Miracle-dz/UniFAR-FTUs huggingface dataset:
Thin and thick primary cutaneous melanomas reveal distinct patterns of somatic copy number alterations

Cutaneous melanoma is one of the most aggressive type of skin tumor. Early stage melanoma can be often cured by surgery; therefore current management guidelines dictate a different approach for thin (<1mm) versus thick (>4mm) melanomas. We have carried out whole-exome sequencing in 5 thin and 5 thick fresh-frozen primary cutaneous melanomas. Unsupervised hierarchical clustering analysis of somatic copy number alterations (SCNAs) identified two groups corresponding to thin and thick melanomas. The most striking difference between them was the much greater abundance of SCNAs in thick melanomas, whereas mutation frequency did not significantly change between the two groups. We found novel mutations and focal SCNAs in genes that are embryonic regulators of axon guidance, predominantly in thick melanomas. Analysis of publicly available microarray datasets provided further support for a potential role of Ephrin receptors in melanoma progression. In addition, we have identified a set of SCNAs, including amplification of BRAF and ofthe epigenetic modifier EZH2, that are specific for the group of thick melanomas that developed metastasis during the follow-up. Our data suggest that mutations occur early during melanoma development, whereas SCNAs might be involved in melanoma progression.
Surgical outcome of Fontan conversion and arrhythmia surgery: Need a pacemaker?

Background Atrial tachyarrhythmias are frequent complications in the late period after the Fontan procedure, and important risk factors for a poor prognosis. The impact of Fontan conversion and arrhythmia surgery in failed Fontan patients has been described in many reports. Objective We evaluated our experience with Fontan conversion procedures, concomitant arrhythmia surgery, and pacemaker implantation. Methods We reviewed the hospital records of 25 consecutive patients who underwent a Fontan conversion procedure from January 2004 to March 2012. Twenty-four patients had arrhythmia surgery using cryoablation and radiofrequency ablation at the time of conversion. A bilateral atrial maze procedure was performed in 6 patients, right-side maze in 15, and isthmus block in 3. Three patients with a diagnosis of corrected transposition of the great arteries underwent simultaneous pacemaker implantation electively. Results There was no early death and one late death during a mean follow-up period of 21.2 months. Three tachyarrhythmia recurrences developed, and there were 4 occurrences of sinus bradycardia. Five of these patients required postoperative pacemaker implantation. Conclusion The mid-term results of Fontan conversion and arrhythmia surgery in our institute were satisfactory. The occurrence of unexpected postoperative pacemaker requirement was high in the patients who underwent a right atrial or bilateral atrial maze procedure. Pacemaker or lead implantation is recommended for patients planned to undergo a right-side or full maze procedure.
Postsynaptic Density Protein 95 in the Striosome and Matrix Compartments of the Human Neostriatum

The human neostriatum consists of two functional subdivisions referred to as the striosome (patch) and matrix compartments. The striosome-matrix dopamine systems play a central role in cortico-thalamo-basal ganglia circuits, and their involvement is thought to underlie the genesis of multiple movement and behavioral disorders, and of drug addiction. Human neuropathology also has shown that striosomes and matrix have differential vulnerability patterns in several striatal neurodegenerative diseases. Postsynaptic density protein 95 (PSD-95), also known as disks large homolog 4, is a major scaffolding protein in the postsynaptic densities of dendritic spines. PSD-95 is now known to negatively regulate not only N-methyl-D-aspartate glutamate signaling, but also dopamine D1 signals at sites of postsynaptic transmission. Accordingly, a neuroprotective role for PSD-95 against dopamine D1 receptor (D1R)-mediated neurotoxicity in striatal neurodegeneration also has been suggested. Here, we used a highly sensitive immunohistochemistry technique to show that in the human neostriatum, PSD-95 is differentially concentrated in the striosome and matrix compartments, with a higher density of PSD-95 labeling in the matrix compartment than in the striosomes. This compartment-specific distribution of PSD-95 was strikingly complementary to that of D1R. In addition to the possible involvement of PSD-95-mediated synaptic function in compartment-specific dopamine signals, we suggest that the striosomes might be more susceptible to D1R-mediated neurotoxicity than the matrix compartment. This notion may provide new insight into the compartment-specific vulnerability of MSNs in striatal neurodegeneration.
Fluid-Mediated Stochastic Self-Assembly at Centimetric and Sub-Millimetric Scales: Design, Modeling, and Control

