Miracle-dz/UniFAR-FTUs huggingface dataset:
HIV cure and eradication: how will we get from the laboratory to effective clinical trials?

Combination antiretroviral therapy (cART) has led to a major reduction in HIV-related mortality and morbidity; however, HIV can still not be cured. Achieving either a functional cure (long-term control of HIV in the absence of cART) or a sterilizing cure (elimination of all HIV-infected cells) remains a major challenge. The most significant barrier to cure is the establishment of a latent or ‘silent’ infection in resting CD4+ T cells. Several randomized clinical trials have demonstrated that treatment intensification with additional antiretrovirals has little impact on latent reservoirs. Some potential other approaches that may reduce the latent reservoir include very early initiation of cART and the use of agents that could reverse latent infection. Drugs such as histone deacetylase inhibitors, currently used and licensed for the treatment of some cancers; methylation inhibitors; cytokines such as IL-7 or activators of nuclear factor kappa B (NF-κB) such as prostratin, show promising activity in reversing latency in vitro when used either alone or in combination. Alternate strategies include using gene therapy to modify expression of CCR5 and therefore make cells resistant to HIV. This review will primarily focus on the advantages and disadvantages of methods currently being used to quantify persistent virus ex vivo in patients receiving cART and strategies aimed at cure that are being tested in vitro or in early clinical development. In addition, we discuss key issues that need to be addressed to successfully move laboratory research to clinical trials aimed at curing HIV.
Coexisting oak species, including rear-edge populations, buffer climate stress through xylem adjustments

The ability of trees to cope with climate change is a pivotal feature of forest ecosystems, especially for rear-edge populations facing warm and dry conditions. To evaluate current and future forests threats, a multi-proxy focus on the growth, anatomical and physiological responses to climate change is needed. We examined the long-term xylem adjustments to climate variability of the temperate Quercus robur L. at its rear edge and the sub-Mediterranean Quercus pyrenaica Willd. Both species coexist at a mesic (ME, humid and warmer) and a xeric (XE, dry and cooler) site in northern Spain, the latter experiencing increasing temperatures in recent decades. We compared xylem traits at each site and assessed their trends, relationships and responses to climate (1960-2008). Traits included basal area increment, earlywood vessel hydraulic diameter, density and theoretical-specific hydraulic conductivity together with latewood oxygen (δ18O) stable isotopes and δ13C-derived water-use efficiency (iWUE). Quercus robur showed the highest growth at ME, likely through enhanced cambial activity. Quercus pyrenaica had higher iWUE at XE compared with ME, but limited plasticity of anatomical xylem traits was found for the two oak species. Similar physiological performance was found for both species. The iWUE augmented in recent years especially at XE, likely explained by stomatal closure given the increasing δ18O signal in response to drier and sunnier growing seasons. Overall, traits were more correlated at XE than at ME. The iWUE improvements were linked to higher growth up to a threshold (~85 μmol mol-1) after which reduced growth was found at XE. Our results are consistent with Q. pyrenaica and Q. robur coexisting at the central and dry edge of the climatic species distribution, respectively, showing similar responses to buffer warmer conditions. In fact, the observed adjustments found for Q. robur point towards growth stability of similar rear-edge oak populations under warmer climate conditions.
Cryopreservation of the Germplasm of Animals Used in Biological and Medical Research: Importance, Impact, Status, and Future Directions

