Miracle-dz/UniFAR-FTUs huggingface dataset:
De Novo Assembly of Human Herpes Virus Type 1 (HHV-1) Genome, Mining of Non-Canonical Structures and Detection of Novel Drug-Resistance Mutations Using Short- and Long-Read Next Generation Sequencing Technologies

Human herpesvirus type 1 (HHV-1) has a large double-stranded DNA genome of approximately 152 kbp that is structurally complex and GC-rich. This makes the assembly of HHV-1 whole genomes from short-read sequencing data technically challenging. To improve the assembly of HHV-1 genomes we have employed a hybrid genome assembly protocol using data from two sequencing technologies: the short-read Roche 454 and the long-read Oxford Nanopore MinION sequencers. We sequenced 18 HHV-1 cell culture-isolated clinical specimens collected from immunocompromised patients undergoing antiviral therapy. The susceptibility of the samples to several antivirals was determined by plaque reduction assay. Hybrid genome assembly resulted in a decrease in the number of contigs in 6 out of 7 samples and an increase in N(G)50 and N(G)75 of all 7 samples sequenced by both technologies. The approach also enhanced the detection of non-canonical contigs including a rearrangement between the unique (UL) and repeat (T/IRL) sequence regions of one sample that was not detectable by assembly of 454 reads alone. We detected several known and novel resistance-associated mutations in UL23 and UL30 genes. Genome-wide genetic variability ranged from <1% to 53% of amino acids in each gene exhibiting at least one substitution within the pool of samples. The UL23 gene had one of the highest genetic variabilities at 35.2% in keeping with its role in development of drug resistance. The assembly of accurate, full-length HHV-1 genomes will be useful in determining genetic determinants of drug resistance, virulence, pathogenesis and viral evolution. The numerous, complex repeat regions of the HHV-1 genome currently remain a barrier towards this goal.
Deep learning of the tissue-regulated splicing code

Motivation: Alternative splicing (AS) is a regulated process that directs the generation of different transcripts from single genes. A computational model that can accurately predict splicing patterns based on genomic features and cellular context is highly desirable, both in understanding this widespread phenomenon, and in exploring the effects of genetic variations on AS. Methods: Using a deep neural network, we developed a model inferred from mouse RNA-Seq data that can predict splicing patterns in individual tissues and differences in splicing patterns across tissues. Our architecture uses hidden variables that jointly represent features in genomic sequences and tissue types when making predictions. A graphics processing unit was used to greatly reduce the training time of our models with millions of parameters. Results: We show that the deep architecture surpasses the performance of the previous Bayesian method for predicting AS patterns. With the proper optimization procedure and selection of hyperparameters, we demonstrate that deep architectures can be beneficial, even with a moderately sparse dataset. An analysis of what the model has learned in terms of the genomic features is presented. Contact: frey@psi.toronto. edu Supplementary information: Supplementary data are available at Bioinformatics online.
Cardiac-Specific LIM Protein FHL2 Modifies the Hypertrophic Response to &bgr;-Adrenergic Stimulation

Background—A deficiency of muscle LIM protein results in dilated cardiomyopathy, but the function of other LIM proteins in the heart has not been assessed previously. We have characterized the expression and function of FHL2, a heart-specific member of the LIM domain gene family. Methods and Results—Expression of FHL2 mRNA and protein was examined by Northern blot, in situ hybridization, and Western blot analyses of fetal and adult mice. FHL2 transcripts are present at embryonic day (E) 7.5 within the cardiac crescent in a pattern that resembles that of Nkx2.5 mRNA. During later stages of cardiac development and in adult animals, FHL2 expression is localized to the myocardium and absent from endocardium, cardiac cushion, outflow tract, or coronary vasculature. The gene encoding FHL2 was disrupted by homologous recombination, and knockout mice devoid of FHL2 were found to undergo normal cardiovascular development. In the absence of FHL2, however, cardiac hypertrophy resulting from chronic infusion of isoproterenol is exaggerated (59% versus 20% increase in heart weight/body weight in FHL null versus wild-type mice;P <0.01). Conclusions—FHL2 is an early marker of cardiogenic cells and a cardiac-specific LIM protein in the adult. FHL2 is not required for normal cardiac development but modifies the hypertrophic response to &bgr;-adrenergic stimulation.
MHC I Stabilizing Potential of Computer-Designed Octapeptides

