gebhart/patrepeval huggingface dataset:
0756 Preclinical Pharmacology of Solriamfetol: Potential Mechanisms for Wake Promotion (2022)

Abstract Introduction Solriamfetol is a wake-promoting agent (WPA) approved for the treatment of excessive daytime sleepiness associated with narcolepsy and obstructive sleep apnea. The wake-promoting mechanism of solriamfetol may result from dopamine and norepinephrine reuptake inhibition. Preclinical pharmacology studies were conducted to further elucidate the molecular targets activated by solriamfetol and compare them to that of known WPAs and traditional stimulants. Methods In vitro binding and functional studies were conducted in a panel of cell lines or membrane preparations expressing transmembrane receptors and monoamine transporters to measure the activity of solriamfetol, comparator WPAs, and traditional stimulants. Electrophysiology studies were conducted in slice preparations from mouse ventral tegmental area (VTA). Studies to measure locomotor activity and wake-promoting effects were conducted in mice. Results In vitro functional studies showed agonist activity of solriamfetol at human, mouse, and rat TAAR1 receptors. hTAAR1 EC50 values (10–16 µM) were within the clinically observed therapeutic solriamfetol plasma concentration range and overlapped with the observed DAT/NET inhibitory potencies of solriamfetol in vitro. TAAR1 agonist activity was unique to solriamfetol; neither the WPA modafinil nor the DAT/NET inhibitor bupropion had TAAR1 agonist activity. Solriamfetol (1–10 µM) dose-dependently inhibited the firing frequency of dopaminergic VTA neurons in mouse brain slices, similar to known TAAR1 agonists; however, these effects were inhibited by a D2 antagonist, suggesting a DAT-mediated effect. Unlike traditional stimulants, solriamfetol did not increase locomotor activity in naive mice, but inhibited the increase in locomotor activity in DAT knockout mice. Conclusion Preclinical studies have identified agonist activity at the TAAR1 receptor and, possibly, lower potency agonist activity at 5-HT1A receptors as potential pharmacological targets for solriamfetol, in addition to its activity as a DAT/NET inhibitor. Given the current understanding of TAAR1 agonists as modulators of monoamine transmission with potential wake-promoting effects in multiple preclinical species, agonist activity at the hTAAR1 receptor may represent an additional pharmacological target underlying the wake-promoting effects for solriamfetol, in addition to its DNRI activity. Support (If Any) Jazz Pharmaceuticals
Towards a Scalable and Unified REST API for Cloud Data Stores. (2014)

In the last years, many database-as-a-service (DBaaS) systems have started to offer their functionalities through REST APIs. Examples are record stores like DynamoDB and Azure Tables, object stores such as Amazon S3 as well as many NoSQL database systems, for instance Riak, CouchDB and ElasticSearch. Yet today, there has been no systematic effort on deriving a unified REST interface which takes into account the different data models, schemas, consistency concepts, transactions, access-control mechanisms and query languages to expose cloud data stores through a common interface without restricting their functionality. This work motivates the design of such a REST API as well as the challenges of providing it in an extensible, scalable and highly-available fashion. To this end, we propose the REST middleware ORESTES that consists of an independently scalable tier of HTTP servers that map the unified REST API to aggregate-oriented (NoSQL) data stores. It extracts a wide range of DBaaS concerns (e.g. schema management and access control) and provides them in a modular, database-independent fashion at the middleware-level. To tackle the latency problem of cloud-based web applications we introduce the Bloom filter-bounded staleness cache consistency algorithm. It leverages the global web caching infrastructure for geo-replication to allow consistent low latency reads. We furthermore show the first steps towards a Polyglot Persistence Mediator that exploits the decoupling of the REST API from the data store to route data and operations based on SLAs.
Nuclear Atypia Is a Necessary Factor for Diagnosis of Primary Ovarian Fibrosarcoma: A Case Report and Literature Review (2020)

Herein we report a case of primary ovarian fibrosarcoma and reviewed all published cases in English. Following the latest trend of diagnosis, multiple prognostic factors were used to determine survival prognosis. These included nuclear atypia, FIGO stage, mitotic counts, treatment methods, and tumor size. Only nuclear atypia was found to be associated with patient prognosis (p < 0.05). FIGO stage (p = 0.383), mitotic count per 10 hpfs (p = 0.155), treatment methods (p = 0.185), and tumor size (p = 0.972) were not found to be associated with survival prognosis. Nuclear atypia was an important factor in prognosis of patients. Using surgery with adjuvant medical treatment was inconclusive regarding patient survival.
How to project customer retention (2007)

