A Petaflops Era Computing Analysis

This report covers a study of the potential for petaflops (1O(exp 15) floating point operations per second) computing. This study was performed within the year 1996 and should be considered as the first step in an on-going effort. 'Me analysis concludes that a petaflop system is technically feasible but not feasible with today's state-of-the-art. Since the computer arena is now a commodity business, most experts expect that a petaflops system will evolve from current technology in an evolutionary fashion. To meet the price expectations of users waiting for petaflop performance, great improvements in lowering component costs will be required. Lower power consumption is also a must. The present rate of progress in improved performance places the date of introduction of petaflop systems at about 2010. Several years before that date, it is projected that the resolution limit of chips will reach the now known resolution limit. Aside from the economic problems and constraints, software is identified as the major problem. The tone of this initial study is more pessimistic than most of the Super-published material available on petaflop systems. Workers in the field are expected to generate more data which could serve to provide a basis for a more informed projection. This report includes an annotated bibliography

Guidelines for implementation of cystic fibrosis newborn screening programs: Cystic Fibrosis Foundation workshop report

Newborn screening for cystic fibrosis offers the opportunity for early intervention and improved outcomes. This summary, resulting from a workshop sponsored by the Cystic Fibrosis Foundation to facilitate implementation of widespread high quality cystic fibrosis newborn screening, outlines the steps necessary for success based on the experience of existing programs. Planning should begin with a workgroup composed of those who will be responsible for the success of the local program, typically including the state newborn screening program director and cystic fibrosis care center directors. The workgroup must develop a screening algorithm based on program resources and goals including mechanisms available for sample collection, regional demographics, the spectrum of cystic fibrosis disease to be detected, and acceptable failure rates of the screen. The workgroup must also ensure that all necessary guidelines and resources for screening, diagnosis, and care be in place prior to cystic fibrosis newborn screening implementation. These include educational materials for parents and primary care providers; systems for screening and for providing diagnostic testing and counseling for screen-positive infants and their families; and protocols for care of this unique population. This summary explores the benefits and risks of various screening algorithms, including complex situations that can occur involving unclear diagnostic results, and provides guidelines and sample materials for state newborn screening programs to develop and implement high quality screening for cystic fibrosis

Proton Image-guided Radiation Assignment for Therapeutic Escalation via Selection of locally advanced head and neck cancer patients [PIRATES]:A Phase I safety and feasibility trial of MRI-guided adaptive particle radiotherapy

Introduction: Radiation dose-escalation for head and neck cancer (HNC) patients aiming to improve cure rates is challenging due to the increased risk of unacceptable treatment-induced toxicities. With “Proton Image-guided Radiation Assignment for Therapeutic Escalation via Selection of locally advanced head and neck cancer patients” (PIRATES), we present a novel treatment approach that is designed to facilitate dose-escalation while minimizing the risk of dose-limiting toxicities for locally advanced HPV-negative HNC patients. The aim of this Phase I trial is to assess the safety & feasibility of PIRATES approach. Methods: The PIRATES protocol employs a multi-faceted dose-escalation approach to minimize the risk of dose-limiting toxicities (DLTs): 1) sparing surrounding normal tissue from extraneous dose with intensity-modulated proton therapy, 2) mid-treatment hybrid hyper-fractionation for radiobiologic normal tissue sparing; 3) Magnetic Resonance Imaging (MRI) guided mid-treatment boost volume adaptation, and 4) iso-effective restricted organ-at-risk dosing to mucosa and bone tissues. The time-to-event Bayesian optimal interval (TITE-BOIN) design is employed to address the challenge of the long DLT window of 6 months and find the maximum tolerated dose. The primary endpoint is unacceptable radiation-induced toxicities (Grade 4, mucositis, dermatitis, or Grade 3 myelopathy, osteoradionecrosis) occurring within 6 months following radiotherapy. The second endpoint is any grade 3 toxicity occurring in 3–6 months after radiation. Discussion: The PIRATES dose-escalation approach is designed to provide a safe avenue to intensify local treatment for HNC patients for whom therapy with conventional radiation dose levels is likely to fail. PIRATES aims to minimize the radiation damage to the tissue surrounding the tumor volume with the combination of proton therapy and adaptive radiotherapy and within the high dose tumor volume with hybrid hyper-fractionation and not boosting mucosal and bone tissues. Ultimately, if successful, PIRATES has the potential to safety increase local control rates in HNC patients with high loco-regional failure risk. Trial registration: ClinicalTrials.gov ID: NCT04870840; Registration date: May 4, 2021. Netherlands Trial Register ID: NL9603; Registration date: July 15, 2021

