Miracle-dz/UniFAR-FTUs huggingface dataset:
Trinitrophenyl-ATP blocks colonic Cl- channels in planar phospholipid bilayers. Evidence for two nucleotide binding sites

Outwardly rectifying 30-50-pS Cl- channels mediate cell volume regulation and transepithelial transport. Several recent reports indicate that rectifying Cl- channels are blocked after addition of ATP to the extracellular bath (Alton, E. W. F. W., S. D. Manning, P. J. Schlatter, D. M. Geddes, and A. J. Williams. 1991. Journal of Physiology. 443:137-159; Paulmichl, M., Y. Li, K. Wickman, M. Ackerman, E. Peralta, and D. Clapham. 1992. Nature. 356:238-241). Therefore, we decided to conduct a more detailed study of the ATP binding site using a higher affinity probe. We tested the ATP derivative, 2',3',O-(2,4,6- trinitrocyclohexadienylidene) adenosine 5'-triphosphate (TNP-ATP), which has a high affinity for certain nucleotide binding sites. Here we report that TNP-ATP blocked colonic Cl- channels when added to either bath and that blockade was consistent with the closed-open-blocked kinetic model. The TNP-ATP concentration required for a 50% decrease in open probability was 0.27 microM from the extracellular (cis) side and 20 microM from the cytoplasmic (trans) side. Comparison of the off rate constants revealed that TNP-ATP remained bound 28 times longer when added to the extracellular side compared with the cytoplasmic side. We performed competition studies to determine if TNP-ATP binds to the same sites as ATP. Addition of ATP to the same bath containing TNP-ATP reduced channel amplitude and increased the time the channel spent in the open and fast-blocked states (i.e., burst duration). This is the result expected if TNP-ATP and ATP compete for block, presumably by binding to common sites. In contrast, addition of ATP to the bath opposite to the side containing TNP-ATP reduced amplitude but did not alter burst duration. This is the result expected if opposite-sided TNP- ATP and ATP bind to different sites. In summary, we have identified an ATP derivative that has a nearly 10-fold higher affinity for reconstituted rectifying colonic Cl- channels than any previously reported blocker (Singh, A. K., G. B. Afink, C. J. Venglarik, R. Wang, and R. J. Bridges. 1991. American Journal of Physiology. 260 [Cell Physiology. 30]:C51-C63). Thus, TNP-ATP should be useful in future studies of ion channel nucleotide binding sites and possibly in preliminary steps of ion channel protein purification. In addition, we have obtained good evidence that there are at least two nucleotide binding sites located on opposite sides of the colonic Cl- channel and that occupancy of either site produces a blocked state.
Wnt signaling in hematopoiesis: Crucial factors for self‐renewal, proliferation, and cell fate decisions

A large number of studies from many different laboratories have implicated the Wnt signaling pathway in regulation of hematopoiesis. However, different inducible gain‐ and loss‐of‐function approaches yielded controversial and some times contradictory results. In this prospect we will review the current ideas on Wnt signaling in hematopoiesis and early lymphopoiesis. Reviewing this large body of knowledge let us to hypothesize that different levels of activation of the pathway, dosages of Wnt signaling required and the interference by other signals in the context of Wnt activation collectively explain these controversies. Besides differences in dosage, differences in biological function of Wnt proteins in various blood cell types also is a major factor to take into account. Our own work has shown that while in the thymus Wnt signaling provides cytokine‐like, proliferative stimuli to developing thymocytes, canonical Wnt signaling in HSC regulates cell fate decisions, in particular self‐renewal versus differentiation. J. Cell. Biochem. 109: 844–849, 2010. © 2010 Wiley‐Liss, Inc.
Differential efficiency, market structure and price

A persistent question in industrial economics is the underpinning of the link between market concentration and price. How much of the link can be attributed to market power and how much to market efficiency? This paper develops a theoretical model to address that question. Applied to the US portland cement industry, the model indicates that both impacts matter. In relative terms, however, the market power effect is twice as large as the efficiency effect. An implication for merger policy is that the beneficial efficiency effects of mergers may not be obtained without the detrimental market power effects as well.
Architecture implications of pads as a scarce resource

