Miracle-dz/UniFAR-FTUs huggingface dataset:
High-Dimensional Robust Mean Estimation in Nearly-Linear Time

We study the fundamental problem of high-dimensional mean estimation in a robust model where a constant fraction of the samples are adversarially corrupted. Recent work gave the first polynomial time algorithms for this problem with dimension-independent error guarantees for several families of structured distributions. In this work, we give the first nearly-linear time algorithms for high-dimensional robust mean estimation. Specifically, we focus on distributions with (i) known covariance and sub-gaussian tails, and (ii) unknown bounded covariance. Given $N$ samples on $\mathbb{R}^d$, an $\epsilon$-fraction of which may be arbitrarily corrupted, our algorithms run in time $\tilde{O}(Nd) / \mathrm{poly}(\epsilon)$ and approximate the true mean within the information-theoretically optimal error, up to constant factors. Previous robust algorithms with comparable error guarantees have running times $\tilde{\Omega}(N d^2)$, for $\epsilon = \Omega(1)$. Our algorithms rely on a natural family of SDPs parameterized by our current guess $\nu$ for the unknown mean $\mu^\star$. We give a win-win analysis establishing the following: either a near-optimal solution to the primal SDP yields a good candidate for $\mu^\star$ -- independent of our current guess $\nu$ -- or the dual SDP yields a new guess $\nu'$ whose distance from $\mu^\star$ is smaller by a constant factor. We exploit the special structure of the corresponding SDPs to show that they are approximately solvable in nearly-linear time. Our approach is quite general, and we believe it can also be applied to obtain nearly-linear time algorithms for other high-dimensional robust learning problems.
HDAC stimulates gene expression through BRD4 availability in response to IFN and in interferonopathies

In contrast to the common role of histone deacetylases (HDACs) for gene repression, HDAC activity provides a required positive function for IFN-stimulated gene (ISG) expression. Here, we show that HDAC1/2 as components of the Sin3A complex are required for ISG transcriptional elongation but not for recruitment of RNA polymerase or transcriptional initiation. Transcriptional arrest by HDAC inhibition coincides with failure to recruit the epigenetic reader Brd4 and elongation factor P-TEFb due to sequestration of Brd4 on hyperacetylated chromatin. Brd4 availability is regulated by an equilibrium cycle between opposed acetyltransferase and deacetylase activities that maintains a steady-state pool of free Brd4 available for recruitment to inducible promoters. An ISG expression signature is a hallmark of interferonopathies and other autoimmune diseases. Combined inhibition of HDAC1/2 and Brd4 resolved the aberrant ISG expression detected in cells derived from patients with two inherited interferonopathies, ISG15 and USP18 deficiencies, defining a novel therapeutic approach to ISG-associated autoimmune diseases.
Recurrence to the Rescue: Towards Causal Spatiotemporal Representations

Recently, three dimensional (3D) convolutional neural networks (CNNs) have emerged as dominant methods to capture spatiotemporal representations, by adding to pre-existing 2D CNNs a third, temporal dimension. Such 3D CNNs, however, are anti-causal (i.e., they exploit information from both the past and the future to produce feature representations, thus preventing their use in online settings), constrain the temporal reasoning horizon to the size of the temporal convolution kernel, and are not temporal resolution-preserving for video sequence-to-sequence modelling, as, e.g., in spatiotemporal action detection. To address these serious limitations, we present a new architecture for the causal/online spatiotemporal representation of videos. Namely, we propose a recurrent convolutional network (RCN), which relies on recurrence to capture the temporal context across frames at every level of network depth. Our network decomposes 3D convolutions into (1) a 2D spatial convolution component, and (2) an additional hidden state $1\times 1$ convolution applied across time. The hidden state at any time $t$ is assumed to depend on the hidden state at $t-1$ and on the current output of the spatial convolution component. As a result, the proposed network: (i) provides flexible temporal reasoning, (ii) produces causal outputs, and (iii) preserves temporal resolution. Our experiments on the large-scale large "Kinetics" dataset show that the proposed method achieves superior performance compared to 3D CNNs, while being causal and using fewer parameters.
Prediction of Online Students Performance by Means of Genetic Programming