Thermal structure in the Venus middle cloud layer

Thermal structure measurements obtained by the two Vega balloons show the Venus atmosphere in the middle cloud layer to be near-adiabatic, on the whole; but discrete air masses are present that differ slightly from one another in potential temperature and entropy. The Vega 1 temperatures are 6.5 K warmer than measured by Vega 2 at given pressures. Measurements taken by the Vega 2 lander on descent through these levels agree with the Vega 2 balloon data

Approximate k-state solutions to the Dirac-Yukawa problem based on the spin and pseudospin symmetry

Using an approximation scheme to deal with the centrifugal (pseudo-centrifugal) term, we solve the Dirac equation with the screened Coulomb (Yukawa) potential for any arbitrary spin-orbit quantum number {\kappa}. Based on the spin and pseudospin symmetry, analytic bound state energy spectrum formulas and their corresponding upper- and lower-spinor components of two Dirac particles are obtained using a shortcut of the Nikiforov-Uvarov method. We find a wide range of permissible values for the spin symmetry constant C_{s} from the valence energy spectrum of particle and also for pseudospin symmetry constant C_{ps} from the hole energy spectrum of antiparticle. Further, we show that the present potential interaction becomes less (more) attractive for a long (short) range screening parameter {\alpha}. To remove the degeneracies in energy levels we consider the spin and pseudospin solution of Dirac equation for Yukawa potential plus a centrifugal-like term. A few special cases such as the exact spin (pseudospin) symmetry Dirac-Yukawa, the Yukawa plus centrifugal-like potentials, the limit when {\alpha} becomes zero (Coulomb potential field) and the non-relativistic limit of our solution are studied. The nonrelativistic solutions are compared with those obtained by other methods.Comment: 21 pages, 6 figure

Possible origins of macroscopic left-right asymmetry in organisms

I consider the microscopic mechanisms by which a particular left-right (L/R) asymmetry is generated at the organism level from the microscopic handedness of cytoskeletal molecules. In light of a fundamental symmetry principle, the typical pattern-formation mechanisms of diffusion plus regulation cannot implement the "right-hand rule"; at the microscopic level, the cell's cytoskeleton of chiral filaments seems always to be involved, usually in collective states driven by polymerization forces or molecular motors. It seems particularly easy for handedness to emerge in a shear or rotation in the background of an effectively two-dimensional system, such as the cell membrane or a layer of cells, as this requires no pre-existing axis apart from the layer normal. I detail a scenario involving actin/myosin layers in snails and in C. elegans, and also one about the microtubule layer in plant cells. I also survey the other examples that I am aware of, such as the emergence of handedness such as the emergence of handedness in neurons, in eukaryote cell motility, and in non-flagellated bacteria.Comment: 42 pages, 6 figures, resubmitted to J. Stat. Phys. special issue. Major rewrite, rearranged sections/subsections, new Fig 3 + 6, new physics in Sec 2.4 and 3.4.1, added Sec 5 and subsections of Sec

