Characterizations of non-normalized discrete probability distributions and their application in statistics

From the distributional characterizations that lie at the heart of Stein’s method we derive explicit formulae for the mass functions of discrete probability laws that identify those distributions. These identities are applied to develop tools for the solution of statistical problems. Our characterizations, and hence the applications built on them, do not require any knowledge about normalization constants of the probability laws. To demonstrate that our statistical methods are sound, we provide comparative simulation studies for the testing of fit to the Poisson distribution and for parameter estimation of the negative binomial family when both parameters are unknown. We also consider the problem of parameter estimation for discrete exponential-polynomial models which generally are non-normalized

Molecular and immunological characterization of profilin from mugwort pollen

In late summer in Europe, pollen of mugwort is one of the major sources of atopic allergens. No information about the complete molecular structure of any mugwort allergen has been published so far. Here we report the isolation and characterization of mugwort pollen cDNA clones coding for two isoforms of the panallergen profilin. Thirtysix percent of the mugwort allergic patients tested displayed IgE antibodies against natural and recombinant profilin, and no significant differences were observed in the IgEbinding properties of the isoforms. One profilin isoform was purified to homogeneity and detailed structural analysis indicated that the protein exists in solution as dimers and tetramers stabilized by sulfydryl and/or ionic interactions. Profilin monomers were detectable only after exposure of multimers to harsh denaturing conditions. Dimers and tetramers did not significantly differ in their ability to bind serum IgE from mugwort pollenallergic patients. However, oligomeric forms might have a higher allergenic potential than monomers because larger molecules would have additional epitopes for IgEmediated histamine release. Profilin isolated from mugwort pollen also formed multimers. Thus, oligomerization is not an artifact resulting from the recombinant production of the allergen. Inhibition experiments showed extensive IgE crossreactivity of recombinant mugwort profilin and profilin from various pollen and food extracts

Molecular Dynamics Simulation of Compressible Fluid Flow in Two-Dimensional Channels

We study compressible fluid flow in narrow two-dimensional channels using a novel molecular dynamics simulation method. In the simulation area, an upstream source is maintained at constant density and temperature while a downstream reservoir is kept at vacuum. The channel is sufficiently long in the direction of the flow that the finite length has little effect on the properties of the fluid in the central region. The simulated system is represented by an efficient data structure, whose internal elements are created and manipulated dynamically in a layered fashion. Consequently the code is highly efficient and manifests completely linear performance in simulations of large systems. We obtain the steady-state velocity, temperature, and density distributions in the system. The velocity distribution across the channel is very nearly a quadratic function of the distance from the center of the channel and reveals velocity slip at the boundaries; the temperature distribution is only approximately a quartic function of this distance from the center to the channel. The density distribution across the channel is non-uniform. We attribute this non-uniformity to the relatively high Mach number, approximately 0.5, in the fluid flow. An equation for the density distribution based on simple compressibility arguments is proposed; its predictions agree well with the simulation results. Validity of the concept of local dynamic temperature and the variation of the temperature along the channel are discussed.Comment: 16 pages (in latex) + 8 figures (in a single ps file). Submitted to the Physical Review

Osmotic pressure of matter and vacuum energy

The walls of the box which contains matter represent a membrane that allows the relativistic quantum vacuum to pass but not matter. That is why the pressure of matter in the box may be considered as the analog of the osmotic pressure. However, we demonstrate that the osmotic pressure of matter is modified due to interaction of matter with vacuum. This interaction induces the nonzero negative vacuum pressure inside the box, as a result the measured osmotic pressure becomes smaller than the matter pressure. As distinct from the Casimir effect, this induced vacuum pressure is the bulk effect and does not depend on the size of the box. This effect dominates in the thermodynamic limit of the infinite volume of the box. Analog of this effect has been observed in the dilute solution of 3He in liquid 4He, where the superfluid 4He plays the role of the non-relativistic quantum vacuum, and 3He atoms play the role of matter.Comment: 5 pages, 1 figure, JETP Lett. style, version accepted in JETP Letter

Predicting Delay in Goal-Directed Action: An Experience Sampling Approach Uncovering Within-Person Determinants Involved in the Onset of Academic Procrastination Behavior

