing. Intracerebroventricular ASO injection in adult SMN2-transgenic mice phenocopies key aspects of adult-onset SMA, including delayed-onset motor dysfunction and relevant histopathological features. SMN2 mis-splicing increases during late-stage disease, likely accelerating disease progression. Systemic ASO injection in adult mice causes peripheral SMN2 mis-splicing and affects prognosis, eliciting marked liver and heart pathologies, with decreased IGF1 levels. ASO dose-response and time-course studies suggest that only moderate SMN levels are required in the adult central nervous system, and treatment with a splicing-correcting ASO shows a broad therapeutic time window. We describe distinctive pathological features of adult-onset and early-onset SMA.
Long-term, continuous intravenous heparin administration by an implantable infusion pump in ambulatory patients with recurrent venous thrombosis. (1980)

We studied the effect of long-term intravenous heparin infusion, delivered by a self-recycling, totally implantable infusion pump developed in our laboratory, in 21 patients with recurrent thromboembolic disease. Continuous infusions were maintained in these patients from 1 to 36 months, during which pumps were refilled by percutaneous needle injection at 4- to 8-week intervals. We maintained plasma heparin levels between 0.1 and 0.3 U/ml plasma. This regimen prevented thromboembolic phenomena in all except one patient, who apparently is refractory to heparin as well as oral anticoagulant drug therapy. Marked reduction of pain and improvement of mobility were reported by several patients with vena cava ligature syndrome. No spontaneous hemorrhagic complications occurred; however, several episodes of pump site hemorrhage were associated with pump refills. Bone mineral densities measured in eight subjects after 1 year of heparin infusion [1.00 +/- 0.06 (SE) gm/cm] were not significantly (P = 0.5) different from baseline values (0.98 +/- 0.08 gm/cm); however, osteoporosis did occur in one subject. Serum calcium, phosphorus, alkaline phosphatase, cholesterol, and triglycerides also remained unchanged in these subjects. These data suggest that continuous long-term heparin infusion is a viable therapeutic alternative in subjects with refractory thromboembolic disease.
Seletividade de imazapic às soqueiras de cana-de-açúcar (Saccharum spp.) (2001)

Esta pesquisa objetivou a avaliar a seletividade de imazapic às soqueiras de cana-de-açúcar, cultivar RB 835089, comparado a imazapyr e tebuthiuron. O estudo foi conduzido no município de Araras-SP, durante o período de 1999/2000, em solo de classe textural franco-argilo-arenosa, devidamente corrigido e adubado. A instalação do experimento foi em blocos, com sete tratamentos casualizados e cinco repetições, a saber: imazapic (73,5; 98,0; e 122,5 g ha-1), imazapyr (125,0 g ha-1) e tebuthiuron (1.100,0 g ha-1). Os herbicidas foram aplicados em pós-emergência inicial da cultura, além das testemunhas com e sem capinas. Foi possível concluir que todos os produtos testados causaram leves sintomas de intoxicação inicial nas plantas de cana-de-açúcar, com total recuperação aos 100 dias após os tratamentos, sem prejuízo da produtividade e qualidade da matéria-prima.
Efficient infection of monkey cells with DNA of simian virus 40. (1981)

With standard protocols for DNA infection, only a small fraction (about 4%) of monkey cells exposed to purified DNA of simian virus 40 (SV40) exhibits signs of infection. We have devised a protocol by which we can extend the time of exposure of BSC-1 cells to DNA in the presence of low concentrations of DEAE-dextran. The efficiency of infection is proportional to the time of exposure. With an 8-hr exposure, we are reproducibly able to infect 25% of the cells, and we have been able to achieve levels of infection as high as 50% with a 16-hr exposure. The percentage of cells infected was measured either by scoring for nuclei positive for SV40 tumor antigen or by an infectious centers assay. We also report the use of ethidium bromide as a nonspecific nuclear counterstain in the immunofluorescence assay for SV40 tumor antigen.
Brain Tumors (1991)