Experimental results are presented for 180 in silico designed octapeptide sequences and their stabilizing effects on the major histocompatibility class I molecule H-2Kb. Peptide sequence design was accomplished by a combination of an ant colony optimization algorithm with artificial neural network classifiers. Experimental tests yielded nine H-2Kb stabilizing and 171 nonstabilizing peptides. 28 among the nonstabilizing octapeptides contain canonical motif residues known to be favorable for MHC I stabilization. For characterization of the area covered by stabilizing and non-stabilizing octapeptides in sequence space, we visualized the distribution of 100,603 octapeptides using a self-organizing map. The experimental results present evidence that the canonical sequence motives of the SYFPEITHI database on their own are insufficient for predicting MHC I protein stabilization.
Violating Social Norms when Choosing Friends: How Rule-Breakers Affect Social Networks

Social networks rely on basic rules of conduct to yield functioning societies in both human and animal populations. As individuals follow established rules, their behavioral decisions shape the social network and give it structure. Using dynamic, self-organizing social network models we demonstrate that defying conventions in a social system can affect multiple levels of social and organizational success independently. Such actions primarily affect actors' own positions within the network, but individuals can also affect the overall structure of a network even without immediately affecting themselves or others. These results indicate that defying the established social norms can help individuals to change the properties of a social system via seemingly neutral behaviors, highlighting the power of rule-breaking behavior to transform convention-based societies, even before direct impacts on individuals can be measured.
Detect and Track Latent Factors with Online Nonnegative Matrix Factorization

Detecting and tracking latent factors from temporal data is an important task. Most existing algorithms for latent topic detection such as Nonnegative Matrix Factorization (NMF) have been designed for static data. These algorithms are unable to capture the dynamic nature of temporally changing data streams. In this paper, we put forward an online NMF (ONMF) algorithm to detect latent factors and track their evolution while the data evolve. By leveraging the already detected latent factors and the newly arriving data, the latent factors are automatically and incrementally updated to reflect the change of factors. Furthermore, by imposing orthogonality on the detected latent factors, we can not only guarantee the unique solution of NMF but also alleviate the partial-data problem, which may cause NMF to fail when the data are scarce or the distribution is incomplete. Experiments on both synthesized data and real data validate the efficiency and effectiveness of our ONMF algorithm.
A review of the efficacy of mitomycin C in glaucoma filtration surgery

The success of trabeculectomy, which is considered the gold standard in the surgical treatment of glaucoma, depends on the wound healing response. The introduction of antiproliferative agents such as mitomycin C (MMC) has increased the success rates of trabeculectomy. However, complications due to these agents can be challenging to manage. Hence, it is important to determine the most efficacious dose and duration of exposure. Multiple studies suggest that many factors, including but not limited to MMC preparation, different concentrations, different exposure times, and method of application may affect success rate, and these factors were reviewed in this article. We concluded that lower concentrations of MMC that are prepared and applied in a standardized fashion, such as that using the Mitosol® kit (for 2–3 minutes) during trabeculectomy, could potentially provide trabeculectomy success rates similar to that reported with off-label preparations, and that such a treatment regime could result in in lower complication rates than higher doses of MMC.
Two families with quadrupedalism, mental retardation, no speech, and infantile hypotonia (Uner Tan Syndrome Type-II); a novel theory for the evolutionary emergence of human bipedalism

