gebhart/patrepeval huggingface dataset:
Phosphodiesterase Inhibitors as Potential Cognition Enhancing Agents (2010)

As might be predicted for an organ designed for cell to cell communication, cyclic nucleotide signaling in the brain is highly organized and regulated. Augmentation of cyclic nucleotide signaling by means of phosphodiesterase inhibition appears to be a viable and tractable means of enhancing neuronal communication. Of the various CNS disorders that have been considered as target indications for phosphodiesterase inhibitors, no condition has received more attention than cognitive dysfunction. This review provides a background for understanding the expanding literature in this field as well as a brief update on the rationale driving the search for selective inhibitors of targets such as PDE1B, PDE2, PDE5 and PDE9.
Multihop R-ALOHA for intervehicle communications at millimeter waves (1997)

With reference to road transport information (RTI) applications, such as cooperative driving, short-range intervehicle communications in a highway environment are investigated in this paper. The research in this field indicates the suitability of the 60-64-GHz band. Due to the distributed nature of the intervehicle communication system, an R-ALOHA protocol is considered; multihop (MH) and single-hop (SH) strategies are compared. Network performance is assessed by considering the joint impact of random access, interference, thermal noise, propagation, and packet capture effect. Several figures of merit are analyzed and discussed: packet success probability (PSP), system stabilization time (SST), first success time (FST), and deadline failure probability (DFP). Network performance is evaluated either by an analytical approach or by a software tool able to simulate a one-lane highway scenario. Both steady-state and transition situations are considered. System performance in terms of PSP (in the presence of two-way Rice fading, noise, and interference with antenna diversity and selection combining) is analytically evaluated to validate the simulation tool and to prove the suitability of an MH network strategy. The simulation approach allows the evaluation of the impact of protocol parameters on network performance, with reference to nonsteady-state situations.
Coordinación eficaz en Prevención de Riesgos Laborales: una propuesta de desarrollo (2003)

Hay un cierto consenso en atribuir los incrementos de accidentalidad que se han producido en los ultimos anos a causas tales como la precariedad en el empleo y la cadena de subcontratacion de trabajos. Las estadisticas actuales nos muestran que la mayor incidencia de la accidentalidad - numero de accidentes por 1.000 trabajadores - se da en la empresa pequena-mediana (26-100 trabajadores) seguida por las de 101-500 trabajadores que tienen un indice de incidencia muy similar a la de la micro empresa (1-25). Sin embargo, la tasa de incidencia de los accidentes graves es muy superior en las empresas pequenas que en las de mas de 100 trabajadores.
Infortunadamente esta estadistica no nos suministra informacion acerca del tamano de las empresas en donde ocurre el accidente, independientemente de si corresponde a personal propio o de contratas, porque es muy probable que se llegara a la conclusion de que aunque la mayor accidentalidad corresponde a trabajadores de empresas pequenas y medianas, el accidente ocurre en centros de empresas medianas y grandes.

Si lo anterior se confirmase, una actuacion sobre las empresas grandes y medianas que propiciase que estas asumiesen un papel de liderazgo en materia de prevencion de los riesgos laborales en su relacion con aquellas empresas con las que contratan obras o servicios, permitiria un avance mucho mas sustancial que el que se deriva de la actual politica de inspeccion/ sancion centrada en las pequenas empresas.
El desarrollo del art. 24 de la Ley de PRL es en este aspecto una buena oportunidad para introducir, dentro de la obligacion general de coordinacion y vigilancia que corresponden a los titulares de los centros, mecanismos que puedan suponer una ventaja competitiva para aquellas empresas contratistas que adoptan sistemas eficaces de prevencion y que, por el contrario, limiten las oportunidades de negocio para aquellos que no presten atencion a los aspectos preventivos. Este enfoque comercial supondria, desde mi punto de vista un estimulo mucho mas importante para la mejora de la prevencion en las empresas que el temor a las sanciones por falta de cumplimiento de la normativa.
En lo que sigue se intenta aportar algunas ideas para ello partiendo de lo ya establecido en el art. 24 de la Ley de PRL y sin necesidad de crear nuevas obligaciones para las empresas, sino simplemente explicitar como cumplir con las ya enunciadas de manera general en dicho art. 24, ni crear nuevas figuras que pudieran contribuir a hacer mas confuso el escenario o difuminar las responsabilidades atribuidas al titular del centro de trabajo.
Management of hepatocellular carcinoma. (2000)

