Miracle-dz/UniFAR-FTUs huggingface dataset:
Notch signaling patterns Drosophila mesodermal segments by regulating the bHLH transcription factor twist

One of the first steps in embryonic mesodermal differentiation is allocation of cells to particular tissue fates. In Drosophila, this process of mesodermal subdivision requires regulation of the bHLH transcription factor Twist. During subdivision, Twist expression is modulated into stripes of low and high levels within each mesodermal segment. High Twist levels direct cells to the body wall muscle fate, whereas low levels are permissive for gut muscle and fat body fate. We show that Su(H)-mediated Notch signaling represses Twist expression during subdivision and thus plays a critical role in patterning mesodermal segments. Our work demonstrates that Notch acts as a transcriptional switch on mesodermal target genes, and it suggests that Notch/Su(H) directly regulates twist, as well as indirectly regulating twist by activating proteins that repress Twist. We propose that Notch signaling targets two distinct `Repressors of twist' - the proteins encoded by the Enhancer of split complex [E(spl)C] and the HLH gene extra machrochaetae (emc). Hence, the patterning of Drosophila mesodermal segments relies on Notch signaling changing the activities of a network of bHLH transcriptional regulators, which, in turn, control mesodermal cell fate. Since this same cassette of Notch, Su(H) and bHLH regulators is active during vertebrate mesodermal segmentation and/or subdivision, our work suggests a conserved mechanism for Notch in early mesodermal patterning.
Alternative start and termination sites of transcription drive most transcript isoform differences across human tissues

Abstract Most human genes generate multiple transcript isoforms. The differential expression of these isoforms can help specify cell types. Diverse transcript isoforms arise from the use of alternative transcription start sites, polyadenylation sites and splice sites; however, the relative contribution of these processes to isoform diversity in normal human physiology is unclear. To address this question, we investigated cell type-dependent differences in exon usage of over 18 000 protein-coding genes in 23 cell types from 798 samples of the Genotype-Tissue Expression Project. We found that about half of the expressed genes displayed tissue-dependent transcript isoforms. Alternative transcription start and termination sites, rather than alternative splicing, accounted for the majority of tissue-dependent exon usage. We confirmed the widespread tissue-dependent use of alternative transcription start sites in a second, independent dataset, Cap Analysis of Gene Expression data from the FANTOM consortium. Moreover, our results indicate that most tissue-dependent splicing involves untranslated exons and therefore may not increase proteome complexity. Thus, alternative transcription start and termination sites are the principal drivers of transcript isoform diversity across tissues, and may underlie the majority of cell type specific proteomes and functions.
Identification of Domains Participating in the Substrate Specificity and Subcellular Localization of the Multidrug Resistance Proteins MRP1 and MRP2*

The human multidrug resistance protein MRP1 and its homolog, MRP2, are both thought to be involved in cancer drug resistance and the transport of a wide variety of organic anions, including the cysteinyl leukotriene C4 (LTC4) (Km = 0.1 and 1 μm). To determine which domain of these proteins is associated with substrate specificity and subcellular localization, we constructed various chimeric MRP1/MRP2 molecules and expressed them in polarized mammalian LLC-PK1 cells. We examined the kinetic properties of each chimeric protein by measuring LTC4 and methotrexate transport in inside-out membrane vesicles, sensitivity to an anticancer agent, etoposide, and subcellular localization by indirect immunofluorescence methods. The following results were determined in these studies: (i) when the NH2-proximal 108 amino acids of MRP2, including transmembrane (TM) helices 1–3, were exchanged with the corresponding region of MRP1, Km(LTC4) values of the chimera decreased ∼4-fold and Km(methotrexate) values increased ∼5-fold relative to those of wild-type MRP2 and MRP1, respectively, whereas resistance to etoposide increased ∼3-fold; (ii) when the NH2-proximal region up to TM9 of MRP2 was exchanged with the corresponding region of MRP1, a further increase in etoposide resistance was observed, and subcellular localization moved from the apical to the lateral membrane; (iii) when two-thirds of MRP2 at the NH2 terminus were exchanged with the corresponding MRP1 region, the chimeric protein transported LTC4 with an efficiency comparable with that achieved by the wild-type MRP1; and (iv) exchange of the COOH-terminal 51 amino acids between MRP1 and MRP2 did not affect the localization of either of the proteins. These results provide a strong framework for further studies aimed at determining the precise domains of MRP1 and MRP2 with affinity for LTC4 and anticancer agents.
Classification of cutaneous T‐cell lymphoma: from Alibert to WHO‐EORTC

