Miracle-dz/UniFAR-FTUs huggingface dataset:
Overlapping gene coexpression patterns in human medullary thymic epithelial cells generate self-antigen diversity

Significance The ability of the immune system to distinguish self from foreign (“self-tolerance”) is largely established in the thymus, a primary lymphoid organ where T cells develop. Intriguingly, T cells encounter most tissue-specific constituents already in the thymus, thus imposing a broad scope of tolerance before T cells circulate through the body. This preemption of the “immunological self” is afforded by the “promiscuous” expression of numerous tissue-specific antigens in medullary thymic epithelial cells. Here, we identified principles by which promiscuous gene expression at the single-cell level adds up to the full diversity of self-antigens displayed at the population level. Promiscuous expression of numerous tissue-restricted self-antigens (TRAs) in medullary thymic epithelial cells (mTECs) is essential to safeguard self-tolerance. A distinct feature of promiscuous gene expression is its mosaic pattern (i.e., at a given time, each self-antigen is expressed only in 1–3% of mTECs). How this mosaic pattern is generated at the single-cell level is currently not understood. Here, we show that subsets of human mTECs expressing a particular TRA coexpress distinct sets of genes. We identified three coexpression groups comprising overlapping and complementary gene sets, which preferentially mapped to certain chromosomes and intrachromosomal gene clusters. Coexpressed gene loci tended to colocalize to the same nuclear subdomain. The TRA subsets aligned along progressive differentiation stages within the mature mTEC subset and, in vitro, interconverted along this sequence. Our data suggest that single mTECs shift through distinct gene pools, thus scanning a sizeable fraction of the overall repertoire of promiscuously expressed self-antigens. These findings have implications for the temporal and spatial (re)presentation of self-antigens in the medulla in the context of tolerance induction.
Localization of a Suprachiasmatic Nucleus Subregion Regulating Locomotor Rhythmicity

The bilaterally symmetrical suprachiasmatic nuclei (SCN) of the hypothalamus are the loci of the mammalian clock controlling circadian rhythms. Previous studies suggested that all regions of the SCN are equipotential as circadian rhythmicity is sustained after partial ablation, as long as ∼25% of the nuclei are spared. In contrast to these results, we found that animals bearing partial lesions of the SCN that spared the subregion delimited by cells containing the calcium-binding protein calbindin-D28K (CaBP), sustained circadian locomotor rhythms. Furthermore, there was a correlation between the strength of the rhythm and the number of spared CaBP cells. Partial lesions that destroyed this region but spared other compartments of the SCN resulted in loss of rhythmicity. The next study indicates that transplants of half-SCN grafts that contain CaBP cells restore locomotor rhythms in SCN-lesioned host animals, whereas transplants containing SCN tissue but lacking cells of this subnucleus fail to restore rhythmicity. Finally, there was a correlation between the number of CaBP-positive cells in the graft and the strength of the restored rhythm. Taken together, the results indicate that pacemakers in the region of the CaBP subnucleus are necessary and sufficient for the control of locomotor rhythmicity and that the SCN is functionally heterogeneous.
An Integrated Design Framework of Fault-Tolerant Wireless Networked Control Systems for Industrial Automatic Control Applications

In this paper, a design framework of fault-tolerant wireless networked control systems (NCSs) is developed for industrial automation applications. The main objective is to achieve an integrated parameterization and design of the communication protocols, the control and fault diagnosis algorithms aiming at meeting high real-time requirements in industrial applications. To illustrate the design framework, a laboratory wireless fault-tolerant NCS platform is presented.
SLIQ: Simple Linear Inequalities for Efficient Contig Scaffolding

