Miracle-dz/UniFAR-FTUs huggingface dataset:
From valid inequalities to heuristics: a unified view of primal-dual approximation algorithms in covering problems

In recent years approximation algorithms based on primal-dual methods have been successfully applied to a broad class of discrete optimization problems. In this paper, we propose a generic primal-dual framework to design and analyze approximation algorithms for integer programming problems of the covering type that uses valid inequalities in its design. The worst-case bound of the proposed algorithm is related to a fundamental relationship (called strength) between the set of valid inequalities and the set of minimal solutions to the covering problems. In this way, we can construct an approximation algorithm simply by constructing the required valid inequalities. We apply the proposed algorithm to several problems, such as covering problems related to totally balanced matrices, cyclic scheduling, vertex cover, general set covering, intersections of polymatroids, and several network design problems attaining (in most cases) the best worst-case bound known in the literature.
Brain Oligomeric &bgr;-Amyloid but Not Total Amyloid Plaque Burden Correlates With Neuronal Loss and Astrocyte Inflammatory Response in Amyloid Precursor Protein/Tau Transgenic Mice

It has long been assumed that &bgr;-amyloid (A&bgr;) had to assemble into fibrillar amyloid plaques to exert its neurotoxic effects in Alzheimer disease. An alternative hypothesis is that soluble oligomers ofA&bgr; play a much larger role in neuronal damage than the insoluble component. We have tested these competing hypotheses in vivo by studying the clinicopathologic correlates of oligomeric A&bgr; species and classic fibrillar amyloid plaques in the brains of double-transgenic APPsw-tauvlw mice up to 17 months of age. Biochemical and immunohistochemical measures of brain oligomeric A&bgr; exponentially increased with age. Oligomeric A&bgr; load correlated with morphological markers of fibrillar A&bgr; deposition. In contrast to total amyloid plaque burden, the amount of oligomeric A&bgr; deposits labeled by the conformational epitope-specific antibody Nab61 closely correlated with neuronal loss and numbers of astrocytes in the entorhinal cortex and the CA1 hippocampal subfield. However, like other morphological A&bgr;measurements, brain oligomeric A&bgr; burden did not correlate well with memory deficits in these mice. The number of glial fibrillary acidic protein-positive astrocytes in entorhinal cortex and CA1 most tightly correlated with memory impairment and neuronal cell loss. Based on these findings, we hypothesize that the astrocyte response, which is likely triggered by brain oligomeric A&bgr; accumulation, adversely affects cognition and might also contribute to neuronal cell death in this model.
Combined Network Design and Multiperiod Pricing: Modeling, Solution Techniques, and Computation

In this paper we describe an efficient algorithm for solving novel optimization models arising in the context of multiperiod capacity expansion of optical networks. We assume that the network operator must make investment decisions over a multiperiod planning horizon while facing rapid changes in transmission technology, as evidenced by a steadily decreasing per-unit cost of capacity. We deviate from traditional and monopolistic models in which demands are given as input parameters, and the objective is to minimize capacity deployment costs. Instead, we assume that the carrier sets end-to-end prices of bandwidth at each period of the planning horizon. These prices determine the demands that are to be met, using a plausible and explicit price-demand relationship; the resulting demands must then be routed, requiring an investment in capacity. The objective of the optimization is now to simultaneously select end-to-end prices of bandwidth and network capacities at each period of the planning horizon, so as to maximize the overall net present value of expanding and operating the network. In the case of typical large-scale optical networks with protection requirements, the resulting optimization problems pose significant challenges to standard optimization techniques. The complexity of the model, its nonlinear nature, and the large size of realistic problem instances motivates the development of efficient and scalable solution techniques. We show that while general-purpose nonlinear solvers are typically not adequate for the task, a specialized decomposition scheme is able to handle large-scale instances of this problem in reasonable time, producing solutions whose net present value is within a small tolerance of the optimum.
Osteogenesis imperfecta: Ultrastructural and histological findings on examination of skin revealing novel insights into genotype-phenotype correlation

