Miracle-dz/UniFAR-FTUs huggingface dataset:
Pseudorandom Correlation Breakers, Independence Preserving Mergers and their Applications

The recent line of study on randomness extractors has been a great success, resulting in exciting new techniques, new connections, and breakthroughs to long standing open problems in the following five seemingly different topics: seeded non-malleable extractors, privacy amplification protocols with an active adversary, independent source extractors (and explicit Ramsey graphs), non-malleable independent source extractors, and non-malleable codes in the split state model. Two key ingredients used in these works are correlation breakers and independence preserving mergers. By giving very efficient constructions of these two objects, we now have close to optimal solutions to the above five problems [Li17]: seeded non-malleable extractors with seed length and entropy requirement O(log n+ log(1/ ) log log(1/ )) for error ; two-round privacy amplification protocols with optimal entropy loss for security parameter up to Ω(k/ log k), where k is the entropy of the shared weak source; two-source extractors for entropy O(log n log log n); nonmalleable two-source extractors for entropy (1− γ)n with error 2−Ω(n/ log ; and non-malleable codes in the 2-split state model with rate Ω(1/ log n). However, in all cases there is still a small gap to optimum and the motivation to close this gap remains strong. On the other hand, previous techniques seem to have reached their limit and insufficient for this purpose. In this paper we introduce new techniques to recycle the entropy used in correlation breakers and independence preserving mergers. This allows us to break the barriers of previous techniques and give further improvements to the above problems. Specifically, we obtain the following results: (1) a seeded non-malleable extractor with seed length O(log n) + log(1/ ) and entropy requirement O(log log n + log(1/ )), where the entropy requirement is asymptotically optimal by a recent result of Gur and Shinkar [GS18]; (2) a two-round privacy amplification protocol with optimal entropy loss for security parameter up to Ω(k), which solves the privacy amplification problem completely; (3) a two-source extractor for entropy O( log n log log n log log log n ), which also gives an explicit Ramsey graph on N vertices with no clique or independent set of size (logN) log log log N log log log log N ; (4) a non-malleable two-source extractor for entropy (1 − γ)n with error 2−Ω(n log log n/ log ; and (5) non-malleable codes in the 2-split state model with rate Ω(log log n/ log n). Some of our techniques are similar in spirit to what has been done in previous constructions of pseudorandom generators for small space computation [Nis92, NZ96], and we believe they can be a promising way to eventually obtain optimal constructions to the five problems mentioned above. ∗Supported by NSF award CCF-1617713. Except for the communication complexity, which is of secondary concern to this problem. ISSN 1433-8092 Electronic Colloquium on Computational Complexity, Report No. 28 (2018)
Structural Insights into the Evolution of a Non-Biological Protein: Importance of Surface Residues in Protein Fold Optimization

Phylogenetic profiling of amino acid substitution patterns in proteins has led many to conclude that most structural information is carried by interior core residues that are solvent inaccessible. This conclusion is based on the observation that buried residues generally tolerate only conserved sequence changes, while surface residues allow more diverse chemical substitutions. This notion is now changing as it has become apparent that both core and surface residues play important roles in protein folding and stability. Unfortunately, the ability to identify specific mutations that will lead to enhanced stability remains a challenging problem. Here we discuss two mutations that emerged from an in vitro selection experiment designed to improve the folding stability of a non-biological ATP binding protein. These mutations alter two solvent accessible residues, and dramatically enhance the expression, solubility, thermal stability, and ligand binding affinity of the protein. The significance of both mutations was investigated individually and together, and the X-ray crystal structures of the parent sequence and double mutant protein were solved to a resolution limit of 2.8 and 1.65 Å, respectively. Comparative structural analysis of the evolved protein to proteins found in nature reveals that our non-biological protein evolved certain structural features shared by many thermophilic proteins. This experimental result suggests that protein fold optimization by in vitro selection offers a viable approach to generating stable variants of many naturally occurring proteins whose structures and functions are otherwise difficult to study.
Autonomic regulation of heart rate and QT interval in nonalcoholic cirrhosis with ascites.