Scaffolding is an important subproblem in de novo genome assembly, in which mate pair data are used to construct a linear sequence of contigs separated by gaps. Here we present SLIQ, a set of simple linear inequalities derived from the geometry of contigs on the line that can be used to predict the relative positions and orientations of contigs from individual mate pair reads and thus produce a contig digraph. The SLIQ inequalities can also filter out unreliable mate pairs and can be used as a preprocessing step for any scaffolding algorithm. We tested the SLIQ inequalities on five real data sets ranging in complexity from simple bacterial genomes to complex mammalian genomes and compared the results to the majority voting procedure used by many other scaffolding algorithms. SLIQ predicted the relative positions and orientations of the contigs with high accuracy in all cases and gave more accurate position predictions than majority voting for complex genomes, in particular the human genome. Finally, we present a simple scaffolding algorithm that produces linear scaffolds given a contig digraph. We show that our algorithm is very efficient compared to other scaffolding algorithms while maintaining high accuracy in predicting both contig positions and orientations for real data sets.
The I mpact of S emantic W eb on E -

interpret data published in a machine-interpretable form on the web. At the present time, only human beings are able to understand the product information published online. The emerging semantic Web technologies have the potential to deeply influence the further development of the Internet Economy. In this paper we propose a scenario based research approach to predict the effects of these new technologies on electronic markets and business models of traders and intermediaries and customers. Over 300 million searches are conducted everyday on the Internet by people trying to find what they need. A majority of these searches are in the domain of consumer ecommerce, where a web user is looking for something to buy. This represents a huge cost in terms of people hours and an enormous drain of resources. Agent enabled semantic search will have a dramatic impact on the precision of these searches. It will reduce and possibly eliminate information asymmetry where a better informed buyer gets the best value. By impacting this key determinant of market prices semantic web will foster the evolution of different business and economic models. We submit that there is a need for developing these futuristic models based on our current understanding of e-commerce models and nascent semantic web technologies. We believe these business models will encourage mainstream web developers and businesses to join the " semantic web revolution. "
Chondrocytes Transdifferentiate into Osteoblasts in Endochondral Bone during Development, Postnatal Growth and Fracture Healing in Mice

One of the crucial steps in endochondral bone formation is the replacement of a cartilage matrix produced by chondrocytes with bone trabeculae made by osteoblasts. However, the precise sources of osteoblasts responsible for trabecular bone formation have not been fully defined. To investigate whether cells derived from hypertrophic chondrocytes contribute to the osteoblast pool in trabecular bones, we genetically labeled either hypertrophic chondrocytes by Col10a1-Cre or chondrocytes by tamoxifen-induced Agc1-CreERT2 using EGFP, LacZ or Tomato expression. Both Cre drivers were specifically active in chondrocytic cells and not in perichondrium, in periosteum or in any of the osteoblast lineage cells. These in vivo experiments allowed us to follow the fate of cells labeled in Col10a1-Cre or Agc1-CreERT2 -expressing chondrocytes. After the labeling of chondrocytes, both during prenatal development and after birth, abundant labeled non-chondrocytic cells were present in the primary spongiosa. These cells were distributed throughout trabeculae surfaces and later were present in the endosteum, and embedded within the bone matrix. Co-expression studies using osteoblast markers indicated that a proportion of the non-chondrocytic cells derived from chondrocytes labeled by Col10a1-Cre or by Agc1-CreERT2 were functional osteoblasts. Hence, our results show that both chondrocytes prior to initial ossification and growth plate chondrocytes before or after birth have the capacity to undergo transdifferentiation to become osteoblasts. The osteoblasts derived from Col10a1-expressing hypertrophic chondrocytes represent about sixty percent of all mature osteoblasts in endochondral bones of one month old mice. A similar process of chondrocyte to osteoblast transdifferentiation was involved during bone fracture healing in adult mice. Thus, in addition to cells in the periosteum chondrocytes represent a major source of osteoblasts contributing to endochondral bone formation in vivo.
Bradycardic onset of spiral wave re-entry: structural substrates.

