Miracle-dz/UniFAR-FTUs huggingface dataset:
Combined free-stream disturbance measurements and receptivity studies in hypersonic wind tunnels by means of a slender wedge probe and direct numerical simulation

Combined free-stream disturbance measurements and receptivity studies in hypersonic wind tunnels were conducted by means of a slender wedge probe and direct numerical simulation. The study comprises comparative tunnel noise measurements at Mach 3, 6 and 7.4 in two Ludwieg tube facilities and a shock tunnel. Surface pressure fluctuations were measured over a wide range of frequencies and test conditions including harsh test environments not accessible to measurement techniques such as Pitot probes and hot-wire anemometry. A good agreement was found between normalized Pitot pressure fluctuations converted into normalized static pressure fluctuations and the wedge probe readings. Quantitative results of the tunnel noise are provided in frequency ranges relevant for hypersonic boundary-layer transition. Complementary numerical simulations of the leading-edge receptivity to fast and slow acoustic waves were performed for the applied wedge probe at conditions corresponding to the experimental free-stream conditions. The receptivity to fast acoustic waves was found to be characterized by an early amplification of the induced fast mode. For slow acoustic waves an initial decay was found close to the leading edge. At all Mach numbers, and for all considered frequencies, the leading-edge receptivity to fast acoustic waves was found to be higher than the receptivity to slow acoustic waves. Further, the effect of inclination angles of the acoustic wave with respect to the flow direction was investigated. An inclination angle was found to increase the response on the wave-facing surface of the probe and decrease the response on the opposite surface for fast acoustic waves. A frequency-dependent response was found for slow acoustic waves. The combined numerical and experimental approach in the present study confirmed the previous suggestion that the slow acoustic wave is the dominant acoustic mode in noisy hypersonic wind tunnels.
Reoperation after breast-conserving surgery for cancer in Australia: statewide cohort study of linked hospital data

Objectives To investigate between-hospital variation in the probability of reoperation within 90 days of initial breast-conserving surgery (BCS), and the contribution of health system-level and other factors. Design Population-based, retrospective cohort study. Setting New South Wales (NSW), Australia. Participants Linked administrative hospitalisation data were used to define a cohort of adult women undergoing initial BCS for breast cancer in NSW between 1 July 2002 and 31 December 2013. Primary outcome measures Multilevel, cross-classified models with patients clustered within hospitals and residential areas were used to examine factors associated with any reoperation, and either re-excision or mastectomy, within 90 days. Results Of 34 458 women undergoing BCS, 29.1% underwent reoperation within 90 days, half of which were mastectomies. Overall, the probability of reoperation decreased slightly over time. However, there were divergent patterns by reoperation type; the probability of re-excision increased alongside a concomitant decrease in the probability of mastectomy. Significant between-hospital variation was observed. Non-metropolitan location and surgery at low-volume hospitals were associated with a higher overall probability of reoperation, and of mastectomy specifically, after accounting for patient-level factors, calendar year and area-level socioeconomic status. The magnitude of association with geographical location and surgical volume decreased over time. Conclusions Reoperation rates within 90 days of BCS varied significantly between hospitals. For women undergoing mastectomy after BCS, this represents a dramatic change in clinical course. Multilevel modelling suggests unwarranted clinical variation may be an issue, likely due to disparities in access to multidisciplinary breast cancer care and preoperative diagnostic procedures. However, the observed reduction in disparities over time is encouraging and indicates that guidelines and policy initiatives have the potential to improve regional breast cancer care.
Multisite Phosphorylation of the Sum1 Transcriptional Repressor by S-Phase Kinases Controls Exit from Meiotic Prophase in Yeast

ABSTRACT Activation of the meiotic transcription factor Ndt80 is a key regulatory transition in the life cycle of Saccharomyces cerevisiae because it triggers exit from pachytene and entry into meiosis. The NDT80 promoter is held inactive by a complex containing the DNA-binding protein Sum1 and the histone deacetylase Hst1. Meiosis-specific phosphorylation of Sum1 by the protein kinases Cdk1, Ime2, and Cdc7 is required for NDT80 expression. Here, we show that the S-phase-promoting cyclin Clb5 activates Cdk1 to phosphorylate most, and perhaps all, of the 11 minimal cyclin-dependent kinase (CDK) phospho-consensus sites (S/T-P) in Sum1. Nine of these sites can individually promote modest levels of meiosis, yet these sites function in a quasiadditive manner to promote substantial levels of meiosis. Two Cdk1 sites and an Ime2 site individually promote high levels of meiosis, likely by preparing Sum1 for phosphorylation by Cdc7. Chromatin immunoprecipitation reveals that the phosphorylation sites are required for removal of Sum1 from the NDT80 promoter. We also find that Sum1, but not its partner protein Hst1, is required to repress NDT80 transcription. Thus, while the phosphorylation of Sum1 may lead to dissociation from DNA by influencing Hst1, it is the presence of Sum1 on DNA that determines whether NDT80 will be expressed.
Acute chest syndrome in sickle cell disease

