Miracle-dz/UniFAR-FTUs huggingface dataset:
A Case for Microtubule Vulnerability in Amyotrophic Lateral Sclerosis: Altered Dynamics During Disease

Amyotrophic lateral sclerosis (ALS) is an aggressive multifactorial disease converging on a common pathology: the degeneration of motor neurons (MNs), their axons and neuromuscular synapses. This vulnerability and dysfunction of MNs highlights the dependency of these large cells on their intracellular machinery. Neuronal microtubules (MTs) are intracellular structures that facilitate a myriad of vital neuronal functions, including activity dependent axonal transport. In ALS, it is becoming increasingly apparent that MTs are likely to be a critical component of this disease. Not only are disruptions in this intracellular machinery present in the vast majority of seemingly sporadic cases, recent research has revealed that mutation to a microtubule protein, the tubulin isoform TUBA4A, is sufficient to cause a familial, albeit rare, form of disease. In both sporadic and familial disease, studies have provided evidence that microtubule mediated deficits in axonal transport are the tipping point for MN survivability. Axonal transport deficits would lead to abnormal mitochondrial recycling, decreased vesicle and mRNA transport and limited signaling of key survival factors from the neurons peripheral synapses, causing the characteristic peripheral “die back”. This disruption to microtubule dependant transport in ALS has been shown to result from alterations in the phenomenon of microtubule dynamic instability: the rapid growth and shrinkage of microtubule polymers. This is accomplished primarily due to aberrant alterations to microtubule associated proteins (MAPs) that regulate microtubule stability. Indeed, the current literature would argue that microtubule stability, particularly alterations in their dynamics, may be the initial driving force behind many familial and sporadic insults in ALS. Pharmacological stabilization of the microtubule network offers an attractive therapeutic strategy in ALS; indeed it has shown promise in many neurological disorders, ALS included. However, the pathophysiological involvement of MTs and their functions is still poorly understood in ALS. Future investigations will hopefully uncover further therapeutic targets that may aid in combating this awful disease.
Integrating Fossils, Phylogenies, and Niche Models into Biogeography to Reveal Ancient Evolutionary History: The Case of Hypericum (Hypericaceae)

In disciplines such as macroevolution that are not amenable to experimentation, scientists usually rely on current observations to test hypotheses about historical events, assuming that “the present is the key to the past. ” Biogeographers, for example, used this assumption to reconstruct ancestral ranges from the distribution of extant species. Yet, under scenarios of high extinction rates, the biodiversity we observe today might not be representative of the historical diversity and this could result in incorrect biogeographic reconstructions. Here, we introduce a new approach to incorporate into biogeographic inference the temporal, spatial, and environmental information provided by the fossil record, as a direct evidence of the extinct biodiversity fraction. First, inferences of ancestral ranges for those nodes in the phylogeny calibrated with the fossil record are constrained to include the geographic distribution of the fossil. Second, we use fossil distribution and past climate data to reconstruct the climatic preferences and potential distribution of ancestral lineages over time, and use this information to build a biogeographic model that takes into account “ecological connectivity” through time. To show the power of this approach, we reconstruct the biogeographic history of the large angiosperm genus Hypericum, which has a fossil record extending back to the Early Cenozoic. Unlike previous reconstructions based on extant species distributions, our results reveal that Hypericum stem lineages were already distributed in the Holarctic before diversification of its crown-group, and that the geographic distribution of the genus has been relatively stable throughout the climatic oscillations of the Cenozoic. Geographical movement was mediated by the existence of climatic corridors, like Beringia, whereas the equatorial tropical belt acted as a climatic barrier, preventing Hypericum lineages to reach the southern temperate regions. Our study shows that an integrative approach to historical biogeography—that combines sources of evidence as diverse as paleontology, ecology, and phylogenetics—could help us obtain more accurate reconstructions of ancient evolutionary history. It also reveals the confounding effect different rates of extinction across regions have in biogeography, sometimes leading to ancestral areas being erroneously inferred as recent colonization events.
Immunoglobulin Heavy Chain Variable Gene Usage and (Super)-antigen Drive in Chronic Lymphocytic Leukemia

Increasing evidence supports the prognostic relevance of specific immunoglobulin heavy chain variable (IGHV) genes or stereotyped B-cell receptors (BCR) in chronic lymphocytic leukemia (CLL). The clonotypic BCRs differ in their specificity and affinity toward classical antigens and/or superantigens. The BCR-triggered mechanisms are distinct but could explain in part the different clinical behavior among CLL subgroups. Clin Cancer Res; 16(2); 373–5
Verrucous Carcinoma of the Vulva: A Case Report

