Miracle-dz/UniFAR-FTUs huggingface dataset:
New Strategies in Melanoma: Entering the Era of Combinatorial Therapy

The treatment of metastatic melanoma has been revolutionized over the past decade as effective molecularly targeted therapies and immunotherapies entered the clinic. It is hoped that deeper insights into the characteristics of patients and tumors that are most responsive will allow more precise patient selection for these therapies while understanding mechanisms of resistance will facilitate the develop of rational combinations or next-generation agents aimed at novel targets. Clin Cancer Res; 21(11); 2424–35. ©2015 AACR.
Low Intensity, High Frequency Vibration Training to Improve Musculoskeletal Function in a Mouse Model of Duchenne Muscular Dystrophy

The objective of the study was to determine if low intensity, high frequency vibration training impacted the musculoskeletal system in a mouse model of Duchenne muscular dystrophy, relative to healthy mice. Three-week old wildtype (n = 26) and mdx mice (n = 22) were randomized to non-vibrated or vibrated (45 Hz and 0.6 g, 15 min/d, 5 d/wk) groups. In vivo and ex vivo contractile function of the anterior crural and extensor digitorum longus muscles, respectively, were assessed following 8 wks of vibration. Mdx mice were injected 5 and 1 days prior to sacrifice with Calcein and Xylenol, respectively. Muscles were prepared for histological and triglyceride analyses and subcutaneous and visceral fat pads were excised and weighed. Tibial bones were dissected and analyzed by micro-computed tomography for trabecular morphometry at the metaphysis, and cortical geometry and density at the mid-diaphysis. Three-point bending tests were used to assess cortical bone mechanical properties and a subset of tibiae was processed for dynamic histomorphometry. Vibration training for 8 wks did not alter trabecular morphometry, dynamic histomorphometry, cortical geometry, or mechanical properties (P≥0.34). Vibration did not alter any measure of muscle contractile function (P≥0.12); however the preservation of muscle function and morphology in mdx mice indicates vibration is not deleterious to muscle lacking dystrophin. Vibrated mice had smaller subcutaneous fat pads (P = 0.03) and higher intramuscular triglyceride concentrations (P = 0.03). These data suggest that vibration training at 45 Hz and 0.6 g did not significantly impact the tibial bone and the surrounding musculature, but may influence fat distribution in mice.
Deep Joint Entity Disambiguation with Local Neural Attention

We propose a novel deep learning model for joint document-level entity disambiguation, which leverages learned neural representations. Key components are entity embeddings, a neural attention mechanism over local context windows, and a differentiable joint inference stage for disambiguation. Our approach thereby combines benefits of deep learning with more traditional approaches such as graphical models and probabilistic mention-entity maps. Extensive experiments show that we are able to obtain competitive or state-of-the-art accuracy at moderate computational costs.
Increases in Overweight After Adenotonsillectomy in Overweight Children With Obstructive Sleep-Disordered Breathing Are Associated With Decreases in Motor Activity and Hyperactivity

Objective. To examine the effect of adenotonsillectomy (T&A) in children with obstructive sleep-disordered breathing on growth, hyperactivity, and sleep and waking motor activity. Methods. We studied 54 children who were aged 6 to 12 years and had adenotonsillar hypertrophy and an obstructive apnea-hypopnea index of ≥1 before and 12 months after they all received adenotonsillectomy (T&A). We measured their height, weight, percentage overweight (patient BMI − BMI at 50th percentile)/BMI at 50th percentile * 100) and obtained a hyperactivity score from parent report on a standardized behavior questionnaire scale. A subset of 21 of these children were also studied for motor activity by wrist actigraphy for 7 consecutive days and nights before and 12 months after T&A. Results. After T&A, mean obstructive apnea-hypopnea index decreased from 7.6 to 0.6. Height percentile did not change, but weight percentile increased; as a consequence, percentage overweight increased from 32.0% to 36.3%. Hyperactivity scores and total daily motor activity were reduced after T&A. From linear regression, the reduction in hyperactivity scores predicted an increase in percentage overweight. Reduced motor activity was correlated with increased percentage overweight. Conclusions. An increase in percentage overweight after T&A in children with obstructive sleep-disordered breathing is correlated to decreased child hyperactivity scores and to decreased measured motor activity in the subset studied. These associations suggest that the increase in overweight may be attributable to reductions in physical activity and fidgeting energy expenditure.
A Model of Monetary Policy and Risk Premia

