507 research outputs found

    Transforming a company’s staffing process: implementing E-recruitment

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    This project discusses the importance of evaluating a company's staffing methods, in order to improve and optimize people recruitment, selection, as well as integration and socialization in the organization. The particular focus is the implementation of Social Media (SM) and e-recruitment in a private sector company, reveling the importance of these digital media to recruit candidates with the desired profile and to support the new collaborators' integration and socialization. A business project is presented, following a scientific-technical approach, in the analysis of functions and in the profiles definitions and on information obtained through semi-structured interviews with human resources specialists who are responsible for recruitment and selection as well as interviews with newly hired workers in the company, demonstrating the effectiveness of these means for jobseekers. At the same time, a project study for the implementation of new digital tools in the company is prepared. This study shows that the development of a new website articulated with SM, for which business pages have been built, in addition to the use of e-recruitment portals, is a real benefit for the organization because they facilitate and increase the performance of the recruitment and selection process at the same time promoting the company's image

    Physiological Functions of Prostatic Acid Phosphatase

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    Prostatic acid phosphatase (PAP) has been linked to prostate cancer since the mid-1930s. The main research approach of PAP over that time has been based on its role in the human prostate. The regulatory mechanisms of expression of the PAP gene have also been studied, giving us information about the regulatory elements in the gene and the transcription factors that affect the gene expression in the prostatic tissue. However, little was known until recently about this protein s role and physiological function in other tissues. Our group generated and used a PAP-deficient mouse and was able to show that PAP is expressed in dorsal root ganglia (DRG) and spinal cord in mice. This is the same protein as thiamine monophosphatase (TMPase) whose enzymatic activity has been used for five decades to mark primary sensory neurons. In these tissues, PAP acts as an ecto-5'-nucleotidase and is able to dephosphorylate AMP to adenosine, and therefore produce an anti-nociceptive effect due to the binding of adenosine to the A1-adenosine receptor. We analyzed the ACPP gene, which enabled us to describe a new transmembrane isoform for PAP (TMPAP). This novel PAP isoform is produced by alternative splicing of the 11th exon of the ACPP gene. The alternative splicing is present in species such as the human, mouse and rat. The newly discovered isoform is widely expressed in human and mouse tissues and contains a tyrosine sequence (YxxΦ) in its carboxyl-terminus, which directs the protein to endocytosis. We have also corroborated its functionality by co-localization studies with different organelle markers in the endosomal/lysosomal pathway (I). The generation of a PAP-deficient mouse also enabled us to study the function/s of PAP in vivo. The lack of PAP in this mouse model led to the gradual changes in the mouse prostate that finally culminated with the development of prostate adenocarcinoma at the age of 12 months. Microarray analyses of different tissues that compared the PAP deficient mouse with the wild type (WT) mouse revealed changes in genes related to the vesicular trafficking, which support our previous results and led us to the conclusion that TMPAP could be involved in the regulation of the vesicular