Miracle-dz/UniFAR-FTUs huggingface dataset:
Complete Unique Genome Sequence, Expression Profile, and Salivary Gland Tissue Tropism of the Herpesvirus 7 Homolog in Pigtailed Macaques

ABSTRACT Human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 are classified as roseoloviruses and are highly prevalent in the human population. Roseolovirus reactivation in an immunocompromised host can cause severe pathologies. While the pathogenic potential of HHV-7 is unclear, it can reactivate HHV-6 from latency and thus contributes to severe pathological conditions associated with HHV-6. Because of the ubiquitous nature of roseoloviruses, their roles in such interactions and the resulting pathological consequences have been difficult to study. Furthermore, the lack of a relevant animal model for HHV-7 infection has hindered a better understanding of its contribution to roseolovirus-associated diseases. Using next-generation sequencing analysis, we characterized the unique genome of an uncultured novel pigtailed macaque roseolovirus. Detailed genomic analysis revealed the presence of gene homologs to all 84 known HHV-7 open reading frames. Phylogenetic analysis confirmed that the virus is a macaque homolog of HHV-7, which we have provisionally named Macaca nemestrina herpesvirus 7 (MneHV7). Using high-throughput RNA sequencing, we observed that the salivary gland tissue samples from nine different macaques had distinct MneHV7 gene expression patterns and that the overall number of viral transcripts correlated with viral loads in parotid gland tissue and saliva. Immunohistochemistry staining confirmed that, like HHV-7, MneHV7 exhibits a natural tropism for salivary gland ductal cells. We also observed staining for MneHV7 in peripheral nerve ganglia present in salivary gland tissues, suggesting that HHV-7 may also have a tropism for the peripheral nervous system. Our data demonstrate that MneHV7-infected macaques represent a relevant animal model that may help clarify the causality between roseolovirus reactivation and diseases. IMPORTANCE Human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 are classified as roseoloviruses. We have recently discovered that pigtailed macaques are naturally infected with viral homologs of HHV-6 and HHV-7, which we provisionally named MneHV6 and MneHV7, respectively. In this study, we confirm that MneHV7 is genetically and biologically similar to its human counterpart, HHV-7. We determined the complete unique MneHV7 genome sequence and provide a comprehensive annotation of all genes. We also characterized viral transcription profiles in salivary glands from naturally infected macaques. We show that broad transcriptional activity across most of the viral genome is associated with high viral loads in infected parotid glands and that late viral protein expression is detected in salivary duct cells and peripheral nerve ganglia. Our study provides new insights into the natural behavior of an extremely prevalent virus and establishes a basis for subsequent investigations of the mechanisms that cause HHV-7 reactivation and associated disease.
Subduction zone forearc serpentinites as incubators for deep microbial life

Significance We document organic matter encapsulated in rock clasts from a oceanic serpentinite mud volcano above the Izu–Bonin–Mariana subduction zone (Pacific Ocean). Although we cannot pinpoint the exact origin of the organic matter, chemical analysis of the constituents resembles molecular signatures that could be produced by microbial life deep within or below the mud volcano. Considering the known temperature limit for life, 122 °C, and the subduction zone forearc geotherm where such mud volcanoes are located, we estimate that life could exist as deep as ∼10,000 m below the seafloor. This is considerably deeper than other active serpentinizing regions such as midocean ridges and could have provided sheltered ecosystems for life to survive the more violent phases of Earth’s history. Serpentinization-fueled systems in the cool, hydrated forearc mantle of subduction zones may provide an environment that supports deep chemolithoautotrophic life. Here, we examine serpentinite clasts expelled from mud volcanoes above the Izu–Bonin–Mariana subduction zone forearc (Pacific Ocean) that contain complex organic matter and nanosized Ni–Fe alloys. Using time-of-flight secondary ion mass spectrometry and Raman spectroscopy, we determined that the organic matter consists of a mixture of aliphatic and aromatic compounds and functional groups such as amides. Although an abiotic or subduction slab-derived fluid origin cannot be excluded, the similarities between the molecular signatures identified in the clasts and those of bacteria-derived biopolymers from other serpentinizing systems hint at the possibility of deep microbial life within the forearc. To test this hypothesis, we coupled the currently known temperature limit for life, 122 °C, with a heat conduction model that predicts a potential depth limit for life within the forearc at ∼10,000 m below the seafloor. This is deeper than the 122 °C isotherm in known oceanic serpentinizing regions and an order of magnitude deeper than the downhole temperature at the serpentinized Atlantis Massif oceanic core complex, Mid-Atlantic Ridge. We suggest that the organic-rich serpentinites may be indicators for microbial life deep within or below the mud volcano. Thus, the hydrated forearc mantle may represent one of Earth’s largest hidden microbial ecosystems. These types of protected ecosystems may have allowed the deep biosphere to thrive, despite violent phases during Earth’s history such as the late heavy bombardment and global mass extinctions.
The Effect of Local Decodability Constraints on Variable-Length Compression

