Using Feedback to Control Deadtime in the CDF Trigger System

The CDF experiment uses a three-level trigger system to select events produced during p{bar p} collisions. As the luminosity of the Tevatron accelerator falls by a factor of four over a 24 hour period, trigger selections are adjusted automatically in order to make full use of the data processing bandwidth. The selections are made to maximize high purity triggers and keep the deadtime as low as possible at any given luminosity throughout the entire course of a run. We describe the algorithms used to obtain these goals and how the changing conditions are accounted for in the analysis of the data

Indicators of biodiversity in an intensively cultivated and heavily human modified landscape

Nowadays, the loss of biodiversity in agroecosystems due to the intensification of farming practices is happening very fast, and therefore, stopping or slowing it down should be a priority for conservation. To detect changes in these environmental contexts, one approach contemplates focusing on a limited set of indicator species that can alert us to ongoing changes in progress. In this research, we aimed to measure the biodiversity of vertebrates using a multi-taxa approach in an intensively cultivated and highly inhabited area located in northern Italy. We investigated the relationships between biodiversity and environmental characteristics and we identified the taxonomic groups that can be used as indicators of biodiversity. Data collection was carried out in 2016 with different methods depending on the taxonomic group, in 131 sampling units chosen using a Tessellation Stratified Sampling. Then we calculated for each sampling unit a standardized Biodiversity Index, which was related to environmental variables concerning the land use and the landscape configuration using Multiple Linear Regression Analysis and Information-Theoretic approach. We used correlation analyses and the Indicator Species Analysis (IndVal) to identify the taxonomic groups and species that can be used as indicators of biodiversity. Biodiversity was positively related to the number of patches of natural vegetation, whereas it was negatively affected by the number of patches of artificial surfaces and by habitat diversity. Our findings agree with those obtained by many other researchers, which pointed out that agroecosystems provide adequate shelters, suitable foraging habitats and nesting sites. The negative effect of habitat diversity was explained by the area-heterogeneity trade-off. Therefore, sites with high heterogeneity will not contain enough cover of residual natural vegetation, essential to maintain high biodiversity, because increasing compositional heterogeneity within a fixed area simultaneously reduces the surface of each cover type. The analyses showed that birds and reptiles might be used as biodiversity indicators of vertebrates. Eurasian Magpie and Green Whip Snake, both generalist species, were associated with sites of low biodiversity, whereas seven birds, both generalists and farmland specialists, were associated with sites of medium biodiversity. In high biodiversity sites there were not indicator species. To conclude, in less natural environments, such as urban and agricultural landscapes, a combination of specialist and generalist indicator species seems adequate to monitor biodiversity changes. Our findings increase the knowledge of these very dynamic ecosystems, being important both to plan strategies for biodiversity conservation and to guarantee ecosystems services useful for humans

Involvement of vascular endothelial growth factor in schizophrenia

Vascular endothelial growth factor (VEGF), which acts as an angiogenic and neurotrophic factor, is involved the regulation of cerebral blood volume and flow in Schizophrenia (SCZ). Several evidence indicates that modification of brain blood circulation due to alterations in the VEGF system affects cognitive performance and brain function in patients with SCZ. The aim of this study is: 1) To analyze the literature data concerning the role of VEGF in modulating the angiogenic response in SCZ. These data are controversial because some studies found elevated VEGF serum levels of VEGF in patients with SCZ, whereas others demonstrated no significant differences between SCZ patients and controls. 2)To analyze the role of VEGF as a predictive factor on the effects of antipsychotics agents used in the treatment of SCZ. In this context, high VEGF levels, associated to better responses to antipsychotics, might be predictive of the use of first generation antipsycotic drugs, whereas low VEGF levels, expression of resistance to therapy, might be predictive for the use of second generation antipsycotic drugs

Exacerbations and Pseudomonas aeruginosa colonization are associated with altered lung structure and function in primary ciliary dyskinesia

