gebhart/patrepeval huggingface dataset:
Synthesis and central nervous system depressant activity of new piperazine and related derivatives. III (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and central nervous system depressant activity of new piperazine and related derivatives. IIIR. B. Petigara, Chimanlal Deliwala, S. S. Mandrekar, N. K. Dadkar, and U. K. ShethCite this: J. Med. Chem. 1969, 12, 5, 865–870Publication Date (Print):September 1, 1969Publication History Published online1 May 2002Published inissue 1 September 1969https://pubs.acs.org/doi/10.1021/jm00305a034https://doi.org/10.1021/jm00305a034research-articleACS PublicationsRequest reuse permissionsArticle Views73Altmetric-Citations2LEARN 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
Multi-disciplinary Optimization of Split-Tip Winglet and Extraction of Design Knowledge by Dimension Reduction Technology (2021)

In this paper, we describe multi-disciplinary optimization (MDO) of a split-tip winglet (STW) model for the TRA2012A commercial jet aircraft model. The STW configuration is expressed by attaching a small wing under the main winglet. The onboard fuel weight, main wing structure weight and the sum of these weights are objective functions, and are minimized respectively in a fixed aircraft operating range for the MDO. The independent component analysis is applied to non-dominated optimal designs obtained from the MDO, and then dominant shape deformation modes are extracted. Design knowledge to improve multi-disciplinary performance is investigated from the modes.
Building an Open Representation for Biological Protocols (2023)

Laboratory protocols are critical to biological research and development, yet difficult to communicate and reproduce across projects, investigators, and organizations. While many attempts have been made to address this challenge, there is currently no available protocol representation that is unambiguous enough for precise interpretation and automation, yet simultaneously “human friendly” and abstract enough to enable reuse and adaptation. The Laboratory Open Protocol language (LabOP) is a free and open protocol representation aiming to address this gap, building on a foundation of UML, Autoprotocol, Aquarium, SBOL RDF, and the Provenance Ontology. LabOP provides a linked-data representation both for protocols and for records of their execution and the resulting data, as well as a framework for exporting from LabOP for execution by either humans or laboratory automation. LabOP is currently implemented in the form of an RDF knowledge representation, specification document, and Python library, and supports execution as manual “paper protocols,” by Autoprotocol or by Opentrons. From this initial implementation, LabOP is being further developed as an open community effort.
Checkpointing for optimistic concurrency control methods (1995)

Restart-oriented concurrency control (CC) methods, such as optimistic CC, outperform blocking-oriented methods, such as standard two-phase locking in a high data contention environment, but this is at the cost of wasted processing due to restarts. Volatile savepoints are considered in this study as a method to reduce this wasted processing and to improve response time. There is the usual tradeoff between the checkpointing overhead and the wasted processing when a transaction is restarted. Our study shows that in a system where objects are accessed and updated uniformly during the lifetime of transactions, significant improvement in performance at high data conflict levels are attainable only when the checkpointing cost is low. This implies few optimally placed checkpoints per transaction. It is observed that checkpointing may result in a significant improvement in performance when access to database hot-spots are deferred to the final steps of transaction execution. The parametric studies reported in this paper are facilitated by closed-form analytic solutions expressing system performance, as well as an iterative solution which takes into account hardware resource contention in addition to data contention.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Degradation of rapamycin: Synthesis of a rapamycin derived fragment containing the tricarbonyl and triene sectors (1993)

A degradation of rapamycin involving retro-Michael and retro-aldol steps retrieves the entire C1-C27 subunit.
Characteristics of circulating megakaryocyte progenitors (CFU‐MK) in patients with primary myelofibrosis (1988)

