Compared with admissions test scores, why are high school grades better at predicting college graduation? We argue that success in college requires not only cognitive ability but also self-regulatory ...competencies that are bette indexed by high school grades. In a national sample of 47,303 students who applied to college for the 2009/2010 academic year, Study 1 affirmed that high school grades out-predicted test scores for 4-year college graduation. In a convenience sample of 1,622 high school seniors in the Class of 2013, Study 2 revealed that the incremental predictive validity of high school grades for college graduation was explained by composite measures of self regulation, whereas the incremental predictive validity of test scores was explained by composite measures of cognitive ability.
Wireless power transmission (WPT) is being studied for a variety of important applications. This paper presents a technique to compute the effect of varying transmitter aperture illumination tapers ...on beaming efficiency and on the power density variation incident on the receive aperture of a WPT system. Results are presented showing the effects on beaming efficiency and on incident power density variation. The optimal choice for transmit illumination taper is discussed.
The observed biological activity in two New Zealand Myrsine species has been shown to be due to the presence of triterpene saponins. From Myrsine australis a series of eight oleanane-type saponins ...was obtained, with compounds 1-4 and 7 and 8 being novel. Also isolated were ardisiacrispin A 5 and ardisiacrispin B 6. The structures of the new compounds were determined by chemical and spectroscopic techniques. Extracts of Myrsine salicina yielded only one saponin, 5. Saponins 1-8 were shown to be combinations of four oleanane triterpenes bonded to beta-D-xylp(1-->2)-beta-D-glcp(1-->4)-beta-D-glcp(1-->2)-alpha-L -arap (compounds 1, 3, 5, 7) and this same tetrasaccharide with alpha-L-rhap replacing the beta-D-xylp unit (compounds 2, 4, 6, 8).
Improvement in the ability to target underlying drivers and vulnerabilities of high-grade serous ovarian cancer (HG-SOC) requires the development of molecularly annotated pre-clinical models ...reflective of clinical responses.
We generated patient-derived xenografts (PDXs) from consecutive, chemotherapy-naïve, human HG-SOC by transplanting fresh human HG-SOC fragments into subcutaneous and intra-ovarian bursal sites of NOD/SCID IL2Rγnull recipient mice, completed molecular annotation and assessed platinum sensitivity.
The success rate of xenografting was 83%. Of ten HG-SOC PDXs, all contained mutations in TP53, two were mutated for BRCA1, three for BRCA2, and in two, BRCA1 was methylated. In vivo cisplatin response, determined as platinum sensitive (progression-free interval ≥100 d, n = 4), resistant (progression-free interval <100 d, n = 3) or refractory (n = 3), was largely consistent with patient outcome. Three of four platinum sensitive HG-SOC PDXs contained DNA repair gene mutations, and the fourth was methylated for BRCA1. In contrast, all three platinum refractory PDXs overexpressed dominant oncogenes (CCNE1, LIN28B and/or BCL2).
Because PDX platinum response reflected clinical outcome, these annotated PDXs will provide a unique model system for preclinical testing of novel therapies for HG-SOC.
•High-grade serous ovarian cancer patient-derived xenografts from fragments (83% success).•In vivo platinum response (sensitive ≥ 100 d) consistent with patient outcome.•Three of four platinum-sensitive PDX contained mutations in BRCA1 or BRCA2.•All three platinum refractory PDX overexpressed dominant oncogenes.•These annotated PDX will enhance preclinical testing of novel therapies.
Post‐operative atrial fibrillation (POAF) is the most common complication after cardiac surgery. Despite implementation of several pharmacological strategies, incidence of POAF remains at ...approximately 30%. An adenovirus vector encoding KCNH2‐G628S has proven efficacious in a porcine model of AF. In this preclinical study, 1.5 × 1010 or 1.5 × 1012 Ad‐KCNH2‐G628S vector particles (vp) were applied to the atrial epicardium or 1.5 × 1012 vp were applied to the whole epicardial surface of New Zealand White rabbits. Saline and vector vehicle served as procedure controls. Animals were followed for up to 42 days. Vector genomes persisted in the atria up to 42 days, with no distribution to extra‐thoracic organs. There were no adverse effects attributable to test article on standard toxicological endpoints or on blood pressure, left atrial or ventricular ejection fractions, electrocardiographic parameters, or serum IL‐6 or troponin concentrations. Mononuclear infiltration of the myocardium of the atrial free walls of low‐dose, but not high‐dose animals was observed at 7 and 21 days, but these changes did not persist or affect cardiac function. After scaling for heart size, results indicate the test article is safe at doses up to 25 times the maximum proposed for the human clinical trial.
The literature on antenna array optimization has recently focused on direct search methods that use random decision making, e.g., genetic/evolutionary algorithms (GA) and particle swarm optimization ...(PSO). In this paper we compare results for test problems from the literature using direct search methods that do not use random decision making, such as Nelder-Mead, with those that do, such as PSO. We also revisit gradient based search methods, specifically Newton-like optimization methods that also do not rely upon randomness. Search efficiency is measured in terms of the total number of function evaluations required to converge to an acceptable pattern. For these test problems it is found that direct search without randomness is far more efficient than direct search with randomness; and that non-random gradient based search is most efficient of all.
Alpha-1 antitrypsin (α1AT) deficiency is a common autosomal recessive disorder characterized by a marked reduction in serum α1AT levels, lung and liver disease. α1AT is mainly produced and secreted ...by hepatocytes, with its primary function to protect the lung against the proteolytic activity of neutrophil elastase. Serum α1AT levels <11 μM are associated with progressive destruction of lung parenchyma and early-onset of panacinar emphysema in the age range 35-45. The current approved treatment for α1AT deficiency is a costly protein augmentation therapy requiring weekly intravenous infusion of purified α1AT from pooled human plasma. Gene therapy offers the advantage of a single vector administration, eliminating the burden of the repeated purified protein infusions, with the consequent reduced overall drug cost and improved compliance. We have developed a novel, highly efficient gene therapy approach for α1AT deficiency based on the administration of AAVrh.10hα1AT, an adeno-associated viral vector serotype rh.10 coding for normal M-type human α1AT via the intrapleural route. On the basis of prior murine studies, this approach provides sustained α1AT proximal to the lung with a highly efficient vector. In support of a clinical trial for this approach, we carried out a study to assess the safety of intrapleural administration of AAVrh.10hα1AT to 280 mice and 36 nonhuman primates. The data demonstrate that this approach is safe, with no toxicity issues. Importantly, there was persistent expression of the human α1AT mRNA in chest cavity cells for the duration of the study (6 months in mice and 1 year in nonhuman primates). Together, these data support the initiation of a clinical trial of intrapleural human AAVrh.10hα1AT for the treatment of α1AT deficiency.
The ability to produce conductive copper tracks using ink-jet printing to allow the routine digital manufacture of patterned electrical interconnects is a long standing industry aim. In this study an ...approach to achieve this goal is investigated that uses an ink-jet printed self-assembled monolayer (SAM) coating as a molecular etch resist. To date, ink-jet printed SAMs on copper have not had sufficient quality to allow them to act in this way. However, recently an improved etching solution that enables similar quality microcontact printed SAM layers to act as resists on copper has been reported. Here this new etch solution is used to attempt to "develop" ink-jet printed SAM patterns on thin copper laminates into conductive tracks. The success of this approach and quality of resulting tracks is tested using optical microscopy, scanning electron microscopy and atomic force microscopy. This allows an assessment of the performance of this novel approach to interconnection manufacture to be made.