A low temperature, 180 °C, amorphous Si (a‐Si:H) process on bonded stainless steel substrates is discussed and a 3.8‐inch QVGA active matrix (AM) electrophoretic display as well as a 64×64 ...electrophoretic display with integrated column drivers are demonstrated. The n‐channel thin‐film transistors (TFTs) exhibited saturation mobilities of 0.7 cm2/V‐sec, median drive currents of 26.2 μA and low defectivity.
A novel peptide, AMG 416 (formerly KAI-4169, and with a United States Adopted Name: velcalcetide), has been identified that acts as an agonist of the calcium-sensing receptor (CaSR). This article ...summarizes the in vitro and in vivo characterization of AMG 416 activity and the potential clinical utility of this novel compound. AMG 416 activates the human CaSR in vitro, acting by a mechanism distinct from that of cinacalcet, the only approved calcimimetic, since it can activate the CaSR both in the presence or the absence of physiologic levels of extracellular calcium. Administration of AMG 416 in vivo into either normal or renally compromised rats results in dose-dependent reductions in parathyroid hormone (PTH) levels and corresponding decreases in serum calcium, regardless of the baseline level of PTH. Treatment of 5/6 nephrectomized rats with AMG 416 resulted in dramatic improvements in their metabolic profile, including lower PTH and serum creatinine levels, reduced amounts of vascular calcification, attenuated parathyroid hyperplasia, and greater expression of the parathyroid gland regulators CaSR, vitamin D receptor, and FGF23 receptor compared with vehicle-treated animals. No drug accumulation was observed under this dosing regimen, and the terminal half-life of AMG 416 was estimated to be 2-4.5 hours. As a long-acting CaSR agonist, AMG 416 is an innovative new therapy for the treatment of hemodialysis patients with secondary hyperparathyroidism.
Recognition that coronary blood flow is tightly coupled with myocardial metabolism has been appreciated for well over half a century. However, exactly how coronary microvascular resistance is tightly ...coupled with myocardial oxygen consumption (MV̇o
) remains one of the most highly contested mysteries of the coronary circulation to this day. Understanding the mechanisms responsible for local metabolic control of coronary blood flow has been confounded by continued debate regarding both anticipated experimental outcomes and data interpretation. For a number of years, coronary venous Po
has been generally accepted as a measure of myocardial tissue oxygenation and thus the classically proposed error signal for the generation of vasodilator metabolites in the heart. However, interpretation of changes in coronary venous Po
relative to MV̇o
are quite nuanced, inherently circular in nature, and subject to confounding influences that remain largely unaccounted for. The purpose of this review is to highlight difficulties in interpreting the complex interrelationship between key coronary outcome variables and the arguments that emerge from prior studies performed during exercise, hemodilution, hypoxemia, and alterations in perfusion pressure. Furthermore, potential paths forward are proposed to help to facilitate further dialogue and study to ultimately unravel what has become the Gordian knot of the coronary circulation.
Although widely studied as a neurotransmitter, T cell-derived acetylcholine (ACh) has recently been reported to play an important role in regulating immunity. However, the role of lymphocyte-derived ...ACh in viral infection is unknown. Here, we show that the enzyme choline acetyltransferase (ChAT), which catalyzes the rate-limiting step of ACh production, is robustly induced in both CD4
and CD8
T cells during lymphocytic choriomeningitis virus (LCMV) infection in an IL-21-dependent manner. Deletion of
within the T cell compartment in mice ablated vasodilation in response to infection, impaired the migration of antiviral T cells into infected tissues, and ultimately compromised the control of chronic LCMV clone 13 infection. Our results reveal a genetic proof of function for ChAT in T cells during viral infection and identify a pathway of T cell migration that sustains antiviral immunity.
This is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of Zephyr Endobronchial Valve (EBV) in patients with little to no collateral ventilation out to 12 ...months.
To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation in the treated lobe.
Subjects were enrolled with a 2:1 randomization (EBV/standard of care SoC) at 24 sites. Primary outcome at 12 months was the ΔEBV-SoC of subjects with a post-bronchodilator FEV
improvement from baseline of greater than or equal to 15%. Secondary endpoints included absolute changes in post-bronchodilator FEV
, 6-minute-walk distance, and St. George's Respiratory Questionnaire scores.