We consider a variable-length source coding problem subject to local decodability constraints. In particular, we investigate the blocklength scaling behavior attainable by encodings of <inline-formula> <tex-math notation="LaTeX">$r$ </tex-math></inline-formula>-sparse binary sequences, under the constraint that any source bit can be correctly decoded upon probing at most <inline-formula> <tex-math notation="LaTeX">$d$ </tex-math></inline-formula> codeword bits. We consider both adaptive and non-adaptive access models, and derive upper and lower bounds that often coincide up to constant factors. Such a characterization for the fixed-blocklength analog of our problem, known as the bit probe complexity of static membership, remains unknown despite considerable attention from researchers over the last few decades. We also show that locally decodable schemes for sparse sequences are able to decode 0s (frequent source symbols) of the source with far fewer probes on average than they can decode 1s (infrequent source symbols), thus rigorizing the notion that infrequent symbols require high probe complexity, even on average. Connections to the fixed-blocklength model and to communication complexity are also briefly discussed.
Tacrolimus/sirolimus vs tacrolimus/methotrexate as GVHD prophylaxis after matched, related donor allogeneic HCT.

Grades 2-4 acute graft-versus-host disease (GVHD) occurs in approximately 35% of matched, related donor (MRD) allogeneic hematopoietic cell transplantation (HCT) recipients. We sought to determine if the combination of tacrolimus and sirolimus (Tac/Sir) was more effective than tacrolimus and methotrexate (Tac/Mtx) in preventing acute GVHD and early mortality after allogeneic MRD HCT in a phase 3, multicenter trial. The primary end point of the trial was to compare 114-day grades 2-4 acute GVHD-free survival using an intention-to-treat analysis of 304 randomized subjects. There was no difference in the probability of day 114 grades 2-4 acute GVHD-free survival (67% vs 62%, P = .38). Grades 2-4 GVHD was similar in the Tac/Sir and Tac/Mtx arms (26% vs 34%, P = .48). Neutrophil and platelet engraftment were more rapid in the Tac/Sir arm (14 vs 16 days, P < .001; 16 vs 19 days, P = .03). Oropharyngeal mucositis was less severe in the Tac/Sir arm (peak Oral Mucositis Assessment Scale score 0.70 vs 0.96, P < .001), but otherwise toxicity was similar. Chronic GVHD, relapse-free survival, and overall survival at 2 years were no different between study arms (53% vs 45%, P = .06; 53% vs 54%, P = .77; and 59% vs 63%, P = .36). Based on similar long-term outcomes, more rapid engraftment, and less oropharyngeal mucositis, the combination of Tac/Sir is an acceptable alternative to Tac/Mtx after MRD HCT. This study was funded by the National Heart, Lung, and Blood Institute and the National Cancer Institute; and the trial was registered at www.clinicaltrials. gov as #NCT00406393.
Terror in time: extending culturomics to address basic terror management mechanisms

