Direct numerical simulation of a tip-leakage flow in a planar duct with a longitudinal slit

A planar duct flow configuration with a cross-flow injected from a longitudinal slit close to the upper wall of the duct is studied by using a direct numerical simulation approach to explore the underlying flow mechanism in relation to the tip-leakage vortex (TLV), which is one of the most important flow phenomena in turbomachinery. Major characteristics of TLV in a rotor of turbomachinery are identified in the current flow model. The analysis of mean and instantaneous flow fields reveals that the interaction between the main (axial) flow and jet (cross) flow is the primary source of the generation of the TLV. The evolution of the TLV is then investigated, and a vortex breakup phenomenon is identified. The evolution of TLV can be divided into three phases, i.e. the formation phase, the break-up phase, and the diffusion phase. Mean streamlines and turbulence kinetic energy (TKE) budgets are analysed, showing that the high TKE central spot in the formation phase is due to the interaction between highly swirling vortex filaments and mean velocity gradient. In the outer part of the TLV, the TKE is mainly produced in the shear-layer and transported towards the centre by the turbulence transport

A Large Sample Study of Red Giants in the Globular Cluster Omega Centauri (NGC 5139)

We present abundances of several light, alpha, Fe-peak, and neutron-capture elements for 66 red giant branch (RGB) stars in the Galactic globular cluster Omega Centauri. Our observations lie in the range 12.0<V<13.5 and focus on the intermediate and metal-rich RGBs. We find that there are at least four peaks in the metallicity distribution function at [Fe/H]=-1.75, -1.45, -1.05, and -0.75, which correspond to about 55%, 30%, 10%, and 5% of our sample, respectively. Additionally, the most metal-rich stars are the most centrally located. Na and Al are correlated despite exhibiting star-to-star dispersions of more than a factor of 10, but the distribution of those elements appears to be metallicity dependent and are divided at [Fe/H]~-1.2. About 40-50% of stars with [Fe/H]<-1.2 have Na and Al abundances consistent with production solely in Type II supernovae and match observations of disk and halo stars at comparable metallicity. The remaining metal-poor stars are enhanced in Na and Al compared to their disk and halo counterparts and are mostly consistent with predicted yields from >5 M_sun asymptotic giant branch (AGB) stars. At [Fe/H]>-1.2, more than 75% of the stars are Na/Al enhanced and may have formed almost exclusively from AGB ejecta. Most of these stars are enhanced in Na by at least 0.2 dex for a given Al abundance than would be expected based on "normal" globular cluster values. All stars in our sample are alpha-rich and have solar-scaled Fe-peak abundances. Eu does not vary extensively as a function of metallicity; however, [La/Fe] varies from about -0.4 to +2 and stars with [Fe/H]>-1.5 have [La/Eu] values indicating domination by the s-process. A quarter of our sample have [La/Eu]>+1 and may be the result of mass transfer in a binary system.Comment: ApJ Accepted; 90 pages, 16 Figures, 5 Table

Ricolinostat plus lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: a multicentre phase 1b trial