trafficking. We also detected the interaction between TMPAP and snapin, a SNARE (Soluble NSF Attachment Protein Receptor) associated protein, by yeast two-hybrid screening, co-localization and FRET (Förster resonance energy transfer) analysis. We concluded that, the disruption of this interaction in the PAP-deficient mouse leads to a disturbance in the vesicular transport of the cell and to the development of prostate adenocarcinoma in the PAP-deficient mouse prostate (II). Furthermore, we showed that the PAP-deficient mice present multiple behavioral and neurochemical alterations including increased size of brain lateral ventricles, hyperdopaminergic deregulation, and altered GABAergic transmission, symptoms that indicate that PAP also disturbes the normal function of the central nervous system (III). Snapin protein in the brain has been described as a protein important for the vesicular transport and for the fusion of vesicles with the plasma membrane, and we observed that the lack of PAP in GABAergic neurons leads to a change in the localization of snapin in the PAP-deficient mouse (III), which could indicate that as in the prostate a dysregulated vesicular trafficking could be the reason for the detected phenotype. The discovery of the new TMPAP and its localization in the endosomal/lysosomal pathway enabled an understanding of the phenotypic changes that occur in the PAP-deficient mouse. We hypothesized that TMPAP regulates vesicular trafficking by interacting with snapin, and its deficiency leads to a dysregulation of the endo-/exocytosis cycle, which produces the observed alterations in the mouse organs and tissues. The results obtained throughout this research project have opened up new lines of research related to PAP physiological function, and a deeper understanding of the expression, regulation and function of this protein could lead to new clinical applications.Eturauhasen hapan fosfataasi (engl. Prostatic acid phosphatase, PAP) on proteiini, jota erittyy eturauhasesta suuria määriä. Se oli ensimmäinen biologinen merkkiaine eturauhassyövän diagnostiikassa. PAP-entsyymin kemialliset ominaisuudet on kuvattu, mutta sen toiminta on ollut tuntematon, kunnes tässä väitöskirjatyössä löydettiin uusi solukalvon läpäisevä PAP:n muoto. Työssä kuvattiin tämä uusi transmembraanimuoto (solukalvomuoto), selvitettiin sen sijainti solussa sekä vuorovaikutus solun sisäistä liikennettä säätelevien proteiinien kanssa. Lisäksi käyttämällä muuntogeenisiä, PAP:ta tuottamattomia hiiriä, havaittiin hiirille kehittyvän eturauhassyöpä, jossa on samanlaisia piirteitä kuin ihmisten eturauhassyövässä. Uuden PAP-muodon löytyminen ja PAP-poistogeeninen hiirimallin hyödyntäminen, osoitti PAP toiminnan kivun säätelymekanismeissä. Tämä johti hiirimallin hermoston jatkotutkimuksiin, erityisesti aivoissa. PAP-poistogeenisissä hiirissä havaittiin muutoksia niiden käyttäytymisessä, sekä aivojen anatomiassa että neurokemiassa. Näiden tulosten perusteella voitiin päätellä, että PAP ei ole ainoastaan välttämätön eturauhasen normaalille kehitykselle, mutta se vaikuttaa myös muiden elinten normaaliin kehitykseen ja toimitaan ja siksi tarvitaankin syvällisempää ymmärrystä PAP:n fysiologisesta toiminnasta. Päätelmämme on, että muutos transmembraani-PAP:n vuorovaikutuksessa eri proteiinien kanssa vaikuttaa eturauhasen ja aivojen normaaliin solun sisäiseen liikenteeseen johtaen näissä elimissä havaittuihin (patofysiologisiin) muutoksiin. PAP:n transmembraanimuodon kuvaaminen ja tämän proteiinin esiintyminen muuallakin elimistössä kuin eturauhasessa on avannut uusia tutkimuslinjoja biolääketieteeseen ja tuonut uusia potentiaalisia sovelluksia PAP:lle esim. hoitona hermokivussa, jota esiintyy pitkälle edenneen eturauhassyövän yhteydessä

    Looking for blazars in a sample of unidentified high-energy emitting Fermi sources

