gebhart/patrepeval huggingface dataset:
DNA sequences of the D-serine deaminase control region and N-terminal portion of the structural gene (1983)

We determined the DNA sequence of the D-serine deaminase promoter region and of the N-terminal region of the structural gene. There are possibilities in the promoter for secondary structure and for initiation recognition sequences, and there is an open reading frame. The N-terminal sequence for the structural gene confirms that part of the amino acid sequence previously determined by E. Schlitz and W. Schmitt (FEBS Lett. 134:57-62, 1981), including the active site of the enzyme, and spans the two regions unresolved by their work.
An AfsK/AfsR system involved in the response of aerial mycelium formation to glucose in Streptomyces griseus The GenBank accession numbers for the afsK-g and afsR-g sequences determined in this work are D45246 and AB025225, respectively. (1999)

In Streptomyces coelicolor A3(2), a protein serine/threonine kinase (AfsK) and its target protein (AfsR) control secondary metabolism. AfsK and AfsR homologues (AfsK-g and AfsR-g) from Streptomyces griseus showed high end-to-end similarity in amino acid sequence with the respective S. coelicolor A3(2) proteins, as determined by cloning and nucleotide sequencing. AfsK-g and a fusion protein between AfsK-g and thioredoxin (TRX-AfsK-g) produced in high yield as inclusion bodies in Escherichia coli were solubilized with urea, purified by column chromatography and then refolded to an active form by dialysis to gradually remove the urea. AfsR-g was also fused to glutathione S-transferase (GST-AfsR-g); the fusion product in the soluble fraction in E. coli was purified. Incubation of AfsK-g or TRX-AfsK-g in the presence of [gamma-32P]ATP yielded autophosphorylated products containing phosphoserine and phosphothreonine residues. In addition, TRX-AfsK-g phosphorylated serine and threonine residues of GST-AfsR-g in the presence of [gamma-32P]ATP. Disruption of chromosomal afsK-g had no effect on A-factor or streptomycin production, irrespective of the culture conditions. The afsK-g disruptants did not form aerial mycelium or spores on media containing glucose at concentrations higher than 1%, but did form spores on mannitol- and glycerol-containing media; this suggests that afsK-g is essential for morphogenesis in the presence of glucose. Introduction of afsK-g restored aerial mycelium formation in the disruptants. The phenotype of afsR-g disruptants was similar to that of afsK-g disruptants; introduction of afsR-g restored the defect in aerial mycelium formation on glucose-containing medium. Thus the AfsK/AfsR system in S. griseus is conditionally needed for morphological differentiation, whereas in S. coelicolor A3(2) it is conditionally involved in secondary metabolism.
Importance of molecular computer modeling in anticancer drug development. (2007)

Increasing insight into the genetics and molecular biology of cancer has resulted in the identification of an increasing number of potential molecular targets for anticancer drug discovery and development. These targets can be approached through exploitation of emerging structural biology, "rational" drug design, screening of chemical libraries, or a combination of these methods. The result is the rapid discovery of new anticancer drugs. The processes used by academic and industrial scientists to discover new drugs has recently experienced a true renaissance with many new and exciting techniques being developed in the past 5-10 years. In this review, we will attempt to outline these latest protocols that chemists and biomedical scientists are currently employing to rapidly bring new drugs to the clinic. Structure-based drug design is perhaps the most elegant approach for discovering compounds exhibiting high specificity and efficacy. Nowadays, a number of recent successful drugs have in part or in whole emerged from a structure-based research approach. Many advances including crystallography and informatics are behind these successes. Of great importance is also the impact these advances in structure-based drug design are likely to have on the economics of drug discovery. As the structures of more and more proteins and nucleic acids become available, molecular docking is increasingly considered for lead discovery. Recent studies consider the hit-rate enhancement of docking screens and the accuracy of docking structure predictions. As more structures are determined experimentally, docking against homology-modeled targets also becomes possible for more proteins. With more docking studies being undertaken, the "drug-likeness" and specificity of docking hits is also being examined. In this article we discuss the application of molecular modeling, molecular docking and virtual molecular high-throughput, targeted drug screening to anticancer drug discovery. Currently, scientists are focusing on designing and discovering potential inhibitors against cancer-related proteins that play critical roles in the development of a variety of tumors. Future research breakthroughs with the aid of computer-aided molecular design and chemo-bioinformatics will bring not only new hope, but also create a new class of anticancer drugs that will help millions of cancer patients.
The Molecular Rearrangement of Sulfenanilides in Alkaline Solution. IV (1936)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Molecular Rearrangement of Sulfenanilides in Alkaline Solution. IVMaurice L. Moore and Treat B. JohnsonCite this: J. Am. Chem. Soc. 1936, 58, 10, 1960–1961Publication Date (Print):October 1, 1936Publication History Published online1 May 2002Published inissue 1 October 1936https://pubs.acs.org/doi/10.1021/ja01301a037https://doi.org/10.1021/ja01301a037research-articleACS PublicationsRequest reuse permissionsArticle Views40Altmetric-Citations5LEARN 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
Mapping ERβ Genomic Binding Sites Reveals Unique Genomic Features and Identifies EBF1 as an ERβ Interactor (2013)

