Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural Basis of Membrane Targeting by the Phox Homology Domain of Cytokine-independent Survival Kinase (CISK-PX)*

The cytokine-independent survival kinase (CISK) in the serum and glucocorticoid-regulated kinase family plays an important role in mediating cell growth and survival. N-terminal to its catalytic kinase domain, CISK contains a phox homology (PX) domain, a phosphoinositide-binding motif that directs the membrane localization of CISK and regulates CISK activity. We have determined the crystal structures of the mouse CISK-PX domain to unravel the structural basis of membrane targeting of CISK. In addition to the specific interactions conferred by the phosphoinositide-binding pocket, the structure suggests that a hydrophobic loop region and a hydrophilic β-turn contribute to the interactions with the membrane. Furthermore, biochemical studies reveal that CISK-PX dimerizes in the presence of the linker between the PX domain and kinase domain, suggesting a multivalent mechanism in membrane localization of CISK.
Knowledge shocks diffusion and the resilience of regional inequality

This paper provides a simplified method of exploring the geographical limits of a knowledge shock over the long run. Using a geographically decomposable distance weighed sum of world GDPs by county, differences in differences regression analysis shows that a new university will not only have a positive impact on the local economy, but also on the GDP of nearby counties. Furthermore, challenging the conventional wisdom that knowledge spillovers affect the local economy, this study provides evidence that the effect expands to the whole national though its strength dilutes with distance. Consistent with the education literature, this investigation provides evidence that the shock will make the relative GDP of foreign competitors worse-off. Results are persistent in the long run, although the effect of time is also decreasing. Resultsare robust to potential endogeneity related to the self-selection of prosperous allocations for new academic institutions.
Management of pediatric choroidal neovascular membranes with intravitreal anti-VEGF agents: a retrospective consecutive case series.

OBJECTIVE To report the results of pediatric choroidal neovascular membranes (CNVMs) secondary to a variety of etiologies treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents. DESIGN Retrospective case series. PARTICIPANTS Four pediatric patients at the Hosptial for Sick Children with CNVMs secondary to a variety of etiologies. METHODS Each patient received multiple treatments with one of the following anti-VEGF agents: pegaptanib sodium, bevacizumab, or ranibizumab. Progress was monitored by clinical exam, optical coherence tomography (OCT), and fluorescein angiography. RESULTS The mean age of our patients was 11.5 years (range, 8-15 years). Patients were followed for a mean of 10 months (range, 4-14 months). One patient was treated with pegaptanib sodium, 2 with bevacizumab, and 1 with ranibizumab. Following treatment, 1 patient showed an improvement and 3 showed stabilization of vision with reduction of fluid on clinical exam and OCT, and cessation of leakage on the fluorescein angiogram. Patients required 2-5 injections of the anti-VEGF agent. No ocular or systemic adverse events were observed in any of our treated patients. CONCLUSIONS Anti-VEGF agents were effective in the treatment of pediatric CNVMs in this case series. However, we do not know how these results would have differed from other treatment modalities, including observation. We did not observe any adverse side effects; however, larger studies are required to document the safety of these medications in the pediatric population where normal angiogenesis is occurring.
CD4 T Cells and Major Histocompatibility Complex Class II Expression Influence Worm Expulsion and Increased Intestinal Muscle Contraction during Trichinella spiralisInfection

