De empresario a político: El auge y la caída del gobernador Wilfredo Oscorima en Ayacucho (2010-2018)

A partir de los diferentes casos de corrupción de autoridades regionales, se pudo conocer el caso de Wilfredo Oscorima, exgobernador regional de Ayacucho 2010-2018, quien fue condenado a cinco años de cárcel en el 2015 y en el 2016 logró salir de prisión y continuar con su gestión. Oscorima ha estado involucrado en más de 14 investigaciones relacionadas a denuncias de corrupción, pero aún así logró ser reelegido en 2014. Por consiguiente, esta tesis busca explicar la continuidad de Wilfredo Oscorima en el Gobierno Regional de Ayacucho. En este sentido, la tesis se centró en las dinámicas políticas a nivel subnacional que permitieron que Oscorima se mantuviera en el poder por ocho años. En este sentido, la tesis se centró en las dinámicas políticas a nivel subnacional que permitieron que Oscorima se mantuviera en el poder por ocho años. Asimismo, se revisaron los datos de la situación socioeconómica y las características políticas de la región, ya que probablemente influyeron en las dinámicas antes mencionadas. La tesis sostiene que, por medio de su solvencia económica, Oscorima pudo establecer relaciones clientelares duraderas con la población, cierto control de los medios locales y conexiones con las autoridades judiciales. Tras analizar las diferentes maneras que permitieran a Oscorima mantener el poder en la región, la investigación encontró que la construcción de grandes proyectos y relacionarse con autoridades y funcionarios locales también le permitió ganar legitimidad entre la población, contribuyendo a la reelección del gobernadora en los comicios de 2014. Por tanto, la tesis examina un caso de dinámicas políticas subnacional que muestran cómo los gobernadores pueden construir un dominio político-electoral sobre una región en Perú. La tesis está basada en fuentes de bibliografía secundaria, una revisión exhaustiva de archivos de medios de comunicación nacionales y regionales y entrevistas a informantes clave con conocimiento profundo sobre la política en Ayacucho

Relaciones entre los gobiernos subnacionales y el Ministerio de Economía y Finanzas a través del Sistema de Inversión Pública

El Sistema Nacional de Inversión Pública es un sistema administrativo que tiene por objetivo optimizar el uso de los recursos públicos, mediante principios, procesos y normas técnicas. Este sistema comprende un ciclo de proyectos en el que participan diferentes actores, entre ellos los alcaldes y funcionarios del Ministerio de Economía, institución encargada de este sistema. Principalmente, este sistema es el que regula la construcción de las infraestructuras públicas, por lo que requiere cierto grado de complejidad. De esta forma, a lo largo de los años se han encontrado algunas fallas que complican los procesos, haciendo que la entrega de proyectos demore más del tiempo planificado. Por consiguiente, el presente trabajo busca explicar en qué medida los requerimientos y procedimientos del Sistema de Inversión Pública resultan beneficiosos para las gestiones de los gobiernos subnacionales, ya que estos dependen en su mayoría de este sistema para su financiamiento y cumplimiento de obras. Para esto, se ha hecho una revisión de los trabajos que exponen algunos problemas del funcionamiento del sistema a nivel subnacional y de las propuestas teóricas que explican la importancia de las transferencias fiscales y administrativas a autoridades subnacionales. Como consecuencia, se sostiene que el grado técnico que maneja el MEF y por lo tanto el sistema de inversión pública, no garantiza que al presentar los proyectos a este sistema se controle de una mejor forma la reproducción del gasto, ya que, puedan surgir prácticas como las de corrupción. Pues, no existe mecanismo para controlar la transparencia de las actividades de los diferentes actores involucrados en los proyectos de Inversión Pública. Para probar estos posibles resultados a nivel subnacional, se han seleccionado tres de los proyectos más importantes de la ciudad de Huamanga (Ayacucho) para analizar el funcionamiento del sistema de inversión pública en esta provincia

Teaching meiosis with the DNA triangle framework: A classroom activity that changes how students think about chromosomes

