Abstract
In the context of the high-luminosity upgrade of the LHC and ATLAS, the microstrip-tracking detector will be redesigned. The main building blocks are substructures with multiple sensors and ...their electronics. Each substructure will have a single interface to the off-detector system, the so-called End-of-Substructure (EoS) card. Its physical realisation is a set of printed circuit boards (PCBs). The PCB integrates ASICs and hybrids, which multiplex or demultipex the data and transmit with a rate up to 10 Gb/s or receive with a rate up to 2.5 Gb/s on optical fibres. These active parts are developed at CERN and are known as lpGBT and VTRx+. The EoS card integrates the active parts with the required electronics for the specified operation and within the mechanical constraints of the detector. In this paper critical design aspects such as the low-impedance powering scheme and the PCB setup are described. The EoS card has reached its final state for a series production, including the required setups for quality control. The achieved transmission quality on the 10 Gb/s links is presented.
•Dietary nitrate as methane mitigation strategy for grazing dairy cows.•Concentrate DMI and milk yield decreased with nitrate addition.•Total DMI was unaffected by treatment.•Methane production and ...yield tended to decrease with nitrate addition.•Ruminal pH fluid and total VFA concentration increased with nitrate addition.
Dietary nitrate supplementation is an effective methane (CH4) mitigation strategy in total mixed ration based diets fed to ruminants. To date, limited information is available on the effect of dietary nitrate on CH4 production from grazing dairy cows. Fifty-four multiparous Jersey cows were subjected to a randomised complete block design (blocked according to milk yield, days in milk and parity) to evaluate the effect of three dietary nitrate levels on enteric CH4 emissions and cow production performance. Additionally, six rumen-cannulated cows in a replicated 3 × 3 Latin square design were used in a rumen study. Dietary treatments consisted of concentrate fed at 5.4 kg of DM/cow per day containing one of three levels of dietary nitrate: 0 g (control), 11 g (low nitrate), and 23 g of nitrate/kg of dry matter (DM; high nitrate). Cows grazed late-summer pasture containing approximately 3 g of nitrate/kg of DM. Concentrates were formulated to be isonitrogenous, by substituting urea, and isoenergetic. Cows were gradually adapted to concentrates over a 3-wk period before the onset of a 57-d experimental period. Enteric CH4 emissions and total dry matter intake (DMI) from 11 cows per treatment were measured during one 6-d measurement period using the sulphur hexafluoride tracer gas technique. Individual pasture DMI was determined using TiO2 and indigestible neutral detergent fibre (NDF). Milk yield decreased by approximately 12% when feeding the high nitrate diet compared with the control and low nitrate diets. Although total DMI was unaffected by treatment, concentrate DMI decreased linearly (5.5–3.7 kg/d) while pasture DMI increased linearly (9.1–11.4 kg/d) with increasing dietary nitrate addition. Methane production (313–280 g/d), CH4 yield (21.8–18.7 g/kg of DMI) and CH4 energy per gross energy intake (6.9–5.9%) tended to decrease linearly with increasing dietary nitrate addition. Diurnal ruminal pH of the high nitrate group was greater, for selective periods after concentrate feeding, than the control and low nitrate groups. Spot sample ruminal pH (6.2–6.3) tended to increase while total volatile fatty acid (VFA) concentration (99.9–104 mM/L) increased quadratically with increasing dietary nitrate addition. Individual VFA concentrations were unaffected by treatment. Rate of NDF disappearance (2.4–2.8%/h) after 18 h of ruminal incubation tended to increase quadratically with increasing dietary nitrate addition. Dietary nitrate fed to grazing dairy cows tended to decrease CH4 emissions while improving the fibrolytic environment of the rumen. However, when feeding high levels of dietary nitrate a decrease in milk yield could be expected due to a decrease in concentrate DMI.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
•Concentrate feeding level as methane mitigation strategy for grazing dairy cows.•Milk yield and dry matter intake increased with increasing concentrate level.•Pasture intake and milk fat content ...decreased with increasing concentrate level.•Only minor effects on ruminal fermentation were observed.•Methane per milk yield (g/kg) decreased linearly with increasing concentrate level.
