The Power Spectrum of Mass Fluctuations Measured from the Lyman-alpha Forest at Redshift z=2.5

We measure the linear power spectrum of mass density fluctuations at redshift z=2.5 from the \lya forest absorption in a sample of 19 QSO spectra, using the method introduced by Croft et al. (1998). The P(k) measurement covers the range 2\pi/k ~ 450-2350 km/s (2-12 comoving \hmpc for \Omega=1). We examine a number of possible sources of systematic error and find none that are significant on these scales. In particular, we show that spatial variations in the UV background caused by the discreteness of the source population should have negligible effect on our P(k) measurement. We obtain consistent results from the high and low redshift halves of the data set and from an entirely independent sample of nine QSO spectra with mean redshift z=2.1. A power law fit to our measured P(k) yields a logarithmic slope n=-2.25 +/- 0.18 and an amplitude \Delta^2(k_p) = 0.57^{+0.26}_{-0.18}, where $\Delta^2$ is the contribution to the density variance from a unit interval of lnk and k_p=0.008 (km/s)^{-1}. Direct comparison of our mass P(k) to the measured clustering of Lyman Break Galaxies shows that they are a highly biased population, with a bias factor b~2-5. The slope of the linear P(k), never previously measured on these scales, is close to that predicted by models based on inflation and Cold Dark Matter (CDM). The P(k) amplitude is consistent with some scale-invariant, COBE-normalized CDM models (e.g., an open model with \Omega_0=0.4) and inconsistent with others (e.g., \Omega=1). Even with limited dynamic range and substantial statistical uncertainty, a measurement of P(k) that has no unknown ``bias factors'' offers many opportunities for testing theories of structure formation and constraining cosmological parameters. (Shortened)Comment: Submitted to ApJ, 27 emulateapj pages w/ 19 postscript fig

Combining asteroid models derived by lightcurve inversion with asteroidal occultation silhouettes

Asteroid sizes can be directly measured by observing occultations of stars by asteroids. When there are enough observations across the path of the shadow, the asteroid's projected silhouette can be reconstructed. Asteroid shape models derived from photometry by the lightcurve inversion method enable us to predict the orientation of an asteroid for the time of occultation. By scaling the shape model to fit the occultation chords, we can determine the asteroid size with a relative accuracy of typically ~ 10%. We combine shape and spin state models of 44 asteroids (14 of them are new or updated models) with the available occultation data to derive asteroid effective diameters. In many cases, occultations allow us to reject one of two possible pole solutions that were derived from photometry. We show that by combining results obtained from lightcurve inversion with occultation timings, we can obtain unique physical models of asteroids.Comment: 33 pages, 45 figures, 4 tables, accepted for publication in Icaru

Human gene copy number spectra analysis in congenital heart malformations

The clinical significance of copy number variants (CNVs) in congenital heart disease (CHD) continues to be a challenge. Although CNVs including genes can confer disease risk, relationships between gene dosage and phenotype are still being defined. Our goal was to perform a quantitative analysis of CNVs involving 100 well-defined CHD risk genes identified through previously published human association studies in subjects with anatomically defined cardiac malformations. A novel analytical approach permitting CNV gene frequency “spectra” to be computed over prespecified regions to determine phenotype-gene dosage relationships was employed. CNVs in subjects with CHD (n = 945), subphenotyped into 40 groups and verified in accordance with the European Paediatric Cardiac Code, were compared with two control groups, a disease-free cohort (n = 2,026) and a population with coronary artery disease (n = 880). Gains (≥200 kb) and losses (≥100 kb) were determined over 100 CHD risk genes and compared using a Barnard exact test. Six subphenotypes showed significant enrichment (P ≤ 0.05), including aortic stenosis (valvar), atrioventricular canal (partial), atrioventricular septal defect with tetralogy of Fallot, subaortic stenosis, tetralogy of Fallot, and truncus arteriosus. Furthermore, CNV gene frequency spectra were enriched (P ≤ 0.05) for losses at: FKBP6, ELN, GTF2IRD1, GATA4, CRKL, TBX1, ATRX, GPC3, BCOR, ZIC3, FLNA and MID1; and gains at: PRKAB2, FMO5, CHD1L, BCL9, ACP6, GJA5, HRAS, GATA6 and RUNX1. Of CHD subjects, 14% had causal chromosomal abnormalities, and 4.3% had likely causal (significantly enriched), large, rare CNVs. CNV frequency spectra combined with precision phenotyping may lead to increased molecular understanding of etiologic pathways

Requirements for an IoT-lock enabling asynchronous physical handovers of temi-trailers in road freight relay-transport