Many biology students struggle to learn about the process of meiosis and have particular difficulty understanding the molecular basis of crossing over and the importance of homologous pairing for proper segregation. To help students overcome these challenges, we designed an activity that uses a newly developed Chromosome Connections Kit® from 3-D Molecular Designs to allow learners to explore meiosis at the molecular level. We took a backwards design approach in constructing an effective classroom activity. We developed evidence-based learning objectives and designed a crossing over activity that targets students\u27 misconceptions and key concepts about meiosis. Assessment questions were designed based on the learning objectives and common student misconceptions. The activity consists of three parts: an interactive introductory video, a model-based activity, and reflection questions. The activity was first beta-tested with a small number of students and revised based on feedback. The revised activity was deployed in a mid-level Cell and Molecular Biology course. Analysis of pre-/post-assessment data from students who completed the activity (n = 83) showed strong learning gains on concepts related to ploidy, homology, segregation, and the mechanism and purpose of crossing over. Additionally, students who participated in the activity outperformed nonparticipants on a Genetics assessment about meiosis the following semester

Annealing Would Improve beta" - Alumina Solid Electrolyte

A pre-operational annealing process is under investigation as a potential means of preventing a sudden reduction of ionic conductivity in a Beta"-alumina solid electrolyte (BASE) during use. On the basis of tests, the sudden reduction of ionic conductivity, followed by a slow recovery, has been found to occur during testing of the solid electrolyte and electrode components of an alkali metal thermal-to-electric converter (AMTEC) cell. At this time, high-temperature tests of limited duration have indicated the superiority of the treated BASE, but reproducible tests over thousands of hours are necessary to confirm that microcracking has been eliminated. The ionic conductivity of the treated BASE is also measured to be higher than untreated BASE at 1,073 K in low-pressure sodium vapor. Microcracking resulting in loss of conductivity was not observed with treated BASE in one high-temperature experiment, but this result must be duplicated over very long testing times to be sure of the effect. Shorter annealing times (10 to 20 hours) were found to result in significantly less loss of mass; it may be necessary for the packed powder mixture to evolve some Na2O before the Na2O can leave the ceramic

Identification of the first ATRIP-deficient patient and novel mutations in ATR define a clinical spectrum for ATR-ATRIP Seckel Syndrome

A homozygous mutational change in the Ataxia-Telangiectasia and RAD3 related (ATR) gene was previously reported in two related families displaying Seckel Syndrome (SS). Here, we provide the first identification of a Seckel Syndrome patient with mutations in ATRIP, the gene encoding ATR-Interacting Protein (ATRIP), the partner protein of ATR required for ATR stability and recruitment to the site of DNA damage. The patient has compound heterozygous mutations in ATRIP resulting in reduced ATRIP and ATR expression. A nonsense mutational change in one ATRIP allele results in a C-terminal truncated protein, which impairs ATR-ATRIP interaction; the other allele is abnormally spliced. We additionally describe two further unrelated patients native to the UK with the same novel, heterozygous mutations in ATR, which cause dramatically reduced ATR expression. All patient-derived cells showed defective DNA damage responses that can be attributed to impaired ATR-ATRIP function. Seckel Syndrome is characterised by microcephaly and growth delay, features also displayed by several related disorders including Majewski (microcephalic) osteodysplastic primordial dwarfism (MOPD) type II and Meier-Gorlin Syndrome (MGS). The identification of an ATRIP-deficient patient provides a novel genetic defect for Seckel Syndrome. Coupled with the identification of further ATR-deficient patients, our findings allow a spectrum of clinical features that can be ascribed to the ATR-ATRIP deficient sub-class of Seckel Syndrome. ATR-ATRIP patients are characterised by extremely severe microcephaly and growth delay, microtia (small ears), micrognathia (small and receding chin), and dental crowding. While aberrant bone development was mild in the original ATR-SS patient, some of the patients described here display skeletal abnormalities including, in one patient, small patellae, a feature characteristically observed in Meier-Gorlin Syndrome. Collectively, our analysis exposes an overlapping clinical manifestation between the disorders but allows an expanded spectrum of clinical features for ATR-ATRIP Seckel Syndrome to be define

