Miracle-dz/UniFAR-FTUs huggingface dataset:
Postsynaptic P/Q-type Ca2+ channel in Purkinje cell mediates synaptic competition and elimination in developing cerebellum

Neural circuits are initially redundant but rearranged through activity-dependent synapse elimination during postnatal development. This process is crucial for shaping mature neural circuits and for proper brain function. At birth, Purkinje cells (PCs) in the cerebellum are innervated by multiple climbing fibers (CFs) with similar synaptic strengths. During postnatal development, a single CF is selectively strengthened in each PC through synaptic competition, the strengthened single CF undergoes translocation to a PC dendrite, and massive elimination of redundant CF synapses follows. To investigate the cellular mechanisms of this activity-dependent synaptic refinement, we generated mice with PC-selective deletion of the Cav2.1 P/Q-type Ca2+ channel, the major voltage-dependent Ca2+ channel in PCs. In the PC-selective Cav2.1 knockout mice, Ca2+ transients induced by spontaneous CF inputs are markedly reduced in PCs in vivo. Not a single but multiple CFs were equally strengthened in each PC from postnatal day 5 (P5) to P8, multiple CFs underwent translocation to PC dendrites, and subsequent synapse elimination until around P12 was severely impaired. Thus, P/Q-type Ca2+ channels in postsynaptic PCs mediate synaptic competition among multiple CFs and trigger synapse elimination in developing cerebellum.
Direct Endothelial Nitric Oxide Synthase Activation Provides Atheroprotection in Diabetes-Accelerated Atherosclerosis

Patients with diabetes have an increased risk of developing atherosclerosis. Endothelial dysfunction, characterized by the lowered bioavailability of endothelial NO synthase (eNOS)–derived NO, is a critical inducer of atherosclerosis. However, the protective aspect of eNOS in diabetes-associated atherosclerosis remains controversial, a likely consequence of its capacity to release both protective NO or deleterious oxygen radicals in normal and disease settings, respectively. Harnessing the atheroprotective activity of eNOS in diabetic settings remains elusive, in part due to the lack of endogenous eNOS-specific NO release activators. We have recently shown in vitro that eNOS-derived NO release can be increased by blocking its binding to Caveolin-1, the main coat protein of caveolae, using a highly specific peptide, CavNOxin. However, whether targeting eNOS using this peptide can attenuate diabetes-associated atherosclerosis is unknown. In this study, we show that CavNOxin can attenuate atherosclerotic burden by ∼84% in vivo. In contrast, mice lacking eNOS show resistance to CavNOxin treatment, indicating eNOS specificity. Mechanistically, CavNOxin lowered oxidative stress markers, inhibited the expression of proatherogenic mediators, and blocked leukocyte-endothelial interactions. These data are the first to show that endogenous eNOS activation can provide atheroprotection in diabetes and suggest that CavNOxin is a viable strategy for the development of antiatherosclerotic compounds.
Pulmonary Artery Aneurysmal Dilatation in Adult Patients With Congenital Heart Disease

Background: Aneurysmal dilatation of the main pulmonary artery and its peripheral branches are rare lesions that account for less than 1% of all thoracic aneurysms and have a number of possible pathogenetic causes such as congenital heart disease (CHD), pulmonary artery hypertension, vasculitis, mycotic aneurysm, neoplasm, iatrogenic causes, trauma-related events, or connective tissue abnormalities. Methods: We conducted a retrospective review of the demographic data and the results of clinical examinations, laboratory tests, echocardiography, and angiography of patients managed at the Adult Congenital Heart Disease Unit of the Complejo Hospitalario Universitario Insular—Materno Infantil, between January 2004 and May 2010. Results: A total of 352 adult patients with CHD were studied. Of these, 8 (2.3%) patients had pulmonary artery aneurysmal dilatation (PAAD): 4 with low pressure of the pulmonary artery and 4 with pulmonary hypertension. Only 1 patient showed PAAD-related symptoms. Patients with CHD having PAAD had significantly higher prevalence of pulmonary artery hypertension and higher levels of C-reactive protein (CRP) than those without PAAD (incidence: 4 patients [50%] vs 18 patients [5.2%], P < .000; CRP in mg/dL: 0.52 [0.4; 1.2] vs 0.2 [0.0; 1.6], P = .016). No significant differences were found in cholesterol levels (total cholesterol, low-density lipoprotein [LDL], high-density lipoprotein [HDL], or triglycerides) between CHD patients with or without PAAD. Conclusion: In patients with CHD, PAAD is a rare finding. The PAAD size, etiology, symptoms, and association with pulmonary hypertension should guide decisions on whether conservative or surgical treatment should be applied.
Bisphosphonate-Related Osteonecrosis of the Jaw: Model and Diagnosis with Cone Beam Computerized Tomography

