Multi-color pyrometer for materials processing in space

The design, construction and calibration of a computer-linked multicolor pyrometer is described. The device was constructed for ready adaptation to a spacecraft and for use in the control of thermal processes for manufacturing materials in space. The pyrometer actually uses only one color at a time, and is relatively insensitive to uncertainties in the heated object's emissivity because the product of the color and the temperature has been selected to be within a regime where the radiant energy emitted from the body increases very rapidly with temperature. The instrument was calibrated and shown to exceed its design goal of temperature measurements between 300 and 2000 C, and its accuracy in the face of imprecise knowledge of the hot object's emissivity was demonstrated

Analysis of the third national health and nutrition examination survey (NHANES III) using expert ratings of job categories

Background Few epidemiologic studies have addressed the exposure–response relationships between work activities and symptomatic knee osteoarthritis (OA). This analysis used data from a national survey and ergonomists' ratings to address this issue. Methods Interview and knee X-ray data were obtained from the Third National Health and Nutrition Examination Survey. Occupational ratings were obtained using ergonomists. A weighted logistic regression was used. Results Among men, a significant exposure–response relationship was found between symptomatic knee OA and kneeling. In both genders, there was a significant trend in heavy lifting and severe symptomatic knee OA. Approximately 20.7% of knee OA can be attributed to kneeling >14% of the workday among men. Conclusions The significant exposure–response relationships suggest that modest reductions in certain occupational activities can reduce the burden of knee OA. The study was limited by unvalidated expert ratings. Research is needed to identify hazardous characteristics of work activities and to clarify exposure–response relationships. Am. J. Ind. Med. 51:37–46, 2008. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57516/1/20512_ftp.pd

Phase I dose-escalation trial of the oral AKT inhibitor uprosertib in combination with the oral MEK1/MEK2 inhibitor trametinib in patients with solid tumors.

PurposeThis study aimed to determine the safety, tolerability, and recommended phase II doses of trametinib plus uprosertib (GSK2141795) in patients with solid tumors likely to be sensitive to MEK and/or AKT inhibition.MethodsThis was a phase I, open-label, dose-escalation, and dose-expansion study in patients with triple-negative breast cancer or BRAF-wild type advanced melanoma. The primary outcome of the expansion study was investigator-assessed response. Among 126 enrolled patients, 63 received continuous oral daily dosing of trametinib and uprosertib, 29 received various alternative dosing schedules, and 34 were enrolled into expansion cohorts. Doses tested in the expansion cohort were trametinib 1.5 mg once daily (QD) + uprosertib 50 mg QD.ResultsAdverse events (AEs) were consistent with those reported in monotherapy studies but occurred at lower doses and with greater severity. Diarrhea was the most common dose-limiting toxicity; diarrhea and rash were particularly difficult to tolerate. Overall, 59% and 6% of patients reported AEs with a maximum severity of grade 3 and 4, respectively. Poor tolerability prevented adequate delivery of uprosertib with trametinib at a concentration predicted to have clinical activity. The study was terminated early based on futility in the continuous-dosing expansion cohorts and a lack of pharmacological or therapeutic advantage with intermittent dosing. The objective response rate was < 5% (1 complete response, 5 partial responses).ConclusionsContinuous and intermittent dosing of trametinib in combination with uprosertib was not tolerated, and minimal clinical activity was observed in all schedules tested

