Copula-Based Modeling of TMI Brightness Temperature With Rainfall Type

Overland rain retrieval using spaceborne microwave radiometer offers a myriad of complications as land presents itself as a radiometrically warm and highly variable background. Hence, land rainfall algorithms of the Tropical Rainfall Measuring Mission (TRMM) Microwave Imager (TMI) have traditionally incorporated empirical relations of microwave brightness temperature (Tb) with rain rate, rather than relying on physically based radiative transfer modeling of rainfall (as implemented in the TMI ocean algorithm). In this paper, sensitivity analysis is conducted using the Spearman rank correlation coefficient as benchmark, to estimate the best combination of TMI low-frequency channels that are highly sensitive to the near surface rainfall rate from the TRMM Precipitation Radar (PR). Results indicate that the TMI channel combinations not only contain information about rainfall wherein liquid water drops are the dominant hydrometeors but also aid in surface noise reduction over a predominantly vegetative land surface background. Furthermore, the variations of rainfall signature in these channel combinations are not understood properly due to their inherent uncertainties and highly nonlinear relationship with rainfall. Copula theory is a powerful tool to characterize the dependence between complex hydrological variables as well as aid in uncertainty modeling by ensemble generation. Hence, this paper proposes a regional model using Archimedean copulas, to study the dependence of TMI channel combinations with respect to precipitation, over the land regions of Mahanadi basin, India, using version 7 orbital data from the passive and active sensors on board TRMM, namely, TMI and PR. Studies conducted for different rainfall regimes over the study area show the suitability of Clayton and Gumbel copulas for modeling convective and stratiform rainfall types for the majority of the intraseasonal months. Furthermore, large ensembles of TMI Tb (from the most sensitive TMI channel combination) were generated conditional on various quantiles (25th, 50th, 75th, and 95th) of the convective and the stratiform rainfall. Comparatively greater ambiguity was observed to model extreme values of the convective rain type. Finally, the efficiency of the proposed model was tested by comparing the results with traditionally employed linear and quadratic models. Results reveal the superior performance of the proposed copula-based technique.

Small molecule inhibitors of HCV replication from Pomegranate

Hepatitis C virus (HCV) is the causative agent of end-stage liver disease. Recent advances in the last decade in anti HCV treatment strategies have dramatically increased the viral clearance rate. However, several limitations are still associated, which warrant a great need of novel, safe and selective drugs against HCV infection. Towards this objective, we explored highly potent and selective small molecule inhibitors, the ellagitannins, from the crude extract of Pomegranate (Punica granatum) fruit peel. The pure compounds, punicalagin, punicalin, and ellagic acid isolated from the extract specifically blocked the HCV NS3/4A protease activity in vitro. Structural analysis using computational approach also showed that ligand molecules interact with the catalytic and substrate binding residues of NS3/4A protease, leading to inhibition of the enzyme activity. Further, punicalagin and punicalin significantly reduced the HCV replication in cell culture system. More importantly, these compounds are well tolerated ex vivo and `no observed adverse effect level' (NOAEL) was established upto an acute dose of 5000 mg/kg in BALB/c mice. Additionally, pharmacokinetics study showed that the compounds are bioavailable. Taken together, our study provides a proof-of-concept approach for the potential use of antiviral and non-toxic principle ellagitannins from pomegranate in prevention and control of HCV induced complications.

Reconstruction of Two-Dimensional Spectra from One-Dimensional Projections-Examples from Solid State NMR

The use of Projection Reconstruction (PR) to obtain two-dimensional (2D) spectra from one-dimensional (1D) data in the solid state is illustrated. The method exploits multiple 1D spectra obtained using magic angle spinning and off-magic angle spinning. The spectra recorded under the influence of scaled heteronuclear scalar and dipolar couplings in the presence of homonuclear dipolar decoupling sequences have been used to reconstruct J/D Resolved 2D-NMR spectra. The use of just two 1D spectra is observed sufficient to reconstruct a J-resolved 2D-spectrum while a Separated Local Field (SLF) 2D-NMR spectrum could be obtained from three 1D spectra. The experimental techniques for recording the 10 spectra and procedure of reconstruction are discussed and the reconstructed results are compared with 20 experiments recorded in traditional methods. The application of the technique has been made to a solid polycrystalline sample and to a uniaxially oriented liquid crystal. Implementation of PR-NMR in solid state provides high-resolution spectra as well as leads to significant reduction in experimental time. The experiments are relatively simple and are devoid of several technical complications involved in performing the 2D experiments.

