1,290 research outputs found

    Measuring surface-area-to-volume ratios in soft porous materials using laser-polarized xenon interphase exchange NMR

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    We demonstrate a minimally invasive nuclear magnetic resonance (NMR) technique that enables determination of the surface-area-to-volume ratio (S/V) of soft porous materials from measurements of the diffusive exchange of laser-polarized 129Xe between gas in the pore space and 129Xe dissolved in the solid phase. We apply this NMR technique to porous polymer samples and find approximate agreement with destructive stereological measurements of S/V obtained with optical confocal microscopy. Potential applications of laser-polarized xenon interphase exchange NMR include measurements of in vivo lung function in humans and characterization of gas chromatography columns.Comment: 14 pages of text, 4 figure

    A functional-cognitive framework for attitude research

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    In attitude research, behaviours are often used as proxies for attitudes and attitudinal processes. This practice is problematic because it conflates the behaviours that need to be explained (explanandum) with the mental constructs that are used to explain these behaviours (explanans). In the current chapter we propose a meta-theoretical framework that resolves this problem by distinguishing between two levels of analysis. According to the proposed framework, attitude research can be conceptualised as the scientific study of evaluation. Evaluation is defined not in terms of mental constructs but in terms of elements in the environment, more specifically, as the effect of stimuli on evaluative responses. From this perspective, attitude research provides answers to two questions: (1) Which elements in the environment moderate evaluation? (2) What mental processes and representations mediate evaluation? Research on the first question provides explanations of evaluative responses in terms of elements in the environment (functional level of analysis); research on the second question offers explanations of evaluation in terms of mental processes and representations (cognitive level of analysis). These two levels of analysis are mutually supportive, in that better explanations at one level lead to better explanations at the other level. However, their mutually supportive relation requires a clear distinction between the concepts of their explanans and explanandum, which are conflated if behaviours are treated as proxies for mental constructs. The value of this functional-cognitive framework is illustrated by applying it to four central questions of attitude research

    Tumour expression of leptin is associated with chemotherapy resistance and therapy-independent prognosis in gastro-oesophageal adenocarcinomas

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    Background: Cytotoxic chemotherapy remains the main systemic therapy for gastro-oesophageal adenocarcinoma, but resistance to chemotherapy is common, resulting in ineffective and often toxic treatment for patients. Predictive biomarkers for chemotherapy response would increase the probability of successful therapy, but none are currently recommended for clinical use. We used global gene expression profiling of tumour biopsies to identify novel predictive biomarkers for cytotoxic chemotherapy. Methods: Tumour biopsies from patients (n=14) with TNM stage IB–IV gastro-oesophageal adenocarcinomas receiving platinum-based combination chemotherapy were used as a discovery cohort and profiled with Affymetrix ST1.0 Exon Genechips. An independent cohort of patients (n=154) treated with surgery with or without neoadjuvant platinum combination chemotherapy and gastric adenocarcinoma cell lines (n=22) were used for qualification of gene expression profiling results by immunohistochemistry. A cisplatin-resistant gastric cancer cell line, AGS Cis5, and the oesophageal adenocarcinoma cell line, OE33, were used for in vitro validation investigations. Results: We identified 520 genes with differential expression (Mann–Whitney U, P<0.020) between radiological responding and nonresponding patients. Gene enrichment analysis (DAVID v6.7) was used on this list of 520 genes to identify pathways associated with response and identified the adipocytokine signalling pathway, with higher leptin mRNA associated with lack of radiological response (P=0.011). Similarly, in the independent cohort (n=154), higher leptin protein expression by immunohistochemistry in the tumour cells was associated with lack of histopathological response (P=0.007). Higher leptin protein expression by immunohistochemistry was also associated with improved survival in the absence of neoadjuvant chemotherapy, and patients with low leptin protein-expressing tumours had improved survival when treated by neoadjuvant chemotherapy (P for interaction=0.038). In the gastric adenocarcinoma cell lines, higher leptin protein expression was associated with resistance to cisplatin (P=0.008), but not to oxaliplatin (P=0.988) or 5fluorouracil (P=0.636). The leptin receptor antagonist SHLA increased the sensitivity of AGS Cis5 and OE33 cell lines to cisplatin. Conclusions: In gastro-oesophageal adenocarcinomas, tumour leptin expression is associated with chemoresistance but a better therapy-independent prognosis. Tumour leptin expression determined by immunohistochemistry has potential utility as a predictive marker of resistance to cytotoxic chemotherapy, and a prognostic marker independent of therapy in gastro-oesophageal adenocarcinoma. Leptin antagonists have been developed for clinical use and leptin and its associated pathways may also provide much needed novel therapeutic targets for gastro-oesophageal adenocarcinoma