At the heart of any contractual or subscription-oriented business model is the notion of the retention rate. An important managerial task is to take a series of past retention numbers for a given group of customers and project them into the future to make more accurate predictions about customer tenure, lifetime value, and so on. As an alternative to common “curve-fitting” regression models, we develop and demonstrate a probability model with a well-grounded “story” for the churn process. We show that our basic model (known as a “shifted-beta-geometric”) can be implemented in a simple Microsoft Excel spreadsheet and provides remarkably accurate forecasts and other useful diagnostics about customer retention. We provide a detailed appendix covering the implementation details and offer additional pointers to other related models.
Epitope Mapping of Neutralizing Monoclonal Antibodies to Human Interferon-γ Using Human-Bovine Interferon-γ Chimeras (2016)

Our aim was to identify conformational epitopes, recognized by monoclonal antibodies (mAbs) made against human (h) interferon (IFN)-γ. Based on the mAbs' (n = 12) ability to simultaneously bind hIFN-γ in ELISA, 2 epitope clusters with 5 mAbs in each were defined; 2 mAbs recognized unique epitopes. Utilizing the mAbs' lack of reactivity with bovine (b) IFN-γ, epitopes were identified using 7 h/bIFN-γ chimeras where the helical regions (A-F) or the C terminus were substituted with bIFN-γ residues. Chimeras had a N-terminal peptide tag enabling the analysis of mAb recognition of chimeras in ELISA. The 2 mAb clusters mapped to region A and E, respectively; the epitopes of several mAbs also involved additional regions. MAbs in cluster A neutralized, to various degrees, IFN-γ-mediated activation of human cells, in line with the involvement of region A in the IFN-γ receptor interaction. MAbs mapping to region E displayed a stronger neutralizing capacity although this region has not been directly implicated in the receptor interaction. The results corroborate earlier studies and provide a detailed picture of the link between the epitope specificity and neutralizing capacity of mAbs. They further demonstrate the general use of peptide-tagged chimeric proteins as a powerful and straightforward method for efficient mapping of conformational epitopes.
Bupropion SR in adults with ADHD: a short-term, placebo-controlled trial. (2005)

Increased attention has been given to the alternatives to stimulants in the treatment of attention deficit hyperactivity disorder (ADHD) in both adults and children. This short-term, double-blind trial was designed to evaluate the extended-release form of bupropion in adult subjects meeting DSM-IV and the Utah Diagnostic Criteria for ADHD. Outcome measures were the Clinical Global Impressions-Improvement (CGI-I) and the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS), which assesses adult ADHD symptoms. Outcome (defined by the CGI-I, average WRAADDS scores, or a 50% improvement on the WRAADDS) favored bupropion SR over placebo, but achieved statistical significance on only one, post hoc measure. Other measures showed trends for improvement with bupropion. Given the small size of this study, these findings deserve further exploration.
Do It All’s loyalty programme ‐ and its impact on customer retention (1996)

Describes a bonus card system and examines the results of an analysis of bonus card transactions giving key customer segments. Looks at retention and acquisition strategies and emphasizes the importance of keeping pace with customer expectations.
Physiological changes in fowl and turkey spermatozoa during<i>in vitro</i>storage (1989)