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    Context. Based on their overwhelming dominance among associated Fermi γ-ray catalogue sources, it is expected that a large fraction of the unidentified Fermi objects are blazars. Through crossmatching between the positions of unidentified γ-ray sources from the First Fermi Catalog of γ-ray sources emitting above 10 GeV (1FHL) and the ROSAT and Swift/XRT catalogues of X-ray objects and between pointed XRT observations, a sample of 36 potential associations was found in previous works with less than 15 arcsec of positional offset. One-third of them have recently been classified; the remainder, though believed to belong to the blazar class, still lack spectroscopic classifications. Aims. We study the optical spectrum of the putative counterparts of these unidentified gamma-ray sources in order to find their redshifts and to determine their nature and main spectral characteristics. Methods. An observational campaign was carried out on the putative counterparts of 13 1FHL sources using medium-resolution optical spectroscopy from the Osservatorio Astronomico di Bologna in Loiano, Italy; the Telescopio Nazionale Galileo and the Nordic Optical Telescope, both in the Canary Islands, Spain; and the Observatorio Astronómico Nacional San Pedro Mártir in Baja California, Mexico. Results. We were able to classify 14 new objects based on their continuum shapes and spectral features. Conclusions. Twelve new blazars were found, along with one new quasar and one new narrow line Seyfert 1 (NLS1) to be potentially associated with the 1FHL sources of our sample. Redshifts or lower limits were obtained when possible alongside central black hole mass and luminosity estimates for the NLS1 and the quasar.Fil: Marchesini, Ezequiel Joaquín. Universidad Nacional de la Plata. Facultad de Ciencias Astronómicas y Geofísicas; ArgentinaFil: Masetti, Nicola. Istituto di Astrofisica Spaziale e Fisica Cosmica di Bologna; ItaliaFil: Chavushyan, V.. Instituto Nacional de Astrofísica, Óptica y Electrónica; MéxicoFil: Cellone, Sergio Aldo. Universidad Nacional de la Plata. Facultad de Ciencias Astronómicas y Geofísicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Andruchow, Ileana. Universidad Nacional de la Plata. Facultad de Ciencias Astronómicas y Geofísicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Bassani, L.. Istituto di Astrofisica Spaziale e Fisica Cosmica di Bologna; ItaliaFil: Bazzano, A.. Istituto di Astrofisica e Planetologia Spaziali; ItaliaFil: Jiménez-Bailón, E.. Universidad Nacional Autónoma de México; MéxicoFil: Landi, R.. Istituto di Astrofisica Spaziale e Fisica Cosmica di Bologna; ItaliaFil: Malizia, A.. Istituto di Astrofisica Spaziale e Fisica Cosmica di Bologna; ItaliaFil: Palazzi, E.. Istituto di Astrofisica Spaziale e Fisica Cosmica di Bologna; ItaliaFil: Patiño Álvarez, V.. Instituto Nacional de Astrofísica, Óptica y Electrónica; MéxicoFil: Rodríguez Castillo, G. A.. Osservatorio Astronomico di Roma; ItaliaFil: Stephen, J. B.. Istituto di Astrofisica Spaziale e Fisica Cosmica di Bologna; ItaliaFil: Ubertini, P.. Istituto di Astrofisica e Planetologia Spaziali; Itali

    Effect of Natriuretic Peptide-Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.

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    Importance: The natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of adverse outcomes. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels ( guided therapy ) with inconsistent results. Objective: To determine whether an amino-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with HF and reduced ejection fraction (HFrEF). Design, Settings, and Participants: The Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study was a randomized multicenter clinical trial conducted between January 16, 2013, and September 20, 2016, at 45 clinical sites in the United States and Canada. This study planned to randomize 1100 patients with HFrEF (ejection fraction ≤40%), elevated natriuretic peptide levels within the prior 30 days, and a history of a prior HF event (HF hospitalization or equivalent) to either an NT-proBNP-guided strategy or usual care. Interventions: Patients were randomized to either an NT-proBNP-guided strategy or usual care. Patients randomized to the guided strategy (n = 446) had HF therapy titrated with the goal of achieving a target NT-proBNP of less than 1000 pg/mL. Patients randomized to usual care (n = 448) had HF care in accordance with published guidelines, with emphasis on titration of proven neurohormonal therapies for HF. Serial measurement of NT-proBNP testing was discouraged in the usual care group. Main Outcomes and Measures: The primary end point was the composite of time-to-first HF hospitalization or cardiovascular mortality. Prespecified secondary end points included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary end point, and adverse events. Results: The data and safety monitoring board recommended stopping the study for futility when 894 (median age, 63 years; 286 [32%] women) of the planned 1100 patients had been enrolled with follow-up for a median of 15 months. The primary end point occurred in 164 patients (37%) in the biomarker-guided group and 164 patients (37%) in the usual care group (adjusted hazard ratio [HR], 0.98; 95% CI, 0.79-1.22; P = .88). Cardiovascular mortality was 12% (n = 53) in the biomarker-guided group and 13% (n = 57) in the usual care group (HR, 0.94; 95% CI; 0.65-1.37; P = .75). None of the secondary end points nor the decreases in the NT-proBNP levels achieved differed significantly between groups. Conclusions and Relevance: In high-risk patients with HFrEF, a strategy of NT-proBNP-guided therapy was not more effective than a usual care strategy in improving outcomes. Trial Registration: clinicaltrials.gov Identifier: NCT01685840