Due to non-ideal technology scaling, delivering a stable supply voltage is increasingly challenging. Furthermore, competition for limited chip interface resources (i.e., C4 pads) between power supply and I/O, and the loss of such resources to electromigration, means that constructing a power delivery network (PDN) that satisfies noise margins without compromising performance is and will remain a critical problem for architects and circuit designers alike. Simple guardbanding will no longer work, as the consequent performance penalty will grow with technology scaling. In this paper, we develop a pre-RTL PDN model, VoltSpot, for the purpose of studying the performance and noise tradeoffs among power supply and I/O pad allocation, the effectiveness of noise mitigation techniques, and the consequent implications of electromigration-induced PDN pad failure. Our simulations demonstrate that, despite their integral role in the PDN, power/ground pads can be aggressively reduced (by conversion into I/O pads) to their electromigration limit with minimal performance impact from extra voltage noise - provided the system implements a suitable noise-mitigation strategy. The key observation is that even though reducing power/ground pads significantly increases the number of voltage emergencies, the average noise amplitude increase is small. Overall, we can triple I/O bandwidth while maintaining target lifetimes and incurring only 1.5% slowdown.
A review of results after implantation of a secondary intraocular lens to correct residual refractive error after cataract surgery

Purpose The purpose of this study was to provide clinical outcomes data related to secondary intraocular lens (IOL) implantation for the correction of residual refractive error after cataract surgery. Patients and methods A chart review was conducted to identify all eyes implanted with the monofocal spherical or toric AddOn® secondary IOL. Data were collated from charts where uncomplicated initial cataract surgery was completed. Measures of interest included the original IOL implanted, the postoperative refractive error (before secondary IOL implantation) and the associated corrected and uncorrected visual acuities (VAs). Postoperative data of interest included the residual refractive error, the best-corrected visual acuity (BCVA) and uncorrected visual acuity (UCVA). Results Refractive and VA data from 1 week to 3 months post-surgery were available for 46 of 70 eyes implanted with a secondary IOL by one surgeon at one practice between 4/15 and 3/17. There was a statistically significant improvement in UCVA of about 2 lines after surgery (p<0.01), with no change in BCVA (p=0.94). No eyes lost a line of BCVA. There was a statistically significant reduction in the absolute magnitude of the residual spherical equivalent refractive error (p<0.01). In the 10 cases with a toric secondary IOL, there was a statistically significant reduction in refractive cylinder (p<0.01). Conclusion The secondary IOL studied here appears to be a viable surgical option to correct residual refractive error after primary IOL implantation.
Barcoded Pyrosequencing Reveals That Consumption of Galactooligosaccharides Results in a Highly Specific Bifidogenic Response in Humans

Prebiotics are selectively fermented ingredients that allow specific changes in the gastrointestinal microbiota that confer health benefits to the host. However, the effects of prebiotics on the human gut microbiota are incomplete as most studies have relied on methods that fail to cover the breadth of the bacterial community. The goal of this research was to use high throughput multiplex community sequencing of 16S rDNA tags to gain a community wide perspective of the impact of prebiotic galactooligosaccharide (GOS) on the fecal microbiota of healthy human subjects. Fecal samples from eighteen healthy adults were previously obtained during a feeding trial in which each subject consumed a GOS-containing product for twelve weeks, with four increasing dosages (0, 2.5, 5, and 10 gram) of GOS. Multiplex sequencing of the 16S rDNA tags revealed that GOS induced significant compositional alterations in the fecal microbiota, principally by increasing the abundance of organisms within the Actinobacteria. Specifically, several distinct lineages of Bifidobacterium were enriched. Consumption of GOS led to five- to ten-fold increases in bifidobacteria in half of the subjects. Increases in Firmicutes were also observed, however, these changes were detectable in only a few individuals. The enrichment of bifidobacteria was generally at the expense of one group of bacteria, the Bacteroides. The responses to GOS and the magnitude of the response varied between individuals, were reversible, and were in accordance with dosage. The bifidobacteria were the only bacteria that were consistently and significantly enriched by GOS, although this substrate supported the growth of diverse colonic bacteria in mono-culture experiments. These results suggest that GOS can be used to enrich bifidobacteria in the human gastrointestinal tract with remarkable specificity, and that the bifidogenic properties of GOS that occur in vivo are caused by selective fermentation as well as by competitive interactions within the intestinal environment.
Fast Non-Monotone Submodular Maximisation Subject to a Matroid Constraint

