Development Tests of a Cryogenic Filter Wheel Assembly for the NIRCam Instrument

The James Webb Space Telescope is an infrared-optimized space telescope scheduled for launch in 201 3. Its 6.5-m diameter primary mirror will collect light from some of the first galaxies formed after the big bang. The Near Infrared camera (NIRCam) will detect the first light from these galaxies, provide the necessary tools for studying the formation of stars, aid in discovering planets around other stars, and adjust the wave front error on the primary mirror (Fig. 1). The instrument and its complement of mechanisms and optics will operate at a cryogenic temperature of 35 K. This paper describes tests and test results of the NIRCam Filter Wheel assembly prototype

MLCK/actin Interaction in the Contracting A7r5 Cell and Vascular Smooth Muscle

Myosin light chain kinase (MLCK) is an enzyme that phosphorylates the serine-19 residue on myosin regulatory light chains (MLCs) which serves to activate the Mg2+-ATPase of myosin. This catalytic activity is thought to be the primary role of MLCK; however, it has recently been suggested that MLCK’s actin binding and bundling properties may also be of importance in smooth muscle contraction. In the absence of calcium and calmodulin (CaM), MLCK will bundle actin filaments with its N-terminus. During calcium influx and subsequent CaM activation, MLCK binding to actin decreases resulting in unbundling of actin filaments and allows myosin and actin to slide past each other for force development. Despite these signals, some contractile agonists develop high levels of force in the relative absence of increased levels of intracellular calcium or MLC phosphorylation. One agonist that falls into this category is phorbol 12,13-dibutyrate (PDBu). PDBu activates the protein kinase C (PKCα) pathway which inhibits myosin light chain phosphatase (MLCP) and allows the MLCs to stay in a phosphorylated state. PKCα can also phosphorylate the kinase domain of MLCK and inhibit activation via CaM. This pathway suggests that MLCK and its ability to bind to actin filaments may still be intact in PDBu-stimulated smooth muscle. Therefore, the present studies look at the interaction between MLCK and α- and β-actin, the two predominant isoforms found in vascular smooth muscle, during PDBu-induced contraction of A7r5 smooth muscle cells in culture and highly differentiated vascular smooth muscle freshly excised from the rat

The Effect Of Butyrate Feeding On Skeletal Muscle And Adipose Tissue Glucose Uptake

A thesis presented to the faculty of the College of Science and Technology at Morehead State University in partial fulfillment of the requirements for the Degree of Master of Science in Biology by Sean Eric Thatcher on May 31, 2002

Effects of treadmill versus overground soccer match simulations on biomechanical markers of anterior cruciate ligament injury risk in side cutting.

Abstract This study aimed to investigate whether treadmill versus overground soccer match simulations have similar effects on knee joint mechanics during side cutting. Nineteen male recreational soccer players completed a 45-min treadmill and overground match simulation. Heart rate (HR) and rating of perceived exertion (RPE) were recorded every 5 min. Prior to exercise (time 0 min), at "half-time" (time 45 min) and 15 min post-exercise (time 60 min), participants performed five trials of 45° side-cutting manoeuvres. Knee abduction moments and knee extension angles were analysed using two-way repeated measures analysis of variance (α = 0.05). Physiological responses were significantly greater during the overground (HR 160 ± 7 beats ∙ min(-1); RPE 15 ± 2) than the treadmill simulation (HR 142 ± 5 beats ∙ min(-1); RPE 12 ± 2). Knee extension angles significantly increased over time and were more extended at time 60 min compared with time 0 min and time 45 min. No significant differences in knee abduction moments were observed. Although knee abduction moments were not altered over time during both simulations, passive rest during half-time induced changes in knee angles that may have implications for anterior cruciate ligament injury risk