Abstract Molecular genetics and developmental biology have created thousands of new strains of laboratory animals, including rodents, Drosophila, and zebrafish. This process will accelerate. A decreasing fraction can be maintained as breeding colonies; hence, the others will be lost irretrievably unless their germplasm can be cryopreserved. Because of the increasingly critical role of cryopreservation, and because of wide differences in the success with which various forms of germplasm can be cryopreserved in various species, the National Institutes of Health National Center for Research Resources held a workshop on April 10–11, 2007, titled “Achieving High-Throughput Repositories for Biomedical Germplasm Preservation. ” The species of concern were mouse, rat, domestic swine, rhesus monkey, and zebrafish. Our review/commentary has several purposes. The first is to summarize the status of the cryopreservation of germplasm from these species as assessed in the workshop. The second is to discuss the nature of the major underlying problems when survivals are poor or highly variable and possible ways of addressing them. Third is to emphasize the importance of a balance between fundamental and applied research in the process. Finally, we assess and comment on the factors to be considered in transferring from a base of scientific information to maximally cost-effective processes for the preservation of this germplasm in repositories. With respect to the first purpose, we discuss the three methods of preservation in use: slow equilibrium freezing, rapid nonequilibrium vitrification, and the use of intracytoplasmic sperm injection to achieve fertilization with sperm rendered nonviable by other preservation treatments. With respect to the last purpose, we comment on and concur with the workshop's recommendations that cryopreservation largely be conducted by large, centralized repositories, and that both sperm (low front-end but high rederivation costs) and embryos (high front-end but modest rederivation costs) be preserved.
A Set of Multilevel Modular Medium-Voltage High Power Converters for 10-MW Wind Turbines

Medium-voltage power conversion is generally favored for future large wind turbines, e.g., 10 MW, in terms of higher power density, reduced current level, associated losses, and cost of power cables, switchgears, etc. This paper has summarized a fundamental rule to construct multilevel modular high power converters for large wind turbine power conversion. Based on that, three potential multilevel modular high power converter topologies are derived and compared. The topology with a 10-kV generator, a modular power converter, and a multi-winding step-up transformer have been specifically investigated. The large dc-link capacitor (not reliable, high cost, large volume) required in the converter is identified as the key limitation of the system used for wind power conversion. The paper proposes to compensate the ripple power by the grid-side inverter of the multilevel modular converter, thus reducing the dc-link capacitor requirement. The paper has validated the effectiveness of proportional-integral-resonant controller for this purpose. Further, the thermal impact of the proposed ripple power compensation scheme on the converter device junction temperature and the transformer secondary windings has been analytically derived. The paper has also analytically revealed that the proposed ripple power compensation scheme will not affect the grid-side power quality, although there are low-frequency harmonics in the transformer secondary windings. Simulation results with a 10-MW, 10-kV system have validated the proposed converter topology and control strategy with reduced dc-link voltage ripple.
The Determinants of Profitability in the Banking Industry: Empirical Research on Selected Balkan Countries

The determinants of bank profitability in general, and of the impact of market structure and efficiency on bank performance in particular, remain a much- researched topic in bank performance analysis. The purpose of this article is to investigate the relevance of the structure-conduct-performance (SCP) hypothesis versus the efficiency hypothesis in explaining bank performance by analyzing 127 commercial banks from six Balkan countries (Slovenia, Croatia, Serbia, Bosnia and Herzegovina, Montenegro, and Macedonia) over the period 2005–2009. In order to account for the dynamic nature of bank profits, it uses a GMM estimator in testing the determinants of bank profitability. The estimation results suggest that profits persist to some extent, indicating that the deviation from a perfectly competitive market structure is marginal. In addition, the findings suggest that efficiency is significantly and positively associated with profitability, whereas the industry concentration variable is insignificant in explaining profitability, indicating support in favor of the efficiency hypothesis. Moreover, among the bank-specific control variables, only size is reported insignificant, and the rest of the variables affect bank profitability in the anticipated manner. Finally, the results suggest that neither inflation nor economic growth has an impact on bank profitability.
Use of a siderophore receptor and porin proteins-based vaccine to control the burden of Escherichia coli O157:H7 in feedlot cattle.

