Miracle-dz/UniFAR-FTUs huggingface dataset:
Structured Post-IQ Domain Governs Selectivity of Myosin X for Fascin-Actin Bundles*

Without guidance cues, cytoskeletal motors would traffic components to the wrong destination with disastrous consequences for the cell. Recently, we identified a motor protein, myosin X, that identifies bundled actin filaments for transport. These bundles direct myosin X to a unique destination, the tips of cellular filopodia. Because the structural and kinetic features that drive bundle selection are unknown, we employed a domain-swapping approach with the nonselective myosin V to identify the selectivity module of myosin X. We found a surprising role of the myosin X tail region (post-IQ) in supporting long runs on bundles. Moreover, the myosin X head is adapted for initiating processive runs on bundles. We found that the tail is structured and biases the orientation of the two myosin X heads because a targeted insertion that introduces flexibility in the tail abolishes selectivity. Together, these results suggest how myosin motors may manage to read cellular addresses.
Trazodone Addition to Paroxetine and Mirtazapine in a Patient with Treatment-Resistant Depression: The Pros and Cons of Combining Three Antidepressants

Dual antidepressant combination for treatment-resistant depression is a strategy well supported by literature and accepted in clinical practice. Rather, the usefulness of the combination of more than two antidepressants is controversial. This may be related to the possibility of higher side-effect burden and to doubts about its pharmacological effectiveness and therapeutic advantage compared to other standard treatment options. We report a relapse of moderate-to-severe depressive symptoms with insomnia that successfully remitted after the addition of trazodone to a dual combination of paroxetine and mirtazapine (in standard effective doses) in a patient with treatment-resistant depression. We also review the literature and discuss the utility of triple antidepressant combination in treatment-resistant depression. This clinical case highlights the utility of combining trazodone as a third antidepressant for the relapse of depressive symptoms after the failure of a dual antidepressant combination. Trazodone may be advantageous in patients presenting recurrence of moderate-to-severe depressive symptoms that include sleep problems and/or insomnia and may be particularly useful when benzodiazepines are not recommended. Although its use may be controversial and associated with higher risk of side-effects, more investigation is needed to determine the efficacy and safety for triple antidepressant combinations as reliable strategies for treatment-resistant depression in clinical practice.
NBER WORKING PAPER SERIES AFFIRMATIVE ACTION AND ITS MYTHOLOGY

Roland G. Fryer, Jr. is Junior Fellow, Harvard University Society of Fellows, Harvard University, and Faculty Research Fellow, National Bureau of Economic Research, both in Cambridge, Massachusetts. Glenn C. Loury is University Professor, Department of Economics, Boston University, Boston, Massachusetts. Their e-mail addresses are rfryer@fas.harvard. edu and gloury@bu.edu, respectively. The views expressed herein are those of the author(s) and do not necessarily reflect the views of the National Bureau of Economic Research.
Toll-like Receptor 2 Mediates Peripheral Nerve Injury-induced NADPH Oxidase 2 Expression in Spinal Cord Microglia*

Background: Microglial NADPH oxidase 2 (Nox2) expression is critical for nerve injury-induced spinal cord microglia activation and subsequent pain hypersensitivity. Results: Toll-like receptor 2 (TLR2) is required for Nox2 expression in spinal cord microglia after spinal nerve injury. Conclusion: TLR2 signaling mediates nerve injury-induced Nox2 expression in spinal cord microglia. Significance: Targeting TLR2-Nox2 pathway may be a new option for preventing neuropathic pain. We have previously reported that NADPH oxidase 2 (Nox2) is up-regulated in spinal cord microglia after spinal nerve injury, demonstrating that it is critical for microglia activation and subsequent pain hypersensitivity. However, the mechanisms and molecules involved in Nox2 induction have not been elucidated. Previous studies have shown that Toll-like receptors (TLRs) are involved in nerve injury-induced spinal cord microglia activation. In this study, we investigated the role of TLR in Nox2 expression in spinal cord microglia after peripheral nerve injury. Studies using TLR knock-out mice have shown that nerve injury-induced microglial Nox2 up-regulation is abrogated in TLR2 but not in TLR3 or -4 knock-out mice. Intrathecal injection of lipoteichoic acid, a TLR2 agonist, induced Nox2 expression in spinal cord microglia both at the mRNA and protein levels. Similarly, lipoteichoic acid stimulation induced Nox2 expression and reactive oxygen species production in primary spinal cord glial cells in vitro. Studies on intracellular signaling pathways indicate that NF-κB and p38 MAP kinase activation is required for TLR2-induced Nox2 expression in glial cells. Conclusively, our data show that TLR2 mediates nerve injury-induced Nox2 gene expression in spinal cord microglia via NF-κB and p38 activation and thereby may contribute to spinal cord microglia activation.
TMTR Codes for Partial Response Channels

