Miracle-dz/UniFAR-FTUs huggingface dataset:
A Flow Cytometric Analysis of the Inhibition of Platelet Reactivity Due to Nitrite Reduction by Deoxygenated Erythrocytes

Nitric oxide (NO), a small gas molecule, has long been known to be a potent inhibitor of platelet function but the physiological and pathological implications of platelet inhibition by NO have not been well clarified. We recently showed that the addition of nitrite to platelet-rich plasma in the presence of erythrocytes could inhibit platelet aggregation and this inhibitory effect of nitrite + erythrocytes was enhanced by deoxygenation of erythrocytes as measured by P-selectin expression and cGMP production. In order to study the nitrite effect on platelets at different oxygen levels, we used the flow cytometric assays to detect platelet membrane surface markers upon activation. The P-selectin and activated gpIIb/IIIa expression on platelet membranes in response to ADP, collagen and thrombin stimulation was measured at various hematocrit and oxygen levels. Nitrite (0.1 to 1.0 μM) significantly decreased the percentage of these surface markers on the platelet membrane at the hematocrit values above 23% and oxygen levels lower than 49 mmHg. The inhibitory effect of nitrite was augmented by increasing hematocrit values and decreasing oxygen saturation. C-PTIO (an NO scavenger) prevented the platelet inhibition by nitrite + erythrocytes whereas the inhibitors of NO synthase and xanthine oxidoreductase had no effect. These results support the proposal that circulating nitrite decreases platelet reactivity in the presence of partially deoxygenated erythrocytes through its reduction to NO, which may also explain certain differences between arterial and venous thrombosis and support directly the role of deoxyhemoglobin in this process. We believe that our flow cytometric assays offer a possibility to identify the individual molecular process involved in these effects.
Planejamento estratégico em pequenas empresas

O presente artigo tem por objetivo elaborar um planejamento estrategico para um escritorio de arquitetura. Afinal as empresas estao inseridas em um mercado cada vez mais competitivo, global, sujeitas a riscos e incertezas a qualquer momento, tudo isso em decorrencia a grande velocidade das mudancas, porem uma empresa com um bom planejamento consegue identificar essas dificuldades antes que elas possam influenciar no rendimento da empresa, tornando-a assim mais competitiva. Realizou-se uma entrevista com o proprietario e questionarios para os colaboradores e alguns clientes, ou seja, serao utilizadas as abordagens qualitativa e quantitativa. Tera uma pesquisa bibliografica onde serao exposto conceitos de estrategia ate plano de acao e a descritiva exploratoria. Por fim, apos analisar os pontos fracos e fortes, as ameacas e oportunidades atraves da Matriz SWOT, foi aplicado o plano de acao 5W2H a fim de minimizar os pontos fracos e ameacas e maximizar os pontos fortes e oportunidades.
Apolipoprotein E4 polymorphism as a genetic predisposition to delirium in critically ill patients*

Objective: To test for an association between apolipoprotein E (APOE) genotypes and duration of intensive care unit delirium. Design: Prospective, observational cohort study. Setting: A 541‐bed, community‐based teaching hospital. Patients: Fifty‐three mechanically ventilated intensive care unit patients. Interventions: None. Measurements and Main Results: All patients were managed with standardized sedation and ventilator weaning protocols as part of an ongoing clinical trial and were evaluated prospectively for delirium with the Confusion Assessment Method for the Intensive Care Unit (CAM‐ICU). DNA was extracted from whole blood samples obtained on enrollment, and APOE genotype was determined using polymerase chain reaction followed by restriction enzyme digestion by investigators blinded to the clinical information. Delirium occurred in 47 (89%) patients at some point during the intensive care unit stay. Of the 53 patients, 12 (23%) had an APOE4 allele (APOE4+) and 41 (77%) had only APOE2 or APOE3 alleles (APOE4−). APOE4+ patients were younger (53.2 ± 21.9 vs. 65.4 ± 13.4, p = .08) and less often admitted for pneumonia (0% vs. 29.3%, p = .05) compared with APOE4− patients, yet they had a duration of delirium that was twice as long: median (interquartile range), 4 (3, 4.5) vs. 2 (1, 4) days (p = .05). No other clinical outcomes were significantly different between the APOE4+ and APOE4− patients. Using multivariable regression analysis to adjust for age, admission diagnosis of sepsis or acute respiratory distress syndrome or pneumonia, severity of illness, and duration of coma, the presence of APOE4 allele was the strongest predictor of delirium duration (odds ratio, 7.32; 95% confidence interval, 1.82–29.51, p = .005). Conclusions: APOE4 allele represents the first demonstrated genetic predisposition to longer duration of delirium in humans.
A Unified View of the Role of Electrostatic Interactions in Modulating the Gating of Cys Loop Receptors*

