Miracle-dz/UniFAR-FTUs huggingface dataset:
Implications of Early Structural-Functional Changes in the Endothelium for Vascular Disease

By location, between the blood and tissues and the multiple functions, the endothelial cells (ECs) play a major role in securing body homeostasis. The ECs sense all variations occurring in the plasma and interstitial fluid, and respond (function of intensity), initially by modulation of their constitutive functions, then by dysfunction, expressed by temporarily altered functions and a phenotypic shift, and ultimately by injury/death. In dyslipidemia/hyperglycemia, the initial response of EC is the modulation of 2 constitutive functions: permeability and biosynthesis. Increased transcytosis of plasma &bgr;-lipoproteins leads to their accumulation within the hyperplasic basal lamina, interaction with matrix proteins, and conversion to modified and reassembled lipoproteins (MRL). This generates a multipart inflammatory process and EC dysfunction characterized by expression of new cell adhesion molecules and MCP-1 that trigger T-lymphocytes and monocyte recruitment, diapedesis, and homing within the subendothelium where activated macrophages become foam cells. The latter, together with the subendothelial accrual of MRL, growth factors, cytokines, and chemokines, and accretion of smooth muscle cells of various sources lead to atheroma formation; in advanced disease, the EC overlaying atheroma take up lipids, become EC-derived foam cells, and the cytotoxic ambient ultimately conducts to EC apoptosis. Understanding the mechanisms of EC dysfunction is a prerequisite for EC-targeted therapy to reduce the incidence of cardiovascular diseases.
Spatial Resolution and Contrast Sensitivity of Single Neurons in Area 19 of Split‐chiasm Cats: A Comparison With Primary Visual Cortex

Electrophysiological recordings were carried out in the callosal recipient zone of area 19 in normal and split‐chiasm cats and, for comparison purposes, at the border of areas 17 and 18 of split‐chiasm cats. The influences of retinothalamic and callosal inputs on a single cortical neurons were thereby evaluated. Extracellular recordings of single cells were made in anaesthetized and paralysed cats in the zone representing the central visual field. Receptive field properties were assessed using sine wave gratings drifting in optimal directions. Results showed that in area 19 and areas 17/18 one‐third of the cells were binocularly driven after section of the optic chiasm. In area 19, the spatial resolution and contrast sensitivity of cells driven via the dominant eye were similar in the normal and split‐chiasm groups. In areas 17/18 and area 19 of split‐chiasm cats, binocular cells showed significant interocular matching of their receptive field properties (spatial resolution and contrast threshold), although small differences were observed. These small interocular differences were related to the cell's Ocular dominance rather than to the signal transmission route (thalamic or callosal).
Correlation between inflammatory markers and insulin resistance in pregnancy

Abstract Gestational diabetes mellitus (GDM) is associated with an increased risk of postpartum type 2 diabetes mellitus and cardiovascular risk factors, such as obesity, hypertension, dyslipidaemia and systemic inflammation. We aimed to evaluate further lipid profile and inflammatory status assessed by high sensitive C-reactive protein (hsCRP) and TNF-α in GDM. Based on oral glucose tolerance testing, participants were stratified into three groups: normal 50 g glucose challenge test (GCT), normal 100 g glucose tolerance test (NOGTT) (control group) (n = 40); abnormal GCT NOGTT (glucose intolerance) (n = 37); and GDM (n = 39), defined by Carpenter and Coustan. The three groups did not demonstrate significantly different hsCRP levels (p = 0.4180) and lipid profile parameters, such as total cholesterol (p = 0.4210) and LDL-cholesterol (p = 0.4440) levels. Triglycerides (p = 0.0150) and atherogenic index of the plasma levels (p = 0.0280) were slightly higher in the GDM group. But, TNF-α levels increased significantly in the GDM (p < 0.0001) and in glucose intolerance (p = 0.0062) groups as compared with the control group. Among the metabolic syndrome components, insulin resistance was apparently associated with TNF-α, whereas dyslipidaemia was slightly associated with hsCRP because of the effects of maternal age on lipid markers. These findings suggest that TNF-α has a stronger correlation with pregnancy-associated insulin resistance than hsCRP at 24 to 28 weeks’ gestation.
Effective Mass Sensing Using Optomechanically Induced Transparency in Microresonator System