ABSTRACT Expulsion of intestinal nematode parasites and the associated increased contraction by intestinal muscle are T cell dependent, since both are attenuated in athymic rodents. The CD4 T-cell subset has been strongly associated with worm expulsion; however, the relationship between these cells, antigen presentation, and worm expulsion is not definitive and the role of these factors in intestinal muscle hypercontractility has not been defined. We infected C57BL/6, athymic, CD4-deficient, CD8α-deficient, and major histocompatibility complex class II (MHC II)-deficient (C2d) mice with Trichinella spiralis larvae. We examined intestinal worm numbers, longitudinal muscle contraction, and MHC II expression. Numerous MHC II-positive cells were identified within the muscularis externa of infected but not uninfected C57BL/6 mice. C57BL/6 and CD8α-deficient mice developed large increases in muscle contraction, expelling the parasite by day 21. Athymic and C2d mice exhibited much smaller increases in muscle contraction and delayed parasite expulsion. CD4-deficient mice exhibited intermediate levels of muscle contraction and delayed parasite expulsion. To further examine the role of MHC II and CD4 T cells, we irradiated C2d mice and reconstituted them with C57BL/6 bone marrow alone or with C57BL/6 CD4 T cells. C57BL/6 bone marrow alone did not affect muscle function or worm expulsion in recipient C2d mice. Partial CD4 T-cell reconstitution was sufficient to restore increased muscle contraction but not worm expulsion. Thus, hematopoietic MHC II expression alone is insufficient for the development of muscle hypercontractility and worm expulsion, but the addition of even small numbers of CD4 T cells was sufficient to induce intestinal muscle pathophysiology.
MR imaging of splenic metastases: ferrite-enhanced detection in rats.

Detection of intrasplenic neoplasms using sonography, CT, and scintigraphy is limited by poor inherent tumor-spleen contrast relative to image noise. Despite the wide range of contrast parameters available for MR imaging, similar limitations have been found with this technique. Magnetopharmaceuticals have the ability to enhance tumor-spleen contrast and improve lesion detectability. In this study, a rodent model of cancer metastasized to the spleen was used to evaluate the potential of superparamagnetic ferrite particles as a tissue-specific reticuloendothelial contrast agent. Other studies have shown ferrite to have little or no toxicity. Without contrast material, metastatic adenocarcinoma of the spleen could not be distinguished from normal splenic parenchyma on in vivo MR images. At a dose of 50 mumol Fe/kg, the T2 relaxation time of spleen decreased by 77%, while tumor T2 was essentially unchanged (p less than .005). Intrasplenic tumors 4-6 mm in size became readily detectable on in vivo MR images after the administration of ferrite particles. Lesion conspicuity, quantitated by the tumor-spleen contrast-to-noise ratio, showed a 43-fold increase. Ferrite particles show great promise as a contrast agent to enhance the detection of focal splenic lesions.
What drives stock market integration? An analysis using agribusiness stocks

This article explores the drivers of regional stock market integration with a focus on the agribusiness sector across relevant regional trade blocs around the world. We implement panel cointegration models to analyze the stock indices of agribusiness firms in the Southern Common Market (MERCOSUR), European Union (EU), Asia-Pacific Economic Cooperation (APEC), and North American Free Trade Agreement (NAFTA). Based on the literature on market integration and stock return pricing, we identify nine possible determinants of stock market integration, which we separate into three categories: individual market performance, macroeconomic conditions, and agricultural trade. In our analysis, we account for agriculture-specific factors to control for possible structural shifts in financial markets regimes by including the two main commodity price bubbles during last 20 years. Our results show that most of the variables included in our categories have been important factors in promoting regional stock market integration. Moreover, integration among regional stock markets was strengthened by the implementation of trade agreements. This effect is stronger in trade blocs with fewer members, such as NAFTA and MERCOSUR, compared with larger and more heterogeneous blocs, such as the EU and APEC. JEL classifications: F36, G15
Clinical and radiographic evaluation of the papilla level adjacent to single-tooth dental implants. A retrospective study in the maxillary anterior region.

BACKGROUND The regeneration of gingival papillae after single-implant treatment is an area of current investigation. This study was designed to determine: 1) whether the distance from the base of the contact point to the crest of the bone would correlate with the presence or absence of interproximal papillae adjacent to single-tooth implants, and 2) whether the surgical technique at uncovering influences the outcome. METHODS A clinical and radiographic retrospective evaluation of the papilla level around single dental implants and their adjacent teeth was performed in the anterior maxilla in 26 patients restored with 27 implants. Six months after insertion, 17 implants were uncovered with a standard technique, while 10 implants were uncovered with a technique designed to generate papilla-like formation around dental implants. Fifty-two papillae were available for clinical and radiographic evaluation. The presence or absence of papillae was determined, and the effects of the following variables were analyzed: the influence of the 2 surgical techniques; the vertical relation between the papilla height and the crest of bone between the implant and adjacent teeth; the vertical relation between the papilla level and the contact point between the crowns of the teeth and the implant; and the distance from the contact point to the crest of bone. RESULTS When the measurement from the contact point to the crest of bone was 5 mm or less, the papilla was present almost 100% of the time. When the distance was > or = 6 mm, the papilla was present 50% of the time or less. The mean distance between the crest of bone and the most coronal papilla level (interproximal soft tissue height) was 3.85 mm (SD = 1.04). When comparing the conventional and modified surgical technique, the relation shifted from 3.77 mm (SD = 1.01) to 4.01 mm (SD = 1.10), respectively. CONCLUSIONS These results clearly show the influence of the bone crest on the presence or absence of papillae between implants and adjacent teeth. The data also show a positive influence for the modified surgical technique, aimed at reconstructing papillae at the implant uncovering.
An Expanded Servicescape Framework as the Driver of Place Attachment and Word of Mouth