ABSTRACT Acute chest syndrome (ACS) is a leading complication of sickle cell disease (SCD) with significant morbidity and mortality. ACS is the most common cause of death and the second most common cause of hospitalization in patients with SCD. Delineating the specific cause of ACS is often difficult, and multiple risk factors that precipitate ACS frequently coexist. The prominent risk factors include infection, hypoxia, bronchial hyperresponsiveness, the SCD genotype, and opioid use. The key to the successful treatment of ACS is early recognition and initiation of treatment without delay. The main goal is to prevent and treat acute respiratory failure and, thus, minimize irreversible lung damage. This review focuses on the risk factors, pathogenesis, clinical presentation, and management of ACS.
Infusion of CD3/CD28 costimulated umbilical cord blood T cells at the time of single umbilical cord blood transplantation may enhance engraftment

Limited cell numbers in umbilical cord blood (UCB) grafts present a major impediment to favorable outcomes in adult transplantation, largely related to delayed or failed engraftment. The advent of UCB transplantation (UCBT) using two grafts successfully circumvents this obstacle, despite the engraftment of only one unit. Preclinical models suggested that the addition of UCB T cells at the time of transplant can enhance engraftment. We tested whether ex vivo activation by CD3/CD28 costimulation and expansion of T cells from a single UCB graft would be safe and feasible in adults with advanced hematologic malignancies, with an overall objective of optimizing engraftment in single unit UCBT. In this phase 1 study, recipients of single UCB units were eligible if the unit was stored in two adequate fractions. Dose limiting toxicity was defined as grade 3 or grade 4 GVHD within 90 days of UCBT. Four patients underwent UCBT; all were treated at the first dose level (105cells/kg). At the 105cells/kg dose level two subjects experienced grade 3 intestinal GVHD, thus meeting stopping criteria. For three subjects, neutrophil engraftment was early (12, 17, and 20 days), while one subject experienced primary graft failure. We observed early donor T cell trafficking and found that expanded T cells produced supraphysiologic levels of cytokines relevant to engraftment and to lymphoid differentiation and function. Taken together, these preliminary data suggest rapid engraftment in recipients of a single UCBT combined with relatively low doses of activated T cells, though potentially complicated by severe GVHD. Am. J. Hematol. 91:453–460, 2016. © 2016 Wiley Periodicals, Inc.
A Possible Trifunctional β-Carotene Synthase Gene Identified in the Draft Genome of Aurantiochytrium sp. Strain KH105

Labyrinthulomycetes have been regarded as a promising industrial source of xanthophylls, including astaxanthin and canthaxanthin, polyunsaturated fatty acids such as docosahexaenoic acid and docosapentaenoic acid, ω-3 oils, and terpenic hydrocarbons, such as sterols and squalene. A Thraustochytrid, Aurantiochytrium sp. KH105 produces carotenoids, including astaxanthin, with strong antioxidant activity. To gain genomic insights into this capacity, we decoded its 97-Mbp genome and characterized genes for enzymes involved in carotenoid biosynthesis. Interestingly, all carotenogenic genes, as well as other eukaryotic genes, appeared duplicated, suggesting that this strain is diploid. In addition, among the five genes involved in the pathway from geranylgeranyl pyrophosphate to astaxanthin, geranylgeranyl phytoene synthase (crtB), phytoene desaturase (crtI) and lycopene cyclase (crtY) were fused into single gene (crtIBY) with no internal stop codons. Functionality of the trifunctional enzyme, CrtIBY, to catalyze the reaction from geranylgeranyl diphosphate to β-carotene was confirmed using a yeast assay system and mass spectrometry. Furthermore, analyses of differential gene expression showed characteristic up-regulation of carotenoid biosynthetic genes during stationary and starvation phases under these culture conditions. This suggests genetic engineering events to promote more efficient production of carotenoids. We also showed an occurrence of crtIBY in other Thraustochytrid species.
Causal Inference via Kernel Deviance Measures

Discovering the causal structure among a set of variables is a fundamental problem in many areas of science. In this paper, we propose Kernel Conditional Deviance for Causal Inference (KCDC) a fully nonparametric causal discovery method based on purely observational data. From a novel interpretation of the notion of asymmetry between cause and effect, we derive a corresponding asymmetry measure using the framework of reproducing kernel Hilbert spaces. Based on this, we propose three decision rules for causal discovery. We demonstrate the wide applicability of our method across a range of diverse synthetic datasets. Furthermore, we test our method on real-world time series data and the real-world benchmark dataset Tubingen Cause-Effect Pairs where we outperform existing state-of-the-art methods.
Enhancing health literacy through co-design: development of culturally appropriate materials on genetic risk and customary consanguineous marriage