ABSTRACT Problem: Online higher education (OHE) failure rates reach 40% worldwide. Prediction of student performance at early stages of the course calendar has been proposed as strategy to prevent student failure. Objective: To investigate the application of genetic programming (GP) to predict the final grades (FGs) of online students using grades from an early stage of the course as the independent variable Method: Data were obtained from the learning management system; we performed statistical analyses over FGs as dependent variable and 11 independent variables; two statistical and one GP models were generated; the prediction accuracies of the models were compared by means of a statistical test. Results: GP model was better than statistical models with confidence levels of 90% and 99% for the training testing data sets respectively. These results suggest that GP could be implemented for supporting decision making process in OHE for early student failure prediction.
The Impact of Pursed-lips Breathing Maneuver on Cardiac, Respiratory, and Oxygenation Parameters in COPD Patients

BACKGROUND: Respiratory system, together with the cardiovascular and central nervous system, is responsible for all processes related to oxygenation and hemodynamics and the defect in the functioning of each of these systems, along with ageing, can have mutual effects on their performance and physiological symptoms. The use of Pursed-lips Breathing (PLB) training is an essential part of the treatment of patients with the obstructive pulmonary disease, PLB stimulates the autonomic nervous system and causes relaxation and improvement of physiological parameters. AIM: This study was conducted to evaluate the effect of PLB on cardiac, pulmonary and oxygenation level in patients with Chronic Obstructive Pulmonary Disease (COPD). METHODS: A three-group clinical trial study with experimental and control which was purposefully conducted with the participation of patients with COPD and healthy individuals referring to Madani hospital Khoy, in 2017. The sample size was selected to be 60 subjects. The patients were randomly allocated to two groups of intervention and control with 20 patients, and 20 healthy subjects were assigned to the healthy intervention group. The demographic, anthropometric information form and checklist recording changes in levels of oxygenation, respiration, temperature, heart rate and blood pressure with cardiopulmonary follow up in three stages before, during and after PLB were used for data collection. Data were analysed using descriptive statistics, repeated measure test, ANOVA, and Chi-square. RESULTS: On evaluation within the COPD patient intervention group in Saturation of Peripheral Oxygen (SPO2) index with the mean difference of 2.05 percent, Respiratory Rate(RR)-0.65 minute and Pulse Rate(PR)-1.6 bpm was significant (p ≤ 0.05), and systolic blood pressure index in healthy subjects was increased (3.35 mmHg). CONCLUSION: The results of this study indicated that using effective PLB as an easy, inexpensive, non- invasive and non-pharmacological method is considered as an important factor in improving the status of oxygenation and physiological indicators in patients with COPD and should be considered as an important part of rehabilitation programs for these patients.
The role of loops B and C in determining the potentiation of GABAA receptors by midazolam

Many benzodiazepines are positive allosteric modulators (PAMs) of GABAA receptors that cause sedation, hypnosis, and anxiolysis. Benzodiazepines bind GABAA receptors at the extracellular interface of the α and γ subunits. Within the α subunit, the benzodiazepine binding site is defined by three highly conserved structural loops, loops A‐C. Although previous mutagenesis studies have identified His102 in Loop A as important for benzodiazepine modulation of GABAA receptors, the functional roles of many of the other conserved residues in loops A‐C remain incompletely understood. In this study, we made single mutations in loops A‐C of the benzodiazepine binding‐site across all six α subunits. We used whole‐cell patch clamp recording to measure the functional effects of these mutations on midazolam potentiation. The results showed that mutating the threonine in loop B and serine in loop C (Thr163 and S206 in human α1) did not abolish the receptors’ responsiveness to midazolam, as the α1(H102R) mutation did. The loop C mutations exhibited a novel array of α‐isoform specific effects on midazolam potentiation. The α3(S230I) and α5(S209I) mutations had the largest effect on midazolam potentiation, increasing the efficacy of midazolam. Novel benzodiazepines targeting loop C may represent a future direction for designing new drugs that specifically alter the activity of α3‐ and α5‐containing GABAA receptors.
Long-Term Monitoring of Crack Patterns in Historic Structures Using UAVs and Planar Markers: A Preliminary Study