Academic procrastination involves the delayed implementation of actions required to fulfill study-related tasks. These behavioral delays are thought to result from momentary failures in self-regulation (i.e., within-person processes). Most previous studies focused on the role of trait-based individual differences in students’ procrastination tendencies. Little is known about the within-person processes involved in the occurrence of procrastination behavior in real-life academic situations. The present study applied an event-based experience sampling approach to investigate whether the onset of task-specific delay behavior can be attributed to unfavorable changes in students’ momentary appraisals of tasks (value, aversiveness, effort, expectations of success), which may indicate failures in self-regulation arise between critical phases of goal-directed action. University students (N = 75) used an electronic diary over eight days to indicate their next days’ intentions to work on academic tasks and their task-specific appraisals (n = 582 academic tasks planned). For each task, a second query requested the next day determined whether students’ task-related appraisals changed and whether they implemented their intention on time or delayed working on the respective task (n = 501 completed task-specific measurements). Students’ general procrastination tendency was assessed at baseline using two established self-report questionnaires. Stepwise two-level logistic regression analyses revealed that within-person changes in task-related appraisals that reflected a devaluation of the study-related tasks increased the risk for an actual delay. The risk to delay decreased when students maintained a positive attitude toward the task. Students’ general procrastination tendency did not predict individual differences in their task-specific delay behavior. We discuss these findings in light of the growing effort to understand the within-person processes that contribute to induce procrastination behavior under real-life academic conditions and illustrate how this knowledge can benefit the design of tasks and instructions that support students’ self-regulation to their best

Proteomics reveals distinct mechanisms regulating the release of cytokines and alarmins during pyroptosis

A major pathway for proinflammatory protein release by macrophages is inflammasome-mediated pyroptotic cell death. As conventional secretion, unconventional secretion, and cell death are executed simultaneously, however, the cellular mechanisms regulating this complex paracrine program remain incompletely understood. Here, we devise a quantitative proteomics strategy to define the cellular exit route for each protein by pharmacological and genetic dissection of cellular checkpoints regulating protein release. We report the release of hundreds of proteins during pyroptosis, predominantly due to cell lysis. They comprise constitutively expressed and transcriptionally induced proteins derived from the cytoplasm and specific intracellular organelles. Many low-molecular-weight proteins including the cytokine interleukin-1b, alarmins, and lysosomal-cargo proteins exit cells in the absence of cell lysis. Cytokines and alarmins are released in an endoplasmic reticulum (ER)-Golgi-dependent manner as free proteins rather than by extracellular vesicles. Our work provides an experimental framework for the dissection of cellular exit pathways and a resource for pyroptotic protein release

Neuronal Activity in Rat Barrel Cortex Underlying Texture Discrimination

Rats and mice palpate objects with their whiskers to generate tactile sensations. This form of active sensing endows the animals with the capacity for fast and accurate texture discrimination. The present work is aimed at understanding the nature of the underlying cortical signals. We recorded neuronal activity from barrel cortex while rats used their whiskers to discriminate between rough and smooth textures. On whisker contact with either texture, firing rate increased by a factor of two to ten. Average firing rate was significantly higher for rough than for smooth textures, and we therefore propose firing rate as the fundamental coding mechanism. The rat, however, cannot take an average across trials, but must make an immediate decision using the signals generated on each trial. To estimate single-trial signals, we calculated the mutual information between stimulus and firing rate in the time window leading to the rat's observed choice. Activity during the last 75 ms before choice transmitted the most informative signal; in this window, neuronal clusters carried, on average, 0.03 bits of information about the stimulus on trials in which the rat's behavioral response was correct. To understand how cortical activity guides behavior, we examined responses in incorrect trials and found that, in contrast to correct trials, neuronal firing rate was higher for smooth than for rough textures. Analysis of high-speed films suggested that the inappropriate signal on incorrect trials was due, at least in part, to nonoptimal whisker contact. In conclusion, these data suggest that barrel cortex firing rate on each trial leads directly to the animal's judgment of texture

