Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacodynamics of a New Cephalosporin, PPI-0903 (TAK-599), Active against Methicillin-Resistant Staphylococcus aureus in Murine Thigh and Lung Infection Models: Identification of an In Vivo Pharmacokinetic-Pharmacodynamic Target

ABSTRACT PPI-0903 is a new cephalosporin with broad-spectrum activity, including beta-lactam-resistant Streptococcus pneumoniae and Staphylococcus aureus. We used the neutropenic murine thigh and lung infection models to examine the pharmacodynamic characteristics of PPI-0903. Serum drug levels following four fourfold-escalating single doses of PPI-0903 were measured by microbiologic assay. In vivo postantibiotic effects (PAEs) were determined after doses of 1.56, 6.25, 25, and 100 mg/kg of body weight in mice infected with S. pneumoniae ATCC 10813, S. aureus ATCC 29213, or Escherichia coli ATCC 25922. Dose fractionation studies over a 24-h dose range of 0.39 to 1,600 mg/kg were administered every 3, 6, 12, or 24 hours. Nonlinear regression analysis was used to determine which pharmacokinetic-pharmacodynamic (PK-PD) index (total and free 65% drug) best correlated with CFU/thigh at 24 h. Similar to other beta-lactam antibiotics, PPI-0903 produced short to modest in vivo PAEs with either S. pneumoniae or E. coli. The percent time that serum concentrations were above the MIC (%T>MIC) was the PK-PD index that best correlated with efficacy (R2 = 84 to 88% for the three organisms, compared with 9 to 41% for peak/MIC and 30 to 82% for the area under the concentration-time curve/MIC). In subsequent studies we used the neutropenic murine thigh infection model to determine if the magnitude of the free-drug %T>MIC needed for efficacy of PPI-0903 varied among pathogens (including resistant strains). Mice infected with one of five isolates of S. pneumoniae, four isolates of S. aureus, or four gram-negative bacilli were treated for 24 h with 0.10 to 400 mg/kg of PPI-0903 every 6 h. A sigmoid dose-response model was used to estimate the doses (mg/kg/24 h) required to achieve a net bacteriostatic affect over 24 h and to produce a reduction in the burden of organisms from the start of therapy by 1 and 2 log10 CFU/thigh. MICs ranged from 0.008 to 1 μg/ml. Mean free-drug %T>MICs ± the standard deviation associated with the static effect endpoint for S. pneumoniae, S. aureus, and gram-negative isolates were 39 ± 9, 26 ± 8, and 32 ± 6, respectively. Methicillin and penicillin resistance did not alter the magnitude of free-drug %T>MIC required for efficacy. The free-drug %T>MIC necessary for efficacy was slightly reduced in animals with normal neutrophil counts. Treatment effect was similar in both the thigh and lung infection models. The pharmacodynamic characteristics of PPI-0903 are similar to those of other compounds within the cephalosporin class.
ATIVAÇÃO SELETIVA DO VASTO MEDIAL POR MEIO DA CINESIOTERAPIA ATIVA Selective activation of vastus medialis in active kinesiotherapy

A proposta deste estudo foi realizar uma revisao bibliografica do musculo vasto medial – VM –, com o objetivo de verificar se existe evidencia cientifica da ativacao seletiva do VM utilizando-se o movimento ativo. Foi feito um estudo de revisao da hipotese de o VM ser responsavel pela extensao terminal do joelho para depois ser concluido que a real funcao do VM e a medializacao da patela. A maioria dos trabalhos revisados tentou validar, por meio de estudos eletromiograficos – EMG –, a ideia corrente do recrutamento seletivo do VM em diferentes situacoes, variando: o tipo de cadeia cinetica – aberta ou fechada; o movimento utilizado; os ângulos do movimento; o tipo de contracao – isometrica, isotonica concentrica e excentrica e isocinetica; o uso do Biofeedback associado ao movimento ativo e o uso do Tapping medializando a patela. Alem disso, foi comparada a atividade do VM em individuos com e sem a “Sindrome da dor femoro-patelar” – SDFP. A maioria dos autores nao encontrou, em nenhuma dessas situacoes, uma atividade preferencial do VM. Conclui-se que nao foi evidenciada a recuperacao seletiva do VM utilizando-se o movimento ativo voluntario.
Mise en évidence et impact de la modulation des jonctions GAP des cellules gliales dans la muqueuse olfactive par l'Endothéline