AIMS The least understood aspect of re-entrant cardiac arrhythmias is how they start spontaneously. The known mechanisms for re-entry induction involve the application of premature electrical stimuli or rapid pacing, whereas in a clinical setting, re-entry often occurs at normal heart rates. Here, we propose a physiological mechanism of re-entry onset at normal and slow heart rates, which is based on structurally determined heterogeneities. METHODS AND RESULTS Using a two-dimensional tissue model with Luo-Rudy II kinetics, we study electrical propagation in the presence of macroscopic coupling heterogeneities. We find that spiral wave re-entry occurs if steep and smooth coupling gradients are situated side by side, with the critical steepness depending on the frequency of stimulation. We demonstrate how bradycardia can unmask a slow endogenous pacemaker in a poorly coupled region, subsequently leading to spiral wave re-entry. CONCLUSION In the presence of coupling heterogeneities, a single excitation coming from the less coupled region may induce spiral wave re-entry.
Multiagent models for police resource allocation and dispatch

In this article we investigate Multi-agent simulation as a way for modeling strategies for resource allocation problems in Public Safety. The goal is to show how simulation can be used to help law enforcement authorities to evaluate, in a controlled environment, different strategies for allocating and dispatching resources, aiming at reducing both response time and the number of unattended calls. We created a Multiagent model to represent police cars that answer to emergency calls. In particular, the environment in which the agents live is a grid in which emergency occurrences appear. Random and Zipfian distributions drive the occurrence of calls. A comparison of the strategies for resource allocation in this environment shows that serving first those calls with low estimated attendance times delivers the best overall performance. However this is practically impossible since prioritization of certain crime types is necessary leading to the increase of the waiting time in the queue. Such degradation may be assimilated in real life scenarios because high priority calls are served first. Also, it is important to implement a policy of aging to avoid the cost of great degradation for low priority crimes.
Diverse dimensions of Yoga

Yoga is a word very commonly used in the world today and carries various connotations depending on its usage. It has been defined in various manners as an art and science, as well as the process of conscious evolution. All human beings can gain a lot from the bountiful dimensions of Yoga, which enables them to manifest their inherent divinity, the universal potentiality that lies dormant unless channelized. "All souls are potentially divine," said Swami Vivekananda and, indeed, they are. This article aims to elucidate the diverse dimensions of Yoga that include the dimensions related to Indian culture as well as those associated with health, therapy, society, education, and research. Various physical, mental, emotional, and spiritual benefits attainable through Yoga are explained in detail, highlighting the multiple sub-dimensions of these major fields. Yoga, which emphasizes the universal, is a perfect foil to those human activities which glorify the personal. In short, it may be safely said that the practice of Yoga as a unified whole helps the individual shift from an "I"-centric approach to a "we"- centric approach. The beauty of Yoga is that these abstract principles become concrete by the daily practice of the techniques available in the integrated system. Once the "seed of Yoga" finds fertile soil, these concepts grow naturally, slowly but surely taking root in all aspects of life.
Strategies against replay attacks

The goal of the paper is to present a set of design principles for avoiding replay attacks in cryptographic protocols. The principles are easily applied to real protocols and they do not consume excessive computing power or communications bandwidth. In particular we describe how to type-tag messages with unique cryptographic functions, how to inexpensively implement the full information principle with hashes, and how to produce unique session keys without assuming mutual trust between the principals. The techniques do not guarantee security of protocols, but they are concrete ways for improving the robustness of the protocol design with relatively low cost.
Methylcobalamin Facilitates Collateral Sprouting of Donor Axons and Innervation of Recipient Muscle in End-to-Side Neurorrhaphy in Rats