Intravenous bisphosphonate (BP) therapy has become the standard of care for the treatment of cancers that metastasize to bone. BPs are associated with osteonecrosis of alveolar bones, a condition known as osteonecrosis of the jaw (ONJ). The incidence or pathogenesis of ONJ is largely unknown. The lesions are characterized by areas of exposed necrotic bone that do not heal after 8 weeks in the absence of radiation to the head and neck. ONJ lesions have been recalcitrant to conventional therapies. Lesions in cancer patients treated with BPs develop in association with periodontal disease, tooth extraction and/or in association with increased mechanical force due to partial/complete dentures. We hypothesized that intravenous BPs in cancer patients impair normal bone remodeling, thereby increasing the incidence of osteonecrotic lesions and that these lesions can be detected using cone beam computerized tomography (CBCT). From CBCTs taken at the University of Missouri at Kansas City School of Dentistry, 26 subjects had a cancer diagnosis and were on BP therapy. From these 26 subjects, 18 presented visible, exposed necrotic bone. We observed both sclerotic and radiolucent lesions. Lesions could be detected and measured in reconstructed images where most were found to expand to large areas of the bone. We were able to identify necrotic bodies or ‘involucrums’ within the ONJ lesions, suggesting that this could be the mechanism for the formation of a clinically visible sequestrum. We propose that CBCT can potentially identify and follow the progression of both pre- and postclinical lesions in ONJ patients, allowing better diagnosis and assessment of disease status.
Geographical challenges for physical therapy continuing education: preferences and influences.

BACKGROUND AND PURPOSE The purpose of this survey was to examine factors influencing participation in continuing education (CE) and preferences for CE program design. Therapists in the more densely populated region of southern Ontario were compared with those in the more rural northern Ontario region. SUBJECTS AND METHODS All physical therapists with licenses in Ontario on February 1, 1994, were in the target population. Simple random sampling was used to sample 470 therapists in southern Ontario. Because there are few physical therapists in northern Ontario, survey instruments were sent to all 314 licensed therapists in that area. A questionnaire and covering letter were mailed to all subjects on March 1, 1994. RESULTS Of the 784 questionnaires that were mailed, 644 (82%) were returned. Principal-component analysis extracted six factors, accounting for 49.7% of the variance for factors influencing participation: timing, presentation quality, work-related cost, course-related cost, socialization, and program content. Results indicated that conferences or workshops should be used as a primary vehicle for the delivery of CE programs and that the use of computer-assisted instruction should be further developed and evaluated. CONCLUSION AND DISCUSSION The information gathered in this study may be useful as a knowledge base from which CE providers can develop future programs.
Passive mechanism of pitch recoil in flapping insect wings

The high torsional flexibility of insect wings allows for elastic recoil after the rotation of the wing during stroke reversal. However, the underlying mechanism of this recoil remains unclear because of the dynamic process of transitioning from the wing rotation during stroke reversal to the maintenance of a high angle of attack during the middle of each half-stroke, when the inertial, elastic, and aerodynamic effects all have a significant impact. Therefore, the interaction between the flapping wing and the surrounding air was directly simulated by simultaneously solving the incompressible Navier–Stokes equations, the equation of motion for an elastic body, and the fluid-structure interface conditions using the three-dimensional finite element method. This direct numerical simulation controlling the aerodynamic effect revealed that the recoil is the residual of the free pitch vibration induced by the flapping acceleration during stroke reversal in the transient response very close to critical damping due to the dynamic pressure resistance of the surrounding air. This understanding will enable the control of the leading-edge vortex and lift generation, the reduction of the work performed by flapping wings, and the interpretation of the underlying necessity for the kinematic characteristics of the flapping motion.
Two-time scale integrated simulation with automatic transition via dot products

