Miracle-dz/UniFAR-FTUs huggingface dataset:
Non-Viral Generation of Marmoset Monkey iPS Cells by a Six-Factor-in-One-Vector Approach

Groundbreaking studies showed that differentiated somatic cells of mouse and human origin could be reverted to a stable pluripotent state by the ectopic expression of only four proteins. The resulting pluripotent cells, called induced pluripotent stem (iPS) cells, could be an alternative to embryonic stem cells, which are under continuous ethical debate. Hence, iPS cell-derived functional cells such as neurons may become the key for an effective treatment of currently incurable degenerative diseases. However, besides the requirement of efficacy testing of the therapy also its long-term safety needs to be carefully evaluated in settings mirroring the clinical situation in an optimal way. In this context, we chose the long-lived common marmoset monkey (Callithrix jacchus) as a non-human primate species to generate iPS cells. The marmoset monkey is frequently used in biomedical research and is gaining more and more preclinical relevance due to the increasing number of disease models. Here, we describe, to our knowledge, the first-time generation of marmoset monkey iPS cells from postnatal skin fibroblasts by non-viral means. We used the transposon-based, fully reversible piggyback system. We cloned the marmoset monkey reprogramming factors and established robust and reproducible reprogramming protocols with a six-factor-in-one-construct approach. We generated six individual iPS cell lines and characterized them in comparison with marmoset monkey embryonic stem cells. The generated iPS cells are morphologically indistinguishable from marmoset ES cells. The iPS cells are fully reprogrammed as demonstrated by differentiation assays, pluripotency marker expression and transcriptome analysis. They are stable for numerous passages (more than 80) and exhibit euploidy. In summary, we have established efficient non-viral reprogramming protocols for the derivation of stable marmoset monkey iPS cells, which can be used to develop and test cell replacement therapies in preclinical settings.
Hematopoietic Stem Cell Function in a Murine Model of Sickle Cell Disease

Previous studies have shown that the sickle environment is highly enriched for reactive oxygen species (ROS). We examined the oxidative effects of sickle cell disease on hematopoietic stem cell function in a sickle mouse model. In vitro colony-forming assays showed a significant decrease in progenitor colony formation derived from sickle compared to control bone marrow (BM). Sickle BM possessed a significant decrease in the KSL (c-kit+, Sca-1+, Lineage−) progenitor population, and cell cycle analysis showed that there were fewer KSL cells in the G0 phase of the cell cycle compared to controls. We found a significant increase in both lipid peroxidation and ROS in sickle-derived KSL cells. In vivo analysis demonstrated that normal bone marrow cells engraft with increased frequency into sickle mice compared to control mice. Hematopoietic progenitor cells derived from sickle mice, however, demonstrated significant impairment in engraftment potential. We observed partial restoration of engraftment by n-acetyl cysteine (NAC) treatment of KSL cells prior to transplantation. Increased intracellular ROS and lipid peroxidation combined with improvement in engraftment following NAC treatment suggests that an altered redox environment in sickle mice affects hematopoietic progenitor and stem cell function.
ELYS regulates the localization of LBR by modulating its phosphorylation state

ABSTRACT Lamin B receptor (LBR), an inner nuclear membrane (INM) protein, contributes to the functional integrity of the nucleus by tethering heterochromatin to the nuclear envelope. We have previously reported that the depletion of embryonic large molecule derived from yolk sac (ELYS; also known as AHCTF1), a component of the nuclear pore complex, from cells perturbs the localization of LBR to the INM, but little is known about the underlying molecular mechanism. In this study, we found that the depletion of ELYS promoted LBR phosphorylation at the residues known to be phosphorylated by cyclin-dependent kinase (CDK) and serine/arginine protein kinases 1 and 2 (SRPK1 and SRPK2, respectively). These phosphorylation events were most likely to be counter-balanced by protein phosphatase 1 (PP1), and the depletion of PP1 from cells consistently caused the mislocalization of LBR. These observations point to a new mechanism regulating the localization of LBR, which is governed by an ELYS-mediated phosphorylation network. This phosphorylation-dependent coordination between INM proteins and the nuclear pore complex might be important for the integrity of the nucleus. Highlighted Article: The nuclear envelope localization of LBR is regulated through a phosphorylation network governed by ELYS, and defects in this phosphorylation network induce the aberrant phosphorylation and mislocalization of LBR.
Bot detection in rhythm games: a physiological approach

