With the approach of winter, many insects switch to an alternative protective developmental program called diapause. Drosophila melanogaster females overwinter as adults by inducing a reproductive arrest that is characterized by inhibition of ovarian development at previtellogenic stages. The insulin producing cells (IPCs) are key regulators of this process, since they produce and release insulin-like peptides that act as diapause-antagonizing hormones. Here we show that in D. melanogaster two neuropeptides, Pigment Dispersing Factor (PDF) and short Neuropeptide F (sNPF) inhibit reproductive arrest, likely through modulation of the IPCs. In particular, genetic manipulations of the PDF-expressing neurons, which include the sNPF-producing small ventral Lateral Neurons (s-LNvs), modulated the levels of reproductive dormancy, suggesting the involvement of both neuropeptides. We expressed a genetically encoded cAMP sensor in the IPCs and challenged brain explants with synthetic PDF and sNPF. Bath applications of both neuropeptides increased cAMP levels in the IPCs, even more so when they were applied together, suggesting a synergistic effect. Bath application of sNPF additionally increased Ca2+ levels in the IPCs. Our results indicate that PDF and sNPF inhibit reproductive dormancy by maintaining the IPCs in an active state.

The widespread adoption of electronic health records (EHRs) and the growing wealth of digitized information sources about patients is ushering in an era of 'Big Data' that may revolutionize clinical research in oncology. Research will likely be more efficient and potentially more accurate than the current gold standard of manual chart review studies. However, EHRs as they exist today have significant limitations: important data elements are missing or are only captured in free text or PDF documents. Using two case studies, we illustrate the challenges of leveraging the data that are routinely collected by the healthcare system in EHRs (e.g., real-world data), specific challenges encountered in the cancer domain and opportunities that can be achieved when these are overcome.

Bladder cancers, the majority of which are urothelial carcinoma, are the most common urinary tract cancers. There are two major disease types, muscle-invasive and non-muscle-invasive, with distinct pathogenesis pathways, molecular features, and clinical outcomes. Recent genomic and transcriptomic data have significantly improved tumor sub-classification and prognostication for both patient groups and are informing improved approaches to treatment of muscle-invasive disease. To view this SnapShot, open or download the PDF.

In this Letter, we address the relationship between the statistical fluctuations of grain displacements for a full quasistatic plane shear experiment, and the corresponding anomalous diffusion exponent α. We experimentally validate a particular case of the Tsallis-Bukman scaling law, α=2/(3-q), where q is obtained by fitting the probability density function (PDF) of the displacement fluctuations with a q-Gaussian distribution, and the diffusion exponent is measured independently during the experiment. Applying an original technique, we are able to evince a transition from an anomalous diffusion regime to a Brownian behavior as a function of the length of the strain window used to calculate the displacements of the grains. The outstanding conformity of fitting curves to a massive amount of experimental data shows a clear broadening of the fluctuation PDFs as the length of the strain window decreases, and an increment in the value of the diffusion exponent-anomalous diffusion. Regardless of the size of the strain window considered in the measurements, we show that the Tsallis-Bukman scaling law remains valid, which is the first experimental verification of this relationship for a classical system at different diffusion regimes. We also note that the spatial correlations show marked similarities to the turbulence in fluids, a promising indication that this type of analysis can be used to explore the origins of the macroscopic friction in confined granular materials.

A diverse range of organisms shows physiological and behavioural rhythms with various periods. Extensive studies have been performed to elucidate the molecular mechanisms of circadian rhythms with an approximately 24 h period in both Drosophila and mammals, while less attention has been paid to ultradian rhythms with shorter periods. We used a video-tracking method to monitor the movement of single flies, and clear ultradian rhythms were detected in the locomotor behaviour of wild type and clock mutant flies kept under constant dark conditions. In particular, the Pigment-dispersing factor mutant (Pdf 01) demonstrated a precise and robust ultradian rhythmicity, which was not temperature compensated. Our results suggest that Drosophila has an endogenous ultradian oscillator that is masked by circadian rhythmic behaviours.

The increasing prevalence of multimedia and research data generated by scientific work affords an opportunity to reformulate the idea of a scientific article from the traditional static document, or even one with links to supplemental material in remote databases, to a self-contained, multimedia-rich interactive publication. This paper describes our concept of such a document, and the design of tools for authoring (Forge) and visualization/analysis (Panorama). They are platform-independent applications written in Java, and developed in Eclipse using its Rich Client Platform (RCP) framework. Both applications operate on PDF files with links to XML files that define the media type, location, and action to be performed. We also briefly cite the challenges posed by the potentially large size of interactive publications, the need for evaluating their value to improved comprehension and learning, and the need for their long-term preservation by the National Library of Medicine and other libraries.