BACKGROUND: Histone deacetylase (HDAC) inhibitors are an important new class of therapeutics for treating multiple myeloma. Ricolinostat (ACY-1215) is the first oral selective HDAC6 inhibitor with reduced class I HDAC activity to be studied clinically. Motivated by findings from preclinical studies showing potent synergistic activity with ricolinostat and lenalidomide, our goal was to assess the safety and preliminary activity of the combination of ricolinostat with lenalidomide and dexamethasone in relapsed or refractory multiple myeloma. METHODS: In this multicentre phase 1b trial, we recruited patients aged 18 years or older with previously treated relapsed or refractory multiple myeloma from five cancer centres in the USA. Inclusion criteria included a Karnofsky Performance Status score of at least 70, measureable disease, adequate bone marrow reserve, adequate hepatic function, and a creatinine clearance of at least 50 mL per min. Exclusion criteria included previous exposure to HDAC inhibitors; previous allogeneic stem-cell transplantation; previous autologous stem-cell transplantation within 12 weeks of baseline; active systemic infection; malignancy within the last 5 years; known or suspected HIV, hepatitis B, or hepatitis C infection; a QTc Fridericia of more than 480 ms; and substantial cardiovascular, gastrointestinal, psychiatric, or other medical disorders. We gave escalating doses (from 40-240 mg once daily to 160 mg twice daily) of oral ricolinostat according to a standard 3 + 3 design according to three different regimens on days 1-21 with a conventional 28 day schedule of oral lenalidomide (from 15 mg [in one cohort] to 25 mg [in all other cohorts] once daily) and oral dexamethasone (40 mg weekly). Primary outcomes were dose-limiting toxicities, the maximum tolerated dose of ricolinostat in this combination, and the dose and schedule of ricolinostat recommended for further phase 2 investigation. Secondary outcomes were the pharmacokinetics and pharmacodynamics of ricolinostat in this combination and the preliminary anti-tumour activity of this treatment. The trial is closed to accrual and is registered at ClinicalTrials.gov, number NCT01583283. FINDINGS: Between July 12, 2012, and Aug 20, 2015, we enrolled 38 patients. We observed two dose-limiting toxicities with ricolinostat 160 mg twice daily: one (2%) grade 3 syncope and one (2%) grade 3 myalgia event in different cohorts. A maximum tolerated dose was not reached. We chose ricolinostat 160 mg once daily on days 1-21 of a 28 day cycle as the recommended dose for future phase 2 studies in combination with lenalidomide 25 mg and dexamethasone 40 mg. The most common adverse events were fatigue (grade 1-2 in 14 [37%] patients; grade 3 in seven [18%]) and diarrhoea (grade 1-2 in 15 [39%] patients; grade 3 in two [5%]). Our pharmacodynamic studies showed that at clinically relevant doses, ricolinostat selectively inhibits HDAC6 while retaining a low and tolerable level of class I HDAC inhibition. The pharmacokinetics of ricolinostat and lenalidomide were not affected by co-administration. In a preliminary assessment of antitumour activity, 21 (55% [95% CI 38-71]) of 38 patients had an overall response. INTERPRETATION: The findings from this study provide preliminary evidence that ricolinostat is a safe and well tolerated selective HDAC6 inhibitor, which might partner well with lenalidomide and dexamethasone to enhance their efficacy in relapsed or refractory multiple myeloma. FUNDING: Acetylon Pharmaceuticals

The Vehicle, Fall 1993

Table of Contents 7/10ths SynthesisPeter F. Essigpage 5 Aug 1992 (My Small Catechism)Jon Montgomerypage 6 Chaos Is-J. Dylan McNeillpage 7 UntouchedTraci Williamspage 8 The JustificationJohn C. Carminepage 8 LincolnJon Montgomerypage 9 Untitled (Photo)Nicole Niemanpage 10 Park PoemJohn Brillhartpage 11 SmokeJulia Ann Canhampage 12 Warming the BenchAnn Moutraypage 12 Cereal KillerJay Harnackpage 13 The Dutiful SonsTom McGrathpage 14 UntitledCatherine DeGraafpage 17 7-up bottleWalt Howardpage 17 BreedDan Trutterpage 18 An Argument Against LoveTony Martinezpage 19 UntitledT. Scott Laniganpage 19 Glassblowers BallStephanie Franzenpage 20 Portrait of a Young GirlJohn C. Carminepage 20 Untitled (artwork)Dan Trutterpage 21 Death of a FriendLizabeth Kulkapage 22 Submission BluesMartin Paul Brittpage 23 To the Fourteen Year Old SuicideScott Langenpage 23 The Flabby PilgrimTom McGrathpage 24 The Fall of ImmortalityBrian Wheelerpage 25 Merging with AirThom Schnarrepage 26 UntitledCatherine DeGraafpage 27 Tree FishSandra Beauchamppage 28 Country SlumberJ. Dylan McNeillpage 29 Untitled (artwork)Dan Trutterpage 33 Authors\u27 Pagepage 34https://thekeep.eiu.edu/vehicle/1060/thumbnail.jp

Predicting the severity of the grass pollen season and the effect of climate change in Northwest Europe