Background: Recurrent bacterial infections of the respiratory tract are one of the major clinical features of the primary ciliary dyskinesia (PCD), a rare genetic disease due to malfunctioning of motile cilia. Chronic infections and persistent inflammation of the respiratory system result in progressive lung disease. Aim of the study was to highlight the main factors associated with clinical, functional and anatomical deterioration in PCD patients. Methods: We retrospectively analyzed data from 58 patients with PCD, 37 adults and 21 children. The demographic and clinical data, forced expiratory volume at 1 s (FEV1) and forced vital capacity (FVC), sputum microbiology and imaging results (chest CT scores-modified Bhalla) were recorded. Patients were stratified according to the number of exacerbations (< 2/year vs 65 2/year) and chronic Pseudomonas aeruginosa (PA) colonization. The possible correlations between lung function and chest CT scores were assessed; we also evaluated the correlation between these parameters and the severity scores for bronchiectasis (BSI, FACED and e-FACED). Results: Chest CT scores showed a significant correlation with FEV1 (p = 0.0002), age (p < 0.0001), BMI (p = 0.0002) and number of lung lobes involved (p < 0.0001). PA colonization had an overall prevalence of 32.6%: no significant difference in FEV1 between PA colonized and non-colonized patients was found (p = 0.70), while chest CT score was significantly worse in chronic PA colonized patients (p = 0.009). Patients with a high number of exacerbation ( 65 2/year) were older (p = 0.01), had lower FEV1 (p = 0.03), greater number of lobes involved (p < 0.001) and worse CT score than patients with low number of exacerbations (p = 0.001); they also had higher prevalence of PA chronic bronchial infection (33.3% versus 13.6%, p = 0.10). Multivariable linear regression analyses adjusted for gender, age and BMI showed positive associations between PA colonization and number of exacerbations with severity of disease (number of lobes involved, CT score, BSI, FACED, and e-FACED). Conclusions: In our PCD population the number of exacerbations ( 65 2/year) and PA colonization were the two most relevant factors associated with severity of disease

Transoral robotic surgery in the management of head and neck tumours.

The article reviews the use of robotic technology for head and neck tumours. The authors discuss the development of transoral robotic surgery (TORS), the current status of the technology, and the set-up in the operating room. The article provides a review of the literature, highlighting the applications, advantages, functional outcomes, and disadvantages of TORS for each anatomic subsite (oropharynx, hypopharynx, larynx, parapharyngeal space, and skull base). New challenges related to reconstruction are also presented. Overall early functional and oncologic outcome data are promising; further long-term prospective trials are still needed to confirm the oncological safety of TORS. Copyright

Endoplasmic Reticulum Associated Aminopeptidase 2 (ERAP2) is released in the secretome of activated MDMs and reduces in vitro HIV-1 infection

Background: Haplotype-specific alternative splicing of the endoplasmic reticulum (ER) aminopeptidase type 2 (ERAP2) gene results in either full-length (FL, haplotype A) or alternatively spliced (AS, haplotype B) mRNA. HapA/HapA homozygous (HomoA) subjects show a reduced susceptibility to HIV-1 infection, probably secondary to the modulation of the antigen processing/presenting machinery. ERAP1 was recently shown to be secreted from the plasma membrane in response to activation; we investigated whether ERAP2 can be released as well and if the secreted form of this enzyme retains its antiviral function. Methods: Human monocyte derived macrophages (MDMs) were differentiated from peripheral blood mononuclear cells (PBMCs) isolated from 6 HomoA healthy controls and stimulated with IFN\u3b3 and LPS. ERAP2-FL secretion was evaluated by mass spectrometry. PBMCs (14 HomoA and 16 HomoB) and CD8-depleted PBMCs (CD8-PBMCs) (4 HomoA and 4 HomoB) were in vitro HIV-infected in the absence/presence of recombinant human ERAP2-FL (rhERAP2) protein; p24 viral antigen quantification was used to assess viral replication. IFN\u3b3 and CD69 mRNA expression, as well as the percentage of perforin-producing CD8+ T Lymphocytes, were analyzed 3 and 7-days post in vitro HIV-1-infection, respectively. The effect of rhERAP2 addition in cell cultures on T cell apoptosis, proliferation, activation, and maturation was evaluated as well on 24 h-stimulated PBMCs. Results: ERAP2 can be secreted from human MDMs in response to IFN\u3b3/LPS stimulation. Notably, the addition of rhERAP2 to PBMC and CD8-PBMC cultures resulted in the reduction of viral replication, though these differences were statistically significant only in PBMCs (p < 0.05 in both HomoA and HomoB). This protective effect was associated with an increase in IFN\u3b3 and CD69 mRNA expression and in the percentage of perforin-expressing CD107+CD8+ cells. RhERAP2 addition also resulted in an increase in CD8+ activated lymphocyte (CD25+HLA-DRII+) and Effector Memory/Terminally differentiated CD8+ T cells ratio. Conclusions: This is the first report providing evidence for the release of ERAP2 in the secretome of immunocompetent cells. Data herein also indicate that exogenous ERAP2-FL exerts its protective function against HIV-1 infection, even in HomoB subjects who do not genetically produce it. Presumably, this defensive extracellular feature is only partially dependent on immune system modulation