1. Although early work on semen storage has been rather empirical in approach, only basic research can provide a framework of biological mechanisms from which improvements in the techniques of cryopreservation and liquid semen storage can progress logically. 2. A major drawback in this work has been the lack of adequate tests for quantitating and differentiating aspects of 'fertility'. 3. Basic research has now provided techniques for assessing: sperm fertilising ability in terms of numbers of fertile eggs; the efficiency of hens' oviducts at accepting and retaining spermatozoa, and sperm 'quality' as motility, metabolism and plasma membrane patency. 4. These techniques may be used for a more critical assessment of the effects of both cryopreservation and liquid semen storage on sperm function, although the integrity of sperm surface proteins may be a more sensitive variable which has yet to be measured. 5. Further improvements in sperm cryopreservation technology are best approached through an understanding of the fundamental cellular and molecular changes which take place during freezing; thus far little is known of such changes in avian spermatozoa. 6. The ideal milieu for maintaining spermatozoa in liquid semen storage should mimic the environment of the oviducal sperm storage tubules; elucidation of the factors involved in progressing steadily.
Multi-Resolution Broadcast/Multicast Systems for MBMS (2007)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> Multimedia Broadcast/Multicast Service (MBMS) supports downlink streaming and download-and-play type services to large groups of users. From the radio perspective, MBMS includes point-to-point (PtP) and point-to-multipoint (PtM) modes. This paper investigates and presents different multi-resolution broadcast systems for Wideband Code Division Multiple Access (WCDMA) cellular mobile networks, namely, multi-code, hierarchical QAM constellations and multi-antenna (MIMO) systems. Each one present performance gains over conventional single-resolution broadcast systems. A comparison is made between the three proposed multi-resolution systems. </para>
An Integrated Resource Management Architecture for Wireless Smart Environments. (2003)

Ultrasonography is a reproducible examination that can be used to assess the damage to elbow ligaments during the acute phase following an injury. This examination could be incorporated into the exploration protocol for elbow injuries during the preoperative assessment and to adapt the treatment.
Unit Value Indexes for Exports – New Developments Using Administrative Trade Data (2022)

Abstract U.S. import and export price indexes replaced unit value indexes forty years ago, given quality concerns of mismeasurement due to unit value bias. The administrative trade data underlying the unit values have greatly improved since that time. The transaction records are now more detailed, available electronically, and compiled monthly with little delay. The data are used by academic researchers to calculate price measures, and unit value indexes based on trade data are used by other national statistical offices (NSOs). The U.S. Bureau of Labor Statistics is now evaluating whether replacing price indexes with unit value indexes for homogeneous products calculated from administrative trade data could expand the number of published official import and export price indexes. Using export transactions, the research calculates detailed unit value indexes from 200 + million trade records from 2012–2017 for 123 export product categories. Results show that 27 of the 123 unit value indexes are homogeneous and closely comparable to published official price indexes. This article presents the concepts and methods considered to calculate and evaluate the unit value indexes and to select the product categories that are homogeneous. Compared to official price indexes, export unit value indexes for the 27 5-digit BEA (U.S. Bureau of Economic Analysis) end-use product categories would deflate real exports of these goods by 13 percentage points less over the period. Incorporating these 27 indexes into the top-level XPI would increase the value of real exports of all merchandise goods by 2.6 percentage points at the end of 2017.
Selective Transport Across the Blood-Brain Barrier (1986)

Letters and Corrections1 September 1986Selective Transport Across the Blood-Brain BarrierWILLIAM A. BANKS, M.D., ABBA J. KASTIN, M.D., EDWARD A. MICHALSWILLIAM A. BANKS, M.D.Search for more papers by this author, ABBA J. KASTIN, M.D.Search for more papers by this author, EDWARD A. MICHALSSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-105-3-472_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Cook and Boyle (1) have recently emphasized the issue of a differential response of the central nervous system to thyroxine and triiodothyronine. Although differential responses of tissues to thyroid hormones may occur at many levels, the hormones must first reach the target organ. In the case of the brain, this means traversing the blood-brain barrier. Triiodothyronine has been shown to be transported across the blood-brain barrier by a saturable, carrier-mediated transport system (2), but by extrapolation it has been widely assumed that thyroxine is transported by the same system. Studies of thyroid levels in the cerebrospinal fluid...References1. COOKBOYLE DP. Rapid reversal of myxedema madness with triiodothyronine [Letter]. Ann Intern Med. 1986;104:893-4. LinkGoogle Scholar2. PARDRIDGE W. Carrier mediated transport of thyroid hormones through the rat blood brain barrier: primary role of albumin-bound hormone. Endocrinology. 1979;105:605-12. CrossrefMedlineGoogle Scholar3. CHERNOWBURMANJOHNSON BKD. T3 may be a better agent than T4 in the critically ill hypothyroid patient: evaluation of transport across the blood-brain barrier in a primate model. Crit Care Med. 1983;11:99-104. CrossrefMedlineGoogle Scholar4. BANKSKASTINMICHALS WAE. Transport of thyroxine across the blood-brain barrier is directed primarily from the brain to the blood in the mouse. Life Sci. 1985;37:2407-14. CrossrefMedlineGoogle Scholar5. BANKSKASTIN WA. A brain-to-blood transport system for small, N-tyrosinated peptides. Pharmacol Biochem Behav. 1984;21:943-6. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Veterans Administration Medical Center Tulane University Medical School New Orleans, LA 70146 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByMitochondrial mechanisms in amyloid beta peptide-induced cerebrovascular degeneration 1 September 1986Volume 105, Issue 3Page: 472-472KeywordsBlood-brain barrierBrainCentral nervous systemCerebrospinal fluidExtrapolationThyroidThyroid hormonesThyroxineTriiodothyronine Issue Published: 1 September 1986 PDF DownloadLoading ...
A Recessive Gene for Primary Vesicoureteral Reflux Maps to Chromosome 12p11-q13 (2009)