Two consanguineous families with Uner Tan Syndrome (UTS) were analyzed in relation to self-organizing processes in complex systems, and the evolutionary emergence of human bipedalism. The cases had the key symptoms of previously reported cases of UTS, such as quadrupedalism, mental retardation, and dysarthric or no speech, but the new cases also exhibited infantile hypotonia and are designated UTS Type-II. There were 10 siblings in Branch I and 12 siblings in Branch II. Of these, there were seven cases exhibiting habitual quadrupedal locomotion (QL): four deceased and three living. The infantile hypotonia in the surviving cases gradually disappeared over a period of years, so that they could sit by about 10 years, crawl on hands and knees by about 12 years. They began walking on all fours around 14 years, habitually using QL. Neurological examinations showed normal tonus in their arms and legs, no Babinski sign, brisk tendon reflexes especially in the legs, and mild tremor. The patients could not walk in a straight line, but (except in one case) could stand up and maintain upright posture with truncal ataxia. Cerebello-vermial hypoplasia and mild gyral simplification were noted in their MRIs. The results of the genetic analysis were inconclusive: no genetic code could be identified as the triggering factor for the syndrome in these families. Instead, the extremely low socio-economic status of the patients was thought to play a role in the emergence of UTS, possibly by epigenetically changing the brain structure and function, with a consequent selection of ancestral neural networks for QL during locomotor development. It was suggested that UTS may be regarded as one of the unpredictable outcomes of self-organization within a complex system. It was also noted that the prominent feature of this syndrome, the diagonal-sequence habitual QL, generated an interference between ipsilateral hands and feet, as in non-human primates. It was suggested that this may have been the triggering factor for the attractor state “bipedal locomotion” (BL), which had visual and manual benefits for our ape-like ancestors, and therefore enhancing their chances for survival, with consequent developments in the psychomotor domain of humans. This was put forward as a novel theory of the evolution of BL in human beings.
Speculative Execution for a Single Job in a MapReduce-Like System

Parallel processing plays an important role for large-scale data analytics. It breaks a job into many small tasks which run parallel on multiple machines such as MapReduce framework. One fundamental challenge faced to such parallel processing is the straggling tasks as they can delay the completion of a job seriously. In this paper, we focus on the speculative execution issue which is used to deal with the straggling problem in the literature. We present a theoretical framework for the optimization of a single job which differs a lot from the previous heuristics-based work. More precisely, we propose two schemes when the number of parallel tasks the job consists of is smaller than cluster size. In the first scheme, no monitoring is needed and we can provide the job deadline guarantee with a high probability while achieve the optimal resource consumption level. The second scheme needs to monitor the task progress and makes the optimal number of duplicates when the straggling problem happens. On the other hand, when the number of tasks in a job is larger than the cluster size, we propose an Enhanced Speculative Execution (ESE) algorithm to make the optimal decision whenever a machine is available for a new scheduling. The simulation results show the ESE algorithm can reduce the job flow time by 50% while consume fewer resources comparing to the strategy without backup.
Dexamethasone intravitreal implant for treatment of patients with recalcitrant macular edema resulting from Irvine-Gass syndrome.