Verrucous carcinoma of the female genital tract is a rare lesion, primarily affecting postmenopausal women. We present a 78-year-old patient with verrucous carcinoma of the vulva, who was admitted to the "Aretaieion" Athens University Hospital. She had complained of vulvar itching during the last two years without visiting a specialist doctor.
Fast Bayesian Optimization of Machine Learning Hyperparameters on Large Datasets

Bayesian optimization has become a successful tool for hyperparameter optimization of machine learning algorithms, such as support vector machines or deep neural networks. Despite its success, for large datasets, training and validating a single configuration often takes hours, days, or even weeks, which limits the achievable performance. To accelerate hyperparameter optimization, we propose a generative model for the validation error as a function of training set size, which is learned during the optimization process and allows exploration of preliminary configurations on small subsets, by extrapolating to the full dataset. We construct a Bayesian optimization procedure, dubbed Fabolas, which models loss and training time as a function of dataset size and automatically trades off high information gain about the global optimum against computational cost. Experiments optimizing support vector machines and deep neural networks show that Fabolas often finds high-quality solutions 10 to 100 times faster than other state-of-the-art Bayesian optimization methods or the recently proposed bandit strategy Hyperband.
Environment manipulation planner for humanoid robots using task graph that generates action sequence

In this paper, we describe a planner for a humanoid robot that is capable of finding a path in an environment with movable objects, whereas previous motion planner only deals with an environment with fixed objects. We address an environment manipulation problem for a humanoid robot that finds a walking path from the given start location to the goal location while displacing obstructing objects on the walking path. This problem requires more complex configuration space than previous researches using a mobile robot especially in a manipulation phase, since a humanoid robot has many degrees of freedom in its arm than a forklift type robot. Our approach is to build environment manipulation task graph that decompose the given task into subtasks which are solved using navigation path planner or whole body motion planner. We also propose a standing location search and a displacing obstacle location search for connecting subtasks. Efficient method to solve manipulation planning that relies on whole body inverse kinematics and motion planning technology is also shown. Finally, we show experimental results in an environment with movable objects such as chairs and trash boxes. The planner finds an action sequence consists of walking paths and manipulating obstructing objects to walk from the start position to the goal position.
Analyzing the Family Tree

FamilySearch holds one of the largest collections of linked family history data in the world. Nearly one billion records of individuals, both deceased and living, have been recorded and placed together into a common tree (“The Family Tree”). The study of this ancestral relationship graph consists of the largest family history network ever analyzed. We have found a number of interesting properties in the network using common graph analysis techniques. We examine the topology of the graph by calculating the connected components within the graph. The total network consists of one giant component consisting of many millions of records plus millions of very small components. We also describe how this topology has changed over time. The paper further describes how an analysis of the strongly connected components and the graph’s diameter can be used to assess the quality of the data. Finally, we describe a heuristic algorithm to determine the “connectedness” of our patrons and find that those who have logged into the system are significantly more connected than those that have not. One third of the potential users are connected to the giant component while 80% of the active users are. We discuss how this analysis could potentially be used to partition the graph to support scaling or distributing the system.
The Interaction between tRNALys 3 and the Primer Activation Signal Deciphered by NMR Spectroscopy

The initiation of reverse transcription of the human immunodeficiency virus type 1 (HIV-1) requires the opening of the three-dimensional structure of the primer tRNALys 3 for its annealing to the viral RNA at the primer binding site (PBS). Despite the fact that the result of this rearrangement is thermodynamically more stable, there is a high-energy barrier that requires the chaperoning activity of the viral nucleocapsid protein. In addition to the nucleotide complementarity to the PBS, several regions of tRNALys 3 have been described as interacting with the viral genomic RNA. Among these sequences, a sequence of the viral genome called PAS for “primer activation signal” was proposed to interact with the T-arm of tRNALys 3, this interaction stimulating the initiation of reverse transcription. In this report, we investigate the formation of this additional interaction with NMR spectroscopy, using a simple system composed of the primer tRNALys 3, the 18 nucleotides of the PBS, the PAS (8 nucleotides) encompassed or not in a hairpin structure, and the nucleocapsid protein. Our NMR study provides molecular evidence of the existence of this interaction and highlights the role of the nucleocapsid protein in promoting this additional RNA-RNA annealing. This study presents the first direct observation at a single base-pair resolution of the PAS/anti-PAS association, which has been proposed to be involved in the chronological regulation of the reverse transcription.
A rare cause of gastrointestinal bleeding in a patient with hyper-IgE syndrome