Cutaneous T‐cell lymphomas (CTCLs) represent a heterogeneous group of neoplasms originating from skin‐homing T cells that show considerable variation in clinical presentation, histological appearance, immuno‐ phenotype, and prognosis. This review provides a historic overview of the classification of CTCLs from the first description of a patient with mycosis fungoides in 1806 to the recently published WHO‐EORTC classification. Practical guidelines for the usage of the WHO‐EORTC classification and relevant features of new or newly defined entities such as subcutaneous panniculitis‐like T‐cell lymphoma, extranodal NK/T‐cell lymphoma, nasal type, primary cutaneous aggressive CD8‐positive cytotoxic T‐cell lymphoma, and cutaneous γ/δ T‐cell lymphoma are presented. The aim of this review is to contribute to a better communication between dermatologist and pathologist and in this way to a better diagnosis and classification of CTCLs.
Preparation, Electrical Conductivity, Photocurrent and Wettability of Carbon Microcoils

In this paper, we report on fabrication and physical properties of carbon microcoils, which are prepared by a chemical vapor deposition (CVD) process with Ni-catalyzed pyrolysis of acetylene, and characterized by a scanning electron microscope, a transmission electron microscope and an infrared spectrometer. The dark electrical conductivity of an isolated carbon microcoil is about 81 S/cm at room temperature, and its temperature dependence follows three-dimensional Mott variable-range hopping (VRH) model. Particularly, evident photocurrent is observed in the carbon microcoil upon cameral flash illumination. In addition, it is found that the surface of microcoil film is hydrophobic, showing a large water contact angle of about 135°. These results indicate that carbon microcoils have excellent physical properties, and can be used as optoelectronic and reinforced materials.
Skin Sensitization in School Children in Northern and Southern Norway

It has been suggested that environmental exposures and living conditions can explain some of the worldwide variation in atopic disorders. Norway has large environmental contrasts within the country. We compared skin prick sensitization rates among school children living in the southern subarctic and in the northern artic part of Norway. Approximately one quarter of the children were sensitized, mostly against pollen and animal dander, while mite and mould sensitization seemed to be a minor problem. Sensitization rates and profiles were similar in the north and south despite differences in living conditions and environmental exposures.
Is blood eosinophilia an effective predictor of acute rejection in living donor liver transplantation? *

The association of blood eosinophilia with acute cellular rejection (ACR) after living donor liver transplantation has not been examined yet. The subjects were the 167 recipients who underwent liver biopsy (314 times). The blood eosinophil counts in the preoperative period (n = 167), 3 days before (n = 314) and on the day of biopsy (n = 314) were compared among the groups stratified by severity of ACR. Among 314 biopsy specimens, the 140 biopsy specimens were diagnosed with ACR. In the 140 ACR episodes, eosinophil counts before and after therapy was compared between the episodes that responded to therapy (n = 80) and those not (n = 60). The sensitivity and specificity of preoperative eosinophilia (eosinophil counts >130 mm3) to predict ACR was 33% and 65%, respectively. The eosinophil counts >400 mm3 3 days before and on the day of biopsy was associated with the severity of ACR (P < 0.0001). The sensitivity to predict ACR was 26% and 33%, and the specificity, 94% and 93%, respectively. There was no significant difference in changes of eosinophil counts between the steroid‐responders versus the nonresponders. The present results suggested the limited role of eosinophilia as a predictor of ACR after living donor liver transplantation.
Investigating the genetic basis of attention to facial expressions: the role of the norepinephrine transporter gene