BACKGROUND/AIMS Autonomic neuropathy, as indicated by alterations in standard cardiovascular tests, is frequently encountered in cirrhosis. We investigated the autonomic modulation of the heart in nonalcoholic cirrhosis with ascites by evaluating the 24-hour heart rate variability (HRV), a powerful noninvasive tool to assess the sympathovagal balance of the heart. METHODS Low (LF) and high frequency (HF) components and their ratio, and time domain indexes of HRV were evaluated in 24-hour, daytime and nighttime periods in 12 patients and 12 healthy subjects, together with the conventional and dynamic QT interval. RESULTS Cirrhotic patients had values of the mean RR interval and frequency domain indexes in the whole 24-hour period similar to those of healthy subjects, despite higher than normal plasma norepinephrine levels. Patients also showed lower LF and higher HF values than controls during the day, a reduction in time domain indexes, and no circadian rhythm of frequency domain indexes. QT parameters were similar in the 2 groups, but patients had a blunted QT rhythm and a reduced QT variability. CONCLUSIONS Patients with nonalcoholic cirrhosis and ascites have an impaired autonomic regulation of the heart, which involves both the sympathetic and the parasympathetic branches of the autonomic nervous system.
Immunohistochemical distribution and serum levels of the Ca(2+)-binding proteins MRP8, MRP14 and their heterodimeric form MRP8/14 in Crohn's disease.

In previous histochemical studies the distribution of the two Ca(2+)-binding proteins MRP8 and MRP14 as well as their heterocomplex MRP8/14 has been demonstrated in different inflammatory diseases. Monoclonal antibodies against MRP8 and MRP14 and their heterodimer MRP8/14 (27E10 epitope) were used to investigate immunohistochemically the distribution of these proteins in routinely processed small and large bowel tissues from patients with Crohn's disease (CD). Furthermore, we used a sandwich immunoassay to measure serum concentrations of MRPs in 62 patients were simultaneously assessed by the Crohn's disease activity index (CDAI) and the severity activity index of Goebell (SAI). In our immunohistochemical study, MRP8, MRP14 and heterocomplex MRP8/14 were demonstrated in the majority of granulocytes and macrophages in active CD. Additionally, a strong complex MRP8/14 immunoreactivity was present in epithelial cells adjacent to ulcerative and fissuring lesions in the bowel. Serum MRP8/14 concentrations were significantly (p < 0.0001) increased in patients with active CD (CDAI > 150, SAI > 120). No correlations were found for level of MRP14 and MRP8 alone, respectively. The follow-up of individual patients with initially active CD showed a further increase in MRP8/14 levels during acute attacks of the inflammatory process. We suggest that our assay for MRP8/14 discriminates well between active and inactive CD and may have considerable potential in the analysis of clinical disease activity in CD patients. Our morphological results confirm the finding of increased MRP8/14 serum levels in patients with active CD.
New mechanistic insights into the motile-to-sessile switch in various bacteria with particular emphasis on Bacillus subtilis and Pseudomonas aeruginosa: a review

Abstract A biofilm is a complex assemblage of microbial communities adhered to a biotic or an abiotic surface which is embedded within a self-produced matrix of extracellular polymeric substances. Many transcriptional regulators play a role in triggering a motile–sessile switch and in consequently producing the biofilm matrix. This review is aimed at highlighting the role of two nucleotide signaling molecules (c-di-GMP and c-di-AMP), toxin antitoxin modules and a novel transcriptional regulator BolA in biofilm formation in various bacteria. In addition, it highlights the common themes that have appeared in recent research regarding the key regulatory components and signal transduction pathways that help Bacillus subtilis and Pseudomonas aeruginosa to acquire the biofilm mode of life.
The complete mitochondrial genome of black-footed ferret, Mustela nigripes (Mustela, Mustelinae)