Stochastic self-assembly provides promising means for building micro-/nano-structures with a variety of properties and functionalities. Numerous studies have been conducted on the control and modeling of the process in engineered self-assembling systems constituted of modules with varied capabilities ranging from completely reactive nano-/micro-particles to intelligent miniaturized robots. Depending on the capabilities of the constituting modules, different approaches have been utilized for controlling and modeling these systems. In the quest of a unifying control and modeling framework and within the broader perspective of investigating how stochastic control strategies can be adapted from the centimeter-scale down to the (sub-)millimeter-scale, as well as from mechatronic to MEMS-based technology, this work presents the outcomes of our research on self-assembly during the past few years. As the first step, we leverage an experimental platform to study self-assembly of water-floating passive modules at the centimeter scale. A dedicated computational framework is developed for real-time tracking, modeling and control of the formation of specific structures. Using a similar approach, we then demonstrate controlled self-assembly of microparticles into clusters of a preset dimension in a microfluidic chamber, where the control loop is closed again through real-time tracking customized for a much faster system dynamics. Finally, with the aim of distributing the intelligence and realizing programmable self-assembly, we present a novel experimental system for fluid-mediated programmable stochastic self-assembly of active modules at the centimeter scale. The system is built around the water-floating 3-cm-sized Lily robots specifically designed to be operative in large swarms and allows for exploring the whole range of fully-centralized to fully-distributed control strategies. The outcomes of our research efforts extend the state-of-the-art methodologies for designing, modeling and controlling massively-distributed, stochastic self-assembling systems at different length scales, constituted of modules from centimetric down to sub-millimetric size. As a result, our work provides a solid milestone in structure formation through controlled self-assembly.
GroupUs: Smartphone Proximity Data and Human Interaction Type Mining

There is an increasing interest in analyzing social interaction from mobile sensor data, and smart phones are rapidly becoming the most attractive sensing option. We propose a new probabilistic relational model to analyze long-term dynamic social networks created by physical proximity of people. Our model can infer different interaction types from the network, revealing the participants of a given group interaction, and discovering a variety of social contexts. Our analysis is conducted on Bluetooth data sensed with smart phones for over one year on the life of 40 individuals related by professional or personal links. We objectively validate our model by studying its predictive performance, showing a significant advantage over a recently proposed model.
Inductive Bias in Context-Free Language Learning

Recurrent neural networks are capable of learning context-free tasks, however learning performance is unsatisfactory. We investigate the e ect of biasing learning towards nding a solution to a context-free prediction task. The rst series of simulations xes various sets of weights of the network to values found in a successful network, limiting the search space of the backpropagation through time learning algorithm. We nd that xing similar sets of weights can have very di erent e ects on learning performance. The second series of simulations employs an evolutionary hill-climbing algorithm with an error measure that more closely resembles the performance measure. We nd that under these conditions, the network nds di erent solutions to those found by backpropagation, and is even biased towards nding these solutions. An unexpected result is that the hill-climbing algorithm is capable of generalisation. The two simulations serve to highlight that seemingly similar biases can have opposite e ects on learning.
Evolutionary Transitions and Artificial Life

A major challenge for artificial life is to synthesize the evolutionary transitions that have repeatedly formed differentiated higher-level entities from cooperative organizations of lower-level entities, producing the nested hierarchical structure of living processes. This article identifies the key elements and relationships that must be incorporated or synthesized in an artificial life system if these transitions are to emerge. The processes currently included in artificial life systems are unable to provide an adequate basis for the emergence of the complex cooperative organization that is essential to the transitions. A new theory of the evolution of cooperative organization is developed that points to the additional processes that must be included in artificial life systems to underpin the emergence of the transitions.
Fixed points of endomorphisms of virtually free groups