A total of 190 subjects (128 EBV and 62 SoC) were randomized. At 12 months, 47.7% EBV and 16.8% SoC subjects had a ΔFEV
greater than or equal to 15% (P < 0.001). ΔEBV-SoC at 12 months was statistically and clinically significant: for FEV
, 0.106 L (P < 0.001); 6-minute-walk distance, +39.31 m (P = 0.002); and St. George's Respiratory Questionnaire, -7.05 points (P = 0.004). Significant ΔEBV-SoC were also observed in hyperinflation (residual volume, -522 ml; P < 0.001), modified Medical Research Council Dyspnea Scale (-0.8 points; P < 0.001), and the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index (-1.2 points). Pneumothorax was the most common serious adverse event in the treatment period (procedure to 45 d), in 34/128 (26.6%) of EBV subjects. Four deaths occurred in the EBV group during this phase, and one each in the EBV and SoC groups between 46 days and 12 months.
Zephyr EBV provides clinically meaningful benefits in lung function, exercise tolerance, dyspnea, and quality of life out to at least 12 months, with an acceptable safety profile in patients with little or no collateral ventilation in the target lobe. Clinical trial registered with www.clinicaltrials.gov (NCT 01796392).
The Deep Convective Clouds and Chemistry (DC3) field experiment produced an exceptional dataset on thunderstorms, including their dynamical, physical, and electrical structures and their impact on ...the chemical composition of the troposphere. The field experiment gathered detailed information on the chemical composition of the inflow and outflow regions of midlatitude thunderstorms in northeast Colorado, west Texas to central Oklahoma, and northern Alabama. A unique aspect of the DC3 strategy was to locate and sample the convective outflow a day after active convection in order to measure the chemical transformations within the upper-tropospheric convective plume. These data are being analyzed to investigate transport and dynamics of the storms, scavenging of soluble trace gases and aerosols, production of nitrogen oxides by lightning, relationships between lightning flash rates and storm parameters, chemistry in the upper troposphere that is affected by the convection, and related source characterization of the three sampling regions. DC3 also documented biomass-burning plumes and the interactions of these plumes with deep convection.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Obesity is associated with chronic inflammation, which may impact recovery from mild traumatic brain injury (mTBI). The objective was to assess the role of obesity in recovery of symptoms, functional ...outcome and inflammatory blood biomarkers after mTBI.
TRACK-TBI is a prospective study of patients with acute mTBI (Glasgow Coma Scale=13-15) who were enrolled ≤24 hours of injury at an emergency department of level 1 trauma centres and followed for 12 months. A total of 770 hospitalised patients who were either obese (body mass index (BMI) >30.0) or healthy mass (BMI=18.5-24.9) were enrolled. Blood concentrations of high-sensitivity C reactive protein (hsCRP), interleukin (IL) 6, IL-10, tumour necrosis factor alpha; Rivermead Post-Concussion Symptoms Questionnaire (RPQ), Quality of Life After Brain Injury and Glasgow Outcome Score-Extended reflecting injury-related functional limitations at 6 and 12 months were collected.
After adjusting for age and gender, obese participants had higher concentrations of hsCRP 1 day after injury (mean difference (MD)=0.65; 95% CI: 0.44 to 0.87, p<0.001), at 2 weeks (MD=0.99; 95% CI: 0.74 to 1.25, p<0.001) and at 6 months (MD=1.08; 95% CI: 0.79 to 1.37, p<0.001) compared with healthy mass participants. Obese participants had higher concentrations of IL-6 at 2 weeks (MD=0.37; 95% CI: 0.11 to 0.64, p=0.006) and 6 months (MD=0.42; 95% CI: 0.12 to 0.72, p=0.006). Obese participants had higher RPQ total score at 6 months (MD=2.79; p=0.02) and 12 months (MD=2.37; p=0.049).
Obesity is associated with higher symptomatology at 6 and 12 months and higher concentrations of blood inflammatory markers throughout recovery following mTBI.
