The role of the sea-surface temperature distribution on numerically simulated cyclogenesis during ERICA

The goal was to quantify the extent to which a sea surface temperature (SST) front can influence cyclogenesis. The approach was to use the Drexel Limited-Area Mesoscale Prediction System (LAMPS) dynamical model to simulate cyclogenesis over various SST fields. Research during the past year focused on the development and testing of a four dimensional data assimilation (FDDA) technique within LAMPS. The technique is a continuous dynamical assimilation where forcing terms are added to the governing model equations to gradually nudge the model solution toward a gridded analysis. Here, the nudging is used as a dynamic initialization tool during a 12 hour preforecast to generate model balanced initial conditions for a subsequent 24 hour numerical prediction. Tests were performed to determine which variables to nudge and how to specify the four dimensional weighting function used to scale the nudging terms. To date, optimal results were obtained by nudging the u and v components of the wind along with the potential temperature. The weighting function ranged from 0 to 1 and varies in time as a quadratic polynomial. It was initialized at 0, reached its maximum at 9 hours into the preforecast, and fell back at 0 to 12 hours. The nudging terms are included in the model equations for all grid points except those within the model predicted oceanic boundary layer. This design attempts to confine changes imposed by the specified SST field to the oceanic boundary layer during the preforecast period

Linked CSF reduction of phosphorylated tau and IL-8 in HIV associated neurocognitive disorder.

HIV-associated neurocognitive disorder (HAND) is a common condition in both developed and developing nations, but its cause is largely unknown. Previous research has inconsistently linked Alzheimer's disease (AD), viral burden, and inflammation to the onset of HAND in HIV-infected individuals. Here we simultaneously measured cerebrospinal fluid (CSF) levels of established amyloid and tau biomarkers for AD, viral copy numbers, and six key cytokines in 41 HIV-infected individuals off combination anti-retroviral therapy (14 with HAND) who underwent detailed clinical and neuropsychological characterization, and compared their CSF patterns with those from young healthy subjects, older healthy subjects with normal cognition, and older people with AD. HAND was associated with the lowest CSF levels of phosphorylated tau (p-Tau181) after accounting for age and race. We also found very high CSF levels of the pro-inflammatory interferon gamma-induced protein 10 (IP-10/CXCL10) in HIV regardless of cognition, but elevated CSF interleukin 8 (IL-8/CXCL8) only in HIV-NC but not HAND. Eleven HIV-infected subjects underwent repeat CSF collection six months later and showed strongly correlated longitudinal changes in p-Tau181 and IL-8 levels (R = 0.841). These data suggest reduced IL-8 relative to IP-10 and reduced p-Tau181 to characterize HAND

Vorticity and Vertical Motions Diagnosed from Satellite Deep-Layer Temperatures

Spatial fields of satellite-measured deep-layer temperatures are examined in the context of quasigeostrophic theory. It is found that midtropospheric geostrophic vorticity and quasigeostrophic vertical motions can be diagnosed from microwave temperature measurements of only two deep layers. The lower- ( 1000-400 hPa) and upper- (400-50 hPa) layer temperatures are estimated from limb-corrected TIROS-N Microwave Sounding Units (MSU) channel 2 and 3 data, spatial fields of which can be used to estimate the midtropospheric thermal wind and geostrophic vorticity fields. Together with Trenberth's simplification of the quasigeostrophic omega equation, these two quantities can be then used to estimate the geostrophic vorticity advection by the thermal wind, which is related to the quasigeostrophic vertical velocity in the midtroposphere. Critical to the technique is the observation that geostrophic vorticity fields calculated from the channel 3 temperature features are very similar to those calculated from traditional, 'bottom-up' integrated height fields from radiosonde data. This suggests a lack of cyclone-scale height features near the top of the channel 3 weighting function, making the channel 3 cyclone-scale 'thickness' features approximately the same as height features near the bottom of the weighting function. Thus, the MSU data provide observational validation of the LID (level of insignificant dynamics) assumption of Hirshberg and Fritsch

Increased tolerance of Anopheles gambiae s.s. to chemical insecticides after exposure to agrochemical mixture