As the online game industry expands, detecting and preventing cheating in games is an increasingly important research topic. Some forms of cheating, such as the use of game bots (auto-playing game clients), are particularly challenging to identify because game bots do not violate any of the game rules; rather, they simply mimic human behavior to play the game without human intervention. The use of bots introduces fairness issues to online games, and therefore robust schemes for detecting game bots are strongly demanded. In this paper, we tackle with bots in rhythm games, which feature gameplay that incorporates eye and body coordination with music, usually a popular song. Bot detection in rhythm games is especially challenging compared with in other game genres because little information is available to distinguish the responses made by a human player from a bot. Based on the long-memoryness of the time series formed by human players' response errors to stimuli, we propose a scheme to detect the presence of human coordination mechanisms during gameplay. Based on a set of traces collected from human players and real-life game bots, we show that our scheme can accurately detect the use of game bots despite of game difficulty levels.
Phobic Anxiety, Depression, and Risk of Ventricular Arrhythmias in Patients With Coronary Heart Disease

Objective: Findings of an association between phobic anxiety and elevated risks of sudden cardiac death suggest that phobic anxiety may be related to increased risk of ventricular arrhythmias. The purpose of this study was to examine whether phobic anxiety is associated with ventricular arrhythmias in patients with documented coronary artery disease (CAD). Methods: Phobic anxiety level was measured using the Crown-Crisp phobic anxiety scale in 940 patients (660 men, 280 women) hospitalized for diagnostic cardiac catheterization between April 1999 and June 2002. Depressive symptomatology was assessed using the Beck Depression Inventory. Patients were followed for a median follow-up period of 3 years, and the occurrence of ventricular arrhythmias was determined through review of medical records. Results: Ventricular arrhythmias occurred in 97 patients and were significantly related to higher phobic anxiety after statistical adjustment for established medical and demographic determinants of arrhythmias (odds ratio = 1.40; p = .012). Depressive symptomatology was significantly correlated with phobic anxiety (r = 0.44, p < .001) and was also related to ventricular arrhythmias (odds ratio = 1.40; p = .006). The composite of depression and phobic anxiety predicted ventricular arrhythmias with a larger effect size than either depression or phobic anxiety score alone (odds ratio = 1.6, 95% confidence interval, 1.2–2.1, p = .002). Conclusions: Both phobic anxiety and depressive symptomatology predict ventricular arrhythmias in patients with CAD and may share a common factor predictive of ventricular arrhythmias. CAD = coronary artery disease; SCD = sudden cardiac death; MI = myocardial infarction; LVEF = left ventricular ejection fraction; BDI = Beck Depression Inventory; NSVT = nonsustained ventricular tachycardia; susVT = sustained ventricular tachycardia; V-fib = ventricular fibrillation; BMI = body mass index; ICD = internal cardiodefibrillator device.
Association between adherence to the Korean Food Guidance System and the risk of metabolic abnormalities in Koreans