Sphingolipid serum profiling in vitamin D deficient and dyslipidemic obese dimorphic adults

Recent studies on Saudi Arabians indicate a prevalence of dyslipidemia and vitamin D deficiency (25(OH)D) in both normal weight and obese subjects. In the present study the sphingolipid pattern was investigated in 23 normolipidemic normal weight (NW), 46 vitamin D deficient dyslipidemic normal weight (-vitDNW) and 60 vitamin D deficient dyslipidemic obese (-vitDO) men and women by HPTLC-primuline profiling and LC-MS analyses. Results indicate higher levels of total ceramide (Cer) and dihydroceramide (dhCers C18\u201322) and lower levels of total sphingomyelins (SMs) and dihydrosphingomyelin (dhSM) not only in -vitDO subjects compared to NW, but also in \u2013vitDNW individuals. A dependency on body mass index (BMI) was observed analyzing specific Cer acyl chains levels. Lower levels of C20 and 24 were observed in men and C24.2 in women, respectively. Furthermore, LC-MS analyses display dimorphic changes in NW, -vitDNW and \u2013vitDO subjects. In conclusion, LC-MS data identify the independency of the axis high Cers, dhCers and SMs from obesity per se. Furthermore, it indicates that long chains Cers levels are specific target of weight gain and that circulating Cer and SM levels are linked to sexual dimorphism status and can contribute to predict obese related co-morbidities in men and women

Insight into GEBR-32a: Chiral Resolution, Absolute Configuration and Enantiopreference in PDE4D Inhibition

Alzheimer's disease is the most common type of dementia, affecting millions of people worldwide. One of its main consequences is memory loss, which is related to downstream effectors of cyclic adenosine monophosphate (cAMP). A well-established strategy to avoid cAMP degradation is the inhibition of phosphodiesterase (PDE). In recent years, GEBR-32a has been shown to possess selective inhibitory properties against PDE type 4 family members, resulting in an improvement in spatial memory processes without the typical side effects that are usually correlated with this mechanism of action. In this work, we performed the HPLC chiral resolution and absolute configuration assignment of GEBR-32a. We developed an efficient analytical and semipreparative chromatographic method exploiting an amylose-based stationary phase, we studied the chiroptical properties of both enantiomers and we assigned their absolute configuration by 1H-NMR (nuclear magnetic resonance). Lastly, we measured the IC50 values of both enantiomers against both the PDE4D catalytic domain and the long PDE4D3 isoform. Results strongly support the notion that GEBR-32a inhibits the PDE4D enzyme by interacting with both the catalytic pocket and the regulatory domains

Protein signature in cerebrospinal fluid and serum of Alzheimer’s disease patients : the case of apolipoprotein A-1 proteoforms

In the diagnosis of Alzheimer\u2019s disease (AD) total tau (T-tau), tau phosphorylated at threonine 181 (P-tau181), and the 42 amino acid isoform of alpha \u3b2-amyloid (A\u3b2) are well established surrogate CSF markers. However, there is a constant need for new diagnostic markers to identify the disease at a very early stage. The identification of new molecules for AD diagnosis and monitoring in CSF is hampered by several \u201cconfounding\u201d factors including intra- and inter-individual, pre-analytical and analytical variabilities. In an attempt to partially overcome patient\u2019s variability and to determine new molecules significantly dysregulated in CSF, we assessed the proteome profile of low molecular weight protein species in CSF and serum of the same patients. CSFs and sera from 36 ADs, 32 iNPHs (idiopathic normal pressure hydrocephalus) and 12 controls were compared by MALDI profiling (non-parametric statistics, CV0.750). After protein identification by mass spectrometry, the proteoform composition was assessed by 2-D DIGE/MS. Results indicated that CSF of iNPH can be used as control. Serum and CSF of AD patients shows a specific protein profile compared to iNPH samples. A variation (p<0.01) of Apo A-1 levels in AD, together with a specific dysregulation of Apo A-1 proteoforms was observed. The profiling of CSF and serum of the same patients, suggests that the decrement of total Apo A-1 occurs specifically in CSF. Serum and CSF of AD shows a characteristic Apo A-1 proteoform pattern suggesting it as potential marker which can support the clinical workflow adopted for AD diagnosis and progression