This paper describes how Unmanned Aerial Vehicles (UAVs) may support the long-term monitoring of crack patterns in the context of architectural heritage preservation. In detail, this work includes: (i) a state of the art about the most used techniques in ancient structural monitoring; (ii) the description of the implemented methods, taking into account the requirements and constraints of the case study; (iii) the results of the experimentation carried out in the lab; and (iv) conclusions and future works.
EBV Positive Gastric Carcinomas and Their Clinicopathological Characteristics

BACKGROUND: The understanding of the etiopathogenesis of gastric carcinoma (GC) can be a base for development of new therapeutic methods to reduce mortality and to increase survival in patients with GC. The percentage of Epstein - Barr virus (EBV) positive gastric carcinomas is uncertain, and the etiologic importance of EBV in the pathogenesis of GC has still not been elucidated. AIM: This study aimed to determine the percentage of EBV associated GC as well as to determine their clinicopathological characteristics. MATERIAL AND METHODS: The study included 80 patients with GC who were analysed for ethnicity, local growth of a tumour (T status), the presence of nodal metastases (N), the presence of distant metastases (M), stage of the disease and degree of carcinoma differentiation. For detection of EBV, immunostainings were performed on tumour tissue and the peripheral non-tumour gastric mucosa. RESULTS: Positive immunostaining with an antibody against EBV was found in 19 (23.75%) of the 80 patients with gastric carcinomas. EBV immunostainings were significantly different in patients with or without metastasis and between patients of Macedonian and Albanian ethnicity (p < 0.0001, p < 0.009, respectively). EBV immunoexpression was significantly associated with the presence of distant metastases and with patients of Albanian ethnicity. CONCLUSION: Association of EBV immunostainings with distant metastasis in patients with GC suggests the influence of EBV infection on the progression of gastric carcinoma. Due to scarce and doubtful literature data on EBV associated GC, further studies are necessary to determine the role of EBV regarding aetiology, treatment and prognosis in patients with EBV associated gastric carcinoma.
Intestinal metastasis from primary ROS1-positive lung adenocarcinoma cancer patients responding to crizotinib

Small intestinal metastases from primary lung cancer are rare. Such patients have a poor prognosis. Early diagnosis of small intestinal metastases is difficult because of the low incidence of clinically apparent symptoms. The standard treatment for small intestinal metastases has not been established. A 69-year-old Chinese man presented for evaluation of a tumor in the right lower lung and mediastinal lymph node enlargement on clinical examination. The clinical stage was cT2N2M0 (stage IIIA). Histologic examination of the tumor revealed lung adenocarcinoma. He could not tolerate surgery; hence, he received two chemotherapy regimens. However, the disease progressed. He had bloating after chemotherapy and decreased flatus. An abdominal CT scan showed an intestinal effusion with local intestinal obstruction. Medical treatment was ineffective; hence, he underwent a diagnostic laparoscopy. The pathologic evaluation suggested an intestinal metastatic adenocarcinoma from the primary lung cancer. Based on an real-time PCR assay, the tumor had a ROS1 fusion and responded well to crizotinib. The progression-free survival was 7 months. Physicians must be aware of the possibility of intestinal metastases from primary lung cancer. With an accurate diagnosis and thorough evaluation, patients may benefit from targeted therapy.
Nanobodies reveal an extra-synaptic population of SNAP-25 and Syntaxin 1A in hippocampal neurons

Synaptic vesicle fusion (exocytosis) is a precisely regulated process that entails the formation of SNARE complexes between the vesicle protein synaptobrevin 2 (VAMP2) and the plasma membrane proteins Syntaxin 1 and SNAP-25. The sub-cellular localization of the latter two molecules remains unclear, although they have been the subject of many recent investigations. To address this, we generated two novel camelid single domain antibodies (nanobodies) specifically binding to SNAP-25 and Syntaxin 1A. These probes penetrated more easily into samples and detected their targets more efficiently than conventional antibodies in crowded regions. When investigated by super-resolution imaging, the nanobodies revealed substantial extra-synaptic populations for both SNAP-25 and Syntaxin 1A, which were poorly detected by antibodies. Moreover, extra-synaptic Syntaxin 1A molecules were recruited to synapses during stimulation, suggesting that these are physiologically-active molecules. We conclude that nanobodies are able to reveal qualitatively and quantitatively different organization patterns, when compared to conventional antibodies.
Destabilization of spindle assembly checkpoint causes aneuploidy during meiosis II in murine post-ovulatory aged oocytes