Using ulnar nerve as donor and musculocutaneous nerve as recipient we found earlier that end-to-side neurorrhaphy resulted in weak functional reinnervation after lengthy survival. End-to-side neurorrhaphy however is the sole choice of nerve repair at times and has the advantage of conserving donor nerve function. Here, we investigated whether myelination-enhancing agent methylcobalamin and motoneuron trophic factor pleiotrophin enhances the recovery after end-to-side neurorrhaphy. Methylcobalamin significantly increased the expression of growth associated protein 43 and S100 protein and βIII tubulin in musculocutaneous nerve 1 month after neurorrhaphy suggesting the ingrowth of ulnar axonal sprouts in reactive Schwann cell environment. Upper limb functional test, compound muscle action potential measurements, motor end plate counts, and axon and myelin analyses showed that methylcobalamin treatment alone or with pleiotrophin improved the recovery significantly, 3 and 6 months post-surgery. There were fewer axons, closer in number to that of the intact recipient nerve, found in the distal repaired nerve of the methylcobalamin-treated than that of the vehicle control, suggesting that methylcobalamin facilitates axonal maturation and eliminates supernumerary sprouts. In conclusion, our results showed that methylcobalamin does indeed enhance the recovery of peripheral nerve repaired in end-to-side configuration.
Estimating completeness of cancer registration: an empirical evaluation of the two source capture-recapture approach in Germany.

STUDY OBJECTIVE--In recent years, capture-recapture methods have become increasingly popular in estimating completeness of disease registries. This study aimed to assess the performance of the two source capture-recapture method in estimating the completeness of cancer registration. DESIGN--The study was conducted in the population based cancer registry of Saarland, Germany, for which there are three main sources of notifications: reports by clinicians and pathologists, and death certificates. For groups of cases notified by one of the three sources, known completeness of registration by the other two sources was compared with the corresponding two source capture-recapture estimates. PATIENTS--A total of 16,020 patients notified to the cancer registry in 1970, 1975, 1980, and 1985 were included in the analysis. MAIN RESULTS--There was a tendency towards underestimation of completeness of notifications from pathologists and death certificates for patients notified by clinicians which was essentially confined to the older age groups. In contrast, capture-recapture methods tended to overestimate completeness of notifications from clinicians and death certificates for patients notified by pathologists. This overestimation was observed consistently in all age groups and for all of the most common cancer sites. Nevertheless, deviations of estimated completeness from known completeness were generally small or moderate. Agreement between estimated and known completeness was closest for patients notified by death certificates, although completeness was somewhat underestimated in patients above age 75. The observed patterns are in agreement with knowledge on clinical aspects and clinical management of cancer patients and with the circumstances of cancer registration in Saarland. CONCLUSIONS--Careful application of capture-recapture methods may provide an alternative to traditional approaches for estimating completeness of cancer registration.
Transient sensitivity to nisin in cold‐shocked Gram negatives

Rapid chilling in the presence of nisin caused a dose‐dependent reduction in the populations of several Gram‐negative bacteria, despite the fact that appreciable structural injury to the outer membrane was not detected. Pseudomonas aeruginosa was most affected, followed by Pseudomonas fragi, Salmonella enteritidis PT4, PT7 and Escherichia coli, respectively. Addition of nisin after the chilling treatment had no effect. The results are ascribed to a transient susceptibility caused by phase changes in the lipids associated with the outer membrane, which are rapidly reversed when the cells return to higher temperatures. Combinations of chilling shock, nisin and EDTA gave much lower reductions of Salmonella and Pseudomonas on chicken skin in comparison with broths. This is attributed to a buffering of the temperature shock experienced by adherent bacteria and binding of the nisin by food particles.
Exercise training lowers plasma visfatin concentrations in patients with type 1 diabetes.