In Figure 1b, the GHG sequence motif in the primary microRNA has been moved to the basal stem and the ruler of the basal stem has been shortened to more precisely delineate 11 base pairs. The changes have been made in the HTML and PDF versions of the manuscript.

BACKGROUND

The Canadian Community Health Survey (CCHS) is a cross-sectional survey that has collected information on health determinants, health status and the utilization of the health system in Canada since 2001. Several hundred articles have been written utilizing the CCHS dataset. Previous analyses of statistical methods utilized in the literature have focused on a particular journal or set of journals to understand the statistical literacy required for understanding the published research. In this study, we describe the statistical methods referenced in the published literature utilizing the CCHS dataset(s).

METHODS

A descriptive study was undertaken of references published in Medline, Embase, Web of Knowledge and Scopus associated with the CCHS. These references were imported into a Java application utilizing the searchable Apache Lucene text database and screened based upon pre-defined inclusion and exclusion criteria. Full-text PDF articles that met the inclusion criteria were then used for the identification of descriptive, elementary and regression statistical methods referenced in these articles. The identification of statistical methods occurred through an automated search of key words on the full-text articles utilizing the Java application.

RESULTS

We identified 4811 references from the 4 bibliographical databases for possible inclusion. After exclusions, 663 references were used for the analysis. Descriptive statistics such as means or proportions were presented in a majority of the articles (97.7%). Elementary-level statistics such as t-tests were less frequently referenced (29.7%) than descriptive statistics. Regression methods were frequently referenced in the articles: 79.8% of articles contained reference to regression in general with logistic regression appearing most frequently in 67.1% of the articles.

CONCLUSIONS

Our study shows a diverse set of analysis methods being referenced in the CCHS literature, however, the literature heavily relies on only a subset of all possible statistical tools. This information can be used in identifying gaps in statistical methods that could be applied to future analysis of public health surveys, insight into training and educational programs, and also identifies the level of statistical literacy needed to understand the published literature.

The art of making structural, polymeric, and metallic glasses is rapidly developing with many applications. A limitation is that under increasing external strain all amorphous solids (like their crystalline counterparts) have a finite yield stress which cannot be exceeded without effecting a plastic response which typically leads to mechanical failure. Understanding this is crucial for assessing the risk of failure of glassy materials under mechanical loads. Here we show that the statistics of the energy barriers ΔE that need to be surmounted changes from a probability distribution function that goes smoothly to zero as ΔE=0 to a pdf which is finite at ΔE=0 . This fundamental change implies a dramatic transition in the mechanical stability properties with respect to external strain. We derive exact results for the scaling exponents that characterize the magnitudes of average energy and stress drops in plastic events as a function of system size.

The small-x gluon in global fits of parton distributions is affected by large uncertainties from the lack of direct experimental constraints. In this Letter, we provide a precision determination of the small-x gluon from the exploitation of forward charm production data provided by LHCb for three different center-of-mass (c.m.) energies: 5 TeV, 7 TeV, and 13 TeV. The LHCb measurements are included in the parton distribution function (PDF) fit by means of normalized distributions and cross-section ratios between data taken at different c.m. values, R_{13/7} and R_{13/5}. We demonstrate that forward charm production leads to a reduction of the PDF uncertainties of the gluon down to x≃10^{-6} by up to an order of magnitude, with implications for high-energy colliders, cosmic ray physics, and neutrino astronomy.

OBJECTIVE

In present study, feeding effect of probiotic dahi containing Lactobacillus casei on immune system in terms of cytokine gene expression in the spleen and Peyer's patches of mice was evaluated.

METHODS

Animals were divided into three groups and fed with; synthetic diet [control group (CD)], dahi containing mixed dahi culture [control dahi-fed group (CDF)]; and probiotic dahi fed group (PDF) for 28 days. The mRNA levels of IL-2, IL-4, IL-6 and IFN-gamma were examined after 14 and 28 days. Total lactobacilli and lactococci counts were determined in the feces.

RESULTS

The mRNA levels of IFN-gamma in both spleen and Peyer's patches was found to be significantly increased in PDF animals after 14 and 28 days (P < 0.05) compared with CD and CDF groups. The abundance of IL-2 mRNA also increased significantly in the Peyer's patches of PDF-fed animals. No significant changes were observed in mRNA levels of IL-4 and IL-6 in both spleen and Peyer's patches during whole experimental period. Further, total fecal lactobacilli and lactococci counts in the PDF group were significantly increased during first 10 days, then remained higher up to day 28 compared to other two groups.

