Dynamic compact thermal models with multiple power sources: application to an ultrathin chip stacking technology

Whereas numerical modeling using finite-element methods (FEM) can provide transient temperature distribution in the component with enough accuracy, it is of the most importance the development of compact dynamic thermal models that can be used for electrothermal simulation. While in most cases single power sources are considered, here we focus on the simultaneous presence of multiple sources. The thermal model will be in the form of a thermal impedance matrix containing the thermal impedance transfer functions between two arbitrary ports. Eachindividual transfer function element ( ) is obtained from the analysis of the thermal temperature transient at node ¿ ¿ after a power step at node ¿ .¿ Different options for multiexponential transient analysis are detailed and compared. Among the options explored, small thermal models can be obtained by constrained nonlinear least squares (NLSQ) methods if the order is selected properly using validation signals. The methods are applied to the extraction of dynamic compact thermal models for a new ultrathin chip stack technology (UTCS).

Mammalian target of rapamycin complex 1 orchestrates invariant NKT cell differentiation and effector function.

Invariant NKT (iNKT) cells play critical roles in bridging innate and adaptive immunity. The Raptor containing mTOR complex 1 (mTORC1) has been well documented to control peripheral CD4 or CD8 T cell effector or memory differentiation. However, the role of mTORC1 in iNKT cell development and function remains largely unknown. By using mice with T cell-restricted deletion of Raptor, we show that mTORC1 is selectively required for iNKT but not for conventional T cell development. Indeed, Raptor-deficient iNKT cells are mostly blocked at thymic stage 1-2, resulting in a dramatic decrease of terminal differentiation into stage 3 and severe reduction of peripheral iNKT cells. Moreover, residual iNKT cells in Raptor knockout mice are impaired in their rapid cytokine production upon αGalcer challenge. Bone marrow chimera studies demonstrate that mTORC1 controls iNKT differentiation in a cell-intrinsic manner. Collectively, our data provide the genetic evidence that iNKT cell development and effector functions are under the control of mTORC1 signaling.

An EORTC phase I itudy of bortezomib in combination with oxaliplatin, leucovorin and 5-fluorouracil in patients with advanced colorectal cancer.

The combination of oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX-4) is still a reference regimen in advanced colorectal cancer; however, the addition of new biologic compounds represents a significant way forward. Bortezomib is an inhibitor of proteasome, a multicatalytic enzyme complex that degrades several intracellular proteins. In this study, escalating doses of Bortezomib were administered along with the standard FOLFOX-4 doses, in order to evaluate the dose-limiting toxicity (DLT), toxicity profile and activity of the combination. Patients with advanced colorectal cancer, unpretreated for metastatic disease, were enroled in the study. Bortezomib starting dose was 1.3mg/m(2), which was to be escalated in the subsequent steps according to the toxicities observed after first cycle. Exploratory pharmacogenetics research was conducted by analysing the association between clinical outcomes and polymorphisms in candidate genes for response to each of the used drugs. Correlation between tumour marker changes and response was also investigated. One mg/m(2) (DL-1) was defined as being the maximum tolerated dose since only 1 DLT was observed in 6 patients. The main toxicities were haematologic, neuropathy, diarrhoea and fatigue. Amongst 13 evaluable patients, five had a partial response, five had a stable disease and three patients progressed. Two patients are long-term survivors after a combined chemosurgical approach. Further trials of the current combination may be justified.

Morphostructural characterization of soil conventionally tilled with mechanized and animal traction with and without cover crop

The structural stability and restructuring ability of a soil are related to the methods of crop management and soil preparation. A recommended strategy to reduce the effects of soil preparation is to use crop rotation and cover crops that help conserve and restore the soil structure. The aim of this study was to evaluate and quantify the homogeneous morphological units in soil under conventional mechanized tillage and animal traction, as well as to assess the effect on the soil structure of intercropping with jack bean (Canavalia ensiformis L.). Profiles were analyzed in April of 2006, in five counties in the Southern-Central region of Paraná State (Brazil), on family farms producing maize (Zea mays L.), sometimes intercropped with jack bean. The current structures in the crop profile were analyzed using Geographic Information Systems (GIS) and subsequently principal component analysis (PCA) to generate statistics. Morphostructural soil analysis showed a predominance of compact units in areas of high-intensity cultivation under mechanized traction. The cover crop did not improve the structure of the soil with low porosity and compact units that hamper the root system growth. In areas exposed to animal traction, a predominance of cracked units was observed, where roots grew around the clods and along the gaps between them.

Unusual association of diseases/symptoms: Encephalitis with herpes simplex-2 in the cerebrospinal fluid and anti-RI (ANNA-2) antibodies: an infectious or a paraneoplastic syndrome?