THE study of brain tumors is especially rewarding today: molecular biology has provided new insights into pathogenesis, neurosurgical technology has increased the capacity for tumor removal, and promising new nonsurgical therapies are being developed. This report will review the contemporary understanding of intracranial tumors, primarily in adults, emphasizing developments within the past five years.Epidemiology and PathogenesisNew brain tumors develop in approximately 35,000 adult Americans each year.1 , 2 These can be divided into primary tumors (those arising from the brain and its coverings) and metastatic tumors (those arising elsewhere in the body). Table 1 presents a list of the most clinically important . . .
Chemical Similarity Using Physiochemical Property Descriptors (1996)

Similarity searches using topological descriptors have proved extremely useful in aiding large-scale screening. We describe alternative forms of the atom pair (Carhart et al. J. Chem. Inf. Comput. Sci. 1985, 25, 64−73.) and topological torsion (Nilakantan et al. J. Chem. Inf. Comput. Sci. 1987, 27, 82−85.) descriptors that use physiochemical atom types. These types are based on binding property class, atomic log P contribution, and partial atomic charges. The new descriptors are meant to be more "fuzzy" than the original descriptors. We propose objective criteria for determining how effective one descriptor is versus another in selecting active compounds from large databases. Using these criteria, we run similarity searches over the Derwent Standard Drug File with ten typical druglike probes. The new descriptors are not as good as the original descriptors in selecting actives if one considers the average over all probes, but the new descriptors do better for several individual probes. Generally we find that whether one descriptor does better than another varies from probe to probe in a way almost impossible to predict a priori. Most importantly, we find that different descriptors typically select very different sets of actives. Thus it is advantageous to run similarity probes with several types of descriptors.
Monocular Free-Head 3D Gaze Tracking with Deep Learning and Geometry Constraints (2017)

Free-head 3D gaze tracking outputs both the eye location and the gaze vector in 3D space, and it has wide applications in scenarios such as driver monitoring, advertisement analysis and surveillance. A reliable and low-cost monocular solution is critical for pervasive usage in these areas. Noticing that a gaze vector is a composition of head pose and eyeball movement in a geometrically deterministic way, we propose a novel gaze transform layer to connect separate head pose and eyeball movement models. The proposed decomposition does not suffer from head-gaze correlation overfitting and makes it possible to use datasets existing for other tasks. To add stronger supervision for better network training, we propose a two-step training strategy, which first trains sub-tasks with rough labels and then jointly trains with accurate gaze labels. To enable good cross-subject performance under various conditions, we collect a large dataset which has full coverage of head poses and eyeball movements, contains 200 subjects, and has diverse illumination conditions. Our deep solution achieves state-of-the-art gaze tracking accuracy, reaching 5.6° cross-subject prediction error using a small network running at 1000 fps on a single CPU (excluding face alignment time) and 4.3° cross-subject error with a deeper network.
VP1, the Putative RNA-Dependent RNA Polymerase of Infectious Bursal Disease Virus, Forms Complexes with the Capsid Protein VP3, Leading to Efficient Encapsidation into Virus-Like Particles (1999)

A cDNA corresponding to the coding region of VP1, the putative RNA-dependent RNA polymerase, of infectious bursal disease virus (IBDV) was cloned and inserted into the genome of a vaccinia virus inducible expression vector. The molecular mass and antigenic reactivity of VP1 expressed in mammalian cells are identical to those of its counterpart expressed in IBDV-infected cells. The results presented here demonstrate that VP1 is efficiently incorporated into IBDV virus-like particles (VLPs) produced in mammalian cells coexpressing the IBDV polyprotein and VP1. Incorporation of VP1 into VLPs requires neither the presence of IBDV RNAs nor that of the nonstructural polypeptide VP5. Immunofluorescence, confocal laser scanning microscopy, and immunoprecipitation analyses conclusively showed that VP1 forms complexes with the structural polypeptide VP3. Formation of VP1-VP3 complexes is likely to be a key step for the morphogenesis of IBDV particles.
STRUCTURAL BASIS OF T CELL RECOGNITION (1999)

