Analysis and Simulation of HV-CMOS Assemblies for the CLIC Vertex Detector

One of the design concepts currently under study for the vertex detector at the proposed Compact Linear Collider is a High-Voltage CMOS sensor, fabricated in a commercial 180 nm technology, capacitively coupled to a hybrid readout chip. Tests of the assemblies were carried out at the CERN SPS using 120 GeV/c pions, covering incident angles ranging from 0$^\circ$ to 80$^\circ$. The measurements have shown an excellent tracking performance with an efficiency above 99.7% and a spatial resolution of 5–7 $\mu$m over the tested angular range. These results were then compared to TCAD simulations carried out using simulations, showing a good agreement for the current-voltage, breakdown and charge collection properties. The simulations have also been used to optimise future sensor design

Simulation and evaluation of HV-CMOS pixel sensors for the CLIC vertex detector

The next steps in particle physics will involve colliders that are able to investigate the TeV energy scale so that many of the unanswered questions can be addressed. The Compact Linear Collider (CLIC) aims to do this through collisions of electrons and positrons at a high luminosity and at centre-of-mass energies of up to 3 TeV. In addition to the accelerator, a detector system is under development that targets precision physics measurements in an environment with a high rate of beam-induced backgrounds. One of the sub-detectors that faces particularly challenging requirements is the pixel vertex detector. To achieve its goals, hybrid readout chips either bump-bonded to planar sensors or capacitively coupled to High-Voltage CMOS (HV-CMOS) sensors, fabricated in a commercial 180 nm technology, are under study. Both of these sensor options have a small pitch of 25 x 25 µm² and are hybridised to 65 nm CLICpix readout ASICs. Initial investigations have shown the feasibility of such technologies, but further, and more detailed studies are needed. This is done through a series of simulations and measurements to assess the suitability of each technology for the CLIC vertex detector. Simulations of the custom designed CCPDv3 HV-CMOS sensor have been carried out using the Sentaurus Technology Computer Aided Design (TCAD) simulation software. Firstly, a comparison of a 2D model and a resource intensive 3D model was carried out, showing an agreement within 15% of the sensor properties, such as electric field, depletion depth and charge collection. However, there is a difference of 40% for the capacitance, indicating 3D simulations are better suited to capacitance measurements. The 2D model was then expanded to include a multi-pixel model for studies of charge sharing. Lab characterisations of planar sensor assemblies were undertaken to determine the quality of the bump-bonds and define regions with an acceptable level of working pixels for three assemblies. Calibrations were performed to convert the Time-over-Threshold (ToT) energy measurements and Digital-to-Analogue (DAC) threshold voltage steps into physical units. For the HV-CMOS assemblies, the analogue output of several pixels was compared to the ToT response of the CLICpix readout chip so that the simulation results could be converted to ToT and compared to the beam test data. The performance of the HV-CMOS assemblies was assessed at the CERN SPS using 120 GeV/c secondary beams. This was done over an incident angle range of 0-80° and showed excellent efficiency above 99.7% and a spatial resolution of 5-7 µm after eta-correction was applied to correct for non-linear charge sharing. The measurements were then compared to the simulations, showing a good agreement for the current-voltage, breakdown and charge collection properties. The validated simulations were used to investigate possible prospects for improved performance that can be applied in future sensor designs. Two avenues of investigation were explored: increasing the bulk resistivity and biasing from the backside. The largest improvement was for a back bias model with a resistivity of 1 kΩcm

An enhanced model for digital reference services

Digital Reference Service (DRS) play a vital role in the Digital Library (DL) research. DRS is a very valuable service provided by DL. Unfortunately, the reference service movement towards digital environment begins late, and this shift was not model based. So, a journey towards a digital environment without following a proper model raises some issues. A few researchers presented a general process model (GPM) in the late 1990s, but this process model could not overcome the problems of DRS. This paper proposes an enhanced model for DRS that use the storage and re-use mechanism with other vital components like DRS search engine and ready reference for solving the issues in DRS. Initially, storage and re-use mechanism are designed and finally, DRS search engine is designed to search appropriate answers in the knowledge base. We improved the GPM by incorporating the new components. The simulation results clearly states that the proposed model increased the service efficiency by reducing the response time from days to seconds for repeated questions and decreased the workload of librarian

