Miracle-dz/UniFAR-FTUs huggingface dataset:
Reconciling migration models to the Americas with the variation of North American native mitogenomes

In this study we evaluated migration models to the Americas by using the information contained in native mitochondrial genomes (mitogenomes) from North America. Molecular and phylogeographic analyses of B2a mitogenomes, which are absent in Eskimo–Aleut and northern Na-Dene speakers, revealed that this haplogroup arose in North America ∼11–13 ka from one of the founder Paleo-Indian B2 mitogenomes. In contrast, haplogroup A2a, which is typical of Eskimo–Aleuts and Na-Dene, but also present in the easternmost Siberian groups, originated only 4–7 ka in Alaska, led to the first Paleo-Eskimo settlement of northern Canada and Greenland, and contributed to the formation of the Na-Dene gene pool. However, mitogenomes also show that Amerindians from northern North America, without any distinction between Na-Dene and non–Na-Dene, were heavily affected by an additional and distinctive Beringian genetic input. In conclusion, most mtDNA variation (along the double-continent) stems from the first wave from Beringia, which followed the Pacific coastal route. This was accompanied or followed by a second inland migratory event, marked by haplogroups X2a and C4c, which affected all Amerindian groups of Northern North America. Much later, the ancestral A2a carriers spread from Alaska, undertaking both a westward migration to Asia and an eastward expansion into the circumpolar regions of Canada. Thus, the first American founders left the greatest genetic mark but the original maternal makeup of North American Natives was subsequently reshaped by additional streams of gene flow and local population dynamics, making a three-wave view too simplistic.
Assessment of cellular and serum proteome from tongue squamous cell carcinoma patient lacking addictive proclivities for tobacco, betel nut, and alcohol: Case study

The intriguing molecular pathways involved in oral carcinogenesis are still ambiguous. The oral squamous cell carcinoma (OSCC) ranks as the most common type constituting more than 90% of the globally diagnosed oral cancers cases. The elevation in the OSCC incidence rate during past 10 years has an alarming impression on human healthcare. The major challenges associated with OSCC include delayed diagnosis, high metastatic rates, and low 5‐year survival rates. The present work foundations on reverse genetic strategy and involves the identification of genes showing expressional variability in an OSCC case lacking addictive proclivities for tobacco, betel nut, and/or alcohol, major etiologies. The expression modulations in the identified genes were analyzed in 16 patients comprising oral pre‐cancer and cancer histo‐pathologies. The genes SCCA1 and KRT1 were found to down regulate while DNAJC13, GIPC2, MRPL17, IG‐Vreg, SSFA2, and UPF0415 upregulated in the oral pre‐cancer and cancer pathologies, implicating the genes as crucial players in oral carcinogenesis.
THE OPTIMUM PERFORMANCE OF POLYMER SOLAR CELLS

A model for an ideal bulk heterojunction solar cell has been developed . The model is compared with measurements from MDMO : PPV / PCBM solar cells . The performance of the cell is found to be governed by the offset of the highest occupied molecular orbital of the electron donor an d the lowest unoccupied molecular orbital of the electron acceptor . It is also governed by the offset of the lowest unoccupied molecular orbital of the acce ptor and the lowest unoccupied molecular orbital of the donor . The res ults also show that the performance depends strongly on the work function of the anode and the thickness of the solar cell . Material development is required for development of low - band gap cells to optimize the utilization of solar radiation . The optimum band gap is about 1.5 e V.
HIV DNA-Adenovirus Multiclade Envelope Vaccine Induces gp41 Antibody Immunodominance in Rhesus Macaques