We report on a 70-year-old woman with partial complex status epilepticus who was initially diagnosed with herpes simplex-2 (HSV-2) encephalitis, based on brain magnetic resonance imaging (MRI) findings, cerebrospinal fluid (CSF) lymphocytic pleocytosis and HSV-2 DNA detection by polymerase chain reaction (PCR) in the CSF, but without improvement on intravenous acyclovir. Anti-Ri antibodies were positive and computed tomography (CT) investigations revealed a small cell carcinoma at biopsy suggesting paraneoplastic encephalitis. The outcome was unfavourable and the autopsy showed typical features of paraneoplastic encephalitis but no evidence of viral inclusions. This case report is interesting because: (1) it is the first report of an autopsy proven paraneoplastic widespread encephalitis with anti-Ri antibodies; (2) despite a positive HSV-2 PCR in the CSF, there was no sign of herpetic infections of the nervous system; and (3) it illustrates the fact that if paraneoplastic antibodies are usually good markers of the underlying tumour, they are not always predictive of neurological deficits.

Effects of long-term irrigation with treated wastewater. Part I: Evolution of soil physico-chemical properties

The long-term impact of irrigation on a Mediterranean sandy soil irrigated with Treated wastewater (TWW) since 1980 was evaluated. The main soil properties (CEC, pH, size distribution, exchangeable cations and chloride, hydraulic conductivity) as well as the organic matter and Cu, Cr and Pb speciation in an irrigated soil and a non-irrigated control soil at various soil depths were monitored and compared during a 2 years experiment. In this first part, the evolution of the physico-chemical soil properties was described. The irrigation with TWW was beneficial with regard to water and nutrient supplying. All the exchangeable cations other than K(+) were higher in the irrigated soil than in the reference one. A part of the exchangeable cations was not fixed on the exchange complex but stored as labile salts or in concentrated soil solution. Despite the very sandy soil texture, both saturated and unsaturated hydraulic conductivity exhibited a significant diminution in the irrigated soil, but remained high enough to allow water percolation during rainy periods and subsequent leaching of accumulated salts, preventing soil salinization. In the irrigated soil, exchangeable sodium percentage (ESP) exhibited high values (20% on average) and the soil organic C was lower than in the reference. No significant effect was noticed on soil mineralogical composition due to irrigation. (C) 2010 Published by Elsevier Ltd.

Complex suicide with homemade nicotine patches.

Suicide by self-poisoning is rather common around the world. This paper presents an exceptional complex suicide in which nicotine was applied in the form of self-made patches soaked with an extraction from fine-cut tobacco. In addition, the 51-year-old suicide victim took a lethal dose of diphenhydramine. Toxicological analysis also revealed the presence of tetrazepam in subtherapeutic concentrations. The scene of death suggested an autoerotic accident at first, as the body was tied with tapes, cables and handcuffs. As a result of the entire investigations, the fatality had to be classified as a suicidal intoxication by nicotine and diphenhydramine.

DNA barcoding of Corsican mayflies (Ephemeroptera) with implications on biogeography, systematics and biodiversity

Mayflies (Ephemeroptera) are known to generally present a high degree of insular endemism: half of the 28 species known from Corsica and Sardinia are considered as endemic. We sequenced the DNA barcode (a fragment of the mitochondrial COI gene) of 349 specimens from 50 localities in Corsica, Sardinia, continental Europe and North Africa. We reconstructed gene trees of eight genera or species groups representing the main mayfly families. Alternative topologies were built to test if our reconstructions suggested a single or multiple Corsican/Sardinian colonization event(s) in each genus or species group. A molecular clock calibrated with different evolution rates was used to try to link speciation processes with geological events. Our results confirm the high degree of endemism of Corsican and Sardinian mayflies and the close relationship between these two faunas. Moreover, we have evidence that the mayfly diversity of the two islands is highly underestimated as at least six new putative species occur on the two islands. We demonstrated that the Corsican and Sardinian mayfly fauna reveals a complex history mainly related to geological events. The Messinian Salinity Crisis, which is thought to have reduced marine barriers, thus facilitating gene flow between insular and continental populations, was detected as the most important event in the speciation of most lineages. Vicariance processes related to the split and rotation of the Corso-Sardinian microplate had a minor impact as they involved only two genera with limited dispersal and ecological range. Colonization events posterior to the Messinian Salinity Crisis had only marginal effects as we had indication of recent gene flow only in two clades. With very limited recent gene flow and a high degree of endemism, mayflies from Corsica and Sardinia present all the criteria for conservation prioritization.

Ultra-high-resolution 3D imaging of atherosclerosis in mice with synchrotron differential phase contrast: a proof of concept study.