Background:Salmonella enterica serovar typhimurium (Styphimurium) causes invasive gastroenteritis in humans, a disease involving significant penetration of the intestinal mucosa. However, few studies have been undertaken to investigate this interaction directly using differentiated human gut tissue. Aims: To investigate the early interactions of an enteropathogenic strain of S typhimurium with human intestinal mucosa using human intestinal in vitro organ culture (IVOC). Methods: Wild-type and mutant derivatives of S typhimurium TML were used to compare interactions with cultured human epithelial cells, bovine ligated loops, and human intestinal IVOC. Results:S typhimurium TML was shown to attach to cultured Caco-2 brush border expressing cells and cause tissue damage and fluid accumulation in a ligated bovine loop model.Styphimurium TML bound predominantly to the mucus layer of human IVOC explants during the first four hours of IVOC incubation. From four to eight hours of IVOC incubation, small but characteristic foci of attaching and invading Styphimurium TML were detected as clusters of bacteria interacting with enterocytes, although there was no evidence for large scale invasion of explant tissues. Ruffling of enterocyte membranes associated with adherent Salmonella was visualised using electron microscopy. Conclusions: Human IVOC can be used as an alternative model for monitoring the interactions between S typhimurium and human intestinal epithelium, thus potentially offering insight into the early stages of human Salmonella induced gastroenteritis.
Privacy-Preserving Audit and Extraction of Digital Contents

A growing number of online services, such as Google, Yahoo! , and Amazon, are starting to charge users for their storage. Customers often use these services to store valuable data such as email, family photos and videos, and disk backups. Today, a customer must entirely trust such external services to maintain the integrity of hosted data and return it intact. Unfortunately, no service is infallible. To make storage services accountable for data loss, we present protocols that allow a thirdparty auditor to periodically verify the data stored by a service and assist in returning the data intact to the customer. Most importantly, our protocols are privacy-preserving, in that they never reveal the data contents to the auditor. Our solution removes the burden of verification from the customer, alleviates both the customer’s and storage service’s fear of data leakage, and provides a method for independent arbitration of data retention contracts.
The Dissonant Self: Contributions from Dissonance Theory to a New Agenda for Studying Political Communication

Due to technological changes in today’s communication environments, the investigation of media use and media effects has become an ever more complex research venture. In order to adequately comprehend the social practices of media users in the age of the Internet, various scholars have recently recommended a new agenda for the future study of political communication. Based on these suggestions, the following paper briefly outlines two research strands of political communication—political polarization and political demobilization—which are currently the focus of significant attention and scientific dispute. In reference to cognitive dissonance theory, we propose one possible strategy for media research to determine future developments of political communication in both research domains by observing citizens’ motivational changes in their exposure to political information.
Investigating Rural Library Usage among Rural Youth in Malaysia: Its Corresponding Determinants and Impacts

The demands for information are increasing nowadays, providing adequate sources of information for the community is a crucial agenda as it is an essential part of community development particularly the youth; the future leader of our community. As information and communication technology (ICT) play significant roles as sources of information, similarly, the rural library in Malaysia can play the same roles in offering updated and needed information of the community. The main objective of this paper is to know the potential factors, benefits and problems in using the services provided in the rural library. Discussion of this paper is based on applied documents and literature analysis. Based on the analyses done, a number of potential benefits offered by the rural community have been identified and certainly information offered is the main benefit available. Potential problems faced by the rural community in using the rural library services need to be overcome to ensure the rural community will profits from the benefits offered. Besides, a number of related factors and theories have been further discussed.
Increased functional connectivity indicates the severity of cognitive impairment in multiple sclerosis

Correlations in spontaneous brain activity provide powerful access to large-scale organizational principles of the CNS. However, making inferences about cognitive processes requires a detailed understanding of the link between these couplings and the structural integrity of the CNS. We studied the impact of multiple sclerosis, which leads to the severe disintegration of the central white matter, on functional connectivity patterns in spontaneous cortical activity. Using a data driven approach based on the strength of a salient pattern of cognitive pathology, we identified distinct networks that exhibit increases in functional connectivity despite the presence of strong and diffuse reductions of the central white-matter integrity. The default mode network emerged as a core target of these connectivity modulations, showing enhanced functional coupling in bilateral inferior parietal cortex, posterior cingulate, and medial prefrontal cortex. These findings imply a complex and diverging relation of anatomical and functional connectivity in early multiple sclerosis and, thus, add an important observation for understanding how cognitive abilities and CNS integrity may be reflected in the intrinsic covariance of functional signals.
Pronunciation variation modeling for ASR : large improvements are possible but small ones are likely to achieve

In this paper a previously proposed method for the automatic construction of a lexicon with pronunciation variants for ASR is further developed and evaluated. The basic idea is to transform a lexicon of canonical forms by means of rewrite rules that are learned automatically on a training corpus of orthographically transcribed utterances. The method is evaluated on the TIMIT corpus, using a speech recognizer incorporating context-independent HMMs and a bigram language model. It appears that reductions of the word error rate of up to 35 % are possible to achieve. However, it also appears that it is more likely to obtain much lower gains.
Global variational method for fingerprint segmentation by three-part decomposition

