julilili42/papers huggingface dataset:
DEKOIS: Demanding Evaluation Kits for Objective in Silico Screening — A Versatile Tool for Benchmarking Docking Programs and Scoring Functions
2011-07-21

For widely applied in silico screening techniques success depends on the rational selection of an appropriate method. We herein present a fast, versatile, and robust method to construct demanding evaluation kits for objective in silico screening (DEKOIS). This automated process enables creating tailor-made decoy sets for any given sets of bioactives. It facilitates a target-dependent validation of docking algorithms and scoring functions helping to save time and resources. We have developed metrics for assessing and improving decoy set quality and employ them to investigate how decoy embedding affects docking. We demonstrate that screening performance is target-dependent and can be impaired by latent actives in the decoy set (LADS) or enhanced by poor decoy embedding. The presented method allows extending and complementing the collection of publicly available high quality decoy sets toward new target space. All present and future DEKOIS data sets will be made accessible at www.dekois.com.
An Efficient SER Estimation Method for Combinational Circuits
2011-07-21

Nanometer CMOS VLSI circuits are highly sensitive to soft errors due to environmental causes such as cosmic radiation, and charged particles. These phenomena, also known as single-event upsets (SEU), induce current pulses at random times and random locations in a digital circuit. In this article, we present a new soft error rate (SER) estimation method for combinational circuits. This method is more efficient than other known methods because it takes into account only those physical factors which have a significant impact on the error rate. We first present an equation for SER irrespective of masking effects in combinational circuits. Then we describe the three masking effects, and augment the SER equation according to these effects. Finally, we present the results of our SER estimation method for several CMOS technologies.
Temperature‐induced stress leads to bleaching in larger benthic foraminifera hosting endosymbiotic diatoms
2011-07-22

Physiological mechanisms of bleaching were studied on larger benthic foraminifera (LBF) hosting endosymbiotic diatoms. Amphistegina radiata , Heterostegina depressa, and Calcarina hispida were exposed to increasing temperatures in static temperature experiments (23°C to 33°C, 6 d). Photosynthetic activity (F v : F m , measured with a pulse‐amplitude modulated fluorometer), chlorophyll a (a proxy for symbiont biomass), and motility (a proxy for overall fitness of the foraminifera) were reduced in specimens at 32°C to 33°C, and cytoplasm color changes associated with bleaching were observed. A 30‐d flow‐through experiment at three temperatures (26°C to 31°C) and three levels of inorganic nitrate concentration (0.5 to 1.4 μmol L −1 ) confirmed negative effects of temperature at 31°C for A. radiata (including growth) and H. depressa . Another Calcarina species, Calcarina mayorii, was not affected. This suggests that temperature effects are species‐specific. However, elevated nutrient concentrations did not affect any of the parameters measured. Temperatures &gt; 30°C stress the foram–diatom endosymbiosis in some LBF species, which may lead to subsequent bleaching of the host. Given that a 2–3°C increase led to rapid bleaching of most species, we propose that, similar to corals, these species are threatened by sea‐surface temperature increase predicted for tropical reef waters in the near future.
Enhanced suicidal erythrocyte death in mice carrying a loss‐of‐function mutation of the adenomatous polyposis coli gene
2011-07-22