The goal of this study was to investigate the performance of 3D synchrotron differential phase contrast (DPC) imaging for the visualization of both macroscopic and microscopic aspects of atherosclerosis in the mouse vasculature ex vivo. The hearts and aortas of 2 atherosclerotic and 2 wild-type control mice were scanned with DPC imaging with an isotropic resolution of 15 μm. The coronary artery vessel walls were segmented in the DPC datasets to assess their thickness, and histological staining was performed at the level of atherosclerotic plaques. The DPC imaging allowed for the visualization of complex structures such as the coronary arteries and their branches, the thin fibrous cap of atherosclerotic plaques as well as the chordae tendineae. The coronary vessel wall thickness ranged from 37.4 ± 5.6 μm in proximal coronary arteries to 13.6 ± 3.3 μm in distal branches. No consistent differences in coronary vessel wall thickness were detected between the wild-type and atherosclerotic hearts in this proof-of-concept study, although the standard deviation in the atherosclerotic mice was higher in most segments, consistent with the observation of occasional focal vessel wall thickening. Overall, DPC imaging of the cardiovascular system of the mice allowed for a simultaneous detailed 3D morphological assessment of both large structures and microscopic details.

Mammalian Target of Rapamycin Complex 2 Controls CD8 T Cell Memory Differentiation in a Foxo1-Dependent Manner.

Upon infection, antigen-specific naive CD8 T cells are activated and differentiate into short-lived effector cells (SLECs) and memory precursor cells (MPECs). The underlying signaling pathways remain largely unresolved. We show that Rictor, the core component of mammalian target of rapamycin complex 2 (mTORC2), regulates SLEC and MPEC commitment. Rictor deficiency favors memory formation and increases IL-2 secretion capacity without dampening effector functions. Moreover, mTORC2-deficient memory T cells mount more potent recall responses. Enhanced memory formation in the absence of mTORC2 was associated with Eomes and Tcf-1 upregulation, repression of T-bet, enhanced mitochondrial spare respiratory capacity, and fatty acid oxidation. This transcriptional and metabolic reprogramming is mainly driven by nuclear stabilization of Foxo1. Silencing of Foxo1 reversed the increased MPEC differentiation and IL-2 production and led to an impaired recall response of Rictor KO memory T cells. Therefore, mTORC2 is a critical regulator of CD8 T cell differentiation and may be an important target for immunotherapy interventions.

Alai! Alai! - a new species of the Gloydius halys (Pallas, 1776) complex (Viperidae, Crotalinae), including a brief review of the complex

During a scientific field expedition to the Alai-Pamir range five specimens of the genus Gloydius have been collected in the larger Alai. A morphological and genetical examination of the specimens has shown that they are part of the G. halys complex, but represent a new taxon which is characterized by the following unique character combination: It is a slender and moderately stout small snake, up to 479 mm total length. The head has nine symmetrical plates on the upper head, 7 supralabial and 8-9 infralabial scales. Body scales in 20-22 rows around midbody, 143-156 ventral and 35-45 usually paired subcaudal scales. The cloacal plate not divided. The general coloration consists of various different tones of olive, tan and brown, having a distinct head, but an indistinct body pattern with, excluding the tail, 26-29 transverse crossbands, which are not extending to the sides of the body. The haplotype network shows the new species within the G. halys complex and close related to both, G. h. halys and G. h. caraganus. So far the new described species is only known from the Alai range. However, various Gloydius specimens are found in Kyrgyzstan and because of the complicated taxonomy those specimens have to re-identified to clarify their status and the status of the new species.

Nanoantenna enhanced emission of lightharvesting complex 2: the role of resonance, polarization, and radiative and non-radiative rates

Nanoantennae show potential for photosynthesis research for two reasons; first by spatially confining light for experiments which require high spatial resolution, and second by enhancing the photon emission of single light-harvesting complexes. For effective use of nanoantennae a detailed understanding of the interaction between the nanoantenna and the light-harvesting complex is required. Here we report how the excitation and emission of multiple purple bacterial LH2s (light-harvesting complex 2) are controlled by single gold nanorod antennae. LH2 complexes were chemically attached to such antennae, and the antenna length was systematically varied to tune the resonance with respect to the LH2 absorption and emission. There are three main findings. (i) The polarization of the LH2 emission is fully controlled by the resonant nanoantenna. (ii) The largest fluorescence enhancement, of 23 times, is reached for excitation with light at λ = 850 nm, polarized along the long antenna-axis of the resonant antenna. The excitation enhancement is found to be 6 times, while the emission efficiency is increased 3.6 times. (iii) The fluorescence lifetime of LH2 depends strongly on the antenna length, with shortest lifetimes of [similar]40 ps for the resonant antenna. The lifetime shortening arises from an 11 times resonant enhancement of the radiative rate, together with a 2–3 times increase of the non-radiative rate, compared to the off-resonant antenna. The observed length dependence of radiative and non-radiative rate enhancement is in good agreement with simulations. Overall this work gives a complete picture of how the excitation and emission of multi-pigment light-harvesting complexes are influenced by a dipole nanoantenna.