Considerable effort by numerous laboratories has resulted in an improved understanding of estrogen and SERM action mediated by the two estrogen receptors, ERα and ERβ. However, many of the targets for ERβ in cell physiology remain elusive. Here, the C4-12/Flag.ERβ cell line which stably expressed Flag.ERβ is used to study ERβ genomic functions without ERα interference. Mapping ERβ binding sites in these cells reveals ERβ unique distribution and motif enrichment patterns. Accompanying our mapping results, nascent RNA profiling is performed on cells at the same treatment time. The combined results allow the identification of ERβ target genes. Gene ontology analysis reveals that ERβ targets are enriched in differentiation, development and apoptosis. Concurrently, E2 treatment suppresses proliferation in these cells. Within ERβ binding sites, while the most prevalent binding motif is the canonical ERE, motifs of known ER interactors are also enriched in ERβ binding sites. Moreover, among enriched binding motifs are those of GFI, REST and EBF1, which are unique to ERβ binding sites in these cells. Further characterization confirms the association between EBF1 and the estrogen receptors, which favors the N-terminal region of the receptor. Furthermore, EBF1 negatively regulates ERs at the protein level. In summary, by studying ERβ genomic functions in our cell model, we confirm the anti-proliferative role of ERβ and discover the novel cross talk of ERβ with EBF1 which has various implications in normal physiology.
Fairness-based adaptive QoS scheduling for LTE (2013)

LTE employs Orthogonal Frequency-Division Multiple Access (OFDMA) to provide high data transmission rate in downlink. Users expose to different network environments, so their exploited services would experience different performance of throughput, delay time, and jitter. In the literature, many studies explored how to allocate resource blocks (RB) to different services efficiently. Famous examples are Proportional Fair (PF) and Modified Largest Weighted Delay First (MLWDF) scheduling algorithms. PF considers fairness-based service priority without Quality of Service (QoS) consideration. MLWDF favors those packets with timing constraints, resulting in uneven resource distribution. In this paper, we propose a fairness-based adaptive QoS scheduling algorithm for LTE downlink. We design an Adaptive Modified Largest Weighted Delay First (AMLWDF) formula, which considers delay time, instantaneous transmission rate, average transmission rate, delay constraints, QCI priority, and fairness at the same time. Simulation results show that AMLWDF outperforms Proportional Fair and Modified Largest Weighted Delay First in various performance indexes.
Gene Expression Profiles Normalized in Psoriatic Skin by Treatment with Brodalumab, a Human Anti–IL-17 Receptor Monoclonal Antibody (2014)

The IL-17 pathway is an established driver of psoriasis pathogenesis. We examined the detailed molecular and cellular effects of blockade of IL-17 signaling in human psoriatic skin before and following treatment with brodalumab, a competitive inhibitor of the IL-17 Receptor A subunit. Thousands of aberrantly expressed genes in lesional skin normalized within 2 weeks following brodalumab treatment, with conversion of the lesional psoriasis transcriptome to resemble that seen in nonlesional skin. Keratinocyte-expressed genes appeared to normalize rapidly, whereas T cell-specific normalization occurred over six weeks. The three IL-17 ligand genes that are upregulated in lesional skin, IL17A, IL17C, and IL17F, were all downregulated in a dose-dependent manner following brodalumab treatment. Cellular measures also showed a similar pattern with dramatic decreases in keratinocyte hyperplasia within one week, and decreases in infiltrating leukocytes occurred over a longer timescale. Individuals with the highest brodalumab exposure showed normalization of both IL-17-responsive genes and the psoriasis transcriptome, whereas subjects with lower exposures showed transient or incomplete molecular responses. Clinical and molecular response appeared dependent on the extent of brodalumab exposure relative to the expression of IL-17 ligand genes, and reduction of IL-17 signaling into the nonlesional range was strongly correlated with normalization of the psoriasis transcriptome. These data indicate that blockade of IL-17 signaling in psoriatic skin leads to rapid transcriptomal changes initially in keratinocyte-expressed genes, followed by normalization in the leukocyte abnormalities, and demonstrates the essential role of the IL-17R on keratinocytes in driving disease pathogenesis.
Dynamic Confocal Imaging in Acute Brain Slices and Organotypic Slice Cultures Using a Spectral Confocal Microscope with Single Photon Excitation (2002)