We develop a dynamic asset pricing model in which monetary policy affects the risk premium component of the cost of capital. Risk-tolerant agents (banks) borrow from risk-averse agents (i.e. take deposits) to fund levered investments. Leverage exposes banks to funding risk, which they insure by holding liquidity buffers. By changing the nominal rate the central bank influences the liquidity premium in financial markets, and hence the cost of taking leverage. Lower nominal rates make liquidity cheaper and raise leverage, resulting in lower risk premia and higher asset prices, volatility, investment, and growth. We analyze forward guidance, a "Greenspan put", and the yield curve.
Effect of the Thyroid State on Myocardial Contractility and Ventricular Ejection Rate in Man

Although the circulatory changes in various thyroid states are well known, the alterations of myocardial contractility of hypothyroidism and hyperthyroidism have remained controversial. The changes in the length of the ejection time (ET) and isovolumic contraction time (ICT) are used as indicative of alterations in inotropic state of the myocardium. Isovolumic contraction time, ejection time, and pre-ejection period were measured externally in 10 normal, 13 hyperthyroid, and five hypothyroid subjects. Cardiac outputs, mean rate of left ventricular ejection index, and predicted ejection times were calculated. More shortening of ICT and ET in hyperthyroid and more prolongation of these intervals in hypothyroid subjects than could be attributed to other factors were interpreted as indicative of increased and decreased myocardial contractility, respectively. Catecholamine depletion in hyperthyroid subjects with adequate administration of intramuscular reserpine induced no changes in cardiac output and oxygen consumption and caused no alteration in different phases of ventricular systole; consequently it had no effect on enhancement of hyperthyroid myocardial contractility.
CFLAP1 and CFLAP2 Are Two bHLH Transcription Factors Participating in Synergistic Regulation of AtCFL1-Mediated Cuticle Development in Arabidopsis

The cuticle is a hydrophobic lipid layer covering the epidermal cells of terrestrial plants. Although many genes involved in Arabidopsis cuticle development have been identified, the transcriptional regulation of these genes is largely unknown. Previously, we demonstrated that AtCFL1 negatively regulates cuticle development by interacting with the HD-ZIP IV transcription factor HDG1. Here, we report that two bHLH transcription factors, AtCFL1 associated protein 1 (CFLAP1) and CFLAP2, are also involved in AtCFL1-mediated regulation of cuticle development. CFLAP1 and CFLAP2 interact with AtCFL1 both in vitro and in vivo. Overexpression of either CFLAP1 or CFLAP2 led to expressional changes of genes involved in fatty acids, cutin and wax biosynthesis pathways and caused multiple cuticle defective phenotypes such as organ fusion, breakage of the cuticle layer and decreased epicuticular wax crystal loading. Functional inactivation of CFLAP1 and CFLAP2 by chimeric repression technology caused opposite phenotypes to the CFLAP1 overexpressor plants. Interestingly, we find that, similar to the transcription factor HDG1, the function of CFLAP1 in cuticle development is dependent on the presence of AtCFL1. Furthermore, both HDG1 and CFLAP1/2 interact with the same C-terminal C4 zinc finger domain of AtCFL1, a domain that is essential for AtCFL1 function. These results suggest that AtCFL1 may serve as a master regulator in the transcriptional regulation of cuticle development, and that CFLAP1 and CFLAP2 are involved in the AtCFL1-mediated regulation pathway, probably through competing with HDG1 to bind to AtCFL1.
New model to explain tooth wear with implications for microwear formation and diet reconstruction