The purpose of this study is to identify the effects of other customers on consumption behavior in shared consumption environments. The proposition is put forth that, like other factors that make up the consumption atmosphere, the mere presence of other customers has a significant impact on customers’ attachment to service organizations. Accordingly, this research proposes a framework that specifies the nature of the relationships among customer homogeneity in the social servicescape, company identification, place attachment, and word-of-mouth referral. To test the hypotheses, data were collected from a sample of 1,094 restaurant patrons in the United States. Results of structural equation analyses supported the overall contention that, in addition to the traditionally identified aspects of the servicescape (e.g., facility attractiveness, ambient conditions, seating comfort, and layout), the mere presence of others can affect the extent to which individuals perceive feelings of attachment to the restaurant. This relationship is demonstrated to take place via the mediating effect of company identification.
Thrombelastography changes in pre-eclampsia and eclampsia.

We have measured platelet count, bleeding time and thrombelastography (TEG) variables and the correlation between these variables in 49 pregnant patients presenting with pre-eclampsia or eclampsia. Eighteen patients (37%) had a platelet count < or = 150 x 10(9) litre-1 and seven (14%) had a platelet count < or = 100 x 10(9) litre-1. Bleeding time was prolonged > 9.5 min in 13 (27%) patients and the TEG was abnormal in four (8%). The TEG variables, k time and maximum amplitude (MA) had a strong correlation with platelet count (k time-platelet count < or = 150 x 10(9) litre-1, r = -0.68, P = 0.003, platelet count < or = 100 x 10(9) litre-1, r = -0.84, P = 0.02; MA--platelet count < or = 150 x 10(9) litre-1, r = 0.72, P = 0.001, platelet count < or = 100 x 10(9) litre-1, r = 0.78, P = 0.04). There was no correlation between bleeding time and thrombocytopenia (platelet count < or = 150 x 10(9) litre-1, r = -0.18, ns; platelet count < or = 100 x 10(9) litre-1, r = 0.09, ns). There was no correlation between bleeding time and any measured TEG variable. Of the 10 (20%) patients with an adequate platelet count (> 100 x 10(9) litre-1) but prolonged bleeding time, the TEG was normal, suggesting adequate haemostasis. An MA of 53 mm, which is the lower limit for normal pregnancy, correlated with a platelet count of 54 x 10(9) litre-1 (95% confidence limits 40-75 x 10(9) litre-1). Although the number of patients with severe thrombocytopenia was small, a platelet count of 75 x 10(9) litre-1 should be associated with adequate haemostasis.
The Influence of Foraging Mode and Arid Adaptation on the Basal Metabolic Rates of Burrowing Mammals

