Miracle-dz/UniFAR-FTUs huggingface dataset:
Nonlinear Kinetics of Imipramine in Low and Medium Plasma Level Ranges

Steady state plasma concentrations of imipramine and desipramine were studied at three to nine different imipramine dose levels in 17 extensive metabolizers of sparteine and at two dose levels in two poor metabolizers of sparteine, all treated for diabetic neuropathy symptoms. The imipramine doses were changed stepwise from doses yielding plasma concentrations of imipramine plus desipramine below 150 nM, up to doses yielding therapeutic drug levels of at least 300–500 nM. The imipramine doses required to achieve therapeutic drug levels was 20 or 25 mg/day in the two poor metabolizers and 50–350 mg/day in the extensive metabolizers. In the extensive metabolizers, the concentration/dose ratio increased for imipramine and desipramine with increasing dose. Dose adjustments based on a simple linear prediction from drug levels at initial dose (50 or 75 mg imipramine/day) thus would result in 0–130% (median, 20%) overestimates, most pronounced in patients with initial low steady state levels. The nonlinear kinetics of imipramine thus may be a significant clinical problem in patients treated for diabetic neuropathy symptoms.
Improved heading estimation for smartphone-based indoor positioning systems

Existing positioning systems such as global positioning system (GPS) or WiFi positioning system (WPS) are limited mainly to outdoor applications or are of poor accuracy without associated maps. Indoor work environment where one spend most of the time and wide adoption of smartphones with numerous embedded sensors provide new opportunities for researches on indoor user positioning. In this paper, we present an indoor positioning scheme using recently introduced smartphones equipped with sensors such as accelerometer, magnetometer, and gyroscope. We propose a practical indoor positioning method to handle complicated human movements and noisy inertial sensors in smartphones. We focus on providing indoor locations with accuracy by applying improved heading estimation solution. The key concept is to reduce errors caused by directional change since the critical component of positioning system is a heading orientation. We have simply used iPhone 4S for experiments and validated its practical usage in indoor environments. The extensive experimental results show that our system is needily applicable as a fundamental system for various mobile services on smartphones providing 2.42 times accuracy over than traditional methods on the average.
Hierarchical VBA based TCSC Robust damping control system design

3 Abstract: A novel Hierarchical virtual bee's algorithm (HVBA) based design method for robust control of Thyristor controlled series compensator (TCSC) is presented in this paper. The design problem of controller is first formulated as an optimization problem. Then HVBA is employed to simultaneously select an appropriate structure of controller and its optimal parameters by minimizing the multi-objective function of supplementary damping control system. The effectiveness of the proposed technique is evaluated and compared with no control and conventional control design. The performance and robustness of the proposed technique is validated through small and large signal simulations in multi-machine power system.
Socio-economic and climate change impacts on agriculture: an integrated assessment, 1990–2080

A comprehensive assessment of the impacts of climate change on agro-ecosystems over this century is developed, up to 2080 and at a global level, albeit with significant regional detail. To this end an integrated ecological–economic modelling framework is employed, encompassing climate scenarios, agro-ecological zoning information, socio-economic drivers, as well as world food trade dynamics. Specifically, global simulations are performed using the FAO/IIASA agro-ecological zone model, in conjunction with IIASAs global food system model, using climate variables from five different general circulation models, under four different socio-economic scenarios from the intergovernmental panel on climate change. First, impacts of different scenarios of climate change on bio-physical soil and crop growth determinants of yield are evaluated on a 5′×5′ latitude/longitude global grid; second, the extent of potential agricultural land and related potential crop production is computed. The detailed bio-physical results are then fed into an economic analysis, to assess how climate impacts may interact with alternative development pathways, and key trends expected over this century for food demand and production, and trade, as well as key composite indices such as risk of hunger and malnutrition, are computed. This modelling approach connects the relevant bio-physical and socio-economic variables within a unified and coherent framework to produce a global assessment of food production and security under climate change. The results from the study suggest that critical impact asymmetries due to both climate and socio-economic structures may deepen current production and consumption gaps between developed and developing world; it is suggested that adaptation of agricultural techniques will be central to limit potential damages under climate change.
Design of Tri-Band Filter Based on Stub Loaded Resonator and DGS Resonator