Detecting and weighing individual nanoparticles is an important approach to studying the behavior and properties of single particles. Here, we illustrate an effective mass sensing scheme using optomechanical resonator system. Based on the optomechanically induced transparency phenomenon, a Stokes’ field reference approach is used to sense the mass of the particle on the microresonator. The field intensity of the transmission field will be changed by the effect of the particle, which avoids the limits of decay-induced spectral width in the resonance shift detection. Exploiting the perturbation method, we theoretically evaluated the dynamical behavior of the system and achieved femtogram-level mass sensing without the need for high cavity $Q$ -value, as well as strong coupling strength in the optomechanical system.
Numerical Simulation and Optimization on Temperature Field of 600 MW Supercritical Swirl Combustion Boiler

The combustion process of low NOx axial swirl burner(LNASB) was numerically studied in a 600 MW supercritical boiler with realizable k-e model.The influence of secondary air flow and swirling intensity on the flow field and the distribution of temperature were studied.the different modification project of the burner was compared.The numerical simulation results had shown that the recirculation zone is hardly affected by the inner secondary air.The extended corner was impacted obviously by the external secondary air.Increasing the velocity of central air could enlarge the root distance of the recirculation zone.Increasing the flow and swirling intensity of the secondary air could make the flame deviation and adherence.The temperature nearby the burner nozzle increased significantly after turning off the center air.The best project is centrally fuel rich which could increase the distance between flame and nozzle.The comparison between the measured values and predicted results shows good agreement.By improving burners and adjusting combustion can settle the problem of malignant coking,it can provide some theoretical basis for the LNASB burner.
Assessing the image quality of pelvic MR images acquired with a flat couch for radiotherapy treatment planning.

OBJECTIVES To improve the integration of MRI with radiotherapy treatment planning, our department fabricated a flat couch top for our MR scanner. Setting up using this couch top meant that the patients were physically higher up in the scanner and, posteriorly, a gap was introduced between the patient and radiofrequency coil. METHODS Phantom measurements were performed to assess the quantitative impact on image quality. A phantom was set up with and without the flat couch insert in place, and measurements of image uniformity and signal to noise were made. To assess clinical impact, six patients with pelvic cancer were recruited and scanned on both couch types. The image quality of pairs of scans was assessed by two consultant radiologists. RESULTS The use of the flat couch insert led to a drop in image signal to noise of approximately 14%. Uniformity in the anteroposterior direction was affected the most, with little change in right-to-left and feet-to-head directions. All six patients were successfully scanned on the flat couch, although one patient had to be positioned with their arms by their sides. The image quality scores showed no statistically significant change between scans with and without the flat couch in place. CONCLUSION Although the quantitative performance of the coil is affected by the integration of a flat couch top, there is no discernible deterioration of diagnostic image quality, as assessed by two consultant radiologists. Although the flat couch insert moved patients higher in the bore of the scanner, all patients in the study were successfully scanned.
Anti-schistosomal Intervention Targets Identified by Lifecycle Transcriptomic Analyses