This paper presents an integrated approach for transient and long-term stability simulations aiming its application for dynamic security assessment. Full time-domain and quasi steady-state analyses are integrated into a single simulation tool, providing short and long-term perspectives simultaneously. The novelty of this work regards the transition from full time-domain simulation to QSS technique (fast simulation). This is performed automatically using energy function based dot products. The dot products are used as an early termination technique as their behavior during the simulation will indicate if the system is stable or unstable. Moreover, in order to achieve a smooth transition between full and fast simulation, an enhanced version of the QSS simulation that do not eliminate any state variable from the original formulation is employed. A framework for power system analyses based on object oriented modeling was used to implement and test the proposed methodology. Preliminary results are presented and show good potential of the integrated approach.
Tourist Motivations and Satisfaction in the Archaeological Ensemble of Madinat Al-Zahra

Madinat Al-Zahra is an ancient Arab palace located in Cordoba, Spain, which was proclaimed as part of the World Heritage of Humanity in 2018. The public administration must know the tourist motivations and interest in this heritage, as well as the satisfaction with Cordoba as destination and this Archaeological Ensemble. This article addresses these issues by analyzing and comparing motivations, expected and perceived value with the destination and those of the monument itself, using a Structural Equation Models methodology. Data was obtained from a survey of 375 tourists and the results showed that there is a high satisfaction with both destination and site, although these people perceive that this heritage is not integrated with the rest of the city attractions. In addition, the survey highlights that the transport system to the site is one of the most important weaknesses, among others. The results of this study offer valuable information related to this heritage.
LOCAL PRODUCTION OF ANTI-CD4 ANTIBODY BY TRANSGENIC ALLOGENEIC GRAFTS AFFORDS PARTIAL PROTECTION1

Background. Immunosuppressive drugs and anti-lymphocyte antibody are used clinically to suppress cellular rejection responses. However, these systemic regimens often led to general immunodeficiency and thus increased susceptibility to opportunistic infection and neoplasia. Immunosuppressive molecules delivered locally may be a way of inhibiting rejection responses, whereas systemic immunity is preserved. To achieve protective local immunosuppression, we produced a graft secreting its own immunomodulator, by deriving transgenic mice expressing a chimeric anti-CD4 antibody (GK2c) in the pancreas. Methods and Results. Transgenic mice in bm1 genetic background expressing a modified anti-mouse CD4 antibody (GK2c) under two promoters have been produced. Tissue expression of GK2c was detected by immunoperoxidase staining. Under the cytomegalovirus promoter, there was abundant GK2c expression in pancreatic exocrine tissue. Under the rat preproinsulin II promoter, there was abundant GK2c expression in pancreatic endocrine tissue only. High-expression transgenic lines had 10–100 &mgr;g/ml GK2c in blood plasma. By flow cytometry, these transgenic mice were devoid of CD4+ cells in their peripheral lymphoid organs. To test transgenic mice as donors, fetal pancreata from transgenic mice were grafted into fully allogeneic CBA mice under the kidney capsule, transgenic grafts had prolonged survival compared with control non-transgenic grafts. Furthermore, GK2c transgenic grafts had reduced infiltration with an absence of CD4+ cells at the graft site without any effect on the cell composition in lymphatic tissues. Conclusion. Transgenic grafts that secrete anti-CD4 antibody can afford some protection against graft rejection, while only affecting the CD4 population at the graft site.
The sleep apnoea syndrome in obesity: risk of sudden death

Abstract. A total of 34 severely obese men with a history of heavy snoring and excessive daytime sleepiness indicative of obstructive sleep apnoea syndrome (OSAS) were studied prospectively. Their mean age was 46 years, and mean body mass index was 41.6 kg m−2. During a 4‐year follow‐up, 15% (5/34) of these subjects died (three cases of acute myocardial infarction and two cases of pulmonary oedema), all of them suddenly and unexpectedly, outside hospital. On autopsy the degree of atherosclerosis was found to be moderate in all cases. In 68% (15/22) of the men a pathological apnoea index (mean value 46 ± 20) confirmed the OSAS diagnosis. Exercise tests and neurological examinations did not reveal any other causes of daytime sleepiness. Mean blood pressure at rest and during exercise was normal, and mean serum lipid and blood glucose levels were normal. Spirometry revealed intrapulmonary restrictive changes that could not be attributed to the heavy thoracic wall. Compliance was reduced to about 50% of reference values, and the mean pCO2 level (5.8 kPa) was close to the upper reference limit. Blood tests suggested that high alcohol consumption may be an important factor contributing to OSAS. These results demonstrate that morbidly obese men with a history of OSAS have a high risk of sudden cardiovascular death, despite the absence of other conventional risk factors.
Depth Perception Evaluation with Different Stereoscopic Techniques: A Case Study