Abstract Loss‐of‐function mutations in human adenomatous polyposis coli (APC) lead to multiple colonic adenomatous polyps eventually resulting in colonic carcinoma. Similarly, heterozygous mice carrying defective APC ( apc Min/+ ) suffer from intestinal tumours. The animals further suffer from anaemia, which in theory could result from accelerated eryptosis, a suicidal erythrocyte death triggered by enhanced cytosolic Ca 2+ activity and characterized by cell membrane scrambling and cell shrinkage. To explore, whether APC‐deficiency enhances eryptosis, we estimated cell membrane scrambling from annexin V binding, cell size from forward scatter and cytosolic ATP utilizing luciferin–luciferase in isolated erythrocytes from apc Min/+ mice and wild‐type mice ( apc +/+ ). Clearance of circulating erythrocytes was estimated by carboxyfluorescein‐diacetate‐succinimidyl‐ester labelling. As a result, apc Min/+ mice were anaemic despite reticulocytosis. Cytosolic ATP was significantly lower and annexin V binding significantly higher in apc Min/+ erythrocytes than in apc +/+ erythrocytes. Glucose depletion enhanced annexin V binding, an effect significantly more pronounced in apc Min/+ erythrocytes than in apc +/+ erythrocytes. Extracellular Ca 2+ removal or inhibition of Ca 2+ entry with amiloride (1 mM) blunted the increase but did not abrogate the genotype differences of annexin V binding following glucose depletion. Stimulation of Ca 2+ ‐entry by treatment with Ca 2+ ‐ionophore ionomycin (10 μM) increased annexin V binding, an effect again significantly more pronounced in apc Min/+ erythrocytes than in apc +/+ erythrocytes. Following retrieval and injection into the circulation of the same mice, apc Min/+ erythrocytes were more rapidly cleared from circulating blood than apc +/+ erythrocytes. Most labelled erythrocytes were trapped in the spleen, which was significantly enlarged in apc Min/+ mice. The observations point to accelerated eryptosis and subsequent clearance of apc Min/+ erythrocytes, which contributes to or even accounts for the enhanced erythrocyte turnover, anaemia and splenomegaly in those mice.
Small-Interfering RNA-Eluting Surfaces as a Novel Concept for Intravascular Local Gene Silencing
2011-07-22

New drug-eluting stent (DES) methods have recently been demonstrated to improve outcomes of intravascular interventions. A novel technique is the design of gene-silencing stents that elute specific small-interfering RNAs (siRNAs) for better vascular wall regeneration. Although siRNAs used to alter gene expression have surpassed expectations in in vitro experiments, the functional and local delivery of siRNAs is still the major obstacle for the in vivo application of RNA interference. In this preliminary in vitro study we investigated a surface-immobilized siRNA delivery technique that would be readily adaptable for local intravascular applications in vivo. The transfection potency of gelatin coatings consisting of a specific siRNA complexed with polyethylenimine (PEI) was examined in primary human endothelial cells by flow cytometry and quantitative real-time polymerase chain reaction. Several media conditions, such as the presence or absence of serum during cultivation, were investigated. Furthermore, different siRNA and PEI amounts, as well as nitrogen/phosphate ratios, were tested for their transfection efficiency. Gelatin coatings consisting of PEI and siRNA against an exemplary endothelial adhesion molecule receptor achieved a significant knockdown of around 70%. The transfection efficiency of the coatings was not influenced by the presence of serum. The results of this preliminary study support the expectation that this novel coating may be favorable for local in vivo gene silencing (for example, when immobilized on stents or balloons for percutanous transluminal coronary angioplasty). However, further animal experiments are needed to confirm the translation into clinical practice. This intriguing technology leads the way to more sophisticated and individualized coatings for the post-DES era, toward silencing of genes involved in the pathway of intimal hyperplasia.
Signal-transduction protein PII from Synechococcus elongatus PCC 7942 senses low adenylate energy charge in vitro
2011-07-22

PII proteins belong to a family of highly conserved signal-transduction proteins that occurs widely in bacteria, archaea and plants. They respond to the central metabolites ATP, ADP and 2-OG (2-oxoglutarate), and control enzymes, transcription factors and transport proteins involved in nitrogen metabolism. In the present study, we examined the effect of ADP on in vitro PII-signalling properties for the cyanobacterium Synechococcus elongatus, a model for oxygenic phototrophic organisms. Different ADP/ATP ratios strongly affected the properties of PII signalling. Increasing ADP antagonized the binding of 2-OG and directly affected the interactions of PII with its target proteins. The resulting PII-signalling properties indicate that, in mixtures of ADP and ATP, PII trimers are occupied by mixtures of adenylate nucleotides. Binding and kinetic activation of NAGK (N-acetyl-L-glutamate kinase), the controlling enzyme of arginine biosynthesis, by PII was weakened by ADP, but relief from arginine inhibition remained unaffected. On the other hand, ADP enhanced the binding of PII to PipX, a co-activator of the transcription factor NtcA and, furthermore, antagonized the inhibitory effect of 2-OG on PII–PipX interaction. These results indicate that S. elongatus PII directly senses the adenylate energy charge, resulting in target-dependent differential modification of the PII-signalling properties.
On the Role of Attention in Binocular Rivalry: Electrophysiological Evidence
2011-07-22