Sexual Dimorphism of Abdominal Aortic Aneurysms

Sex is the largest nonmodifiable risk factor for the development of abdominal aortic aneurysms (AAAs) in humans and experimental models. Data from several studies consistently demonstrate a higher AAA prevalence in males than in females, contributing to divergent recommendations for AAA screening in men and women. Despite a higher AAA prevalence in males, females have more rapid rates of aneurysm dilation, and aneurysms rupture at smaller sizes. Unfortunately, no therapies have been effective to retard aneurysm dilation in either sex. Results from experimental AAA models indicate a protective role for estrogen in AAA development and progression, while male testosterone has been demonstrated to markedly promote angiotensin II (AngII)‐induced AAAs. Potential mechanisms implicated in sex hormone regulation of AAAs include regulation of inflammation, matrix metalloproteinases, aromatase activity, oxidative stress, stem cells, and transforming growth factor‐beta. In addition to sex hormones, sex chromosomes have been implicated in diseases of the aorta. Turner\u27s syndrome (monosomy X) patients have a high incidence of thoracic aortic rupture. Recent studies indicate a novel approach to define the relative role of sex hormones versus sex chromosomes in experimental AAAs. Further studies are warranted to determine interactions between sex hormones and sex chromosomes in AAA development and progression

Deficiency of ACE2 in Bone-Marrow-Derived Cells Increases Expression of TNF-α in Adipose Stromal Cells and Augments Glucose Intolerance in Obese C57BL/6 Mice

Deficiency of ACE2 in macrophages has been suggested to promote the development of an inflammatory M1 macrophage phenotype. We evaluated effects of ACE2 deficiency in bone-marrow-derived stem cells on adipose inflammation and glucose tolerance in C57BL/6 mice fed a high fat (HF) diet. ACE2 activity was increased in the stromal vascular fraction (SVF) isolated from visceral, but not subcutaneous adipose tissue of HF-fed mice. Deficiency of ACE2 in bone marrow cells significantly increased mRNA abundance of F4/80 and TNF-α in the SVF isolated from visceral adipose tissue of HF-fed chimeric mice, supporting increased presence of inflammatory macrophages in adipose tissue. Moreover, deficiency of ACE2 in bone marrow cells modestly augmented glucose intolerance in HF-fed chimeric mice and increased blood levels of glycosylated hemoglobin. In summary, ACE2 deficiency in bone marrow cells promotes inflammation in adipose tissue and augments obesity-induced glucose intolerance

Ureterocutaneous Fistula in Setting of Recurrent Gluteal Abscesses: A Case Report

Ureteral fistulas are a rare occurrence that can arise from iatrogenic trauma, radiation, malignancy, and inflammation. Treatment options of urinary tract fistulas are handled on a case-by-case basis and can necessitate a surgical approach. We present the case of an 85-year-old patient with a ureterocutaneous fistula where conservative management with PCN is a viable alternative to surgical intervention

Exogenous 17-β Estradiol Administration Blunts Progression of Established Angiotensin II-Induced Abdominal Aortic Aneurysms in Female Ovariectomized Mice

BACKGROUND: Abdominal aortic aneurysms (AAAs) occur predominately in males. However, AAAs in females have rapid growth rates and rupture at smaller sizes. Mechanisms contributing to AAA progression in females are undefined. We defined effects of ovariectomy, with and without 17-β estradiol (E2), on progression of established angiotensin II (AngII)-induced AAAs in female mice. METHODS: We used neonatal testosterone exposures at 1 day of age to promote susceptibility to AngII-induced AAAs in adult female Ldlr-/- mice. Females were infused with AngII for 28 days to induce AAAs, and then stratified into groups that were sham, ovariectomized (Ovx, vehicle), or Ovx with E2 administration for 2 months of continued AngII infusions. Aortic lumen diameters were quantified by ultrasound and analyzed by linear mixed model, and maximal AAA diameters were analyzed by one-way ANOVA. Atherosclerosis was quantified en face in the aortic arch. AAA tissue sections were analyzed for cellular composition. We quantified effects of E2 on abdominal aortic smooth muscle cell (SMC) growth, α-actin and transforming growth factor-beta (TGF-β) production, and wound healing. RESULTS: Serum E2 concentrations were increased significantly by E2. Aortic lumen diameters increased over time in sham-operated and Ovx (vehicle) females, but not in Ovx females administered E2. At day 70, E2 administration decreased significantly aortic lumen diameters compared to Ovx vehicle and sham-operated females. Compared to Ovx females (vehicle), maximal AAA diameters were reduced significantly by E2. AAA tissue sections from Ovx females administered E2 exhibited significant increases in α-actin and decreases in neutrophils compared to Ovx females administered vehicle. In abdominal aortic SMCs, E2 resulted in a concentration-dependent increase in α-actin, elevated TGF-β, and more rapid wound healing. E2 administration to Ovx females also significantly reduced atherosclerotic lesions compared to sham-operated females. This effect was accompanied by significant reductions in serum cholesterol concentrations. CONCLUSIONS: E2 administration to Ovx females abolished progressive growth and decreased severity of AngII-induced AAAs. These effects were accompanied by increased SMC α-actin, elevated TGF-β, and reduced neutrophils. Similarly, E2 administration reduced AngII-induced atherosclerosis. These results suggest that loss of E2 in post-menopausal females may contribute to progressive growth of AAAs