Bone marrow mesenchymal stromal cell-derived extracellular matrix displays altered glycosaminoglycan structure and impaired functionality in Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) comprise a heterogeneous group of hematologic malignancies characterized by clonal hematopoiesis, one or more cytopenias such as anemia, neutropenia, or thrombocytopenia, abnormal cellular maturation, and a high risk of progression to acute myeloid leukemia. The bone marrow microenvironment (BMME) in general and mesenchymal stromal cells (MSCs) in particular contribute to both the initiation and progression of MDS. However, little is known about the role of MSC-derived extracellular matrix (ECM) in this context. Therefore, we performed a comparative analysis of in vitro deposited MSC-derived ECM of different MDS subtypes and healthy controls. Atomic force microscopy analyses demonstrated that MDS ECM was significantly thicker and more compliant than those from healthy MSCs. Scanning electron microscopy showed a dense meshwork of fibrillar bundles connected by numerous smaller structures that span the distance between fibers in MDS ECM. Glycosaminoglycan (GAG) structures were detectable at high abundance in MDS ECM as white, sponge-like arrays on top of the fibrillar network. Quantification by Blyscan assay confirmed these observations, with higher concentrations of sulfated GAGs in MDS ECM. Fluorescent lectin staining with wheat germ agglutinin and peanut agglutinin demonstrated increased deposition of N-acetyl-glucosamine GAGs (hyaluronan (HA) and heparan sulfate) in low risk (LR) MDS ECM. Differential expression of N-acetyl-galactosamine GAGs (chondroitin sulfate, dermatan sulfate) was observed between LR- and high risk (HR)-MDS. Moreover, increased amounts of HA in the matrix of MSCs from LR-MDS patients were found to correlate with enhanced HA synthase 1 mRNA expression in these cells. Stimulation of mononuclear cells from healthy donors with low molecular weight HA resulted in an increased expression of various pro-inflammatory cytokines suggesting a contribution of the ECM to the inflammatory BMME typical of LR-MDS. CD34+ hematopoietic stem and progenitor cells (HSPCs) displayed an impaired differentiation potential after cultivation on MDS ECM and modified morphology accompanied by decreased integrin expression which mediate cell-matrix interaction. In summary, we provide evidence for structural alterations of the MSC-derived ECM in both LR- and HR-MDS. GAGs may play an important role in this remodeling processes during the malignant transformation which leads to the observed disturbance in the support of normal hematopoiesis

Resilience and economic empowerment: A qualitative investigation of entrepreneurial Indonesian Women

The development of female entrepreneurs in Indonesia is an integral part of Muslim women\u27s economic contributions and empowerment. However, there is a lack of reliable research about female entrepreneurship and how gender may affect the experiences of business ownership in Indonesia. Therefore, the aim of this study is to explore the challenges encountered by these women entrepreneurs on a daily basis. Qualitative in-depth interviews were conducted with 30 female Indonesian entrepreneurs. Participants were recruited using theoretical and maximum variation sampling techniques. Content analysis was then used to analyze the data. Results revealed high levels of variations, both within and between women, suggesting that the quality of business entrepreneurship and success depended largely on the personal characteristics of these women, rather than on any system of formal education or training. This study also found that many women displayed resilient coping strategies when dealing with business failures. As a consequence, they were able to thrive despite restrictive social, cultural and political constraints. The paper highlights the importance of the experiences of female entrepreneurs in a developing country and the need to integrate the development of female entrepreneurship as a part of women empowerment effort

Thyrotropin-releasing hormone (TRH) promotes wound re-epithelialisation in frog and human skin

There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis) skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH) as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression). Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters

Sustainable management of groundwater extraction: An Australian perspective on current challenges

Study focus: Our incomplete knowledge of groundwater systems and processes imposes barriers in attempting to manage groundwater sustainably. Challenges also arise through complex institutional arrangements and decision-making processes, and the difficulty in involving stakeholders. In some areas, these difficulties have led to water table decline and impacts on groundwater users and groundwater-dependent ecosystems. However, there is potential to improve the sustainable use of groundwater resources through improvements in management practices. We discuss some of the challenges, and present survey results of research, government, and industry professionals across the groundwater sector in Australia. New hydrological insights for the region: The highest-ranked challenge identified in the survey was the difficulty in determining regional-scale volumetric water extraction limits. This is surprising given the criticism in the international literature of volumetric based approaches for groundwater management, and the decreased reliance on this approach in Australia and elsewhere in recent years. Other major challenges are the difficulty in determining and implementing maximum drawdown criteria for groundwater levels, determining water needs of ecosystems, and managing groundwater impacts on surface water. Notwithstanding these gaps in technical understanding and tools and a lack of resources for groundwater studies, improvements in stakeholder communication should enable more effective decision-making and improve compliance with regulations designed to protect groundwater and dependent ecosystems

Exclusion zones for variable rate nitrogen fertilisation in grazed dairy pasture systems in New Zealand