Dietary supplementation has been well documented as an effective enteric methane (CH4) mitigation strategy. However, limited studies have demonstrated the effect of concentrate level on enteric CH4 emissions from grazing dairy cows, and to our knowledge none of these studies included a pasture-only diet or reported on rumen fermentation measures. Sixty multiparous (4.0 ± 1.51 SD) Jersey cows, of which six were rumen-cannulated, were used in a randomised complete block design, and the cannulated cows were used in a separate replicated 3 × 3 Latin square design, to investigate the effect of concentrate supplementation (0, 4, and 8 kg/cow per day; as fed) on enteric CH4 emissions, milk production, dry matter intake (DMI), and rumen fermentation of dairy cows grazing perennial ryegrass pasture during spring, following a 14-d adaptation period. The sulphur hexafluoride tracer gas technique was used to measure enteric CH4 emissions from 10 cows of each treatment group over a single 9-d measurement period. Parallel with the CH4 measurement period, pasture DMI was determined using TiO2 and indigestible neutral detergent fibre as external and internal markers, respectively, while milk yield, milk composition, cow condition, and pasture pre- and post-grazing measurements were also recorded. Total DMI (13.4 to 18.0 kg/d), milk yield (12.9 to 19.2 kg/d), energy corrected milk (14.6 to 20.7 kg/d), milk lactose content (46.2 to 48.1 g/kg) and gross energy intake (239 to 316 MJ/d) increased, while milk fat content (50.0 to 44.2 g/kg) decreased with increasing concentrate feeding level. Volatile fatty acid concentrations and ruminal pH were mostly unaffected by treatment, while dry matter disappearance decreased and NH3-N concentration increased with increasing concentrate feeding level. Methane production (258 to 302 g/d) and CH4 yield (20.6 to 16.9 g/kg of DMI) were similar for all cows, while pasture DMI (13.4 to 10.8 kg/d) and CH4 intensity (20.4 to 15.9 g of CH4/kg of milk yield) decreased linearly with increasing concentrate feeding level. Results indicate that concentrate supplementation on high quality pasture-only diets have the potential to effectively reduce CH4 emissions per unit of milk yield from grazing cows during spring.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
•Dietary nitrate was supplemented to dairy cows grazing ryegrass pasture.•Milk yield, total DMI and pasture DMI was unaffected by treatment.•Methane emissions were unaffected by treatment.•Rumen ...fermentation parameters were unaffected by treatment.•Lack of treatment response could be due to high nitrate levels in pasture.
Limited studies investigated the effect of dietary nitrate addition as methane (CH4) mitigation strategy for dairy cows grazing pasture. This study aimed to investigate the effect of dietary nitrate addition on daily enteric CH4 emissions, production performance and rumen fermentation of multiparous Jersey cows grazing perennial ryegrass pasture (containing approximately 7.3 g of nitrate/kg of dry matter (DM)). Thirty-two intact and eight rumen-cannulated multiparous Jersey cows were subjected to a replicated 2 × 2 Latin square design with 16 intact cow replicates and four rumen-cannulated cow replicates supplemented with one of two concentrates containing either urea (urea treatment), or urea and nitrate (nitrate treatment) as nonprotein nitrogen source (NPN; containing 0.3 and 15.2 g of nitrate/kg of DM, respectively). Concentrates were formulated to be isonitrogenous and isoenergetic, and was fed at 5.4 kg of DM/cow per d along with a strict daily herbage allowance of 14 kg of DM/cow. Cows were gradually adapted to concentrates over a 3-wk period. Total nitrate intake was 5.2 and 9.7 g of nitrate/kg of DM for the urea and nitrate treatment groups, respectively. Daily enteric CH4 emissions of 28 cows were measured with the sulphur hexafluoride tracer gas technique for six consecutive days during each experimental period with parallel total DM intake (DMI) estimates. Pasture DMI was calculated from faecal output and pasture digestibility using TiO2 and indigestible neutral detergent, respectively. Total DMI (18.1 and 17.8 kg/d), milk yield (19.0 and 18.9 kg/cow per d) and daily CH4 emissions (400 and 405 g/d) were unaffected by dietary treatment for the urea and nitrate group, respectively. Total milk solids content (135 vs. 133 g/kg), milk lactose content (47.3 vs. 46.7 g/kg) and milk urea nitrogen concentration (MUN; 12.6 vs. 11.6 mg/dL) were higher for the nitrate group. Rumen fermentation parameters such as volatile fatty acid profile, ammonium nitrogen, and DM and fibre disappearance were unaffected by treatment. Minor effects on ruminal pH were observed with an increasing tendency towards the nitrate group. In this study, dietary nitrate supplementation was not an effective CH4 mitigation strategy for dairy cows grazing perennial ryegrass. This can be ascribed to the unforeseen high nitrate content of the grazed pasture causing a relative small margin in total nitrate intake between the urea and nitrate treatment diets.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Through a prospective clinical sequencing program for advanced cancers, four index cases were identified which harbor gene rearrangements of FGFR2, including patients with cholangiocarcinoma, breast ...cancer, and prostate cancer. After extending our assessment of FGFR rearrangements across multiple tumor cohorts, we identified additional FGFR fusions with intact kinase domains in lung squamous cell cancer, bladder cancer, thyroid cancer, oral cancer, glioblastoma, and head and neck squamous cell cancer. All FGFR fusion partners tested exhibit oligomerization capability, suggesting a shared mode of kinase activation. Overexpression of FGFR fusion proteins induced cell proliferation. Two bladder cancer cell lines that harbor FGFR3 fusion proteins exhibited enhanced susceptibility to pharmacologic inhibition in vitro and in vivo. Because of the combinatorial possibilities of FGFR family fusion to a variety of oligomerization partners, clinical sequencing efforts, which incorporate transcriptome analysis for gene fusions, are poised to identify rare, targetable FGFR fusions across diverse cancer types.