In long-distance road freight transport, capacity utilization of semi-trailers is less than 30 % due to mandatory steering and rest periods. Truck parking spaces are overcrowded while resulting parking search traffic leads to additional emissions. At the same time, the acute driver shortage and customers' expectations of ever faster functioning supply chains force the highest efficiency in transport means and personnel. Multi-carrier relay-transport represents an approach to solving these problems and exploiting untapped efficiency potentials: Via a digital platform, long distances are intelligently divided into short route sections which are distributed among different carriers. At predefined switching points, the asynchronous handover of semi-trailers to rested drivers takes place. To enable a secure cross-company physical handover, IoT-locking mechanisms play a crucial role. This paper details the asynchronous handover process and introduces the technical design of an IoT-lock which provides effective theft protection while the trailer is parked and reliably connects tractor and semi-trailer during transport. Based on an analysis of stakeholder requirements, software functionalities and mechanical properties of the IoT-lock are derived, which ensure effective theft protection as well as real-time data transmission for relay transports. In addition, legal requirements for asynchronous transfers are investigated to determine liability in case of damage or loss. These form the basis for digital handover protocols that record the condition of the freight and trailer during the handover process

Using Data-Centric Platforms To Improve Demand Forecasting And Capacity Utilization For Less Digitized Multi-Site Quarrying Businesses

The quarrying industry, which largely consists of less digitized SMEs, is an integral part of the German economy. More than 95% of the primary raw materials produced are used by the domestic construction industry. Quarrying companies operate demand-oriented with short planning horizons at several locations simultaneously. Due to the low level of digitization and the reluctance to share data, untapped efficiency potential in data-based demand forecasting and capacity planning arises. The situation is aggravated by the fact that SMEs have a heterogeneous mobile machinery so as not to become dependent on individual suppliers, and that transport distances of over 50 kilometers are uneconomical due to high transport costs and low material values. Within the research project PROmining a data-centric platform which improves demand forecast accuracy and multi-site capacity utilization is developed. One of the core functionalities of this platform is an industry-specific demand forecasting model. Against this background, this paper presents a methodology for establishing this forecasting model. To this end, expected demands of secondary industry sectors will be analyzed to improve mid-term volume-forecasting accuracy for the local quarrying industry. The data-centric platform will connect demand forecasting data with relevant key performance indicators of multi-site asset utilization. Following this methodology, operational planning horizons can be extended while significantly improving overall production efficiency. Thus, quarrying businesses are enabled to respond to fluctuating demand volumes effectively and can increase their personnel and machine utilization across multiple quarry sites

A Central Support System Can Facilitate Implementation and Sustainability of a Classroom-Based Undergraduate Research Experience (CURE) in Genomics

In their 2012 report, the President\u27s Council of Advisors on Science and Technology advocated “replacing standard science laboratory courses with discovery-based research courses”—a challenging proposition that presents practical and pedagogical difficulties. In this paper, we describe our collective experiences working with the Genomics Education Partnership, a nationwide faculty consortium that aims to provide undergraduates with a research experience in genomics through a scheduled course (a classroom-based undergraduate research experience, or CURE). We examine the common barriers encountered in implementing a CURE, program elements of most value to faculty, ways in which a shared core support system can help, and the incentives for and rewards of establishing a CURE on our diverse campuses. While some of the barriers and rewards are specific to a research project utilizing a genomics approach, other lessons learned should be broadly applicable. We find that a central system that supports a shared investigation can mitigate some shortfalls in campus infrastructure (such as time for new curriculum development, availability of IT services) and provides collegial support for change. Our findings should be useful for designing similar supportive programs to facilitate change in the way we teach science for undergraduates

Forty-one years of surgical experience with congenital supravalvular aortic stenosis

AbstractObjective: Several techniques for symmetric reconstruction of the aortic root in congenital supravalvular aortic stenosis have been developed, but it remains unclear whether these prove superior to patch enlargement of the noncoronary sinus alone. We reviewed our experience with surgical treatment of supravalvular aortic stenosis and investigated the impact of the surgical technique on long-term results. Methods and results: Seventy-five patients underwent operations to treat congenital supravalvular aortic stenosis at our institution between 1957 and 1998. Surgical procedures included patch enlargement of the noncoronary sinus only (n = 34), inverted bifurcated patch plasty (n = 35), and 3-sinus reconstruction of the aortic root (n = 6). There were 7 early deaths. Among those who survived the operation, 100% were alive at 5 years, 96% were alive at 10 years, and 77% were alive at 20 years. According to time-related analysis diffuse stenosis of the ascending aorta proved a risk factor for both survival and reoperation (P < .01 for each). Patients with multiple-sinus reconstructions of the aortic root accounted for only 2 of the 14 reoperations and none of the late deaths (both P < .001). Residual gradients were lower after multiple-sinus reconstruction of the aortic root (median 10 mm Hg vs 20 mm Hg for patch enlargement of the noncoronary sinus only, P = .008), as was the prevalence of moderate aortic regurgitation at follow-up (3% vs 22%, P = .05). Conclusions: Results of operations for supravalvular aortic stenosis improved greatly after the introduction of more symmetric reconstructions of the aortic root. Multiple-sinus reconstructions (inverted bifurcated patch plasty and 3-sinus reconstruction) resulted in superior hemodynamics and were associated with reductions in both mortality rate and need for reoperation. (J Thorac Cardiovasc Surg 1999;118:874-85