Hepatocellular carcinoma (HCC) is responsible for a significant amount of morbidity and mortality throughout the world. In many countries, including the United States, a definite increase in the incidence of HCC has been reported recently, largely attributable to the increasing incidence of hepatitis C infection. Unfortunately, the current management of HCC is confusing due to the large number of treatment options available. The difficulty of managing a patient with HCC is compounded by the lack of well-designed, randomized clinical trials comparing the various treatment modalities. Nevertheless, many exciting management options are currently available that may prove valuable in the treatment of this disease. Partial hepatic resection or, in some instances, liver transplantation offers the best chance for cure. However, various ablative therapies, including percutaneous ethanol injection, radiofrequency ablation, and cryosurgery, may produce a survival benefit. In the future, systemic chemotherapy and transarterial chemoembolization, employed either alone or as adjuncts to ablation or resection, may play an increasing role in palliating or down-staging a patient with advanced HCC. This overview of the state-of-the-art management of HCC attempts to guide the practicing physician in selecting the best treatment plan for an individual with HCC.
Static microdroplet arrays: a microfluidic device for droplet trapping, incubation and release for enzymatic and cell-based assays (2008)

We describe the design, fabrication and use of a single-layered poly(dimethylsiloxane) microfluidic structure for the entrapment and release of microdroplets in an array format controlled entirely by liquid flow. Aqueous picoliter droplets are trapped en masse and optically monitored for extended periods of time. Such an array-based approach is used to characterize droplet shrinkage, aggregation of encapsulated E. coli cells and enzymatic reactions. We also demonstrate that trapped droplets may be recovered from the microfluidic array for further processing.
Isolation and Biochemical Characterization of the Human Dkk-1 Homologue, a Novel Inhibitor of Mammalian Wnt Signaling (1999)

In an effort to isolate novel growth factors, we identified a human protein, designated Sk, that co-eluted with Neuregulin during chromatographic separation of conditioned medium from the SK-LMS-1 human leiomyosarcoma cell line. Degenerate oligonucleotides based on amino-terminal sequence analysis of the purified protein were used to isolate the corresponding cDNA from a library generated from this cell line. Sk is a novel 266-amino acid protein that contains a signal peptide sequence and two cysteine-rich domains with no similarity to other known growth factors. A single major 2-kilobase transcript was expressed in several embryonic tissues. Transfection of mammalian cells demonstrated that the protein was secreted and expressed as a doublet of approximately 35 kDa. In vitro translation and endoglycosylase analysis indicated that this doublet, which was also observed in cells expressing the endogenous protein, arises from posttranslational modification. A search of the GenBankTM data base revealed a match of Sk with Dkk-1, which is a novel secreted protein required for head induction in amphibian embryos and a potent Wnt inhibitor. When coexpressed with Wnt-2 in NIH3T3 cells, human Sk/Dkk-1 caused reversion of Wnt-2 induced morphological alterations and inhibited the Wnt-2 induced increase in uncomplexed beta-catenin levels. These results provide biochemical evidence that human Sk/Dkk-1 antagonizes Wnt signaling upstream of its effect on beta-catenin regulation.
A Unique Activating Mutation in JAK2 (V617F) Is at the Origin of Polycythemia Vera and Allows a New Classification of Myeloproliferative Diseases (2005)