Abstract Next-generation sequencing (NGS) has enabled genome-wide personalized oncology efforts at centers and companies with the specialty expertise and infrastructure required to identify and ...prioritize actionable variants. Such approaches are not scalable, preventing widespread adoption. Likewise, most targeted NGS approaches fail to assess key relevant genomic alteration classes. To address these challenges, we predefined the catalog of relevant solid tumor somatic genome variants (gain-of-function or loss-of-function mutations, high-level copy number alterations, and gene fusions) through comprehensive bioinformatics analysis of >700,000 samples. To detect these variants, we developed the Oncomine Comprehensive Panel (OCP), an integrative NGS-based assay compatible with < 20 ng of DNA/RNA from formalin-fixed paraffin-embedded (FFPE) tissues, coupled with an informatics pipeline to specifically identify relevant predefined variants and created a knowledge base of related potential treatments, current practice guidelines, and open clinical trials. We validated OCP using molecular standards and more than 300 FFPE tumor samples, achieving >95% accuracy for KRAS, epidermal growth factor receptor , and BRAF mutation detection as well as for ALK and TMPRSS2:ERG gene fusions. Associating positive variants with potential targeted treatments demonstrated that 6% to 42% of profiled samples (depending on cancer type) harbored alterations beyond routine molecular testing that were associated with approved or guideline-referenced therapies. As a translational research tool, OCP identified adaptive CTNNB1 amplifications/mutations in treated prostate cancers. Through predefining somatic variants in solid tumors and compiling associated potential treatment strategies, OCP represents a simplified, broadly applicable targeted NGS system with the potential to advance precision oncology efforts.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The control of the initial outbreak and spread of SARS-CoV-2/COVID-19 via the application of population-wide non-pharmaceutical mitigation measures have led to remarkable successes in dampening the ...pandemic globally. However, with countries beginning to ease or lift these measures fully to restart activities, concern is growing regarding the impacts that such reopening of societies could have on the subsequent transmission of the virus. While mathematical models of COVID-19 transmission have played important roles in evaluating the impacts of these measures for curbing virus transmission, a key need is for models that are able to effectively capture the effects of the spatial and social heterogeneities that drive the epidemic dynamics observed at the local community level. Iterative forecasting that uses new incoming epidemiological and social behavioral data to sequentially update locally-applicable transmission models can overcome this gap, potentially resulting in better predictions and policy actions. Here, we present the development of one such data-driven iterative modelling tool based on publicly available data and an extended SEIR model for forecasting SARS-CoV-2 at the county level in the United States. Using data from the state of Florida, we demonstrate the utility of such a system for exploring the outcomes of the social measures proposed by policy makers for containing the course of the pandemic. We provide comprehensive results showing how the locally identified models could be employed for accessing the impacts and societal tradeoffs of using specific social protective strategies. We conclude that it could have been possible to lift the more disruptive social interventions related to movement restriction/social distancing measures earlier if these were accompanied by widespread testing and contact tracing. These intensified social interventions could have potentially also brought about the control of the epidemic in low- and some medium-incidence county settings first, supporting the development and deployment of a geographically-phased approach to reopening the economy of Florida. We have made our data-driven forecasting system publicly available for policymakers and health officials to use in their own locales, so that a more efficient coordinated strategy for controlling SARS-CoV-2 region-wide can be developed and successfully implemented.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•PKE was incorporated into dairy concentrate at 0, 200 and 400g/kg.•PKE can partially replace maize in concentrates for dairy cows grazing ryegrass.•Body weight and condition score stayed ...unchanged.•Milk yield and milk composition stayed unchanged.•Practically recommended to include PKE up to 200g/kg in dairy concentrate.