Objective Levels of norepinephrine (NE) in the brain are related to attention ability in animals and risk of attention-deficit hyperactivity disorder in humans. Given the modulation of the norepinephrine transporter (NET) on NE levels in the brain and the link between NE and attention impairment of attention-deficit hyperactivity disorder, it was possible that the NET gene underpinned individual differences in attention processes in healthy populations. Methods To investigate to what extent NET could modulate one’s attention orientation to facial expressions, we categorized individuals according to the genotypes of the −182 T/C (rs2242446) polymorphism and measured individuals’ attention orientation with the spatial cueing task. Results Our results indicated that the −182 T/C polymorphism significantly modulated attention orientation to facial expressions, of which the CC genotype facilitated attention reorientation to the locations where cued faces were previously presented. However, this polymorphism showed no significant effects on the regulations of emotional cues on attention orientation. Conclusion Our findings suggest that the NET gene modulates the individual difference in attention to facial expressions, which provides new insights into the roles of NE in social interactions.
Signal Transduction in Smooth Muscle Invited Review : The circle of life : cell cycle regulation in airway smooth muscle

Ammit, Alaina J., and Reynold A. Panettieri, Jr. Invited Review: The circle of life: cell cycle regulation in airway smooth muscle. J Appl Physiol 91: 1431–1437, 2001. —Severe asthma is characterized by increased airway smooth muscle (ASM) mass, due predominantly to ASM hyperplasia. Diverse stimuli, which include growth factors, plasmaor inflammatory cell-derived mediators, contractile agonists, cytokines, and extracellular matrix proteins, induce ASM proliferation. Mitogens act via receptor tyrosine kinase, G protein-coupled receptors, or cytokine receptors, to activate p21ras and stimulate two parallel signaling pathways in ASM cells, namely, the extracellular signal-regulated kinase (ERK) or the phosphatidylinositol 3-kinase (PI3K) pathways. ERK and PI3K regulate cell cycle protein expression and thus modulate cell cycle traversal. ERK activation and downstream effectors of PI3K, such as Rac1 and Cdc42, stimulate expression of cyclin D1, a key regulator of G1 progression in the mammalian cell cycle. In addition, PI3K activates 70-kDa ribosomal S6 kinase, an enzyme that also regulates the translation of many cell cycle proteins, including the elongation factor E2F. The present review examines the mitogens and critical signal transduction pathways that stimulate ASM cell proliferation. Further study in this area may reveal new therapeutic targets to abrogate ASM hyperplasia in diseases such as asthma and chronic obstructive pulmonary disease.
Pairwise Rotation Invariant Co-Occurrence Local Binary Pattern

Designing effective features is a fundamental problem in computer vision. However, it is usually difficult to achieve a great tradeoff between discriminative power and robustness. Previous works shown that spatial co-occurrence can boost the discriminative power of features. However the current existing co-occurrence features are taking few considerations to the robustness and hence suffering from sensitivity to geometric and photometric variations. In this work, we study the Transform Invariance (TI) of co-occurrence features. Concretely we formally introduce a Pairwise Transform Invariance (PTI) principle, and then propose a novel Pairwise Rotation Invariant Co-occurrence Local Binary Pattern (PRICoLBP) feature, and further extend it to incorporate multi-scale, multi-orientation, and multi-channel information. Different from other LBP variants, PRICoLBP can not only capture the spatial context co-occurrence information effectively, but also possess rotation invariance. We evaluate PRICoLBP comprehensively on nine benchmark data sets from five different perspectives, e.g., encoding strategy, rotation invariance, the number of templates, speed, and discriminative power compared to other LBP variants. Furthermore we apply PRICoLBP to six different but related applications-texture, material, flower, leaf, food, and scene classification, and demonstrate that PRICoLBP is efficient, effective, and of a well-balanced tradeoff between the discriminative power and robustness.
Ca2+-independent phospholipase A2 enhances store-operated Ca2+ entry in dystrophic skeletal muscle fibers