Non-EST-based prediction of novel alternatively spliced cassette exons with cell signaling function in Caenorhabditis elegans and human

To better understand the complex role that alternative splicing plays in intracellular signaling, it is important to catalog the numerous splice variants involved in signal transduction. Therefore, we developed PASE (Prediction of Alternative Signaling Exons), a computational tool to identify novel alternative cassette exons that code for kinase phosphorylation or signaling protein-binding sites. We first applied PASE to the Caenorhabditis elegans genome. In this organism, our algorithm had an overall specificity of ≥76.4%, including 33 novel cassette exons that we experimentally verified. We then used PASE to analyze the human genome and made 804 predictions, of which 308 were found as alternative exons in the transcript database. We experimentally tested 384 of the remaining unobserved predictions and discovered 26 novel human exons for a total specificity of ≥41.5% in human. By using a test set of known alternatively spliced signaling exons, we determined that the sensitivity of PASE is ∼70%. GO term analysis revealed that our exon predictions were found in the introns of known signal transduction genes more often than expected by chance, indicating PASE enriches for splice variants that function in signaling pathways. Overall, PASE was able to uncover 59 novel alternative cassette exons in C. elegans and humans through a genome-wide ab initio prediction method that enriches for exons involved in signaling

ZNF265—a novel spliceosomal protein able to induce alternative splicing

The formation of the active spliceosome, its recruitment to active areas of transcription, and its role in pre-mRNA splicing depends on the association of a number of multifunctional serine/arginine-rich (SR) proteins. ZNF265 is an arginine/serine-rich (RS) domain containing zinc finger protein with conserved pre-mRNA splicing protein motifs. Here we show that ZNF265 immunoprecipitates from splicing extracts in association with mRNA, and that it is able to alter splicing patterns of Tra2-β1 transcripts in a dose-dependent manner in HEK 293 cells. Yeast two-hybrid analysis and immunoprecipitation indicated interaction of ZNF265 with the essential splicing factor proteins U1-70K and U2AF35. Confocal microscopy demonstrated colocalization of ZNF265 with the motor neuron gene product SMN, the snRNP protein U1-70K, the SR protein SC35, and with the transcriptosomal components p300 and YY1. Transfection of HT-1080 cells with ZNF265–EGFP fusion constructs showed that nuclear localization of ZNF265 required the RS domain. Alignment with other RS domain–containing proteins revealed a high degree of SR dipeptide conservation. These data show that ZNF265 functions as a novel component of the mRNA processing machinery

Surgery for bilateral outflow tract obstruction in elastin arteriopathy

AbstractObjective: A number of patients with Williams syndrome or other forms of elastin arteriopathy have stenoses of pulmonary arteries in addition to supravalvular aortic stenosis. We sought to investigate the effect of the degree of pulmonary arterial stenosis on the prognosis after an operation for supravalvular aortic stenosis to help define the optimal treatment strategy for patients with severe forms of elastin arteriopathy. Methods: Between 1960 and 1999, 33 patients underwent operations for supravalvular aortic stenosis while having significant stenoses of the pulmonary arteries. We retrospectively reviewed patient charts, obtained current follow-up information, and determined risk factors for survival and reoperation. Results: Fifteen patients with moderate right-sided obstructions (confirmed by pulmonary artery Z-scores and right ventricular/descending aortic pressure ratio) underwent operations for supravalvular aortic stenosis only. Eighteen patients had more severe right-sided obstructions and underwent surgical relief of pulmonary arterial stenoses or right ventricular outflow tract obstruction in addition to operations for supravalvular aortic stenosis. Eight patients had undergone preoperative balloon dilations of stenotic pulmonary arteries. There were 6 early deaths and 1 late death in our series. Survival at 10 and 20 years was 76% (70% confidence interval, 68%-84%) and freedom from reintervention was 59% (70% confidence interval, 46%-71%) at 10 years and 49% (70% confidence interval, 35%-62%) at 20 years. Multivariate analysis revealed that patients with a right ventricular/descending aortic pressure ratio of 1.0 or more were at higher risk for reintervention but not for death. Conclusions: Surgical treatment of pulmonary artery obstructions in elastin arteriopathy is palliative but, in conjunction with balloon dilation of peripheral pulmonary arteries, offers good long-term survival to patients with the severest form of elastin arteriopathy. (J Thorac Cardiovasc Surg 2000;120:755-63