DEVELOPMENT OF A RECORDING SYSTEM TO EMPIRICALLY ANALYSE THE SHOOTING CHARACTERISTICS OF A CLAY PIGEON SHOOTER

There is a dearth of published information with regard to the sport of clay pigeon shooting. The discipline involves the shooter firing a shotgun at a disc of clay, which is released within a known area but with an unknown trajectory. If the shooter hits the target, the clay breaks and the shooter receives instant feedback on the outcome of the shot. However, if the shooter misses the target the situation requires more analysis. The coach would hugely benefit from a method which gives empirical evidence outlining the kinematics of the shot. This project wil first attempt to identify the relavent characteristics i.e. timings within the shot, acceleration/movement of the gun. Once identified, the variability within these characteristics will be evaluated against the shot outcome results from a commercially available shooting simulator (Dryfire, Derby, UK)

H.A. Swanton Correspondence

Entries include the brief biographical information of a mechanical draftsman turned Maine farmer, a typed note concerning Edwin Arlington Robinson, and a typed transcript copy of a biographical letter from Swanton

Cancer cell-intrinsic mechanisms driving acquired immune tolerance

Immune evasion is a hallmark of cancer, enabling tumors to survive contact with the host immune system and evade the cycle of immune recognition and destruction. Here, we review the current understanding of the cancer cell-intrinsic factors driving immune evasion. We focus on T cells as key effectors of anti-cancer immunity and argue that cancer cells evade immune destruction by gaining control over pathways that usually serve to maintain physiological tolerance to self. Using this framework, we place recent mechanistic advances in the understanding of cancer immune evasion into broad categories of control over T cell localization, antigen recognition, and acquisition of optimal effector function. We discuss the redundancy in the pathways involved and identify knowledge gaps that must be overcome to better target immune evasion, including the need for better, routinely available tools that incorporate the growing understanding of evasion mechanisms to stratify patients for therapy and trials

Evaluation of the complementary use of the ceramic (Kosim) filter and Aquatabs in Northern Region, Ghana

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering, 2008.Includes bibliographical references (p. 130-136).The Kosim filter is a ceramic water filter that is currently used in Northern Ghana. Based on prior MIT research in Northern Ghana, this technology is effective at removing 92% of turbidity, 99.4% of total coliforms, and 99.7% of E. Coli from unimproved water sources. However, the product water is still microbially contaminated. The purpose of this thesis is to explore the effectiveness of combining two household water treatment technologies, the Kosim filter and Aquatabs, in order to achieve a more effective and complete water treatment system. Aquatabs are sodium dichlorisocyanurate chlorine tablets that are used on the household scale. They are particularly effective at killing pathogenic bacteria; however, they have predominantly been applied in emergency relief situations and have never, apart from one research study conducted by the Center for Disease Control, previously been applied in Ghana. In this study, 59 rural households (24 in a lower-class community and 35 in a lower middle-class community) in possession of Kosim filters were visited as part of a three week pilot study. During the initial visit, households were surveyed about the use and perception of their Kosim filters, they were trained in the use and given a one week supply of Aquatabs, and their Kosim filtered water (without Aquatabs) was tested. After one week, the same households were re-visited. A similar survey was conducted about the use and perception of the combined Kosim filter and Aquatabs system, and the filtered and chlorine disinfected water was tested. The addition of Aquatabs to the Kosim filtered water significantly reduced the microbial contamination; however, it did not completely remove pathogenic bacteria.(cont.) The average total coliform concentration in the drinking water was reduced by 50% compared to the filtered-only water, and the percentage of households with no total coliform concentration increased from 44% to 64%. Furthermore, the percentage of households with no E. Coli in their drinking water increased from 88% to 98%. In terms of user acceptability, all of the survey respondents indicated that the Aquatabs "improved the taste of the water" as they associated it with municipally treated or bottled water, suggesting that the chlorine taste is acceptable to these potential consumers.by Andrew A. Swanton.M.Eng

Weed-induced Crop Yield Loss: A New Paradigm and New Challenges

Direct competition for resources is generally considered the primary mechanism for weed-induced yield loss. A re-evaluation of physiological evidence suggests weeds initially impact crop growth and development through resource-independent interference. We suggest weed perception by crops induce a shift in crop development, before resources become limited, which ultimately reduce crop yield, even if weeds are subsequently removed. We present the mechanisms by which crops perceive and respond to weeds and discuss the technologies used to identify these mechanisms. These data lead to a fundamental paradigm shift in our understanding of how weeds reduce crop yield and suggest new research directions and opportunities to manipulate or engineer crops and cropping systems to reduce weedinduced yield losses

A Breast Cancer Meta-Analysis of Two Expression Measures of Chromosomal Instability Reveals a Relationship with Younger Age at Diagnosis and High Risk Histopathological Variables

