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Background:We evaluated smell identification as a biomarker for Alzheimer disease (AD) by assessing its utility in differentiating normal aging from an amnestic disorder and determining its predictive value for conversion from amnestic mild cognitive impairment (aMCI) to AD.Methods:Cross-sectional study (AD = 262, aMCI = 110, controls = 194) measuring smell identification (University of Pennsylvania Smell Identification Test [UPSIT]) and cognitive status was performed, as well as longitudinal analysis of aMCI participants (n = 96) with at least 1 year follow-up (mean 477.6 ± 223.3 days), to determine conversion by National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association criteria.Results:Odor identification and disease status were highly correlated after correcting for age, sex, andAPOE(p< 0.001). Receiver operating characteristic (ROC)/area under the curve (AUC) was similar for the 40-item UPSIT, the top 10 smells in our study, and the 10-item subset previously proposed. Smeller/nonsmeller based on the 10-item subset with a cutoff of 7 (≤7, nonsmeller; >7, smeller) had a sensitivity and specificity of 88% and 71% for identifying AD and 74% sensitivity and 71% specificity for identifying an amnestic disorder. A total of 36.4% of participants with impaired olfaction and 17.3% with intact olfaction converted to AD (p= 0.03). The ROC/AUC for prediction of conversion to AD was 0.62.Conclusions:Olfactory identification deficit is a useful screening tool for AD-related amnestic disorder, with sensitivity and specificity comparable to other established biomarkers, with benefits such as ease of administration and low cost. Olfactory identification deficit can be utilized to stratify risk of conversion from aMCI to AD and enrich clinical trials of disease-modifying therapy.Classification of evidence:This study provides Class III evidence that smell identification (10-item UPSIT subset) accurately identifies patients with amnestic disorders.

To extend the current understanding of the effects of liquid carryover on compressor performance, a detailed analysis including the aerothermodynamics of the compression process and the flow field within the compressor is required. This paper presents a CFD analysis of a two-stage, in-line centrifugal compressor, operating in a two-phase flow environment of a single constituent, refrigerant R134a. The computational method implemented in this analysis accounts for the real gas behavior, and also incorporates the effects of interphase heat, mass and momentum transfer, as well as the droplet dynamics. The investigations revealed that liquid carryover altered the flow field within the compressor, causing both stages to operate at off-design conditions. This effect was observed to be more pronounced for the second stage. The overall effects of liquid carryover were shown to be detrimental to the compressor performance. Increasing the amount of liquid carryover resulted in further lowering of the performance. On the other hand, the effects of the size of the ingested droplets were seen to be negligible.

Traumatic brain injury (TBI) remains a major cause ofmorbidity and mortality in North America for individualsbelow the age of 45 [70], in the US there are about 1.4–1.7million cases of TBI leading to 300,000 hospital admissions,50,000 deaths and over 80,000 patients with significant dis-ability each year [35,46]. Moderate or mild hypothermia(defined as a reduction in core temperature to 32–34

Inappropriate responses to normal commensal bacteria trigger immune activation in both inflammatory bowel disease and experimental colitis. How gut flora contribute to the pathogenesis of inflammatory bowel disease is unclear, but may involve entrapment of leukocytes and remodeling of the vascular system. Here we evaluated how the progression and tissue remodeling in experimental colitis differ in a germ- free model of mouse colitis. Four treatment groups were used: control, antibiotic-treated (ABX), dextran sulfate colitis (DSS) and DSS pre- and co-treated with antibiotics (DSS + ABX). In days 0 - 3 of the study, germ-free mice received antibiotics (vancomycin, neomycin, and metronidazole). During the next 11 days, antibiotics were continued and DSS (3%) added to “colitis” groups. Disease activity, weight, stool form and blood were monitored daily. Mice were sacrificed and tissue samples harvested. Histopathological scores in controls (0.00) and in ABX (1.0+/–0.81) were significantly (p –0). Extents of injury, inflammation and crypt damage were all improved in DSS + ABX. The Disease Activity Index score (day 11) was significantly worse in the DSS group compared to the DSS + ABX group. Stool blood and form scores were also significantly improved among these groups. Importantly, myeloper- oxidase was significantly reduced in DSS + ABX, indicating that neutrophil infiltration was blocked. Colitis was associated with an increase in blood and lymphatic vessels; both of these events were also significantly reduced by gut sterilization. Our experiment shows that clinical and histopathological severity of colitis was significantly worse in the DSS colitis group compared to the DSS + ABX group, supporting the hypothesis that development of IBD is likely to be less severe with appropriate antibiotic treatment. In particular, gut sterilization effectively reduces leuko- cyte-dependent (PMN) injury to improve outcomes and may be an important target for therapy.

The role of power system is to supply the power to the various load center. Today's power system is designed to operate effectively and efficiently. In earlier years, Electric power system was small and localized. In order to improve stability of the system, real and reactive power compensation in the transmission line is important. This paper describes theory & modeling of one of the Flexible Alternating Current Transmission System (FACTS) devices, called as Static Synchronous Series Compensator (SSSC). Generally SSSC is connected to the bus through Voltage Source Inverter (VSI), but it is having demerits like limited output voltage, restriction on simultaneous switching of upper & lower switches etc. All these issues are sort out if Z source inverter (ZSI) is used instead of VSI. This paper presents modeling of SSSC based on Z - Source Inverter (ZSI) with SPWM technique. The system's behavior with and without SSSC have been studied.