Significance Dental microwear is among the most common proxies paleontologists use for diet reconstruction. Recent models have suggested that while quartz grit adherent to food produces wear of tooth enamel, softer particles, such as silica phytoliths found in many plants, do not. Some have therefore suggested that microwear patterns better reflect habitat than diet. This is important to paleobiologists because reconstructions of species from the earliest vertebrates to human ancestors have relied on dental microwear as a proxy for diet. Here we present an in vitro study demonstrating that softer particles produce microwear under conditions mimicking chewing. Enamel wear occurs not because an abrasive is hard but because it exceeds the binding force of proteins that hold together hydroxyapatite crystallites. Paleoanthropologists and vertebrate paleontologists have for decades debated the etiology of tooth wear and its implications for understanding the diets of human ancestors and other extinct mammals. The debate has recently taken a twist, calling into question the efficacy of dental microwear to reveal diet. Some argue that endogenous abrasives in plants (opal phytoliths) are too soft to abrade enamel, and that tooth wear is caused principally by exogenous quartz grit on food. If so, variation in microwear among fossil species may relate more to habitat than diet. This has important implications for paleobiologists because microwear is a common proxy for diets of fossil species. Here we reexamine the notion that particles softer than enamel (e.g., silica phytoliths) do not wear teeth. We scored human enamel using a microfabrication instrument fitted with soft particles (aluminum and brass spheres) and an atomic force microscope (AFM) fitted with silica particles under fixed normal loads, sliding speeds, and spans. Resulting damage was measured by AFM, and morphology and composition of debris were determined by scanning electron microscopy with energy-dispersive X-ray spectroscopy. Enamel chips removed from the surface demonstrate that softer particles produce wear under conditions mimicking chewing. Previous models posited that such particles rub enamel and create ridges alongside indentations without tissue removal. We propose that although these models hold for deformable metal surfaces, enamel works differently. Hydroxyapatite crystallites are “glued” together by proteins, and tissue removal requires only that contact pressure be sufficient to break the bonds holding enamel together.
CD25 Indicates the Neoplastic Phenotype of Mast Cells: A Novel Immunohistochemical Marker for the Diagnosis of Systemic Mastocytosis (SM) in Routinely Processed Bone Marrow Biopsy Specimens

The diagnosis of systemic mastocytosis (SM) is based primarily on the histologic and immunohistochemical evaluation of a bone marrow trephine biopsy specimen. Although mast cell (MC) specific antigens like tryptase and chymase are detectable in routinely processed tissue, no immunohistochemical markers that can be used to discriminate between normal and neoplastic MCs are yet available. We have investigated the diagnostic value of an antibody against CD25 for the immunohistochemical detection of MCs in bone marrow sections in 73 patients with SM and 75 control cases (reactive marrow, n = 54; myelogenous neoplasms, n = 21) and correlated the results with the presence of c-kit mutations. While MCs in almost all patients with SM (72 of 73) expressed CD25, none of the control samples contained CD25-positive MCs. Irrespective of the SM subtype, most of neoplastic MCs expressed CD25. In 3 patients with advanced MC disease, pure populations of neoplastic MCs were obtained and found to express CD25 mRNA by RT-PCR analysis. In addition, all patients with CD25-positive MCs contained c-kit mutations, while all control cases exhibited wild type c-kit. CD25 therefore appears to be a reliable immunohistochemical marker for the discrimination of neoplastic from normal/reactive MCs, with potential as a diagnostic tool in SM.
Mutual Distance Bounding Protocols

A distance bounding protocol enables one entity to determine an upper bound on the physical distance to the other entity as well as to authenticate the other entity. It has been actively researched during the recent years as distance-based attacks like Mafia fraud attacks become a threat in wireless environment, especially in RFID systems. Almost all distance bounding protocols deal with unilateral authentication as they consider authentication of a passive RFID tag to a reader. Recently, a distance bounding protocol providing mutual authentication has been proposed by Yum et al. asserting that it provides a lower false acceptance rate under Mafia fraud attack. However, we show in two ways that their security margins have been overestimated. First, we show that their analysis is not correct. Second, we introduce a new attack that achieves a higher false acceptance rate. Furthermore, we introduce a method that can modify existing distance bounding protocols with unilateral authentication to ones providing mutual authentication.
Children’s perceptions of emotion regulation strategy effectiveness: links with attachment security

ABSTRACT Six- and nine-year-old children (N = 97) heard illustrated stories evoking anger in a story character and provided evaluations of the effectiveness of eight anger regulation strategies. Half the stories involved the child’s mother as social partner and the other half involved a peer. Attachment security was assessed via the Security Scale. Children reported greater effectiveness for seeking support from adults and peers in the peer context than the mother context, but perceived venting as more effective with mothers. Children with higher security scores were more likely to endorse problem solving and less likely to endorse aggression in both social contexts than those with lower security scores. Early evidence for gender differences was found in that boys endorsed the effectiveness of distraction while girls endorsed venting their emotion.
Stomatopod Interrelationships: Preliminary Results Based on Analysis of three Molecular Loci

