gebhart/patrepeval huggingface dataset:
Abnormal regulation of the leptin gene in the pathogenesis of obesity (1998)

A subset of obese humans has relatively low plasma levels of leptin. This finding has suggested that in some cases abnormal regulation of the leptin gene in adipose tissue is etiologic in the pathogenesis of the obese state. The possibility that a relative decrease in leptin production can lead to obesity was tested by mating animals carrying a weakly expressed adipocyte specific aP2-human leptin transgene to C57BL/6J ob/ob mice (which do not express leptin). The transgene does not contain the regulatory elements of the leptin gene and is analogous to a circumstance in which the cis elements and/or trans factors regulating leptin RNA production are abnormal. The ob/ob mice carrying the transgene had a plasma leptin level of 1. 78 ng/ml, which is approximately one-half that found in normal, nontransgenic mice (3.72 ng/ml, P < 0.01). The ob/ob animals expressing the leptin transgene were markedly obese though not as obese as ob/ob mice without the transgene. The infertility as well as several of the endocrine abnormalities generally evident in ob/ob mice were normalized in the ob/ob transgenic mice. However, the ob/ob transgenic mice had an abnormal response when placed at an ambient temperature of 4 degreesC, suggesting that different thresholds exist for the different biologic effects of leptin. Leptin treatment of the ob/ob transgenic mice resulted in marked weight loss with efficacy similar to that seen after treatment of wild-type mice. In aggregate these data suggest that dysregulation of leptin gene can result in obesity with relatively normal levels of leptin and that this form of obesity is responsive to leptin treatment.
Ingestible Osmotic Pill for In-vivo Sampling of Gut Microbiome (2019)

Abstract Technologies capable of non-invasively sampling different locations in the gut upstream of the colon will enable new insights into the role of organ-specific microbiota in human health. We present an ingestible, biocompatible, battery-less, 3D-printed micro-engineered pill with integrated osmotic sampler and microfluidic channels for in vivo sampling of the gut lumen and its microbiome upstream of the colon. The pill’s sampling performance was characterized using realistic in vitro models and validated in vivo in pigs and primates. Our results show that the bacterial populations recovered from the pills’ microfluidic channels closely resemble the bacterial population demographics of the microenvironment to which the pill was exposed. We believe such lab-on-a-pill devices will revolutionize our understanding of the spatial diversity of the gut microbiome and its response to medical conditions and treatments.
Pump-linewidth-tolerant optical data exchange between 16QAM and QPSK with 50-GHz channel-spacing using coherent DFB pump (2014)

We propose and experimentally demonstrate optical data exchange scheme between 16QAM and QPSK with narrow spacing of 50GHz. The use of coherent pump makes it free of phase noise from pumps, and enables the use of low-cost DFB as pump source.
Divorce Mediation: An Introduction (1985)

This chapter is an introduction to a form of intervention designed to counter the detrimental effects of the adversary legal system—divorce mediation. Following a history of the movement, the author discusses differences between mediation and marital and family psychotherapy. The different types of mediation services currently being offered are described. Mediation is evaluated in terms of who uses the services and factors affecting utilization; the effectiveness of mediation; client, dispute, and mediator factors related to mediation success; and client satisfaction. The limitations of mediation, as well as its promise, are also delineated.
Architecting Web Sites for High Performance (2002)

Web site applications are some of the most challenging high‐performance applications currently being developed and deployed. The challenges emerge from the specific combination of high variability in workload characteristics and of high performance demands regarding the service level, scalability, availability, and costs. In recent years, a large body of research has addressed the Web site application domain, and a host of innovative software and hardware solutions have been proposed and deployed. This paper is an overview of recent solutions concerning the architectures and the software infrastructures used in building Web site applications. The presentation emphasizes three of the main functions in a complex Web site: the processing of client requests, the control of service levels, and the interaction with remote network caches.
Alibi Routing (2015)