Background Novel methods to identify anthelmintic drug and vaccine targets are urgently needed, especially for those parasite species currently being controlled by singular, often limited strategies. A clearer understanding of the transcriptional components underpinning helminth development will enable identification of exploitable molecules essential for successful parasite/host interactions. Towards this end, we present a combinatorial, bioinformatics-led approach, employing both statistical and network analyses of transcriptomic data, for identifying new immunoprophylactic and therapeutic lead targets to combat schistosomiasis. Methodology/Principal Findings Utilisation of a Schistosoma mansoni oligonucleotide DNA microarray consisting of 37,632 elements enabled gene expression profiling from 15 distinct parasite lifecycle stages, spanning three unique ecological niches. Statistical approaches of data analysis revealed differential expression of 973 gene products that minimally describe the three major characteristics of schistosome development: asexual processes within intermediate snail hosts, sexual maturation within definitive vertebrate hosts and sexual dimorphism amongst adult male and female worms. Furthermore, we identified a group of 338 constitutively expressed schistosome gene products (including 41 transcripts sharing no sequence similarity outside the Platyhelminthes), which are likely to be essential for schistosome lifecycle progression. While highly informative, statistics-led bioinformatics mining of the transcriptional dataset has limitations, including the inability to identify higher order relationships between differentially expressed transcripts and lifecycle stages. Network analysis, coupled to Gene Ontology enrichment investigations, facilitated a re-examination of the dataset and identified 387 clusters (containing 12,132 gene products) displaying novel examples of developmentally regulated classes (including 294 schistosomula and/or adult transcripts with no known sequence similarity outside the Platyhelminthes), which were undetectable by the statistical comparisons. Conclusions/Significance Collectively, statistical and network-based exploratory analyses of transcriptomic datasets have led to a thorough characterisation of schistosome development. Information obtained from these experiments highlighted key transcriptional programs associated with lifecycle progression and identified numerous anti-schistosomal candidate molecules including G-protein coupled receptors, tetraspanins, Dyp-type peroxidases, fucosyltransferases, leishmanolysins and the netrin/netrin receptor complex.
Orthodontists' Perceptions of the Impact of Phase 1 Treatment for Class II Malocclusion on Phase 2 Needs

The most appropriate timing for the treatment of Class II malocclusions is controversial. Some clinicians advocate starting a first phase in the mixed dentition, followed by a phase 2 in the permanent dentition. Others see no clear advantage to that approach and recommend that the entire treatment be done in the late mixed or early permanent dentition. This study examines how orthodontists, blinded to treatment approach, perceive the impact of phase 1 treatment on phase 2 needs. The sample consisted of 242 Class II subjects, aged 10 to 15, who had completed phase 1 or observation in a randomized clinical trial (RCT). For each subject, video orthodontic records, a questionnaire, a fact sheet, and a cephalometric tracing were sent to five randomly selected reviewing orthodontists blinded to subject group and study purpose. Reviewing orthodontists were asked to assess treatment need, general approach, need for extractions, priority, difficulty, and determinants. Orthodontists agreed highly on treatment need (95%) and moderately on treatment approach (84%) and extraction need (80%). They did not perceive differences in need, approach, or extractions between treated and control groups. Treated subjects were judged as less difficult (p = 0.0001) and to have a lower treatment priority (p = 0.0001) than controls. In ranking problems that affect treatment decisions, the orthodontists ranked dental Class II (p = 0.005) and skeletal relationships (p = 0.004) more highly in control than in treated patients. These data indicate that orthodontists do not perceive phase 1 treatment for Class II as preventing the need for a second phase or as offering any particular advantage with respect to preventing the need for extractions or other skeletal treatments in that second phase. They do view early Class II treatment as an effective means of reducing the difficulty of and priority for phase 2.
Follow-up papers - Aortic and aneurysmal Long-term results of endovascular aortic repair for thoracic pseudoaneurysms after previous surgical coarctation repair

Objectives: Late aneurysm formation has been reported after every type of surgical coarctation repair in up to 10%, with rupture of such aneurysms being responsible for approximately 7% of all deaths. Secondary surgical repair carries a significant mortality (up to 15%) and morbidity rate (recurrent laryngeal nerve paralysis ~20%, phrenic nerve injury ~5%). According to the positive experience with endovascular therapy of atherosclerotic thoracic aortic aneurysms, it is worthwhile to evaluate the concept of minimally invasive endovascular stent grafting for secondary repair of postsurgical aneurysms. Methods: Data were collected prospectively on consecutive patients who presented with postcoarctation false aneurysms. Results: Since 1999, in a cohort of 210 endovascularly treated patients with thoracic and thoracoabdominal aortic pathologies, four patients with postcoarctation false aneurysms underwent endoluminal stent-graft placement. All of these procedures were technically successful without 30-day or one-year procedure-related mortality. After a follow-up of 71 months in median (range, 7–93 months; mean, 60.5 months), all aneurysms remain excluded without any endoleak. Conclusions: According to the current limited experience of small series, the endoluminal repair seems to be a promising alternative to redo open operations for postsurgical thoracic aneurysms associated with coarctation repair. Long-term follow-up of our small cohort confirmed the durability of the stent-graft treatment.  2011 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.
Repetitive traumatic brain injury, psychological symptoms, and suicide risk in a clinical sample of deployed military personnel.