ABSTRACT Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders of bone formation, resulting in low bone mass and an increased propensity to fracture. Over 90% of patients with OI have a mutation in COL1A1/COL1A2, which shows an autosomal dominant pattern of inheritance. In-depth phenotyping and in particular, studies involving manifestations in the skin connective tissue have not previously been undertaken in OI. The aims of the study were to perform histological and ultrastructural examination of skin biopsies in a cohort of patients with OI; to identify common and distinguishing features in order to inform genotype-phenotype correlation; and to identify common and distinguishing features between the different subtypes of OI. As part of the RUDY (Rare Diseases in Bone, Joints and/or Blood Vessels) study, in collaboration with the NIHR Rare Diseases Translational Research Collaboration, we undertook a national study of skin biopsies in patients with OI. We studied the manifestations in the skin connective tissue and undertook in-depth clinical and molecular phenotyping of 16 patients with OI. We recruited 16 patients: analyses have shown that in type 1 collagen mutation positive patients (COL1A1/ COL1A2) (n-4/16) consistent findings included: variable collagen fibril diameter (CFD) and presence of collagen flowers. Histological examination in these patients showed an increase in elastic fibers that are frequently fragmented and clumped. These observations provide evidence that collagen flowers and CFD variability are consistent features in OI due to type 1 collagen defects and reinforce the need for accurate phenotyping in conjunction with genomic analyses.
Effect of cyclic loading on axial displacement of abutment into implant with internal tapered connection: a pilot study

statistically significant. Results: The mean axial displacement after 10,000 cycles were 0.714 ± 0.488 ㎛ in Ext group, 5.286 ± 1.604 ㎛ in Int-1 group, and 11.429 ± 1.902 ㎛ in Int-2 group. In the pattern analysis, Int-1 and Int-2 group showed continuous axial displacement at 10,000 cycles. There was no declining pattern of axial displacement in the Ext group. Conclusion: The pattern of linear mixed model in Ext group showed no axial displacement. There were continuous axial displacements in abutment-implant assemblies in the Int-1 and Int-2 group at 10,000 cycles. More axial displacement was found in Int-2 group than in Int-1 group. (J Korean Acad Prosthodont 2013;51:315-22)
Prognostic Value of Flow‐Mediated Vasodilation in Brachial Artery and Fingertip Artery for Cardiovascular Events: A Systematic Review and Meta‐Analysis

Background Endothelial dysfunction plays a pivotal role in cardiovascular disease progression, and is associated with adverse events. The purpose of this systematic review and meta‐analysis was to investigate the prognostic magnitude of noninvasive peripheral endothelial function tests, brachial artery flow‐mediated dilation (FMD), and reactive hyperemia–‐peripheral arterial tonometry (RH‐PAT) for future cardiovascular events. Methods and Results Databases of MEDLINE, EMBASE, and the Cochrane Library were systematically searched. Clinical studies reporting the predictive value of FMD or RH‐PAT for cardiovascular events were identified. Two authors selected studies and extracted data independently. Pooled effects were calculated as risk ratio (RR) for continuous value of FMD and natural logarithm of RH‐PAT index (Ln_RHI) using random‐effects models. Thirty‐five FMD studies of 17 280 participants and 6 RH‐PAT studies of 1602 participants were included in the meta‐analysis. Both endothelial function tests significantly predicted cardiovascular events (adjusted relative risk [95% CI]: 1% increase in FMD 0.88 [0.84–0.91], P<0.001, 0.1 increase in Ln_RHI 0.79 [0.71–0.87], P<0.001). There was significant heterogeneity in the magnitude of the association across studies. The magnitude of the prognostic value in cardiovascular disease subjects was comparable between these 2 methods; a 1 SD worsening in endothelial function was associated with doubled cardiovascular risk. Conclusions Noninvasive peripheral endothelial function tests, FMD and RH‐PAT, significantly predicted cardiovascular events, with similar prognostic magnitude. Further research is required to determine whether the prognostic values of these 2 methods are independent of each other and whether an endothelial function–guided strategy can provide benefit in improving cardiovascular outcomes.
To use or not to use: A stage-based approach to understanding condom use among homeless youth