Consumption of a diet consistent with dietary guidelines is believed to have a beneficial effect on the prevention of chronic diseases and the promotion of general health. This study was conducted to explore the relationship between adherence to the Korean Food Guidance System (KFGS), which was based on the 2010 revised KDRIs, and the risk of metabolic abnormalities. Five hundred and ninety-six Korean adults between 30 and 59 years of age were recruited by advertisement to the Bundang Jesaeng General Hospital (BJGH), and those not taking regular medications and without diagnoses of fulminant disease were included. Data were collected on anthropometric measurements, diagnostic parameters for metabolic syndrome (MetS), and 3-day dietary intakes from individuals in the study. The number of servings consumed from each food group was compared to the KFGS recommended servings for each of the 6 food groups. Poor adherence to the recommendations for servings of milk and dairy products (OR: 2.038, 1.128-3.682) was associated with a higher risk of MetS, and poor adherence to the guidelines for fruit consumption (OR: 1.849, 1.027-3.329) was associated with a higher risk for the existence an elevated waist circumference. Conversely, the consumption of meat, fish, eggs, and beans above the recommended number of servings was associated with a lower risk of having an elevated waist circumference (OR: 0.523, 0.288-0.950), and the consumption of vegetables above the recommended number of servings was associated with a reduced risk of having elevated fasting glucose (OR: 0.533, 0.298-0.954). These results suggest that adherence to the KFGS guidelines helps to prevent the development of MetS, but this association needs to be confirmed by prospective studies.
Decision problems for 3-manifolds and their fundamental groups

We survey the status of some decision problems for 3-manifolds and their fundamental groups. This includes the classical decision problems for finitely presented groups (Word Problem, Conjugacy Problem, Isomorphism Problem), and also the Homeomorphism Problem for 3-manifolds and the Membership Problem for 3-manifold groups.
High-speed event detector for embedded nanopore bio-systems

Biological measurements of microscopic phenomena often deal with discrete-event signals. The ability to automatically carry out such measurements at high-speed in a miniature embedded system is desirable but compromised by high-frequency noise along with practical constraints on filter quality and sampler resolution. This paper presents a real-time event-detection method in the context of nanopore sensing that helps to mitigate these drawbacks and allows accurate signal processing in an embedded system. Simulations show at least a 10× improvement over existing on-line detection methods.
Stochastic Deficiencies Using Precise Point Positioning

Precise Point Positioning (PPP) can be used for a wide range of applications in geodetic positioning. Providing precise clock and orbit information, a single station can be positioned in a reference frame. This leads to a very efficient processing procedure since the normal equation system is very small compared to network processing. PPP achieves very robust solutions comparable to network solutions. A drawback of PPP is that it does not respect the principle of adjacent points, because correlations between neighbouring stations are not considered. This drawback leads to a disadvantageous stochastic behaviour between adjacent stations. However, as the point positions are computed using identical orbit and clock information, correlations between the estimated coordinates still remain. The presentation focus on this fact and determines correlations between station coordinates.
A Signal Correlation Guided ATPG solver and its applications for solving difficult industrial cases

The developments of efficient SAT solvers have attracted tremendous research interest in recent years. The merits of these solvers are often compared in terms of their performance based upon a wide spread of benchmarks. In this paper, we extend an earlier-proposed solver design concept called (SCGL) Signal Correlation Guided Learning that is ATPG-based into a family of heuristics. Along with this SCGL family of heuristics, we classify benchmark examples according to their performance using the SCGL heuristics. With this study, we identify the class of problems that are uniquely suitable to be solved by using the SCGL approach. In particular, for solving difficult circuit-based problems at INTEL, our SCGL-based ATPG solver is able to achieve at least an order of magnitude speedup over the state-of-the-art SAT solvers. Our conclusion is that SCGL is a unique solver design concept that can complement heuristics proposed by others for solving circuit-oriented difficult problems.
Selection criteria for drug‐like compounds

The fast identification of quality lead compounds in the pharmaceutical industry through a combination of high throughput synthesis and screening has become more challenging in recent years. Although the number of available compounds for high throughput screening (HTS) has dramatically increased, large‐scale random combinatorial libraries have contributed proportionally less to identify novel leads for drug discovery projects. Therefore, the concept of ‘drug‐likeness’ of compound selections has become a focus in recent years. In parallel, the low success rate of converting lead compounds into drugs often due to unfavorable pharmacokinetic parameters has sparked a renewed interest in understanding more clearly what makes a compound drug‐like. Various approaches have been devised to address the drug‐likeness of molecules employing retrospective analyses of known drug collections as well as attempting to capture ‘chemical wisdom’ in algorithms. For example, simple property counting schemes, machine learning methods, regression models, and clustering methods have been employed to distinguish between drugs and non‐drugs. Here we review computational techniques to address the drug‐likeness of compound selections and offer an outlook for the further development of the field. © 2003 Wiley Periodicals, Inc. Med Res Rev, 23, No. 3, 302‐321, 2003
A Unified Approach To Control Design Using A Cooperative Co-Evolutionary Bisection Algorithm