Detecting differential allelic expression using high-resolution melting curve analysis: application to the breast cancer susceptibility gene CHEK2

<p>Abstract</p> <p>Background</p> <p>The gene <it>CHEK2 </it>encodes a checkpoint kinase playing a key role in the DNA damage pathway. Though <it>CHEK2 </it>has been identified as an intermediate breast cancer susceptibility gene, only a small proportion of high-risk families have been explained by genetic variants located in its coding region. Alteration in gene expression regulation provides a potential mechanism for generating disease susceptibility. The detection of differential allelic expression (DAE) represents a sensitive assay to direct the search for a functional sequence variant within the transcriptional regulatory elements of a candidate gene. We aimed to assess whether <it>CHEK2 </it>was subject to DAE in lymphoblastoid cell lines (LCLs) from high-risk breast cancer patients for whom no mutation in <it>BRCA1</it> or <it>BRCA2</it> had been identified.</p> <p>Methods</p> <p>We implemented an assay based on high-resolution melting (HRM) curve analysis and developed an analysis tool for DAE assessment.</p> <p>Results</p> <p>We observed allelic expression imbalance in 4 of the 41 LCLs examined. All four were carriers of the truncating mutation 1100delC. We confirmed previous findings that this mutation induces non-sense mediated mRNA decay. In our series, we ruled out the possibility of a functional sequence variant located in the promoter region or in a regulatory element of <it>CHEK2 </it>that would lead to DAE in the transcriptional regulatory milieu of freely proliferating LCLs.</p> <p>Conclusions</p> <p>Our results support that HRM is a sensitive and accurate method for DAE assessment. This approach would be of great interest for high-throughput mutation screening projects aiming to identify genes carrying functional regulatory polymorphisms.</p

Ghrelin, Sleep Reduction and Evening Preference: Relationships to CLOCK 3111 T/C SNP and Weight Loss

Circadian Locomotor Output Cycles Kaput (CLOCK), an essential element of the positive regulatory arm in the human biological clock, is involved in metabolic regulation. The aim was to investigate the behavioral (sleep duration, eating patterns and chronobiological characteristics) and hormonal (plasma ghrelin and leptin concentrations) factors which could explain the previously reported association between the CLOCK 3111T/C SNP and weight loss.We recruited 1495 overweight/obese subjects (BMI: 25-40 kg/m(2)) of 20-65 y. who attended outpatient obesity clinics in Murcia, in southeastern Spain. We detected an association between the CLOCK 3111T/C SNP and weight loss, which was particularly evident after 12-14 weeks of treatment (P = 0.038). Specifically, carriers of the minor C allele were more resistant to weight loss than TT individuals (Mean±SEM) (8.71±0.59 kg vs 10.4±0.57 kg) C and TT respectively. In addition, our data show that minor C allele carriers had: 1. shorter sleep duration Mean ± SEM (7.0±0.05 vs 7.3±0.05) C and TT respectively (P = 0.039), 2. higher plasma ghrelin concentrations Mean ± SEM (pg/ml) (1108±49 vs 976±47)(P = 0.034); 3. delayed breakfast time; 4. evening preference and 5. less compliance with a Mediterranean Diet pattern, as compared with TT homozygotes.Sleep reduction, changes in ghrelin values, alterations of eating behaviors and evening preference that characterized CLOCK 3111C carriers could be affecting weight loss. Our results support the hypothesis that the influence of the CLOCK gene may extend to a broad range of variables linked with human behaviors

Big issues for small feet : developmental, biomechanical and clinical narratives on children's footwear

The effects of footwear on the development of children's feet has been debated for many years and recent work from the developmental and biomechanical literature has challenged long-held views about footwear and the impact on foot development. This narrative review draws upon existing studies from developmental, biomechanical and clinical literature to explore the effects of footwear on the development of the foot. The emerging findings from this support the need for progress in [children's] footwear science and advance understanding of the interaction between the foot and shoe. Ensuring clear and credible messages inform practice requires a progressive evidence base but this remains big issue in children's footwear research

Abundance and distribution of sperm whales in the Canary Islands : can sperm whales in the Archipelago sustain the current level of ship-strike mortalities?