Structural Modeling of Voltage-Gated Ion Channel Interactions with Drugs Using Rosetta

Many different types of drugs–from antibiotics to blood pressure medication–tend to interfere with the body’s ability to control heart rhythm by disrupting the proteins in heart cells that control the movement of charged atoms (ions) across the cell membrane known as voltage-gated ion channels (VGICs). These drugs can cause dangerous arrhythmias (abnormal heart rhythms) that can increase risk for heart failure, stroke, or death. Early and efficient assessment of cardiotoxicity is essential to the drug development process and to reducing drug development costs. Current methods for assessing safety are sensitive but not specific and can often result in false identification of unsafe treatments and the failure of potentially life-saving treatments to reach the public. Structural characterization of VGICs and their modulating interactions are necessary for rational design of safe therapeutics. Human Ether-a-go-go-Related Gene (hERG) encodes a potassium-selective voltage-gated ion channel (KV11.1) essential for normal electrical activity in the heart. Genetic hERG mutations and blockage of the channel pore by drugs can cause long QT syndrome (LQTS). LQTS predisposes individuals to arrhythmia and puts them at risk for stroke or sudden cardiac arrest. A major problem in antiarrhythmic drug therapies is the proclivity for these drugs to promote fatal arrhythmias through hERG channel blockade. However, not all hERG channel blocking drugs are pro-arrhythmic, and their differential affinities to discrete channel conformational states and/or their state stability modulations have been suggested to contribute to arrhythmogenicity. Voltage-gated calcium (CaV) channels play a key role in muscular contraction, neuronal excitation, gene expression regulation, and release of hormones or neurotransmitters. Dysregulation of CaV channels and the associated intracellular calcium homeostasis have been associated with various types of cardiac and neurological disorders. Found throughout the body, often as part of large complexes and/or clusters, the L-type CaV1.2 channel mediates the influx of Ca2+ into the cell in response to membrane depolarization. Mutations or blockage of the channel by drug molecules leading to altered functions of human CaV1.2 have been linked to cardiac arrhythmias, autism, bipolar disorder, and immunodeficiency. Many CaV channel blockers targeting the alpha-1-subunit of CaV1.2 are used to treat hypertension, coronary artery disease and other cardiovascular medical conditions. However, only a few drugs have been approved for clinical use due to severe side effects (including cardiotoxicity) or limited efficacy.In this study, Rosetta electron density refinement and homology modeling protocols were used to build voltage sensing and pore domain structural models of wild-type hERG channel in open and closed states, open-state hERG mutant variants (Y652A, F656A, and Y652A/F656A double mutant) based on cryo-electron microscopy (cryo-EM) structures of hERG (PDBID: 5VA2) and EAG1 (PDBID: 5K7L) channels as well as open- and closed-state models of the wild-type CaV1.2 alpha-1-subunit using cryo-EM CaV1.1 (PDBID: 5GJV), and NaV1.4 (PDB ID: 6AGF) structures, respectively. The hERG channel models were developed as protein targets for Rosetta-based molecular docking studies of charged and neutral forms of amiodarone, nifekalant, dofetilide, d- and l-sotalol, flecainide, and moxifloxacin–a diverse set of pharmaceuticals chosen based on their different arrhythmogenic potentials and abilities to facilitate hERG current. The CaV1.2 models were used as targets for Rosetta docking studies with verapamil and amlodipine– representatives of two different calcium channel blocking classes: phenylalkylamines and dihydropyridines, respectively. We present here the results of our docking studies that provide structural insights into the molecular and state-dependent drug interactions with hERG and CaV1.2 channels that play a key role in differentiating safe and harmful ion channel blockers.Key Findings:1. Pattern of hERG-drug interactions with the hydrophobic pocket is consistent with experimental data suggesting facilitating drugs may act as a wedge to bias hERG channel equilibrium towards the open state and increase hERG current amplitude in response to low-voltage depolarization. 2. Open-state WT hERG interface scores are lower than, or similar to, Y652A mutants suggesting that these poses are relevant for amiodarone, nifekalant, flecainide, moxifloxacin, d-sotalol, and dofetilide, based on comparison to existing experimental data. 3. Open-state WT hERG interface scores are not lower than the F656A mutants for nifekalant, neutral flecainide, neutral moxifloxacin, d-sotalol, l-sotalol, and dofetilide, suggesting limitations of our study using only two conformational states or limitations of Rosetta to model allosteric contributions of F656. 4. Percentage of poses remaining within the closed-state hERG channels suggest that closed channels can accommodate known trapped drugs (nifekalant, flecainide, d/l-sotalol, and dofetilide), but not amiodarone or moxifloxacin (non-trapped drugs). 5. Amlodipine and verapamil docked to rCaV1.2 models in open and closed states recapitulated known binding orientations and similar positioning within pore but did not reproduce known binding determinants necessitating revision of model development to include additional structural densities and increasing search radius in docking protocol in future studies