PURPOSE To evaluate the effectiveness of a single intravitreal injection of dexamethasone implant, over 6 months in patients with recalcitrant CME due to Irvine-Gass syndrome. METHODS Retrospective review of the medical records of nine patients with refractory macular edema (ME) due to Irvine-Gass syndrome, who underwent a single intravitreal injection of dexamethasone implant, Ozurdex, between November 2010 and January 2012, at the Instituto de Microcirurgia Ocular, Barcelona, Spain. All patients underwent a complete ophthalmic evaluation, including best-corrected visual acuity (BCVA) using standardized ETDRS charts, tonometry, fluorescein angiography, and spectral-domain optical coherence tomography with foveal thickness (FT) measurement. RESULTS The mean duration of CME before treatment with Ozurdex was 9.1 months (range, 6-13 months). At baseline, the mean FT was 542.22 ± 134.78 μm. Mean (SD) values of FT did decrease to 350.88 ± 98.71 μm (P = 0.001) at month 1 and 319.22 ± 60.96 μm (P = 0.002) at month 3. Data on the 6-month follow-up showed a mild increase 398.33 ± 127.89 μm (P = 0.031). The mean (SD) change from baseline FT was 191.33 μm (a decrease value of 35%) at month 1, and 223.00 μm (decrease value of 41%) and 143.89 μm (decrease value of 26%) at month 3 and month 6, respectively. The baseline BCVA data were 0.62 ± 0.15 logarithm of the minimum angle of resolution (logMAR). The mean BCVA improved to 0.47 ± 0.21 logMAR (P = 0.008) and 0.37 ± 0.24 logMAR (P = 0.001) after month 1 and month 3, respectively. At the last visit (6-month follow-up), the mean BCVA was 0.37 ± 0.26 logMAR (P = 0.002). CONCLUSIONS In this study, both mean FT and mean BCVA had improved from baseline by 1 month after treatment with a dexamethasone implant, and the improvement remained statistically significant throughout the 6-month study.
Error-Resilient Optimal Data Compression

The problem of communication and computation in the presence of errors is difficult, and general solutions can be time consuming and inflexible (particularly when implemented with a prescribed error detection/correction). A reasonable approach is to investigate reliable communication in carefully selected areas of fundamental interest where specific solutions may be more practical than general purpose techniques. In this paper, we study the problem of error-resilient communication and computation in a particularly challenging area, adaptive lossless data compression, where the devastating effect of error propagation is a long-standing open problem that was posed in the papers of Lempel and Ziv in the late 1970s. In fact, the non-error resilience of adaptive data compression has been a practical drawback of its use in many applications. Protocols that require the receiver to request retransmission from the sender when an error is detected can be impractical for many applications where such two-way communication is not possible or is self-defeating (e.g., with data compression, retransmission may be tantamount to losing the data that could have been transmitted in the mean time). In addition, bits of encoded data that are corrupted while data is in storage will in general not be recoverable and may corrupt the entire decompressed file. By error resilience, we mean that even though errors may not be detected, there are strong guarantees that their effects will not propagate. Our main result is a provable error-resilient adaptive lossless data-compression algorithm which nevertheless maintains optimal compression over the usual input distributions (e.g., stationary ergodic sources). We state our result in the context of a more general model that we call dynamic dictionary communication, where a sender and receiver work in a "lock-step" cooperation to maintain identical copies of a dictionary D that is constantly changing. For lossless data compression, the dictionary stores a set of strings that have been seen in the past and data is compressed by sending only indices of strings over the channel. Other applications of our model include robotics (e.g., remote terrain mapping) and computational learning theory.
FDG PET: elevated plasma glucose reduces both uptake and detection rate of pancreatic malignancies.

UNLABELLED The aim of the study was to evaluate the effects of elevated plasma glucose levels on tumor detection. METHODS One-hundred and seventy-one fasted patients (100 malignant pancreatic tumors, 46 chronic pancreatitis and 25 patients with other benign pancreatic lesions) were studied with 18F-fluorodeoxyglucose (FDG) PET before planned resective pancreatic surgery. Nineteen of 171 patients had elevated plasma glucose levels above 130 mg/dl, and 24 of 171 had diabetes mellitus. Standard uptake values (SUVs) with and without glucose correction, tumor-to-muscle ratios and tumor-to-liver ratios were measured of the pancreatic lesion respective of the area with the highest uptake within the pancreas. The original qualitative PET reports concerning the dignity of the pancreatic lesion were translated into a five-point malignancy scale. Tumor detection rates and SUVs were compared according to plasma glucose levels above and below 130 mg/dl, the presence of diabetes and by using receiver operating characteristic (ROC) analysis. RESULTS The detection rates (and mean SUVs) for pancreatic malignancies were 86% and 42% (4.2 and 2.3) if fasted plasma glucose levels were below and above 130 mg/dl, respectively. The sensitivities (and mean SUVs of malignant tumors) were 83% and 69% (3.3 and 2.5) for patients without and with known diabetes. Areas under ROC curves were nearly equal for glucose corrected SUV and visual qualitative results (0.86 and 0.85), followed by uncorrected SUV (0.83), tumor-to-liver ratios (0.80) and tumor-to-muscle ratios (0.79). SUVs for chronic pancreatitis, muscle and liver had a tendency to increase with elevated plasma glucose levels. CONCLUSION Negative PET results of patients with elevated plasma glucose should be interpreted with caution.
Diffusion abnormalities in temporal lobes of children with temporal lobe epilepsy: a preliminary diffusional kurtosis imaging study and comparison with diffusion tensor imaging