In this work we present the first practical $\left(\frac{1}{e}-\epsilon\right)$-approximation algorithm to maximise a general non-negative submodular function subject to a matroid constraint. Our algorithm is based on combining the decreasing-threshold procedure of Badanidiyuru and Vondrak (SODA 2014) with a smoother version of the measured continuous greedy algorithm of Feldman et al. (FOCS 2011). This enables us to obtain an algorithm that requires $O(\frac{nr^2}{\epsilon^4} \big(\frac{a+b}{a}\big)^2 \log^2({\frac{n}{\epsilon}}))$ value oracle calls, where $n$ is the cardinality of the ground set, $r$ is the matroid rank, and $ b, a \in \mathbb{R}^+$ are the absolute values of the minimum and maximum marginal values that the function $f$ can take i.e.: $ -b \leq f_S(i) \leq a$, for all $i\in E$ and $S\subseteq E$, (here, $E$ is the ground set). The additional value oracle calls with respect to the work of Badanidiyuru and Vondrak come from the greater spread in the sampling of the multilinear extension that the possibility of negative marginal values introduce.
Online and stochastic survivable network design

Consider the edge-connectivity survivable network design problem: given a graph G = (V,E) with edge-costs, and edge-connectivity requirements rij for every pair of vertices i,j, find an (approximately) minimum-cost network that provides the required connectivity. While this problem is known to admit good approximation algorithms in the offline case, no algorithms were known for this problem in the online setting. In this paper, we give a randomized O(rmax log3 n) competitive online algorithm for this edge-connectivity network design problem, where rmax = maxij rij. Our algorithms use the standard embeddings of graphs into random subtrees (i.e., into singly connected subgraphs) as an intermediate step to get algorithms for higher connectivity. Our results for the online problem give us approximation algorithms that admit strict cost-shares with the same strictness value. This, in turn, implies approximation algorithms for (a) the rent-or-buy version and (b) the (two-stage) stochastic version of the edge-connected network design problem with independent arrivals. For these two problems, if we are in the case when the underlying graph is complete and the edge-costs are metric (i.e., satisfy the triangle inequality), we improve our results to give O(1)-strict cost shares, which gives constant-factor rent-or-buy and stochastic algorithms for these instances.
Efficient Ranking on Entity Graphs with Personalized Relationships

Authority flow techniques like PageRank and ObjectRank can provide personalized ranking of typed entity-relationship graphs. There are two main ways to personalize authority flow ranking: Node-based personalization, where authority originates from a set of user-specific nodes; edge-based personalization, where the importance of different edge types is user-specific. We propose the first approach to achieve efficient edge-based personalization using a combination of precomputation and runtime algorithms. In particular, we apply our method to ObjectRank, where a personalized weight assignment vector (WAV) assigns different weights to each edge type or relationship type. Our approach includes a repository of rankings for various WAVs. We consider the following two classes of approximation: (a) SchemaApprox is formulated as a distance minimization problem at the schema level; (b) DataApprox is a distance minimization problem at the data graph level. SchemaApprox is not robust since it does not distinguish between important and trivial edge types based on the edge distribution in the data graph. In contrast, DataApprox has a provable error bound. Both SchemaApprox and DataApprox are expensive so we develop efficient heuristic implementations, ScaleRank and PickOne respectively. Extensive experiments on the DBLP data graph show that ScaleRank provides a fast and accurate personalized authority flow ranking.
Common genome‐wide patterns of transcript accumulation underlying the wing polyphenism and polymorphism in the pea aphid (Acyrthosiphon pisum)