Resistance of mosquitoes to insecticides is mainly attributed to their adaptation to insecticide-based vector control interventions. Although pesticides used in agriculture have been frequently mentioned as an additional force driving the selection of resistance, only a few studies were dedicated to validate this hypothesis. The objective of this study was to investigate the effect of exposure of the malaria mosquito, Anopheles gambiae s.s. larvae for 72h to sub-lethal concentrations of the agrochemical mixture (pesticides, herbicides and fungicides). Their subsequent tolerances were measured to deltamethrin (pyrethroid), DDT (organochlorine) and bendiocarb (carbamate) currently used for vector control. The mean LC50 was determined and tolerance ratios for larvae exposed to agrochemical comparatively with unexposed larvae were calculated and expressed as fold increased tolerance. Bioassays revealed a significant increase in larval tolerance to detamethrin (1.83-2.86 fold), DDT (1.31-1.53 fold) and bendiocarb (1.14-1.19 fold) following exposure to 0.1 µM and 1µM agrochemical mixture. The observed increased tolerance in this study is likely to be based on metabolic resistance mechanisms. Overall, this study reveals the potential of agrochemicals to increase the tolerance of mosquito larvae to chemical insecticides

Unlocking biomarker discovery: Large scale application of aptamer proteomic technology for early detection of lung cancer

Lung cancer is the leading cause of cancer deaths, because ~84% of cases are diagnosed at an advanced stage. Worldwide in 2008, ~1.5 million people were diagnosed and ~1.3 million died – a survival rate unchanged since 1960. However, patients diagnosed at an early stage and have surgery experience an 86% overall 5-year survival. New diagnostics are therefore needed to identify lung cancer at this stage. Here we present the first large scale clinical use of aptamers to discover blood protein biomarkers in disease with our breakthrough proteomic technology. This multi-center case-control study was conducted in archived samples from 1,326 subjects from four independent studies of non-small cell lung cancer (NSCLC) in long-term tobacco-exposed populations. We measured >800 proteins in 15uL of serum, identified 44 candidate biomarkers, and developed a 12-protein panel that distinguished NSCLC from controls with 91% sensitivity and 84% specificity in a training set and 89% sensitivity and 83% specificity in a blinded, independent verification set. Performance was similar for early and late stage NSCLC. This is a significant advance in proteomics in an area of high clinical need

Involvement of Purinergic P2X4 Receptors in Alcohol Intake of High-Alcohol-Drinking (HAD) Rats

Background: The P2X4 receptor is thought to be involved in regulating alcohol-consuming behaviors and ethanol (EtOH) has been reported to inhibit P2X4 receptors. Ivermectin is an anti-parasitic agent that acts as a positive allosteric modulator of the P2X4 receptor. The current study examined the effects of systemically- and centrally-administered ivermectin on alcohol drinking of replicate lines of high-alcohol-drinking (HAD-1/HAD-2) rats, and the effects of lentiviral-delivered short-hairpin RNAs (shRNAs) targeting P2rx4 on EtOH intake of female HAD2 rats. Method: For the 1st experiment, adult male HAD-1 & HAD-2 rats were given 24-hr free-choice access to 15% EtOH vs. water. Dose-response effects of ivermectin (1.5 to 7.5 mg/kg i.p.) on EtOH intake were determined; the effects of ivermectin were then examined for 2% w/v sucrose intake over 5 consecutive days. In the 2nd experiment, female HAD-2 rats were trained to consume 15% EtOH under 2-hr limited access conditions, and dose-response effects of intracerebroventricular (ICV) administration of ivermectin (0.5 to 2.0 μg) were determined over 5 consecutive days. The 3rd experiment determined the effects of microinfusion of a lentivirus expressing P2rx4 shRNAs into the posterior ventral tegmental area (VTA) on 24-hr EtOH free-choice drinking of female HAD-2 rats. Results: The highest i.p. dose of ivermectin reduced alcohol drinking (30-45%) in both rat lines, but did not alter sucrose intake. HAD-2 rats appeared to be more sensitive than HAD1 rats to the effects of ivermectin. ICV administration of ivermectin reduced 2-hr limited access intake (∼35%) of femal

Candida myocarditis without valvulitis

Thirty-one patients with systemic candidiasis at postmortem examination were found to have Candida involvement of the myocardium without valvulitis. Retrospective examination of their clinical course demonstrated that a new conduction disturbance was seen in 10, supraventricular arrhythmias in 5, QRS changes mimicking myocardial infarction in 3, and pronounced T wave changes in 13. Hypotension or shock was seen in 13 patients and could not be explained by coexistent bacteremia or blood loss in 8. One patient died suddenly. Of 19 patients with systemic candidiasis without myocardial invasion, 4 had minor T wave changes and one had a supraventricular arrhythmia. Candida invasion of the heart significantly complicates the clinical course in systemic candidiasis and should be suspected when a young person without preexistent heart disease has cultures positive for a Candida organism, a significant arrhythmia, conduction disturbance or other dramatic QRS change. The effect of therapy on Candida invasion of the heart is unknown.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/21634/1/0000015.pd