Evidence for subsidence rate variation in the Newark Basin and its influence on the deposition of fluvial sediments of the Stockton Formation

The Stockton Formation of the Newark Basin represents an exciting time in Earth history during the early stages of rifting of the North Atlantic, with rapid subsidence and sediment deposition. Much of the previous work on this formation has been done using drill cores, with development limiting surface exposure. While this allows us to build a full stratigraphic sequence of deposition, it has the potential to miss smaller-scale variability and sedimentary structures. It is also difficult to understand the three-dimensional geometries, architecture and relationships between the depositional elements from drill core alone. An outcrop in North Bergen, NJ that was recently exposed during construction provided an opportunity to study the primary and secondary sedimentary structures of a previously hidden part of the Stockton Formation. These sediments and structures were investigated in the field and laboratory, with geochemical data assisting in the interpretation of their origin and history. Despite its small size, this outcrop provides strong evidence for varying rates of basin subsidence, with rocks deposited during more rapid subsidence also showing secondary structures associated with major earthquakes. Rapid subsidence during fluvial deposition resulted in the preservation of more fine-grained, lower-porosity sediments. Recently the Newark Basin has been identified as having characteristics that are favourable for CO2 storage, however, a detailed understanding of sedimentary lithologies is essential to assessing that potential. If these periods of rapid subsidence have similar lithological consequences basin-wide, this could potentially impact the capacity for carbon sequestration, by reducing porosity and permeability in many areas, and potentially creating barriers to flow

Rapid Induction of the Unfolded Protein Response and Apoptosis by Estrogen Mimic TTC-352 for the Treatment of Endocrine-Resistant Breast Cancer

Patients with long-term estrogen-deprived breast cancer (BC), after resistance to tamoxifen or aromatase inhibitors develops, can experience tumor regression when treated with estrogens. Estrogen’s anti-tumor effect is attributed to apoptosis via the estrogen receptor (ER). Estrogen treatment can have unpleasant gynecological and non-gynecological adverse events thus the development of safer estrogenic agents remains a clinical priority. Here, we study synthetic selective estrogen mimics (SEMs) BMI-135 and TTC-352, and the naturally-occurring estrogen estetrol (E4), which are proposed as safer estrogenic agents compared to 17β-estradiol (E2), for the treatment of endocrine-resistant BC. TTC-352 and E4 are being evaluated in BC clinical trials. Cell viability assays, real-time polymerase chain reaction, immunoblotting, ERE DNA pull downs, Mass spectrometry, X-ray crystallography, docking and molecular dynamic simulations, live cell imaging, and annexin V staining were conducted in 11 biologically-different BC models. Results were compared with the potent full agonist E2, less potent full agonist E4, the benchmark partial agonist triphenylethylene bisphenol (BPTPE), and antagonists 4-hydroxytamoxifen and endoxifen. We report ERα’s regulation and coregulators’ binding profiles with SEMs and E4. We describe TTC-352’s pharmacology as a weak full agonist and anti-tumor molecular mechanisms. This study highlights TTC-352’s benzothiophene scaffold that yields an H-bond with Glu353, which allows Asp351-to-helix 12 (H12) interaction; sealing ERα’s ligand binding domain, recruiting E2-enriched coactivators, and triggering rapid ERα-induced unfolded protein response (UPR) and apoptosis, as the basis of its anti-cancer properties. BPTPE’s phenolic OH yields an H-Bond with Thr347, which disrupts Asp351-to-H12 interaction; delaying UPR and apoptosis, and increasing clonal evolution risk