ABSTRACT Dominant antibody responses in vaccinees who received the HIV-1 multiclade (A, B, and C) envelope (Env) DNA/recombinant adenovirus virus type 5 (rAd5) vaccine studied in HIV-1 Vaccine Trials Network (HVTN) efficacy trial 505 (HVTN 505) targeted Env gp41 and cross-reacted with microbial antigens. In this study, we asked if the DNA/rAd5 vaccine induced a similar antibody response in rhesus macaques (RMs), which are commonly used as an animal model for human HIV-1 infections and for testing candidate HIV-1 vaccines. We also asked if gp41 immunodominance could be avoided by immunization of neonatal RMs during the early stages of microbial colonization. We found that the DNA/rAd5 vaccine elicited a higher frequency of gp41-reactive memory B cells than gp120-memory B cells in adult and neonatal RMs. Analysis of the vaccine-induced Env-reactive B cell repertoire revealed that the majority of HIV-1 Env-reactive antibodies in both adult and neonatal RMs were targeted to gp41. Interestingly, a subset of gp41-reactive antibodies isolated from RMs cross-reacted with host antigens, including autologous intestinal microbiota. Thus, gp41-containing DNA/rAd5 vaccine induced dominant gp41-microbiota cross-reactive antibodies derived from blood memory B cells in RMs as observed in the HVTN 505 vaccine efficacy trial. These data demonstrated that RMs can be used to investigate gp41 immunodominance in candidate HIV-1 vaccines. Moreover, colonization of neonatal RMs occurred within the first week of life, and immunization of neonatal RMs during this time also induced a dominant gp41-reactive antibody response. IMPORTANCE Our results are critical to current work in the HIV-1 vaccine field evaluating the phenomenon of gp41 immunodominance induced by HIV-1 Env gp140 in RMs and humans. Our data demonstrate that RMs are an appropriate animal model to study this phenomenon and to determine the immunogenicity in new HIV-1 Env trimer vaccine designs. The demonstration of gp41 immunodominance in memory B cells of both adult and neonatal RMs indicated that early vaccination could not overcome gp41 dominant responses.
Effect of silica fume addition on physical properties of metakaolin-lime sludge bricks for low cost housing

Housing is a great problem in today's world. The most basic building materials used in building are the usual burnt clay brick, hollow concrete block and light weight sand brick. A significant quantity of fuel is utilized in these industries. This study aimed to investigate the use of solid waste materials in fabrication of low cost building brick. The solid wastes used in this investigation were silica fume and lime sludge. The kaolinites were activated at 800°C for 2 hours. The metakaolin and lime sludge were mixed in a ratio of 1: 1 by weight as well as silica fume were added by 0, 5, 10 and 15% of blended metakaolin-lime sludge weight. The water/binder ratio of blended pastes was mixed with the water of consistency. The results of this investigation showed that, the compressive strength of blended paste containing 10% silica fume reaches higher value than those of other blends at latter ages of hydration.
A novel trial of topotecan, ifosfamide, and carboplatin (TIC) in children with recurrent solid tumors

Ifosfamide, carboplatin, and etoposide (ICE) in children with refractory or recurrent solid tumors and lymphomas has resulted in good overall response rates (ORR). Etoposide, a topoisomerase‐II inhibitor, however, has been associated with a significant increase in secondary leukemia. The rationale for substituting topotecan, a topoisomerase‐I inhibitor, for etoposide in this regimen, a topoisomerase‐II inhibitor, includes its limited toxicity profile and decreased leukemogenicity. Furthermore, topotecan in combination with both alkylators and platinating agents are additive and/or synergistic against a variety of solid tumors.
Pubertal testis volume, age at pubertal onset, and adolescent blood pressure: Evidence from Hong Kong's “Children of 1997” birth cohort

A warning from Health Canada suggests that testosterone increases blood pressure (BP). No evidence from large randomized controlled trials is available, and observational studies are confounded by ill‐health lowering serum testosterone. To address the evidence gap, we assessed the association of pubertal testicular volume, as a reflection of testosterone production, with BP.
Cost of severe hypoglycaemia in nine European countries

