Convective Heat Transfer Coefficients and Mechanical Loss Evaluation of Oil Splashing in Direct Cooled Electrically Excited Hairpin Motors

There in an increasing trend in the use of the direct oil cooling in electric motors for automotive because of the increasing demand of high power/torque density as well as overload capability. One of the most immediate solution is to fill the housing with some oil level and benefit of the heat transfer from the oil splashing. The mechanical losses coming from the rotor rotation are well known and they represent a significant challenge, especially at high speed and high oil level. Therefore, the derivation and prediction of these losses have not been properly investigated leading to a lack in the current literature. Moving Particles Simulation (MPS) method is used in Particleworks to calculate the mechanical losses caused by the oil viscosity and convective heat transfer coefficients (HTC) are extracted for a 250 kW Electrically Excited Synchronous Machine at different speeds and oil levels

DOF-binding sites additively contribute to guard cell-specificity of AtMYB60 promoter

<p>Abstract</p> <p>Background</p> <p>We previously demonstrated that the <it>Arabidopsis thaliana </it>AtMYB60 protein is an R2R3MYB transcription factor required for stomatal opening. <it>AtMYB60 </it>is specifically expressed in guard cells and down-regulated at the transcriptional levels by the phytohormone ABA.</p> <p>Results</p> <p>To investigate the molecular mechanisms governing <it>AtMYB60 </it>expression, its promoter was dissected through deletion and mutagenesis analyses. By studying different versions of <it>AtMYB60 </it>promoter::GUS reporter fusions in transgenic plants we were able to demonstrate a modular organization for the <it>AtMYB60 </it>promoter. Particularly we defined: a minimal promoter sufficient to confer guard cell-specific activity to the reporter gene; the distinct roles of different DOF-binding sites organised in a cluster in the minimal promoter in determining guard cell-specific expression; the promoter regions responsible for the enhancement of activity in guard cells; a promoter region responsible for the negative transcriptional regulation by ABA. Moreover from the analysis of single and multiple mutants we could rule out the involvement of a group of DOF proteins, known as CDFs, already characterised for their involvement in flowering time, in the regulation of <it>AtMYB60 </it>expression.</p> <p>Conclusions</p> <p>These findings shed light on the regulation of gene expression in guard cells and provide new promoter modules as useful tools for manipulating gene expression in guard cells, both for physiological studies and future biotechnological applications.</p

The grapevine guard cell-related VvMYB60 transcription factor is involved in the regulation of stomatal activity and is differentially expressed in response to ABA and osmotic stress

- Background: Under drought, plants accumulate the signaling hormone abscisic acid (ABA), which induces the rapid closure of stomatal pores to prevent water loss. This event is trigged by a series of signals produced inside guard cells which finally reduce their turgor. Many of these events are tightly regulated at the transcriptional level, including the control exerted by MYB proteins. In a previous study, while identifying the grapevine R2R3 MYB family, two closely related genes, VvMYB30 and VvMYB60 were found with high similarity to AtMYB60, an Arabidopsis guard cell-related drought responsive gene. - Results: Promoter-GUS transcriptional fusion assays showed that expression of VvMYB60 was restricted to stomatal guard cells and was attenuated in response to ABA. Unlike VvMYB30, VvMYB60 was able to complement the loss-of-function atmyb60-1 mutant, indicating that VvMYB60 is the only true ortholog of AtMYB60 in the grape genome. In addition, VvMYB60 was differentially regulated during development of grape organs and in response to ABA and drought-related stress conditions. - Conclusions: These results show that VvMYB60 modulates physiological responses in guard cells, leading to the possibility of engineering stomatal conductance in grapevine, reducing water loss and helping this species to tolerate drought under extreme climatic conditions

Expression of Caveolin-1 Is Required for the Transport of Caveolin-2 to the Plasma Membrane RETENTION OF CAVEOLIN-2 AT THE LEVEL OF THE GOLGI COMPLEX