IMPORTANCE Traumatic brain injury (TBI) is believed to be one factor contributing to rising suicide rates among military personnel and veterans. This study investigated the association of cumulative TBIs with suicide risk in a clinical sample of deployed military personnel referred for a TBI evaluation. OBJECTIVE To determine whether suicide risk is more frequent and heightened among military personnel with multiple lifetime TBIs than among those with no TBIs or a single TBI. DESIGN Patients completed standardized self-report measures of depression, posttraumatic stress disorder (PTSD), and suicidal thoughts and behaviors; clinical interview; and physical examination. Group comparisons of symptom scores according to number of lifetime TBIs were made, and generalized regression analyses were used to determine the association of cumulative TBIs with suicide risk. PARTICIPANTS Patients included 161 military personnel referred for evaluation and treatment of suspected head injury at a military hospital's TBI clinic in Iraq. MAIN OUTCOMES AND MEASURES Behavioral Health Measure depression subscale, PTSD Checklist-Military Version, concussion symptoms, and Suicide Behaviors Questionnaire-Revised. RESULTS Depression, PTSD, and TBI symptom severity significantly increased with the number of TBIs. An increased incidence of lifetime suicidal thoughts or behaviors was associated with the number of TBIs (no TBIs, 0%; single TBI, 6.9%; and multiple TBIs, 21.7%; P = .009), as was suicidal ideation within the past year (0%, 3.4%, and 12.0%, respectively; P = .04). The number of TBIs was associated with greater suicide risk (β [SE] = .214 [.098]; P = .03) when the effects of depression, PTSD, and TBI symptom severity were controlled for. A significant interaction between depression and cumulative TBIs was also found (β = .580 [.283]; P = .04). CONCLUSIONS AND RELEVANCE Suicide risk is higher among military personnel with more lifetime TBIs, even after controlling for clinical symptom severity. Results suggest that multiple TBIs, which are common among military personnel, may contribute to increased risk for suicide.
Toward the elimination of lymphatic filariasis by 2020: treatment update and impact assessment for the endgame

Lymphatic filariasis (LF) is an important public health problem endemic in 73 countries, where it is a major cause of acute and chronic morbidity and a significant impediment to socioeconomic development. It is targeted for elimination by 2020, through preventive chemotherapy using albendazole in combination with either ivermectin or diethylcarbamazine citrate. Preventive chemotherapy enables the regular and coordinated administration of safe, single-dose medications delivered through mass drug administration (MDA). Many countries are now scaling down MDA activities after achieving 100% geographic coverage and instituting monitoring and evaluation procedures to establish the impact of several consecutive rounds of MDA and determine if transmission has been interrupted. At the same time, countries yet to initiate MDA for elimination of LF will adopt improved mapping and coverage assessment protocols to accelerate the efforts for achieving global elimination by 2020. This review provides an update on treatment for LF and describes the current global status of the elimination efforts, transmission control processes and strategies for measuring impact and continuing surveillance after MDA has ceased.
Sequence operators: specifying behavioral interfaces of Smalltalk blocks

The ability to treat code as data within a programming language is a powerful feature. Smalltalk introduces an object called a block that represents code as data. We propose a formal description technique to specify the behavior of Smalltalk blocks. The traditional Hoare-style pre- and postcondition technique is extended to incorporate two new predicate composition operators called a sequence operator and a sequential quantifier. The sequence operator combines two predicates by identifying the post-state of the first predicate and the pre-state of the second predicate. The sequential quantifier is an extension of sequence operator to a sequence of predicates. We illustrate our approach by using Smalltalk blocks, but the approach is not in any way Smalltalk specific. It can be applied to closures in other programming languages.
Colorectal Cancer and the Relationship Between Genes and the Environment