A TMTR code is specified as (k evne 1 = 2, k odd 1 = 3, k) constraint. In this work, an approach for constructing (k even 1 = 2, k odd 1 = 3, k) codes is presented. Based on this construction, a rate 8/9 code with k=7 is found. This code can achieve better timing recovery performance compared to the proposed previously TMTR code with k= 11. An enumerating encoder and decoder exist for constructed (k even 1 = 2, k odd 1 = 3, k) codes. A look-up table for the encoder/decoder is not required. Simulation results on an E 2 PRIV recording channel reveal that the TMTR code provides 2.2 dB gain over an uncoded case.
Neuronal Cell Death and Degeneration through Increased Nitroxidative Stress and Tau Phosphorylation in HIV-1 Transgenic Rats

The underlying mechanisms for increased neurodegeneration and neurocognitive deficits in HIV-infected people are unclear. Therefore, this study was aimed to investigate the mechanisms of increased neurodegeneration in 5-month old male HIV-1 Transgenic (Tg) rats compared to the age- and gender-matched wild-type (WT) by evaluating histological changes and biochemical parameters of the key proteins involved in the cell death signaling and apoptosis. Histological and immunohistochemical analyses revealed decreased neuronal cells with elevated astrogliosis in HIV-1 Tg rats compared to WT. Mechanistic studies revealed that increased levels of nitroxidative stress marker proteins such as NADPH-oxidase, cytochrome P450-2E1 (CYP2E1), inducible nitric oxide synthase (iNOS), the stress-activated mitogen-activated protein kinases such as JNK and p38K, activated cell-cycle dependent CDK5, hypoxia-inducible protein-1α, nitrated proteins, hyperphosphorylated tau, and amyloid plaques in HIV-Tg rats were consistently observed in HIV-1 Tg rats. Confocal microscopy and cell viability analyses showed that treatment with an antioxidant N-acetylcysteine or a specific inhibitor of iNOS 1400W significantly prevented the increased apoptosis of neuro-2A cells by HIV-1 Tat or gp120 protein, demonstrating the causal role of HIV-1 mediated nitroxidative stress and protein nitration in promoting neuronal cell death. Immunoprecipitation and immunoblot analysis confirmed nitration of Hsp90, evaluated as an example of nitrated proteins, suggesting possible involvement of nitrated proteins in neuronal damage. Further, activated p-JNK directly binds tau and phosphorylates multiple amino acids, suggesting an important role of p-JNK in tau hyperphosphorylation and tauopathy. These changes were accompanied with elevated levels of many apoptosis-related proteins Bax and cleaved (activated) caspase-3 as well as proinflammatory cytokines including TNF-α, IL-6 and MCP-1. Collectively, these results indicate that raised nitroxidative stress accompanied by elevated inflammation, cell death signaling pathway including activated p-JNK, C-terminal C99 amyloid fragment formation and tau hyperphosphorylation are responsible for increased apoptosis of neuronal cells and neurodegeneration in 5-month old HIV-Tg rats.
Clusterability Detection and Cluster Initialization

The need for a preliminary assessment of the clustering tendency or clusterability of massive data sets is known. A good clusterability detection method should serve to influence a decision as to whether to cluster at all, as well as provide useful seed input to a chosen clustering algorithm. We present a framework for the definition of the clusterability of a data set from a distance-based perspective. We discuss a graph-based system for detecting clusterability and generating seed information including an estimate of the value of k – the number of clusters in the data set, an input parameter to many distancebased clustering methods. The output of our method is tunable to accommodate a wide variety of clustering methods. We have conducted a number of experiments using our methodology with stock market data and with the well-known BIRCH data sets, in two as well as higher dimensions. Based on our experiments and results we find that our methodology can serve as the basis for much future work in this area. We report our results and discuss promising future directions.
Development of Genomic Microsatellite Markers in Carthamus tinctorius L. (Safflower) Using Next Generation Sequencing and Assessment of Their Cross-Species Transferability and Utility for Diversity Analysis

