Instrumentation design study for testing a hypersonic ramjet engine on the x-15 a-2. volume 2- preliminary design of in-flight thrust/drag measuring device

Inflight thrust and drag measuring device for hypersonic ramjet engine on X-15A-2 aircraf

The Influence of Trickle Irrigation on the Quality of Irrigation Return Flow

The influence of trickle irrigation on the quality of irrigation return flow was investigated in a field study and by means of computer simulation models. Six undisturbed buried monolith lysimeters were utilized to quantify the leachate from treatment including two different qualities of irrigation water applied through a trickle irrigation system. Both moisture and salt balances were followed inside and outside the lysimeters during a growing season the remainder of the calendar year. A sorghum crop was grown on the lysimeters and in the adjacent area. Irrigation was scheduled based on pan evaporation losses. The irrigation water of high salt content was obtained from a deep well while the irrigation water of low salt content was drawn from the district irrigation canal. The water balance monitored by the neutron probe showed that differences between inside and outside lysimeters were small. The soil contained significant amounts of salt at the begining of the experiment and trends in the leachate concentration resulting from irrigation treatment are difficult to see after one year of monitoring. Differences between paired lysimeters are large indicating large variability in soil characteristics across the field. Differences in water use inside and outside the lysimeters indicated that during the 1974 growing season, which was dryer than normal, the sorghum crop may have extracted approximately 8% of the water required from the water table. Yield and growth data indicated that the plant root environment inside and outside lysimeters were relatively comparable. Nitrogen, saline water and irrigation treatments did not significantly influ- ence growth and yields of sorghum in 1974. During the test period, N03-N loss in effluents ranged from a low of 14 kg/ha from a lysimeter treated with 112kg/ha to a high of a- bout 75 kg/ha from a lysimeter treated with 224 kg/ha of N. Nitrate losses were negligible compared to checks when N application rates to sorghum were 112 kg/ha. Most of the N03-N losses occurred during non-cropped periods when lysimeter drainage volumes were at a maximum. Total salt in drainage waters ranged from about 2600 to 4200 kg/ha during the test period. Inherent soil variability was an important factor in salt and nitrate loss in drainage waters from the lysimeters

An Investigation of the Return Flow from Irrigated Land

Recent trends in agricultural have lead to the intensification of crop production in areas with long growing seasons and ample solar radiation. Unfortunately, these areas also often have limited water supplies, and the water available is often salty. When this water is used for irrigation, the salts are concentrated in soil solution. The application of fertilizer also increases the concentration of certain salts in soil. Thus, the water that leaches from an irrigated field will have greater concentrations of ion than the irrigation water applied. Little information exists, however, on the flux of ions or soil solution below the root zone of cropped fields. Such information is needed before we can learn how we might better manage our activities to minimize the pollution that may be associated with the leachate from agricultural fields. This project included both a field study and a modeling effort both directed at elucidating the influence of irrigation water quality on the quantity and quality of irrigation return flow by leaching below the root zone. The field work consisted of the installation of six large buried monolith lysimeters equipped with appropriate drainage devices. Suction water samples were collected for 8 months including the cropping season. The sorghum crop grown on paired lysimeters was irrigated with a high salt and low salt water and was fertilized with different levels of nitrogen. Although care was taken to secure lysimeters with similar soil, large differences between the volume of leachate and the concentration of ions in the leachate were found. During the period the measurements were made, the changes in concentration of leachate were not attributable to the treatments applied. The modeling effort was directed toward assembling and testing the following components of an overall water-salt-nutrients balance model: a.: Water and heat flow model to calculate the influence of moisture and temperature gradients on the movement of water between the source(s) and sinks within the system, b. An ion exchange equilibrium model to calculate the salt balance, c. A nitrogen model to calculate complex nitrogen transfers which take place within the soil, and d. A root oxygen supply model to calculate the sink strength for oxygen and ultimately the distribution of root water uptake within the soil profile. These components of the overall model have been programmed, tested, documented, and are presented in this report

Genetic association between APOE*4 and neuropsychiatric symptoms in patients with probable Alzheimer's disease is dependent on the psychosis phenotype