During binocular rivalry visual consciousness fluctuates between two dissimilar monocular images. We investigated the role of attention in this phenomenon by comparing event-related potentials (ERPs) when binocular-rivalry stimuli were attended with when they were unattended. Stimuli were dichoptic, orthogonal gratings that yielded binocular rivalry and dioptic, identically oriented gratings that yielded binocular fusion. Events were all possible orthogonal changes in orientation of one or both gratings. We had two attention conditions: In the attend-to-grating condition, participants had to report changes in perceived orientation, focussing their attention on the gratings. In the attend-to-fixation condition participants had to report changes in a central fixation target, taking attention away from the gratings. We found, surprisingly, that attending to rival gratings yielded a smaller ERP component (the N1, from 160-210 ms) than attending to the fixation target. To explain this paradoxical effect of attention, we propose that rivalry occurs in the attend-to-fixation condition (we found an ERP signature of rivalry in the form of a sustained negativity from 210-300 ms) but that the mechanism processing the stimulus changes is more adapted in the attend-to-grating condition than in the attend-to-fixation condition. This is consistent with the theory that adaptation gives rise to changes of visual consciousness during binocular rivalry.
Three Potential Role Models for the Korean Innovation System: USA, Japan and Germany
2011-07-23

This article analyzes the Korean innovation system and presents suggestions for its further improvement on the basis of three other country models, that of the U.S., Japan and Germany. We suggest that innovation systems are embedded in their respective managerial, economic, socio-political, and ultimately cultural context and that those contextual factors exert a significant influence on a national innovation system. Furthermore, we propose that the influence of those contextual factors result in innovation systems that are either more transformational or incremental in nature. We conclude that Korea has (like Japan) due to its societal context a particular strength in incremental innovations but will increasingly need to build up its ability to generate also transformational innovations (a particular strength of the US model). Due to distinct differences in the societal context, it might be difficult, however, for Korea to follow the U.S. model. We suggest, therefore, that Korea might find some valuable lessons in the German innovation system, particularly regarding small and medium enterprises.
A 2 × 2 taxonomy of multilevel latent contextual models: Accuracy–bias trade-offs in full and partial error correction models.
2011-07-25

In multilevel modeling, group-level variables (L2) for assessing contextual effects are frequently generated by aggregating variables from a lower level (L1). A major problem of contextual analyses in the social sciences is that there is no error-free measurement of constructs. In the present article, 2 types of error occurring in multilevel data when estimating contextual effects are distinguished: unreliability that is due to measurement error and unreliability that is due to sampling error. The fact that studies may or may not correct for these 2 types of error can be translated into a 2 × 2 taxonomy of multilevel latent contextual models comprising 4 approaches: an uncorrected approach, partial correction approaches correcting for either measurement or sampling error (but not both), and a full correction approach that adjusts for both sources of error. It is shown mathematically and with simulated data that the uncorrected and partial correction approaches can result in substantially biased estimates of contextual effects, depending on the number of L1 individuals per group, the number of groups, the intraclass correlation, the number of indicators, and the size of the factor loadings. However, the simulation study also shows that partial correction approaches can outperform full correction approaches when the data provide only limited information in terms of the L2 construct (i.e., small number of groups, low intraclass correlation). A real-data application from educational psychology is used to illustrate the different approaches.
Response of the benthic foraminiferal community to a simulated short-term phytodetritus pulse in the abyssal North Pacific
2011-07-25