In the Cys loop superfamily of ligand-gated ion channels, a global conformational change, initiated by agonist binding, results in channel opening and the passage of ions across the cell membrane. The detailed mechanism of channel gating is a subject that has lent itself to both structural and electrophysiological studies. Here we defined a gating interface that incorporates elements from the ligand binding domain and transmembrane domain previously reported as integral to proper channel gating. An overall analysis of charged residues within the gating interface across the entire superfamily showed a conserved charging pattern, although no specific interacting ion pairs were conserved. We utilized a combination of conventional mutagenesis and the high precision methodology of unnatural amino acid incorporation to study extensively the gating interface of the mouse muscle nicotinic acetylcholine receptor. We found that charge reversal, charge neutralization, and charge introduction at the gating interface are often well tolerated. Furthermore, based on our data and a reexamination of previously reported data on γ-aminobutyric acid, type A, and glycine receptors, we concluded that the overall charging pattern of the gating interface, and not any specific pairwise electrostatic interactions, controls the gating process in the Cys loop superfamily.
High-efficiency gene inactivation and replacement system for gram-positive bacteria

A system for high-efficiency single- and double-crossover homologous integration in gram-positive bacteria has been developed, with Lactococcus lactis as a model system. The system is based on a thermosensitive broad-host-range rolling-circle plasmid, pG+host5, which contains a pBR322 replicon for propagation in Escherichia coli at 37 degrees C. A nested set of L. lactis chromosomal fragments cloned onto pG+host5 were used to show that the single-crossover integration frequency was logarithmically proportional to the length of homology for DNA fragments between 0.35 and 2.5 kb. Using random chromosomal 1-kb fragments, we showed that homologous integration can occur along the entire chromosome. We made use of the reported stimulatory effect of rolling-circle replication on intramolecular recombination to develop a protocol for gene replacement. Cultures were first maintained at 37 degrees C to select for a bacterial population enriched for plasmid integrants; activation of the integrated rolling-circle plasmid by a temperature shift to 28 degrees C resulted in efficient plasmid excision by homologous recombination and replacement of a chromosomal gene by the plasmid-carried modified copy. More than 50% of cells underwent replacement recombination when selection was applied for the replacing gene. Between 1 and 40% of cells underwent replacement recombination when no selection was applied. Chromosomal insertions and deletions were obtained in this way. These results show that gene replacement can be obtained at an extremely high efficiency by making use of the thermosensitive rolling-circle nature of the delivery vector. This procedure is applicable to numerous gram-positive bacteria.
Reductive Explanation and the ‘Explanatory Gap’

Can phenomenal consciousness be given a reductive natural explanation? Exponents of an ‘explanatory gap’ between physical, functional and intentional facts, on the one hand, and the facts of phenomenal consciousness, on the other, argue that there are reasons of principle why phenomenal consciousness cannot be reductively explained: Jackson (1982), (1986); Levine (1983), (1993), (2001); McGinn (1991); Sturgeon (1994), (2000); Chalmers (1996), (1999). Some of these writers claim that the existence of such a gap would warrant a belief in some form of ontological dualism (Jackson, 1982; Chalmers, 1996), whereas others argue that no such entailment holds (Levine, 1983; McGinn, 1991; Sturgeon, 1994). In the other main camp, there are people who argue that a reductive explanation of phenomenal consciousness is possible in principle (Block and Stalnaker, 1999), and yet others who claim, moreover, to have provided such an explanation in practice (Dennett, 1991; Dretske, 1995; Tye, 1995,2000; Lycan, 1996; Carruthers, 2000).
Network controlled Device-to-Device (D2D) and cluster multicast concept for LTE and LTE-A networks