Background Safflower (Carthamus tinctorius L.), an Asteraceae member, yields high quality edible oil rich in unsaturated fatty acids and is resilient to dry conditions. The crop holds tremendous potential for improvement through concerted molecular breeding programs due to the availability of significant genetic and phenotypic diversity. Genomic resources that could facilitate such breeding programs remain largely underdeveloped in the crop. The present study was initiated to develop a large set of novel microsatellite markers for safflower using next generation sequencing. Principal Findings Low throughput genome sequencing of safflower was performed using Illumina paired end technology providing ~3.5X coverage of the genome. Analysis of sequencing data allowed identification of 23,067 regions harboring perfect microsatellite loci. The safflower genome was found to be rich in dinucleotide repeats followed by tri-, tetra-, penta- and hexa-nucleotides. Primer pairs were designed for 5,716 novel microsatellite sequences with repeat length ≥ 20 bases and optimal flanking regions. A subset of 325 microsatellite loci was tested for amplification, of which 294 loci produced robust amplification. The validated primers were used for assessment of 23 safflower accessions belonging to diverse agro-climatic zones of the world leading to identification of 93 polymorphic primers (31.6%). The numbers of observed alleles at each locus ranged from two to four and mean polymorphism information content was found to be 0.3075. The polymorphic primers were tested for cross-species transferability on nine wild relatives of cultivated safflower. All primers except one showed amplification in at least two wild species while 25 primers amplified across all the nine species. The UPGMA dendrogram clustered C. tinctorius accessions and wild species separately into two major groups. The proposed progenitor species of safflower, C. oxyacantha and C. palaestinus were genetically closer to cultivated safflower and formed a distinct cluster. The cluster analysis also distinguished diploid and tetraploid wild species of safflower. Conclusion Next generation sequencing of safflower genome generated a large set of microsatellite markers. The novel markers developed in this study will add to the existing repertoire of markers and can be used for diversity analysis, synteny studies, construction of linkage maps and marker-assisted selection.
Estimates of the Potential Insurance Value of Disability Insurance for Individuals with Mental Health Impairments

Since the mid-1980s there has been dramatic growth in the number and fraction of DI and SSI beneficiaries with mental illness. With longer life expectancies and younger ages of disability onset than beneficiaries with physical impairments, their growth exerts added fiscal pressure on the programs. While not specifically focused on mental illness, fears of an increase in the duration (and thus prevalence) of disability claims that may result from this demographic shift have generated calls to tighten eligibility rules again. Using data from the Health and Retirement Study linked to SSA administrative records, we created statistically matched control groups of non-beneficiaries with severe mental illness. We then estimated the earnings, income, and health insurance coverage among rejected DI/SSI applicants with mental illness who have characteristics comparable to persons awarded benefits on the basis of mental impairments. We found that even after controlling for health and demographic characteristics, DI beneficiaries were substantially worse off than rejected applicants in terms of wealth and income. While these rejected applicants with mental illness were worse off than those with physical impairments, our findings suggests that the programs successfully select applicants with the greatest income needs, and that retrenchment could result in significant hardship.
The influence of cellular apoptotic capacity on N-nitrosodimethylamine-induced loss of heterozygosity mutations in human cells.

The induction of loss of heterozygosity (LOH) by the environmental carcinogen N-nitrosodimethylamine (NDMA), and the factors that influence the recovery of LOH mutations were studied in two directly related human lymphoblastoid cell lines, AHH-1 (h2E1.v2) and MCL-5. Initially, the NDMA-induced mutation frequency at the heterozygous tk locus in AHH-1 cells was observed to be 5-fold higher in AHH-1 compared with MCL-5. Molecular analysis of NDMA-induced TK- mutants indicated that the induced mutant fraction attributable to small intragenic mutations was similar in both cell lines. However, the induced mutant fraction, because of LOH, was 18-fold greater in AHH-1. In addition, LOH mutations were more extensive among TK- mutants derived from AHH-1 cells. We hypothesized that the increased recovery of large LOH mutations in AHH-1 cells could be attributable to reduced apoptotic capacity, as it has been reported that AHH-1 cells carry a heterozygous mutation in the p53 locus, whereas MCL-5 cells are homozygous wild-type. Analysis of the kinetics of apoptosis showed that the apoptotic response of the AHH-1 cell line was diminished and delayed compared with MCL-5. Based on the analyses presented here, and several recent reports, it is suggested that the recovery of LOH mutations in p53 deficient cell lines is affected not only by abnormalities in cellular apoptotic response, but also involves a number of p53-mediated responses to DNA damage.
Tumor Quantification in Clinical Positron Emission Tomography

Positron emission tomography (PET) is used extensively in clinical oncology for tumor detection, staging and therapy response assessment. Quantitative measurements of tumor uptake, usually in the form of standardized uptake values (SUVs), have enhanced or replaced qualitative interpretation. In this paper we review the current status of tumor quantification methods and their applications to clinical oncology. Factors that impede quantitative assessment and limit its accuracy and reproducibility are summarized, with special emphasis on SUV analysis. We describe current efforts to improve the accuracy of tumor uptake measurements, characterize overall metabolic tumor burden and heterogeneity of tumor uptake, and account for the effects of image noise. We also summarize recent developments in PET instrumentation and image reconstruction and their impact on tumor quantification. Finally, we offer our assessment of the current development needs in PET tumor quantification, including practical techniques for fully quantitative, pharmacokinetic measurements.
South African teachers’ perspectives on support received in implementing curriculum changes