SUMMARY The pea aphid, Acyrthosiphon pisum, exhibits several environmentally cued polyphenisms, in which discrete, alternative phenotypes are produced. At low‐density, parthenogenetic females produce unwinged female progeny, but at high‐density females produce progeny that develop with wings. These alternative phenotypes represent a solution to the competing demands of dispersal and reproduction. Males also develop as either winged or unwinged, but these alternatives are determined by a genetic polymorphism. Winged and unwinged males are morphologically less distinct from each other than winged and unwinged females, possibly because males experience fewer trade‐offs between dispersal and reproduction. To assess whether shared physiological differences mirror the shared morphological differences that characterize the wing polyphenism and polymorphism, we used a cDNA microarray representing an estimated 10% of the coding genome (1734 genes) to examine differential transcript accumulation between winged and unwinged females and males. We identified several transcripts that differentially accumulate between winged and unwinged morphs in both sexes, the majority of which are involved in energy production. Unexpectedly, the extent of differential transcript accumulation between winged and unwinged morphs was greater for adult males than for adult females. Together, these results suggest not only that similar physiological differences underlie the polyphenism and polymorphism, but that male morphs, like females, are subject to trade‐offs between reproduction and dispersal that are reflected in levels of transcript accumulation and possibly genome‐wide patterns of gene regulation. These data also provide a baseline for future studies of the molecular and physiological basis of life‐history trade‐offs.
The rise of the body bots [robotic exoskeletons]

This paper discusses the current status of the research and development on robotic exoskeletons for both commercial and military applications in Japan and the US. Designed to help elderly and disabled people walk, climb stairs, and carry things around, the Japanese exoskeleton, called HAL-5, is set to hit the market in November 2005. Meanwhile, in the US, the most advanced exoskeleton projects are currently underway at the University of California and at Sacros Research Corp. Both groups are working on a second-generation exoskeleton that is a huge improvement over its predecessor. These projects appear to be the first of a platoon of considerably more capable exoskeletons aimed at real-world uses that may soon become part of the mainstream. While most of these systems are designed for the physically weak or disabled people, researchers are quick to mention other commercial possibilities including their use for rescue and emergency operations, moving furniture and other heavy objects, and even construction work.
Humanoid robot orientation stabilization by shoulder joint motion during locomotion

Arm swing action is a natural phenomenon that emerges in biped locomotion. A shoulder torque reference generation method is introduced in this paper to utilize arms of a humanoid robot during locomotion. Main idea of the technique is the employment of shoulder joint actuation torques in order to stabilize body orientation. The reference torques are computed by a method which utilizes proportional and derivative actions. Body orientation angles serve as the inputs of this system. The approach is tested via simulations with the 3D full-dynamics model of the humanoid robot SURALP (Sabanci University Robotics Research Laboratory Platform). Results indicate that the method is successful in reducing oscillations of body angles during bipedal walking.
Solving geometric constraints by iterative projections and backprojections

Most geometric constraint problems can be reduced to give coordinates to a set of points from a subset of their pairwise distances. By exploiting this fact, this paper presents an algorithm that solves geometric constraint systems by iteratively reducing and expanding the dimension of the problem. In general, these projection/backprojection iterations permit tightening the ranges for the possible solutions but, if at a given point no progress is made, the algorithm bisects the search space and proceeds recursively for both subproblems. This branch-and-prune strategy is shown to converge to all solutions.
Compactifications of heterotic theory on non-Kähler complex manifolds, I

We study new compactifications of the SO(32) heterotic string theory on compact complex non-K? hler manifolds. These manifolds have many interesting features like fewer moduli, torsional constraints, vanishing Euler character and vanishing first Chern class, which make the four-dimensional theory phenomenologically attractive. We take a particular compact example studied earlier and determine various geometrical properties of it. In particular we calculate the warp factor and study the sigma model description of strings propagating on these backgrounds. The anomaly cancellation condition and enhanced gauge symmetry are shown to arise naturally in this framework, if one considers the effect of singularities carefully. We then give a detailed mathematical analysis of these manifolds and construct a large class of them. The existence of a holomorphic (3,0) form is important for the construction. We clarify some of the topological properties of these manifolds and evaluate the Betti numbers. We also determine the superpotential and argue that the radial modulus of these manifolds can actually be stabilized.
Adipose inflammation and macrophage infiltration after binge ethanol and burn injury.