Characteristics of circulating CFU-MK and the effect of serum and plasma on CFU-MK growth were studied in 14 patients with primary myelofibrosis (MF) using short- and long-term culture methods. The number of CFU-MK in short-term cultures was significantly increased in the non-splenectomized patient group (p less than 0.01). Without added PHA-LCM and normal serum, spontaneous colony formation was found in 9 out of 10 patients. In long-term blood cultures from 6 MF patients, 3 untreated patients formed confluent adherent layers and produced in suspension an equal number or an even greater number of nucleated cells, megakaryocytes and CFU-MK than those obtained in long-term bone marrow culture from normal individuals. 2 splenectomized patients showed neither an increased numbers of CFU-MK nor the capacity to develop an adherent layer. The serum and plasma of MF patients failed to stimulate megakaryocyte colony formation by normal bone marrow in a normal fashion. These findings indicate a megakaryocytopoietic abnormality, and a central role of the spleen in extramedullary haematopoiesis in MF.
Abundance of Amino Acid Transporters and mTOR Pathway Components in the Gastrointestinal Tract of Lactating Holstein Cows (2023)

Data from non-ruminants indicate that amino acid (AA) transport into cells can regulate mTOR pathway activity and protein synthesis. Whether mTOR is expressed in the ruminant gastrointestinal tract (GIT) and how it may be related to AA transporters and the AA concentrations in the tissue is unknown. Ruminal papillae and the epithelia of the duodenum, jejunum, and ileum collected at slaughter from eight clinically healthy Holstein in mid-lactation were used. Metabolites and RNA were extracted from tissue for liquid chromatography-mass spectrometry and RT-qPCR analysis. The glycine and asparagine concentrations in the rumen were greater than those in the intestine (<i>p</i> < 0.05), but the concentrations of other AAs were greater in the small intestine than those in the rumen. Among the 20 AAs identified, the concentrations of glutamate, alanine, and glycine were the greatest. The mRNA abundances of <i>AKT1</i> and <i>MTOR</i> were greater in the small intestine than those in the rumen (<i>p</i> < 0.05). Similarly, the <i>SLC1A1</i>, <i>SLC6A6</i>, <i>SLC7A8</i>, <i>SLC38A1</i>, <i>SLC38A7</i>, and <i>SLC43A2</i> mRNA abundances were greater (<i>p</i> < 0.05) in the small intestine than those in the rumen. The mRNA abundances of <i>SLC1A5</i>, <i>SLC3A2,</i> and <i>SLC7A5</i> were greater in the rumen than those in the small intestine (<i>p</i> < 0.05). Overall, the present study provides fundamental data on the relationship between mTOR pathway components and the transport of AAs in different sections of the gastrointestinal tract.
Inflammatory bowel disease is associated with a TNF polymorphism that affects an interaction between the OCT1 and NF-kappaB transcription factors (2002)

Tumour necrosis factor-alpha (TNF) expression is increased in inflammatory bowel disease (IBD), and TNF maps to the IBD3 susceptibility locus. Transmission disequilibrium and case-control analyses, in two independent Caucasian cohorts, showed a novel association of the TNF(-857C) promoter polymorphism with IBD (overall P=0.001 in 587 IBD families). Further genetic associations of TNF(-857C) with IBD sub-phenotypes were seen for ulcerative colitis and for Crohn's disease, but only in patients not carrying common NOD2 mutations. The genetic data suggest a recessive model of inheritance, and we observed ex vivo lipopolysaccharide-stimulated whole-blood TNF production to be higher in healthy TNF(-857C) homozygotes. We show the transcription factor OCT1 binds TNF(-857T) but not TNF(-857C), and interacts in vitro and in vivo with the pro-inflammatory NF(-kappa)B transcription factor p65 subunit at an adjacent binding site. Detailed functional analyses of these interactions in gut macrophages, in addition to further genetic mapping of this gene-dense region, will be critical to understand the significance of the observed association of TNF(-857C) with IBD.
Chemoattraction of bone marrow-derived stem cells towards human endometrial stromal cells is mediated by estradiol regulated CXCL12 and CXCR4 expression (2015)