Stereoscopy techniques such as anaglyph, shutter glasses and polarized glasses are used as resources to offer a sense of immersion in three-dimensional virtual environments. These techniques use different mechanisms to cause depth perception in the human brain when observing a scene or image. Although there are many virtual reality studies that employ such techniques, little has been done to measure the effectiveness of different approaches. This article evaluates the depth effect realized by volunteers when using three different stereoscopy techniques in a three-dimensional virtual environment and provides an analysis of variance with ANOVA. An experiment conducted with volunteers showed that there is no significant statistical differences among the three techniques used, and it provided evidences that it is possible to build low-cost immersive applications when the main goal is provide depth sense.
Proteomics Reveals Open Reading Frames inMycobacterium tuberculosis H37Rv Not Predicted by Genomics

ABSTRACT Genomics revealed the sequence of 3924 genes of the H37Rv strain ofMycobacterium tuberculosis. Proteomics complements genomics in showing which genes are really expressed, and here we show the expression of six genes not predicted by genomics, as proved by two-dimensional electrophoresis and matrix-assisted laser desorption ionization and nano-electrospray mass spectrometry.
Evolution and Virulence of Serogroup 6 Pneumococci on a Global Scale

ABSTRACT To study the evolution and virulence of pneumococcal populations, we used multilocus sequence typing to identify the major clones among 212 carriage and invasive isolates expressing capsular serogroup 6 from 39 countries. The global population consisted of 8 major complexes and 6 minor complexes of related clones and 32 clones of diverse origin. Surprisingly, serotype 6A clones evolved by mutation nearly as often as by recombination, whereas serotype 6B clones evolved almost exclusively by recombination (P = 0.0029). This is the first report of population genetic differences among serotypes of this species. The largest clonal complex was associated with invasive disease (P = 0.019) and included a common ancestor for five previously identified drug-resistant clones. The putative ancestors of the major clonal complexes were represented by a greater proportion of carriage isolates than were their descendents (P = 0.001), and the ancestors tended to be less virulent than their descendents in a mouse model of infection. These data suggested that virulent serogroup 6 clones have evolved multiple times from less-virulent ancestral clones.
Laninamivir octanoate: a new long-acting neuraminidase inhibitor for the treatment of influenza

Oseltamivir and zanamivir are well-established and well-researched drugs for the treatment of influenza in Japan and the rest of the world. A new neuraminidase inhibitor, laninamivir octanoate, has been approved for use in Japanese clinics. Laninamivir octanoate is an inhaled drug with unique characteristics. The inhaled laninamivir octanoate is converted into its active form, laninamivir, in the lungs where a high concentration persists for a long period of time. The concentration of laninamivir exceeds the level necessary for influenza virus replication inhibition for at least 5 days, thus influenza can be treated with a single administration. The drug is delivered using one device requiring four inhalations for children and two devices requiring eight inhalations for adults. Clinical trials have shown comparable efficacy for laninamivir octanoate and oseltamivir. Laninamivir octanoate also displayed a sufficient antiviral effect to treat infection with H275Y-mutated oseltamivir-resistant virus. Laninamivir octanoate has displayed clinical efficacy comparable to that of oseltamivir and zanamivir against the H1N1 pandemic influenza strain from 2009, seasonal H3N2 influenza and influenza B viruses. The prophylactic efficacy of laninamivir octanoate has been shown in animal models. The effectiveness of laninamivir against the highly pathogenic avian influenza virus H5N1 has also been shown in vitro and in animal models. A major clinical benefit of this drug is that the single administration is very convenient for both the patient and doctor, which leads to improved compliance. Furthermore, this drug shows promise for the treatment of influenza in future pandemics.
Sensitivity of nicotine‐containing and de‐nicotinized cigarette consumption to alternative non‐drug reinforcement: a behavioral economic analysis