Confocal imaging in living brain slices allows the resolution of submicrometre structures of nerve cells, glia and brain vessels. Imaging living brain slices is in many respects different from conventional fixed histological preparations for which confocal microscopes were designed originally. Several problems (i.e. mechanical and thermal drift, and autofluorescence) resulting from the optical and structural properties of brain slices are discussed. Fluorescent indicators may be used to monitor numerous intracellular parameters such as pH and Ca(2+) concentration, but not all of them are equally suitable for this type of work. Genetically engineered fluorescent proteins can be used to visualise the fine dendritic structure of neurones or track particular intracellular structures and proteins. They have also been used to generate indicators for Ca(2+), cAMP and other molecules. While conventional chemical indicators can be either loaded into neurones via patch pipettes or as membrane-permeable esters, protein indicators can be expressed in various types of cells using adenoviral vectors. Adenoviral transgenesis can be performed in vitro in both acute slices and organotypic slice cultures. Organotypic slice cultures give excellent optical access to neurones loaded with either conventional fluorescent indicators or transfected with adenovirus to express fluorescent proteins. They are most suitable for experiments where both conventional and genetically engineered indicators are combined. Single photon imaging in brain slices is limited to the superficial layers (approximately<or=50 microm), while multiphoton excitation has a much greater depth of penetration. However, the overall optical resolution achievable in single photon mode is at least as good as when using multiphoton excitation.
<i>ERG</i>oncogene modulates prostaglandin signaling in prostate cancer cells (2011)

Androgen dependent induction of the ETS related gene (ERG) expression in more than half of all prostate cancers results from gene fusions involving regulatory sequence of androgen regulated genes (i.e. TMPRSS2, SLC45A3 and NDRG1) and protein coding sequence of the ERG. Emerging studies in experimental models underscore the functions of ERG in prostate tumorigenesis. However, biological and biochemical functions of ERG in prostate cancer (CaP) remain to be elucidated. This study suggests that ERG activation plays a role in prostaglandin signaling because knockdown of ERG expression in TMPRSS2-ERG fusion containing CaP cells leads to altered levels of the 15-hydroxy-prostaglandin dehydrogenase (HPGD), a tumor suppressor and prostaglandin catabolizing enzyme, and prostaglandin E2 (PGE2) . We demonstrate that HPGD expression is regulated by the binding of the ERG protein to the core promoter of this gene. Moreover, prostaglandin E2 dependent cell growth and urokinase-type plasminogen activator (uPA) expression are also affected by ERG knockdown. Together, these data imply that the ERG oncoprotein in CaP cells positively influence prostaglandin mediated signaling, which may contribute to tumor progression.
Variable Impedance Control - A Reinforcement Learning Approach (2010)

One of the hallmarks of the performance, versatility, and robustness of biological motor control is the ability to adapt the impedance of the overall biomechanical system to different task requirements and stochastic disturbances. A transfer of this principle to robotics is desirable, for instance to enable robots to work robustly and safely in everyday human environments. It is, however, not trivial to derive variable impedance controllers for practical high DOF robotic tasks. In this contribution, we accomplish such gain scheduling with a reinforcement learning approach algorithm, PI 2 (Policy Improvement with Path Integrals). PI 2 is a model-free, sampling based learning method derived from first principles of optimal control. The PI 2 algorithm requires no tuning of algorithmic parameters besides the exploration noise. The designer can thus fully focus on cost function design to specify the task. From the viewpoint of robotics, a particular useful property of PI 2 is that it can scale to problems of many DOFs, so that RL on real robotic systems becomes feasible. We sketch the PI 2 algorithm and its theoretical properties, and how it is applied to gain scheduling. We evaluate our approach by presenting results on two different simulated robotic systems, a 3-DOF Phantom Premium Robot and a 6-DOF Kuka Lightweight Robot. We investigate tasks where the optimal strategy requires both tuning of the impedance of the end-effector, and tuning of a reference trajectory. The results show that we can use path integral based RL not only for planning but also to derive variable gain feedback controllers in realistic scenarios. Thus, the power of variable impedance control is made available to a wide variety of robotic systems and practical applications.
NMR observability of ATP: preferential depletion of cytosolic ATP during ischemia in perfused rat liver (1988)

The extent to which cellular metabolites are NMR observable is of fundamental importance in the interpretation of in vivo NMR studies. Analysis of ischemic rat liver shows that ATP resonances measured by 31P NMR decrease considerably faster than total tissue ATP measured in extracts. This discrepancy demonstrates that, in liver, ATP is not 100% observable. Furthermore, the data are consistent with the supposition that in situ mitochondrial ATP resonances are not normally observable by in vivo NMR techniques. The specificity of the NMR measurement for cytosolic ATP indicates that 31P NMR can be a valuable tool for the specific measurement of ATP in this compartment.
Molecular characterization of the nodulation gene, <i>nodT</i>, from two biovars of <i>Rhizobium leguminosarum</i> (1990)