Le systeme nerveux central repose sur deux reseaux cellulaires partenaires : le reseau neuronal et le reseau de cellules gliales. Longtemps considerees comme simple support structural du systeme nerveux, il est desormais demontre que les cellules gliales sont des acteurs a part entiere dans les processus de communication neuronaux. Parallelement, alors que les neurones olfactifs ont ete largement etudiees, le role des cellules gliales de la muqueuse olfactive reste peu connu. En effet, s'il est desormais bien etabli que les cellules de soutien contribuent a maintenir la structure et l'equilibre ionique de la muqueuse et que les cellules engainantes assurent la protection et le guidage des axones vers le bulbe olfactif, une implication de ces cellules dans le traitement de l'information sensorielle reste a demontrer. Au cours de ma these, en me basant sur des approches d'imagerie calcique et d'electrophysiologie, j'ai pu montrer que les cellules gliales de la muqueuse olfactive fonctionnent en reseau relies par jonctions GAP. Parmi les potentiels modulateurs locaux, j'ai caracterise les reponses de l'endotheline dans la muqueuse olfactive et montre qu'elle entrainait des effets similaires a des applications de carbenoxolone (agent pharmacologique et decouplant les jonctions GAP). De plus, en utilisant des approches comportementales et electrophysiologiques, j'ai pu montrer que la modulation de l'etat d'ouverture de ces jonctions GAP module l'activite neuronale. Mes travaux s'inscrivent donc dans la demonstration de l'implication et de l'importance des cellules gliales (SCs et OECs) dans le fonctionnement d'un systeme nerveux peripherique comme cela est deja desormais bien admis dans le systeme nerveux central.
Human motion recognition employing infrared radiation camera images

This paper proposes a method of motion recognition in real night environment employing an infrared radiation camera. We record a video employing an infrared radiation camera to perform motion recognition at night. We use Directional Motion History Images (DMHIs) and Directional Motion Energy Images (DMEIs) for human motion representation. For the recognition of the motions, we employ the eigenspace method. In the experiment, it was confirmed that the human motion recognition at night is possible.
An ADD-based algorithm for shortest path back-tracing of large graphs

Symbolic computation techniques play a fundamental role in logic synthesis and formal hardware verification algorithms. Recently, Algebraic Decision Diagrams, i.e., BDDs with a set of constant values different to the set /spl lcub/0,1/spl rcub/, have been used to solve general purpose problems, such as matrix multiplication, shortest path calculation, and solution of linear systems, as well as logic synthesis and formal verification problems, such as timing analysis, probabilistic analysis of finite state machines, and state space decomposition for approximate finite state machine traversal. ADD-based procedures for single-source and all-pairs shortest path weight calculation have appeared to be very effective for the manipulation of large graphs (over 10/sup 27/ vertices and 10/sup 36/ edges). However, for those procedures to be applicable to real problems, for example flow network problems, computing only shortest path weights is not enough; what it is needed is an algorithm that, given the weight of a shortest path between two vertices of a graph, actually determines the sequence of vertices belonging to the shortest path. This paper proposes a symbolic algorithm to execute shortest path back-tracing which exploits the compactness of the ADD data structure to handle large graphs. <<ETX>>
BUMPLESS TRANSFER AND FADING MEMORY FOR ADAPTIVE SWITCHING CONTROL

This dissertation mainly focuses on implementation techniques for adaptive switching control. Adaptive switching control can generate bad transients in controller output. These bad transients can be reduced by various bumpless transfer techniques. A new bumpless transfer technique is developed based on slow-fast controller decomposition. This technique is especially well-suited to situations in which the plant model is poor or yet to be identified, as may be the case in adaptive switching control. A new cost function with fading memory and a finite-duration time-window is introduced in order to reduce the effect of old data in unfalsified adaptive control applications where the plant varies slowly or infrequently with time. The effectiveness of the approach is demonstrated via a simple simulation. The result demonstrates that a time-windowed/fading-memory cost function for unfalsified control is useful for adaptive control system with time-varying plants, even when the plant fails to satisfy the usual ’feasibility’ requirement of unfalsified control that it must be stabilizable by at least one of the candidate controllers.
Emergence of the four layer dynamical regime in turbulent pipe flow