    Influence of Nanoparticle Size and Shape on Oligomer Formation of an Amyloidogenic Peptide

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    Understanding the influence of macromolecular crowding and nanoparticles on the formation of in-register β\beta-sheets, the primary structural component of amyloid fibrils, is a first step towards describing \emph{in vivo} protein aggregation and interactions between synthetic materials and proteins. Using all atom molecular simulations in implicit solvent we illustrate the effects of nanoparticle size, shape, and volume fraction on oligomer formation of an amyloidogenic peptide from the transthyretin protein. Surprisingly, we find that inert spherical crowding particles destabilize in-register β\beta-sheets formed by dimers while stabilizing β\beta-sheets comprised of trimers and tetramers. As the radius of the nanoparticle increases crowding effects decrease, implying smaller crowding particles have the largest influence on the earliest amyloid species. We explain these results using a theory based on the depletion effect. Finally, we show that spherocylindrical crowders destabilize the ordered β\beta-sheet dimer to a greater extent than spherical crowders, which underscores the influence of nanoparticle shape on protein aggregation

    To be financed or not : the role of patents for venture capital financing

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    This paper investigates how patent applications and grants held by new ventures improve their ability to attract venture capital (VC) financing. We argue that investors are faced with considerable uncertainty and therefore rely on patents as signals when trying to assess the prospects of potential portfolio companies. For a sample of VC-seeking German and British biotechnology companies we have identified all patents filed at the European Patent Office (EPO). Applying hazard rate analysis, we find that in the presence of patent applications, VC financing occurs earlier. Our results also show that VCs pay attention to patent quality, financing those ventures faster which later turn out to have high-quality patents. Patent oppositions increase the likelihood of receiving VC, but ultimate grant decisions do not spur VC financing, presumably because they are anticipated. Our empirical results and interviews with VCs suggest that the process of patenting generates signals which help to overcome the liabilities of newness faced by new ventures

    Neutrophils in cancer: neutral no more

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    Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

    Feasibility study for a correlation electron cyclotron emission turbulence diagnostic based on nonlinear gyrokinetic simulations

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    This paper describes the use of nonlinear gyrokinetic simulations to assess the feasibility of a new correlation electron cyclotron emission (CECE) diagnostic that has been proposed for the Alcator C-Mod tokamak (Marmar et al 2009 Nucl. Fusion 49 104014). This work is based on a series of simulations performed with the GYRO code (Candy and Waltz 2003 J. Comput. Phys. 186 545). The simulations are used to predict ranges of fluctuation level, peak poloidal wavenumber and radial correlation length of electron temperature fluctuations in the core of the plasma. The impact of antenna pattern and poloidal viewing location on measurable turbulence characteristics is addressed using synthetic diagnostics. An upper limit on the CECE sample volume size is determined. The modeling results show that a CECE diagnostic capable of measuring transport-relevant, long-wavelength (k[subscript θ]ρ[subscript s] < 0.5) electron temperature fluctuations is feasible at Alcator C-Mod.United States. Dept. of Energy (DE-FC02-C99ER54512-CMOD
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