To assess the variability of total soil nitrogen (TN) on grazed and irrigated pastures, TN was quantified from spatially distinct “areas” within the paddock (irrigated and non-irrigated areas, around the gates, and around the troughs) on two dairy farms located in Canterbury, New Zealand. During soil sampling, each area was sub-divided and multiple soil samples were taken to ensure adequate spatial representation of each area. The results showed there were no differences in TN between the farms, but differences were detected between the paddocks (P< 0.001), largely due to the significant interaction between the areas (gates and troughs) in different paddocks (P< 0.001). The greatest variability in TN was around the gates, due to either much higher or lower TN near the entrance of the gates. The TN levels returned to concentrations that were similar to those in the surrounding pasture after 4 m distance from the gates. This study shows while TN concentrations are relatively consistent spatially within pastures, there is high variability in TN in proximity to some farm infrastructure, such as gates and troughs

The reductive activation of CO2 across a Ti═Ti double bond: synthetic, structural, and mechanistic studies

[Image: see text] The reactivity of the bis(pentalene)dititanium double-sandwich compound Ti(2)Pn(†)(2) (1) (Pn(†) = 1,4-{Si(i)Pr(3)}(2)C(8)H(4)) with CO(2) is investigated in detail using spectroscopic, X-ray crystallographic, and computational studies. When the CO(2) reaction is performed at −78 °C, the 1:1 adduct 4 is formed, and low-temperature spectroscopic measurements are consistent with a CO(2) molecule bound symmetrically to the two Ti centers in a μ:η(2),η(2) binding mode, a structure also indicated by theory. Upon warming to room temperature the coordinated CO(2) is quantitatively reduced over a period of minutes to give the bis(oxo)-bridged dimer 2 and the dicarbonyl complex 3. In situ NMR studies indicated that this decomposition proceeds in a stepwise process via monooxo (5) and monocarbonyl (7) double-sandwich complexes, which have been independently synthesized and structurally characterized. 5 is thermally unstable with respect to a μ-O dimer in which the Ti–Ti bond has been cleaved and one pentalene ligand binds in an η(8) fashion to each of the formally Ti(III) centers. The molecular structure of 7 shows a “side-on” bound carbonyl ligand. Bonding of the double-sandwich species Ti(2)Pn(2) (Pn = C(8)H(6)) to other fragments has been investigated by density functional theory calculations and fragment analysis, providing insight into the CO(2) reaction pathway consistent with the experimentally observed intermediates. A key step in the proposed mechanism is disproportionation of a mono(oxo) di-Ti(III) species to yield di-Ti(II) and di-Ti(IV) products. 1 forms a structurally characterized, thermally stable CS(2) adduct 8 that shows symmetrical binding to the Ti(2) unit and supports the formulation of 4. The reaction of 1 with COS forms a thermally unstable complex 9 that undergoes scission to give mono(μ-S) mono(CO) species 10. Ph(3)PS is an effective sulfur transfer agent for 1, enabling the synthesis of mono(μ-S) complex 11 with a double-sandwich structure and bis(μ-S) dimer 12 in which the Ti–Ti bond has been cleaved

Identification of a small molecule yeast TORC1 inhibitor with a flow cytometry-based multiplex screen

TOR (target of rapamycin) is a serine/threonine kinase, evolutionarily conserved from yeast to human, which functions as a fundamental controller of cell growth. The moderate clinical benefit of rapamycin in mTOR-based therapy of many cancers favors the development of new TOR inhibitors. Here we report a high throughput flow cytometry multiplexed screen using five GFPtagged yeast clones that represent the readouts of four branches of the TORC1 signaling pathway in budding yeast. Each GFP-tagged clone was differentially color-coded and the GFP signal of each clone was measured simultaneously by flow cytometry, which allows rapid prioritization of compounds that likely act through direct modulation of TORC1 or proximal signaling components. A total of 255 compounds were confirmed in dose-response analysis to alter GFP expression in one or more clones. To validate the concept of the high throughput screen, we have characterized CID 3528206, a small molecule most likely to act on TORC1 as it alters GFP expression in all five GFP clones in an analogous manner to rapamycin. We have shown that CID 3528206 inhibited yeast cell growth, and that CID 3528206 inhibited TORC1 activity both in vitro and in vivo with EC50s of 150 nM and 3.9 μM, respectively. The results of microarray analysis and yeast GFP collection screen further support the notion that CID 3528206 and rapamycin modulate similar cellular pathways. Together, these results indicate that the HTS has identified a potentially useful small molecule for further development of TOR inhibitors