A previous report from our laboratory showed similar measures of reinforcing efficacy for nicotine‐containing and de‐nicotinized cigarettes when each cigarette type was presented alone. The present experiment further compared the reinforcing efficacy of nicotine‐containing and de‐nicotinized cigarettes by assessing the effects of alternative non‐drug reinforcement on self‐administration of both cigarette types. Eight human subjects responded on a progressive‐ratio schedule in which the number of plunger pulls required for standardized cigarette puffs increased across sessions. Responding for the two types of cigarette was examined when each was available alone and when the concurrent opportunity to earn money was available. Consumption of nicotine‐containing and de‐nicotinized cigarettes was decreased by both increases in price and by the concurrent availability of money. The two cigarettes types did not differ in their sensitivity to price or alternative non‐drug reinforcement. These results replicate our previous report of similar measures of reinforcing efficacy for the two cigarette types when each was presented alone, and extend our previous findings to a choice situation involving an alternative non‐drug reinforcer. These data suggest the importance of further examination of non‐pharmacological variables in the maintenance of drug taking and the sensitivity of drug taking to alternative non‐drug sources of reinforcement. Factors potentially contributing to the maintenance of smoking the de‐nicotinized cigarettes (i.e. conditioned reinforcement, primary reinforcement by respiratory stimulation, instructional control, demand characteristics) are also discussed.
The involvement of NAD(P)H dehydrogenase subunits, NdhD3 and NdhF3, in high‐affinity CO2 uptake in Synechococcus sp. PCC7002 gives evidence for multiple NDH‐1 complexes with specific roles in cyanobacteria

Random gene tagging was used to obtain new mutants of the marine cyanobacterium, Synechococcus sp. PCC7002, with defects in the CO2‐concentrating mechanism (CCM). Two of these mutants, K22 and A41, showed poor growth at limiting CO2. Isolation and sequencing of a 6.6 kb genomic region revealed the existence of five potential protein‐coding regions, all arranged in the same transcriptional direction. These regions code for an RbcR homologue, NdhF3 (subunit 5 of type 1 NAD(P)H dehydrogenase; NDH‐1 complex), NdhD3 (subunit 4 of NDH‐1), ORF427 and ORF133 (hypothetical proteins). Insertional mutants in ndhD3, ndhF3 and ORF427, like A41 and K22, were all incapable of inducing high‐affinity CO2 uptake and were not fully capable of inducing high‐affinity HCO3− transport. ndhD3 and ndhF3 mutants displayed P700 re‐reduction rates identical to wild‐type cells, suggesting that NdhD3 is part of a specific NDH‐1 complex that is not involved in photosynthetic cyclic electron transport. Thus, it is feasible that NdhD3, NdhF3 and ORF427 might form part of a novel NDH‐1 complex located on the cytoplasmic membrane and involved in tightly coupled energization of high‐affinity CO2 transport. The possibility of multiple, functionally distinct NDH‐1 complexes in cyanobacteria is discussed.
Hunting, Law Enforcement, and African Primate Conservation

Abstract: Primates are regularly hunted for bushmeat in tropical forests, and systematic ecological monitoring can help determine the effect hunting has on these and other hunted species. Monitoring can also be used to inform law enforcement and managers of where hunting is concentrated. We evaluated the effects of law enforcement informed by monitoring data on density and spatial distribution of 8 monkey species in Taï National Park, Côte d’Ivoire. We conducted intensive surveys of monkeys and looked for signs of human activity throughout the park. We also gathered information on the activities of law‐enforcement personnel related to hunting and evaluated the relative effects of hunting, forest cover and proximity to rivers, and conservation effort on primate distribution and density. The effects of hunting on monkeys varied among species. Red colobus monkeys (Procolobus badius) were most affected and Campbell's monkeys (Cercopithecus campbelli) were least affected by hunting. Density of monkeys irrespective of species was up to 100 times higher near a research station and tourism site in the southwestern section of the park, where there is little hunting, than in the southeastern part of the park. The results of our monitoring guided law‐enforcement patrols toward zones with the most hunting activity. Such systematic coordination of ecological monitoring and law enforcement may be applicable at other sites.