Cells Producing Their Own Nemesis: Understanding Methylglyoxal Metabolism

Methylglyoxal, which is technically known as 2-oxopropanal or pyruvaldehyde, shows typical reactions of carbonyl compounds as it has both an aldehyde and a ketone functional group. It is an extremely cytotoxic physiological metabolite, which is generated by both enzymatic and nonenzymatic reactions. The deleterious nature of the compound is due to its ability to glycate and crosslink macromolecules like protein and DNA, respectively. However, despite having toxic effects on cellular processes, methylglyoxal retains its efficacy as an anticancer drug. Indeed, methylglyoxal is one of the well-known anticancer therapeutic agents used in the treatment. Several studies on methylglyoxal biology revolve around the manifestations of its inhibitory effects and toxicity in microbial growth and diabetic complications, respectively. Here, we have revisited the chronology of methylglyoxal research with emphasis on metabolism of methylglyoxal and implications of methylglyoxal production or detoxification on bacterial pathogenesis and disease progression. (C) 2014 IUBMB Life, 66(10): 667-678, 2014

Sensing of Stimulus Artifact Suppressed Signals From Electrode Interfaces

Stimulus artifacts inhibit reliable acquisition of biological evoked potentials for several milliseconds if an electrode contact is utilized for both electrical stimulation and recording purposes. This hinders the measurement of evoked short-latency biological responses, which is otherwise elicited by stimulation in implantable prosthetic devices. We present an improved stimulus artifact suppression scheme using two electrode simultaneous stimulation and differential readout using high-gain amplifiers. Substantial reduction of artifact duration has been shown possible through the common-mode rejection property of an instrumentation amplifier for electrode interfaces. The performance of this method depends on good matching of electrode-electrolyte interface properties of the chosen electrode pair. A novel calibration algorithm has been developed that helps in artificial matching of impedance and thereby achieves the required performance in artifact suppression. Stimulus artifact duration has been reduced down to 50 mu s from the stimulation-cum-recording electrodes, which is similar to 6x improvement over the present state of the art. The system is characterized with emulated resistor-capacitor loads and a variety of in-vitro metal electrodes dipped in saline environment. The proposed method is going to be useful for closed-loop electrical stimulation and recording studies, such as bidirectional neural prosthesis of retina, cochlea, brain, and spinal cord.

Early postnatal exposure to lithium in vitro induces changes in AMPAR mEPSCs and vesicular recycling at hippocampal glutamatergic synapses

Lithium is an effective mood stabilizer but its use is associated with many side effects. Electrophysiological recordings of miniature excitatory postsynaptic currents (mEPSCs) mediated by glutamate receptor AMPA-subtype (AMPARs) in hippocampal pyramidal neurons revealed that CLi (therapeutic concentration of 1 mM lithium, from days in vitro 4-10) decreased the mean amplitude and mean rectification index (RI) of AMPAR mEPSCs. Lowered mean RI indicate that contribution of Ca2+-permeable AMPARs in synaptic events is higher in CLi neurons (supported by experiments sensitive to Ca2+-permeable AMPAR modulation). Co-inhibiting PKA, GSK-3 beta and glutamate reuptake was necessary to bring about changes in AMPAR mEPSCs similar to that seen in CLi neurons. FM1-43 experiments revealed that recycling pool size was affected in CLi cultures. Results from minimum loading, chlorpromazine treatment and hyperosmotic treatment experiments indicate that endocytosis in CLi is affected while not much difference is seen in modes of exocytosis. CLi cultures did not show the high KCl associated presynaptic potentiation observed in control cultures. This study, by calling attention to long-term lithium-exposure-induced synaptic changes, might have implications in understanding the side effects such as CNS complications occurring in perinatally exposed babies and cognitive dulling seen in patients on lithium treatment.

Differential viability response of prokaryotes and eukaryotes to high strength pulsed magnetic stimuli

The present study examines the efficacy of a high strength pulsed magnetic field (PMF) towards bacterial inactivation in vitro, without compromising eukaryotic cell viability. The differential response of prokaryotes Staphylococcus aureus (MESA), Staphylococcus epidermidis, and Escherichia coli], and eukaryotes C2C12 mouse myoblasts and human mesenchymal stem cells, hMSCs] upon exposure to varying PMF stimuli (1-4 T, 30 pulses, 40 ms pulse duration) is investigated. Among the prokaryotes, similar to 60% and similar to 70% reduction was recorded in the survival of staphylococcal species and E. coli, respectively at 4 T PMF as evaluated by colony forming unit (CPU) analysis and flow cytometry. A 2-5 fold increase in intracellular ROS (reactive oxygen species) levels suggests oxidative stress as the key mediator in PMF induced bacterial death/injury. The 4 T PMF treated staphylococci also exhibited longer doubling times. Both TEM and fluorescence microscopy revealed compromised membranes of PMF exposed bacteria. Under similar PMF exposure conditions, no immediate cytotoxicity was recorded in C2C12 mouse myoblasts and hMSCs, which can be attributed to the robust resistance towards oxidative stress. The ion interference of iron containing bacterial proteins is invoked to analytically explain the PMF induced ROS accumulation in prokaryotes. Overall, this study establishes the potential of PMF as a bactericidal method without affecting eukaryotic viability. This non-invasive stimulation protocol coupled with antimicrobial agents can be integrated as a potential methodology for the localized treatment of prosthetic infections. (C) 2015 Elsevier B.V. All rights reserved.