Colorectal cancer (CRC) is a significant cause of morbidity and mortality in developed countries, with both genetic and environmental factors contributing to the etiology and progression of the disease. Several risk factors have been identified, including positive family history, red meat intake, smoking, and alcohol intake. Protective factors include vegetables, calcium, hormone replacement therapy, folate, nonsteroidal anti-inflammatory drugs, and physical activity. The interaction between these environmental factors, in particular diet and genes, is an area of growing interest. Currently, oncogenes, tumor suppressor genes, and mismatch repair genes are believed to play an essential role in colorectal carcinogenesis. When considering the genetics of CRC, only 10% of cases are inherited and only 2-6% can be ascribed to the highly penetrant genes, such as APC, hMLH1 and hMSH2. Lower penetrance genes combined with a Western-style diet contribute to the majority of sporadic CRCs. The purpose of this article is to give a brief overview of the epidemiologic studies that have been conducted and present the major findings. Here, we examine the molecular events in CRC, with particular focus on the interaction between genes and environment, and review the most current research in this area.
Leishmania donovani Exploits Host Deubiquitinating Enzyme A20, a Negative Regulator of TLR Signaling, To Subvert Host Immune Response

TLRs, which form an interface between mammalian host and microbe, play a key role in pathogen recognition and initiation of proinflammatory response thus stimulating antimicrobial activity and host survival. However, certain intracellular pathogens such as Leishmania can successfully manipulate the TLR signaling, thus hijacking the defensive strategies of the host. Despite the presence of lipophosphoglycan, a TLR2 ligand capable of eliciting host-defensive cytokine response, on the surface of Leishmania, the strategies adopted by the parasite to silence the TLR2-mediated proinflammatory response is not understood. In this study, we showed that Leishmania donovani modulates the TLR2-mediated pathway in macrophages through inhibition of the IKK–NF-κB cascade and suppression of IL-12 and TNF-α production. This may be due to impairment of the association of TRAF6 with the TAK–TAB complex, thus inhibiting the recruitment of TRAF6 in TLR2 signaling. L. donovani infection drastically reduced Lys 63-linked ubiquitination of TRAF6, and the deubiquitinating enzyme A20 was found to be significantly upregulated in infected macrophages. Small interfering RNA-mediated silencing of A20 restored the Lys 63-linked ubiquitination of TRAF6 as well as IL-12 and TNF-α levels with a concomitant decrease in IL-10 and TGF-β synthesis in infected macrophages. Knockdown of A20 led to lower parasite survival within macrophages. Moreover, in vivo silencing of A20 by short hairpin RNA in BALB/c mice led to increased NF-κB DNA binding and host-protective proinflammatory cytokine response resulting in effective parasite clearance. These results suggest that L. donovani might exploit host A20 to inhibit the TLR2-mediated proinflammatory gene expression, thus escaping the immune responses of the host.
The role of histidine residues in modulation of the rat P2X2 purinoceptor by zinc and pH

P2X2 receptor currents are potentiated by acidic pH and zinc. To identify residues necessary for proton and zinc modulation, alanines were singly substituted for each of the nine histidines in the extracellular domain of the rat P2X2 receptor. Wild‐type and mutant receptors were expressed in Xenopus oocytes and analysed with two‐electrode voltage clamp. All mutations caused less than a 2‐fold change in the EC50 of the ATP concentration‐response relation. Decreasing the extracellular pH from 7.5 to 6.5 potentiated the responses to 10 μm ATP of wild‐type P2X2 and eight mutant receptors more than 4‐fold, but the response of the mutant receptor H319A was potentiated only 1.4‐fold. The H319A mutation greatly attenuated the maximal potentiation that could be produced by a drop in pH, shifted the pKa (‐log of dissociation constant) of the potentiation to a more basic pH as compared with P2X2 and revealed a substantial pH‐dependent decrease in the maximum response with a pKa near 6.0. Substituting a lysine for H319 reduced the EC50 for ATP 40‐fold. Zinc (20 μm) potentiated the responses to 10 μm ATP of wild‐type P2X2 and seven histidine mutants by ∼8‐fold but had virtually no effect on the responses of two mutants, H120A and H213A. Neither H120A nor H213A removed the voltage‐independent inhibition caused by high concentrations of zinc. The observation that different mutations selectively eliminated pH or zinc potentiation implies that there are two independent sites of action, even though the mechanisms of pH and zinc potentiation appear similar.