    Rationale and design of the GUIDE-IT study: Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure.

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    OBJECTIVES: The GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) study is designed to determine the safety, efficacy, and cost-effectiveness of a strategy of adjusting therapy with the goal of achieving and maintaining a target N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of BACKGROUND: Elevations in natriuretic peptide (NP) levels provide key prognostic information in patients with HF. Therapies proven to improve outcomes in patients with HF are generally associated with decreasing levels of NPs, and observational data show that decreases in NP levels over time are associated with favorable outcomes. Results from smaller prospective, randomized studies of this strategy thus far have been mixed, and current guidelines do not recommend serial measurement of NP levels to guide therapy in patients with HF. METHODS: GUIDE-IT is a prospective, randomized, controlled, unblinded, multicenter clinical trial designed to randomize approximately 1,100 high-risk subjects with systolic HF (left ventricular ejection fraction ≤40%) to either usual care (optimized guideline-recommended therapy) or a strategy of adjusting therapy with the goal of achieving and maintaining a target NT-proBNP level of CONCLUSIONS: The GUIDE-IT study is designed to definitively assess the effects of an NP-guided strategy in high-risk patients with systolic HF on clinically relevant endpoints of mortality, hospitalization, quality of life, and medical resource use. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure [GUIDE-IT]; NCT01685840)

    Seasonality of African Precipitation from 1996 to 2009

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    Abstract A precipitation climatology of Africa is documented using 12 years of satellite-derived daily data from the Global Precipitation Climatology Project (GPCP). The focus is on examining spatial variations in the annual cycle and describing characteristics of the wet season(s) using a consistent, objective, and well-tested methodology. Onset is defined as occurring when daily precipitation consistently exceeds its local annual daily average and ends when precipitation systematically drops below that value. Wet season length, rate, and total are then determined. Much of Africa is characterized by a single summer wet season, with a well-defined onset and end, during which most precipitation falls. Exceptions to the single wet season regime occur mostly near the equator, where two wet periods are usually separated by a period of relatively modest precipitation. Another particularly interesting region is the semiarid to arid eastern Horn of Africa, where there are two short wet seasons separated by nearly dry periods. Chiefly, the summer monsoon spreads poleward from near the equator in both hemispheres, although in southern Africa the wet season progresses northwestward from the southeast coast. Composites relative to onset are constructed for selected points in West Africa and in the eastern Horn of Africa. In each case, onset is often preceded by the arrival of an eastward-propagating precipitation disturbance. Comparisons are made with the satellite-based Tropical Rainfall Measuring Mission (TRMM) and gauge-based Famine Early Warning System (FEWS NET) datasets. GPCP estimates are generally higher than TRMM in the wettest parts of Africa, but the timing of the annual cycle and average onset dates are largely consistent

    2,4-dihydroxy benzaldehyde derived Schiff bases as small molecule Hsp90 inhibitors: rational identification of a new anticancer lead