In this paper we introduce a reliable multicast concept for Device-to-Device (D2D) communication integrated into cellular network. In addition to the introduction of the basic concept, initial simulation results are presented as well. Clustering closely located devices which have local communication needs is a feasible and efficient way of solving the increasing data traffic requirements in the future cellular network. Reliable D2D multicast concept introduced in this paper is designed to be scalable and efficient solution for local communication needs such as file transfer and even streaming services. Due to the network involvement in controlling the local D2D communication, sufficient quality of service can be guaranteed. In addition, due to the flexible mode switching between direct and cellular modes in the integrated operation the service continuity can be provided.
A rare case of isolated testicular tuberculosis and review of literature

Testicular tuberculosis (TB) is a rare form of genitourinary TB. It is usually presented as painful or painless testicular swelling with or without scrotal ulceration or discharging sinus. Infertility may occur. Epididymal involvement is usually seen in testicular TB. In most cases, genital TB is associated with TB involvement of kidneys or lower urinary tract. Ultrasound (USG) and USG-guided fine needle aspiration cytology of testicular swelling confirm the diagnosis. Anti-TB chemotherapy is the mainstay of treatment to ensure the complete resolution of the lesion. However, in very few cases, orchidectomy is required for both diagnosis and treatment. Here, we report a very rare case of left sided isolated testicular TB in a 20-year-old male who was completely cured with 6 months regimen of anti-TB chemotherapy.
Least Power Point Tracking Method for Photovoltaic Differential Power Processing Systems

Differential power processing (DPP) systems are a promising architecture for future photovoltaic (PV) power systems that achieve high system efficiency through processing a faction of the full PV power, while achieving distributed local maximum power point tracking (MPPT). In the PV-to-bus DPP architecture, the power processed through the DPP converters depends on the string current, which must be controlled to minimize the power processed through the DPP converters. A real-time least power point tracking (LPPT) method is proposed to minimize power stress on PV DPP converters. Mathematical analysis shows the uniqueness of the least power point for the total power processed through the system. The perturb-and-observe LPPT method is presented that enables the DPP converters to maintain optimal operating conditions, while reducing the total power loss and converter stress. This work validates through simulation and experimentation that LPPT in the string-level converter successfully operates with MPPT in the DPP converters to maximize output power for the PV-to-bus architecture. Hardware prototypes were developed and tested at 140 and 300 W, and the LPPT control algorithm showed effective operation under steady-state operation and an irradiance step change. Peak system efficiency achieved with a 140-W prototype DPP system employing LPPT is 95.7%.
The effect of application of tourniquets to the legs on cardiac output and renal function in normal human subjects.

When blood is pooled in the lower extremities by the application of tourniquets at subdiastolic pressures to the thighs, prompt reductions occur in effective renal plasma flow (RPF), glomerular filtration rate (GFR) and renal excretion of water and electrolytes (1, 2). Similar alterations in renal function have been shown to occur in chronic congestive heart failure (3) and in head-up tilting of the normal subject (4). Since venous congestion of the lower extremities is demonstrable in all of the above situations, it has been proposed that this factor may be causally related to the functional disturbances observed in the kidney. This study represents an investigation of the pathogenesis of the changes in kidney function which occur when blood is pooled in the lower extremities by tourniquets, particularly in regard to the possible role of cardiac output.
Strong mitigation: nesting search for good policies within search for good reward