A tri-band bandpass filter using stub loaded resonator (SLR) and defected ground structure (DGS) resonator is proposed in this letter. The DGS resonator on the lower plane constructs the first pass-band, and the SLR on the upper plane forms the second and third pass-bands, in which a DGS loop is properly used to provide the coupling between the SLRs. The three pass-bands are combined together with a common T-shaped feed line, and a reasonable tuning method is adopted to tune the three pass-bands with smooth responses. A compact tri-band filter with three pass-bands centered at 2.45, 3.5, and 5.25 GHz is designed and fabricated. The measurement results agree well with the full-wave electromagnetic designed responses.
Estudio farmacogenético de variantes polimórficas en genes reparadores del ADN y otros marcadores de resistencia en pacientes con cáncer de cabeza y cuello

El cancer escamoso de cabeza y cuello (CECC) tiene una gran complejidad anatomica y funcional, constituye un grupo heterogeneo de tumores que engloba diversas estructuras anatomicas, la cavidad oral, nasofaringe, orofaringe, laringe e hipofaringe, y es la septima neoplasia con mayor incidencia en la poblacion mundial. Nuestro objetivo fue evaluar la asociacion entre SNPs implicados en la via del platino/radiacion con la respuesta, supervivencia y toxicidad en pacientes con CECC localmente avanzado que recibieron quimioradioterapia concomitante basada en platino. Para seleccionar los genes y SNPs candidatos se hizo una busqueda bibliografica de la literatura en la base de datos MEDLINE (http:/www.ncbi.nlm.nih.gov/PubMed/) hasta enero de 2011 utilizando descriptores. Se analizo un panel de marcadores farmacogeneticos con 36 SNPs, para estudiar la asociacion con la tasa de respuesta, supervivencia y toxicidades en pacientes de CECC localmente avanzado. Se realizo un estudio prospectivo en 110 pacientes, (edad media 58,6 anos, 89% hombres), a cada paciente se le extrajo sangre periferica para la extraer el ADN y los SNPs fueron analizados mediante la tecnologia MassARRAY® iPLEX Gold (Sequenom®) Nuestros resultados sugieren que los polimorfismos en los genes ABCB1 C3435T y ERCC2 (Asp312Asn, Arg132Arg y Lys751Gln) pueden ser marcadores predictivos de respuesta a la quimiorradioterapia basada en platino. Alelos variantes de MMP2 y ABCC2 se asociaron con una mejor supervivencia libre de progresion. La interaccion gen-gen y analisis de haplotipos mostro mas informacion acerca de la tasa de respuesta al tratamiento que el analisis individual. No se encontraron asociaciones con polimorfismos implicados en la via de reparacion por escision de bases. Varios SNPs individuales que participan en el flujo/eflujo de farmacos, el metabolismo, la detoxicacion y la reparacion de los danos del ADN sugieren mayor riesgo de toxicidad. El numero de pacientes en el estudio fue relativamente bajo y ninguno de los SNPs analizados supero la correccion de Bonferroni, lo que no nos permite sacar conclusiones firmes. La inclusion de los estudios farmacogeneticos en los ensayos de cancer de cabeza y cuello podrian ayudar a personalizar el tratamiento y optimizar la evolucion del paciente.
The Star Formation Relation in Nearby Galaxies

Abstract I review observational studies of the large-scale star formation process in nearby galaxies. A wealth of new multi-wavelength data provide an unprecedented view on the interplay of the interstellar medium and (young) stellar populations on a few hundred parsec scale in 100+ galaxies of all types. These observations enable us to relate detailed studies of star formation in the Milky Way to the zoo of galaxies in the distant universe. Within the disks of spiral galaxies, recent star formation strongly scales with the local amount of molecular gas (as traced by CO) with a molecular gas depletion time of ∼2 Gyr. This is consistent with the picture that stars form in giant molecular clouds that have about universal properties. Galaxy centers and star-bursting galaxies deviate from this normal trend as they show enhanced star formation per unit gas mass suggesting systematic changes in the molecular gas properties and especially the dense gas fraction. In the outer disks of spirals and in dwarf galaxies, the decreasing availability of atomic gas inevitably limits the amount of star formation, though with large local variations. The critical step for the gas-stars cycle seems therefore to be the formation of a molecular gas phase, a process that shows complex dependencies on various environmental properties and is being investigated by intensive simulational work.
Interactions between drebrin and Ras regulate dendritic spine plasticity