There are several mechanisms by which users can gain insight into where their packets have gone, but no mechanisms allow users undeniable proof that their packets did not traverse certain parts of the world while on their way to or from another host. This paper introduces the problem of finding "proofs of avoidance": evidence that the paths taken by a packet and its response avoided a user-specified set of "forbidden" geographic regions. Proving that something did not happen is often intractable, but we demonstrate a low-overhead proof structure built around the idea of what we call "alibis": relays with particular timing constraints that, when upheld, would make it impossible to traverse both the relay and the forbidden regions.
High-Resolution Crystal Structure of Plant Carboxylesterase AeCXE1, from Actinidia eriantha, and Its Complex with a High-Affinity Inhibitor Paraoxon, (2007)

Carboxylesterases (CXEs) are widely distributed in plants, where they have been implicated in roles that include plant defense, plant development, and secondary metabolism. We have cloned, overexpressed, purified, and crystallized a carboxylesterase from the kiwifruit species Actinidia eriantha (AeCXE1). The structure of AeCXE1 was determined by X-ray crystallography at 1.4 A resolution. The crystal structure revealed that AeCXE1 is a member of the alpha/beta-hydrolase fold superfamily, most closely related structurally to the hormone-sensitive lipase subgroup. The active site of the enzyme, located in an 11 A deep hydrophobic gorge, contains the conserved catalytic triad residues Ser169, Asp276, and His306. Kinetic analysis using artificial ester substrates showed that the enzyme can hydrolyze a range of carboxylester substrates with acyl groups ranging from C2 to C16, with a preference for butyryl moieties. This preference was supported by the discovery of a three-carbon acyl adduct bound to the active site Ser169 in the native structure. AeCXE1 was also found to be inhibited by organophosphates, with paraoxon (IC50 = 1.1 muM) a more potent inhibitor than dimethylchlorophosphate (DMCP; IC50 = 9.2 muM). The structure of AeCXE1 with paraoxon bound was determined at 2.3 A resolution and revealed that the inhibitor binds covalently to the catalytic serine residue, with virtually no change in the structure of the enzyme. The structural information for AeCXE1 provides a basis for addressing the wider functional roles of carboxylesterases in plants.
Chemically Programmed Antibodies As HIV-1 Attachment Inhibitors (2013)

Herein we describe the design and application of two small-molecule anti-HIV compounds for the creation of chemically programmed antibodies. N-acyl-β-lactam derivatives of two previously described molecules BMS-378806 and BMS-488043 that inhibit the interaction between HIV-1 gp120 and T-cells were synthesized and used to program the binding activity of aldolase antibody 38C2. Discovery of a successful linkage site to BMS-488043 allowed for the synthesis of chemically programmed antibodies with affinity for HIV-1 gp120 and potent HIV-1 neutralization activity. Derivation of a successful conjugation strategy for this family of HIV-1 entry inhibitors enables its application in chemically programmed antibodies and vaccines and may facilitate the development of novel bispecific antibodies and topical microbicides.
Cardiac output in polycythemia vera. (1969)

Abstract The effects of chronic change in blood volume and hematocrit on cardiac output were studied in 31 subjects: 24 with polycythemia vera (PV) and 7 normal controls. Some of the patients with PV had been treated so that their blood volumes, though not necessarily their hematocrits, were normal, and it was possible to compare normal subjects (7), patients with PV whose blood volumes were elevated at time of study (9), and patients with PV whose blood volumes were normal at time of study (15). Patients with PV who have been treated so that their blood volumes are equivalent to those normal individuals have a lower cardiac output, lower stroke output, and lower blood volume turnover than do normal individuals. There is a direct correlation between blood volume and cardiac output in PV. There is an inverse correlation between hematocrit and cardiac output in PV. The observed effect upon cardiac output depends in part upon the interaction of these 2 independent variables.
Oxygenation of iron(II) picket-fence porphyrin bound to amphiphilic block copolymer in water (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOxygenation of iron(II) picket-fence porphyrin bound to amphiphilic block copolymer in waterKiyotaka Shigehara, Kenichi Shinohara, Yoshinori Sato, and Eishun TsuchidaCite this: Macromolecules 1981, 14, 5, 1153–1161Publication Date (Print):September 1, 1981Publication History Published online1 May 2002Published inissue 1 September 1981https://pubs.acs.org/doi/10.1021/ma50006a003https://doi.org/10.1021/ma50006a003research-articleACS PublicationsRequest reuse permissionsArticle Views136Altmetric-Citations9LEARN 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
Characterization of green wastes' transformations occuring while composting (1999)