Recent work has defined an optimal reward problem (ORP) in which an agent designer, with an objective reward function that evaluates an agent's behavior, has a choice of what reward function to build into a learning or planning agent to guide its behavior. Existing results on ORP show weak mitigation of limited computational resources, i.e., the existence of reward functions so that agents when guided by them do better than when guided by the objective reward function. These existing results ignore the cost of finding such good reward functions. We define a nested optimal reward and control architecture that achieves strong mitigation of limited computational resources. We show empirically that the designer is better off using the new architecture that spends some of its limited resources learning a good reward function instead of using all of its resources to optimize its behavior with respect to the objective reward function.
Digital Technology Use Among Individuals with Schizophrenia: Results of an Online Survey

Background Despite growing interest in the use of digital technology by individuals with schizophrenia, little is known about how these individual relate to, own, and use technology in their daily life and in the context of their symptoms. Objective The goal of this study is to better characterize technology use in those with schizophrenia. Methods A Web-based survey of individuals’ use of and attitudes toward technology for those 18 years and older self-identifying as having schizophrenia, schizoaffective disorder, or schizophrenia spectrum disorders was conducted. Consumer input was sought in the design of the survey. Results In total, 457 individuals responded to this Web-based survey. Ninety percent owned more than one device (personal computer, landline telephone, tablet, public computer, mobile phone without applications or Internet, or smartphone), with many reporting high utilization of multiple devices, and 61% having 2 devices. The respondents reported that Web-based technology helped with support from family and friends, as well as in gathering information. Many respondents used Web-based technology to help identify coping strategies (24% very often or often) including music to help block or manage voices (42%), while others used technology to set alarms/reminders for medication management (28%). Younger respondents in particular anticipated the role of technology growing over time with respect to their recovery. Conclusions Survey respondents reported that technology access was common, with utilization involving coping, reminders for medications and appointments, and connection. Overall, attitudes were largely positive. Overuse was a concern for 30% of respondents. The study is limited in its generalizability as the population was highly engaged in mental health treatment (87%), self-identified as living with the disorder, and had awareness of their illness. This survey demonstrates high engagement for a subset of technology-oriented individuals living with schizophrenia. It is not known what percent of individuals with schizophrenia are represented by these technology-oriented survey respondents.
Nature of Tumor Control by Permanently and Transiently Modified GD2 Chimeric Antigen Receptor T Cells in Xenograft Models of Neuroblastoma

Singh and colleagues show that RNA-CAR T cells mediate rapid and long-term tumor destruction when delivered locally but not when delivered systemically due to the inability of RNA-CAR T cells to penetrate the tumor microenvironment. Chimeric antigen receptor (CAR) therapy has begun to demonstrate success as a novel treatment modality for hematologic malignancies. The success observed thus far has been with T cells permanently engineered to express chimeric receptors. T cells engineered using RNA electroporation represent an alternative with the potential for similar efficacy and greater safety when initially targeting novel antigens. Neuroblastoma is a common pediatric solid tumor with the potential to be targeted using immunotherapy. We performed xenograft studies in NSG mice in which we assessed the efficacy of both permanently modified and transiently modified CAR T cells directed against the neuroblastoma antigen GD2 in both local and disseminated disease models. Disease response was monitored by tumor volume measurement and histologic examination, as well as in vivo bioluminescence. RNA-modified GD2 CAR T cells mediated rapid tumor destruction when delivered locally. A single infusion of lentivirally modified GD2 CAR T cells resulted in long-term control of disseminated disease. Multiple infusions of RNA GD2 CAR T cells slowed the progression of disseminated disease and improved survival, but did not result in long-term disease control. Histologic examination revealed that the transiently modified cells were unable to significantly penetrate the tumor environment when delivered systemically, despite multiple infusions of CAR T cells. Thus, we demonstrate that RNA-modified GD2 CAR T cells can mediate effective antitumor responses in vivo, and permanently modified cells are able to control disseminated neuroblastoma in xenograft mice. Lack of long-term disease control by RNA-engineered cells resulted from an inability to penetrate the tumor microenvironment. Cancer Immunol Res; 2(11); 1059–70. ©2014 AACR.
Increased Expression of Chitinase 3-Like 1 in Aorta of Patients with Atherosclerosis and Suppression of Atherosclerosis in Apolipoprotein E-Knockout Mice by Chitinase 3-Like 1 Gene Silencing