Aim To develop a simple health literacy intervention aimed at supporting informed reproductive choice among members of UK communities practising customary consanguineous marriage. Background The contribution of ‘health literacy’ to reducing health inequalities and improving primary health-care efficiency is increasingly recognised. Enhancing genetic literacy has received particular attention recently. Consanguineous marriage is customarily practised among some UK minority ethnic communities and carries some increased risk of recessive genetic disorders among offspring compared with unions among unrelated partners. The need to enhance genetic literacy on this issue has been highlighted, but no national response has ensued. Instead, a range of undocumented local responses are emerging. Important knowledge gaps remain regarding how the development and implementation of culturally appropriate, effective and sustainable responses can be achieved. Methods Our co-design approach involved active participation by local people. Initial insight generation employed six focus group discussions and 14 individual interviews to describe current understandings and information needs. A total of 11 personas (heuristic narrative portraits of community ‘segments’) resulted; four participatory workshops provided further understanding of: preferred information channels; feasible information conveyance; and responses to existing materials. Prototype information resources were then developed and feedback gathered via two workshops. Following further refinement, final feedback from health-care professionals and community members ensured accuracy and appropriateness. Findings The project demonstrated the utility of co-design for addressing an issue often considered complex and sensitive. With careful planning and orchestration, active participation by diverse community members was achieved. Key learning included: the importance of establishing trusting and respectful relationships; responding to diversity within the community; and engendering a creative and enjoyable experience. The resultant materials were heavily shaped by local involvement. Evaluative work is now needed to assess impacts on knowledge and service uptake. Longer term sustainability will depend on whether innovative community-level work is accompanied by broader strategy including investment in services and professional development.
Laparoscopic excision of deep rectovaginal endometriosis in BSGE endometriosis centres: a multicentre prospective cohort study

Objective To estimate the effectiveness and safety of laparoscopic surgical excision of rectovaginal endometriosis. Design A multicentre, prospective cohort study. Setting 51 hospitals accredited as specialist endometriosis centres. Participants 5162 women of reproductive age with rectovaginal endometriosis of which 4721 women had planned laparoscopic excision. Interventions Laparoscopic surgical excision of rectovaginal endometriosis requiring dissection of the pararectal space. Main outcome measures Standardised symptom questionnaires enquiring about chronic pelvic pain, bladder and bowel symptoms, analgesia use and quality of life (EuroQol) completed prior to surgery and at 6, 12 and 24 months postoperatively. Serious perioperative and postoperative complications including major haemorrhage, infection and visceral injury were recorded. Results At 6 months postsurgery, there were significant reductions in premenstrual, menstrual and non-cyclical pelvic pain, deep dyspareunia, dyschezia, low back pain and bladder pain. In addition, there were significant reductions in voiding difficulty, bowel frequency, urgency, incomplete emptying, constipation and passing blood. These reductions were maintained at 2 years, with the exception of voiding difficulty. Global quality of life significantly improved from a median pretreatment score of 55/100 to 80/100 at 6 months. There was a significant improvement in quality of life in all measured domains and in quality-adjusted life years. These improvements were sustained at 2 years. All analgesia use was reduced and, in particular, opiate use fell from 28.1% prior to surgery to 16.1% at 6 months. The overall incidence of complications was 6.8% (321/4721). Gastrointestinal complications (enterotomy, anastomotic leak or fistula) occurred in 52 (1.1%) operations and of the urinary tract (ureteric/bladder injury or leak) in 49 (1.0%) procedures. Conclusion Laparoscopic surgical excision of rectovaginal endometriosis appears to be effective in treating pelvic pain and bowel symptoms and improving health-related quality of life and has a low rate of major complications when performed in specialist centres.
Performance Analysis of Cloud Applications

Many popular cloud applications are large-scale distributed systems with each request involving tens to thousands of RPCs and large code bases. Because of their scale, performance optimizations without actionable supporting data are likely to be ineffective: they will add complexity to an already complex system often without chance of a benefit. This paper describes the challenges in collecting actionable data for Gmail, a service with more than 1 billion active accounts. Using production data from Gmail we show that both the load and the nature of the load changes continuously. This makes Gmail performance difficult to model with a synthetic test and difficult to analyze in production. We describe two techniques for collecting actionable data from a production system. First, coordinated bursty tracing allows us to capture bursts of events across all layers of our stack simultaneously. Second, vertical context injection enables us combine high-level events with low-level events in a holistic trace without requiring us to explicitly propagate this information across our software stack.
Synthesis and Biological Evaluation of Stilbene Analogues as Hsp90 C‐Terminal Inhibitors