Abstract In this study, the complete mitochondrial genome sequence of black-footed ferret, Mustela nigripes, is determined for the first time. This mitogenome is 16,556 bp in length and contains 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 control region (D-loop). The overall base composition is A (32.9%), C (26.1%), G (13.8%), and T (27.2%), so the percentage of A and T (60.1%) is higher than that of G and C. Most of the genes are encoded on H-strand, except for the ND6 subunit gene and six tRNA genes. The complete mitochondrial genome sequence reported here would be useful for further phylogenetic analysis and conservation genetic studies in M. nigripes.
Ten-Year Clinical Outcome After Circumferential Pulmonary Vein Isolation Utilizing the Hamburg Approach in Patients With Symptomatic Drug-Refractory Paroxysmal Atrial Fibrillation

Background: Circumferential pulmonary vein isolation (CPVI) is increasingly performed for the treatment of symptomatic drug-refractory paroxysmal atrial fibrillation. Long-term data for >10 years after CPVI are sparse. We investigated the long-term clinical outcome and progression of paroxysmal atrial fibrillation after double-lasso and 3-dimensional electroanatomical mapping–guided CPVI. Methods and Results: From 2003 to 2004, 161 patients (mean age: 60±10 years) with symptomatic drug-refractory paroxysmal atrial fibrillation were prospectively enrolled and underwent electroanatomical mapping–guided CPVI. Right-sided and left-sided continuous circular lesions encircling the ipsilateral pulmonary veins were placed with irrigated radiofrequency energy. The procedural end point was the absence of pulmonary vein spikes 30 minutes after CPVI verified by 2 spiral catheters placed within the ipsilateral pulmonary veins (double-lasso technique). Major periprocedural complications occurred in 5 of 161 patients (3.1%). Follow-up was based on outpatient clinic visits, including Holter-ECGs and telephonic interviews. After a single procedure and median follow-up of 129.0 months (interquartile range, 124.7–133.1 months), stable sinus rhythm was present in 53 of 161 (32.9%) patients. Multiprocedural outcome after a mean of 1.73±0.9 procedures and a median follow-up of 123.4 months (interquartile range, 61.0–131.0 months) resulted in stable sinus rhythm in 101 of 161 patients (62.7%). Progression toward persistent atrial fibrillation was observed in 10 of 161 patients (6.2%). Conclusion: Ten-year single-procedural outcome of CPVI in patients with paroxysmal atrial fibrillation resulted in stable sinus rhythm in 32.9% and in 62.7% of patients after multiple procedures. The progression rate to persistent AF was remarkably low.
Caveolin-1 regulates oxidative stress-induced senescence in nucleus pulposus cells primarily via the p53/p21 signaling pathway in vitro

Previous studies have indicated that cellular senescence is a critical underlying mechanism of intervertebral disc degeneration. However, the precise mechanism by which cellular senescence accelerates disc degeneration has not been fully elucidated. Caveolin-1 has recently emerged as an important regulator of cellular senescence. Therefore, the aim of the present study was to investigate whether caveolin-1 is involved in nucleus pulposus (NP) cellular senescence during oxidative stress. PCR was used to detect caveolin-1 mRNA expression and protein expression was detected by western blotting. Caveolin-1 expression at the mRNA and protein levels was markedly increased following treatment with tert-butyl hydroperoxide, and an increase in premature senescence was observed, as determined by senescence-associated β-galactosidase staining and the decline of cellular proliferative ability. In addition, caveolin-1 gene expression was successfully knocked down by lentivirus-mediated RNA interference, which exerted a protective effect against the cellular senescence induced by oxidative stress. Notably, p53 and p21 protein expression, though not p16 protein expression, decreased with caveolin-1 silencing. The results suggested that caveolin-1 may be involved in NP cellular senescence during oxidative stress in vitro, mainly via the p53/p21 signaling pathway. Thus, caveolin-1 may represent a novel therapeutic target for the prevention of intervertebral disc degeneration.
Improving Hip-Worn Accelerometer Estimates of Sitting Using Machine Learning Methods