Structural Modeling of Voltage-Gated Ion Channel Interactions with Drugs Using Rosetta

Many different types of drugs–from antibiotics to blood pressure medication–tend to interfere with the body’s ability to control heart rhythm by disrupting the proteins in heart cells that control the movement of charged atoms (ions) across the cell membrane known as voltage-gated ion channels (VGICs). These drugs can cause dangerous arrhythmias (abnormal heart rhythms) that can increase risk for heart failure, stroke, or death. Early and efficient assessment of cardiotoxicity is essential to the drug development process and to reducing drug development costs. Current methods for assessing safety are sensitive but not specific and can often result in false identification of unsafe treatments and the failure of potentially life-saving treatments to reach the public. Structural characterization of VGICs and their modulating interactions are necessary for rational design of safe therapeutics. Human Ether-a-go-go-Related Gene (hERG) encodes a potassium-selective voltage-gated ion channel (KV11.1) essential for normal electrical activity in the heart. Genetic hERG mutations and blockage of the channel pore by drugs can cause long QT syndrome (LQTS). LQTS predisposes individuals to arrhythmia and puts them at risk for stroke or sudden cardiac arrest. A major problem in antiarrhythmic drug therapies is the proclivity for these drugs to promote fatal arrhythmias through hERG channel blockade. However, not all hERG channel blocking drugs are pro-arrhythmic, and their differential affinities to discrete channel conformational states and/or their state stability modulations have been suggested to contribute to arrhythmogenicity. Voltage-gated calcium (CaV) channels play a key role in muscular contraction, neuronal excitation, gene expression regulation, and release of hormones or neurotransmitters. Dysregulation of CaV channels and the associated intracellular calcium homeostasis have been associated with various types of cardiac and neurological disorders. Found throughout the body, often as part of large complexes and/or clusters, the L-type CaV1.2 channel mediates the influx of Ca2+ into the cell in response to membrane depolarization. Mutations or blockage of the channel by drug molecules leading to altered functions of human CaV1.2 have been linked to cardiac arrhythmias, autism, bipolar disorder, and immunodeficiency. Many CaV channel blockers targeting the alpha-1-subunit of CaV1.2 are used to treat hypertension, coronary artery disease and other cardiovascular medical conditions. However, only a few drugs have been approved for clinical use due to severe side effects (including cardiotoxicity) or limited efficacy.In this study, Rosetta electron density refinement and homology modeling protocols were used to build voltage sensing and pore domain structural models of wild-type hERG channel in open and closed states, open-state hERG mutant variants (Y652A, F656A, and Y652A/F656A double mutant) based on cryo-electron microscopy (cryo-EM) structures of hERG (PDBID: 5VA2) and EAG1 (PDBID: 5K7L) channels as well as open- and closed-state models of the wild-type CaV1.2 alpha-1-subunit using cryo-EM CaV1.1 (PDBID: 5GJV), and NaV1.4 (PDB ID: 6AGF) structures, respectively. The hERG channel models were developed as protein targets for Rosetta-based molecular docking studies of charged and neutral forms of amiodarone, nifekalant, dofetilide, d- and l-sotalol, flecainide, and moxifloxacin–a diverse set of pharmaceuticals chosen based on their different arrhythmogenic potentials and abilities to facilitate hERG current. The CaV1.2 models were used as targets for Rosetta docking studies with verapamil and amlodipine– representatives of two different calcium channel blocking classes: phenylalkylamines and dihydropyridines, respectively. We present here the results of our docking studies that provide structural insights into the molecular and state-dependent drug interactions with hERG and CaV1.2 channels that play a key role in differentiating safe and harmful ion channel blockers.Key Findings:1. Pattern of hERG-drug interactions with the hydrophobic pocket is consistent with experimental data suggesting facilitating drugs may act as a wedge to bias hERG channel equilibrium towards the open state and increase hERG current amplitude in response to low-voltage depolarization. 2. Open-state WT hERG interface scores are lower than, or similar to, Y652A mutants suggesting that these poses are relevant for amiodarone, nifekalant, flecainide, moxifloxacin, d-sotalol, and dofetilide, based on comparison to existing experimental data. 3. Open-state WT hERG interface scores are not lower than the F656A mutants for nifekalant, neutral flecainide, neutral moxifloxacin, d-sotalol, l-sotalol, and dofetilide, suggesting limitations of our study using only two conformational states or limitations of Rosetta to model allosteric contributions of F656. 4. Percentage of poses remaining within the closed-state hERG channels suggest that closed channels can accommodate known trapped drugs (nifekalant, flecainide, d/l-sotalol, and dofetilide), but not amiodarone or moxifloxacin (non-trapped drugs). 5. Amlodipine and verapamil docked to rCaV1.2 models in open and closed states recapitulated known binding orientations and similar positioning within pore but did not reproduce known binding determinants necessitating revision of model development to include additional structural densities and increasing search radius in docking protocol in future studies