Background: Neuropsychiatric symptoms such as psychosis are prevalent in patients with probable Alzheimer's disease (AD) and are associated with increased morbidity and mortality. Because these disabling symptoms are generally not well tolerated by caregivers, patients with these symptoms tend to be institutionalized earlier than patients without them. The identification of protective and risk factors for neuropsychiatric symptoms in AD would facilitate the development of more specific treatments for these symptoms and thereby decrease morbidity and mortality in AD. The E4 allele of the apolipoprotein E (APOE) gene is a well-documented risk factor for the development of AD. However, genetic association studies of the APOE 4 allele and BPS in AD have produced conflicting findings.Methods: This study investigates the association between APOE and neuropsychiatric symptoms in a large sample of clinically well-characterized subjects with probable AD (n=790) who were systematically evaluated using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Behavioral Rating Scale for Dementia (BRSD).Results: Our study found that hallucinations were significantly more likely to occur in subjects with no APOΕ4 alleles than in subjects with two Ε4 alleles (15% of subjects and 5% of subjects, respectively; p=.0066), whereas there was no association between the occurrence of delusions, aberrant motor behavior, or agitation and the number of Ε4 alleles. However, 94% of the subjects with hallucinations also had delusions (D+H).Conclusion: These findings suggest that in AD the Ε4 allele is differentially associated with D+H but not delusions alone. This is consistent with the hypothesis that distinct psychotic subphenotypes may be associated with the APOE allele. © 2012 Christie et al.; licensee BioMed Central Ltd

Genetic risk for schizophrenia and psychosis in Alzheimer disease

Psychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alzheimer disease (AD), affecting ~40 to 60% of individuals with AD (AD with psychosis (AD+P)). In comparison with AD subjects without psychosis, AD+P subjects have more rapid cognitive decline and poor outcomes. Prior studies have estimated the heritability of psychosis in AD at 61%, but the underlying genetic sources of this risk are not known. We evaluated a Discovery Cohort of 2876 AD subjects with (N=1761) or without psychosis (N=1115). All subjects were genotyped using a custom genotyping array designed to evaluate single-nucleotide polymorphisms (SNPs) with evidence of genetic association with AD+P and include SNPs affecting or putatively affecting risk for schizophrenia and AD. Results were replicated in an independent cohort of 2194 AD subjects with (N=734) or without psychosis (N=1460). We found that AD+P is associated with polygenic risk for a set of novel loci and inversely associated with polygenic risk for schizophrenia. Among the biologic pathways identified by the associations of schizophrenia SNPs with AD+P are endosomal trafficking, autophagy and calcium channel signaling. To the best of our knowledge, these findings provide the first clear demonstration that AD+P is associated with common genetic variation. In addition, they provide an unbiased link between polygenic risk for schizophrenia and a lower risk of psychosis in AD. This provides an opportunity to leverage progress made in identifying the biologic effects of schizophrenia alleles to identify novel mechanisms protecting against more rapid cognitive decline and psychosis risk in AD

A Case for Humans-in-the-Loop: Decisions in the Presence of Erroneous Algorithmic Scores

The increased use of algorithmic predictions in sensitive domains has been accompanied by both enthusiasm and concern. To understand the opportunities and risks of these technologies, it is key to study how experts alter their decisions when using such tools. In this paper, we study the adoption of an algorithmic tool used to assist child maltreatment hotline screening decisions. We focus on the question: Are humans capable of identifying cases in which the machine is wrong, and of overriding those recommendations? We first show that humans do alter their behavior when the tool is deployed. Then, we show that humans are less likely to adhere to the machine's recommendation when the score displayed is an incorrect estimate of risk, even when overriding the recommendation requires supervisory approval. These results highlight the risks of full automation and the importance of designing decision pipelines that provide humans with autonomy.Comment: Accepted at ACM Conference on Human Factors in Computing Systems (ACM CHI), 202