Two competing but nonexclusive hypotheses to explain the reduced basal metabolic rate (BMR) of mammals that live and forage underground (fossorial species) are examined by comparing this group with burrowing mammals that forage on the surface (semifossorial species). These hypotheses suggest that the low BMR of fossorial species either compensates for the enormous energetic demands of subterranean foraging (the cost‐of‐burrowing hypothesis) or prevents overheating in closed burrow systems (the thermal‐stress hypothesis). Because phylogentically informed allometric analysis showed that arid burrowing mammals have a significantly lower BMR than mesic ones, fossorial and semifossorial species were compared within these groups. The BMRs of mesic fossorial and semifossorial mammals could not be reliably distinguished, nor could the BMRs of large (>77 g) arid fossorial and semifossorial mammals. This finding favours the thermal‐stress hypothesis, because the groups appear to have similar BMRs despite differences in foraging costs. However, in support of the cost‐of‐burrowing hypothesis, small (<77 g) arid fossorial mammals were found to have a significantly lower BMR than semifossorial mammals of the similar size. Given the high mass‐specific metabolic rates of small animals, they are expected to be under severe energy and water stress in arid environments. Under such conditions, the greatly reduced BMR of small fossorial species may compensate for the enormous energetic demands of subterranean foraging.
Immunoglobulins Treatment in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Intravenously administered immunoglobulins (IgG) treatment has several modes of action that can regulate the immune response during different steps of the inflammatory process in experimental autoimmune encephalomyelitis (EAE) and Multiple Sclerosis (MS). The immunomodulatory effects IgG are largely dependent on their ability to interact with membrane molecules of lymphocytes and monocytes. Better understanding of these mechanisms of action in relation to the pathogenesis of MS, is important in order to decide the time of initiation and the duration of treatment in MS patients. In order to have the best beneficial effect on disease course, future research should focus on the initial events that activate the disease and on the early treatment modalities of IgG in MS.
Characterization of an SNR gene locus in Saccharomyces cerevisiae that specifies both dispensible and essential small nuclear RNAs

A genetic locus is described that specifies two Saccharomyces cerevisiae small nuclear RNAs (snRNAs). The genes specifying the two snRNAs are separated by only 67 base pairs and are transcribed in the same direction. The product RNAs contain 128 and 190 nucleotides and are designated snR128 and snR190, respectively. These RNAs resemble snRNAs of other eucaryotes in nuclear localization and possession of a 5' trimethylguanosine cap. Neither snRNA is related in sequence to previously described vertebrate or yeast snRNAs. Both RNAs exhibit properties consistent with nucleolar organization and hydrogen bonding to pre-rRNA species, suggesting possible roles in ribosome biogenesis. The snR128 species cosediments with deproteinized 27S pre-rRNA, whereas snR190 is associated with a 20S intermediate. Gene disruption in vitro followed by replacement of the chromosomal alleles reveals that SNR128 is essential, whereas SNR190 is not.
Inflammatory Levels of Nitric Oxide Inhibit Airway Epithelial Cell Migration by Inhibition of the Kinase ERK1/2 and Activation of Hypoxia-inducible Factor-1α*

Increased synthesis of NO during airway inflammation, caused by induction of nitric-oxide synthase 2 in several lung cell types, may contribute to epithelial injury and permeability. To investigate the consequence of elevated NO production on epithelial function, we exposed cultured monolayers of human bronchial epithelial cells to the NO donor diethylenetriaamine NONOate. At concentrations generating high nanomolar levels of NO, representative of inflammatory conditions, diethylenetriaamine NONOate markedly reduced wound closure in an in vitro scratch injury model, primarily by inhibiting epithelial cell migration. Analysis of signaling pathways and gene expression profiles indicated a rapid induction of the mitogen-activated protein kinase phosphatase (MPK)-1 and decrease in extracellular signal-regulated kinase (ERK)1/2 activation, as well as marked stabilization of hypoxia-inducible factor (HIF)-1α and activation of hypoxia-responsive genes, under these conditions. Inhibition of ERK1/2 signaling using U0126 enhanced HIF-1α stabilization, implicating ERK1/2 dephosphorylation as a contributing mechanism in NO-mediated HIF-1α activation. Activation of HIF-1α by the hypoxia mimic cobalt chloride, or cell transfection with a degradation-resistant HIF-1α mutant construct inhibited epithelial wound repair, implicating HIF-1α in NO-mediated inhibition of cell migration. Conversely, NO-mediated inhibition of epithelial wound closure was largely prevented after small interfering RNA suppression of HIF-1α. Finally, NO-mediated inhibition of cell migration was associated with HIF-1α-dependent induction of PAI-1 and activation of p53, both negative regulators of epithelial cell migration. Collectively, our results demonstrate that inflammatory levels of NO inhibit epithelial cell migration, because of suppression of ERK1/2 signaling, and activation of HIF-1α and p53, with potential consequences for epithelial repair and remodeling during airway inflammation.
Test Specifications, Correct Modeling, and Sensitivity of Long-Run Abnormal Returns in Hedge Fund Target Firms