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    Hsp90 is a molecular chaperone that heals diverse array of biomolecules ranging from multiple oncogenic proteins to the ones responsible for development of resistance to chemotherapeutic agents. Moreover they are over-expressed in cancer cells as a complex with co-chaperones and under-expressed in normal cells as a single free entity. Hence inhibitors of Hsp90 will be more effective and selective in destroying cancer cells with minimum chances of acquiring resistance to them. In continuation of our goal to rationally develop effective small molecule azomethines against Hsp90, we designed few more compounds belonging to the class of 2,4-dihydroxy benzaldehyde derived imines (1-13) with our validated docking protocol. The molecules exhibiting good docking score were synthesized and their structures were confirmed by IR, (1)H NMR and mass spectral analysis. Subsequently, they were evaluated for their potential to suppress Hsp90 ATPase activity by Malachite green assay. The antiproliferative effect of the molecules were examined on PC3 prostate cancer cell lines by adopting 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay methodology. Finally, schiff base 13 emerged as the lead molecule for future design and development of Hsp90 inhibitors as anticancer agents.Fil: Dutta Gupta, Sayan. Osmania University; India. Jawaharlal Nehru Technological University; IndiaFil: Revathi, B.. Osmania University; IndiaFil: Mazaira, Gisela Ileana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Galigniana, Mario Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Subrahmanyam, C. V. S.. Osmania University; IndiaFil: Gowrishankar, N. L.. Swami Vivekananda Institute of Pharmaceutical Sciences; IndiaFil: Raghavendra, N. M.. Osmania University; Indi

    The nuclear receptor field: a historical overview and future challenges

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    In this article we summarize the birth of the field of nuclear receptors, the discovery ofuntransformed and transformed isoforms of ligand-binding macromolecules, the discovery of thethree-domain structure of the receptors, and the properties of the Hsp90-based heterocomplexresponsible for the overall structure of the oligomeric receptor and many aspects of the biologicaleffects. The discovery and properties of the subfamily of receptors called orphan receptors is alsooutlined. Novel molecular aspects of the mechanism of action of nuclear receptors and challengesto resolve in the near future are discussed.Fil: Mazaira, Gisela Ileana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Zgajnar, Nadia Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lotufo, Cecilia Maricel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Daneri Becerra, Cristina del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Sivils, Jeffrey C.. University of Texas at El Paso; Estados UnidosFil: Soto, Olga B.. University of Texas at El Paso; Estados UnidosFil: Cox, Marc B.. University of Texas at El Paso; Estados UnidosFil: Galigniana, Mario Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentin

    Atención prenatal en grupo: efectividad y retos de su implementación

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    Group prenatal care is an alternative model of care during pregnancy, replacing standard individual prenatal care. The model has shown maternal benefits and has been implemented in different contexts. We conducted a narrative review of the literature in relation to its effectiveness, using databases such as PubMed, EBSCO, Science Direct, Wiley Online and Springer for the period 2002 to 2018. In addition, we discussed the challenges and solutions of its implementation based on our experience in Mexico. Group prenatal care may improve prenatal knowledge and use of family planning services in the postpartum period. The model has been implemented in more than 22 countries and there are challenges to its implementation related to both supply and demand. Supply-side challenges include staff, material resources and organizational issues; demand-side challenges include recruitment and retention of participants, adaptation of material, and perceived privacy. We highlight specific solutions that can be applied in diverse health systems.La atención prenatal en grupo es un modelo alternativo de atención durante el embarazo, que sustituye la atención prenatal individual estándar. El modelo ha mostrado beneficios maternos y se ha implementado en diferentes contextos. Llevamos a cabo una revisión narrativa de la literatura en relación a su efectividad, utilizando bases de datos como PubMed, EBSCO, Science Direct, Wiley Online y la editorial Springer, para el periodo 2002 a 2018. Adicionalmente, discutimos los retos y soluciones de su implementación desde nuestra experiencia en México. La atención prenatal en grupo puede mejorar el conocimiento prenatal y el uso de servicios de planificación familiar en el postparto. El modelo se ha implementado en más de 22 países y existen retos de su implementación desde la oferta y la demanda. Los retos desde la oferta incluyen al personal, recursos materiales y cuestiones organizacionales; desde la demanda, el reclutamiento y retención de participantes, adaptación del material y privacidad percibida. Resaltamos soluciones concretas que pueden aplicar a diversos sistemas de salud
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