Role of thrombin receptor in breast cancer invasiveness

Invasion, the ability of an epithelial cancer cell to detach from and move through a basement membrane, is a central process in tumour metastasis. Two components of invasion are proteolysis of extracellular matrix and cellular movement through it. A potential promoter of these two processes is thrombin, the serine proteinase derived from the ubiquitous plasma protein prothrombin. Thrombin promotes the invasion of MDA-MB231 breast tumour cells (a highly aggressive cell line) in an in vitro assay. Invasion by MDA-MB436 and MCF-7 cells, less aggressive cell lines, is not promoted by thrombin. Thrombin, added to the cells, is a stimulator of cellular movement; fibroblast-conditioned medium is the chemotaxin. Thrombin-promoted invasion is inhibited by hirudin. Stimulation of invasion is a receptor-mediated process that is mimicked by a thrombin receptor-activating peptide. Thrombin has no effect on chemotaxis in vitro. Thrombin receptor is detectable on the surface of MDA-MB231 cells, but not on the other two cell lines. Introduction of oestrogen receptors into MDA-MB231 cells by transfection with pHEO had no effect on thrombin receptor expression, in the presence or absence of oestradiol. This paper demonstrates that thrombin increases invasion by the aggressive breast cancer cell line MDA-MB231 by a thrombin receptor-dependent mechanism. © 1999 Cancer Research Campaig

Effect of Pembrolizumab Plus Neoadjuvant Chemotherapy on Pathologic Complete Response in Women With Early-Stage Breast Cancer: An Analysis of the Ongoing Phase 2 Adaptively Randomized I-SPY2 Trial.

Importance: Approximately 25% of patients with early-stage breast cancer who receive (neo)adjuvant chemotherapy experience a recurrence within 5 years. Improvements in therapy are greatly needed. Objective: To determine if pembrolizumab plus neoadjuvant chemotherapy (NACT) in early-stage breast cancer is likely to be successful in a 300-patient, confirmatory randomized phase 3 neoadjuvant clinical trial. Design, Setting, and Participants: The I-SPY2 study is an ongoing open-label, multicenter, adaptively randomized phase 2 platform trial for high-risk, stage II/III breast cancer, evaluating multiple investigational arms in parallel. Standard NACT serves as the common control arm; investigational agent(s) are added to this backbone. Patients with ERBB2 (formerly HER2)-negative breast cancer were eligible for randomization to pembrolizumab between November 2015 and November 2016. Interventions: Participants were randomized to receive taxane- and anthracycline-based NACT with or without pembrolizumab, followed by definitive surgery. Main Outcomes and Measures: The primary end point was pathologic complete response (pCR). Secondary end points were residual cancer burden (RCB) and 3-year event-free and distant recurrence-free survival. Investigational arms graduated when demonstrating an 85% predictive probability of success in a hypothetical confirmatory phase 3 trial. Results: Of the 250 women included in the final analysis, 181 were randomized to the standard NACT control group (median [range] age, 47 [24.77] years). Sixty-nine women (median [range] age, 50 [27-71] years) were randomized to 4 cycles of pembrolizumab in combination with weekly paclitaxel followed by AC; 40 hormone receptor (HR)-positive and 29 triple-negative. Pembrolizumab graduated in all 3 biomarker signatures studied. Final estimated pCR rates, evaluated in March 2017, were 44% vs 17%, 30% vs 13%, and 60% vs 22% for pembrolizumab vs control in the ERBB2-negative, HR-positive/ERBB2-negative, and triple-negative cohorts, respectively. Pembrolizumab shifted the RCB distribution to a lower disease burden for each cohort evaluated. Adverse events included immune-related endocrinopathies, notably thyroid abnormalities (13.0%) and adrenal insufficiency (8.7%). Achieving a pCR appeared predictive of long-term outcome, where patients with pCR following pembrolizumab plus chemotherapy had high event-free survival rates (93% at 3 years with 2.8 years\u27 median follow-up). Conclusions and Relevance: When added to standard neoadjuvant chemotherapy, pembrolizumab more than doubled the estimated pCR rates for both HR-positive/ERBB2-negative and triple-negative breast cancer, indicating that checkpoint blockade in women with early-stage, high-risk, ERBB2-negative breast cancer is highly likely to succeed in a phase 3 trial. Pembrolizumab was the first of 10 agents to graduate in the HR-positive/ERBB2-negative signature. Trial Registration: ClinicalTrials.gov Identifier: NCT01042379