Following the literature on test-specifications, correct-modeling, and detectability of long-run stock performance in event study framework, this study tests the performance of monthly stock returns of 589 firms targeted by 112 hedge funds over the period of January 2000 to December 2013. For an estimation window of (-12, 36) months, it addresses two fundamental questions; first, whether active targets (13D) outperform the passive targets (13G) in recent financial crisis; and second, whether long-horizon abnormal returns still pronounce when corrected for biases and test-specifications. To investigate these concerns, a number of methodologies including cumulative abnormal returns, buy-and-hold abnormal returns, and calendar -- time portfolio approach using various matching criteria are applied. Our initial findings suggest that 13D firms perform relatively better than 13G firms, however, underperform the PE targets. Moreover, when matching criteria are well-defined, then estimates appear generally significant with the improved power of the tests.
A Randomized, Double-Blind, Parallel-Group Study Comparing the Analgesic Effect of Etoricoxib to Placebo, Naproxen Sodium, and Acetaminophen With Codeine Using the Dental Impaction Pain Model

Objective:To compare the overall analgesic effect, including time to onset, peak and duration of effect for etoricoxib 120 mg, a new COX-2 selective inhibitor, in patients with acute pain to that of placebo. Naproxen sodium 550 mg and acetaminophen/codeine 600/60 mg were the active comparators. Methods:A total of 201 patients with moderate to severe pain following surgical extraction of ≥2 third molars, of which at least the mandibular tooth was impacted, were randomly allocated to receive single oral doses of placebo (n = 50), etoricoxib 120 mg (n = 50), naproxen sodium 550 mg (n = 51), or acetaminophen/codeine 600/60 mg (n = 50). The endpoints included total pain relief over 8 hours (TOPAR8, primary end point), sum of pain intensity difference over 8 hours, patient’s global evaluation, onset, peak, and duration of analgesia. Results:Etoricoxib 120 mg had a significantly greater least squares (LS) mean TOPAR8 score than placebo (20.9 vs 5.4; P < 0.001) and acetaminophen/codeine 600/60 mg (20.9 vs 11.5; P < 0.001), and a similar LS mean TOPAR8 score to naproxen sodium 550 mg (20.9 vs 21.3). All three active treatments had rapid onset of analgesia, median time ~30 minutes. The duration of analgesic effect, defined as median time to rescue medication use, was >24 hours for etoricoxib, 20.8 hours for naproxen sodium, 3.6 hours for acetaminophen/codeine, and 1.6 hours for placebo. Discussion:Etoricoxib is a new COX-2 selective inhibitor under development for treatment of osteoarthritis, rheumatoid arthritis, and acute pain. In this study, etoricoxib 120 mg provided rapid and long-lasting pain relief to patients with moderate-to-severe postdental surgery pain. Etoricoxib was generally well tolerated.
Bilateral Multiple Variations in Carotid Arteries-A Case Report

to enter the oropharynx to supply the palatine tonsil. Anatomical variations occur throughout the course of carotid arteries. Variations may occur in origin, branching pattern and level of bifurcation. aBstRaCt The common carotid arteries are the largest bilateral arteries of the head and neck. The common carotid arteries may bifurcate higher or lower than the usual levels. A higher bifurcation is more common. Tortuous arteries if present may be asymptomatic if it is mild but may lead to ischaemia of the organs if severe. The cause could be genetic, or may be thickening of the arteries. During routine dissection of an adult male cadaver in the department of Anatomy, BLDEU’s Shri BM Patil Medical college, Vijaypur, we found the bilateral multiple variations in the carotid arteries regarding the bifurcation level of common carotid arteries, tortuous external and internal carotid arteries and the number of branches arising from external carotid arteries. The knowledge of such variations of carotid arteries is of great importance in radiological examinations especially per cutaneous carotid angiography. It is necessary to understand the anatomy of these vessels and its variations to carry out surgeries with minimum complications.