The performance of a compressor is known to be affected by the ingestion of liquid droplets. Heat, mass and momentum transfer as well as the droplet dynamics are some of the important mechanisms that govern the two-phase flow. This paper presents numerical investigations of three-dimensional two-phase flow in a two-stage centrifugal compressor, incorporating the effects of the above mentioned mechanisms. The results of the two-phase flow simulations are compared with the simulation involving only the gaseous phase. The implications for the compressor performance, viz. the pressure ratio, the power input and the efficiency are discussed. The role played by the droplet-wall interactions on the rate of vaporization, and on the compressor performance is also highlighted.Copyright © 2015 by ASME and United Technologies Corporation

The performance of an axial compressor rotor is known to be affected by the variations in tip clearance during its operation. This effect is pronounced for the rear stages of a multistage compressor. This paper describes a novel design that is shown to aerodynamically desensitize the rotor tip to the tip clearance variations. The effect of tip clearance variations on the performance of a baseline low speed, high hub-to-tip ratio axial compressor rotor is studied using CFD. Based on the understanding developed from this flow analysis, the baseline rotor is redesigned by tailoring the tip and redistributing the blade loading over the span. The tip tailoring results in a blade with split dihedral, i.e. of applied dihedral variable from the leading edge to the trailing edge. CFD analysis of the tip tailored configuration shows lower pressure drop with increasing tip clearance as compared to the baseline design. The simulation results are validated through testing in a low speed axial compressor rig, thereby giving experimental support to the desensitization of the rotor to the studied tip clearance variations by tip tailoring.

The role of the venous system in the pathogenesis of inflammatory neurological/neurodegenerative diseases remains largely unknown and underinvestigated. Aside from cerebral venous infarcts, thromboembolic events, and cerebrovascular bleeding, several inflammatory central nervous system (CNS) diseases, such as multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), and optic neuritis, appear to be associated with venous vascular dysfunction, and the neuropathologic hallmark of these diseases is a perivenous, rather than arterial, lesion. Such findings raise fundamental questions about the nature of these diseases, such as the reasons why their pathognomonic lesions do not develop around the arteries and what exactly are the roles of cerebral venous inflammation in their pathogenesis. Apart from this inflammatory-based view, a new hypothesis with more focus on the hemodynamic features of the cerebral and extracerebral venous system suggests that MS pathophysiology might be associated with the venous system that drains the CNS. Such a hypothesis, if proven correct, opens new therapeutic windows in MS and other neuroinflammatory diseases. Here, we present a comprehensive review of the pathophysiology of MS, ADEM, pseudotumor cerebri, and optic neuritis, with an emphasis on the roles of venous vascular system programming and dysfunction in their pathogenesis. We consider the fundamental differences between arterial and venous endothelium, their dissimilar responses to inflammation, and the potential theoretical contributions of venous insufficiency in the pathogenesis of neurovascular diseases.

Background Ulcerative colitis (UC) is the most common form of inflammatory bowel disease in the USA. A key component of UC is the increase in inflammatory angiogenesis of the colon during active disease. This increase is driven to a great extent by the over expression of VEGF-A. Recently, VEGF165b (VEGF164b in mouse), an anti-angiogenic form of VEGF-A was described and its regulation was determined to be disturbed in many pathologies such as cancer and pre-eclampsia. Results The aims of this study were to examine the role of this inhibitory VEGF by expressing this molecule in a model of intestinal inflammation, and to evaluate its expression as a potential new therapeutic approach for treating UC. A modified model of TNBS colitis was used to determine the effects of rVEGF164b expression on colon inflammation. Expansion of the vascular system was assessed by immunhistochemical methods and macro- and microscopic measurements of inflammation in the colon were measured. Leukocyte invasion of the tissue was measured by myeloperoxidase assay and identification and counting of lymphoid follicles. Both angio- and lymphangiogenesis were reduced by expression of rVEGF164b, which correlated with reduction in both gross and microscopic inflammatory scores. Leukocyte invasion of the tissue was also reduced by rVEGF164b expression. Conclusions This is the first report using an endogenous inhibitory VEGF-A isoform for therapy in a model of experimental colitis. Inhibitory VEGF molecules play an important role in maintenance of gut homeostasis and may be dysregulated in UC. The results of this study suggest that restoration of rVEGF164b expression has anti-inflammatory activity in a TNBS model and warrants further examination as a possible therapeutic for UC.

Objectives We previously reported a correlation between levels of microparticles carrying CD31 (PMP CD31+) and disease activity in MS. However, the effects of long term (12 month) treatment with high dose, high frequency interferon-β1a (Rebif™) on plasma levels of PMPCD31+, PMPCD146+, and PMPCD54+ and MRI measures of disease activity have not yet been assessed. Methods During this prospective 1-year study, we used flow cytometry to measure changes in plasma microparticles (PMP) bearing CD31 (PMPCD31+), CD146 (PMPCD146+), and CD54/ICAM-1 (PMPCD54+) in 16 consecutive patients with relapsing-remitting MS (RRMS) before and after 3, 6, and 12 months of subcutaneous therapy with interferon-beta1a (44 micrograms, 3X weekly). At each visit, clinical exams and expanded disability status scale (EDSS) scores were recorded. Results Plasma levels of PMPCD31+, and PMPCD54+ were significantly reduced by treatment with IFN-β1a. PMPCD146+ appeared to decrease only at 3 months and did not persist at 6 and 12 months (p = 0.0511). In addition, the decrease in plasma levels of PMPCD31+ and PMPCD54+ levels at 12 months were associated with a significant decrease in the number and volume of contrast enhancing T1-weigthed lesions. Conclusion Our data suggest that serial measurement of plasma microparticles (PMP), particularly in the initial stages of MS (when neuro-inflammatory cascades are more intense), may serve as reliable and reproducible surrogate markers of response to IFN-β1a therapy for MS. In addition, the progressive decline in plasma levels of PMPCD31+ and PMPCD54+ further supports the concept that IFN-β1a exerts stabilizing effect on the cerebral endothelial cells during pathogenesis of MS.