Unconjugated Bilirubin exerts Pro-Apoptotic Effect on Platelets via p38-MAPK activation

Thrombocytopenia is one of the most frequently observed secondary complications in many pathological conditions including liver diseases, where hyperbilirubinemia is very common. The present study sought to find the cause of thrombocytopenia in unconjugated hyperbilirubinemic conditions. Unconjugated bilirubin (UCB), an end-product of heme catabolism, is known to have pro-oxidative and cytotoxic effects at high serum concentration. We investigated the molecular mechanism underlying the pro-apoptotic effect of UCB on human platelets in vitro, and followed it up with studies in phenylhydrazine-induced hyperbilirubinemic rat model and hyperbilirubinemic human subjects. UCB is indeed found to significantly induce platelet apoptotic events including elevated endogenous reactive oxygen species generation, mitochondrial membrane depolarization, increased intracellular calcium levels, cardiolipin peroxidation and phosphatidylserine externalization (p < 0.001) as evident by FACS analysis. The immunoblots show the elevated levels of cytosolic cytochrome c and caspase activation in UCB-treated platelets. Further, UCB is found to induce mitochondrial ROS generation leading to p38 activation, followed by downstream activation of p53, ultimately resulting in altered expression of Bcl-2 and Bax proteins as evident from immunoblotting. All these parameters conclude that elevated unconjugated bilirubin causes thrombocytopenia by stimulating platelet apoptosis via mitochondrial ROS-induced p38 and p53 activation.

Phytomedicinal importance of Saraca asoca (Ashoka): an exciting past, an emerging present and a promising future

Since the dawn of civilization, natural resources have remained the mainstay of various remedial approaches of humans vis-a-vis a large number of illnesses. Saraca asoca (Roxb.) de Wilde (Saraca indica L.) belonging to the family Caesalpiniaceae has been regarded as a universal panacea in old Indian Ayurvedic texts and has especially been used to manage gynaecological complications and infections besides treating haemmorhagic dysentery, uterine pain, bacterial infections, skin problems, tumours, worm infestations, cardiac and circulatory problems. Almost all parts of the plant are considered pharmacologically valuable. Extensive folkloric practices and ethnobotanical applications of this plant have even lead to the availability of several commercial S. asoca formulations recommended for different indications though adulteration of these remains a pressing concern. Though a wealth of knowledge on this plant is available in both the classical and modern literature, extensive research on its phytomedicinal worth using state-of-the-art tools and methodologies is lacking. Recent reports on bioprospecting of S. asoca endophytic fungi for industrial bioproducts and useful pharmacologically relevant metabolites provide a silver lining to uncover single molecular bio-effectors from its endophytes. Here, we describe socio-ethnobotanical usage, present the current pharmacological status and discuss potential bottlenecks in harnessing the proclaimed phytomedicinal worth of this prescribed Ayurvedic medicinal plant. Finally, we also look into the possible future of the drug discovery and pharmaceutical R&D efforts directed at exploring its pharma legacy.

La incidencia del trabajo infantil en Argentina

Resumen: El tema “trabajo infantil” es complejo de abordar debido a la falta de unicidad en su conceptualización y por la heterogeneidad y multiplicidad que lo caracteriza. No obstante, la diversidad de análisis (tanto descriptivos como estadísticos) en diferentes países sobre la cuestión, ha probado el gran avance en el sorteamiento de estas dificultades, como también brindado la base del diseño de planes de erradicación eficientes. Argentina ha sido una excepción a la regla. A pesar de la existencia de reportes e informes provenientes de organismos gubernamentales nacionales e internacionales se encuentra muy poco desarrollada la investigación basada en las herramientas econométricas. Por consiguiente, este análisis busca ampliar los conocimientos sobre el trabajo infantil en Argentina mediante la construcción de un modelo Logit binario que permita así examinar tanto la incidencia de los factores condicionantes más populares de la bibliografía internacional, así como la llamada “paradoja de la riqueza” planteada por Bhalotra y; por último la obtención de conclusiones sobre el impacto de las asistencias sociales en el trabajo infantil.