Verifying an identity claim by fingerprint recognition is a commonplace experience for millions of people in their daily life, e.g. for unlocking a tablet computer or smartphone. The first processing step after fingerprint image acquisition is segmentation, i.e. dividing a fingerprint image into a foreground region which contains the relevant features for the comparison algorithm, and a background region. We propose a novel segmentation method by global three-part decomposition (G3PD). Based on global variational analysis, the G3PD method decomposes a fingerprint image into cartoon, texture and noise parts. After decomposition, the foreground region is obtained from the non-zero coefficients in the texture image using morphological processing. The segmentation performance of the G3PD method is compared to five state-of-the-art methods on a benchmark which comprises manually marked ground truth segmentation for 10560 images. Performance evaluations show that the G3PD method consistently outperforms existing methods in terms of segmentation accuracy.
Stellar encounters: a stimulus for disc fragmentation?

An interaction between a star-disc system and another star will perturb the disc, possibly resulting in a significant modification of the disc structure and its properties. It is still unclear if such an encounter can trigger fragmentation of the disc to form brown dwarfs or gas giant planets. This paper details high-resolution smoothed particle hydrodynamics (sph) simulations investigating the influence of stellar encounters on disc dynamics. Star–star encounters (where the primary has a self-gravitating, marginally stable protostellar disc, and the secondary has no disc) were simulated with various orbital parameters to investigate the resulting disc structure and dynamics. This work is the first of its kind to incorporate realistic radiative transfer techniques to realistically model the resulting thermodynamics. The results suggest that the effect of stellar encounters is to prohibit fragmentation – compressive and shock heating stabilizes the disc, and the radiative cooling is insufficient to trigger gravitational instability. The encounter strips the outer regions of the disc (either through tidal tails or by capture of matter to form a disc around the secondary), which triggers a readjustment of the primary disc to a steeper surface density profile (and a flatter Toomre Q profile). The disc around the secondary plays a role in the potential capture of the secondary to form a binary. However, this applies only to orbits that are parabolic – hyperbolic encounters do not form a secondary disc, and are not captured.
Chronic VEGF Blockade Worsens Glomerular Injury in the Remnant Kidney Model

VEGF inhibition can promote renal vascular and parenchymal injury, causing proteinuria, hypertension and thrombotic microangiopathy. The mechanisms underlying these side effects are unclear. We investigated the renal effects of the administration, during 45 days, of sunitinib (Su), a VEGF receptor inhibitor, to rats with 5/6 renal ablation (Nx). Adult male Munich-Wistar rats were distributed among groups S+V, sham-operated rats receiving vehicle only; S+Su, S rats given Su, 4 mg/kg/day; Nx+V, Nx rats receiving V; and Nx+Su, Nx rats receiving Su. Su caused no change in Group S. Seven and 45 days after renal ablation, renal cortical interstitium was expanded, in association with rarefaction of peritubular capillaries. Su did not worsen hypertension, proteinuria or interstitial expansion, nor did it affect capillary rarefaction, suggesting little angiogenic activity in this model. Nx animals exhibited glomerulosclerosis (GS), which was aggravated by Su. This effect could not be explained by podocyte damage, nor could it be ascribed to tuft hypertrophy or hyperplasia. GS may have derived from organization of capillary microthrombi, frequently observed in Group Nx+Su. Treatment with Su did not reduce the fractional glomerular endothelial area, suggesting functional rather than structural cell injury. Chronic VEGF inhibition has little effect on normal rats, but can affect glomerular endothelium when renal damage is already present.
Credit Gap in Small Businesses: Some New Evidence

What is the magnitude of credit constraint affecting small businesses? This paper provides estimate of the credit gap – defined as the difference between the desired and actual levels of debt for credit constrained small businesses. The estimated credit gap is approximately 20 percent, i.e., credit constrained small business on the average would desire 20 percent more debt. This credit gap varies considerably across industries, with manufacturing firms facing a significantly larger gap than firms in the wholesale or service industries.
Equilibrium at a Bottleneck When Long-Run and Short-Run Scheduling Preferences Diverge

We consider equilibrium and optimum use of a Vickrey road bottleneck, distinguishing between long-run and short-run scheduling preferences in an otherwise stylized scheduling model. The preference structure reflects that there is a distinction between the (exogenous) 'long-run preferred arrival time', which would be relevant if consumers were unconstrained in the scheduling of their activities, versus the 'short-run preferred arrival time', which is the result of an adaptation of travel routines in the face of constraints caused by, in particular, time-varying congestion levels. We characterize the unpriced equilibrium, the social optimum as well as second-best situations where the availability of the pricing instruments is restricted. All of them imply a dispersed distribution of short-run preferred arrival times. The extent of dispersion in the unpriced equilibrium, however, is higher than socially optimal.