Allergic rhinitis is an inflammation in the nose caused by overreaction of the immune system to allergens in the air. Managing allergic rhinitis symptoms is challenging and requires timely intervention. The following are major questions often posed by those with allergic rhinitis: How should I prepare for the forthcoming season? How will the season's severity develop over the years? No country yet provides clear guidance addressing these questions. We propose two previously unexplored approaches for forecasting the severity of the grass pollen season on the basis of statistical and mechanistic models. The results suggest annual severity is largely governed by preseasonal meteorological conditions. The mechanistic model suggests climate change will increase the season severity by up to 60%, in line with experimental chamber studies. These models can be used as forecasting tools for advising individuals with hay fever and health care professionals how to prepare for the grass pollen season

Finishing a whole-genome shotgun: Release 3 of the Drosophila melanogaster euchromatic genome sequence

BACKGROUND: The Drosophila melanogaster genome was the first metazoan genome to have been sequenced by the whole-genome shotgun (WGS) method. Two issues relating to this achievement were widely debated in the genomics community: how correct is the sequence with respect to base-pair (bp) accuracy and frequency of assembly errors? And, how difficult is it to bring a WGS sequence to the accepted standard for finished sequence? We are now in a position to answer these questions. RESULTS: Our finishing process was designed to close gaps, improve sequence quality and validate the assembly. Sequence traces derived from the WGS and draft sequencing of individual bacterial artificial chromosomes (BACs) were assembled into BAC-sized segments. These segments were brought to high quality, and then joined to constitute the sequence of each chromosome arm. Overall assembly was verified by comparison to a physical map of fingerprinted BAC clones. In the current version of the 116.9 Mb euchromatic genome, called Release 3, the six euchromatic chromosome arms are represented by 13 scaffolds with a total of 37 sequence gaps. We compared Release 3 to Release 2; in autosomal regions of unique sequence, the error rate of Release 2 was one in 20,000 bp. CONCLUSIONS: The WGS strategy can efficiently produce a high-quality sequence of a metazoan genome while generating the reagents required for sequence finishing. However, the initial method of repeat assembly was flawed. The sequence we report here, Release 3, is a reliable resource for molecular genetic experimentation and computational analysis

Establishing a core outcome set for peritoneal dialysis : report of the SONG-PD (standardized outcomes in nephrology-peritoneal dialysis) consensus workshop

Outcomes reported in randomized controlled trials in peritoneal dialysis (PD) are diverse, are measured inconsistently, and may not be important to patients, families, and clinicians. The Standardized Outcomes in Nephrology-Peritoneal Dialysis (SONG-PD) initiative aims to establish a core outcome set for trials in PD based on the shared priorities of all stakeholders. We convened an international SONG-PD stakeholder consensus workshop in May 2018 in Vancouver, Canada. Nineteen patients/caregivers and 51 health professionals attended. Participants discussed core outcome domains and implementation in trials in PD. Four themes relating to the formation of core outcome domains were identified: life participation as a main goal of PD, impact of fatigue, empowerment for preparation and planning, and separation of contributing factors from core factors. Considerations for implementation were identified: standardizing patient-reported outcomes, requiring a validated and feasible measure, simplicity of binary outcomes, responsiveness to interventions, and using positive terminology. All stakeholders supported inclusion of PD-related infection, cardiovascular disease, mortality, technique survival, and life participation as the core outcome domains for PD

Acute Severe Pain Is a Common Consequence of Sexual Assault

Sexual assault (SA) is common, but the epidemiology of acute pain after SA has not previously been reported. We evaluated the severity and distribution of pain symptoms in the early aftermath of SA among women receiving sexual assault nurse examiner (SANE) care, and the treatment of pain by SANE nurses. Severe pain (≥7 on a 0–10 numeric rating scale) was reported by 53/83 women sexual assault survivors (64% [95% CI, 53%–74%]) at the time of SANE evaluation and 43/83 women (52% [95% CI, 41%–63%]) one week later. Pain in four or more body regions was reported by 44/83 women (53% [95% CI, 42%–64%]) at the time of initial evaluation and 49/83 women (59% [95% CI, 48%–70%]) at one week follow-up. Among survivors with severe pain at the time of initial post-assault evaluation, only 7/53 (13% [95% CI, 6%–26%]) received any pain medication at the time of initial SANE treatment. These findings suggest that pain is common in SA survivors in the early post-assault period, but rarely treated