In this preliminary study, we aimed to investigate the abnormalities of water diffusion in children with temporal lobe epilepsy (TLE). Eight children with unilateral TLE (according to electroencephalography, EEG) and eight age‐ and sex‐matched controls were recruited. Diffusion tensor imaging (DTI)/diffusional kurtosis imaging (DKI) acquisitions were performed. Radial diffusivity (λ⊥), axial diffusivity (λ∥), mean diffusivity (MD) and fractional anisotropy (FA) maps were calculated for both DTI and DKI, and radial kurtosis (K⊥), axial kurtosis (K∥) and mean kurtosis (MK) maps were calculated for DKI only. Mann–Whitney test showed that, for white matter in the temporal lobe, DKI‐derived λ∥, MD and K∥ were significantly different in bilateral temporal lobes and EEG‐abnormal and EEG‐normal sides of the temporal lobe between patients and controls, whereas DTI showed no abnormalities. For gray matter, DKI detected significantly higher MD and MK in the same three comparisons, whereas DTI detected abnormalities only in the comparison between bilateral temporal lobes and between EEG‐normal sides in cases and left–right matched sides in controls. No significant difference was observed between EEG‐abnormal and EEG‐normal sides in cases. These preliminary results indicate that DKI is more sensitive than DTI for the detection of diffusion abnormalities in the temporal lobes of children with TLE, even when EEG signals are normal. These findings pave the way for the application of DKI for in‐depth studies on TLE in children. Copyright © 2012 John Wiley & Sons, Ltd.
A Genetic Screen for Mycobacterium tuberculosis Mutants Defective for Phagosome Maturation Arrest Identifies Components of the ESX-1 Secretion System

ABSTRACT After phagocytosis, the intracellular pathogen Mycobacterium tuberculosis arrests the progression of the nascent phagosome into a phagolysosome, allowing for replication in a compartment that resembles early endosomes. To better understand the molecular mechanisms that govern phagosome maturation arrest, we performed a visual screen on a set of M. tuberculosis mutants specifically attenuated for growth in mice to identify strains that failed to arrest phagosome maturation and trafficked to late phagosomal compartments. We identified 10 such mutants that could be partitioned into two classes based on the kinetics of trafficking. Importantly, four of these mutants harbor mutations in genes that encode components of the ESX-1 secretion system, a pathway critical for M. tuberculosis virulence. Although ESX-1 is required, the known ESX-1 secreted proteins are dispensable for phagosome maturation arrest, suggesting that a novel effector required for phagosome maturation arrest is secreted by ESX-1. Other mutants identified in this screen had mutations in genes involved in lipid synthesis and secretion and in molybdopterin biosynthesis, as well as in genes with unknown functions. Most of these trafficking mutants exhibited a corresponding growth defect during macrophage infection, but two mutants grew like wild-type M. tuberculosis during macrophage infection. Our results support the emerging consensus that multiple factors from M. tuberculosis, including the ESX-1 secretion system, are involved in modulating trafficking within the host.