Foraminifera are an important faunal element of the abyssal ecosystem and largely depend on deposited particulate organic matter from the photic zone to sustain their metabolism for growth and reproduction. However, their role in the carbon cycle in deep-sea sediments is insufficiently studied. We investigated benthic foraminifera at Station M (4000 m depth) in the Northeast Pacific and assessed the response of individual species to a simulated phytodetritus pulse during an in situ feeding experiment. Sediments were incubated for 4 d with 13C-labeled diatoms (Thalassiosira weissflogii) applied to the sediment surface. The living foraminiferal community (&gt;0.063 mm) of the upper 3 cm contained &gt;100 species and was strongly dominated by a few taxa of soft-walled saccamminids. Population density of the entire living foraminiferal community was highest at the sediment surface (mean ± SD = 279 ± 72 ind. 10 cm−3 in background and 13C-incubated cores) and decreased gradually with depth. Large differences were observed in the uptake of the algal material among species and between depth levels. During the experiment, 0.82 mg C m−2 were ingested, mainly by calcareous (~60%) and agglutinated (~40%) foraminifera. Uptake was highest at the sediment surface and 3 to 5 times less in deeper sediment horizons. Despite clear signs of vitality and a strong representation in the foraminiferal community, none of the soft-walled species showed a noticeable response to the offered algal material. We conclude that soft-walled foraminifera may not be important to the short-term phytodetrital matter cycling at the abyssal sea floor.
Gas Phase Structures, Energetics, and Potential Energy Surfaces of Disilacyclohexanes
2011-07-25

The molecular structures of 1,4-, 1,3-, and 1,2-disilacyclohexanes (denoted as 14, 13, and 12, respectively) were investigated by means of gas electron diffraction (GED). Each molecule was found to possess a chair as the most stable conformation in the gas phase, the point group being C(2h), C(s), and C(2), respectively. Experimental GED structures are in good agreement with theoretical calculations (MP2/cc-pVTZ and B3LYP/cc-pVTZ). A qualitative ring strain analysis suggests 14 to be the most stable and 12 the least stable of the parent disilacyclohexanes. Relative energy calculations with the G4 model chemistry protocol, on the other hand, predict 13 to be the most stable isomer, 5.9 and 14.2 kcal/mol more stable than 14 and 12, respectively. The enhanced stability of 13 compared to 14 is in agreement with an analysis on endocyclic bond lengths and bond polarities. The heats of formation (G4 calculations) are predicted to be -12.3, -18.1, and -3.9 kcal/mol for 14, 13, and 12, respectively. The potential energy surface (PES) and the lowest energy path for the chair-to-chair inversion have been calculated for each isomer. In addition to the two chair forms in each case and some half-chair or sofa-like transition states (four in the case of 14, and two in the case of 13), there are two twist forms found as stationary points on the PES of 14, six twist and six boat forms on the PES of 13, and four twist and six boat forms on the PES of 12.
Testing the language of German cerebral palsy patients with right hemispheric language organization after early left hemispheric damage
2011-07-25

Language functions are generally represented in the left cerebral hemisphere. After early (prenatally acquired or perinatally acquired) left hemispheric brain damage language functions may be salvaged by reorganization into the right hemisphere. This is different from brain lesions acquired in adulthood which normally lead to aphasia. Right hemispheric reorganized language (RL) is not associated with obvious language deficits. In this pilot study we compared a group of German-speaking patients with left hemispheric brain damage and RL with a group of matched healthy controls. The novel combination of reliable language lateralization as assessed by neuroimaging (functional magnetic resonance imaging) and specific linguistic tasks revealed significant differences between patients with RL and healthy controls in both language comprehension and production. Our results provide evidence for the hypothesis that RL is significantly different from normal left hemispheric language. This knowledge can be used to improve counselling of parents and to develop specific therapeutic approaches.
Early-life environment influencing susceptibility to cytomegalovirus infection: evidence from the Leiden Longevity Study and the Longitudinal Study of Aging Danish Twins
2011-07-25