The mantis shrimps (Stomatopoda) are quintessential marine predators. The combination of powerful raptorial appendages and remarkably developed sensory systems place the stomatopods among the most effi cient invertebrate predators. High level phylogenetic analyses have been so far based on morphology. Crown-group Unipeltata appear to have diverged in two broad directions from the outset – one towards highly effi cient ‘spearing’ with multispinous dactyli on the raptorial claws (dominated by Lysiosquilloidea and Squilloidea), and the other towards ‘smashing’ (Gonodactyloidea). In a preliminary molecular study of stomatopod interrelationships, we assemble molecular data for mitochondrial 12S and 16S regions, combined with new sequences from the 16S and two regions of the nuclear 28S rDNA to compare with morphological hypotheses. Nineteen species representing 9 of 17 extant families and 3 of 7 superfamilies were analysed. The molecular data refl ect the overall patterns derived from morphology, especially in a monophyletic Squilloidea, a monophyletic Lysiosquilloidea and a monophyletic clade of gonodactyloid smashers. Molecular analyses, however, suggest the novel possibility that Hemisquillidae and possibly Pseudosquillidae, rather than being basal or near basal in Gonodactyloidea, may be basal overall to the extant stomatopods. In this context, it is signifi cant that in many respects, hemisquillids resemble the stem-lineage condition more so than any other extant forms.
Incidence trends for childhood type 1 diabetes in India

It is estimated that India is housing about 97,700 children with type 1 diabetes mellitus (T1DM). A study of 30 children with insulin-dependent diabetes with age at diagnosis ≤15 years, conducted in 1992, reported a prevalence of 0.26/1000 children. The peak age at diagnosis was 12 years. This was the first population-based study of prevalence of insulin-dependent diabetes in South India and shows that insulin-dependent diabetes is not rare and is higher than that reported from many other Asian countries. The Karnataka state T1DM registry listed an incidence of 3.7/100,000 in boys and 4.0/100,000 in girls over 13 years of data collection. At Karnal, in Haryana, the prevalence of T1DM is 26.6/100,000 in urban and 4.27/100,000 in rural areas of the district, leading to an average prevalence of 10.20/100,000 population. Karnal city has a relatively high prevalence of T1DM (31.9/100,000). An estimated 18,000 children under the age of 15 were newly diagnosed for T1DM in the year 2011 in the above-mentioned regions. The prevalence of T1DM in children is 111,500 according to a World Health Organization report of the International Diabetes Federation for the South-East Asian Region.
Career Values of Public Administration and Public Policy Students in China, Malaysia and the United States

With governments around the world needing to attract talented professionals, this exploratory, cross-cultural research analyzes career values of 384 MPA and MPP students at major universities in the capitals of China, Malaysia and the United States. Malaysians and Americans structured 23 goals along dimensions that contrasted sharply to those of the Chinese. Moreover, Malaysians and Americans cared more about self-actualization and less about co-worker comradeship than did the Chinese. All three groups prioritized elements of altruism and affluence. Segmentation analysis uncovered six distinct subgroups (Acheivers, Altruistic Analysts, Administrators, Altruistic Affluents, Acquiescents, and Apathetics) with their distributions varying by country.
Salience and Taxation: Theory and Evidence

Using two strategies, we show that consumers underreact to taxes that are not salient. First, using a field experiment in a grocery store, we find that posting tax-inclusive price tags reduces demand by 8 percent. Second, increases in taxes included in posted prices reduce alcohol consumption more than increases in taxes applied at the register. We develop a theoretical framework for applied welfare analysis that accommodates salience effects and other optimization failures. The simple formulas we derive imply that the economic incidence of a tax depends on its statutory incidence, and that even policies that induce no change in behavior can create efficiency losses.
Analysis of core circadian feedback loop in suprachiasmatic nucleus of mCry1-luc transgenic reporter mouse