CRENÇAS E ATITUDES LINGUÍSTICAS NAS FRONTEIRAS BRASIL/ARGENTINA E BRASIL/PARAGUAI: CAMINHOS E ENCONTROS

Neste artigo pretendemos discutir a teoria e a metodologia da pesquisa que está sendo desenvolvida no Programa de Pós-Graduação – Mestrado em Letras, sobre crenças e atitudes linguísticas. O objetivo principal da pesquisa é analisar as crenças e atitudes linguísticas de moradores das fronteiras Brasil/Argentina sobre o espanhol, a partir dos dados coletados em Santo Antônio do Sudoeste-BR, Capanema-BR, e da fronteira Brasil/Paraguai, na cidade de Guaíra-BR. As entrevistas que compõem o corpus da pesquisa foram realizadas no Projeto Crenças e Atitudes linguísticas: um estudo da relação do português com línguas de contato (SELLA; AGUILERA, 2009). Para nortear o estudo, utilizamos o escopo teórico da Sociolinguística (LABOV, 1976), das Crenças e Atitudes Linguísticas (LAMBERT, 1967; AGUILERA, 2008)

Journals accepting case reports.

BACKGROUND: Few resources exist to support finding journals that accept case reports by specialty. In 2016, Katherine Akers compiled a list of 160 journals that accepted case reports, which many librarians continue to use 7 years later. Because journals editorial policies and submission guidelines evolve, finding publication venues for case reports poses a dynamic problem, consisting of reviewing a journals author guidelines to determine if the journal accepts case report manuscripts. This project aimed to create a more up to date and extensive list of journals that currently accept case reports. CASE PRESENTATION: 1,874 journal titles were downloaded from PubMed. The team reviewed each journal and identified journal titles that accept case reports. Additional inclusion factors included being indexed in MEDLINE, accessible on the internet, and accepting and publishing English language submissions. DISCUSSION: The new journal list includes 1,028 journals covering 129 specialties and is available on the Open Science Framework public page