Abstract This paper proposes a novel algorithm named as a Co-evolutionary Cooperative Bisection (CCB) algorithm as master tool for solving variety of control problems. The proposed algorithm is computationally attractive and has very favorable convergence properties. The numerical superiority of the CCB-algorithm is back to two main factors, the numerical efficiency of γ-Bisection algorithm, and the multi-population evolutionary algorithm proposed in this paper ( Cooperation + Parallelism ). To demonstrate the potential of the proposed algorithm a method for designing fixed-structure controllers that minimize an upper bound on the singular value µ is presented. The problem considered here is of significant practical interest, since many industrial controllers are constrained in order/structure and required to meet high robustness demands. Moreover, even if the controller order or structure are not restricted, the proposed algorithm has the advantage of being able to optimize over for stability multipliers and controllers simultaneously, thereby improving the chances of converging to the global minimum. Numerical examples given here confirm the computational efficiency and the excellent convergence properties of the proposed CCB-algorithm.
CBID: A Customer Behavior Identification System Using Passive Tags

Different from online shopping, in-store shopping has few ways to collect the customer behaviors before purchase. In this paper, we present the design and implementation of an on-site Customer Behavior Identification system based on passive RFID tags, named CBID. By collecting and analyzing wireless signal features, CBID can detect and track tag movements and further infer corresponding customer behaviors. We model three main objectives of behavior identification by concrete problems and solve them using novel protocols and algorithms. The design innovations of this work include a Doppler effect based protocol to detect tag movements, an accurate Doppler frequency estimation algorithm, a multi-RSS based tag localization protocol, and a tag clustering algorithm using cosine similarity. We have implemented a prototype of CBID in which all components are built by off-the-shelf devices. We have deployed CBID in real environments and conducted extensive experiments to demonstrate the accuracy and efficiency of CBID in customer behavior identification.
EyeSpy: supporting navigation through play

This paper demonstrates how useful content can be generated as a by-product of an enjoyable mobile multiplayer game. In EyeSpy, players tag geographic locations with photos or text. By locating the places in which other players' tags were created and 'confirming' them, players earn points for themselves and verify the tags' locations. As a side effect of game-play, EyeSpy produces a collection of recognisable and findable geographic details, in the form of photographs and text tags, that can be repurposed to support navigation tasks. Two user trials of the game successfully produced an archive of geo-located photographs and tags, and in a follow-up experiment we compared performance in a navigation task using photographs from the game, with geo-referenced photos collected from the Flickr website. Our experiences with EyeSpy support reflection upon the design challenges presented by 'human computation' and the production of usable by-products through mobile game-play.
Altered calcium handling in left ventricular pressure-overload hypertrophy as detected with aequorin in the isolated, perfused ferret heart.