SUMMARY Human cytomegalovirus (CMV) is a common herpesvirus establishing lifelong persisting infection, which has been implicated in immunosenescence and mortality in the elderly. Little is known about how and when susceptibility to CMV infection is determined. We measured CMV seroprevalence in two genetically informative cohorts. From the Leiden Longevity Study (LLS) we selected long-lived sib-pairs ( n =844) and their middle-aged offspring and the offspring's partners ( n =1452). From the Longitudinal Study of Aging Danish Twins (LSADT) 604 (302 pairs) same-sex monozygotic (MZ) and dizygotic (DZ) twins aged 73–94 years were included ( n =302 pairs). Offspring of the long-lived LLS participants had significantly lower seroprevalence of CMV compared to their partners (offspring: 42% vs . partners: 51%, P =0·003). Of 372 offspring living with a CMV-positive partner, only 58% were infected. The corresponding number for partners was 71% ( P &lt;0·001). In the LSADT, MZ and DZ twins had high and similar CMV-positive concordance rates (MZ: 90% vs . DZ: 88%, P =0·51) suggesting that shared family environment accounts for the similarity within twin pairs. Our findings suggest that susceptibility to CMV infection – even under continuous within-partnership exposure – appears to be more strongly influenced by early-life environment than by genetic factors and adult environment.
New approaches to boolean quantifier elimination
2011-07-25

We present four different approaches for existential Boolean quantifier elimination, based on model enumeration, resolution, knowledge compilation with projection, and substitution. We point out possible applications in the area of verification and we present preliminary benchmark results of the different approaches.
Boolean Gröbner bases in SAT solving
2011-07-25

We want to incorporate the reasoning power of Boolean Gröbner bases into modern SAT solvers. There are many starting points where to plug in the Gröbner bases engine in the SAT solving process. As a first step we chose the learning part where new consequences (lemmas) of the original formula are deduced. This paper shows first promising results, also published at the CASC 2010 in Armenia [1].
Common variants at VRK2 and TCF4 conferring risk of schizophrenia
2011-07-26

Common sequence variants have recently joined rare structural polymorphisms as genetic factors with strong evidence for association with schizophrenia. Here we extend our previous genome-wide association study and meta-analysis (totalling 7 946 cases and 19 036 controls) by examining an expanded set of variants using an enlarged follow-up sample (up to 10 260 cases and 23 500 controls). In addition to previously reported alleles in the major histocompatibility complex region, near neurogranin (NRGN) and in an intron of transcription factor 4 (TCF4), we find two novel variants showing genome-wide significant association: rs2312147[C], upstream of vaccinia-related kinase 2 (VRK2) [odds ratio (OR) = 1.09, P = 1.9 × 10(-9)] and rs4309482[A], between coiled-coiled domain containing 68 (CCDC68) and TCF4, about 400 kb from the previously described risk allele, but not accounted for by its association (OR = 1.09, P = 7.8 × 10(-9)).
Spontaneous re‐eruption of a permanent maxillary central incisor after 15 years of ankylosis – a case report
2011-07-26

Abstract – Intrusion injuries are considered among the most severe forms of dental trauma, potentially leading to ankylosis as a late consequence. In 1991, a 7‐year‐old boy suffered a traumatic intrusion leading to an infraposition of tooth 21 along with its immobility. Based on the clinical findings, including bright‐sounding percussion testing, disappearance of the periodontal space and a failed attempt at orthodontic movement, a diagnosis of ankylosis was made. Following prosthetic restoration of the infrapositioned tooth, spontaneous re‐eruption occurred 15 years later. With the help of a partial multibracket appliance, the tooth could be adjusted to occlusal level and was then restored to the patient’s satisfaction. Radiographically, it was demonstrated that extrusion of the tooth had been accompanied by a significant gain in local alveolar bone volume. While a wait‐and‐see strategy cannot be recommended as a treatment option following ankylosis, considering that spontaneous re‐eruption after several years is an extremely rare finding, elucidating the mechanisms at work in spontaneous re‐eruption at a cellular level might create an opportunity for iatrogenic triggering of re‐eruption, thus paving the way to new forms of therapy.