A fixed point theorem is proved for inverse transducers, leading to an automata-theoretic proof of the fixed point subgroup of an endomorphism of a finitely generated virtually free group being finitely generated. If the endomorphism is uniformly continuous for the hyperbolic metric, it is proved that the set of regular fixed points in the hyperbolic boundary has finitely many orbits under the action of the finite fixed points. In the automorphism case, it is shown that these regular fixed points are either exponentially stable attractors or exponentially stable repellers.
Targeted Transduction of CNS Neurons with Adenoviral Vectors Carrying Neurotrophic Factor Genes Confers Neuroprotection That Exceeds the Transduced Population

Application of neurotrophic factors (NFs) to the cut stump of motor nerves of neonatal rats confers neuroprotection from trauma-induced neuronal death. To test whether motoneurons are capable of responding to endogenously produced NFs, facial motoneurons were genetically modified in vivo to express several NFs and then tested for their response to peripheral nerve damage. Replication-defective adenoviral vectors [Adv.Rous sarcoma virus (RSV)-nf] representing three families of NFs were constructed that carried genes for brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), glial cell-derived neurotrophic factor (GDNF), and nerve growth factor. Media from cultured cells transduced with Adv.RSV-nf contained NFs that supported the survival of cultured chick sensory neurons in the same manner as recombinant NF standards. When Adv.RSV-nfor an adenoviral vector containing the β-galactosidase gene (Adv.RSV-β-gal) were injected into the facial muscles of neonatal rats the vectors were retrogradely transported to the facial nucleus where the NFs or β-gal were expressed. A fraction (∼10%) of the neurons were transduced as demonstrated by reverse transcriptase-PCR, histochemistry, and immunocytochemistry. In the case of Adv.RSV-BDNF, Adv.RSV-CNTF, and Adv.RSV-GDNF, a significant portion of the facial nucleus neurons was protected, 16.5, 18.2, and 53.3%, respectively, from death after axotomy, showing that neurons are capable of transporting the Adv.RSV-nf, expressing the recombinant NF genes, and responding to the NFs. In the case of Adv.RSV-GDNF, a greater number of facial nucleus motoneurons survived than were transduced, indicating that neighboring untransduced neurons were protected by the GDNF expressed by the transduced neurons by a paracrine mechanism.
Inadequate food intake at high temperatures is related to depressed mitochondrial respiratory capacity

ABSTRACT Animals, especially ectotherms, are highly sensitive to the temperature of their surrounding environment. Extremely high temperature, for example, induces a decline of average performance of conspecifics within a population, but individual heterogeneity in the ability to cope with elevating temperatures has rarely been studied. Here, we examined inter-individual variation in feeding ability and consequent growth rate of juvenile brown trout Salmo trutta acclimated to a high temperature (19°C), and investigated the relationship between these metrics of whole-animal performances and among-individual variation in mitochondrial respiration capacity. Food was provided ad libitum, yet intake varied ten-fold amongst individuals, resulting in some fish losing weight whilst others continued to grow. Almost half of the variation in food intake was related to variability in mitochondrial capacity: low intake (and hence growth failure) was associated with high leak respiration rates within liver and muscle mitochondria, and a lower coupling of muscle mitochondria. These observations, combined with the inability of fish with low food consumption to increase their intake despite ad libitum food levels, suggest a possible insufficient capacity of the mitochondria for maintaining ATP homeostasis. Individual variation in thermal performance is likely to confer variation in the upper limit of an organism's thermal niche and might affect the structure of wild populations in warming environments. Summary: Variation in performance among individual fish is associated with differences in their mitochondrial leak respiration rate and respiratory control ratio.
A Note on the Unification of Adaptive Online Learning