The purpose of this study was to test the hypothesis that systolic and diastolic dysfunction in left ventricular pressure-overload hypertrophy is caused by abnormal intracellular calcium handling. Experiments were performed with intact, buffer-perfused, isovolumic ferret hearts (n = 9 hypertrophied, n = 9 control) that were loaded with the bioluminescent indicator aequorin to monitor changes in cytoplasmic calcium. In each experiment, left ventricular pressure and intracellular calcium transients were simultaneously recorded. Compared with their age-matched controls, significant hypertrophy of the left ventricle developed 4 weeks after postvalvular aortic banding; at the time the animals were killed, the left ventricular weight/body weight ratio was increased in the banded animals (5.3 x 10(-3) versus 3.6 x 10(-3), p less than 0.001). As indicated by the diastolic pressure-volume relation, left ventricular distensibility was significantly diminished in the hypertrophied hearts. In comparison to the controls, the hypertrophied hearts demonstrated a prolonged duration of isovolumic contraction (time to 90% decline from peak: 278 +/- 5.4 versus 247 +/- 10.2 msec, p less than 0.05), but a marked decrease in peak systolic midwall stress (22.4 +/- 5.0 versus 38.6 +/- 5.7 g/cm2, p less than 0.05). The increased duration of isovolumic contraction correlated with a similar prolongation of the calcium transient (time to 90% decline from peak: 245 +/- 19.5 versus 127 +/- 13.2 msec, p less than 0.05), indicating that the rate of sequestration and perhaps release of calcium by the sarcoplasmic reticulum is decreased in hypertrophy. (ABSTRACT TRUNCATED AT 250 WORDS)
Terminological Systems Revisited: Terminology = Schema + Views

Traditionally, the core of a Termino-logical Knowledge Representation System (TKRS) consists of a so-called TBox, where concepts are introduced, and an ABox, where facts about individuals are stated in terms of these concepts. This design has a drawback because in most applications the TBox has to meet two functions at a time: on the one hand, similar to a database schema, framelike structures with typing information are introduced through primitive concepts and primitive roles; on the other hand, views on the objects in the knowledge base are provided through de-ned concepts. We propose to account for this conceptual separation by partitioning the TBox into two components for primitive and deened concepts, which we call the schema and the view part. We envision the two parts to diier with respect to the language for concepts , the statements allowed, and the semantics. We argue that by this separation we achieve more conceptual clarity about the role of primitive and deened concepts and the semantics of terminological cycles. Moreover, three case studies show the computational beneets to be gained from the reened architecture.
Predictors of Pediatric Emergency Patients Discharged Against Medical Advice

Based on a retrospective 5-year medical record review, this study characterizes factors associated with patients discharged against medical advice (AMA) from a tertiary pediatric emergency department (ED) and compares rates of return to the ED and admission to the hospital with those of patients routinely discharged. Data from 94 patients discharged AMA are compared with those of 188 control patients. Pediatric patients at risk for discharge AMA are older than 15 years (odds ratio [OR], 3.561; 95% confidence interval [CI], 1.695-7.482), self-register independent of a parent (OR, 3.100; 95% CI, 1.818-152.770), arrive by ambulance (OR, 2.761; 95% CI, 1.267-6.018), involve a consultant (OR, 2.592; 95% CI, 1.507-4.458), and have a chief complaint of abdominal pain (OR, 3.095; 95% CI, 1.154-8.303). Negative predictors include urgent triage (OR, 0.155; 95% CI, 0.039-0.618), a chief complaint of upper respiratory tract illness or otitis media (OR, 0.229; 95% CI, 0.075-0.702), and discharge diagnoses of infection (adjusted OR, 0.053; 95% CI, 0.004-0.767), disease of the nervous system and sense organs (adjusted OR, 0.066; 95% CI, 0.005-0.898), respiratory illness (adjusted OR, 0.072; 95% CI, 0.007-0.718), and gastrointestinal disease (adjusted OR, 0.050; 95% CI, 0.006-0.419). Certain key elements of discharge AMA are well documented, including consequences of discharge AMA (74.5%) and instructions for care (54.3%). Other elements such as alternative therapies (1.1%) are poorly documented. Patients discharged AMA have a significantly higher return rate (24.5%) within 15 days compared with patients who have routine discharge (6.4%) (χ2 = 18.85, P < .001). Ninety-six percent of patients who return to the ED have the same chief complaint at both visits if discharged AMA compared with 50% of patients who are discharged routinely (P = .003), with 25% admission rates at the time of second visit for both types of discharges. Adolescents who register themselves are at increased risk for discharge AMA. Patients who are triaged as urgent or nonurgent or who have minor illnesses are likely to be dispositioned routinely. Patients discharged AMA are more likely to return to the ED with the same complaint than patients who are routinely discharged.