Mammalian oocyte quality degrades over time after ovulation in vitro, which can cause fatal defects such as chromosomal aneuploidy. As various oocyte manipulations employed in assisted reproductive technology are time consuming, post-ovulatory aging is a serious problem to overcome in reproductive medicine or ova research. In this study, we investigated the effects of postovulatory aging on the incidence of chromosome aneuploidy during meiosis II, with a focus on the expression of functional proteins from the spindle assembly checkpoint (SAC). Chromosome analysis was used to assess the rate of aneuploidy in in vitro aged oocytes, or in early embryos derived from aged oocytes. Immunofluorescent staining was used to detect the localization of MAD2, which is a SAC signal that monitors the correct segregation of sister chromatids. Immunoblotting was used to quantify cohesin subunits, which are adhesion factors connecting sister chromatids at the metaphase II (MII) centromere. It was shown that post-ovulatory oocyte aging inhibits MAD2 localization to the sister kinetochore. Furthermore, oocyte aging prevented cohesin subunits from being maintained or degraded at the appropriate time. These data suggest that the destabilization of SAC signaling causes sister chromatid segregation errors in MII oocytes, and consequently increases the incidence of aneuploidy in early embryos. Our findings have provided distinct evidence that the post-ovulatory aging of oocytes might also be a risk factor for aneuploidy, irrespective of maternal age.
Connexin-43 Gap Junctions Are Responsible for the Hypothalamic Tanycyte-Coupled Network

Tanycytes are hypothalamic radial glia-like cells that form the basal wall of the third ventricle (3V) where they sense glucose and modulate neighboring neuronal activity to control feeding behavior. This role requires the coupling of hypothalamic cells since transient decreased hypothalamic Cx43 expression inhibits the increase of brain glucose-induced insulin secretion. Tanycytes have been postulated as possible hypothalamic neuronal precursors due to their privileged position in the hypothalamus that allows them to detect mitogenic signals and because they share the markers and characteristics of neuronal precursors located in other neurogenic niches, including the formation of coupled networks through connexins. Using wild-type (WT), Cx30−/– and Cx30−/–, Cx43fl/fl:glial fibrillary acidic protein (GFAP)-Cre (double knockout, dKO) mouse lines, we demonstrated that tanycytes are highly coupled to each other and also give rise to a panglial network specifically through Cx43. Using the human GFAP (hGFAP)-enhanced green fluorescent protein (EGFP) transgenic mouse line, we provided evidence that the main parenchymal-coupled cells were astrocytes. In addition, electrophysiological parameters, such as membrane resistance, were altered when Cx43 was genetically absent or pharmacologically inhibited. Finally, in the dKO mouse line, we detected a significant decrease in the number of hypothalamic proliferative parenchymal cells. Our results demonstrate the importance of Cx43 in tanycyte homotypic and panglial coupling and show that Cx43 function influences the proliferative potential of hypothalamic cells.
Contextual and individual determinants of non‐utilization of dental services among Brazilian adults