Direct numerical simulations of fully developed turbulent pipe flow that span the Reynolds number range 90 ≲ δ+ ≲ 1000 are used to investigate the evolution of the mean momentum field in and beyond the transitional regime. It is estimated that the four layer regime for pipe flow is nominally established for δ+ ⩾ 180, which is also close to the value found for channel flow. Primary attention is paid to the magnitude ordering and scaling behaviors of the terms in the mean momentum equation. Once the ordering underlying the existence of four distinct balance layers is attained, this ordering is sustained for all subsequent increases in Reynolds number. Comparisons indicate that pipe flow develops toward the four layer regime in a manner similar to that for channel flow, but distinct from that for the boundary layer. Small but discernible differences are observed in the mean momentum field development in pipes and channels. These are tentatively attributed to variations in the manner by which the outer region.
Cefpodoxime 10 μg disc screening test for detection of Neisseria gonorrhoeae with mosaic PBP2 and decreased susceptibility to extended‐spectrum cephalosporins for public health purposes

Limnios A, Tapsall J, Kahlmeter J, Hogan T, Ray S, Lam A, Unemo M. Cefpodoxime 10 μg disc screening test for detection of Neisseria gonorrhoeae with mosaic PBP2 and decreased susceptibility to extended‐spectrum cephalosporins for public health purposes. APMIS 2011; 119: 356–63.
Cholesterol depletion with physiological concentrations of a statin decreases the formation of the Alzheimer amyloid Abeta peptide.

Epidemiological studies have demonstrated that hypercholsterolemia is a significant risk factor for Alzheimer's disease (AD). The mechanism by which increased cholesterol may contribute to AD is unknown. However, as the generation and accumulation of the amyloid Abeta peptide in the brain appears to be significant for the initiation and progression of AD, it is possible that cholesterol levels can regulate Abeta formation and/or clearance. To test the effects of altering cholesterol on Abeta formation, we incubated cells in the presence of lipid depleted serum, with or without the active metabolite of the HMG-CoA reductase inhibitor lovastatin. After confirming that cholesterol was depleted in the cells, we then measured the fraction of Abeta formed from its precursor betaPP under each condition. We observed that cholesterol depletion led to a profound decrease in the levels of Abeta released from the cells. This effect of lovastatin acid was observed at concentrations of 0.05-5 &mgr;M, ranges where this compound is effective at inhibiting HMG-CoA reductase, thereby inhibiting cholesterol synthesis. In contrast, the release of an additional AbetaPP fragment, AbetaPPs, was only modestly reduced by cholesterol treatment. In further studies, we determined that the decreased release of Abeta was not due to its accumulation in the cell, but rather due to decreased formation of Abeta. Finally, we were able to exclude decreased maturation (glycosylation and sulfation) of newly synthesized AbetaPP as a cause for the effects of lovastatin acid on betaPP processing and Abeta formation. Our results demonstrate that reducing cellular cholesterol by the use of an HMG-CoA reductase inhibitor regulates Abeta formation. This effect may involve alterations in the trafficking of AbetaPP and/or alterations in the activity of the proteases that cleave AbetaPP. The results suggest a mechanism by which hypercholesterolemia may increase risk for AD and indicate that reduction in cholesterol may delay the onset and/or slow the progression of AD.
Sistemas conexionistas en el procesado de señales biomédicas

En este trabajo se analiza la aplicacion de tecnicas de Sistemas Conexionistas en el procesado de senales biomedicas. En este campo establecer un diagnostico correcto es tan importante como realizarlo con tiempo suficiente para permitir un tratamiento eficaz. En consecuencia, el personal medico puede encontrar en las herramientas de prediccion del estado del paciente una ayuda valiosa para su trabajo. En estos sistemas normalmente es prioritaria la exactitud de la prediccion, por encima de la extension temporal de la misma. En particular estas tecnicas consisten en una serie de pasos comunes: - Procesado previo de la senal: adaptacion de la senal a los requisitos de entrada del sistema, como los valores limite, las frecuencias de corte y de muestreo, etc. - Entrenamiento del Sistema Conexionista utilizando un conjunto de patrones de entrenamiento generados a partir de las senales recogidas previamente. - Presentacion de una ventana temporal de la senal a la entrada del sistema. - Obtencion de la prediccion de la senal a la salida del sistema. Con el fin de comprobar la adecuacion de estas tecnicas se ha desarrollado una aplicacion basada en Redes de Neuronas Artificiales para la prediccion de la frecuencia cardiaca de pacientes ingresados en Unidades de Cuidados Intensivos. En este caso se utiliza una red de neuronas tipo FeedForward con un esquema de aprendizaje por retropropagacion del error, una capa oculta y 23 elementos de procesado en cada capa. El procesado previo de la senal consiste en un filtrado en frecuencia. En el caso practico desarrollado se han obtenido resultados adecuados con un sistema relativamente simple. Se esperan obtener resultados mas precisos utilizando otro tipo de redes (con retardos temporales, por ejemplo). En trabajos futuros se contemplara la posibilidad de ampliar el numero de patrones de entrenamiento, y generalizar el sistema al uso de otras senales distintas a la de la frecuencia cardiaca.
Human endothelial cells synthesize and release ADAMTS‐13