Purpose This study aimed to improve estimates of sitting time from hip-worn accelerometers used in large cohort studies by using machine learning methods developed on free-living activPAL data. Methods Thirty breast cancer survivors concurrently wore a hip-worn accelerometer and a thigh-worn activPAL for 7 d. A random forest classifier, trained on the activPAL data, was used to detect sitting, standing, and sit–stand transitions in 5-s windows in the hip-worn accelerometer. The classifier estimates were compared with the standard accelerometer cut point, and significant differences across different bout lengths were investigated using mixed-effect models. Results Overall, the algorithm predicted the postures with moderate accuracy (stepping, 77%; standing, 63%; sitting, 67%; sit-to-stand, 52%; and stand-to-sit, 51%). Daily level analyses indicated that errors in transition estimates were only occurring during sitting bouts of 2 min or less. The standard cut point was significantly different from the activPAL across all bout lengths, overestimating short bouts and underestimating long bouts. Conclusions This is among the first algorithms for sitting and standing for hip-worn accelerometer data to be trained from entirely free-living activPAL data. The new algorithm detected prolonged sitting, which has been shown to be the most detrimental to health. Further validation and training in larger cohorts is warranted.
Automatic Quantification of Tumour Hypoxia From Multi-Modal Microscopy Images Using Weakly-Supervised Learning Methods

In recently published clinical trial results, hypoxia-modified therapies have shown to provide more positive outcomes to cancer patients, compared with standard cancer treatments. The development and validation of these hypoxia-modified therapies depend on an effective way of measuring tumor hypoxia, but a standardized measurement is currently unavailable in clinical practice. Different types of manual measurements have been proposed in clinical research, but in this paper we focus on a recently published approach that quantifies the number and proportion of hypoxic regions using high resolution (immuno-)fluorescence (IF) and hematoxylin and eosin (HE) stained images of a histological specimen of a tumor. We introduce new machine learning-based methodologies to automate this measurement, where the main challenge is the fact that the clinical annotations available for training the proposed methodologies consist of the total number of normoxic, chronically hypoxic, and acutely hypoxic regions without any indication of their location in the image. Therefore, this represents a weakly-supervised structured output classification problem, where training is based on a high-order loss function formed by the norm of the difference between the manual and estimated annotations mentioned above. We propose four methodologies to solve this problem: 1) a naive method that uses a majority classifier applied on the nodes of a fixed grid placed over the input images; 2) a baseline method based on a structured output learning formulation that relies on a fixed grid placed over the input images; 3) an extension to this baseline based on a latent structured output learning formulation that uses a graph that is flexible in terms of the amount and positions of nodes; and 4) a pixel-wise labeling based on a fully-convolutional neural network. Using a data set of 89 weakly annotated pairs of IF and HE images from eight tumors, we show that the quantitative results of methods (3) and (4) above are equally competitive and superior to the naive (1) and baseline (2) methods. All proposed methodologies show high correlation values with respect to the clinical annotations.
Low LDL cholesterol, PCSK9 and HMGCR genetic variation, and risk of Alzheimer’s disease and Parkinson’s disease: Mendelian randomisation study

ObjeCtive To test the hypothesis that low density lipoprotein (LDL) cholesterol due to genetic variation in the genes responsible for LDL cholesterol metabolism and biosynthesis( PCSK9 and 3-hydroxy-3-methylglutaryl-CoA reductase ( HMGCR ), respectively) is associated with a high risk of Alzheimer’s disease, vascular dementia, any dementia, and Parkinson’s disease in the general population. in genetic complete data on age, sex, genotypes, and endpoints.
International employee perspectives on disability management