Funding was provided through an agreement between the Canary Islands Government and the Spanish Ministries of the Environment and Defence. Additional survey effort on the Amanay, Banquete and Concepción seamounts was funded by the Fundación Biodiversidad-MAGRAMA via the LIFE-INDEMARES project.Sperm whales are present in the Canary Islands year-round, suggesting that the archipelago is an important area for this species in the North Atlantic. However, the area experiences one of the highest reported rates of sperm whale ship-strike in the world. Here we investigate if the number of sperm whales found in the archipelago can sustain the current rate of ship-strike mortality. The results of this study may also have implications for offshore areas where concentrations of sperm whales may coincide with high densities of ship traffic, but where ship-strikes may be undocumented. The absolute abundance of sperm whales in an area of 52933 km2, covering the territorial waters of the Canary Islands, was estimated from 2668 km of acoustic line-transect survey using Distance sampling analysis. Data on sperm whale diving and acoustic behaviour, obtained from bio-logging, were used to calculate g(0) = 0.92, this is less than one because of occasional extended periods when whales do not echolocate. This resulted in an absolute abundance estimate of 224 sperm whales (95% log-normal CI 120-418) within the survey area. The recruitment capability of this number of whales, some 2.5 whales per year, is likely to be exceeded by the current ship-strike mortality rate. Furthermore, we found areas of higher whale density within the archipelago, many coincident with those previously described, suggesting that these are important habitats for females and immature animals inhabiting the archipelago. Some of these areas are crossed by active shipping lanes increasing the risk of ship-strikes. Given the philopatry in female sperm whales, replacement of impacted whales might be limited. Therefore, the application of mitigation measures to reduce the ship-strike mortality rate seems essential for the conservation of sperm whales in the Canary Islands.Publisher PDFPeer reviewe

Testing the Accuracy of Aerial Surveys for Large Mammals: An Experiment with African Savanna Elephants (Loxodonta africana)

Accurate counts of animals are critical for prioritizing conservation efforts. Past research, however, suggests that observers on aerial surveys may fail to detect all individuals of the target species present in the survey area. Such errors could bias population estimates low and confound trend estimation. We used two approaches to assess the accuracy of aerial surveys for African savanna elephants (Loxodonta africana) in northern Botswana. First, we used double-observer sampling, in which two observers make observations on the same herds, to estimate detectability of elephants and determine what variables affect it. Second, we compared total counts, a complete survey of the entire study area, against sample counts, in which only a portion of the study area is sampled. Total counts are often considered a complete census, so comparing total counts against sample counts can help to determine if sample counts are underestimating elephant numbers. We estimated that observers detected only 76% ± SE of 2% of elephant herds and 87 ± 1% of individual elephants present in survey strips. Detectability increased strongly with elephant herd size. Out of the four observers used in total, one observer had a lower detection probability than the other three, and detectability was higher in the rear row of seats than the front. The habitat immediately adjacent to animals also affected detectability, with detection more likely in more open habitats. Total counts were not statistically distinguishable from sample counts. Because, however, the double-observer samples revealed that observers missed 13% of elephants, we conclude that total counts may be undercounting elephants as well. These results suggest that elephant population estimates from both sample and total counts are biased low. Because factors such as observer and habitat affected detectability of elephants, comparisons of elephant populations across time or space may be confounded. We encourage survey teams to incorporate detectability analysis in all aerial surveys for mammals