OBJECTIVES To examine the association of contextual and individual determinants with non-utilization of dental services among Brazilian adults. METHODS Data were from adults aged 35-44 years (N = 7,265) from the 2010 Brazilian Oral Health Survey (SB Brasil Project). Non-utilization of dental services was assessed whether the individual has never had a dental visit over the whole life time. Independent variables were selected according to Andersen's behavioral model. Contextual variables included Human Development Index-longevity (HDI-Longevity) (predisposing demographic), HDI-Education and Gini index (predisposing social), integration of oral health teams into Primary Care (enabling health policy), and HDI-Income (enabling financing). Individual data were age and sex (predisposing demographic), ethnicity and schooling (predisposing social), family monthly income (predisposing enabling), perceived dental treatment (perceived need), and decayed teeth (evaluated need). The relationship of contextual and individual variables with non-utilization of dental services was assessed through multilevel logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (95% CI). RESULTS The prevalence of non-utilization of dental services was 4.7 percent. Adults living in cities with high HDI-Income were less likely to never have a dental visit. The odds of non-utilization of dental services were lower for adults living in cities with high HDI-Longevity. Sex, skin color, dental treatment needs, poor socioeconomic characteristics, perceived dental treatment needs, and decayed teeth were also associated with non-utilization of dental services. CONCLUSIONS The results suggest that contextual enabling and predisposing factors, individual sociodemographic, and needs-related characteristics influence non-utilization of dental services by Brazilian adults.
The relationships among verbal ability, executive function, and theory of mind in young children with cochlear implants

Abstract This study aims to examine the complex relationships among verbal ability (VA), executive function (EF), and theory of mind (ToM) in young Chinese children with cochlear implants (CCI). All participants were tested using a set of nine measures: one VA, one non-VA, three EF, and four ToM. Our study cohort comprised 82 children aged from 3.8 to 6.9 years, including 36 CCI and 46 children with normal hearing (CNH). CNH outperformed CCI on measures of VA, EF, and ToM. One of the EF tasks, inhibitory control, was significantly associated with ToM after controlling for VA. VA was the primary predictor of EF, while inhibitory control significantly predicted ToM. Our findings suggest that inhibitory control explains the association between EF and ToM, thereby supporting the hypothesis that EF may be a prerequisite for ToM.
The cis-regulatory logic underlying abdominal Hox-mediated repression versus activation of regulatory elements in Drosophila

Hox genes encode a family of transcription factors that, despite having similar in vitro DNA binding preferences, regulate distinct genetic programs along the metazoan anterior-posterior axis. To better define mechanisms of Hox specificity, we compared and contrasted the ability of abdominal Hox factors to regulate two cis-regulatory elements within the Drosophila embryo. Both the Ultrabithorax (Ubx) and Abdominal-A (Abd-A) Hox factors form cooperative complexes with the Extradenticle (Exd) and Homothorax (Hth) transcription factors to repress the distal-less leg selector gene via the DCRE, whereas only Abd-A interacts with Exd and Hth on the RhoA element to activate a rhomboid serine protease gene that stimulates Epidermal Growth Factor secretion. By swapping binding sites between these elements, we found that the RhoA Exd/Hth/Hox site configuration that mediates Abd-A specific activation can also convey transcriptional repression by both Ubx and Abd-A when placed into the DCRE, but only in one orientation. We further show that the orientation and spacing of Hox sites relative to additional transcription factor binding sites within the RhoA and DCRE elements is critical to mediate appropriate cell- and segment-specific output. These results indicate that the interaction between Hox, Exd, and Hth neither determines activation vs repression specificity nor defines Ubx vs Abd-A specificity. Instead the precise integration of Hox sites with additional TF inputs is required for accurate transcriptional output. Taken together, these studies provide new insight into the mechanisms of Hox target and regulatory specificity as well as the constraints placed on regulatory elements to convey appropriate outputs. Author Summary The Hox genes encode a family of transcription factors that give cells within each region along the developing body plan a unique identity in animals from worms to mammals. Surprisingly, however, most of the Hox factors bind the same or highly similar DNA sequences. These findings raise a paradox: How can proteins that have highly similar DNA binding properties perform different functions in the animal by regulating different sets of target genes? In this study, we address this question by studying how two Hox factors regulate the expression of target genes that specify leg development and the making of liver-like cells in the developing fly. By comparing and contrasting how Hox target genes are activated and/or repressed, we found that the same Hox binding sites can mediate either activation or repression in a manner that depends upon context. In addition, we found that a Hox binding site that is normally regulated by only one Hox factor, can also be used by more than one Hox factor swapped into another target gene. These findings indicate that the specificity of a Hox factor to regulate target genes does not rely solely upon DNA binding specificity but also requires regulatory specificity.