The aim of the study was to determine the effect of different inclusion levels of palm kernel expeller (PKE) in dairy concentrates for grazing Jersey cows on lactation performance and rumen fermentation patterns. Forty-eight multiparous, Jersey cows, grazing kikuyu-ryegrass during spring, were blocked according to 4% fat corrected milk, days in milk and lactation number and randomly allocated to three treatments based on PKE level in the concentrate. The PKE inclusion in the control (C), low PKE (LP), and high PKE (HP) treatment concentrates was 0, 200, and 400g/kg, respectively, and was fed for a 60 d period, preceded by a 21 d adaptation period. The PKE partially substituted some of the maize and soybean in the concentrate. Additionally, eight rumen-fistulated, lactating dairy cows were randomly allocated to the C and HP treatment in a two period cross-over design. Cows received 6kg (as is) concentrate per day divided over two milkings and strip-grazed pasture as one group. Milk yield and milk fat content did not differ between treatments and were 21.3, 21.3 and 20.7kg/cow/d and 46.3, and 46.5, and 46.6g/kg for the C, LP and HP treatment, respectively. Milk protein, milk urea nitrogen, body weight and body condition score did not differ between cows on all treatments. Total volatile fatty acid, mean ruminal pH, ammonia nitrogen, and in situ pasture dry matter and neutral detergent fibre degradability did not differ between cows on all treatments. The acetic to propionic acid ratio was higher (P=0.006) for cows receiving treatment HP compared to cows receiving treatment C (3.40 vs. 3.22). It was concluded that PKE can sustain milk yield and milk fat components at a level of up to 400g/kg of concentrate when fed at 6kg/cow/d to cows grazing kikuyu-ryegrass pasture. A more practical recommendation might be to limit PKE to 200g/kg of concentrate due to potential palatability problems and a slow rate of intake when fed during milking in the parlour.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract
The building blocks of the upgraded ATLAS Strip Tracker for HL-LHC are modules that host silicon sensors and front-end ASICs. The modules are mounted on carbon-fibre substructures hosting up ...to 14 modules per side. An End-of-Substructure (EoS) card on each substructure side connects up to 28 differential data lines at 640 Mbit/s to lpGBT and VTRx+ ASICs that provide data serialisation and 10 Gbit/s optical data transmission to the off-detector systems respectively. Prototype EoS cards have been designed and extensively tested using lpGBT and VTRx+ prototypes. The status of the electronics design and recent test results are presented.
Time domain radio astronomy observing campaigns frequently generate large volumes of data. Our goal is to develop automated methods that can identify events of interest buried within the larger data ...stream. The V-FASTR fast transient system was designed to detect rare fast radio bursts within data collected by the Very Long Baseline Array. The resulting event candidates constitute a significant burden in terms of subsequent human reviewing time. We have trained and deployed a machine learning classifier that marks each candidate detection as a pulse from a known pulsar, an artifact due to radio frequency interference, or a potential new discovery. The classifier maintains high reliability by restricting its predictions to those with at least 90% confidence. We have also implemented several efficiency and usability improvements to the V-FASTR web-based candidate review system. Overall, we found that time spent reviewing decreased and the fraction of interesting candidates increased. The classifier now classifies (and therefore filters) 80%-90% of the candidates, with an accuracy greater than 98%, leaving only the 10%-20% most promising candidates to be reviewed by humans.
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BFBNIB, NMLJ, NUK, PNG, UL, UM, UPUK
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