DNA sequencing of the nodIJ region from Rhizobium leguminosarum biovar trifolii revealed the nodT gene immediately downstream of nodJ. DNA hybridizations using a nodT-specific probe showed that nodT is present in several R. leguminosarum strains. Interestingly, a flavonoid-inducible nodT gene homologue in R. leguminosarum bv. viciae is not in the nodABCIJ operon but is located downstream of nodMN. The sequence of the nodT gene from bv. viciae was determined and a comparison of the predicted amino-acid sequences of the two nodT genes shows them to be conserved; the predicted protein sequences appear to have a potential transit sequence typical of outer-membrane proteins. Mutations affecting nodT in either biovar had no observed effect on nodulation of the legumes tested.
A new set of BXD recombinant inbred lines from advanced intercross populations in mice (2004)

The combined BXD strain set is the largest mouse RI mapping panel. It is a powerful tool for collaborative analysis of quantitative traits and gene function that will be especially useful to study variation in transcriptome and proteome data sets under multiple environments. Additional strains also extend the value of the extensive phenotypic characterization of the previously available strains. A final advantage of expanding the BXD strain set is that both progenitors have been sequenced, and approximately 1.8 million SNPs have been characterized. This provides unprecedented power in screening candidate genes and can reduce the effective length of QTL intervals. It also makes it possible to reverse standard mapping strategies and to explore downstream effects of known sequence variants.
T-cell/histiocyte-rich B-cell lymphoma: Clinical presentation, management and prognostic factors: report on 61 patients and review of literature (2007)

T-cell/histiocyte-rich B-cell lymphoma (TC/HRBCL) is a rare subtype of diffuse large B-cell non-Hodgkin's lymphoma (DLBCL) with characteristic morphologic and immunophenotypic features, often misdiagnosed as Hodgkin's lymphoma and peripheral T-cell lymphoma. Few and conflicting clinical data are available in the literature addressing optimal treatment, prognosis and outcome. We retrospectively reviewed all patients diagnosed and managed at our institution between 1995 and 2004 diagnosed with T-cell-rich-B-cell lymphoma by WHO criteria. Sixty-one patients were identified. Initial pathology was incorrect in 82% of referred cases. The median age was 30 years. Seventy-one patients were males. Stage distribution was I - II in 21 patients, and III - IV in 40. Fifty-two percent of patients (32) had splenic involvement and thirty-seven patients (61%) presented with extranodal disease (22 >or= 2 sites). The International Prognostic Index (IPI) score was >or=2 in 62% of patients. All 59 newly diagnosed TC/HRBCL patients were treated with CHOP or R-CHOP combination chemotherapy +/- radiation therapy. The overall response rate was 85% and nine patients progressed on therapy. Fourteen patients relapsed with a median time of relapse of 6 months (range, 2 - 28). At a median follow-up of 22 months (range 1 - 132); 32 patients (52%) are alive with no evidence of disease. The 5-year overall survival and event free survival rates were 46% and 39% respectively. To conclude, TC/HRBCL is difficult to recognize without immunohistochemistry. It has an aggressive course and poor outcome; with most of patients presenting with advanced disease stage together with high IPI score. Treatment outcome seems to be similar to IPI matched DLBCL counterpart.
Generation of gene disruptions by transcription activator-like effector nucleases (TALENs) in Xenopus tropicalis embryos (2013)

Transcription activator-like effector nucleases (TALENs) are novel engineered DNA nucleases, and have been proven to be effective for gene specific targeting in various species. Recently we reported gene disruptions in Xenopus embryos by using TALENs. Here we summarize the protocol that is used in our studies for gene disruption. This protocol covers selection of TALEN targeting sites, TALEN assembly with a modified Golden Gate method, and injection of TALEN mRNAs into Xenopus tropicalis embryos. We also provide details for detection of somatic and germ line transmitted mutations. And finally, we briefly describe establishment of knockout Xenopus lines. This protocol will facilitate broader applications of TALENs in studies of Xenopus biology.
Viscoelasticity of the Onion Phase (1996)

We studied the viscoelasticity of two lyotropic lamellar systems prepared in the so-called “onion phase”. This state consists of monodisperse multilamellar vesicles filling up space. The elastic (G‘) modulus is measured as a function of the frequency in the linear regime (small amplitude of the oscillations) for different onion sizes and characteristic distances between membranes. The results are interpreted in terms of the elastic deformation of smectic beads.