Caveolins-1 and -2 are normally co-expressed, and they form a hetero-oligomeric complex in many cell types. These caveolin hetero-oligomers are thought to represent the assembly units that drive caveolae formation in vivo. However, the functional significance of the interaction between caveolins-1 and -2 remains unknown. Here, we show that caveolin-1 co-expression is required for the transport of caveolin-2 from the Golgi complex to the plasma membrane. We identified a human erythroleukemic cell line, K562, that expresses caveolin-2 but fails to express detectable levels of caveolin-1. This allowed us to stringently assess the effects of recombinant caveolin-1 expression on the behavior of endogenous caveolin-2. We show that expression of caveolin-1 in K562 cells is sufficient to reconstitute the de novo formation of caveolae in these cells. In addition, recombinant expression of caveolin-1 allows caveolin-2 to form high molecular mass oligomers that are targeted to caveolae-enriched membrane fractions. In striking contrast, in the absence of caveolin-1 expression, caveolin-2 forms low molecular mass oligomers that are retained at the level of the Golgi complex. Interestingly, we also show that expression of caveolin-1 in K562 cells dramatically up-regulates the expression of endogenous caveolin-2. Northern blot analysis reveals that caveolin-2 mRNA levels remain constant under these conditions, suggesting that the expression of caveolin-1 stabilizes the caveolin-2 protein. Conversely, transient expression of caveolin-2 in CHO cells is sufficient to up-regulate endogenous caveolin-1 expression. Thus, the formation of a hetero-oligomeric complex between caveolins-1 and -2 stabilizes the caveolin-2 protein product and allows caveolin-2 to be transported from the Golgi complex to the plasma membrane