Impacto de la evolución científico-tecnológica en la Bioética neonatal-perinatal

Resumen: Los avances científico-tecnológicos en neonatología en los últimos 40 años han permitido una importante mejoría en la sobrevida de recién nacidos de extremo bajo peso al nacer, sin embargo la mortalidad neonatal aun representa un porcentaje muy grande de la mortalidad infantil. Esto esta principalmente relacionado a las muertes por prematuridad y sus complicaciones, anomalías congénitas y asfixia perinatal. La mayoría de los recién nacidos son tratados favorablemente en sala de partos y son admitidos a la Unidad de Cuidados Intensivos Neonatales (UCIN). La incertidumbre en el pronóstico de los prematuros extremos en el límite de la viabilidad con alto riesgo de morir en la UCIN o presentar alguna discapacidad, presenta un difícil dilema ético. Se deberá considerar cada caso en forma individual y evaluar el riesgo-beneficio entre las conductas a seguir y el “mejor interés para el niño” y los deseos de los padres que guiarán a decisiones éticas. Diferentes guías de cuidado y variaciones en la práctica médica en los límites de la viabilidad fetal se han descripto dentro y entre países. El objetivo es proveer a los padres una comunicación abierta, directa y transparente con suficiente entendimiento de los factores más relevantes en relación a la situación clínica, el pronóstico y las opciones de tratamiento para que ellos puedan tener una significativa participación en la toma de decisiones. Aceptar que en neonatología, hacer todo lo que uno puede hacer puede ser perjudicial, no útil o beneficioso. No todo lo técnicamente posible es éticamente correcto. El dilema afecta tanto al origen de la vida como a la terminación de la vida.

Carne e bits : reflexões sobre a indiscernibilidade das fronteiras entre mentes e máquinas e os sistemas cognitivos híbridos

Faz reflexões sobre as várias formas de relação entre sujeitos e objetos-técnicos, com ênfase para a utilização dos computadores digitais e, particularmente, os softwares chamados agentes inteligentes. Analisa o espaço e suas mudanças qualitativas na atualidade, a partir do conceito do espaço como produção humana, analisando como as transformações em curso no ambiente afetam nossas subjetividades e, reciprocamente, como afetamos nossos ambientes. Discutidas as possibilidades de sobrevivência do homem nu nesses novos espaços, sem que esteja devidamente atualizado com as últimas novidades tecnológicas - próteses sensoriais e motoras. Perpassa a discussão sobre o pensamento que se utiliza do espaço como elemento constituinte do próprio pensamento e reflete sobre o espaço abstrato por excelência, os mundos virtuais. Discute o padrão de apropriação de artefatos pelo homem e seus efeitos na subjetividade, a manutenção do padrão de apropriação dos objetos-técnicos materiais em relação às formas de apropriação dos objetos-técnicos intangíveis (softwares). Traz reflexões sobre a possibilidade de autonomização completa dos agentes inteligentes e a sua instituição, ipso facto, como agentes - a chamada Inteligência Artificial.

The Role of the Subthalamic Nucleus in L-DOPA Induced Dyskinesia in 6-Hydroxydopamine Lesioned Rats

14 p.

Monitorización avanzada en el posoperatorio de las cardiopatías congénitas : motorización hemodinámica avanzada en el posoperatorio de cardiopatías congénitas mediante termodilución transpulmonar y espectroscopia cercana al infrarrojo

196 p. : graf.

Laminar Burning Velocities and Markstein Lengths of Premixed Methane/Air Flames near the Lean Flammability Limit in Microgravity

Effects of flame stretch on the laminar burning velocities of near-limit fuel-lean methane/air flames have been studied experimentally using a microgravity environment to minimize the complications of buoyancy. Outwardly propagating spherical flames were employed to assess the sensitivities of the laminar burning velocity to flame stretch, represented by Markstein lengths, and the fundamental laminar burning velocities of unstretched flames. Resulting data were reported for methane/air mixtures at ambient temperature and pressure, over the specific range of equivalence ratio that extended from 0.512 (the microgravity flammability limit found in the combustion chamber) to 0.601. Present measurements of unstretched laminar burning velocities were in good agreement with the unique existing microgravity data set at all measured equivalence ratios. Most of previous 1-g experiments using a variety of experimental techniques, however, appeared to give significantly higher burning velocities than the microgravity results. Furthermore, the burning velocities predicted by three chemical reaction mechanisms, which have been tuned primarily under off-limit conditions, were also considerably higher than the present experimental data. Additional results of the present investigation were derived for the overall activation energy and corresponding Zeldovich numbers, and the variation of the global flame Lewis numbers with equivalence ratio. The implications of these results were discussed. 2010 The Combustion Institute. Published by Elsevier Inc. All rights reserved.