South African education has experienced significant curricular reform since the mid-1990s, but its implementation has not matched expectations. This study explores teachers’ perspectives on implementing these reforms in schools, with the aim of ascertaining the challenges they faced in the process, and the kind of support, guidance and professional development programmes they received from the Department of Basic Education to facilitate the changes. This article focuses on their experiences of the government-based Foundations for Learning Campaign in schools in the uThungulu district, KwaZulu-Natal, South Africa. Teachers from grades One to Six teaching languages and Mathematics were targeted, and a sample of 20 was purposefully selected. Using an interpretive qualitative research approach, data was collected by means of in-depth interviews, with open-ended questions, and classified by themes. The findings revealed that teachers felt inadequately provided with sustainable professional development programmes, and had minimal meaningful opportunities for classroom support, guidance and monitoring to assist in implementing the changes required. This small-scale investigation offers a stepping-stone for further analysis of assistance being offered to teachers across the country in times of curriculum reform, and thereby contributes towards preparing the ground for a new and integrated framework offering much-needed effective, systematic, ongoing professional development programmes that translate into improved teaching practice and learning success. Keywords: continuing professional development; curriculum implementation; curriculum reform; Foundations for Learning Campaign; monitoring; support
A simple and effective genetic algorithm for the two-stage capacitated facility location problem q

This paper presents a simple and effective Genetic Algorithm (GA) for the two-stage capacitated facility location problem (TSCFLP). The TSCFLP is a typical location problem which arises in freight transportation. In this problem, a single product must be transported from a set of plants to meet customers demands, passing out by intermediate depots. The objective is to minimize the operation costs of the underlying two-stage transportation system thereby satisfying demand and capacity constraints of its agents. For this purpose, a GA is proposed and computational results are reported comparing the heuristic results with those obtained by two state-of-the-art Lagrangian heuristics proposed in the literature for the problem. 2014 Elsevier Ltd. All rights reserved.
Effects of exchange rate volatility on exports

This paper reviews a part of the most important literature on the impact of exchange rate volatility over exports. The first section reviews particularities and limits in the literature about the connection between the two variables, while the second part reviews the effects of exchange rate volatility over exports volume in different circumstances. Currency depreciation, normally, should stimulate exports, because they become cheaper to foreign products and by contrast, appreciation leads to export decrease. Our main results show that the theorethic area may be contradicted by practical cases.
A Situationally Aware Voice‐commandable Robotic Forklift Working Alongside People in Unstructured Outdoor Environments

One long‐standing challenge in robotics is the realization of mobile autonomous robots able to operate safely in human workplaces, and be accepted by the human occupants. We describe the development of a multiton robotic forklift intended to operate alongside people and vehicles, handling palletized materials within existing, active outdoor storage facilities. The system has four novel characteristics. The first is a multimodal interface that allows users to efficiently convey task‐level commands to the robot using a combination of pen‐based gestures and natural language speech. These tasks include the manipulation, transport, and placement of palletized cargo within dynamic, human‐occupied warehouses. The second is the robot's ability to learn the visual identity of an object from a single user‐provided example and use the learned model to reliably and persistently detect objects despite significant spatial and temporal excursions. The third is a reliance on local sensing that allows the robot to handle variable palletized cargo and navigate within dynamic, minimally prepared environments without a global positioning system. The fourth concerns the robot's operation in close proximity to people, including its human supervisor, pedestrians who may cross or block its path, moving vehicles, and forklift operators who may climb inside the robot and operate it manually. This is made possible by interaction mechanisms that facilitate safe, effective operation around people. This paper provides a comprehensive description of the system's architecture and implementation, indicating how real‐world operational requirements motivated key design choices. We offer qualitative and quantitative analyses of the robot operating in real settings and discuss the lessons learned from our effort.
Using Texture Descriptor and Radon Transform to Characterize Protein Structure and Build Fast Fold Recognition

One of the most important research aims is to understand the relationship between structure and function of protein. Inspired by this motivation, automatic classification of protein structure becomes one of major research approaches. However, how to extract compact and effective feature to characterize protein structure is still a challenge to it. In this paper, 3-D tertiary structure of protein fold is mapped into 2-D distance matrix which can be further regarded as gray level image. Firstly, gray level co-occurrence matrix (CoM) of distance matrix image (DMI) is calculated and four descriptors based on it are taken as the first group of features. Next, DMI is transformed into projection view by Radon transform. In succession, the projection magnitudes are analyzed by histogram of which four central moments are taken as the second group of features. After that, we depict the structural meanings of gray distribution, various angles and pixels distance of CoM respectively, and determine the angle band used in Radon transform by the second derivation of the variance of the projections along different orientations. Finally, the presented feature extraction is validated by classification of 27 types of folds, compared with several feature methods based on sequence or structure. The results show that the presented method achieves significant improvement than other methods in terms of both low feature dimension and high classification accuracy.