Objective: We investigated how aging effects human chondrocyte yield, proliferation, post-expansion chondrogenic capacity, and response to specific growth factors supplemented during expansion.
...Methods: Fifty-two samples of human articular cartilage were harvested from cadavers 20 to 91 years old and grouped into age decades. Cell yields were normalised to tissue wet weight. Cell proliferation rates were calculated during expansion in medium without (CTR) or with TGFβ1, FGF-2 and PDGF-BB (TFP). Chondrogenic capacity of CTR- and TFP-expanded cells was assessed by cultivation as 3D pellets in a defined serum-free medium, followed by histological, immunohistochemical, biochemical and real-time RT-PCR analyses.
Results: Cell yields were similar in donors up to 40 years of age and significantly lower (1.8-fold) in older donors. Cell proliferation rates in CTR medium significantly decreased after 30 years of age and remained similar in older donors. In the presence of TFP, proliferation rates were higher (up to 3.7-fold) in all age groups and decreased only slightly with age. The glycosaminoglycan (GAG) content of pellets obtained from CTR-expanded cells was not correlated with age. Pellets from TFP-expanded cells reproducibly contained more GAG (up to 3.2-fold) than those from CTR-expanded cells only if donors were younger than 40. Safranin O staining intensity and collagen type II expression and accumulation were consistent with GAG contents.
Conclusion: Medium supplementation with the growth factor combination TFP during chondrocyte expansion supports higher proliferation rates at any age and higher post-expansion chondrogenic capacity in donors up to 40 years. These findings may be relevant for chondrocyte-based cartilage repair procedures.
Recently much research has focused on the development of new polymer dielectric materials to fabricate capacitors for use in the inverters of next generation hybrid electric vehicles (HEV). The ...capacitors used in HEVs inverters will be required to operate at 150°C, 600 V, and have an energy density of 0.9 J/cm 3 . Polymer based thin film capacitors are ideal for this application due to their relatively high energy density, low cost, and high dielectric breakdown strength. We have polymerized several ring strained monomers using ring opening metathesis polymerization (ROMP) and have identified a promising polymer system based on N-Phenyl-7-oxanorbornene-5,6-dicarboximide (PhONDI). Several of its copolymers with norbornene have been evaluated for possible use as next generation high temperature polymer dielectrics in thin film capacitors. The copolymers were cast into thin films and Au electrodes were deposited on the polymer film. The electrical properties were evaluated as a function of temperature. The polymer system exhibited very good high temperature dielectric properties and is potentially useful as a high temperature capacitor dielectric.
Accelerated development of coronary atherosclerosis is a defining characteristic of familial hypercholesterolemia (FH). However, the recent data highlight a significant cardiovascular risk prior to ...the development of critical coronary stenosis. We, therefore, examined the hypothesis that FH produces coronary microvascular dysfunction and impairs coronary vascular control at rest and during exercise in a swine model of FH. Coronary vascular responses to drug infusions and exercise were examined in chronically instrumented control and FH swine. FH swine exhibited ~tenfold elevation of plasma cholesterol and diffuse coronary atherosclerosis (20–60 % plaque burden). Similar to our recent findings in the systemic vasculature in FH swine, coronary smooth muscle nitric oxide sensitivity was increased in vivo and in vitro with maintained endothelium-dependent vasodilation in vivo in FH. At rest and during exercise, FH swine exhibited increased myocardial O
2
extraction resulting in reduced coronary venous SO
2
and PO
2
versus control. During exercise in FH swine, the transmural distribution of coronary blood flow was unchanged; however, a shift toward anaerobic cardiac metabolism was revealed by increased coronary arteriovenous H
+
concentration gradient. This shift was associated with a worsening of cardiac efficiency (relationship between cardiac work and O
2
consumption) in FH during exercise owing, in part, to a generalized reduction in stroke volume which was associated with increased left atrial pressure in FH. Our data highlight a critical role for coronary microvascular dysfunction as a contributor to impaired myocardial O
2
balance, cardiac ischemia, and impaired cardiac function prior to the development of critical coronary stenosis in FH.
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