Exciting breakthroughs in the last two years have begun to elucidate the structural basis of cellular immune recognition. Crystal structures have been determined for full-length and truncated forms of alpha beta T cell receptor (TCR) heterodimers, both alone and in complex with their peptide-MHC (pMHC) ligands or with anti-TCR antibodies. In addition, a truncated CD8 coreceptor has been visualized with a pMHC. Aided in large part by the substantial body of knowledge accumulated over the last 25 years on antibody structure, a number of general conclusions about TCR structure and its recognition of antigen can already be derived from the relatively few TCR structures that have been determined. Small, but important, variations between TCR and antibody structures bear on their functional differences as well as on their specific antigen recognition requirements. As observed in antibodies, canonical CDR loop structures are already emerging for some of the TCR CDR loops. Highly similar docking orientations of the TCR V alpha domains in the TCR/pMHC complex appear to play a primary role in dictating orientation, but the V beta positions diverge widely. Similar TCR contact positions, but whose exact amino acid content can vary, coupled with relatively poor interface shape complementarity, may explain the flexibility and short half-lives of many TCR interactions with pMHC. Here we summarize the current state of this field, and suggest that the knowledge gap between the three-dimensional structure and the signaling function of the TCR can be bridged through a synthesis of molecular biological and biophysical techniques.
Oligonucleotide N-alkylphosphoramidates: synthesis and binding to polynucleotides (1988)

A few different methods for the preparation of oligonucleotide N-alkylphosphoramidates were compared directly. One of these, involving the use of protected nucleoside phosphites as building blocks, provided the requisite N-alkylphosphoramidates via oxidation of the intermediate dinucleoside methyl phosphites with iodine in the presence of the appropriate alkylamine. This method was found to have several attractive features, including the use of building blocks identical with those employed for the synthesis of DNA and compatibility with procedures and instruments employed for the stepwise synthesis of oligonucleotides by solution and solid-phase methods. This procedure was used to make several di-, tri-, and tetranucleotide N-alkylphosphoramidates derived from deoxyadenosine and thymidine; alkyl substituents included N,N-dimethyl, N-butyl, N-octyl, N-dodecyl, and N-(5-aminopentyl). The aminoalkyl derivative of d(TpT) (24) was used to demonstrate the feasibility of introducing an intercalative agent to the alkylphosphoramidate moiety of such derivatives. The oligonucleotide N-alkylphosphoramidates were separated into their component diastereomers and characterized structurally by a number of techniques including circular dichroism, high-field 1H NMR spectroscopy, FAB mass spectrometry, and enzymatic digestion to authentic nucleosides and nucleotides. Physicochemical characterization of several di- and trinucleotide alkyl-phosphoramidates revealed that the adenine nucleotide analogues formed stable complexes with poly-(thymidylic acid). The stabilities of these complexes were found to increase with increasing chain length of the N-alkylphosphoramidate substituents. The finding that N-alkylphosphoramidate substituents can enhance the binding of certain oligonucleotides to their complementary polynucleotides suggests the existence of a novel source of polynucleotide affinity.
Modulation of Synthetic Tracheal Grafts with Extracellular Matrix Coatings (2021)

Synthetic scaffolds for the repair of long-segment tracheal defects are hindered by insufficient biocompatibility and poor graft epithelialization. In this study, we determined if extracellular matrix (ECM) coatings improved the biocompatibility and epithelialization of synthetic tracheal grafts (syn-TG). Porcine and human ECM substrates (pECM and hECM) were created through the decellularization and lyophilization of lung tissue. Four concentrations of pECM and hECM coatings on syn-TG were characterized for their effects on scaffold morphologies and on in vitro cell viability and growth. Uncoated and ECM-coated syn-TG were subsequently evaluated in vivo through the orthotopic implantation of segmental grafts or patches. These studies demonstrated that ECM coatings were not cytotoxic and, enhanced the in vitro cell viability and growth on syn-TG in a dose-dependent manner. Mass spectrometry demonstrated that fibrillin, collagen, laminin, and nephronectin were the predominant ECM components transferred onto scaffolds. The in vivo results exhibited similar robust epithelialization of uncoated and coated syn-TG patches; however, the epithelialization remained poor with either uncoated or coated scaffolds in the segmental replacement models. Overall, these findings demonstrated that ECM coatings improve the seeded cell biocompatibility of synthetic scaffolds in vitro; however, they do not improve graft epithelialization in vivo.