This study used a stage-based approach to understand condom use behavior in a representative sample of 309 sexually active homeless youth recruited from shelters, drop-in centers, and street sites in Los Angeles County. Focusing on the youth's most recent sexual event, the three stages of condom use examined were: (1) whether the partners decided prior to the event about using condoms; (2) whether a condom was available at the event; and (3) whether a condom was used at the event. Logistic regression analysis was used to identify attitudinal, relationship, and contextual correlates of each of these three stages. Deciding ahead of time about condom use was associated with being Hispanic, level of education, condom attitudes, and various relationship characteristics (e.g., partner type, monogamy, relationship abuse), with the nature of these associations varying depending on the type of decision (i.e., deciding to use, deciding to not use). Condom availability was more likely to be reported by males, if the event was described as being special in some way, or if the event lacked privacy. Condom use was more likely among youth with more positive condom attitudes and among youth who decide ahead of time to use a condom, but less likely among those in monogamous relationships or when hard drugs were used prior to sex. Whether sexual intercourse is protected or unprotected is the end result of a series of decisions and actions by sexual partners. Results from this study illustrate how condom use can be better understood by unpacking the stages and identifying influential factors at each stage. Each stage may, in and of itself, be an important target for intervention with homeless youth.
Quasi-static Evolution in Nonassociative Plasticity: The Cap Model

Non-associative elasto-plasticity is the working model of plasticity for soil and rocks mechanics. Yet, it is usually viewed as non-variational. In this work, we prove a contrario the existence of a variational evolution for such a model under a natural capping assumption on the hydrostatic stresses and a less natural mollication of the stress admissibility constraint. The obtained elasto-plastic evolution is expressed for times that are conveniently rescaled.
A1C Variability and the Risk of Microvascular Complications in Type 1 Diabetes

OBJECTIVE—Debate remains as to whether short- or long-term glycemic instability confers a risk of microvascular complications in addition to that predicted by mean glycemia alone. In this study, we analyzed data from the Diabetes Control and Complications Trial (DCCT) to assess the effect of A1C variability on the risk of retinopathy and nephropathy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS—A1C was collected quarterly during the DCCT in 1,441 individuals. The mean A1C and the SD of A1C variability after stabilization of glycemia (from 6 months onwards) were compared with the risk of retinopathy and nephropathy with adjustments for age, sex, disease duration, treatment group, and baseline A1C. RESULTS—Multivariate Cox regression showed that the variability in A1C added to mean A1C in predicting the risk of development or progression of both retinopathy (hazard ratio 2.26 for every 1% increase in A1C SD [95% CI 1.63–3.14], P < 0.0001) and nephropathy (1.80 [1.37–2.42], P < 0.0001), with the relationship a feature in conventionally treated patients in particular. CONCLUSIONS—This study has shown that variability in A1C adds to the mean value in predicting microvascular complications in type 1 diabetes. Thus, in contrast to analyses of DCCT data investigating the effect of short-term glucose instability on complication risk, longer-term fluctuations in glycemia seem to contribute to the development of retinopathy and nephropathy in type 1 diabetes.
Variable asialoglycoprotein receptor 1 expression in liver disease: Implications for therapeutic intervention

One of the most promising strategies for the treatment of liver diseases is targeted drug delivery via the asialoglycoprotein receptor (ASGPR). The success of this approach heavily depends on the ASGPR expression level on parenchymal liver cells. In this study, we assessed the mRNA and protein expression levels of the major receptor subunit, ASGR1, in hepatocytes both in vitro and in vivo.
High Expression of FGFR4 Enhances Tumor Growth and Metastasis in Nasopharyngeal Carcinoma