Dendritic spines are major sites of morphological plasticity in the CNS, but the molecular mechanisms that regulate their dynamics remain poorly understood. Here we show that the association of drebrin with actin filaments plays a major role in regulating dendritic spine stability and plasticity. Overexpressing drebrin or the internal actin‐binding site of drebrin in rat hippocampal neurons destabilized mature dendritic spines so that they lost synaptic contacts and came to resemble immature dendritic filopodia. Drebrin‐induced spine destabilization was dependent on Ras activation: expression of constitutively active Ras destabilized spine morphology whereas drebrin‐induced spine destabilization was rescued by co‐expressing dominant negative Ras. Conversely, RNAi‐mediated drebrin knockdown prevented Ras‐induced destabilization and promoted spine maturation in developing neurons. Together these data demonstrate a novel mechanism in which the balance between stability and plasticity in dendritic spines depends on binding of drebrin to actin filaments in a manner that is regulated by Ras.
Swiveling and decatenation of replicating simian virus 40 genomes in vivo

We have found that type II topoisomerase inhibitors have two effects on replicating simian virus 40 genomes in vivo: production of catenated dimers and slowed replication of the last 5% of the genome. This suggests that type II topoisomerase simultaneously decatenates and facilitates replication fork movement at this stage of DNA replication. On the basis of this observation, a detailed model is proposed for the roles of topoisomerases I and II in simian virus 40 DNA replication.
Revisión sistemática de literatura. Declinación funcional en ancianos hospitalizados

Los ancianos requieren con frecuencia admision hospitalaria, durante la cual se generan riesgos para desarrollar eventos adversos, que en ocasiones no se relacionan con las caracteristicas del anciano ni la enfermedad aguda, sino con tratamientos medicos, el ambiente y las rutinas de cuidado hospitalario. Los ancianos con enfermedad aguda son un grupo heterogeneo y vulnerable debido a multiples compromisos en las esferas biopsicosociales como disminucion de la reserva funcional, comorbilidad, polifarmacia, alteraciones cognoscitivas, compromiso funcional y alteraciones en las esferas social y familiar. Estas caracteristicas ubican al anciano en riesgo para desarrollar durante la hospitalizacion declinacion funcional, por lo cual se debe realizar identificacion oportuna de los factores de riesgo con el objetivo de prevenir y manejar esta condicion mediante un equipo interdisciplinario. La implementacion de modelos de atencion que prevengan y mejoren el compromiso funcional deber ser una prioridad para las instituciones y personal de salud que atienden ancianos. Estos modelos incluyen revision del manejo farmacologico, rehabilitacion interdisciplinaria temprana, programas de ejercicio y diseno del egreso geriatrico planeado.
Inhibition of Aminoglycoside Acetyltransferase Resistance Enzymes by Metal Salts

ABSTRACT Aminoglycosides (AGs) are clinically relevant antibiotics used to treat infections caused by both Gram-negative and Gram-positive bacteria, as well as Mycobacteria. As with all current antibacterial agents, resistance to AGs is an increasing problem. The most common mechanism of resistance to AGs is the presence of AG-modifying enzymes (AMEs) in bacterial cells, with AG acetyltransferases (AACs) being the most prevalent. Recently, it was discovered that Zn2+ metal ions displayed an inhibitory effect on the resistance enzyme AAC(6′)-Ib in Acinetobacter baumannii and Escherichia coli. In this study, we explore a wide array of metal salts (Mg2+, Cr3+, Cr6+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, and Au3+ with different counter ions) and their inhibitory effect on a large repertoire of AACs [AAC(2′)-Ic, AAC(3)-Ia, AAC(3)-Ib, AAC(3)-IV, AAC(6′)-Ib′, AAC(6′)-Ie, AAC(6′)-IId, and Eis]. In addition, we determine the MIC values for amikacin and tobramycin in combination with a zinc pyrithione complex in clinical isolates of various bacterial strains (two strains of A. baumannii, three of Enterobacter cloacae, and four of Klebsiella pneumoniae) and one representative of each species purchased from the American Type Culture Collection.
In Vitro Susceptibility Testing of Borrelia burgdorferi Sensu Lato Isolates Cultured from Patients with Erythema Migrans before and after Antimicrobial Chemotherapy