Though the process of composting offers technical advantages and leads to the production of compost used as amendment or fertilizer in agriculture, it often encounters some limitations due to a lack of control parameters and some difficulties to characterize the stabilization of organic matter. In order to better understand the process and characterize the compost's stabilization, we studied green wastes'transformations occuring while composting at an industrial plant. Characterization consisted in granulometric fractionation and chemical analysis of the fractions and the global solid : dry matter, organic matter, organic carbon, Kjeldahl nitrogen. Aqueous extractions of the solids have been realized and pH, chemical oxygen demand, Kjeldahl nitrogen and ammonium ions of the extracts have been measured. The solid organic matter characterization shows it fast doesn't change except Kjeldahl nitrogen contents which have a sensitive relative evolution. The calculation of organic matter elimination rate describes well the biodegradation slowing down. The concentrations variations in the aqueous extracts are more sensible and chemical oxygen demand is indicative of the different steps of the process. / Bien que le procédé de compostage offre de nombreux atouts techniques et conduise à la production d'un compost utilisable en tant qu'amendement ou fertilisant en agriculture, il présente un certain nombre de limites liées à une mauvaise connaissance de paramètres de contrôle et à certaines difficultés à caractériser la stabilisation de la matière organique. Dans l'objectif de mieux comprendre le procédé et de caractériser la stabilisation de la matière organique, nous avons étudié les transformations de déchets verts traités par compostage sur site industriel. La caractérisation a consisté en un fractionnement granulométrique et une analyse chimique de fractions et de solide global : matière sèche, matière organique, carbone organique, azote kjeldahl. Des extractions en phase aqueuse des solides ont été réalisées et le pH, la demande chimique en oxygène, l'azote kjeldahl et l'ammoniac des extraits aqueux ont été dosés. La caractérisation de la matière organique initialement solide montre que sa composition ne change presque pas à l'exception de sa concentration en azote dont la variation est plus sensible. Le calcul des taux d'élimination de la matière organique décrit bien le ralentissement de la biodégradabilité. Les variations de concentration dans les extraits aqueux sont en revanche plus significatives et l'évolution de la demande chimique en oxygène traduit bien les différentes étapes du procédé.
Observation of a Low-Temperature, Dynamically Driven Structural Transition in a Polypeptide by Solid-State NMR Spectroscopy (2008)

At reduced temperatures, proteins and other biomolecules are generally found to exhibit dynamic as well as structural transitions. This includes a so-called protein glass transition that is universally observed in systems cooled between 200 and 230 K, and which is generally attributed to interactions between hydrating solvent molecules and protein side chains. However, there is also experimental and theoretical evidence for a low-temperature transition in the intrinsic dynamics of the protein itself, absent any solvent. Here, we use low-temperature solid-state NMR to examine site-specific fluctuations in atomic structure and dynamics in the absence of solvents. In particular, we employ magic angle spinning NMR to examine a structural phase transition associated with dynamic processes in a solvent-free polypeptide, N-f-MLF-OH, lattice at temperatures as low as 90 K. This transition is characterized by the appearance of an extra set of lines in 1D (15)N spectra as well as additional cross peaks in 2D (13)C-(13)C and (13)C-(15)N spectra. Interestingly, the gradual, temperature-dependent appearance of the new spectral component is not accompanied by the line broadening typical of dynamic transitions. A direct comparison between the spectra of N-f-MLF-OH and the analog N-f-MLF-OMe, which does not display this transition, indicates a correlation of the structural transition to the temperature dependent motion of the aromatic phenylalanine side chain. Several quantitative solid state NMR experiments were employed to provide site-specific measurements of structural and motional features of the observed transition.
RESTORATION OF ERECTILE FUNCTION AND SEXUAL BEHAVIOR IN ATHEROSCLEROTIC MONKEYS FOLLOWING MAXI-K GENE TRANSFER WITH A SMOOTH MUSCLE-SPECIFIC PROMOTER (2008)