Background: FGF receptor (FGFR) family can be activated by FGFs and play important roles in regulating cell growth, differentiation, migration and angiogenesis. Recent studies suggested that FGFR4 could regulate several processes including tumor progression. Nasopharyngeal carcinoma (NPC) is a malignancy with a high occurrence in Southeast Asia and Southern China. However, the molecule mechanism and the potential roles of FGFR4 in NPC remain unknown Methods: Immunohistochemistry and western blot were used to investigate the expression of FGFR4 in NPC samples. Then we used statistical analysis to evaluate the diagnostic value and the associations of FGFR4 expression with clinical parameters. In vitro studies, the effects of FGFR4 on proliferation and migration of NPC cell line CNE2 were measured by the starvation-refeeding experiment, CCK8 assay, wounding healing assay and transwell migration assay. The changes of the epithelial-mesenchymal transition (EMT) markers in CNE2 cells after knocking down the expression of FGFR4 were measured by Western blot and immunofluorescence analysis. Results: FGFR4 was overexpressed in NPC as compared with the inflammatory tissues. High expression of FGFR4 was correlated with Ki67 expression, clinical stages and prognosis in NPC patients (P<0.05). While in vitro, the upregulation of FGFR4 was accompanied with CNE2 cells released from serum starvation. Moreover, it could increase cell proliferation and migration by regulating EMT markers in CNE2 cells. Conclusion: Our data suggested that FGFR4 might induce NPC progression and act as a potential therapeutic target in NPC.
Genetic background and epigenetic modifications in the core of the nucleus accumbens predict addiction-like behavior in a rat model

Significance Determining the factors that render an individual more susceptible or resilient to cocaine addiction has great implications for treatment. We exploit a unique model to demonstrate that genetic differences in vulnerability to cocaine addiction exist in the rat. We examined gene expression and the epigenetic regulation of two genes—fibroblast growth factor (FGF2) and the dopamine D2 receptor (D2)—in the nucleus accumbens core. Low levels of D2 mRNA, via epigenetic modifications, may play a role in susceptibility to cocaine addiction. Specifically, binding of a repressive mark on histones (H3K9me3) at the D2 promoter is associated with the propensity to relapse. In contrast, low levels of FGF2, which persist even following prolonged self-administration, may protect individuals from cocaine addiction. This study provides a demonstration in the rat of a clear genetic difference in the propensity for addiction-related behaviors following prolonged cocaine self-administration. It relies on the use of selectively bred high-responder (bHR) and low-responder (bLR) rat lines that differ in several characteristics associated with “temperament,” including novelty-induced locomotion and impulsivity. We show that bHR rats exhibit behaviors reminiscent of human addiction, including persistent cocaine-seeking and increased reinstatement of cocaine seeking. To uncover potential underlying mechanisms of this differential vulnerability, we focused on the core of the nucleus accumbens and examined expression and epigenetic regulation of two transcripts previously implicated in bHR/bLR differences: fibroblast growth factor (FGF2) and the dopamine D2 receptor (D2). Relative to bHRs, bLRs had lower FGF2 mRNA levels and increased association of a repressive mark on histones (H3K9me3) at the FGF2 promoter. These differences were apparent under basal conditions and persisted even following prolonged cocaine self-administration. In contrast, bHRs had lower D2 mRNA under basal conditions, with greater association of H3K9me3 at the D2 promoter and these differences were no longer apparent following prolonged cocaine self-administration. Correlational analyses indicate that the association of H3K9me3 at D2 may be a critical substrate underlying the propensity to relapse. These findings suggest that low D2 mRNA levels in the nucleus accumbens core, likely mediated via epigenetic modifications, may render individuals more susceptible to cocaine addiction. In contrast, low FGF2 levels, which appear immutable even following prolonged cocaine exposure, may serve as a protective factor.
Oral Complications and Management Strategies for Patients Undergoing Cancer Therapy