ABSTRACT Building on Google's efforts to scan millions of books, this article introduces methodology using a database of annual word frequencies of the 40,000 most frequently occurring words in the American literature between 1800 and 2009. The current paper uses this methodology to replicate and identify terror management processes in historical context. Variation in frequencies of word usage of constructs relevant to terror management theory (e.g. death, worldview, self-esteem, relationships) are investigated over a time period of 209 years. Study 1 corroborated previous TMT findings and demonstrated that word use of constructs related to death and of constructs related to patriotism and romantic relationships significantly co-vary over time. Study 2 showed that the use of the word “death” most strongly co-varies over time with the use of medical constructs, but also co-varies with the use of constructs related to violence, relationships, religion, positive sentiment, and negative sentiment. Study 3 found that a change in the use of death related words is associated with an increase in the use of fear related words, but not in anxiety related words. Results indicate that the described methodology generates valuable insights regarding terror management theory and provide new perspectives for theoretical advances.
Bacteriophage GC1, a Novel Tectivirus Infecting Gluconobacter Cerinus, an Acetic Acid Bacterium Associated with Wine-Making

The Gluconobacter phage GC1 is a novel member of the Tectiviridae family isolated from a juice sample collected during dry white wine making. The bacteriophage infects Gluconobacter cerinus, an acetic acid bacterium which represents a spoilage microorganism during wine making, mainly because it is able to produce ethyl alcohol and transform it into acetic acid. Transmission electron microscopy revealed tail-less icosahedral particles with a diameter of ~78 nm. The linear double-stranded DNA genome of GC1 (16,523 base pairs) contains terminal inverted repeats and carries 36 open reading frames, only a handful of which could be functionally annotated. These encode for the key proteins involved in DNA replication (protein-primed family B DNA polymerase) as well as in virion structure and assembly (major capsid protein, genome packaging ATPase (adenosine triphosphatase) and several minor capsid proteins). GC1 is the first tectivirus infecting an alphaproteobacterial host and is thus far the only temperate tectivirus of gram-negative bacteria. Based on distinctive sequence and life-style features, we propose that GC1 represents a new genus within the Tectiviridae, which we tentatively named “Gammatectivirus”. Furthermore, GC1 helps to bridge the gap in the sequence space between alphatectiviruses and betatectiviruses.
Development of a Lethal Intranasal Exposure Model of Ebola Virus in the Cynomolgus Macaque

Ebola virus (EBOV) is a filovirus that can cause Ebola virus disease (EVD). No approved vaccines or therapies exist for filovirus infections, despite an urgent need. The development and testing of effective countermeasures against EBOV requires use of animal models and a thorough understanding of how the model aligns with EVD in humans. The majority of published studies report outcomes of parenteral exposures for emulating needle stick transmission. However, based on data from EVD outbreaks, close contact exposures to infected bodily fluid seems to be one of the primary routes of EBOV transmission. Thus, further work is needed to develop models that represent mucosal exposure. To characterize the outcome of mucosal exposure to EBOV, cynomolgus macaques were exposed to EBOV via intranasal (IN) route using the LMA® mucosal atomization device (LMA® MAD). For comparison, four non-human primates (NHPs) were exposed to EBOV via intramuscular (IM) route. This IN exposure model was uniformly lethal and correlated with a statistically significant delay in time to death when compared to exposure via the IM route. This more closely reflects the timeframes observed in human infections. An IN model of exposure offers an attractive alternative to other models as it can offer insight into the consequences of exposure via a mucosal surface and allows for screening countermeasures via a different exposure route.
Trimer Enhancement Mutation Effects on HIV-1 Matrix Protein Binding Activities