Abstract Objective: Complications contribute largely to the economic gravity of diabetes mellitus (DM). How they arise and are treated differs substantially between countries. This paper assesses the total annual, direct, and indirect cost of severe hypoglycemia events (SHEs) in nine European countries: Bulgaria, Croatia, the Czech Republic, Greece, Hungary, Macedonia/the former Yugoslav Republic of Macedonia (MK), Poland, Slovenia, and Spain. Methods: Data was collected on epidemiology, treatment structure, SHE-driven resource consumption, and unit costs. Two systematic reviews—on the SHE rates and the resources used for treatment—and data on the days-of-work lost due to SHE along with salaries and employment rates were used. The total SHE cost in each country was calculated and how the differences are driven by individual parameters was analysed. Results: The annual costs of SHEs varied in absolute terms from €379,951.25 in MK up to €58,429,684.40 in Spain, or—when expressed per one drug-treated DM patient—from €5.47 in Bulgaria up to €17.74 in Spain. Indirect cost constituted between 6.01% (MK) and 26.49% (Hungary) of the total cost. The differences between countries are driven mostly by the cost of treating a single event, and this is related to general differences in prices. Limitations: The main limitation is the lack of good quality data in some parts, and the necessity to use mean-value imputations, experts’ opinions, etc. Additionally, we only considered DM treatment as the SHE driver, while other elements, e.g. style of living, may contribute substantially. Conclusions: A common framework can be applied to estimate the economic burden of SHE in various countries, allowing one to identify the drivers of differences in cost. Treating DM is complex, and so no resolute conclusions ought to be drawn as to whether SHE management is better in one country than another.
Probabilistic Computational Methods in Structural Failure Analysis

Probabilistic methods are used in engineering where a computational model contains random variables. Each random variable in the probabilistic calculations contains uncertainties. Typical sources of uncertainties are properties of the material and production and/or assembly inaccuracies in the geometry or the environment where the structure should be located. The paper is focused on methods for the calculations of failure probabilities in structural failure and reliability analysis with special attention on newly developed probabilistic method: Direct Optimized Probabilistic Calculation (DOProC), which is highly efficient in terms of calculation time and the accuracy of the solution. The novelty of the proposed method lies in an optimized numerical integration that does not require any simulation technique. The algorithm has been implemented in mentioned software applications, and has been used several times in probabilistic tasks and probabilistic reliability assessments.
Analysis and correction of background velocity offsets in phase‐contrast flow measurements using magnetic field monitoring

The value of phase‐contrast magnetic resonance imaging for quantifying tissue motion and blood flow has been long recognized. However, the sensitivity of the method to system imperfections can lead to inaccuracies limiting its clinical acceptance. A key source of error relates to eddy current‐induced phase fluctuations, which can offset the measured object velocity significantly. A higher‐order dynamic field camera was used to study the spatiotemporal evolution of background phases in cine phase‐contrast measurements. It is demonstrated that eddy current‐induced offsets in phase‐difference data are present up to the second spatial order. Oscillatory temporal behaviors of offsets in the kHz range suggest mechanical resonances of the MR system to be non‐negligible in phase‐contrast imaging. By careful selection of the echo time, their impact can be significantly reduced. When applying field monitoring data for correcting eddy current and mechanically induced velocity offsets, errors decrease to less than 0.5% of the maximum velocity for various sequence settings proving the robustness of the correction approach. In vivo feasibility is demonstrated for aortic and pulmonary flow measurements in five healthy subjects. Using field monitoring data, mean error in stroke volume was reduced from 10% to below 3%. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
The Human Microbiome and Understanding the 16S rRNA Gene in Translational Nursing Science

Background As more is understood regarding the human microbiome, it is increasingly important for nurse scientists and healthcare practitioners to analyze these microbial communities and their role in health and disease. 16S rRNA sequencing is a key methodology in identifying these bacterial populations that has recently transitioned from use primarily in research to having increased utility in clinical settings. Objectives The objectives of this review are to (a) describe 16S rRNA sequencing and its role in answering research questions important to nursing science; (b) provide an overview of the oral, lung, and gut microbiomes and relevant research; and (c) identify future implications for microbiome research and 16S sequencing in translational nursing science. Discussion Sequencing using the 16S rRNA gene has revolutionized research and allowed scientists to easily and reliably characterize complex bacterial communities. This type of research has recently entered the clinical setting, one of the best examples involving the use of 16S sequencing to identify resistant pathogens, thereby improving the accuracy of bacterial identification in infection control. Clinical microbiota research and related requisite methods are of particular relevance to nurse scientists—individuals uniquely positioned to utilize these techniques in future studies in clinical settings.
Birth and death: Evidence for the same biologic clock