CONCLUSIONS

It is concluded that feeding probiotic dahi enhanced the expression of Th1 type cytokines (IFN-gamma and IL-2), especially in the mucosal immune organ (Peyer's patches) rather than in systemic organs (the spleen). This indicates that feeding with probiotic dahi may strengthen the host immune system and protect against the progression of various immune-mediated diseases.

We present a general method for the computation of PDF-based characteristics of the tissue micro-architecture in MR imaging. The approach relies on the approximation of the MR signal by a series expansion based on Spherical Harmonics and Laguerre-Gaussian functions, followed by a simple projection step that is efficiently done in a finite dimensional space. The resulting algorithm is generic, flexible and is able to compute a large set of useful characteristics of the local tissues structure. We illustrate the effectiveness of this approach by showing results on synthetic and real MR datasets acquired in a clinical time-frame.

We developed an online multimedia tool designed to enhance the student-learning environment in neurosciences through multi-sensory engagement. The combined use of scrolling text, narrations, and visual imagery engages multiple sensory modalities for effective learning, and it assists students in visualizing complex processes in the nervous system. The initial rollout of the online tool is for instruction in Parkinson's disease (PD), but its structure is flexible and can be used for teaching a variety of subjects. The instructor can access the tool online during lecture, and students can access the same information via the internet outside of class. In addition, each chapter is stand-alone and thus can be accessed online by other faculty or students to supplement other courses. Within each chapter or module, information is presented in outline format with greater detail accessible via sequential drop-down menus. This layering of related topics creates a spatial and motor-accessed path for learning. These multiple forms of engagement offer rich information representations to improve students' knowledge encoding, storing, and retrieval via multiple pathways. For instance, the tool includes student-controlled 2-D and 3-D animations, and video clip demonstrations of both patient case studies and on-campus research projects directly related to the subject material. Supplemental readings consist of current research articles (in Adobe Acrobat PDF file format) accessed within each educational topic. The teaching tool for PD is online at http://geroauen.usc.edu/Gero414_Beta/.

Negatively skewed data arise occasionally in statistical practice; perhaps the most familiar example is the distribution of human longevity. Although other generalizations of the normal distribution exist, we demonstrate a new alternative that apparently fits human longevity data better. We propose an alternative approach of a normal distribution whose scale parameter is conditioned on attained age. This approach is consistent with previous findings that longevity conditioned on survival to the modal age behaves like a normal distribution. We derive such a distribution and demonstrate its accuracy in modeling human longevity data from life tables. The new distribution is characterized by 1. An intuitively straightforward genesis; 2. Closed forms for the pdf, cdf, mode, quantile, and hazard functions; and 3. Accessibility to non-statisticians, based on its close relationship to the normal distribution.

BACKGROUND

An important aspect of proteomic mass spectrometry involves quantifying and interpreting the isotope distributions arising from mixtures of macromolecules with different isotope labeling patterns. These patterns can be quite complex, in particular with in vivo metabolic labeling experiments producing fractional atomic labeling or fractional residue labeling of peptides or other macromolecules. In general, it can be difficult to distinguish the contributions of species with different labeling patterns to an experimental spectrum and difficult to calculate a theoretical isotope distribution to fit such data. There is a need for interactive and user-friendly software that can calculate and fit the entire isotope distribution of a complex mixture while comparing these calculations with experimental data and extracting the contributions from the differently labeled species.

RESULTS

Envelope has been developed to be user-friendly while still being as flexible and powerful as possible. Envelope can simultaneously calculate the isotope distributions for any number of different labeling patterns for a given peptide or oligonucleotide, while automatically summing these into a single overall isotope distribution. Envelope can handle fractional or complete atom or residue-based labeling, and the contribution from each different user-defined labeling pattern is clearly illustrated in the interactive display and is individually adjustable. At present, Envelope supports labeling with 2H, 13C, and 15N, and supports adjustments for baseline correction, an instrument accuracy offset in the m/z domain, and peak width. Furthermore, Envelope can display experimental data superimposed on calculated isotope distributions, and calculate a least-squares goodness of fit between the two. All of this information is displayed on the screen in a single graphical user interface. Envelope supports high-quality output of experimental and calculated distributions in PNG or PDF format. Beyond simply comparing calculated distributions to experimental data, Envelope is useful for planning or designing metabolic labeling experiments, by visualizing hypothetical isotope distributions in order to evaluate the feasibility of a labeling strategy. Envelope is also useful as a teaching tool, with its real-time display capabilities providing a straightforward way to illustrate the key variable factors that contribute to an observed isotope distribution.