ABSTRACT Clinical treatment failures have been reported to occur in early Lyme borreliosis (LB) for many suitable antimicrobial agents. Investigations of possible resistance mechanisms of the Borrelia burgdorferi complex must analyze clinical isolates obtained from LB patients, despite their receiving antibiotic treatment. Here, borrelial isolates obtained from five patients with erythema migrans (EM) before the start of antibiotic therapy and again after the conclusion of treatment were investigated. The 10 isolates were characterized by restriction fragment length polymorphism analysis and plasmid profile analysis and subjected to susceptibility testing against a variety of antimicrobial agents including those used for initial chemotherapy. Four out of five patients were infected by the same genospecies (Borrelia afzelii, n = 3; Borrelia garinii, n = 1) at the site of the EM lesion before and after antimicrobial therapy. In one patient the genospecies of the initial isolate (B. afzelii) differed from that of the follow-up isolate (B. garinii). No significant changes in the in vitro susceptibilities became obvious for corresponding clinical isolates before the start and after the conclusion of antimicrobial therapy. This holds true for the antimicrobial agents used for specific chemotherapy of the patients, as well as for any of the additional agents tested in vitro. Our study substantiates borrelial persistence in some EM patients at the site of the infectious lesion despite antibiotic treatment over a reasonable time period. Borrelial persistence, however, was not caused by increasing MICs or minimal borreliacidal concentrations in these isolates. Therefore, resistance mechanisms other than acquired resistance to antimicrobial agents should be considered in patients with LB resistant to treatment.
Under Pressure: Homeopathy UK and Its Detractors

Though homeopathy has been in successful and continuous use for well over 200 years, in the United Kingdom it is under growing pressure, from scientific detractors and sections of the media. As such, homeopathy’s free National Health Service provision is threatened because it is derided as ‘unproven’, ‘unscientific’, and even ‘deadly’. While refuting these and other detractions, this paper considers possible reasons for the current plight of homeopathy UK. Thus, the current attacks against homeopathy should be viewed more in the context of the globalised pharmaceutical industry which is itself in crisis, and a succession of UK governments seemingly supine in the face of legislation originating from the European Union.
The role of immunohistochemistry for smooth-muscle actin, p63, CD10 and cytokeratin 14 in the differential diagnosis of papillary lesions of the breast

Background: Histological differentiation of mammary papillary lesions can be difficult. The evaluation of myoepithelial cells can be helpful, with benign papilloma showing a continuous myoepithelial cell layer, which becomes attenuated or absent in malignant papillary lesions. Methods: A large series of 100 papillomas (28 papillomas with florid epithelial hyperplasia) and 68 papillary carcinomas (9 invasive, 44 in situ, and 15 ductal carcinomas in situ (DCIS) involving papillomas) of the breast were stained for myoepithelial cells by immunohistochemistry using antibodies to smooth-muscle actin (SMA), p63, CD10 and cytokeratin (CK) 14. Results: In the papillomas, using these four antibodies, myoepithelial cells were positive in 88%, 99%, 91% and 95% of cases, respectively, with SMA showing marked stromal component cell staining and CD10 showing epithelial and stromal staining. CK14 also showed epithelial staining in 71% of papillomas and 96% of papillomas with florid epithelial hyperplasia. In the papillary carcinomas, 36 (53%) cases showed staining of myoepithelial cells that were scattered, discontinuous and diminished in number and the remaining 32 (47%) cases did not show myoepithelial cells. Invasive papillary carcinoma has the lowest proportion (33%) with myoepithelial cells, and DCIS involving papillomas had the highest proportion (87%). Conclusions: p63 had the highest sensitivity and did not cross-react with stromal cells and only rarely with epithelial cells. CK14 has the added ability to distinguish between florid epithelial hyperplasia involving papilloma and DCIS involving papillomas. CK14 and p63 may be used as an adjunct in assessing difficult papillary lesions of the breast.
Taxonomy in a changing world: seeking solutions for a science in crisis.