Bone marrow derived cells engraft to the uterine endometrium and contribute to endometriosis. The mechanism by which these cells are mobilized and directed to the endometrium has not been previously characterized. We demonstrate that human endometrial stromal cells (hESCs) produce the chemokine CXCL12 and that bone marrow cells (BMCs) express the CXCL12 receptor, CXCR4. Treatment with physiological levels of estradiol (E2) induced both CXCL12 and CXCR4 expression in hESCs and BMCs, respectively. BMCs migrated towards hESCs conditioned media; a CXCR4 antagonist blocked migration indicating that CXCL12 acting through its receptor, CXCR4, is necessary for chemoattraction of BM cells to human endometrial cells. E2 increased both CXCL12 expression in endometrial cells and CXCR4 expression in BM cells, further enhancing chemoattraction. E2 induced CXCL12/CXCR4 expression in endometrium and BM, respectively, drives migration of stem cells to the endometrium. The E2-CXCL12/CXCR4 signaling pathway may be useful in determining treatments for endometrial disorders, and may be antagonized to block stem cell migration to endometriosis.
Views: Letter from Melbourne: War on wabbits (2011)

From time to time, I come across references to chemicals used to control Australia's rabbit population. Given our record of success in this endeavour, 'attempt to control' might be more appropriate. These days the dominant chemical is pindone, 2-pivaloyl-1,3-indanedione, the structure of which is related to that of warfarin, both being based on 4-hydroxycoumarin. They have similar biological actions, thinning the blood of mammals, but while one is used (in carefully monitored doses) to treat cardiac patients, the other is used against the bunnies. In the hands of licensed operators, pindone is absorbed into carrot slices, which are distributed in places frequented by rabbits. This chemical warfare can be quite effective in reducing populations, although complete eradication has long been put aside as an unrealisable dream.
Coalition Formation Game for Cooperative Content Delivery in Network Coding Assisted D2D Communications (2020)

Device-to-device (D2D) communications have shown a huge potential in cellular offloading and become a potential technology in 5G and beyond. In D2D networks, the requested contents by user devices (UDs) can be delivered via D2D links, thus offloading the content providers (CPs). In this work, we address the problem of minimizing the delay of delivering content in a <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">decentralized</i> and <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">partially</i> D2D connected network using network coding (NC) and cooperation among the UDs. The proposed optimization framework considers UDs’ acquired and missing contents, their limited coverage zones, NC, and content’s erasure probability. As such, the completion time for delivering all missing contents to all UDs is minimized. The problem is modeled as a coalition game with cooperative-players wherein the payoff function is derived so that increasing individual payoff results in the desired cooperative behavior. Given the intractability of the formulation, the coalition game is relaxed to a coalition formation game (CFG). A distributed coalition formation algorithm relying on merge-and-split rules is developed for solving the relaxed problem at each transmission. The effectiveness of the proposed solution is validated through computer simulation against existing schemes.
Analysis of the Ability of Pramlintide To Inhibit Amyloid Formation by Human Islet Amyloid Polypeptide Reveals a Balance between Optimal Recognition and Reduced Amyloidogenicity (2015)