You have accessJournal of Urology1 Apr 2008RESTORATION OF ERECTILE FUNCTION AND SEXUAL BEHAVIOR IN ATHEROSCLEROTIC MONKEYS FOLLOWING MAXI-K GENE TRANSFER WITH A SMOOTH MUSCLE-SPECIFIC PROMOTER George J Christ, Karl-Erik Andersson, Koudy Williams, Weixin Zhao, Ralph D'Agostino, Jay Kaplan, Tamer A Aboushwareb, James J Yoo, Kelvin P Davis, and Arnold Melman George J ChristGeorge J Christ More articles by this author , Karl-Erik AnderssonKarl-Erik Andersson More articles by this author , Koudy WilliamsKoudy Williams More articles by this author , Weixin ZhaoWeixin Zhao More articles by this author , Ralph D'AgostinoRalph D'Agostino More articles by this author , Jay KaplanJay Kaplan More articles by this author , Tamer A AboushwarebTamer A Aboushwareb More articles by this author , James J YooJames J Yoo More articles by this author , Kelvin P DavisKelvin P Davis More articles by this author , and Arnold MelmanArnold Melman More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(08)61248-3AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "RESTORATION OF ERECTILE FUNCTION AND SEXUAL BEHAVIOR IN ATHEROSCLEROTIC MONKEYS FOLLOWING MAXI-K GENE TRANSFER WITH A SMOOTH MUSCLE-SPECIFIC PROMOTER." The Journal of Urology, 179(4S), pp. 425–426 © 2008 by American Urological AssociationFiguresReferencesRelatedDetails Volume 179Issue 4SApril 2008Page: 425-426 Advertisement Copyright & Permissions© 2008 by American Urological AssociationMetricsAuthor Information George J Christ More articles by this author Karl-Erik Andersson More articles by this author Koudy Williams More articles by this author Weixin Zhao More articles by this author Ralph D'Agostino More articles by this author Jay Kaplan More articles by this author Tamer A Aboushwareb More articles by this author James J Yoo More articles by this author Kelvin P Davis More articles by this author Arnold Melman More articles by this author Expand All Advertisement PDF downloadLoading ...
Complete regression of xenografted human carcinomas by camptothecin analogue-carboxymethyl dextran conjugate (T-0128). (2000)

Clinically available camptothecins (CPTs), such as irinotecan (CPT-11) and topotecan, represent one of the most promising classes of antitumor agents, despite their toxicity. To improve their pharmacological profiles, a new macromolecular prodrug, denoted T-0128, was synthesized. This prodrug is a novel CPT analogue (T-2513)-carboxymethyl (CM) dextran conjugate via a triglycine spacer, with a molecular weight of Mr 130,000. This study was designed to test the concept that the rational design of a CPT-polymer conjugate would increase the efficacy of the parent drug. The in vivo antitumor study against Walker-256 carcinoma demonstrated that T-0128 was 10 times as active as T-2513, supporting this concept. Additionally, comparative efficacy studies of T-0128, T-2513, CPT-11, and topotecan were performed using a panel of human tumor xenografts in nude mice, showing the advantage of T-0128 over these CPTs. The maximal tolerated doses (MTDs) of T-0128, T-2513, and CPT-11 were comparable. Even a single i.v. injection of T-0128 at 6 mg/kg (based on the amount of T-2513 bound to CM dextran) induced complete regression of MX-1 mammary carcinoma. T-0128 at 10 mg/kg weekly for 3 weeks (one-tenth of its MTD) cured LX-1 lung carcinoma. Also, T-0128 below its MTD consistently cured or regressed St-4 gastric and HT-29 colorectal tumor xenografts that are highly refractory to CPTs. These demonstrate the broad range of therapeutic doses achieved with T-0128. Pharmacokinetic studies were performed to correlate the efficacy results obtained for T-0128 with plasma and tissue drug concentrations using Walker-256 tumor-bearing rats. Results showed that after i.v. administration of T-0128, the conjugate continued to circulate at a high concentration for an extended period, resulting in tumor accumulation. In the tumor, the sustained release of T-2513 occurred. In contrast, T-2513 disappeared rapidly from the body. The significant increases in the amount and exposure time of released T-2513 in the tumor explain well the enhanced efficacy of T-0128. In conclusion, this study indicated that T-0128 improved the potency of T-2513, demonstrating the proof of the above concept.
Experimental and Numerical Characterization of a Raised Floor Data Center Using Rapid Operational Flow Curves Model (2015)

