THE ROLE OF STREPTOCOCCUS GALLOLYTICUS SUBSPECIES GALLOLYTICUS IN COLON CANCER DEVELOPMENT

Colorectal cancer (CRC) is the third most common cancer in men and women and is also the third most common cause of cancer death. A large body of evidence points towards the possibility that bacteria can have a significant impact on the development of cancer. It has been suggested that Streptococcus gallolyticus subsp. gallolyticus, a group D streptococci, may play a role in the development of CRC. Sg, formerly S. bovis biotype I, has been shown to be highly associated with CRC. In observing patients with either Sg bacteremia or endocarditis it was found that 25-80% of patients with Sg bacteremia had tumors and 18-62% of patients with Sg endocarditis had colonic neoplasias. However, other closely related Streptococcal strains, such as S. pasterianus and S. infantarius, have not been shown to have this strong association with CRC. In fact, it has been shown that biotype I is more often associated with CRC (94%) as compared to biotype II (18%). This knowledge has important clinical implications, and yet little is known about the role of Sg on CRC and the underlying mechanisms. Here we show that mice treated with Sg had significantly more tumors, higher tumor burden and dysplasia grade, and increased cell proliferation and β-catenin level in colonic crypts compared to mice treated with control bacteria. Sg strains that promoted proliferation were also more efficient at adhering to CRC cell lines and colonizing a mouse model. Additionally, in human patients Sg was highly prevalent in CRC patients and tumor tissues had an increased Sg burden in comparison to normal adjacent tissues. These results provide exciting new information and establish a tumor-promoting role of Sg that involves specific bacterial and host factors

Mathematical modeling, simulation, and optimization of loading schemes for isometric resistance training

In this thesis, we present a novel mathematical model-based approach to optimize loading schemes of isometric resistance training (RT) sessions for different training goals. To this end, we develop a nonlinear ordinary differential equation model of the time course of maximum voluntary isometric (MVIC) force under external isometric loading. To validate the model, we set up multi-experiment parameter estimation problems using a comprehensive dataset from the literature. We solve these problems numerically via direct multiple shooting and the generalized Gauss-Newton method. Moreover, we use the proposed model to examine hypotheses about fatigue and recovery of MVIC force. Then, we mathematically formulate key performance indicators and optimality criteria for loading schemes of isometric RT sessions identified in sports science and incorporate these into multi-stage optimal control problems. We solve these problems numerically via direct multiple shooting and structure-exploiting sequential quadratic programming. We discuss the results from a numerical and sports scientific point of view. Based on the proposed model, we additionally formulate the estimation of critical torque as a nonlinear program. This allows us to reduce the experimental effort compared to conventional testing when estimating these quantities. Furthermore, we formulate multi-stage optimum experimental design problems to reduce the statistical uncertainty of the parameter estimates when calibrating the model. We solve these problems numerically via direct single shooting and sequential quadratic programming. We discuss the solutions from a numerical and physiological point of view. For our approach, a small amount of data obtained in a single testing session is sufficient. Our approach can be extended to more elaborate physiological models and other forms of resistance training once suitable models become available

Linguistic Relativity: Transforming The Relative Into The Insensible: A Reply To Clarke Et Al. 1

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98121/1/j.1467-1770.1982.tb00528.x.pd

Selective Dry Etch for Defining Ohmic Contacts for High Performance ZnO TFTs

Recently, gigahertz RF performance has been demonstrated in zinc oxide (ZnO) TFT. However, the need arises for sub-micron channel length (Lc) dimensions to extend these results into X-band frequency range of operation. This thesis is a pioneering effort identifying device access materials to be selectively etched to ZnO via plasma-assisted etch (PAE) to avoid processing limitations from traditional optical lithography channel definition methods. A subtractive etch process using CF4/O2 gas mixture was completed with various Ohmic contact materials to ZnO providing foundational research upon which nano-scale, high-frequency ZnO thin-film transistors (TFTs) could be fabricated. Molybdenum, tantalum, titanium tungsten 10-90, and tungsten metallic contact schemes to ZnO are investigated for their etch selectivities to ZnO and etch profiles. Tungsten displayed promising device scalability results with excellent aspect ratio and 200nm Lc. A new semiconductor-semiconductor contact interface to ZnO using nc-Si is initially reported with 15mA/mm current density and 18mS/mm transconductance. Nc-Si also displays promising scaling results through the subtractive etch process defined with e-beam lithography. Results included 157nm channel length, high aspect ratio, and high extrapolated current density of nearly 1A/mm at 100nm Lc and gate and drain voltages of 10V

Differential effects of anti-B7-1 and anti-B7-2 monoclonal antibody treatment on the development of diabetes in the nonobese diabetic mouse.

Insulin-dependent diabetes mellitus (IDDM) is thought to be an immunologically mediated disease resulting in the complete destruction of the insulin-producing islets of Langerhans. It has become increasingly clear that autoreactive T cells play a major role in the development and progression of this disease. In this study, we examined the role of the CD28/B7 costimulation pathway in the development and progression of autoimmune diabetes in the nonobese diabetic (NOD) mouse model. Female NOD mice treated at the onset of insulitis (2-4 wk of age) with CTLA4Ig immunoglobulin (Ig) (a soluble CD28 antagonist) or a monoclonal antibody (mAb) specific for B7-2 (a CD28 ligand) did not develop diabetes. However, neither of these treatments altered the disease process when administered late, at > 10 wk of age. Histological examination of islets from the various treatment groups showed that while CTLA4Ig and anti-B7-2 mAb treatment blocked the development of diabetes, these reagents had little effect on the development or severity of insulitis. Together these results suggest that blockade of costimulatory signals by CTLA4Ig or anti-B7-2 acts early in disease development, after insulitis but before the onset of frank diabetes. NOD mice were also treated with mAbs to another CD28 ligand, B7-1. In contrast to the previous results, the anti-B7-1 treatment significantly accelerated the development of disease in female mice and, most interestingly, induced diabetes in normally resistant male mice. A combination of anti-B7-1 and anti-B7-2 mAbs also resulted in an accelerated onset of diabetes, similar to that observed with anti-B7-1 mAb treatment alone, suggesting that anti-B7-1 mAb's effect was dominant. Furthermore, treatment with anti-B7-1 mAbs resulted in a more rapid and severe infiltrate. Finally, T cells isolated from the pancreas of these anti-B7-1-treated animals exhibited a more activated phenotype than T cells isolated from any of the other treatment groups. These studies demonstrate that costimulatory signals play an important role in the autoimmune process, and that different members of the B7 family have distinct regulatory functions during the development of autoimmune diabetes