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Nucleic Acid Therapeutics for Hematologic Malignancies—Theoretical Considerations

Abstract: Our work is motivated by the belief that RNA targeted gene silencing agents can be developed into effective drugs for treating hematologic malignancies. In many experimental systems, antisense nucleic acids of various composition, including antisense oligodeoxynucleotides (AS ODNs) and short interfering RNA (siRNA), have been shown to perturb gene expression in a sequence specific manner. Nevertheless, our clinical experience, and those of others, have led us to conclude that the antisense nucleic acids (ASNAs) we, and others, employ need to be optimized with regard to intracellular delivery, targeting, chemical composition, and efficiency of mRNA destruction. We have hypothesized that addressing these critical issues will lead to the development of practical and effective nucleic acid drugs. An overview of our recent work which seeks to addresses these core issues is contained within this review.
Biochemical and pharmacological effects of the direct thrombin inhibitor AR-H067637

Summary AZD0837 is in development as a new oral anticoagulant for use in thromboembolic disorders. In vivo, AZD0837 is converted to AR-H067637, a selective and reversible direct thrombin inhibitor. Established biochemical methods were used to assess and measure the biochemical and pharmacological properties of AR-H067637. Both direct Biacore binding studies of AR-H067637 with immobilised α-thrombin and inhibition studies using pre-steady state kinetics with thrombin in the fluid phase confirmed that AR-H067637 is a rapid-binding, reversible and potent (inhibition constant K i = 2–4 nM), competitive inhibitor of thrombin, as well as of thrombin bound to fibrin (clot-bound thrombin) or to thrombomodulin. The total amount of free thrombin generated in platelet-poor clotting plasma was inhibited concentration-dependently by AR-H067637, with a concentration giving half maximal inhibition (IC50) of 0.6 μM. Moreover, AR-H067637 is, with the exception of trypsin, a se-lective inhibitor for thrombin without inhibiting other serine proteases involved in haemostasis. Furthermore, no anticoagulant effect of the prodrug was found. AR-H067637 prolonged the clotting time concentration-dependently in a range of plasma coagulation assays including activated partial thromboplastin time, prothrombin time, prothrombinase-induced clotting time, thrombin time and ecarin clotting time. The two latter assays were found to be most sensitive for assessing the anticoagulant effect of AR-H067637 (plasma IC50 93 and 220 nM, respectively). AR-H067637 also inhibited thrombin-induced platelet activation (by glycoprotein IIb/IIIa exposure, IC50 8.4 nM) and aggregation (IC50 0.9 nM). In conclusion, AR-H067637 is a selective, reversible, competitive inhibitor of α-thrombin, with a predictable anticoagulant effect demonstrated in plasma coagulation assays.
Design of planar antenna using micro strip feed for biomedical applications 

A compact 3D stacked patch antenna is presented for microwave head imaging application. Stacked patch technique is utilized to achieve unidirectional radiation pattern and folding technique is used to achieve resonance at lower frequency that are the requirements for imaging system. Shorting wall is introduced to minimize the overall antenna structure. The proposed antenna resonance frequency is 2.65– 2.91 GHz with an average gain of 6.6 dBi at 2.7 GHz. The dimension of the antenna is 25 × 25 × 10.5 mm 3 . The operating frequency of the proposed antenna is suitable for human brain imaging. The sensor characteristic of the proposed antenna is affiliated via connection with the imaging entity, miniaturized dimension and high radiation efficiency. Raster scanning is deployed to achieve the 2D image of the target phantom and it is shown that the proposed highly directional antenna can detect tumor inside the human brain phantom.