Duchenne muscular dystrophy is caused by deficiency of dystrophin and leads to progressive weakness. It has been proposed that the muscle degeneration occurring in this disease is caused by increased Ca2+ influx due to enhanced activity of cationic channels that are activated either by stretch of the plasma membrane (stretch-activated channels) or by Ca2+-store depletion (store-operated channels). Using both cytosolic Ca2+ measurements with Fura-2 and the manganese quench method, we show here that store-operated Ca2+ entry is greatly enhanced in dystrophic skeletal flexor digitorum brevis fibers isolated from mdx5cv mice, a mouse model of Duchenne muscular dystrophy. Moreover, we show for the first time that store-operated Ca2+ entry in these fibers is under the control of the Ca2+-independent phospholipase A2 and that the exaggerated Ca2+ influx can be completely attenuated by inhibitors of this enzyme. Enhanced store-operated Ca2+ entry in dystrophic fibers is likely to be due to a near twofold overexpression of Ca2+-independent phospholipase A2. The Ca2+-independent phospholipase A2 pathway therefore appears as an attractive target to reduce excessive Ca2+ influx and subsequent degeneration occurring in dystrophic fibers.
Learning Orthographic Features in Bi-directional LSTM for Biomedical Named Entity Recognition

End-to-end neural network models for named entity recognition (NER) have shown to achieve effective performances on general domain datasets (e.g. newswire), without requiring additional hand-crafted features. However, in biomedical domain, recent studies have shown that hand-engineered features (e.g. orthographic features) should be used to attain effective performance, due to the complexity of biomedical terminology (e.g. the use of acronyms and complex gene names). In this work, we propose a novel approach that allows a neural network model based on a long short-term memory (LSTM) to automatically learn orthographic features and incorporate them into a model for biomedical NER. Importantly, our bi-directional LSTM model learns and leverages orthographic features on an end-to-end basis. We evaluate our approach by comparing against existing neural network models for NER using three well-established biomedical datasets. Our experimental results show that the proposed approach consistently outperforms these strong baselines across all of the three datasets.
A Fast Ellipse Detector Using Projective Invariant Pruning

Detecting elliptical objects from an image is a central task in robot navigation and industrial diagnosis, where the detection time is always a critical issue. Existing methods are hardly applicable to these real-time scenarios of limited hardware resource due to the huge number of fragment candidates (edges or arcs) for fitting ellipse equations. In this paper, we present a fast algorithm detecting ellipses with high accuracy. The algorithm leverages a newly developed projective invariant to significantly prune the undesired candidates and to pick out elliptical ones. The invariant is able to reflect the intrinsic geometry of a planar curve, giving the value of −1 on any three collinear points and +1 for any six points on an ellipse. Thus, we apply the pruning and picking by simply comparing these binary values. Moreover, the calculation of the invariant only involves the determinant of a $3\times 3$ matrix. Extensive experiments on three challenging data sets with 648 images demonstrate that our detector runs 20%–50% faster than the state-of-the-art algorithms with the comparable or higher precision.
Cardiovascular Autonomic Dysfunction in Africans Infected with Human Immunodeficiency Virus

The effects of human immunodeficiency virus (HIV) on cardiovascular autonomic function have been little investigated in African patients. We performed standard heart-rate and blood pressure tests on 75 consecutive consenting patients referred for an HIV test in Yaounde, Cameroon. 54 patients proved to be HIV-infected (30 having progressed to AIDS). Cardiovascular autonomic dysfunction was present in 8 (28%) patients with AIDS and in 1 (4%) HIV-positive patient without AIDS; no HIV-negative individuals had abnormal results. If borderline results are included, over 80% of HIV-positive patients had cardiovascular autonomic dysfunction. In HIV-infected patients, simple tests such as blood pressure responses to standing or handgrip can warn of cardiovascular autonomic dysfunction, thus signalling the need for added precautions when invasive procedures are proposed.
MENTAL DISEASE AMONG FOREIGN-BORN IN CANADA, 1950-1952, IN RELATION TO PERIOD OF IMMIGRATION.