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

WARP: a double phase Argon programme for Dark Matter detection

WARP (Wimp ARgon Programme) is a double phase Argon detector for Dark Matter detection under construction at Laboratori Nazionali del Gran Sasso. We present recent results obtained operating deep underground a prototype detector with sensitive mass 2.3 litres. 1. WARP: a double phase argon detector for Dark Matter detection. A double phase Argon detector offers unique sensitivity for the search of dark matter in the form of WIMPs: such detector has the highest discrimination of background events in favour of potential WIMP interactions, which are expected to produce low energy Ar recoils with typical energies of a few tens keV. The basic concept of the detector is the measurement of both the scintillation and the ionization produced by particle interactions inside a liquid argon sensitive volume. Two simultaneous criteria can be applied to select Ar recoils eventually produced by WIMPs: i) Prompt scintillation versus ionization. The prompt scintillation light produced by a particle interacting in the liquid argon phase is detected by PMs. The ionization electrons are extracted from the liquid into the gas and accelerated by an appropriate electric field to produce a proportional (high gain), secondary light pulse seen by the same PMs. The pulse ratio S2/S1 of secondary light S2 (from drift time-delayed ionization) over prompt scintillation light S1 is strongly dependent from columnar recombination of the ionising tracks: therefore nuclear recoils produce typical signals with pulse ratio S2/S1 about 60 times lower than electrons. ii) Pulse shape discrimination of primary scintillation: the primary light is emitted with two components with very large difference in decay times (fast 7 ns, and slow 1.8 μs). The relative amount of the slow component strongly depends from the interacting particle, being around 0.7 for electrons and. 0.1 for heavy charged paricles. The WARP liquid argon detector under construction has a sensitive volume of 100 liters. The goal scintillation yield is of the order of 1 collected photoelectron per keV and the detection threshold for the WIMPs 30 keV. A detailed description of the 100 liters detector can be find in reference [1]. 1 INFN and Dept. of Physics University of Pavia: P. Benetti, E. Calligarich, M. Cambiaghi, C. De Vecchi, R. Dolfini, L. Grandi, A. Menegolli, C. Montanari, M. Prata, A. Rappoldi, G.L. Raselli, M. Roncadelli, M. Rossella, C. Rubbia (Spokesperson), C. Vignoli. INFN and Dept. of Physics University of Napoli "Federico II": F. Carbonara, A.G. Cocco, G. Fiorillo, G. Mangano, R. Santorelli. INFN Laboratori Nazionali del Gran Sasso and University of L'Aquila: F. Cavanna, N. Ferrari, O. Palamara,. L. Pandola. Princeton University, Physics Department: F. Calaprice, C. Galbiati, Y. Zhao. Institute of Nuclear Physics, Krakow : A. Szelc. Figure 1. Energy spectrum observed with the WARP 2.3 liters prototype in the LNGS underground laboratory inside a 10 cm thick Pb shielding. The overlapped red histogram is the expected (montecarlo-simulated) background by interactions of environmental gamma rays. The residual events below 650 keV are produced by Ar and Kr contaminations inside the liquid Argon. Figure 2. Residual energy spectrum after subtraction of the estimated background from environmental gamma rays. The residual spectrum (upper blue curve) is perfectly fitted by the sum of the beta spectra of Ar (green curve, end-point 565 keV, rate 1.1 Bq/litre) and Kr (red curve, end-point 687 keV, rate 0.5 Bq/litre). The vertical scale is expressed in counts/sec/keV. 2. The WARP 2.3 liters prototype detector In order to perfect the detection method, a 2.3 liters prototype detector is in operation at Laboratori Nazionali del Gran Sasso since February 2005. The detector has been equipped, in subsequent phases, with 2'' and 3'' PMs made of low background materials for an onsite detailed study of the backgrounds. The structure is a down-scaled version of the 100 liters detector, with field-shaping electrodes and gas to liquid extraction and acceleration grids. The chamber is filled with ultra-purified argon in order to allow for long drift times of free electrons. Purity is maintained stable by means of continuous argon recirculation. 2.1.1. Study of the β and γ detector backgrounds. The overall background of the 2.3 litres prototype installed underground inside a 10 cm thick Pb shielding has been carefully measured and identified. The total trigger rate above a threshold of 30 keV is about 5 Hz. From a detailed study of the energy spectrum shape (Figure 1) it is shown that about 2 Hz are produced by gamma ray interactions from radioactivity of materials surrounding the sensitive volume; the remaining 3 Hz are produced by the β decays of Kr and Ar dissolved in the liquid argon. In particular, the specific activity of Ar was found to be 1.1 ± 0.4 Bq/litre of liquid Argon, in very good agreement with ref. [2]. We notice that no particular care in the selection of materials was adopted, since in this test phase the background itself helps in the identification of the rejection power. Most of the backgrounds will be strongly reduced in the 100 litres setup. Figure 3. R-like events recorded with the 2.3 liters chamber during 13.4 days of live time in june 2005. The plot shows the primary signal energy (in keV) along the drift time, expressed in μs. The fiducial volume is defined by drift times between 10 and 35 microseconds. Figure 4. Energy distribution of R-like events inside the cathode (upper plot), and inside the fiducial volume (lower plot). The red histogram in the lower plot is the result of a simulation of the expected signal from environmental neutrons in the underground area. 2.1.2. Analysis of Recoil-like events. Data recorded during 13.4 days of live time in a run done in june 2005 have been analyzed looking for recoil-like events by applying the two selection criteria described in section 1. About 6.5 millions events have been processed. The spatial and energy distribution of the 580 selected R-like events (see Figure 3) suggests the following origin for the signals: i) R-like events in the cathode region are mostly induced by decays of Rn daughters. Rn is introduced in the chamber during the filling together with the Ar: being electrically neutral it is uniformly distributed inside the chamber. Daughter nuclei, produced into an ionized state, are drifted to the cathode by the electric field, where they stick. Subsequent decays may end up: (a) with the heavy ion entering the cathode and the α or β travelling in the LAr; (b) with the heavy ion travelling in the LAr and producing the observed R-like signal. The two peaks observed in the energy spectrum (Figure 4, upper plot) are coherently explained by the nuclear recoils from α decays Po Pb (ER=110 keV) and Po Bi (ER=144 keV), assuming a light yield of 0.7 photoelectrons/keV. ii) R-like events inside the fiducial volume are induced by environmental neutrons. Both the event rate and the shape of the energy spectrum (Figure 4, lower plot) are compatible with the expected interactions induced by environmental neutrons inside the underground area (represented by the red histogram). The WARP 2.3 liters chamber in operation at LNGS proofs that the double discrimination technique is effective for separation of recoil events. The first results of the 2.3 liters test (with no neutron shielding) show that the observed background is understood, and that recoil-like signals are compatible with the expected neutron background in the underground area. References [1] WARP proposal, available online at http://warp.pv.infn.it/proposal.pdf [2] H.H. Loosli and H. Oeschger, Earth and Plan. Sci. Lett. 7 (1969) 6

Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study

Background Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by elevated plasma levels of LDL-cholesterol that confers an increased risk of premature atherosclerotic cardiovascular disease. Early identification and treatment of FH patients can improve prognosis and reduce the burden of cardiovascular mortality. Aim of this study was to perform the mutational analysis of FH patients identified through a collaboration of 20 Lipid Clinics in Italy (LIPIGEN Study). Methods We recruited 1592 individuals with a clinical diagnosis of definite or probable FH according to the Dutch Lipid Clinic Network criteria. We performed a parallel sequencing of the major candidate genes for monogenic hypercholesterolemia (LDLR, APOB, PCSK9, APOE, LDLRAP1, STAP1). Results A total of 213 variants were detected in 1076 subjects. About 90% of them had a pathogenic or likely pathogenic variants. More than 94% of patients carried pathogenic variants in LDLR gene, 27 of which were novel. Pathogenic variants in APOB and PCSK9 were exceedingly rare. We found 4 true homozygotes and 5 putative compound heterozygotes for pathogenic variants in LDLR gene, as well as 5 double heterozygotes for LDLR/APOB pathogenic variants. Two patients were homozygous for pathogenic variants in LDLRAP1 gene resulting in autosomal recessive hypercholesterolemia. One patient was found to be heterozygous for the ApoE variant p.(Leu167del), known to confer an FH phenotype. Conclusions This study shows the molecular characteristics of the FH patients identified in Italy over the last two years. Full phenotypic characterization of these patients and cascade screening of family members is now in progress

Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO2/FiO2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk

MtDNA-maintenance defects: syndromes and genes

A large group of mitochondrial disorders, ranging from early-onset pediatric encephalopathic syndromes to late-onset myopathy with chronic progressive external ophthalmoplegia (CPEOs), are inherited as Mendelian disorders characterized by disturbed mitochondrial DNA (mtDNA) maintenance. These errors of nuclear-mitochondrial intergenomic signaling may lead to mtDNA depletion, accumulation of mtDNA multiple deletions, or both, in critical tissues. The genes involved encode proteins belonging to at least three pathways: mtDNA replication and maintenance, nucleotide supply and balance, and mitochondrial dynamics and quality control. In most cases, allelic mutations in these genes may lead to profoundly different phenotypes associated with either mtDNA depletion or multiple deletions. Communicated by: Shamima Rahman Presented at the Annual Symposium of the Society for the Study of Inborn Errors of Metabolism, Rome, Italy, September 6–9, 2016This work was supported by: ERC FP7-322424 grant (to MZ), CoEN grant 3038 (to MZ and CV) and the MRC core grant to the Mitochondrial Biology Unit

Familial hypercholesterolemia: The Italian Atherosclerosis Society Network (LIPIGEN)

BACKGROUND AND AIMS: Primary dyslipidemias are a heterogeneous group of disorders characterized by abnormal levels of circulating lipoproteins. Among them, familial hypercholesterolemia is the most common lipid disorder that predisposes for premature cardiovascular disease. We set up an Italian nationwide network aimed at facilitating the clinical and genetic diagnosis of genetic dyslipidemias named LIPIGEN (LIpid TransPort Disorders Italian GEnetic Network). METHODS: Observational, multicenter, retrospective and prospective study involving about 40 Italian clinical centers. Genetic testing of the appropriate candidate genes at one of six molecular diagnostic laboratories serving as nationwide DNA diagnostic centers. RESULTS AND CONCLUSIONS: From 2012 to October 2016, available biochemical and clinical information of 3480 subjects with familial hypercholesterolemia identified according to the Dutch Lipid Clinic Network (DLCN) score were included in the database and genetic analysis was performed in 97.8% of subjects, with a mutation detection rate of 92.0% in patients with DLCN score 656. The establishment of the LIPIGEN network will have important effects on clinical management and it will improve the overall identification and treatment of primary dyslipidemias in Italy