BACKGROUND Ethanol (EtOH) exposure prior to traumatic injury, such as a burn, elevates systemic and local inflammatory responses and increases morbidity and mortality. Adipose is a large tissue mass that is often inflamed during obesity or other stresses, which disturbs metabolic homeostasis. To date, there has been little investigation into the inflammatory response of adipose tissue after combined EtOH exposure and burn injury. METHODS Two EtOH exposure regimens were utilized to examine the role of inflammation in adipose tissue after EtOH and burn injury. Mice were either given a single or episodic binge exposure to EtOH or saline followed by scald (burn) or sham injury 30 minutes later. Twenty-four hours post injury, serum and adipose tissue were collected for assessment of inflammatory mediators. RESULTS Single binge EtOH alone induced no inflammation in adipose when compared with sham vehicle-treated mice. However, single binge EtOH followed by burn injury induced significant elevations in mRNA and protein concentrations of pro-inflammatory mediators interleukin-6 (IL-6), KC, and monocyte chemoattractant protein 1 compared with either insult alone or sham vehicle group. Additionally, EtOH exposure and burn injury significantly blunted inducible nitric oxide synthase (iNOS), indicating a complex inflammatory response. Episodic binge EtOH exposure followed by burn injury exacerbated the postburn adipose inflammatory response. The magnitude of the episodic binge-induced inflammatory parameters postburn were 2- to 5-fold greater than the response detected after a single exposure of EtOH, indicating EtOH-induced potentiation of burn-induced inflammatory response. Finally, inflammatory loci and crown-like structures in adipose were significantly increased by episodic binge EtOH and burn injury. CONCLUSIONS This is the first report of binge and burn-induced crown-like structure formation. Evidence presented herein suggests an important role for alcohol and burn as an additional mediator of adipose inflammation in postburn injury, a common complication in burn patients.
Abnormal diffusion-weighted magnetic resonance images in Creutzfeldt-Jakob disease.

BACKGROUND Traditional imaging methods, including computed tomography, routine magnetic resonance imaging (MRI), and magnetic resonance spectroscopy, have not been particularly useful in the diagnosis of Creutzfeldt-Jakob disease (CJD). Although abnormalities can be seen using these methods, the findings are evident only late in the disease or lack specificity or sensitivity. OBJECTIVE To describe abnormalities on diffusion-weighted MRIs in 4 patients with proven CJD. METHODS Diffusion-weighted MRIs were obtained on 4 patients with CJD as part of a routine MRI brain examination. RESULTS In all 4 patients, diffusion-weighted MRIs of the brain demonstrated bilateral hyperintensity in the basal ganglia. In 1 patient, the most conspicuous abnormality seen in diffusion-weighted images was in the thalamus. Two patients also demonstrated hyperintensity in the cerebral cortex on diffusion-weighted images. Only 2 of 4 patients demonstrated clear abnormalities on routine (non-diffusion-weighted) MRIs. Diffusion abnormalities were visible in 1 patient within 1 month of symptom onset. The findings were most conspicuous and extensive in the patient with the longest duration of symptoms (7 months). CONCLUSIONS Diffusion-weighted MRI might provide a noninvasive method of identifying patients with CJD. However, further investigations must be performed to determine the specificity of these findings for CJD.
FSGS permeability factor-associated nephrotic syndrome : remission after oral galactose therapy

Some cases of nephrotic syndrome in focal and segmental glomerulosclerosis (FSGS) are associated with a circulating factor, the FSGS permeability factor (FSPF). Galactose has a high affinity for FSPF, and experimental data suggest that it could reduce its activity. We describe the case of a 48-year-old male with a nephrotic syndrome found to be resistant to corticosteroids, immunosuppression and plasmaphaeresis. The patient was given oral galactose as a last resort treatment, which was followed by a remission of his nephrotic syndrome that correlated with a reduction of FSPF activity. This case is the first report of a long-standing remission of an FSPF-associated nephrotic syndrome on oral galactose therapy.