Abstract Purpose: To provide an international analysis of employees’ views of the influence of disability management (DM) on the workplace. Methodology: An international research team with representation from Australia, Canada, China, and Switzerland collected survey data from employees in public and private companies in their respective regions. Due to lack of availability of current measures, a research team-created survey was used and a total of 1201 respondents were collected across the four countries. Analysis: Multiple linear (enter) regression was also employed to predict DM’s influence on job satisfaction, physical health, mental health, workplace morale and reduced sickness absence, from respondents’ perceptions of whether their company provided disability prevention, stay-at-work, and return-to-work initiatives within their organization. One-way ANOVA comparisons were used to examine differences on demographic variables including company status (public versus private), union status (union versus nonunion), and gender. Results: The perceived influence of DM programs was related to perceptions of job satisfaction; whereas, relationships with mental health, physical health, morale, and sickness absence were variable according to type of DM program and whether the response was related to self or others. Difference analyses (ANOVA) revealed significantly more positive perceptions for private and nonunion organizations; no gender effects were found. Conclusions: There is perceived value of DM from the perspective of employees, especially with respect to its value for coworkers. Implications for Rehabilitation Rehabilitation efforts should continue to focus attention on the value of disability management (DM). In particular, DM that is fully committed to the biopsychosocial model would be supported by this research. Employees reported the most value in the psychosocial variables addressed by DM, such that rehabilitation professionals could focus on these valued aspects to improve buy-in from employees. The interest in coworker value may provide another avenue for rehabilitation efforts to increase uptake, by highlighting the value of intervention efforts for employee coworkers. Rehabilitation professionals in union environments may need to be particularly cognizant of the need for encouraging psychosocial and coworker value potentially seen by employees in order to increase acceptance and participation for organizational DM efforts.
Antitumor effects of baicalin on ovarian cancer cells through induction of cell apoptosis and inhibition of cell migration in vitro

Baicalin, an active flavone isolated from Scutellaria baicalensis Georgi, has been demonstrated to induce various beneficial biochemical effects such as anti-inflammatory, anti-viral, and antitumor effects. However, the antitumor mechanism of baicalin is not well understood. In the present study, baicalin was demonstrated to inhibit the viability and migration of a widely used ovarian cancer cell line, A2780, in a dose-dependent manner. MTT assays revealed that cell viability significantly decreased in ovarian cancer cells treated with baicalin compared with untreated cells, without effect on normal ovarian cells. Flow cytometric analysis indicated that baicalin suppressed cell proliferation by inducing apoptosis. The underlying mechanisms involved were indicated to be downregulation of the anti-apoptotic protein B-cell lymphoma 2 apoptosis regulator and activation of caspase-3 and −9. In addition, wound healing and transwell assays revealed that cell migratory potential and expression of matrix metallopeptidase (MMP)-2 and MMP-9 were significantly inhibited when cells were exposed to baicalin, compared with untreated cells. The present study therefore suggested that baicalin has the potential to be used in novel anti-cancer therapeutic formulations for treatment of ovarian cancer.
Computer-Aided Knee Joint Magnetic Resonance Image Segmentation - A Survey

Osteoarthritis (OA) is one of the major health issues among the elderly population. MRI is the most popular technology to observe and evaluate the progress of OA course. However, the extreme labor cost of MRI analysis makes the process inefficient and expensive. Also, due to human error and subjective nature, the inter- and intra-observer variability is rather high. Computer-aided knee MRI segmentation is currently an active research field because it can alleviate doctors and radiologists from the time consuming and tedious job, and improve the diagnosis performance which has immense potential for both clinic and scientific research. In the past decades, researchers have investigated automatic/semi-automatic knee MRI segmentation methods extensively. However, to the best of our knowledge, there is no comprehensive survey paper in this field yet. In this survey paper, we classify the existing methods by their principles and discuss the current research status and point out the future research trend in-depth.
Distributed Manufacturing Scheduling Using Intelligent Agents

Manufacturing scheduling is an optimization process that allocates limited manufacturing resources over time among parallel and sequential manufacturing activities. This allocation must obey a set of rules or constraints that reflect the temporal relationships between manufacturing activities and the capacity limitations of a set of shared resources. The allocation also affects a schedule's optimality with respect to criteria such as cost, lateness, or throughput. The globalization of manufacturing makes such optimization increasingly important. To survive in this competitive market, manufacturing enterprises must increase their productivity and profitability through greater shop floor agility. Agent-based manufacturing scheduling systems are a promising way to provide this optimization.