As the number of data centers is exponentially growing globally, pragmatic characterization schemes are considered to be a necessity for measuring and modeling the load capacity and flow pattern of the facility. This paper contains experimental and numerical characterization of a new data center laboratory using practical measurements methods, including tiles and CRAH flow measurements. Then a full physics based CFD model is built to simulate/predict the measured data. A rapid flow curve method is used showing high accuracy and low computational expense. Detailed descriptions of the data center structure, dimensions, layout (Appendix, A-1) and flow devices are given. Also, modeling parameters are mentioned in details to provide a baseline for any investigative parametric or sensitivity studies. Four experimental room level flow constraint scenarios are applied at which measurements were taken, (Appendix, A-2). The model is then built and calibrated then used to predict measurements. Measurements of the cooling unit were performed using hot wire anemometry with a traverse duct installed at the top of the CRAH. The tiles measurements were carried out using a flow hood with back pressure compensation. A detailed CFD model is constructed to predict the four experimental cases. For modeling the interdependency between the flow and pressure in flow devices flow curve approach is used. This is a rapid modeling technique that relies on experimentally measured (for IT) or approximated (for CRAH) flow curves. Applying the operational flow curves boundary conditions at the vents of the flow device results in a very accurate simulation model. It is also shown that the flow curves can be used to predict the real-time flow rate of servers at known RPM. This greatly simplifies flow rate measurements of IT in the data center.
Transcription of human respiratory syncytial virus genome RNA in vitro: requirement of cellular factor(s) (1992)

Extracts made from human respiratory syncytial virus (RSV)-infected Hep-2 cells synthesized mRNAs encoded by all known viral genes. In contrast, RSV ribonucleoproteins purified from infected cells failed to transcribe in vitro; transcription was restored by addition of a cytoplasmic extract of uninfected Hep-2 cells, demonstrating that a cellular factor(s) has a role in RSV gene expression. Quantitation of the individual gene mRNAs transcribed in vitro revealed polarity of transcription of the genome.
Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells (2016)

Converging evidence indicates that microRNAs (miRNAs) may contribute to disease risk for schizophrenia (SZ). We show that microRNA-9 (miR-9) is abundantly expressed in control neural progenitor cells (NPCs) but also significantly downregulated in a subset of SZ NPCs. We observed a strong correlation between miR-9 expression and miR-9 regulatory activity in NPCs as well as between miR-9 levels/activity, neural migration, and diagnosis. Overexpression of miR-9 was sufficient to ameliorate a previously reported neural migration deficit in SZ NPCs, whereas knockdown partially phenocopied aberrant migration in control NPCs. Unexpectedly, proteomic- and RNA sequencing (RNA-seq)-based analysis revealed that these effects were mediated primarily by small changes in expression of indirect miR-9 targets rather than large changes in direct miR-9 targets; these indirect targets are enriched for migration-associated genes. Together, these data indicate that aberrant levels and activity of miR-9 may be one of the many factors that contribute to SZ risk, at least in a subset of patients.