Breast cancer in younger patients often presents with adverse histopathological features, including increased frequency of estrogen receptor negative and lymph node positive disease status. Chromosomal instability (CIN) is increasingly recognised as an important prognostic variable in solid tumours. In a breast cancer meta-analysis of 2423 patients we examine the relationship between clinicopathological parameters and two distinct chromosomal instability gene expression signatures in order to address whether younger age at diagnosis is associated with increased tumour genome instability. We find that CIN, assessed by the two independently derived CIN expression signatures, is significantly associated with increased tumour size, ER negative or HER2 positive disease, higher tumour grade and younger age at diagnosis in ER negative breast cancer. These data support the hypothesis that chromosomal instability may be a defining feature of breast cancer biology and clinical outcome

A breast cancer meta-analysis of two expression measures of chromosomal instability reveals a relationship with younger age at diagnosis and high risk histopathological variables

Breast cancer in younger patients often presents with adverse histopathological features, including increased frequency of estrogen receptor negative and lymph node positive disease status. Chromosomal instability (CIN) is increasingly recognised as an important prognostic variable in solid tumours. In a breast cancer meta-analysis of 2423 patients we examine the relationship between clinicopathological parameters and two distinct chromosomal instability gene expression signatures in order to address whether younger age at diagnosis is associated with increased tumour genome instability. We find that CIN, assessed by the two independently derived CIN expression signatures, is significantly associated with increased tumour size, ER negative or HER2 positive disease, higher tumour grade and younger age at diagnosis in ER negative breast cancer. These data support the hypothesis that chromosomal instability may be a defining feature of breast cancer biology and clinical outcome

Body Mass Index Associations Between Mother and Offspring from Birth to Age 18: The Fels Longitudinal Study

Background: Parental obesity is a known determinant of childhood obesity. Previous research has shown a strong maternal influence on body mass index (BMI) during infancy and early childhood. Objectives: The purpose of this research was to investigate the BMI associations between mother and offspring from birth to age 18 years. Methods: Participants were selected from the Fels Longitudinal Study. The current study sample includes 427 (215 mother/son and 212 mother/daughter) mother/child pairs. These pairs are repeatedly measured at multiple age groups in children, resulting in a total of 6,263 (3,215 mother/son, 3,048 mother/daughter) observations for data analysis. Inclusion criteria were children with measured height and weight for BMI collected at ages 0 to 18 years and their mother with BMI data. Maternal influences of BMI on offspring BMI from birth to early adulthood were analyzed by Spearman correlations and linear regression analyses. Results: Mother/son BMI correlations became statistically significant (p ≤ 0.05) at age 5–6 years and were significant through puberty and into early adulthood at age 18 years. Mother/daughter correlations became significant at age 1.5 years and also continued through adolescence, puberty and early adulthood at age 18 years. Associations persisted after the study sample was grouped into life stages and adjusted for decade of birth and parity. Conclusions: The mother/daughter relationship was more strongly correlated than the mother/son relationship and also became statistically significant at an earlier age than boys

Restoration of mutant bestrophin-1 expression, localisation and function in a polarised epithelial cell model

Autosomal recessive bestrophinopathy (ARB) is a retinopathy caused by mutations in the bestrophin-1 protein, which is thought to function as a Ca2+-gated Cl− channel in the basolateral surface of the retinal pigment epithelium (RPE). Using a stably transfected polarised epithelial cell model, we show that four ARB mutant bestrophin-1 proteins were mislocalised and subjected to proteasomal degradation. In contrast to the wild-type bestrophin-1, each of the four mutant proteins also failed to conduct Cl− ions in transiently transfected cells as determined by whole-cell patch clamp. We demonstrate that a combination of two clinically approved drugs, bortezomib and 4-phenylbutyrate (4PBA), successfully restored the expression and localisation of all four ARB mutant bestrophin-1 proteins. Importantly, the Cl− conductance function of each of the mutant bestrophin-1 proteins was fully restored to that of wild-type bestrophin-1 by treatment of cells with 4PBA alone. The functional rescue achieved with 4PBA is significant because it suggests that this drug, which is already approved for long-term use in infants and adults, might represent a promising therapy for the treatment of ARB and other bestrophinopathies resulting from missense mutations in BEST1

Resolving genetic heterogeneity in cancer

To a large extent, cancer conforms to evolutionary rules defined by the rates at which clones mutate, adapt and grow. Next-generation sequencing has provided a snapshot of the genetic landscape of most cancer types, and cancer genomics approaches are driving new insights into cancer evolutionary patterns in time and space. In contrast to species evolution, cancer is a particular case owing to the vast size of tumour cell populations, chromosomal instability and its potential for phenotypic plasticity. Nevertheless, an evolutionary framework is a powerful aid to understand cancer progression and therapy failure. Indeed, such a framework could be applied to predict individual tumour behaviour and support treatment strategies