Sustainability, certification, and regulation of biochar

Biochar has a relatively long half-life in soil and can fundamentally alter soil properties, processes, and ecosystem services. The prospect of global-scale biochar application to soils highlights the importance of a sophisticated and rigorous certification procedure. The objective of this work was to discuss the concept of integrating biochar properties with environmental and socioeconomic factors, in a sustainable biochar certification procedure that optimizes complementarity and compatibility between these factors over relevant time periods. Biochar effects and behavior should also be modelled at temporal scales similar to its expected functional lifetime in soils. Finally, when existing soil data are insufficient, soil sampling and analysis procedures need to be described as part of a biochar certification procedure.O “biochar” tem um tempo de meia-vida no solo relativamente longo e pode alterar substancialmente as propriedades, processos e funções do solo. A perspectiva da aplicação de “biochar” aos solos, em escala global, evidencia a importância de se lhe atribuir um processo de certificação sofisticado e rigoroso. O objetivo deste trabalho foi discutir o conceito da integração das propriedades do “biochar” com os fatores ambientais e socioeconômicos relevantes do local de aplicação selecionado, como parte de um procedimento de certificação sustentável que otimize a complementaridade e a compatibilidade entre esses fatores, em períodos de tempo relevantes. Os efeitos e o comportamento do “biochar” devem, também, ser modelados em escalas temporais similares às de seu tempo de vida funcional nos solos do local selecionado. Finalmente, onde os dados existentes sobre as características do solo forem insuficientes, procedimentos de amostragem e análise do solo devem ser descritos como parte do procedimento de certificação do “biochar”.publishe

Postcopulatory sexual selection

The female reproductive tract is where competition between the sperm of different males takes place, aided and abetted by the female herself. Intense postcopulatory sexual selection fosters inter-sexual conflict and drives rapid evolutionary change to generate a startling diversity of morphological, behavioural and physiological adaptations. We identify three main issues that should be resolved to advance our understanding of postcopulatory sexual selection. We need to determine the genetic basis of different male fertility traits and female traits that mediate sperm selection; identify the genes or genomic regions that control these traits; and establish the coevolutionary trajectory of sexes

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Genome-wide gene expression analysis supports a developmental model of low temperature tolerance gene regulation in wheat (Triticum aestivum L.)

<p>Abstract</p> <p>Background</p> <p>To identify the genes involved in the development of low temperature (LT) tolerance in hexaploid wheat, we examined the global changes in expression in response to cold of the 55,052 potentially unique genes represented in the Affymetrix Wheat Genome microarray. We compared the expression of genes in winter-habit (winter Norstar and winter Manitou) and spring-habit (spring Manitou and spring Norstar)) cultivars, wherein the locus for the vernalization gene <it>Vrn-A1 </it>was swapped between the parental winter Norstar and spring Manitou in the derived near-isogenic lines winter Manitou and spring Norstar. Global expression of genes in the crowns of 3-leaf stage plants cold-acclimated at 6°C for 0, 2, 14, 21, 38, 42, 56 and 70 days was examined.</p> <p>Results</p> <p>Analysis of variance of gene expression separated the samples by genetic background and by the developmental stage before or after vernalization saturation was reached. Using gene-specific ANOVA we identified 12,901 genes (at <it>p </it>< 0.001) that change in expression with respect to both genotype and the duration of cold-treatment. We examined in more detail a subset of these genes (2,771) where expression was highly influenced by the interaction between these two main factors. Functional assignments using GO annotations showed that genes involved in transport, oxidation-reduction, and stress response were highly represented. Clustering based on the pattern of transcript accumulation identified genes that were up or down-regulated by cold-treatment. Our data indicate that the cold-sensitive lines can up-regulate known cold-responsive genes comparable to that of cold-hardy lines. The levels of expression of these genes were highly influenced by the initial rate and the duration of the gene's response to cold. We show that the <it>Vrn-A1 </it>locus controls the duration of gene expression but not its initial rate of response to cold treatment. Furthermore, we provide evidence that <it>Ta.Vrn-A1 </it>and <it>Ta.Vrt1 </it>originally hypothesized to encode for the same gene showed different patterns of expression and therefore are distinct.</p> <p>Conclusion</p> <p>This study provides novel insight into the underlying mechanisms that regulate the expression of cold-responsive genes in wheat. The results support the developmental model of LT tolerance gene regulation and demonstrate the complex genotype by environment interactions that determine LT adaptation in winter annual cereals.</p