CONCLUSIONS

Envelope is a powerful tool for the interactive calculation and visualization of complex isotope distributions for comparison to experimental data. It is available under the GNU General Public License from http://williamson.scripps.edu/envelope/.

Most long limb bones in terrestrial mammals exhibit a longitudinal curvature and have been found to be loaded in bending. Bone curvature poses a paradox in terms of the mechanical function of limb bones, for many believe the curvature in these bones increases bending stress, potentially reducing the bone's load carrying capacity (i.e., its mechanical strength). The aim of this study is to investigate the role of longitudinal bone curvature in the design of limb bones. In particular, it has been hypothesized that bone curvature results in a trade-off between the bone's mechanical strength and its bending predictability. We employed finite element analysis (FEA) of abstract and realistic human femora to address this issue. Geometrically simplified human femur models with different curvatures were developed and analyzed with a commercial FEA tool to examine how curvature affects the bone's bending predictability and load carrying capacity. Results were post-processed to yield probability density functions (PDFs) describing the circumferential location of maximum equivalent stress for various curvatures in order to assess bending predictability. To validate our findings, a finite element model was built from a CT scan of a real human femur and compared to the simplified femur model. We found general agreement in trends but some quantitative differences most likely due to the geometric differences between the digitally reconstructed and the simplified finite element models. As hypothesized by others, our results support the hypothesis that bone curvature can increase bending predictability, but at the expense of bone strength.

We have applied convolution methods to account for some of the effects of respiratory induced motion in clinical treatment planning of the lung. The 3-D displacement of the GTV center-of-mass (COM) as determined from breath-hold exhale and inhale CT scans was used to approximate the breathing induced motion. The time-course of the GTV-COM was estimated using a probability distribution function (PDF) previously derived from diaphragmatic motion [Med. Phys. 26, 715-720 (1990)] but also used by others for treatment planning in the lung [Int. J. Radiat. Oncol., Biol., Phys. 53, 822-834 (2002); Med. Phys. 30, 1086-1095 (2003)]. We have implemented fluence and dose convolution methods within a Monte Carlo based dose calculation system with the intent of comparing these approaches for planning in the lung. All treatment plans in this study have been calculated with Monte Carlo using the breath-hold exhale CT data sets. An analysis of treatment plans for 3 patients showed substantial differences (hot and cold spots consistently greater than +/- 15%) between the motion convolved and static treatment plans. As fluence convolution accounts for the spatial variance of the dose distribution in the presence of tissue inhomogeneities, the doses were approximately 5% greater than those calculated with dose convolution in the vicinity of the lung. DVH differences between the static, fluence and dose convolved distributions for the CTV were relatively small, however, larger differences were observed for the PTV. An investigation of the effect of the breathing PDF asymmetry on the motion convolved dose distributions showed that reducing the asymmetry resulted in increased hot and cold spots in the motion convolved distributions relative to the static cases. In particular, changing from an asymmetric breathing function to one that is symmetric results in an increase in the hot/cold spots of +/- 15% relative to the static plan. This increase is not unexpected considering that the target spends relatively more time at inhale as the asymmetry decreases (note that the treatment plans were generated using the exhale CT scans).

The probability density function (PDF) of light scattering intensity can be used to characterize the scattering medium. We have recently shown that in optical coherence tomography (OCT), a PDF formalism can be sensitive to the number of scatterers in the probed scattering volume and can be represented by the K-distribution, a functional descriptor for non-Gaussian scattering statistics. Expanding on this initial finding, here we examine polystyrene microsphere phantoms with different sphere sizes and concentrations, and also human skin and fingernail in vivo. It is demonstrated that the K-distribution offers an accurate representation for the measured OCT PDFs. The behavior of the shape parameter of K-distribution that best fits the OCT scattering results is investigated in detail, and the applicability of this methodology for biological tissue characterization is demonstrated and discussed.

We present updated predictions for the cross sections for pair production of squarks and gluinos at the LHC Run II. First of all, we update the calculations based on NLO+NLL partonic cross sections by using the NNPDF3.0NLO global analysis. This study includes a full characterization of theoretical uncertainties from higher orders, PDFs and the strong coupling. Then we explore the implications for this calculation of the recent NNPDF3.0 PDFs with NLO+NLL threshold resummation. We find that the shift in the results induced by the threshold-improved PDFs is within the total theory uncertainty band of the calculation based on NLO PDFs. However, we also observe that the central values of the NLO+NLL cross sections are modified both in a qualitative and a quantitative way, illustrating the relevance and impact of using threshold-improved PDFs together with resummed partonic cross sections. The updated NLO+NLL cross sections based on NNPDF3.0NLO are publicly available in the NLL-fast format, and should be an important ingredient for the interpretation of the searches for supersymmetric particles at Run II.