Introduction. The purpose of this study was to investigate the changes of chitinase 3-like 1 (CHI3L1) in the aorta of patients with coronary atherosclerosis and to determine whether inhibition of CHI3L1 by lentivirus-mediated RNA interference could stabilize atherosclerotic plaques in apolipoprotein E-knockout (ApoE−/−) mice. Methods. We collected discarded aortic specimens from patients undergoing coronary artery bypass graft surgery and renal arterial tissues from kidney donors. A lentivirus carrying small interfering RNA targeting the expression of CHI3L1 was constructed. Fifty ApoE−/− mice were divided into control group and CHI3L1 gene silenced group. A constrictive collar was placed around carotid artery to induce plaques formation. Then lentivirus was transfected into carotid plaques. Results. We found that CHI3L1 was overexpressed in aorta of patients with atherosclerosis and its expression was correlated with the atherosclerotic risk factors. After lentivirus transduction, mRNA and protein expression of CHI3L1 were attenuated in carotid plaques, leading to reduced plaque content of lipids and macrophages, and increased plaque content of collagen and smooth muscle cells. Moreover, CHI3L1 gene silencing downregulated the expression of local proinflammatory mediators. Conclusions. CHI3L1 is overexpressed in aorta from patients with atherosclerosis and the lentivirus-mediated CHI3L1 gene silencing could represent a new strategy to inhibit plaques progression.
A Tethered Bilayer Assembled on Top of Immobilized Calmodulin to Mimic Cellular Compartmentalization

Background Biomimetic membrane models tethered on solid supports are important tools for membrane protein biochemistry and biotechnology. The supported membrane systems described up to now are composed of a lipid bilayer tethered or not to a surface separating two compartments: a ”trans” side, one to a few nanometer thick, located between the supporting surface and the membrane; and a “cis” side, above the synthetic membrane, exposed to the bulk medium. We describe here a novel biomimetic design composed of a tethered bilayer membrane that is assembled over a surface derivatized with a specific intracellular protein marker. This multilayered biomimetic assembly exhibits the fundamental characteristics of an authentic biological membrane in creating a continuous yet fluid phospholipidic barrier between two distinct compartments: a “cis” side corresponding to the extracellular milieu and a “trans” side marked by a key cytosolic signaling protein, calmodulin. Methodology/Principal Findings We established and validated the experimental conditions to construct a multilayered structure consisting in a planar tethered bilayer assembled over a surface derivatized with calmodulin. We demonstrated the following: (i) the grafted calmodulin molecules (in trans side) were fully functional in binding and activating a calmodulin-dependent enzyme, the adenylate cyclase from Bordetella pertussis; and (ii) the assembled bilayer formed a continuous, protein-impermeable boundary that fully separated the underlying calmodulin (trans side) from the above medium (cis side). Conclusions The simplicity and robustness of the tethered bilayer structure described here should facilitate the elaboration of biomimetic membrane models incorporating membrane embedded proteins and key cytoplasmic constituents. Such biomimetic structures will also be an attractive tool to study translocation across biological membranes of proteins or other macromolecules.
Experimental Demonstration of the Oscillatory Phenomenon Taut-Slack

In this paper a mechanism for reproducing the phenomenon known as "taut-slack" in a cable-body system is presented. The operation of the mechanism consists in forcing an oscillation of a point from which a body immersed in liquid is suspended by means of a cord. For particular values of ad-hoc design parameters of the mechanism, the body can oscillate nonlinearly mainly because the cable transits from a taut to a slack condition cyclically. Both body and suspension point positions are sensed in order to detect the periodicity of the resulting body motion. The modeling of the system dynamics yields a set of two Mathieu differential equations that are combined piecewise according to the cable taut-slack condition. The periodicity detection implemented in this work is based on the analysis of Cauchy series obtained from the Poincare maps. From the experimental results it could be obtained period doubling with the presence of the taut-slack phenomenon. Through comparison with simulated bifurcation diagrams and Poincare maps it could be noticed a good concordance between the signal profiles and also a comparable evidence of the behavior diversity