Summary. Hepatic stellate cells have been considered to be a primary source for human plasma ADAMTS‐13, the von Willebrand factor (VWF)‐cleaving metalloprotease. In this study, ADAMTS‐13 antigen was detected by immunofluorescence in both venous (HUVECs) and arterial endothelial cells (HUAECs) using both polyclonal antibodies made against peptides found in various domains of human ADAMTS‐13, as well as by a monoclonal antibody against the ADAMTS‐13 metalloprotease domain. ADAMTS‐13 antigen had an intra‐cellular distribution in endothelial cells distinct from the Weibel–Palade body location of VWF, and was released from the cells during 48 h in culture. The mRNA for ADAMTS13 was detected in HUVECs and HUAECs using reverse transcription‐polymerase chain reaction (RT‐PCR), indicating that the enzyme is synthesized in these cells. The ADAMTS‐13 protein was immunoprecipitated from HUVECs and had an approximate Mr of 170 kDa, similar to the molecular mass of recombinant ADAMTS‐13. The ADAMTS‐13 in HUVEC and HUAEC lysates had enzymatic activity using both static and flow assays. We conclude that ADAMTS‐13 is synthesized in human endothelial cells, and released constitutively. The vast number of endothelial cells in the body may be an important source of ADAMTS‐13.
Aktuelle Standards und neue Technologien in heterogenen Workstation-Netzen

Prof. Dr. Alexander Schill, Lehrstuhlinhaber „Rechnemetze" und Institutsdirektor an der TU Dresden. Studium der Informatik an der Universität Karlsruhe 1982-S6, Promotion und HabiUtation zu verteilten Systemen in Karlsruhe, 1989 bzw. 1993. Forschungsaufenthalt am IBM T. J. Watson Research Center, Yorktown Heights, New York, 1990-91. Forschungsschwerpunkte: Rechnernetze, verteilte Systeme, Anwendungsunterstützung für Hochleistungsund Mobilnetze.
A decreased production of IL12 in vitro is associated with isolation of cytopathic HIV‐1 strains in HIV‐1‐infected patients

The changes in type 1 (IL12, IFNγ, IL2) and type 2 (IL4, IL10) cytokine profiles may be associated with virological parameters of progression of the disease in HIV‐1‐infected patients. The production of cytokines was studied in LPS + PHA‐activated whole‐blood culture in HIV‐1‐infected individuals at different stages of the disease. The association was investigated between IL12p40 and IL12p70 profiles and other cytokines (IFNγ, IL4, IL10), as well as the isolation of cytopathogenic HIV‐1 strains. The phenotype of HIV strains was studied by a micromethod based on P4 cell line, allowing detection of cytopathic effects of HIV‐1 isolates (syncytium‐induction and cell‐killing without syncytium induction). The individual variations in IL12p40 and IL12p70 production were limited in the healthy controls. Low values were observed in HIV‐1‐infected patients. The production of IL12 (p40 and p70) and the IL12p70/IL4 ratio and the IFNγ/IL4 ratio were significantly lower in patients with cytopathic isolates compared with patients with noncytopathic isolates, and a correlation was obtained between the values of IL12 (IL12p40 and IL12p70) and those of IFNγ/IL4 ratio. There was no increase in the secretion of IL4 and IL10 in patients with cytopathic strains compared with other patients. The results indicate a decreased production of type 1 cytokines (IL12, IFNγ) in the presence of a relatively preserved production of type 2 cytokines (IL4, IL10) in HIV‐1‐infected patients. In conclusion, the defect of production of IL12 by whole blood is associated with virological correlates of progression of HIV‐1 disease. J. Med. Virol. 55:209–214, 1998. © 1998 Wiley‐Liss, Inc.
Suggestive Linkage of the Parathyroid Receptor Type 1 to Osteoporosis