ABSTRACT The HIV-1 matrix (MA) protein is the amino-terminal domain of the HIV-1 precursor Gag (Pr55Gag) protein. MA binds to membranes and RNAs, helps transport Pr55Gag proteins to virus assembly sites at the plasma membranes of infected cells, and facilitates the incorporation of HIV-1 envelope (Env) proteins into virions by virtue of an interaction with the Env protein cytoplasmic tails (CTs). MA has been shown to crystallize as a trimer and to organize on membranes in hexamer lattices. MA mutations that localize to residues near the ends of trimer spokes have been observed to impair Env protein assembly into virus particles, and several of these are suppressed by the 62QR mutation at the hubs of trimer interfaces. We have examined the binding activities of wild-type (WT) MA and 62QR MA variants and found that the 62QR mutation stabilized MA trimers but did not alter the way MA proteins organized on membranes. Relative to WT MA, the 62QR protein showed small effects on membrane and RNA binding. However, 62QR proteins bound significantly better to Env CTs than their WT counterparts, and CT binding efficiencies correlated with trimerization efficiencies. Our data suggest a model in which multivalent binding of trimeric HIV-1 Env proteins to MA trimers contributes to the process of Env virion incorporation. IMPORTANCE The HIV-1 Env proteins assemble as trimers, and incorporation of the proteins into virus particles requires an interaction of Env CT domains with the MA domains of the viral precursor Gag proteins. Despite this knowledge, little is known about the mechanisms by which MA facilitates the virion incorporation of Env proteins. To help elucidate this process, we examined the binding activities of an MA mutant that stabilizes MA trimers. We found that the mutant proteins organized similarly to WT proteins on membranes, and that mutant and WT proteins revealed only slight differences in their binding to RNAs or lipids. However, the mutant proteins showed better binding to Env CTs than the WT proteins, and CT binding correlated with MA trimerization. Our results suggest that multivalent binding of trimeric HIV-1 Env proteins to MA trimers contributes to the process of Env virion incorporation.
Effects of different amounts of exercise on preventing depressive symptoms in community-dwelling older adults: a prospective cohort study in Taiwan

Objectives To compare the effects of four different amounts of exercise for preventing depressive symptoms in community-dwelling older adults. Design Prospective cohort study. Setting A nationally representative sample in Taiwan. Participants Four waves of the survey ‘Taiwan Longitudinal Study on Aging (TLSA)’ from 1996 to 2007 were analysed. A total of 2673 older adults aged 65 years and over were recruited. Primary and secondary outcome measures Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale (CESD). Four different types/amounts of exercise were examined including: (1) 3 times/week, 15 min/time; (2) 3 times/week, 30 min/time; (3) 6 times/week, 15 min/time; and (4) 6 times/week, 30 min/time. All exercise types were required to have at least moderate intensity. The impacts of different amounts of exercise on depressive symptoms were analysed using generalised linear mixed models. Results More than one-fifth of the elder individuals under consideration had depressive symptoms (CESD ≥10). About 38.6% of older adults met the lowest criteria for exercise type 1, and fewer (28.0%) met the highest criteria for type 4. Only exercise type 4 in the current survey was initially related to lower depressive symptoms (OR=0.8, 95% CI 0.66 to 0.95). However, after considering the interaction between time and changes in exercise patterns, the results showed that all persistent exercise models, even if a very low amount (3 times/week, 15 min/time), had significantly preventive effects on depressive symptoms (OR=0.56~0.67). Conclusion Consistent exercise with at least 15 min per time, three times a week of moderate intensity is significantly associated with lower risk of depressive symptoms. This low amount of exercise may be easier to promote at the community and population level than other alternatives. Trial registration Registry number 104040 of the Institutional Ethics Committee of Chia-Yi Christian Hospital.
Characterizing Spouse/Partner Depression and Alcohol Problems Over the Course of Military Deployment

Objective: Spouse/partners of military personnel demonstrate elevated levels of distress during military deployments, yet there is insufficient information about courses of adjustment over time. The current study identified trajectories of depression and alcohol use problems and predictors of those trajectories across the deployment cycle. Method: National Guard soldiers (N = 1973) and spouses/intimate partners (N = 1020) completed assessments of risk/protective factors and baseline measures of mental health functioning 2 to 5 months prior to soldiers’ 1-year deployments (Time 1) to Kuwait/Iraq in support of Operation New Dawn or Afghanistan in support of Operation Enduring Freedom. Partners’ mental health was reassessed at 4 months (Time 2) and 8 months (Time 3) after soldiers deployed, and both spouses/partners and soldiers were reassessed 2–3 months postdeployment (Time 4). Results: Latent class growth modeling of partner depression symptoms over time revealed 4 groups: Resilience (79.9%), Deployment Distress (8.9%), Anticipatory Distress (8.4%), and Post-Deployment Distress (2.7%). Three alcohol misuse trajectories were identified: Resilience (91.3%), Deployment Onset (5.4%), and Deployment Desistance (3.3%). Predeployment predictors of partners’ depression symptom trajectories varied by group and included soldier reports of stressors and social support and partner levels of neuroticism, introversion, disconstraint, and reported stressors. Predeployment predictors of alcohol misuse trajectories varied by group, and included soldier levels of alcohol misuse as well as partner neuroticism, disconstraint, and family readiness. Conclusions: Delineating and predicting trajectories of partner adjustment can allow for better targeted interventions toward those most at risk for heightened distress or alcohol problems over the deployment cycle.
Does depression increase the risk of stroke in patients with rheumatoid arthritis? A population-based cohort study