In online convex optimization, adaptive algorithms, which can utilize the second-order information of the loss function’s (sub)gradient, have shown improvements over standard gradient methods. This paper presents a framework Follow the Bregman Divergence Leader that unifies various existing adaptive algorithms from which new insights are revealed. Under the proposed framework, two simple adaptive online algorithms with improvable performance guarantee are derived. Furthermore, a general equation derived from a matrix analysis generalizes the adaptive learning to nonlinear case with kernel trick.
Screening of Human Tumor Antigens for CD4+ T Cell Epitopes by Combination of HLA-Transgenic Mice, Recombinant Adenovirus and Antigen Peptide Libraries

Background As tumor antigen-specific CD4+ T cells can mediate strong therapeutic anti-tumor responses in melanoma patients we set out to establish a comprehensive screening strategy for the identification of tumor-specific CD4+ T cell epitopes suitable for detection, isolation and expansion of tumor-reactive T cells from patients. Methods and Findings To scan the human melanoma differentiation antigens TRP-1 and TRP-2 for HLA-DRB1*0301-restricted CD4+ T cell epitopes we applied the following methodology: Splenocytes of HLA-DRB1*0301-transgenic mice immunized with recombinant adenovirus encoding TRP-1 (Ad5.TRP-1) or TRP-2 (Ad5.TRP-2) were tested for their T cell reactivity against combinatorial TRP-1- and TRP-2-specific peptide libraries. CD4+ T cell epitopes thus identified were validated in the human system by stimulation of peripheral blood mononuclear cells (PBMC) from healthy donors and melanoma patients. Using this strategy we observed that recombinant Ad5 induced strong CD4+ T cell responses against the heterologous tumor antigens. In Ad5.TRP-2-immunized mice CD4+ T cell reactivity was detected against the known HLA-DRB1*0301-restricted TRP-260–74 epitope and against the new epitope TRP-2149–163. Importantly, human T cells specifically recognizing target cells loaded with the TRP-2149–163-containing library peptide or infected with Ad5.TRP-2 were obtained from healthy individuals, and short term in vitro stimulation of PBMC revealed the presence of epitope-reactive CD4+ T cells in melanoma patients. Similarly, immunization of mice with Ad5.TRP-1 induced CD4+ T cell responses against TRP-1-derived peptides that turned out to be recognized also by human T cells, resulting in the identification of TRP-1284–298 as a new HLA-DRB1*0301-restricted CD4+ T cell epitope. Conclusions Our screening approach identified new HLA-DRB1*0301-restricted CD4+ T cell epitopes derived from melanoma antigens. This strategy is generally applicable to target antigens of other tumor entities and to different HLA class II molecules even without prior characterization of their peptide binding motives.
Treatment of facial vascular lesions with intense pulsed light.

BACKGROUND Various lasers, particularly the flashlamp-pulsed dye laser, have been proven to be effective in the treatment of facial vascular lesions. Nevertheless, the post-treatment side effects, such as pronounced purpura and changes in pigmentation, have been a matter of concern to patients. OBJECTIVE To test the efficacy of an alternative treatment option that uses intense pulsed light to provide patients with a more tolerable post-treatment outcome. METHODS A total of 200 patients were treated with an intense pulsed light source (PhotoDerm VL) using various treatment parameters. The patients were treated for facial veins (primarily telangiectasia), facial hemangiomas, rosacea and port wine stains. RESULTS Of the 188 patients who returned for follow-up after 2 months, 174 achieved 75% to 100% clearance in one to four treatment sessions. The post-treatment side effects were minimal and well tolerated by the patients. There were no instances of scarring or other permanent side effects. CONCLUSION The PhotoDerm VL provides a highly effective and safe alternative to the laser for treatment of facial vascular lesions. The device may achieve improved results for lesions that are resistant to laser therapy. The rate and degree of cosmetic side effects are considerably less than with laser treatment.
An Examination of the Leisure Involvement—Agency Commitment Relationship