Quantitative morphometrical characterization of human pronuclear zygotes

BACKGROUND Identification of embryos with high implantation potential remains a challenge in in vitro fertilization (IVF). Subjective pronuclear (PN) zygote scoring systems have been developed for that purpose. The aim of this work was to provide a software tool that enables objective measuring of morphological characteristics of the human PN zygote. METHODS A computer program was created to analyse zygote images semi-automatically, providing precise morphological measurements. The accuracy of this approach was first validated by comparing zygotes from two different IVF centres with computer-assisted measurements or subjective scoring. Computer-assisted measurement and subjective scoring were then compared for their ability to classify zygotes with high and low implantation probability by using a linear discriminant analysis. RESULTS Zygote images coming from the two IVF centres were analysed with the software, resulting in a series of precise measurements of 24 variables. Using subjective scoring, the cytoplasmic halo was the only feature which was significantly different between the two IVF centres. Computer-assisted measurements revealed significant differences between centres in PN centring, PN proximity, cytoplasmic halo and features related to nucleolar precursor bodies distribution. The zygote classification error achieved with the computer-assisted measurements (0.363) was slightly inferior to that of the subjective ones (0.393). CONCLUSIONS A precise and objective characterization of the morphology of human PN zygotes can be achieved by the use of an advanced image analysis tool. This computer-assisted analysis allows for a better morphological characterization of human zygotes and can be used for classificatio

Prolonged High Fat Diet Reduces Dopamine Reuptake without Altering DAT Gene Expression

The development of diet-induced obesity (DIO) can potently alter multiple aspects of dopamine signaling, including dopamine transporter (DAT) expression and dopamine reuptake. However, the time-course of diet-induced changes in DAT expression and function and whether such changes are dependent upon the development of DIO remains unresolved. Here, we fed rats a high (HFD) or low (LFD) fat diet for 2 or 6 weeks. Following diet exposure, rats were anesthetized with urethane and striatal DAT function was assessed by electrically stimulating the dopamine cell bodies in the ventral tegmental area (VTA) and recording resultant changes in dopamine concentration in the ventral striatum using fast-scan cyclic voltammetry. We also quantified the effect of HFD on membrane associated DAT in striatal cell fractions from a separate group of rats following exposure to the same diet protocol. Notably, none of our treatment groups differed in body weight. We found a deficit in the rate of dopamine reuptake in HFD rats relative to LFD rats after 6 but not 2 weeks of diet exposure. Additionally, the increase in evoked dopamine following a pharmacological challenge of cocaine was significantly attenuated in HFD relative to LFD rats. Western blot analysis revealed that there was no effect of diet on total DAT protein. However, 6 weeks of HFD exposure significantly reduced the 50 kDa DAT isoform in a synaptosomal membrane-associated fraction, but not in a fraction associated with recycling endosomes. Our data provide further evidence for diet-induced alterations in dopamine reuptake independent of changes in DAT production and demonstrates that such changes can manifest without the development of DIO

Specificity of emotion sequences in borderline personality disorder compared to posttraumatic stress disorder, bulimia nervosa, and healthy controls: an e-diary study

Background: Patients with borderline personality disorder (BPD) exhibit dysregulated emotion sequences in daily life compared to healthy controls (HC). Empirical evidence regarding the specificity of these findings is currently lacking. Methods: To replicate dysregulated emotion sequences in patients with BPD and to investigate the specificity of the sequences, we used e-diaries of 43 female patients with BPD, 28 patients with posttraumatic stress disorder (PTSD), 20 patients with bulimia nervosa (BN), and 28 HC. To capture the rapid dynamics of emotions, we prompted participants every 15 min over a 24-h period to assess their current perceived emotions. We analyzed group differences in terms of activation, persistence, switches, and down-regulation of emotion sequences. Results: By comparing patients with BPD to HC, we replicated five of the seven previously reported dysregulated emotion sequences, as well as 111 out of 113 unaltered sequences. However, none of the previously reported dysregulated emotion sequences exhibited specificity, i.e., none revealed higher frequencies compared to the PTSD group or the BN group. Beyond these findings, we revealed a specific finding for patients with BN, as they most frequently switched from anger to disgust. Conclusions: Replicating previously found dysregulated and unaltered emotional sequences strengthens the significance of emotion sequences. However, the lack of specificity points to emotion sequences as transdiagnostic features