In a study( 1) of the relative incidence of mental disease among native and foreignborn in Canada, it was shown that the latter had a higher rate. But when factors such as differences in age distribution and in density of population were considered, the rate for foreign-born proved to be in excess by only 4% which was not a significant difference. The rate of first admissions among foreign-born is influenced by age, but it may also be affected by the duration of residence. The over-all rate is an average for foreigners whose durations of residence vary from less than a year to periods of a half-century or more. The question therefore arises as to possibility of variation in the average annual rates of first admissions to mental hospitals in correlation with the duration of residence. It has been shown that there is, indeed, such a correlation(2). In 1910, there were 15,523 foreign-born white admissions to all mental hospitals in the United States, or a rate of 116.3 per 100,000 population. The foreign-born who had been in the United States 10 or more years had a rate of 130.1. Those who were resident from 5 to 10 years had a rate of 133.2. But those who had been resident less than 5 years had a rate of only 69.7. It was recognized that the latter group was younger than the others, and would, for this reason alone, tend to have a lower over-all rate. But no statistical corrections were made for this factor. Such a correction was made by Malzberg and Lee with respect to migration in New York State in 1940(3). Native-born white
Chinese Herbal Medicine for Aspirin Resistance: A Systematic Review of Randomized Controlled Trials

Aspirin resistance (AR) is a prevalent phenomenon and leads to significant clinical consequences, but the current evidence for effective interventional strategy is insufficient. The objective of this systematic review is thus to assess the efficacy and safety of Chinese herbal medicine (CHM) for AR. A systematical literature search was conducted in 6 databases until December 2012 to identify randomized controlled trials (RCTs) of CHM for AR. As a result, sixteen RCTs with a total of 1011 subjects were identified, suggesting that the interests of the medical profession and the public in the use of CHM for AR have grown considerably in the recent years. Tongxinluo capsule and Danshen-based prescriptions were the most frequently used herbal prescriptions, while danshen root, milkvetch root, Leech, and Rosewood were the most frequently used single herbs. Despite the apparent reported positive findings, it is premature to determine the efficacy and safety of CHM for the treatment of AR due to poor methodological quality and insufficient safety data. However, CHMs appeared to be well tolerated in all included studies. Thus, CHM as a promising candidate is worthy of improvement and development for further clinical AR trials. Large sample-size and well-designed rigorous RCTs are needed.
The Usability of OPAC Interface Features: The Perspective of Postgraduate Students at International Islamic University Malaysia (IIUM)

Introduction Interface for user input and system output is among the components of IR system. Different Online Catalogs (online IR systems) have different user interfaces which would allow user to navigate or search information within and outside their library collections. Due to the increase in web technology, designers in user-interface industry compete in making different designs to allow ease-of-use of these interfaces so that users can have access to information they need. Yet, most of the designs of OPACs' interfaces are not that much effective in helping the users during their search for information. Some interface designs in university libraries' OPACs are less user-friendly and would not allow interactivity with the user during search sessions rendered them less effective, inefficient and bring low satisfaction on users. Libraries' Online Public Access Catalogs (OPCs) are one of the highly visible end user searching tools. Online catalog user studies have revealed, among other findings, that catalog users have the most difficulty with information searching and place the highest priority for improvements on various information search enhancements (Markey, 1983; Hildreth, 1985). The OPACs allow users to access resources of libraries, publishers, and online vendors (GuhaS Galitz& Wiley, 2002; and Mayhew & Kaufmann, 1999). This study intends to investigate the usability and effectiveness of user-interface features of Library OPAC among postgraduate students of International Islamic University Malaysia (IIUM), in relation to variables that influence the usability and the extent that the interface features can enhance search and informational retrieval for the users (i. …