In mammals, there exists a strong correlation between the average life span (in years) and the length of gestation (in days), suggesting that the same biologic clock mechanisms control both of these physiologic events. Life span is determined by a complex sequence of events leading to organismal senescence, and ultimately death. Although multiple biochemical and cellular phenomena are believed to be involved, progressive telomere shortening due to oxidative stress and loss during DNA replication is believed to be an important determinant contributing to aging, senescence, and adult death. We hypothesize that similar biochemical and cellular phenomena occur in the placenta and fetal membranes resulting in their aging during gestation, their senescence at term, and their apoptotic death resulting in the release of an inflammatory mediator in the form of fetal cell‐free DNA. This article reviews the evidence supporting this “telomere gestational clock” hypothesis which proposes that progressive telomere shortening in gestational tissue (especially the placenta and fetal membranes) leads to apoptosis and fetal cell‐free DNA release, thereby stimulating the proinflammatory signaling cascade that drives the progression of parturition.
Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice

Significance Th17 cells accumulate in the gut, where they mediate barrier defenses and repair but can also provoke inflammatory disease. In mice, segmented filamentous bacteria (SFB) is sufficient to induce Th17 cells in the gut, but functionally analogous microbes in humans have not been defined. Here, we identified Bifidobacterium adolescentis as one of several human symbiont bacterial species that could, alone, induce Th17 cells in the small intestine of mice. B. adolescentis and SFB exhibited overlapping but also distinct activities, suggesting multiple routes to intestinal Th17 induction. Like SFB, B. adolescentis exacerbated autoimmune arthritis, arguing for its pathological relevance. Our results help to inform the search for therapeutic targets in diseases associated with Th17 responses and mucosal dysfunction. Th17 cells accrue in the intestine in response to particular microbes. In rodents, segmented filamentous bacteria (SFB) induce intestinal Th17 cells, but analogously functioning microbes in humans remain undefined. Here, we identified human symbiont bacterial species, in particular Bifidobacterium adolescentis, that could, alone, induce Th17 cells in the murine intestine. Similar to SFB, B. adolescentis was closely associated with the gut epithelium and engendered cognate Th17 cells without attendant inflammation. However, B. adolescentis elicited a transcriptional program clearly distinct from that of SFB, suggesting an alternative mechanism of promoting Th17 cell accumulation. Inoculation of mice with B. adolescentis exacerbated autoimmune arthritis in the K/BxN mouse model. Several off-the-shelf probiotic preparations that include Bifidobacterium strains also drove intestinal Th17 cell accumulation.
Adjuvant everolimus in high-risk diffuse large B-cell lymphoma: final results from the PILLAR-2 randomized phase III trial

Background Patients with diffuse large B-cell lymphoma (DLBCL) with an International Prognostic Index (IPI) ≥3 are at higher risk for relapse after a complete response (CR) to first-line rituximab-based chemotherapy (R-chemo). Everolimus has single-agent activity in lymphoma. PILLAR-2 aimed to improve disease-free survival (DFS) with 1 year of adjuvant everolimus. Patients and methods Patients with high-risk (IPI ≥3) DLBCL and a positron emission tomography/computed tomography-confirmed CR to first-line R-chemo were randomized to 1 year of everolimus 10 mg/day or placebo. The primary end point was DFS; secondary end points were overall survival, lymphoma-specific survival, and safety. Results Between August 2009 and December 2013, 742 patients were randomized to everolimus (n = 372) or placebo (n = 370). Median follow-up was 50.4 months (range 24.0-76.9). Overall, 47% of patients were ≥65 years, 50% were male, and 42% had an IPI of 4 or 5. 48% and 67% completed everolimus and placebo, respectively. Primary reasons for everolimus discontinuation versus placebo were adverse events (AEs; 30% versus 12%) and relapsed disease (6% versus 13%). Everolimus did not significantly improve DFS compared with placebo (hazard ratio 0.92; 95% CI 0.69-1.22; P = 0.276). Two-year DFS rate was 77.8% (95% CI 72.7-82.1) with everolimus and 77.0% (95% CI 72.1-81.1) with placebo. Common grade 3/4 AEs with everolimus were neutropenia, stomatitis, and decreased CD4 lymphocytes. Conclusions Adjuvant everolimus did not improve DFS in patients already in PET/CT-confirmed CR. Future approaches should incorporate targeted agents such as everolimus with R-CHOP rather than as adjuvant therapy after CR has been obtained. ClinicalTrials.gov NCT00790036.
Tobacco Smoke and Risk of Childhood Acute Non-Lymphocytic Leukemia: Findings from the SETIL Study