With cancer survival rate climbing up over the past three decades, quality of life for cancer patients has become an issue of major concern. Oral health plays an important part in one's overall quality of life. However, oral health status can be severely hampered by side effects of cancer therapies including surgery, chemotherapy, radiotherapy, and hematopoietic stem cell transplantation. Moreover, prevention and treatment of these complications are often overlooked in clinical practice. The present paper aims at drawing health care professionals' attention to oral complications associated with cancer therapy by giving a comprehensive review. Brief comments on contemporary cancer therapies will be given first, followed by detailed description of oral complications associated with cancer therapy. Finally, a summary of preventive strategies and treatment options for common oral complications including oral mucositis, oral infections, xerostomia, and dysgeusia will be given.
Neural mechanisms underlying the induction and relief of perceptual curiosity

Curiosity is one of the most basic biological drives in both animals and humans, and has been identified as a key motive for learning and discovery. Despite the importance of curiosity and related behaviors, the topic has been largely neglected in human neuroscience; hence little is known about the neurobiological mechanisms underlying curiosity. We used functional magnetic resonance imaging (fMRI) to investigate what happens in our brain during the induction and subsequent relief of perceptual curiosity. Our core findings were that (1) the induction of perceptual curiosity, through the presentation of ambiguous visual input, activated the anterior insula and anterior cingulate cortex (ACC), brain regions sensitive to conflict and arousal; (2) the relief of perceptual curiosity, through visual disambiguation, activated regions of the striatum that have been related to reward processing; and (3) the relief of perceptual curiosity was associated with hippocampal activation and enhanced incidental memory. These findings provide the first demonstration of the neural basis of human perceptual curiosity. Our results provide neurobiological support for a classic psychological theory of curiosity, which holds that curiosity is an aversive condition of increased arousal whose termination is rewarding and facilitates memory.
Cat hindlimb motoneurons during locomotion. II. Normal activity patterns.

Activity patterns were recorded from 51 motoneurons in the fifth lumbar ventral root of cats walking on a motorized treadmill at a range of speeds between 0.1 and 1.3 m/s. The muscle of destination of recorded motoneurons was identified by spike-triggered averaging of EMG recordings from each of the anterior thigh muscles. Forty-three motoneurons projected to one of the quadriceps (vastus medialis, vastus lateralis, vastus intermedius, or rectus femoris) or sartorius (anterior or medial) muscles of the anterior thigh. Anterior thigh motoneurons always discharged a single burst of action potentials per step cycle, even in multifunctional muscles (e.g., sartorius anterior) that exhibited more than one burst of EMG activity per step cycle. The instantaneous firing rates of most motoneurons were lowest upon recruitment and increased progressively during a burst, as long as the EMG was still increasing. Firing rates peaked midway through each burst and tended to decline toward the end of the burst. The initial, mean, and peak firing rates of single motoneurons typically increased for faster walking speeds. At any given walking speed, early recruited motoneurons typically reached higher firing rates than late recruited motoneurons. In contrast to decerebrated cats, initial doublets at the beginning of bursts were seen only rarely. In the 4/51 motoneurons that showed initial doublets, both the instantaneous frequency of the doublet and the probability of starting a burst with a doublet decreased for faster walking speeds. The modulations in firing rate of every motoneuron were found to be closely correlated to the smoothed electromyogram of its target muscle. For 32 identified motoneurons, the unit's instantaneous frequencygram was scaled linearly by computer to the rectified smoothed EMG recorded from each of the anterior thigh muscles. The covariance between unitary frequencygram and muscle EMG was computed for each muscle. Typically, the EMG profile of the target muscle accounted for 0.88-0.96 of the variance in unitary firing rate. The EMG profiles of the other anterior thigh muscles, when tested in the same way, usually accounted only for a significantly smaller fraction of the variance. Brief amplitude fluctuations observed in the EMG envelopes were usually also reflected in the individual motoneuron frequencygrams. To further demonstrate the relationship between unitary frequencygrams and EMG, EMG envelopes recorded during walking were used as templates to generate depolarizing currents that were applied intracellularly to lumbar motoneurons in an acute spinal preparation. (ABSTRACT TRUNCATED AT 400 WORDS)