The design, synthesis, and biological evaluation of stilbene‐based novobiocin analogues is reported. Replacement of the biaryl amide side chain with a triazole side chain produced compounds that exhibited good antiproliferative activities. Heat shock protein 90 (Hsp90) inhibition was observed when N‐methylpiperidine was replaced with acyclic tertiary amines on the stilbene analogues that also contain a triazole‐derived side chain. These studies revealed that ≈24 Å is the optimal length for compounds that exhibit good antiproliferative activity as a result of Hsp90 inhibition.
Location-Aided Pilot Contamination Avoidance for Massive MIMO Systems

Pilot contamination, defined as the interference during the channel estimation process due to reusing the same pilot sequences in neighboring cells, can severely degrade the performance of massive multiple-input multiple-output systems. In this paper, we propose a location-based approach to mitigating the pilot contamination problem for uplink multiple-input multiple-output systems. Our approach makes use of the approximate locations of mobile devices to provide good estimates of the channel statistics between the mobile devices and their corresponding base stations. Specifically, we aim at avoiding pilot contamination even when the number of base station antennas is not very large, and when multiple users from different cells, or even in the same cell, are assigned the same pilot sequence. First, we characterize a desired angular region of the target user at the serving base station based on the number of base station antennas and the location of the target user, and make the observation that in this region the interference is close to zero due to the spatial separability. Second, based on this observation, we propose pilot coordination methods for multi-user multi-cell scenarios to avoid pilot contamination. The numerical results indicate that the proposed pilot contamination avoidance schemes enhance the quality of the channel estimation and thereby improve the per-cell sum rate offered by target base stations.
Involvement of Calcium Signaling and the Actin Cytoskeleton in the Membrane Block to Polyspermy in Mouse Eggs1

Abstract This study examines the effects of actin microfilament-disrupting drugs on events of fertilization, with emphasis on gamete membrane interactions. Mouse eggs, freed of their zonae pellucidae, were treated with drugs that perturb the actin cytoskeleton by different mechanisms (cytochalasin B, cytochalasin D, jasplakinolide, latrunculin B) and then inseminated. Cytochalasin B, jasplakinolide, and latrunculin B treatments resulted in a decrease in the percentage of eggs fertilized and the average number of sperm fused per egg. However, cytochalasin D treatment resulted in an increase in the average number of sperm fused per egg and the percentage of polyspermic eggs. This increase in polyspermy occurred despite the observation that cytochalasin D treatment caused a decrease in sperm-egg binding and did not affect spontaneous acrosome reactions or sperm motility. This suggested that cytochalasin D-treated eggs had an impaired ability to establish a block to polyspermy at the level of the plasma membrane. The effect of cytochalasin D on the block to polyspermy was not due to a general disruption of egg activation because sperm-induced calcium oscillations and cortical granule exocytosis were similar in cytochalasin D-treated and control eggs. However, buffering of intracellular calcium levels with the calcium chelator BAPTA-AM resulted in an increase in polyspermy. Together, these data suggest that a postfertilization decrease in egg membrane receptivity to sperm requires functions of the egg actin cytoskeleton that are disrupted by cytochalasin D. Furthermore, egg activation-associated increased intracellular calcium levels are necessary but not sufficient to affect postfertilization membrane dynamics that contribute to a membrane block to polyspermy.
Anatomy of Mississippi Delta growth and its implications for coastal restoration

Prehistoric rates of land gain in a large portion of the Mississippi Delta are significantly outpaced by present-day rates of land loss. The decline of several of the world’s largest deltas has spurred interest in expensive coastal restoration projects to make these economically and ecologically vital regions more sustainable. The success of these projects depends, in part, on our understanding of how delta plains evolve over time scales longer than the instrumental record. Building on a new set of optically stimulated luminescence ages, we demonstrate that a large portion (~10,000 km2) of the late Holocene river–dominated Mississippi Delta grew in a radially symmetric fashion for almost a millennium before abandonment. Sediment was dispersed by deltaic distributaries that formed by means of bifurcations at the coeval shoreline and remained active throughout the life span of this landform. Progradation rates (100 to 150 m/year) were surprisingly constant, producing 6 to 8 km2 of new land per year. This shows that robust rates of land building were sustained under preindustrial conditions. However, these rates are several times lower than rates of land loss over the past century, indicating that only a small portion of the Mississippi Delta may be sustainable in a future world with accelerated sea-level rise.