Myeloproliferative disorders (MPDs) are heterogeneous diseases that occur at the level of a multipotent hematopoietic stem cell. They are characterized by increased blood cell production related to cytokine hypersensitivity and virtually normal cell maturation. The molecular pathogenesis of the MPDs has been poorly understood, except for chronic myeloid leukemia (CML), where the Bcr-Abl fusion protein exhibits constitutive kinase activity. Since some rare MPDs are also related to a dysregulated kinase activity, a similar mechanism was thought to be likely responsible for the more frequent MPDs. We investigated the mechanisms of endogenous erythroid colony formation (EEC) by polycythemia vera (PV) erythroid progenitor cells and found that EEC formation was abolished by a pharmacological inhibitor of JAK2 as well as an siRNA against JAK2. JAK2 sequencing revealed a unique mutation in the JH2 domain leading to a V617F substitution in more than 80% of the PV samples. This mutation in the pseudokinase autoinhibitory domain results in constitutive kinase activity and induces cytokine hypersensitivity or independence of factor-dependent cell lines. Retroviral transduction of the mutant JAK2 into murine HSC leads to the development of an MPD with polycythemia. The same mutation was found in about 50% of patients with idiopathic myelofibrosis (IMF) and 30% of patients with essential thrombocythemia (ET). Using different approaches, four other teams have obtained similar results. The identification of the JAK2 mutation represents a major advance in our understanding of the molecular pathogenesis of MPDs that will likely permit a new classification of these diseases and the development of novel therapeutic approaches.
Construction of the Bicyclic Core Structure of the Enediyne Antibiotic Esperamicin-A1 in Either Enantiomeric Form from (-)-Quinic Acid (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConstruction of the Bicyclic Core Structure of the Enediyne Antibiotic Esperamicin-A1 in Either Enantiomeric Form from (-)-Quinic AcidGerardo Ulibarri, William Nadler, Troels Skrydstrup, Helene Audrain, Angele Chiaroni, Claude Riche, and David S. GriersonCite this: J. Org. Chem. 1995, 60, 9, 2753–2761Publication Date (Print):May 1, 1995Publication History Published online1 May 2002Published inissue 1 May 1995https://pubs.acs.org/doi/10.1021/jo00114a025https://doi.org/10.1021/jo00114a025research-articleACS PublicationsRequest reuse permissionsArticle Views835Altmetric-Citations40LEARN 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
Influence of pH on Stability and Dynamic Properties of Asphaltenes and Other Amphiphilic Molecules at the Oil−Water Interface (2005)

Oil-in-water emulsions are currently being investigated to facilitate the transport of viscous heavy oils. The behavior of these emulsions is largely controlled by the interfaces between oil drops and water. The surface-active components of crude oil, such as asphaltenes and naphthenic acids, compete among themselves at these interfaces and also with possibly added synthetic surfactant emulsifier. Here, we present a study of dynamic interfacial tension of interfaces between water and a model oil (toluene) in which variable amounts of asphaltenes are solubilized. We show that pH has a strong influence on interfacial properties of asphaltenes at the oil/water interface. At high or low pH, asphaltenes functional groups become charged, enhancing its surface activity. The influence of lower-molecular-weight surface-active species, such as the natural naphthenic acids contained in maltenes (crude oil without asphaltenes), has been investigated, and an interaction between asphaltenes and maltenes that facilitates molecular arrangement at the interface was detected. Several micropipette experiments, in which micrometric drops have been manipulated, are also described and indicate that very little coalescence of water droplets is observed at high or low pH. The microscopic properties of the interface and the macroscopic behavior of the emulsion are determined to be correlated.
InGaAsP multiple quantum well lasers with planar buried heterostructure prepared by metalorganic chemical vapor deposition (1988)

Planar buried heterostructure InGaAsP multiple quantum well (MQW) lasers consisting of six InGaAsP (λg =1.34 μm at room temperature) wells and five InP barriers were prepared by low-pressure metalorganic chemical vapor deposition. The threshold current was 35 mA, and the differential quantum efficiency was 45% at an emission wavelength of 1.3 μm. In the temperature range from −35 to 30 °C, the characteristic temperature was T0=57 K. No significant improvement in T0 was observed in these MQW lasers. However, stable single longitudinal mode operation could be obtained in a wide range of injection current without any mode changes. This effect was considered to be a result of gain narrowing of the MQW lasers.
Mini-Mental State Examination (1993)