OBJECTIVE To quantify the efficacy of a siderophore receptor and porin (SRP) proteins-based vaccine on the burden of Escherichia coli O157:H7 in feedlot cattle. METHODS Two research trials were conducted in field conditions. In each trial, cattle (n = 1252 in trial #1; n = 1284 in trial #2) were systematically divided into 20 pens and were administered either the E. coli O157 SRP vaccine or a placebo (trial #1: days 0 and 21; trial #2: days 0, 21, and 42). Rectal fecal samples were collected on day 0, and pen floor samples were collected on days 21, 35, 70, and 85 for trial #1 and on days 42 and 98 for trial #2. On day 85 of trial #1, rectoanal mucosal swab samples and hide swab samples were collected. Cattle were weighed on days 0, 21, and 85 (trial #1) or 1 week before harvest (trial #2). RESULTS In trial #1, prevalence of E. coli in the feces was lower in vaccinates compared to control animals (p = 0.04). On day 85, the likelihood of an animal being positive at any site was less among vaccinates than controls (p = 0.02). In trail #2, vaccination with SRP was associated with reduced shedding by 85.2% on day 98 (p < 0.01) but not on days 0 or 42. Vaccination with SRP was associated with a 98.2% reduction in concentration of E. coli O157 in fecal samples (2.54 vs. 0.80 log MPN/g of feces; p < 0.01). Cattle performance was not affected by SRP administration. CONCLUSIONS The E. coli O157:H7 SRP-based vaccine might serve as a preharvest intervention to reduce the burden of E. coli O157:H7 on cattle presented for harvest.
The politics of belonging in Australia : multiculturalism, citizenship and Islamophobia

In the decade since the events of 9/11, Muslims and Islam came to act as symbols for the putative correlation between immigration and the erosion of social cohesion in a number of Western countries, including Australia. Increasingly, immigrant integration was believed to be key to the maintenance of social cohesion and individual immigrant integration was seen as the main factor in successful integration. The Howard Government distanced itself from multicultural policies by rejecting group identities for ‘ethnic’ minorities, while, conversely, strengthening group identity in terms of nationalism and citizenship. Following other Western societies, the integration of Muslims in Australia became characterised as a security imperative and the responsibilities of Muslim citizens increasingly became embedded within the discourse of terrorism, where Muslim citizens are simultaneously suspected as potential terrorists and encouraged to act as community watchdogs. Politicians also came to see terrorism as something harboured within Islamic communities in Australia and Muslim lack of belonging came to be viewed as having ‘cultural’ and ‘religious’ underpinnings. As a result of the securitisation of Islam and the view that Islam and Muslims are problematic, all Muslims were characterised as potential terrorists and negative ideas and actions toward Muslims, what some have called Tslamophobia’, were normalised and justified. There has, however, been remarkably little systematic attempt to examine any continuity between broader understandings of the official definitions of belonging and how and why Muslims are viewed as incapable of belonging. This research demonstrates the links between ideas about the ‘Other’ and their place in Australian society and how these ideas give meaning to the ways Muslims and Islam are thought not to belong. The focus on Muslim Australians as refusing integration and challenging Australia’s national identity is contextualised within the wider framework of Australian national identity, immigration policies (entry, settlement and citizenship) and the wider prevalence of Tslamophobia’ in Australia. This dissertation explicitly politicises the concept of belonging in order to demonstrate the social and political barriers to belonging for Muslim Australians. This dissertation uses Allen’s (2010) concept of Tslamophobia as ideology’ to empirically examine discourses about Islam and Muslims in the House of Representatives (2000-2006). The findings indicate that deeplyentrenched views about who belongs (and who does not), and how they belong in Australia, informed parliamentary discourse on Muslims and Islam. Islamophobia in the Australian House of Representatives demonstrates the ways in which discourses about the ‘Other’ are systematically used to strengthen negative meaning about Islam and Muslims and to consistently present them as anathema to everything ‘Australian’.
Control by H-2 genes of the Th1 response induced against a foreign antigen expressed by attenuated Salmonella typhimurium

Attenuated salmonellae represent an attractive vehicle for the delivery of heterologous protective antigens to the immune system. Here, we have investigated the influence of the genetic background of the host which regulates the growth and elimination of Salmonella cells on the cellular response induced against a foreign antigen delivered by an aroA Salmonella strain. We have tested CD4+ T-cell responses (cell proliferation and cytokine production) in various mouse strains following immunization with Salmonella typhimurium SL3261 expressing a high level of the recombinant Escherichia coli MalE protein. We were able to detect a CD4+ T-cell response against the recombinant MalE protein only in a restricted number of mouse strains, whereas all mice produced good levels of anti-MalE immunoglobulin G antibodies. The Ity gene did not play a major role in these differences in T-cell responses, since both Ity-resistant and -susceptible strains of mice were found to be unresponsive to MalE delivered by recombinant salmonellae. In contrast, when B10 congenic mice were used, a correlation was established between MalE-specific T-cell unresponsiveness and H-2 genes. The discrepancies described in this paper in the ability of various strains of mice to develop an efficient Th1 response against a recombinant antigen displayed by a live Salmonella vaccine underscore the difficulties that can be encountered in the vaccination of human populations by such a strategy.
Understanding the Property–Activity Relationships of Polyhedral Cuprous Oxide Nanocrystals in Terms of Reactive Crystallographic Facets