CONTEXT Exercise training exerts beneficial effects on metabolic and vascular risk factors in patients with type 1 diabetes mellitus (T1DM). It is unknown whether training also influences concentrations of visfatin, a novel insulin-mimetic adipocytokine. OBJECTIVES In this study, we have investigated whether plasma visfatin concentrations are altered by training in patients with T1DM. DESIGN AND PATIENTS Fasting plasma visfatin concentrations and metabolic parameters were measured in 18 patients with T1DM who participated in a supervised aerobic exercise program for 4 months. Three subjects discontinued training prematurely after 2 months. Samples were obtained before and during training and 8 months after the end of regular exercise. Fourteen healthy young subjects served as controls. RESULTS At baseline, patients with T1DM had higher visfatin concentrations than controls (64.1 +/- 12.0 vs. 1.3 +/- 0.0 ng/ml, P < 0.01). Exercise reduced visfatin after 2 and 4 months to 27.8 +/- 2.6 (n = 18) and 17.5 +/- 3.4 ng/ml (n = 15), respectively (P < 0.001 for n = 15 subjects who participated in all visits, ANOVA). This effect was maintained 8 months after cessation of training, with visfatin concentrations of 19.7 +/- 5.0 ng/ml (n = 15). Metabolic parameters were not affected by the training program. CONCLUSION Elevated visfatin concentrations in patients with T1DM can be lowered by regular physical exercise. It is unknown whether glucose tolerance is affected by changes in visfatin concentrations.
Multi-Arm Bandit Models for 2 D Sample Based Grasp Planning with Uncertainty

For applications such as warehouse order fulfillment, robot grasps must be robust to uncertainty arising from sensing, shape, mechanics, and control. One way to achieve this is to evaluate the performance of candidate grasps by sampling perturbations in shape, pose, and control, computing the probability of force closure for each candidate to identify the grasp with the highest expected quality. Prior work has turned to cloud computing because evaluating the quality of each grasp is computationally demanding. To improve efficiency and extend this work, we consider how Multi-Armed Bandit (MAB) models for optimizing decisions can be applied in this context. We formulate robust grasp planning as a MAB problem and evaluate grasp planning convergence time using 100 object shapes randomly selected from the Brown Vision 2D Lab Dataset from 1000 uniformly distributed candidate grasp angles. We consider the case where shape uncertainty is represented as a Gaussian process implicit surface (GPIS) and there is Gaussian uncertainty in pose, gripper approach angle, and coefficient of friction. Uniform allocation and iterative pruning, the non-MAB methods, converge slowly. In contrast, Thompson Sampling and the Gittins index method, the MAB methods we consider, converged to within 3% of the optimal grasp 5x faster than iterative pruning.
Revisiting the Knowledge Base of Social Work: A Framework for Practice

The starting point for this paper is the view that social work practice is a highly skilled activity and one that calls for an extensive knowledge base and considerable intellectual abilities. However, considerable confusion remains about what constitutes the knowledge base of social work and how this can be applied to the dilemmas regularly encountered in direct work. This article begins with an account of key writing on the subject of knowledge and, drawing on these works, it describes a framework that includes three interweaving features: (i) theoretical knowledge (or theory); (ii) factual knowledge (including research); and (iii) practice/practical/personal knowledge. A particular feature of this paper is that it locates the knowledge that service users and carers bring to the encounter within the same framework as the knowledge demonstrated by social workers, other professionals and involved individuals. Since most of the published works on the subject of social work knowledge tend to be written by academics, a central aim of this paper is to make this subject accessible to social work practitioners, students, service users and carers in order to encourage their contribution to the debate on what constitutes the knowledge base of social work.
Interpersonal Judgments: Moral Responsibility and Blame

A deterministic perspective, believing choices are a function of hereditary and environmental factors, could theoretically impact perceived moral responsibility and lead to decreased blame in judging others. However, little consistent support has been found relating individual differences in deterministic attitudes to blame/tolerance for others. Perhaps, though, providing information regarding past background hardships affecting an individual's current lifestyle could potentially mediate harsh moralistic judgments of that individual. In the two studies reported here, we further explored the relation of free will/determinism scales to attitudes toward others as well as the effect of manipulating background information on the assignment of blame. As in previous research, little support was found for the relation of deterministic attitudes to tolerance toward others. However, judgments following manipulated information about hypothetical target persons supported the conclusion that target individuals are blamed less and given more sympathy if more information related to previous hardships is provided. In addition, in the second study perceived similarity to a target individual was associated with decreased blame/greater sympathy for a target with alcohol abuse problems.