The Mini-Mental State Examination (MMSE), first introduced by Folstein and colleagues in 1975,<sup>1</sup>has become a standard tool for cognitive assessment in the clinical setting. The MMSE facilitates the detection of mental status changes, particularly in the elderly, and thereby enhances patient care. Bedside mental status testing without a standardized approach is subject to considerable interpretive bias, dependent on the skill and experience of the examiner, and often completely neglected. The MMSE provides a structured approach to mental status testing that screens for intellectual impairment and allows comparison of performance across time and among patients or studies.<sup>2</sup>The publication in this issue of<i>JAMA</i>of new data from Crum et al<sup>3</sup>regarding the influence of age and education on the interpretation of the MMSE is welcome and further improves the utility of this instrument. See also p 2386. <h3>MMSE Elements</h3> The MMSE comprises 30 questions with 10
Spacer Site Modifications for the Improvement of the in Vitro and in Vivo Binding Properties of 99mTc-N3S-X-Bombesin[2−14] Derivatives (2009)

It has been shown that gastrin releasing peptide receptors (GRPRs) are overexpressed in various types of cancer cells. Bombesin is an analogue of the mammalian GRP that binds with high specificity and affinity to GRPRs. Significant research efforts have been lately devoted to the design of radiolabeled 8 or 14 aminoacid bombesin (BN) peptides for the detection (either with gamma or positron emitting radionuclides) and therapy (with beta(-) emitting radionuclides) of cancer. The specific aim of the present study was to further investigate the radiolabeled peptide structure and to determine whether the total absence of a linker or the use of a basic diverse amino acid linker could influence the biodistribution profile of the new compounds for specific targeting of human prostate cancer. Thus, two new derivatives with the structure Gly-Gly-Cys-X-BN[2-14], where linker X is either zero (I) or Orn-Orn-Orn (Orn: ornithine) (II) were designed and synthesized. The corresponding (99m)Tc-BN derivatives were obtained with high radiochemical yield (>98%) and had almost identical retention times in RP-HPLC with the (185/187)Re complexes, which were also characterized by ESI-MS. Metabolic stability was found to be high in human plasma, moderate in PC-3 cells, and rather low in mouse liver and kidney homogenates for both BN derivatives studied. The BN derivative without the spacer was less stable in cell culture and liver homogenates. A satisfactory binding affinity to GRPRs, in the nanomolar range, was obtained for both BN derivatives as well as for their Re complexes, with BN (II) demonstrating the highest one. In vitro internalization/externalization assays indicated that approximately 6% of BN (I) and approximately 25% of BN (II) were internalized into PC-3 cells. In vivo evaluation in normal Swiss mice and in tumor bearing SCID mice showed that BN (II) presented higher tumor and pancreas uptake than BN (I). Small animal SPECT dynamic imaging, carried out after an injection of BN (II) in mice bearing PC-3 tumors, resulted in PC-3 tumor delineation with low background activity. Overall, this study performed for two new N(3)S-X-BN[2-14] derivatives indicated that hydrophilicity and charge strongly affected the in vitro and in vivo binding properties and the biodistribution pattern. This finding is confirmed by SPECT imaging of BN (II), which is under further in vivo evaluation for detecting cancer-positive GRPRs.
Effect of mutations and deletions in a bicistronic mRNA on the synthesis of influenza B virus NB and NA glycoproteins (1989)