The hormone human islet amyloid polypeptide (hIAPP or amylin) plays a role in glucose metabolism, but forms amyloid in the pancreas in type 2 diabetes (T2D) and is associated with β-cell death and dysfunction in the disease. Inhibitors of islet amyloid have therapeutic potential; however, there are no clinically approved inhibitors, and the mode of action of existing inhibitors is not well understood. Rat IAPP (rIAPP) differs from hIAPP at six positions, does not form amyloid, and is an inhibitor of amyloid formation by hIAPP. Five of the six differences are located within the segment of residues 20-29, and three of them are Pro residues, which are well-known disruptors of β-sheet structure. rIAPP is thus a natural example of a "β-breaker inhibitor", a molecule that combines a recognition element with an entity that inhibits β-sheet formation. Pramlintide (PM) is a peptide drug approved for use as an adjunct to insulin therapy for treatment of diabetes. PM was developed by introducing the three Pro substitutions found in rIAPP into hIAPP. Thus, it more closely resembles the human peptide than does rIAPP. Here we examine and compare the ability of rIAPP, PM, and a set of designed analogues of hIAPP to inhibit amyloid formation by hIAPP, to elucidate the factors that lead to effective peptide-based inhibitors. Our results reveal, for this class of molecules, a balance between the reduced amyloidogenicity of the inhibitory sequence on one hand and its ability to recognize hIAPP on the other.
Capacitive sensors coupled to a scanning tunneling microscope piezoscanner for accurate measurements of the tip displacements (1994)

This article studies the use of capacitive sensors for in situ calibration of the piezoscanner of a scanning tunneling microscope (STM). Nonlinearities, hysteresis, and creeps of piezoactuators are the main sources of the uncertainty in the tip position while scanning the sample surface to be imaged. In order to compensate for these effects in the reconstruction of the surface topography, capacitive sensors have been coupled to a piezoscanner of a STM operating in air. This scanner provides x,y,z displacements up to about 130 μm×130 μm×30 μm, and consists of bimorph plates mounted in a parallelogram arrangement. The capacitive sensors are inserted in a differential configuration to minimize capacitance variations due to changes in humidity and temperature of the air and to compensate for thermal drifts of the structure. As a performance test, the piezoscanner displacements were independently measured by means of a differential interferometer. A linearity within 3% and a deviation within 0.3% from the expected capacitance versus displacement dependence were achieved for scanner range up to 130 μm, with a resolution of 5 nm. Perspective improvements of the present setup are also discussed.
Apolipoprotein AV Accelerates Plasma Hydrolysis of Triglyceriderich Lipoproteins by Interaction with Proteoglycan-bound Lipoprotein Lipase (2005)

Apolipoprotein A5 (APOA5) is associated with differences in triglyceride levels and familial combined hyperlipidemia. In genetically engineered mice, apoAV plasma levels are inversely correlated with plasma triglycerides. To elucidate the mechanism by which apoAV influences plasma triglycerides, metabolic studies and in vitro assays resembling physiological conditions were performed. In human APOA5 transgenic mice (hAPOA5tr), catabolism of chylomicrons and very low density lipoprotein (VLDL) was accelerated due to a faster plasma hydrolysis of triglycerides by lipoprotein lipase (LPL). Hepatic VLDL and intestinal chylomicron production were not affected. The functional interplay between apoAV and LPL was further investigated by cross-breeding a human LPL transgene with the apoa5 knock-out and the hAPOA5tr to an lpl-deficient background. Increased LPL activity completely normalized hypertriglyceridemia of apoa5-deficient mice; however, overexpression of human apoAV modulated triglyceride levels only slightly when LPL was reduced. To reflect the physiological situation in which LPL is bound to cell surface proteoglycans, we examined hydrolysis in the presence or absence of proteoglycans. Without proteoglycans, apoAV derived either from triglyceride-rich lipoproteins, hAPOA5tr high density lipoprotein, or a recombinant source did not alter the LPL hydrolysis rate. In the presence of proteoglycans, however, apoAV led to a significant and dose-dependent increase in LPL-mediated hydrolysis of VLDL triglycerides. These results were confirmed in cell culture using a proteoglycan-deficient cell line. A direct interaction between LPL and apoAV was found by ligand blotting. It is proposed, that apoAV reduces triglyceride levels by guiding VLDL and chylomicrons to proteoglycan-bound LPL for lipolysis.
A Novel 3D Viscoelastic Acoustic Wave Equation Based Update Method for Reservoir History Matching (2014)