Cytogenetic study of 50 Brazilian patients with primary myelodysplastic syndrome

In this work we analyzed cytogenetically 50 patients with primary myelodysplastic syndrome from several hospitals of Rio de Janeiro, Brazil. The frequency of cytogenetic abnormalities was 32%. Patients with refractory anemia, or refractory anemia with ringed sideroblasts, presented normal karyotypes or single abnormalities such as del(5q) or -Y, while patients with refractory anemia with an excess of blasts, refractory anemia with an excess of blasts in transformation or chronic myelomonocytic leukemia showed complex karyotypes and single abnormalities involving chromosomes 7 or 8, which are related to a bad prognosis and an elevated risk of evolution to acute myeloid leukemia.

Association of MICA gene polymorphisms with liver fibrosis in schistosomiasis patients in the Dongting Lake region

Major histocompatibility complex class I chain-related A (MICA) is a highly polymorphic gene located within the MHC class I region of the human genome. Expressed as a cell surface glycoprotein, MICA modulates immune surveillance by binding to its cognate receptor on natural killer cells, NKG2D, and its genetic polymorphisms have been recently associated with susceptibility to some infectious diseases. We determined whether MICA polymorphisms were associated with the high rate of Schistosoma parasitic worm infection or severity of disease outcome in the Dongting Lake region of Hunan Province, China. Polymerase chain reaction-sequence specific priming (PCR-SSP) and sequencing-based typing (SBT) were applied for high-resolution allele typing of schistosomiasis cases (N = 103, age range = 36.2-80.5 years, 64 males and 39 females) and healthy controls (N = 141, age range = 28.6-73.3 years, 73 males and 68 females). Fourteen MICA alleles and five short-tandem repeat (STR) alleles were identified among the two populations. Three (MICA*012:01/02, MICA*017 and MICA*027) showed a higher frequency in healthy controls than in schistosomiasis patients, but the difference was not significantly correlated with susceptibility to S. japonicum infection (Pc > 0.05). In contrast, higher MICA*A5 allele frequency was significantly correlated with advanced liver fibrosis (Pc < 0.05). Furthermore, the distribution profile of MICA alleles in this Hunan Han population was significantly different from those published for Korean, Thai, American-Caucasian, and Afro-American populations (P < 0.01), but similar to other Han populations within China (P > 0.05). This study provides the initial evidence that MICA genetic polymorphisms may underlie the severity of liver fibrosis occurring in schistosomiasis patients from the Dongting Lake region.

Emergence of clonal complex 5 (CC5) methicillin-resistant Staphylococcus aureus (MRSA) isolates susceptible to trimethoprim-sulfamethoxazole in a Brazilian hospital

In this study, genotyping techniques including staphylococcal chromosomal cassette mec (SCCmec) typing, pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and restriction-modification tests were used to compare the molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered at two times within a 10-year interval (1998 and 2008) from a tertiary Brazilian hospital. In addition, the antimicrobial susceptibility profiles were analyzed. All 48 MRSA isolates from 1998 and 85.7% from 2008 (48/56 isolates) displayed multidrug-resistance phenotypes and SCCmec III. All but one of the 13 representative SCCmec III isolates belonged to CC8 and had PFGE patterns similar to that of the BMB9393 strain (Brazilian epidemic clone of MRSA; BEC). In 2008, we found an increased susceptibility to rifampicin and chloramphenicol among the SCCmec III isolates. In addition, we detected the entrance of diverse international MRSA lineages susceptible to trimethoprim-sulfamethoxazole (SXT), almost all belonging to CC5. These non-SCCmec III isolates were related to the USA 300 (ST8-SCCmec IV; PFGE-type B), USA 800 (ST5-SCCmec IV; subtype D1), USA 100 (ST5-SCCmec II; subtype D2), and EMRSA-3/Cordobes (ST5-SCCmec I, type C) clones. To the best of our knowledge, this is the first report of the emergence of isolates genetically related to the EMRSA-3/Cordobes clone in southeast Brazil. In this regard, these isolates were the most common non-SCCmec III MRSA in our institution, accounting for 8.9% of all isolates recovered in 2008. Thus, despite the supremacy of BEC isolates in our country, significant changes may occur in local MRSA epidemiology, with possible consequences for the rationality of MRSA empiric therapy.