The mRNA derived from influenza B virus RNA segment 6 is functionally bicistronic and encodes the NB and NA glycoproteins in different, overlapping reading frames. NB protein synthesis is initiated at the 5'-proximal AUG codon, and 4 nucleotides downstream there is a second AUG codon which is used to initiate NA protein synthesis. The nucleotide sequence context of the first AUG codon conforms closely with the established 5'-CC(A/G)CCAUGG-3' consensus sequence (M. Kozak, Nucleic Acids Res. 15:8125-8148, 1987), which should favor initiation of NB protein synthesis at this site, yet NB and NA are found to accumulate in approximately equal amounts in infected cells. To determine the features important for allowing initiation at the second 5'-proximal AUG codon, we made changes in the 5'-terminal region of the mRNA, including deletions, insertions, and site-specific mutations. The recombinant DNA molecules were expressed in eucaryotic cells, and the accumulation of NB and NA was quantitated. The data indicate that changes in the immediate sequence around the first AUG codon do not make a large difference in the amounts of NB and NA that accumulate, but that when the first AUG codon is displaced from its normal position it is now quite efficient at preventing downstream initiation events. In addition, the data indicate that an element of the B/NB/NA mRNA 5' untranslated leader region acts in cis to enhance the expression of NB and NA.
Novel Phosphoinositide 3-Kinase/mTOR Dual Inhibitor, NVP-BGT226, Displays Potent Growth-Inhibitory Activity against Human Head and Neck Cancer Cells In Vitro and In Vivo (2011)

These data indicate that BGT226 is a potential drug in the treatment of head and neck cancer.
Nematicidal Epipolysulfanyldioxopiperazines from Gliocladium roseum (2005)

Five new verticillin-type epipolysulfanyldioxopiperazines, gliocladine A (1), B (2), C (3), D (4), and E (5), were isolated from wheat solid-substrate fermentation of Gliocladium roseum 1A, along with four known compounds, verticillin A (6), 11'-deoxyverticillin A (7), Sch52900 (8), and Sch52901 (9). Their structures were elucidated by extensive 1D and 2D NMR studies, MS, and chemical transformations. In vitro immersion tests showed that all nine compounds exhibited antinematodal activity against Caenorhabditis elegans and Panagrellus redivivus. The monomeric epipolysulfanydioxopiperazines (3-5), with the indole moiety, were found to be less active than the dimeric compounds (1, 2, 6-8).
Human Telomerase Reverse Transcriptase Expression in Diff-Quik-stained FNA Samples From Thyroid Nodules (2001)

Fine-needle aspiration (FNA) is a highly sensitive method in the differential diagnosis of thyroid nodules. However, 10% of thyroid FNAs are indeterminate for cancer, and thus additional markers may be useful diagnostically. The authors have demonstrated previously that human telomerase reverse transcriptase (hTERT) gene expression is useful in the distinction of benign lesions from malignant lesions. They therefore wondered whether the detection of hTERT gene expression was feasible using archival slides. To establish an experimental system, ribonucleic acid was extracted from human anaplastic thyroid carcinoma cell line (ARO) in cytologic specimens, and reverse transcription-polymerase chain reaction (RT-PCR) for hTERT expression was performed. RT-PCR analysis for hTERT gene detection was then performed using 58 Diff-Quik-stained archival FNA samples collected retrospectively. RT-PCR for human thyroglobulin (hTg) or beta-actin gene expression served as a positive control. Successful PCR results were obtained from 48 of the 58 cases. All 10 slides in which no RT-PCR products were noted were older than 3 years. hTERT gene expression was demonstrated in FNAs from two of seven cases (29%) of hyperplastic nodule, one of one case (100%) of Hashimoto's thyroiditis, three of eight cases (38%) of follicular adenoma, three of eight cases (38%) of Hürthle cell adenoma, three of four cases (75%) of follicular carcinoma, two of two cases (100%) of Hürthle cell carcinoma, and 11 of 18 cases (61%) of papillary carcinoma. All but one of the available 33 corresponding frozen samples exhibited the same RT-PCR results. This study demonstrates that Diff-Quik-stained thyroid FNA specimens less than 3 years old can be used for the detection of hTERT gene expression by RT-PCR. This test, along with careful cytopathologic examination, may improve our ability to differentiate benign lesions from malignant lesions in indeterminate FNA samples from thyroid nodules.