The probability density function (PDF) of a global measure in a large class of highly correlated systems has been suggested to be of the same functional form. Here, we identify the analytical form of the PDF of one such measure, the order parameter in the low temperature phase of the 2D XY model. We demonstrate that this function describes the fluctuations of global quantities in other correlated equilibrium and nonequilibrium systems. These include a coupled rotor model, Ising and percolation models, models of forest fires, sandpiles, avalanches, and granular media in a self-organized critical state. We discuss the relationship with both Gaussian and extremal statistics.

We present an approximation to a molecule's N-dimensional conformational probability density function (pdf) in terms of marginal pdfs of highest order l, where l is much less than N. The approximation is constructed as a product of conditional pdfs derived by recursive application of the generalized Kirkwood superposition approximation. Furthermore, an algorithm is presented to sample conformations from the approximate full-dimensional pdf based upon all input marginal pdfs. The sampling algorithm is tested for three small molecule systems by using the algorithm to sample conformations at levels l=1, 2, or 3 and comparing the distributions of sampled conformations with those from the molecular dynamics (MD) simulations. The distributions of conformations sampled at third (l=3) order resemble the MD distributions rather well and significantly better than those sampled at second (l=2) or first (l=1) order. In addition to highlighting the importance of correlations among internal degrees of freedom, these results suggest that low-order correlations suffice to describe most of the conformational fluctuations of molecules in a thermal environment.

In fruit flies Drosophila melanogaster, courtship is an elaborate ritual comprising chasing, dancing and singing by males to lure females for mating. Courtship interactions peak in the night and heterosexual couples display enhanced nighttime activity. What we do not know is if such socio-sexual interactions (SSI) leave long-lasting after-effects on circadian clock(s). Here we report the results of our study aimed at examining the after-effects of SSI (as a result of co-habitation of males and females in groups) between males and females on their circadian locomotor activity rhythm. Males undergo reduction in the evening activity peak and lengthening of circadian period, while females show a decrease in overall activity. Such after-effects, at least in males, require functional circadian clocks during SSI as loss-of-function clock mutants and wild type flies interacting under continuous light (LL), do not display them. Interestingly, males with electrically silenced Pigment Dispersing Factor (PDF)-positive ventral lateral (LNv) clock neurons continue to show SSI mediated reduction in evening activity peak, suggesting that the LNv clock neurons are dispensable for SSI mediated after-effects on locomotor activity rhythm. Such after-effects in females may not be clock-dependent because clock manipulated females with prior exposure to males show decrease in overall activity, more or less similar to rhythmic wild type females. The expression of SSI mediated after-effects requires a functional olfactory system in males because males with compromised olfactory ability do not display them. These results suggest that SSI causes male-specific, long-lasting changes in the circadian clocks of Drosophila, which requires the presence of functional clocks and intact olfactory ability in males.

The distribution of a random variable is determined by the probability density functions (PDF) of all other random variables with which the variable in question is jointly distributed. If the PDF of the random variable of interest is normal, or skewed normal, then the distributions with which it is jointly distributed determine its mean and standard deviation. In the case described here (where hemolysis time of the red blood cell is a function of the permeability coefficient and geometric variables of the cell) the mean and standard deviation of the permeability coefficient and the known distributions of the geometric variables on which the hemolysis time depends determine a predicted distribution of hemolysis time. An observed distribution of the hemolysis time is obtained spectrophotometrically. By choosing the mean and standard deviation of the permeability coefficient so that the predicted PDF of the hemolysis time matches the observed PDF best by least-squares criterion, the complete distribution of the permeability coefficient is determined.

The cultivation of cells in vitro is an important tool for biomedical research and production purposes. The supplementation of animal/human cell culture media with sera (components) of animal origin remains still standard, providing for e.g. necessary nutrition, shear protection, growth factors and cytokines. Because of undefined composition, risk of contaminations, the cost factor and also animal welfare considerations concerning the production of sera, the conversion to serum free alternatives is promoted by regulatory authorities, industry and the research community in general. To support this trend and to help save one of the scientists most valuable resources -- time -- a data bank was compiled of commercially available formulations, searchable for products, applications, cell lines and manufacturers. The database is accessible free of charge in HTML format and as PDF download, the informations are checked and updated twice a year. Problems concerning serum free cell culture are discussed at and comments are welcome.