The oil and gas industry has been revolutionized within the last decade, with horizontal drilling and hydraulic fracturing enabling the extraction of huge amounts of shale gas in areas previously considered impossible and the recovering of hydrocarbons in harsh environments like the arctic or in previously unimaginable depths like the off-shore exploration in the South China sea and Gulf of Mexico. With the development of 4D seismic, engineers and scientists have been enabled to map the evolution of fluid fronts within the reservoir and determine the displacement caused by the injected fluids. This in turn has led to enhanced production strategies, cost reduction and increased profits. Conventional approaches to incorporate seismic data into the history matching process have been to invert these data for constraints that are subsequently employed in the history matching process. This approach makes the incorporation computationally expensive and requires a lot of manual processing for obtaining the correct interpretation due to the potential artifacts that are generated by the generally ill-conditioned inversion problems. I have presented here a novel approach via including the time-lapse cross-well seismic survey data directly into the history matching process. The generated time-lapse seismic data are obtained from the full wave 3D viscoelastic acoustic wave equation. Furthermore an extensive analysis has been performed showing the robustness of the method and enhanced forecastability of the critical reservoir parameters, reducing uncertainties and exhibiting the benefits of a full wave 3D seismic approach. Finally, the improved performance has been statistically confirmed. The improvements illustrate the significant improvements in forecasting that are obtained via readily available seismic data without the need for inversion. This further optimizes oil production in addition to increasing return-on-investment on oil &amp; gas field development projects, especially in offshore environments.
Persistent p55TNFR expression impairs T cell responses during chronic tuberculosis and promotes reactivation (2016)

The pleiotropic activities of TNF are mediated by two structurally related but functionally distinct type I transmembrane receptors, p55TNFR and p75TNFR expressed in most cell types, that can be cleaved and act as TNF scavengers. Here, we investigated the effect of persistent p55TNFR cell surface expression during aerosol inhalation challenge with virulent M. tuberculosis H37Rv. We demonstrated that persistency of p55TNFR in macrophage cultures increased the synthesis of soluble TNF, p75TNFR and NO, however, had no effects on bacteria killing ability. Furthermore, it did not facilitate enhanced protection to primary acute M. tuberculosis infection in p55<sup>∆NS</sup> mice. Without exacerbated lung inflammation, we found a compensatory increase in p75TNFR shedding and decrease in bioactive TNF in BAL of p55<sup>∆NS</sup> mice after M. tuberculosis challenge. Defective expressions of CD44 and INFγ attributed to an impaired T cell response during persistent p55TNFR expression that caused marginal transient susceptibility during chronic infection. Moreover, persistent p55TNFR expression induced early reactivation during latent tuberculosis infection. These data indicate a prominent role of p55TNFR shedding in Th1 mediated protection against chronic and latent tuberculosis infection.
The influence of brain inflammation upon neuronal adenosine A2Breceptors (2003)

Alzheimer's disease (AD) is associated with glial activation and increased levels of pro-inflammatory cytokines. Epidemiological results suggest that anti-inflammatory therapies can slow the onset of AD. Adenosine, acting at type-2 receptors, is an effective endogenous anti-inflammatory agent that can modulate inflammation both in the periphery and the brain. We investigated changes in the expression of adenosine type-2B (A2B) receptors and a related intracellular second messenger during chronic brain inflammation and following treatment with the non-steroidal anti-inflammatory drug flurbiprofen and its nitric oxide (NO)-donating derivative, HCT1026. Chronic infusion of lipopolysaccharide (LPS) into the 4th ventricle of young rats induced brain inflammation that was associated with microglial activation and reduced neuronal immunoreactivity for adenosine A2B receptors in the cortex. Daily administration of HCT1026, but not flurbiprofen, reduced microglial activation, prevented the down-regulation of A2B receptors and elevated tissue levels of cAMP. The results suggest that a therapy using an NO-releasing NSAID might significantly attenuate the processes that drive the pathology associated with AD and that this process may involve the activation of adenosine A2B receptors.