Building from the existing literature, we tested a model suggesting that leisure involvement is an antecedent of commitment to a public leisure service provider (N = 860). Leisure involvement was conceptualized as a multidimensional construct consisting of attraction, centrality, and self-expression. Agency commitment was also conceptualized as multidimensional construct consisting of five components; place identity, place dependence, affective attachment, value congruence, and social bonding. The analyses offered partial support for our hypothesized model. Place dependence and affective attachment were positively influenced by attraction, whereas place identity and value congruence were positively influenced by self-expression. Finally, social bonding was positively influenced by self-expression and centrality, but negatively influenced by attraction. This work adds to a growing body of empirical work suggesting that individuals progress though a developmental process where involvement with a leisure activity leads to the development of specific service preferences.
Advantages and Limitations of Androgen Receptor-Based Methods for Detecting Anabolic Androgenic Steroid Abuse as Performance Enhancing Drugs

Testosterone (T) and related androgens are performance enhancing drugs (PEDs) abused by some athletes to gain competitive advantage. To monitor unauthorized androgen abuse, doping control programs use mass spectrometry (MS) to detect androgens, synthetic anabolic-androgenic steroids (AASs) and their metabolites in an athlete’s urine. AASs of unknown composition will not be detected by these procedures. Since AASs achieve their anabolic effects by activating the Androgen Receptor (AR), cell-based bioassays that measure the effect of a urine sample on AR activity are under investigation as complementary, pan-androgen detection methods. We evaluated an AR BioAssay as a monitor for androgen activity in urine pre-treated with glucuronidase, which releases T from the inactive T-glucuronide that predominates in urine. AR BioAssay activity levels were expressed as ‘T-equivalent’ concentrations by comparison to a T dose response curve. The T-equivalent concentrations of androgens in the urine of hypogonadal participants supplemented with T (in whom all androgenic activity should arise from T) were quantitatively identical to the T measurements conducted by MS at the UCLA Olympic Analytical Laboratory (0.96 ± 0.22). All 17 AASs studied were active in the AR BioAssay; other steroids were inactive. 12 metabolites of 10 commonly abused AASs, which are used for MS monitoring of AAS doping because of their prolonged presence in urine, had reduced or no AR BioAssay activity. Thus, the AR BioAssay can accurately and inexpensively monitor T, but its ability to monitor urinary AASs will be limited to a period immediately following doping in which the active AASs remain intact.
Myth of the Color-Blind Judge: An Empirical Analysis of Racial Harassment Cases

This empirical study of over 400 federal cases, representing workplace racial harassment jurisprudence over a twenty-year period, found that judges' race significantly affects outcomes in these cases. African American judges rule differently than White judges, even when we take into account their political affiliation and case characteristics. At the same time, our findings indicate that judges of all races are attentive to relevant facts of the cases but interpret them differently. Thus, while we cannot predict how an individual judge might act, our study results strongly suggest that African American judges as a group and White judges as a group perceive racial harassment differently. These findings counter the traditional myth of judicial decision-making that the race of a judge would not make a difference, since the decision-making process is presumed to be rational and objective. Given the underrepresentation of minority judges on the federal bench, the growing minority population in the U.S., and minority skepticism of judicial fairness, this article offers empirical support for a more racially-diverse judiciary. Having more judges of color promises to increase diverse perspectives in the judicial system and to unveil the complex reality of racial dynamics in the workplace.
Neuro-Immune and Self-Organizing Map Approaches to Anomaly Detection: A Comparison

The purpose of this work is to investigate a hybrid approach (neuro-immune technique) for anomaly detection on time series data. In many anomaly detection applications, only positive (normal) samples are available for training purpose. However, conventional classication algorithms need both positive and negative samples. The proposed approach uses normal samples to generate abnormal samples that are subsequently used as training data for a neural network. The approach is compared against an anomaly detection technique that uses self-organizing maps to cluster the normal data sets (samples). 1