The property-activity relationship is usually established to understand the toxicity mechanism of nanomaterials. In the present study, different morphological Cu2O nanocrystals, octahedrons, truncated octahedrons, cuboctahedrons, and cubes, were synthesized to precisely tuning the {100} and {111} facet percentages in purpose of systematically investigating the toxicity role of crystallographic facets in BEAS-2B and RAW 264.7 cells. It was found that the toxicity of polyhedral Cu2O nanocrystals was highly dependent on the exposed {100} surface after short-term exposure because {100} facets could produce more reactive oxygen species (ROS) than {111} facets; however, after long-term exposure, their toxicity showed again the correlation with total surface property because toxic copper ions were largely released from the whole nanocrystal surface irrespective of {100} or {111} facet and this copper dissolution caused the collapse of surface crystals and the vanishing of ROS. This study reveals the potential hazard of crystallographic facets based on ROS and metal dissolution mechanism at the different exposure time.
Vitamin D: The “sunshine” vitamin

Vitamin D insufficiency affects almost 50% of the population worldwide. An estimated 1 billion people worldwide, across all ethnicities and age groups, have a vitamin D deficiency (VDD). This pandemic of hypovitaminosis D can mainly be attributed to lifestyle (for example, reduced outdoor activities) and environmental (for example, air pollution) factors that reduce exposure to sunlight, which is required for ultraviolet-B (UVB)-induced vitamin D production in the skin. High prevalence of vitamin D insufficiency is a particularly important public health issue because hypovitaminosis D is an independent risk factor for total mortality in the general population. Current studies suggest that we may need more vitamin D than presently recommended to prevent chronic disease. As the number of people with VDD continues to increase, the importance of this hormone in overall health and the prevention of chronic diseases are at the forefront of research. VDD is very common in all age groups. As few foods contain vitamin D, guidelines recommended supplementation at suggested daily intake and tolerable upper limit levels. It is also suggested to measure the serum 25-hydroxyvitamin D level as the initial diagnostic test in patients at risk for deficiency. Treatment with either vitamin D2 or vitamin D3 is recommended for deficient patients. A meta-analysis published in 2007 showed that vitamin D supplementation was associated with significantly reduced mortality. In this review, we will summarize the mechanisms that are presumed to underlie the relationship between vitamin D and understand its biology and clinical implications.
Decentralized supervisory control of fuzzy discrete event systems

Fuzzy discrete event systems (FDESs), proposed recently by Lin Feng and Ying Hao, are possible to effectively cope with some problems having fuzziness, impreciseness, and subjectivity. Qiu, and Cao and Ying independently developed supervisory control theory of FDESs. We note that the controllability of events in Qiu's work is fuzzy but the observability of events is crisp, and, both the observability and the controllability of events in Cao and Ying's work are crisp. In this work, both the observability and the controllability of events are considered to be fuzzy. We set up the decentralized supervisory control theorem of FDESs in the more generic framework. In particular, based on Qiu's work, we present a detailed computing approach to verify whether the controllability and co-observability conditions hold, and this method can decide the existence of the decentralized supervisors. As well, this computing method can be applied to check the existence of the decentralized supervisors in classical discrete event systems.
Detection of Carcinogenic Human Papillomavirus in Specimens Collected with a Novel Self-Sampling Device