Primary vesicoureteral reflux (pVUR) is one of the most common causes of pediatric kidney failure. Linkage scans suggest that pVUR is genetically heterogeneous with two loci on chromosomes 1p13 and 2q37 under autosomal dominant inheritance. Absence of pVUR in parents of affected individuals raises the possibility of a recessive contribution to pVUR. We performed a genome-wide linkage scan in 12 large families segregating pVUR, comprising 72 affected individuals. To avoid potential misspecification of the trait locus, we performed a parametric linkage analysis using both dominant and recessive models. Analysis under the dominant model yielded no signals across the entire genome. In contrast, we identified a unique linkage peak under the recessive model on chromosome 12p11-q13 (D12S1048), which we confirmed by fine mapping. This interval achieved a peak heterogeneity LOD score of 3.6 with 60% of families linked. This heterogeneity LOD score improved to 4.5 with exclusion of two high-density pedigrees that failed to link across the entire genome. The linkage signal on chromosome 12p11-q13 originated from pedigrees of varying ethnicity, suggesting that recessive inheritance of a high frequency risk allele occurs in pVUR kindreds from many different populations. In conclusion, this study identifies a major new locus for pVUR and suggests that in addition to genetic heterogeneity, recessive contributions should be considered in all pVUR genome scans.
Ferromagnetic Exchange Interactions for Cu<sub>6</sub><sup>12+</sup>and Mn<sub>6</sub><sup>12+</sup>Hexagons Sandwiched by Two B-α-[XW<sub>9</sub>O<sub>33</sub>]<sup>9-</sup>(X = As<sup>III</sup>and Sb<sup>III</sup>) Ligands in<i>D</i><sub>3</sub><i><sub>d</sub></i>-Symmetric Polyoxotungstates (2006)

Two novel Cu6 and Mn6 hexagon sandwiched polyoxometalates, [(CuCl)6(AsW9O33)2]12- (1a) and [(MnCl)6(SbW9O33)2]12- (2a), have been synthesized and characterized by X-ray single-crystal analysis and magnetic measurements. These complexes are D3d symmetric and were isolated as [n-BuNH3]+ salts from aqueous solutions: (n-BuNH3)12[(CuCl)6(AsW9O33)2].6H2O (1), rhombohedral, R, a = 20.33(1) A, c = 26.35(2) A, Z = 3 and (n-BuNH3)12[(MnCl)6(SbW9O33)2].6H2O (2). Six Cu (or Mn) atoms, each of which shows 5-fold coordination, make an approximately equatorial hexagon with a first-neighboring Cu...Cu (Mn...Mn) distance of 2.913(2) A (3.248(1) A) and a Cu-O-Cu (Mn-O-Mn) bond angle of 94.5(2) degrees (100.4(2) degrees ). The magnetic behavior investigated by magnetic susceptibility measurements shows the ferromagnetic exchange interactions with J/k = +12.7 K (J/hc = +8.82 cm(-1)) and a S = 3 ground state for 1 and J/k = +0.20 K (J/hc = +0.14 cm(-1)) and a S = 15 ground state for 2, when only J refers to the isotropic magnetic-exchange interactions for first-neighbor atoms of the approximately equilateral Cu6(12+) and Mn6(12+) hexagons. The single-crystal ESR spectroscopy of 1 under the orientation of the magnetic field along a Cu6 hexagon's nearly 6-fold axis equal to the c axis on the variation of temperature supports the S = 3 ground state and allows an estimate of the zero-field (fine-structure) energy separation between Sz = 0 and Sz = +/-1 of D = -0.182 K to be obtained.
The effect of IFN-gamma and colony-stimulating factors on the expression of neutrophil cell membrane receptors. (1989)