Objectives Comorbid depression is common and undertreated in patients with rheumatoid arthritis (RA). It remains uncertain whether comorbid depression provoked the risk of poor clinical outcome, stroke in particular, among patients with RA. This work aimed to determine if depression onset during the treatment process increases stroke risk for patients with RA as compared with those with (1) neither RA nor depression, (2) RA only and (3) depression only. Design A nationwide, population-based cohort study. Setting Taiwan's Longitudinal Health Insurance Database. Participants We identified 8045 subjects with a newly diagnosed RA between 1997 and 2010, together with 32 600 subjects without RA matched by age, gender and index date. All subjects were further divided into four groups based on whether they were diagnosed with comorbid depression during the follow-up period. Main outcome measure The incidence rate and HR for incident stroke were estimated by the end of 2012 using Cox proportional hazard regression. Results We discovered that patients with RA with the comorbid depression exhibited the highest risk of stroke, with an adjusted HR of 2.18 (95% CI 1.87 to 2.54). Those with RA only or those with depression only still had the higher risk of stroke by 43% and 57% as compared with subjects without either condition. Multivariate analysis showed RA subjects who were male or older, incurred the onset of depression, or had comorbidities such as hypertension, diabetes as well as heart disease, had a greater risk of stroke. Conclusions This study cleared up the significant association between RA and the subsequent risk of stroke, and further highlighted that the onset of depression within the treatment process may increase stroke risk for RA subjects. Findings could assist healthcare providers to pinpoint individuals with RA with a higher predisposition of stroke, which could facilitate the provision of appropriate rehabilitation.
Overcoming challenges in primary care education: a trial of a longitudinal integrated clerkship in a rural community hospital setting in Japan

CHALLENGES WE FACE ⦁ Clinical placements have been organised as short-term clerkships where learners undertake a succession of clinical learning experiences focused on single organ-specific systems. ⦁ Even community-based clinics are traditionally focused on specific specialties, such as internal medicine, paediatrics or psychiatry and it has been very challenging to develop a generalist culture in our context. ⦁ Medical education has not been positioned in more rural areas but there is an increasing shortage of community-based doctors and the need for generalists is increasing, especially in remoter areas.
Naturalistic decision-making in expert badminton players

This paper reports on a study of naturalistic decision-making in expert badminton players. These decisions are frequently taken under time-pressured conditions, yet normally lead to successful performance. Two male badminton teams participated in this study. Self-confrontation interviews were used to collect data. Inductive data analysis revealed three types of intentions during a rally: to maintain the rally; to take the advantage; and to finish the point. It also revealed eight types of decision taken in this situation: to ensure an action; to observe the opponent's response to an action; to realize a limited choice; to influence the opponent's decision; to put pressure on an opponent; to surprise the opponent; to reproduce an efficient action; and to play wide. A frequent decision was to put pressure on the opponent. Different information and knowledge was linked to specific decisions. The results are discussed in relation to research that has considered naturalistic decision-making.
Synthesis, Electrical and Optical Characterization of Semiconductor Nanowires

ii Dedication . iv Acknowledgements . x Vita . vi Publications . vi Field of study . vi Table of Content . vii List of Tables . x List of Figures . xi Chapter 1: Introduction . 1 Chapter 2: Fabrication Techniques . 5 2.