ABSTRACT We compared the detection of carcinogenic human papillomavirus DNA in cervicovaginal specimens self-collected using a novel device to the detection in physician-collected cervical specimens from 137 women. The kappa value was 0.66 (95% confidence interval, 0.53 to 0.78), with an 83% overall test agreement and a 68% positive test agreement.
Root Metabolite Differences in Two Maize Varieties Under Lead (Pb) Stress

To assess root metabolic differences of maize varieties in their response to lead (Pb) stress, the lead-tolerant variety Huidan No. 4 and the lead-sensitive variety Ludan No. 8 were tested under Pb-free and Pb-stressed conditions. Changes in metabolites were measured using ultra-performance liquid chromatography–mass spectrometry. Pb stress changed the levels of the amino acids proline, glutamine, lysine, and arginine in both varieties, whereas glutamate and phenylalanine levels changed only in Huidan No. 4. Pb stress altered cystine, valine, methionine, and tryptophan levels only in Ludan No. 8. Therefore, the synthesis and decomposition of amino acids may affect the response of maize to Pb stress. The degree of change in differential metabolites for Huidan No. 4 was greater than that for Ludan No. 8. In cell wall subcellular components, increases in superoxide dismutase (SOD), peroxidases (PODs), and Pb concentrations were greater in Huidan No. 4 than in Ludan No. 8. Therefore, the greater Pb tolerance of Huidan No. 4 could be due to better sequestration of Pb in cell walls and more effective removal of reactive oxygen species (ROS) from the plant. The levels of certain metabolites only increased in Ludan No. 8, indicating that Pb-sensitive varieties may use different metabolic pathways to cope with Pb stress. Both varieties showed increased levels of some metabolites related to antioxidant protection and osmotic regulation. This study provides an understanding of maize Pb tolerance mechanisms and a basis for further development of tools for use in maize breeding.
A Randomized Trial on the Safety and Efficacy of Endovascular Treatment of Unruptured Intracranial Aneurysms is Feasible

The safety and efficacy of endovascular treatment of unruptured intracranial aneurysms remain undetermined. A randomized trial may be the best way to demonstrate the potential benefits of endovascular management. We propose a randomized, prospective, controlled trial comparing the incidence of subarachnoid haemorrage of patients treated by endovascular coiling as compared to conservative management. We would also study a composite outcome combining SAH and the morbidity of treatment. All patients with one or more unruptured aneurysm >> 3 mm eligible for endovascular treatment would be proposed to participate. The study would be conducted in 40–50 centres. The entire study would enrol 1800 patients, recruited over three years and followed for five years, but would be preceded by a feasibility study on 200 patients. A randomized trial comparing endovascular and conservative treatment could have an important impact on the clinical management of intracranial aneurysms
Association of hemodialysis treatment time and dose with mortality and the role of race and sex.

BACKGROUND The association of survival with characteristics of thrice-weekly hemodialysis (HD) treatment, including dose or duration of treatment, has not been completely elucidated, especially in different race and sex categories. STUDY DESIGN We examined associations of time-averaged and quarterly varying (time-dependent) delivered HD dose and treatment time and 5-year (July 2001-June 2006) survival. SETTING & PARTICIPANTS 88,153 thrice-weekly-treated HD patients from DaVita dialysis clinics. PREDICTORS HD treatment dose (single-pool Kt/V) and treatment time. OUTCOMES & OTHER MEASUREMENTS 5-Year mortality. RESULTS Thrice-weekly treatment time < 3 hours (but > or = 2.5 hours) per HD session compared with > or = 3.5 hours (but < 5 hours) was associated with increased death risk independent of Kt/V dose. The greatest survival gain of higher HD dose was associated with a Kt/V approaching the 1.6-1.8 range, beyond which survival gain was minimal, nonexistent, or even tended to reverse in African American men and those with 4-5 hours of HD treatment. In non-Hispanic white women, Kt/V > 1.8 continued to show survival advantage trends, especially in time-dependent models. LIMITATIONS Our results may incorporate uncontrolled confounding. Achieved Kt/V may have different associations than targeted Kt/V. CONCLUSIONS HD treatment dose and time appear to have different associations with survival in different sex or race groups. Randomized controlled trials may be warranted to examine these associations across different racial and demographic groups.