The suprachiasmatic nucleus (SCN) coordinates circadian rhythms that adapt the individual to solar time. SCN pacemaking revolves around feedback loops in which expression of Period (Per) and Cryptochrome (Cry) genes is periodically suppressed by their protein products. Specifically, PER/CRY complexes act at E-box sequences in Per and Cry to inhibit their transactivation by CLOCK/BMAL1 heterodimers. To function effectively, these closed intracellular loops need to be synchronized between SCN cells and to the light/dark cycle. For Per expression, this is mediated by neuropeptidergic and glutamatergic extracellular cues acting via cAMP/calcium-responsive elements (CREs) in Per genes. Cry genes, however, carry no CREs, and how CRY-dependent SCN pacemaking is synchronized remains unclear. Furthermore, whereas reporter lines are available to explore Per circadian expression in real time, no Cry equivalent exists. We therefore created a mouse, B6.Cg-Tg(Cry1-luc)01Ld, carrying a transgene (mCry1-luc) consisting of mCry1 elements containing an E-box and E′-box driving firefly luciferase. mCry1-luc organotypic SCN slices exhibited stable circadian bioluminescence rhythms with appropriate phase, period, profile, and spatial organization. In SCN lacking vasoactive intestinal peptide or its receptor, mCry1 expression was damped and desynchronized between cells. Despite the absence of CREs, mCry1-luc expression was nevertheless (indirectly) sensitive to manipulation of cAMP-dependent signaling. In mPer1/2-null SCN, mCry1-luc bioluminescence was arrhythmic and no longer suppressed by elevation of cAMP. Finally, an SCN graft procedure showed that PER-independent as well as PER-dependent mechanisms could sustain circadian expression of mCry1. The mCry1-luc mouse therefore reports circadian mCry1 expression and its interactions with vasoactive intestinal peptide, cAMP, and PER at the heart of the SCN pacemaker.
Revised equations for estimated GFR from serum creatinine in Japan.

BACKGROUND Estimation of glomerular filtration rate (GFR) is limited by differences in creatinine generation among ethnicities. Our previously reported GFR-estimating equations for Japanese had limitations because all participants had a GFR less than 90 mL/min/1.73 m2 and serum creatinine was assayed in different laboratories. STUDY DESIGN Diagnostic test study using a prospective cross-sectional design. New equations were developed in 413 participants and validated in 350 participants. All samples were assayed in a central laboratory. SETTING & PARTICIPANTS Hospitalized Japanese patients in 80 medical centers. Patients had not participated in the previous study. REFERENCE TEST Measured GFR (mGFR) computed from inulin clearance. INDEX TEST Estimated GFR (eGFR) by using the modified isotope dilution mass spectrometry (IDMS)-traceable 4-variable Modification of Diet in Renal Disease (MDRD) Study equation using the previous Japanese Society of Nephrology Chronic Kidney Disease Initiative (JSN-CKDI) coefficient of 0.741 (equation 1), the previous JSN-CKDI equation (equation 2), and new equations derived in the development data set: modified MDRD Study using a new Japanese coefficient (equation 3), and a 3-variable Japanese equation (equation 4). MEASUREMENTS Performance of equations was assessed by means of bias (eGFR - mGFR), accuracy (percentage of estimates within 15% or 30% of mGFR), root mean squared error, and correlation coefficient. RESULTS In the development data set, the new Japanese coefficient was 0.808 (95% confidence interval, 0.728 to 0.829) for the IDMS-MDRD Study equation (equation 3), and the 3-variable Japanese equation (equation 4) was eGFR (mL/min/1.73 m2) = 194 x Serum creatinine(-1.094) x Age(-0.287) x 0.739 (if female). In the validation data set, bias was -1.3 +/- 19.4 versus -5.9 +/- 19.0 mL/min/1.73 m2 (P = 0.002), and accuracy within 30% of mGFR was 73% versus 72% (P = 0.6) for equation 3 versus equation 1 and -2.1 +/- 19.0 versus -7.9 +/- 18.7 mL/min/1.73 m(2) (P < 0.001) and 75% versus 73% (P = 0.06) for equation 4 versus equation 2 (P = 0.06), respectively. LIMITATION Most study participants had chronic kidney disease, and some may have had changing GFRs. CONCLUSION The new Japanese coefficient for the modified IDMS-MDRD Study equation and the new Japanese equation are more accurate for the Japanese population than the previously reported equations.