Background Parental smoking and exposure of the mother or the child to environmental tobacco smoke (ETS) as risk factors for Acute non-Lymphocytic Leukemia (AnLL) were investigated. Methods Incident cases of childhood AnLL were enrolled in 14 Italian Regions during 1998–2001. We estimated odds ratios (OR) and 95% confidence intervals (95%CI) conducting logistic regression models including 82 cases of AnLL and 1,044 controls. Inverse probability weighting was applied adjusting for: age; sex; provenience; birth order; birth weight; breastfeeding; parental educational level age, birth year, and occupational exposure to benzene. Results Paternal smoke in the conception period was associated with AnLL (OR for ≥11 cigarettes/day = 1.79, 95% CI 1.01–3.15; P trend 0.05). An apparent effect modification by maternal age was identified: only children of mothers aged below 30 presented increased risks. We found weak statistical evidence of an association of AnLL with maternal exposure to ETS (OR for exposure>3 hours/day = 1.85, 95%CI 0.97–3.52; P trend 0.07). No association was observed between AnLL and either maternal smoking during pregnancy or child exposure to ETS. Conclusions This study is consistent with the hypothesis that paternal smoke is associated with AnLL. We observed statistical evidence of an association between maternal exposure to ETS and AnLL, but believe bias might have inflated our estimates.
Rocaglates as dual-targeting agents for experimental cerebral malaria

Significance Severe complications of malaria, such as anemia and cerebral malaria (CM) (neuroinflammation), are responsible for ∼25% of infant mortality in certain regions of Africa. Notwithstanding current effective antiplasmodial treatment, drug resistance is on the increase in the Plasmodium parasites, and therapy to treat CM is nonexistent. Here, we show that rocaglates derived from a natural product originally identified from plants of the Aglaia species, effectively block blood-stage parasite replication in several mouse models and in infected human RBCs. Importantly, neurological inflammation is mitigated and survival is promoted in experimental CM, highlighting the strong potential of this class of compounds to treat complicated malaria. Cerebral malaria (CM) is a severe and rapidly progressing complication of infection by Plasmodium parasites that is associated with high rates of mortality and morbidity. Treatment options are currently few, and intervention with artemisinin (Art) has limited efficacy, a problem that is compounded by the emergence of resistance to Art in Plasmodium parasites. Rocaglates are a class of natural products derived from plants of the Aglaia genus that have been shown to interfere with eukaryotic initiation factor 4A (eIF4A), ultimately blocking initiation of protein synthesis. Here, we show that the rocaglate CR-1-31B perturbs association of Plasmodium falciparum eIF4A (PfeIF4A) with RNA. CR-1-31B shows potent prophylactic and therapeutic antiplasmodial activity in vivo in mouse models of infection with Plasmodium berghei (CM) and Plasmodium chabaudi (blood-stage malaria), and can also block replication of different clinical isolates of P. falciparum in human erythrocytes infected ex vivo, including drug-resistant P. falciparum isolates. In vivo, a single dosing of CR-1-31B in P. berghei-infected animals is sufficient to provide protection against lethality. CR-1-31B is shown to dampen expression of the early proinflammatory response in myeloid cells in vitro and dampens the inflammatory response in vivo in P. berghei-infected mice. The dual activity of CR-1-31B as an antiplasmodial and as an inhibitor of the inflammatory response in myeloid cells should prove extremely valuable for therapeutic intervention in human cases of CM.