Computational Fluid Dynamics Applied to Transport Systems in Trees

Our ecosystem is dependent upon the ability of photosynthetic plants to convert solar energy into a form of energy useable to biological organisms. Even so, much remains to become understood about how plants function. With such expansive bodies,how do trees cyclewaterand nutrients throughouttheir bodies

The Science of Pronominal Usage: He and It in Co-Reference to Inanimate Objects in Late Middle English Texts on Alchemy

This is the author's accepted manuscript. The published version can be found at http://dx.doi.org/10.1177/0075424210384225This article explores the variation between he and it in coreference to inanimate entities (such as mercury, sulfur, and salt). Using alchemical texts from the fifteenth century as material, the article demonstrates that there was much more variation in pronominal reference in this period than has previously been shown. Of the possible explanations suggested by previous research, the earlier grammatical gender system and transference from Latin do not seem to play a role, while pronoun clustering and pronominal reanalysis appear to influence the quantitative distribution. The scale of individuation used by Siemund and Stenroos to explain similar usage is shown not to be a straightforward predictor. Other factors such as personification and perceived similarities between animate and inanimate entities may affect the degree of perceived individuation. The choice of he over she seems to be influenced by pronominal reanalysis and straightforward personification in some cases. In other instances, it is speculated that the he usage reflects (stereotypical) gender conceptions in the Middle Ages

Speech Communication

Contains table of contents for Part IV, table of contents for Section 1 and reports on five research projects.Apple Computer, Inc.C.J. Lebel FellowshipNational Institutes of Health (Grant T32-NS07040)National Institutes of Health (Grant R01-NS04332)National Institutes of Health (Grant R01-NS21183)National Institutes of Health (Grant P01-NS23734)U.S. Navy / Naval Electronic Systems Command (Contract N00039-85-C-0254)U.S. Navy - Office of Naval Research (Contract N00014-82-K-0727

Speech Communication

Contains reports on five research projects.C.J. Lebel FellowshipNational Institutes of Health (Grant 5 T32 NSO7040)National Institutes of Health (Grant 5 R01 NS04332)National Institutes of Health (Grant 5 R01 NS21183)National Institutes of Health (Grant 5 P01 NS13126)National Institutes of Health (Grant 1 PO1-NS23734)National Science Foundation (Grant BNS 8418733)U.S. Navy - Naval Electronic Systems Command (Contract N00039-85-C-0254)U.S. Navy - Naval Electronic Systems Command (Contract N00039-85-C-0341)U.S. Navy - Naval Electronic Systems Command (Contract N00039-85-C-0290)National Institutes of Health (Grant RO1-NS21183), subcontract with Boston UniversityNational Institutes of Health (Grant 1 PO1-NS23734), subcontract with the Massachusetts Eye and Ear Infirmar

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Endpoints in Phase II trials for advanced non-small cell lung cancer

Introduction We investigated the relationships between progression-free survival (PFS), response, confirmed response, and failure-free survival (FFS) with overall survival (OS) to assess their suitability as primary endpoints in phase II (P2) trials for advanced NSCLC. Methods Individual data of 284 patients from 4 P2 trials were pooled. Progression status and response were modeled as time dependent variables in a multivariable (adjusted for baseline age, gender, stage, and performance status) Cox proportional hazards (PH) model for OS, stratified by trial. Subsequently, Cox PH models were used to assess the impact of PFS, response, confirmed response and FFS on subsequent survival, using landmark analysis at 8, 12, 16, 20, and 24 weeks. Model discrimination was evaluated using the concordance (c) index. Results The overall median OS, PFS and FFS were 9.6, 3.7 and 2.8 months, and the response and confirmed response rates were 21% and 15% respectively. Both progression status and response as time dependent covariates were significantly associated with OS (p\u3c0.0001; p=0.009). PFS and FFS at 12 weeks significantly predicted for subsequent survival with the strongest c-index and hazard ratio (HR) combination in landmark analyses (HR, c-index: PFS - 0.39, 0.67; FFS - 0.37, 0.67). The c-indices for response and confirmed response were low (0.59-0.60), indicating their inability to sufficiently discriminate subsequent patient survival outcomes. Conclusions Failure-free survival or progression-free survival at 12 weeks is a stronger predictor of subsequent patient survival compared to tumor response, and should be routinely used as endpoints in phase II trials for advanced NSCLC