We have investigated the role of 23 candidate genes in the control of bone mineral density (BMD) by linkage studies in families of probands with osteoporosis (lumbar spine [LS] or femoral neck [FN] BMD T score < −2.5) and low BMD relative to an age‐ and gender‐matched cohort (Z score < −2.0). One hundred and fifteen probands (35 male, 80 female) and 499 of their first‐ or second‐degree relatives (223 males and 276 females) were recruited for the study. BMD was measured at the LS and FN using dual‐energy X‐ray absorptiometry and expressed as age‐ and gender‐matched Z scores corrected for body mass index. The candidate genes studied were the androgen receptor, type I collagen A1 (COLIA1), COLIA2, COLIIA1, vitamin D receptor (VDR), colony‐stimulating factor 1, calcium‐sensing receptor, epidermal growth factor (EGF), estrogen receptor 1 (ESR1), fibrillin type 1, insulin‐like growth factor 1, interleukin‐1 alpha (IL‐1α), interleukin‐4 (IL‐4), interleukin‐6 (IL‐6), interleukin‐11 (IL‐11), osteopontin, parathyroid hormone (PTH), PTH‐related peptide, PTH receptor type 1 (PTHR1), transforming growth factor‐beta 1, and tumor necrosis factors alpha and beta. Sixty‐four microsatellites lying close to or within these genes were investigated for linkage with BMD. Using the program MapMaker/Sibs there was suggestive evidence of linkage between BMD and PTHR1 (maximum LOD score obtained [MLS] 2.7–3.5). Moderate evidence of linkage was also observed with EGF (MLS 1.8), COLIA1 (MLS 1.7), COLIIA1/VDR (MLS 1.7), ESR1 (MLS 1.4), IL‐1α (MLS 1.4), IL‐4 (MLS 1.2), and IL‐6 (MLS 1.2). Variance components analysis using the program ACT, correcting for proband‐wise ascertainment, also showed evidence of linkage (p ≤ 0.05) at markers close to or within the candidate genes IL‐1α, PTHR1, IL‐6, and COLIIA1/VDR. Further studies will be required to confirm these findings, to refine the location of gene responsible for the observed linkage, and to screen the candidate genes targeted at these loci for mutations.
Host resistance to visceral leishmaniasis: prevalence and prevention

ABSTRACT Visceral leishmaniasis (VL) is a chronic parasitic disease caused by the vector-borne Leishmania donovani and Leishmania (L.) infantum chagasi parasites. The disease affects about 12 million humans in more than 90 countries worldwide. If not treated, the visceral form of Leishmania infection is potentially fatal, yielding about 50000 deaths per year. In the vertebrate host, the Leishmania species causing VL spread systematically to propagate in macrophage reservoirs distributed in the tissues of internal organs, primarily the liver, spleen, bone marrow and the lymph nodes. The infection is associated with evolved mechanisms from the parasite to subvert the host immune system in order to establish a persistent infection. Currently, efforts are being deployed to develop new anti-leishmanial therapies in VL combining immunomodulatory treatment regimens that burst the host immune responses together with leishmanicidal drugs that target the parasite growth. Discoveries in this field are discussed in this article.
Immunonutrition enhances the expression and secretion of mouse intestinal defensins

The nutrient rich lumen of the small intestine provides a favourable environment for microbial cell growth. Secretion of defensins from Paneth cells constitutes a key source of antimicrobial peptide activity in the crypt lumen.1 In addition, defensins also recruit the adaptive immune system.2,3 Chronic disease, major surgery, trauma, or malnutrition results in immune compromise and can increase the risk of infection and sepsis.4 Several clinical studies have demonstrated that patients fed an immune enhancing formula had significantly fewer infectious complications, needed less antibiotics, and had a shorter hospital stay than patients fed standard diets.5 However, the mechanism by which these formulas bolster the immune system is unclear. We hypothesised that a nutrient enriched diet bolsters the immune system by upregulating defensin expression in the jejunum and ileum, the two parts where cryptdins (mouse intestinal defensins) are highly expressed. To study the effect of an immune enhancing diet (Perative; Ross Products, Abbott Laboratories, USA) on intestinal defensin expression, …