The recombinant cytokines IFN-gamma, granulocyte-macrophage (GM)-CSF, and granulocyte (G)-CSF are all known to affect the function of neutrophils. We have investigated their ability to alter the surface expression of neutrophil Fc gamma R and CR. FcRI, formerly considered to be mononuclear phagocyte specific, was found on a variable percentage of neutrophils after 12 h of tissue culture. These levels could be readily enhanced by IFN-gamma at 0.5 U/ml suggesting that neutrophil FcRI is extremely sensitive IFN-gamma. In addition, membrane expression of FcRIII, the most abundant receptor of neutrophils, could also be increased by IFN-gamma and by GM-CSF and G-CSF. However, the opposite effect was observed in samples in which the initial levels of FcRIII were high. In these situations IFN-gamma and GM-CSF caused a decrease in receptor expression. No consistent alterations were found in the levels of FcRII. Cytokine-induced increases in both FcRI and FcRIII were not evident within the first hour of treatment suggesting that these molecules are not available in an intracellular compartment but must be newly synthesized. In contrast, the CR, CR1 and CR3, could be rapidly induced by GM-CSF indicating that this cytokine causes the mobilization of preformed molecules to the membrane. G-CSF and IFN-gamma did not alter the expression of CR1 and CR3. Thus, the very different effects of IFN-gamma, GM-CSF, and G-CSF suggest that the neutrophil functional profile will be distinctively affected by exposure to each of these cytokines.
Generation of hematopoietic repopulating cells from human embryonic stem cells independent of ectopic<i>HOXB4</i>expression (2005)

Despite the need for alternative sources of human hematopoietic stem cells (HSCs), the functional capacity of hematopoietic cells generated from human embryonic stem cells (hESCs) has yet to be evaluated and compared with adult sources. Here, we report that somatic and hESC-derived hematopoietic cells have similar phenotype and in vitro clonogenic progenitor activity. However, in contrast with somatic cells, hESC-derived hematopoietic cells failed to reconstitute intravenously transplanted recipient mice because of cellular aggregation causing fatal emboli formation. Direct femoral injection allowed recipient survival and resulted in multilineage hematopoietic repopulation, providing direct evidence of HSC function. However, hESC-derived HSCs had limited proliferative and migratory capacity compared with somatic HSCs that correlated with a distinct gene expression pattern of hESC-derived hematopoietic cells that included homeobox (HOX) A and B gene clusters. Ectopic expression of HOXB4 had no effect on repopulating capacity of hESC-derived cells. We suggest that limitations in the ability of hESC-derived HSCs to activate a molecular program similar to somatic HSCs may contribute to their atypical in vivo behavior. Our study demonstrates that HSCs can be derived from hESCs and provides an in vivo system and molecular foundation to evaluate strategies for the generation of clinically transplantable HSC from hESC lines.
Cationic alkyl aluminium ethylene polymerization catalysts based on monoanionic N,N,N-pyridyliminoamide ligands (1998)

Treatment of the 2,6-bis(imino)pyridines {[2,6-(ArNCR)2C5H3N]} [R = H, Ar = 2,6-i-Pr2C6H3 or 2,4,6-Me3C6H2; R = Me, Ar = 2,6-i-Pr2C6H3] with AlMe3 at elevated temperature gives, via migration of a methyl group to the ligand backbone, the pseudo-five coordinate dimethylaluminium species {2-[ArNCR(Me)],6-(ArNCR)C5H3N}- AlMe2 (1a–c); upon treatment with B(C6F5)3, 1a–c cleanly afford the cationic methyl complexes [{2-[ArNCR(Me)],6-(ArNCR)C5H3N}AlMe]+[MeB(C6F5)3]– (2a–c) which are active for ethylene polymerization.