Does sensory relearning improve tactile function after carpal tunnel decompression? A pragmatic, assessor-blinded, randomized clinical trial

Despite surgery for carpal tunnel syndrome (CTS) being effective in 80-90% of cases, chronic numbness and hand disability can occur. The aim of this study was to investigate whether sensory relearning improves tactile discrimination and hand function after decompression. In a multi-centre, pragmatic, randomized, controlled trial, 104 patients were randomized to sensory relearning (n=52) or control (n=52) group. 93 patients completed 12 week follow-up. Primary outcome was the Shape-Texture Identification (STI) test at 6 weeks. Secondary outcomes were touch threshold, touch localisation, dexterity and self-reported hand function. No significant group differences were seen for the primary outcome (STI) at 6 weeks or 12 weeks. Similarly, no significant group differences were observed on secondary outcomes, with the exception of self-reported hand function. A secondary Complier-Averaged-CausalEffects (CACE) analysis showed no statistically significant treatment effect on the primary outcome. Sensory relearning for tactile sensory and functional deficits after carpal tunnel decompression is not effective

Association of psychological distress, quality of life and costs with carpal tunnel syndrome severity: a crosssectional analysis of the PALMS cohort

Objectives: The PALMS study is designed to identify prognostic factors for outcome from corticosteroid injection and surgical decompression for carpal tunnel syndrome (CTS) and predictors of cost over 2 years. The aim of this paper is to explore the cross-sectional association of baseline patient-reported and clinical severity with anxiety, depression, health-related quality of life and costs of CTS in patients referred to secondary care. Methods: Prospective, multi-centre cohort study initiated in 2013. We collected baseline data on patientreported symptom severity (CTS-6), psychological status (HADS), hand function (Michigan Hand Questionnaire) comorbidities, EQ5D-3L and sociodemographic variables. Nerve conduction tests classified patients into five severity grades (mild to very severe). Data were analysed using a general linear model. Results: 753 patients with CTS provided complete baseline data. Multivariable linear regression adjusting for age, sex, ethnicity, duration of CTS, smoking status, alcohol consumption, employment status, body mass index and comorbidities showed a highly statistically significant relationship between CTS-6 and anxiety, depression and the EQ-5D (p<0.0001 in each case). Likewise, a significant relationship was observed between electrodiagnostic severity and anxiety (p=0.027) but not with depression (p=0.986) or the EQ-5D (p=0.257). NHS and societal costs in the 3 months prior to enrolment were significantly associated with self-reported severity (p<0.0001) but not with electrodiagnostic severity. Conclusions: Patient-reported symptom severity in carpal tunnel syndrome is significantly and positively associated with anxiety, depression, health-related quality of life and NHS and societal costs even when adjusting for age, gender, body mass index, comorbidities, smoking, drinking and occupational status. In contrast there is little or no evidence of any relationship with objectively derived CTS severity. Future research is needed to understand the impact of approaches and treatments that address psychosocial stressors as well as biomedical factors on relief of symptoms from carpal tunnel syndrome.CJH was funded by the National Institute for Health Research (NIHR) through a NIHR Senior Research Fellowship. ECFW is funded by the NIHR Cambridge Biomedical Research Centre

First Steps into Practical Engineering for Freshman Students Using MATLAB and LEGO Mindstorms Robots

Besides lectures on basic theoretical topics, contemporary teaching and learning concepts for first semester students give more and more consideration to practically motivated courses. In this context, a new first-year introductory course in practical engineering has been established in the first semester curriculum of Electrical Engineering at RWTH Aachen University, Germany. Based on a threefold learning concept, programming skills in MATLAB are taught to 309 students within a full-time block course laboratory. The students are encouraged to transfer known mathematical basics to program algorithms and real-world applications performed by 100 LEGO Mindstorms robots. A new MATLAB toolbox and twofold project tasks have been developed for this purpose by a small team of supervisors. The students are supervised by over 60 tutors at 23 institutes, and are encouraged to create their own robotics applications. We describe how the laboratory motivates the students to act and think like engineers and to solve real-world issues with limited resources. The evaluation results show that the proposed practical course concept successfully boosts students’ motivation, advances their programming skills, and encourages the peer learning process.

Unstable states in QED of strong magnetic fields

We question the use of stable asymptotic scattering states in QED of strong magnetic fields. To correctly describe excited Landau states and photons above the pair creation threshold the asymptotic fields are chosen as generalized Licht fields. In this way the off-shell behavior of unstable particles is automatically taken into account, and the resonant divergences that occur in scattering cross sections in the presence of a strong external magnetic field are avoided. While in a limiting case the conventional electron propagator with Breit-Wigner form is obtained, in this formalism it is also possible to calculate $S$-matrix elements with external unstable particles.Comment: Revtex, 7 pages. To appear in Phys. Rev. D53(2