Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase II Study of Nilotinib in Melanoma Harboring KIT Alterations Following Progression to Prior KIT Inhibition

Purpose: Although durable responses can be achieved with tyrosine kinase inhibitors such as imatinib in melanomas harboring KIT mutations, the efficacy of alternative inhibitors after progression to imatinib and the activity of these agents on brain metastases are unknown. Experimental Design: We conducted a phase II study of nilotinib 400 mg twice a day in two cohorts of patients with melanomas harboring KIT mutations or amplification: (A) those refractory or intolerant to a prior KIT inhibitor; and (B) those with brain metastases. The primary endpoint was 4-month disease control rate. Secondary endpoints included response rate, time-to-progression (TTP), and overall survival (OS). A Simon two-stage and a single-stage design was planned to assess for the primary endpoint in cohorts A and B, respectively. Results: Twenty patients were enrolled and 19 treated (11 in cohort A; 8 in cohort B). Three patients on cohort A [27%; 95% confidence interval (CI), 8%–56%] and 1 on cohort B (12.5%; 90% CI, 0.6%–47%) achieved the primary endpoint. Two partial responses were observed in cohort A (18.2%; 90% CI, 3%–47%); none were observed in cohort B. The median TTP and OS was 3.3 (90% CI, 2.1–3.9 months) and 9.1 months (90% CI, 4.3–14.2 months), respectively, in all treated patients. Conclusions: Nilotinib may achieve disease control in patients with melanoma harboring KIT alterations and whose disease progressed after imatinib therapy. The efficacy of this agent in KIT-altered melanoma with brain metastasis is limited. Clin Cancer Res; 21(10); 2289–96. ©2015 AACR.
Seamount‐Volcanic Island Transition and Evolution From Fissural to Central Activity Inferred by the Magnetic Modeling of Salina Island (Tyrrhenian Sea)

Volcanic islands represent the later stage of an early submarine volcanic activity and show different morphologies reflecting the geometry of shallow plumbing systems, magma output rate, gravitational instability, and erosive phases. Two end‐member morphologies may be recognized: (a) rift‐like elongated edifices and ‘stellate’ volcanoes and (b) cone‐shaped, central‐type volcanoes. While the evolution from early conical shapes to stellate shapes is relatively well known, the reverse is less constrained, commonly lacking geophysical and geological data to support it. We present magnetic forward and 3‐D inverse models of the volcanic island of Salina (244‐15 ka; Aeolian Arc, Southern Tyrrhenian Sea) to characterize its shallow plumbing system. The detected magnetic sources are interpreted as the crystallized portions of dykes and vertical conduits. The dykes mainly characterize the offshore of Salina Island, whereas subcircular conduits are located onshore. The results show that the early, mainly submarine phases of Salina concentrated along dykes following weakness zones of tectonic significance. As the volcanism proceeded, the subaerial activity focused on two main cone‐shaped stratovolcanoes (Monte Fossa delle Felci and Monte dei Porri). The intersections among dykes and the progressive loading of volcanic products during the early growth of Salina are responsible for the transition from an early fissural basaltic activity to a later, basaltic to a last, more evolved central‐type volcanism. We conclude that intrusions along pre‐existing tectonic structures, dyke intersections, and loading processes related to the formation of a volcanic pile regulate the morphology and structural evolution of volcanic islands from the early, submarine phase to the later subaerial activity.
Representing Continuous Change in the Abductive Event Calculus

In this paper we extend the Abductive Event Calculus, a variant and extension of the Event Calculus of Kowalski and Sergot, with a representation for continuous change. We assume the change is not exactly known and use constraints to represent the available knowledge. The resulting logic program can be executed by the SLDNFA abductive procedure of Denecker and De Schreye. We show how our representation of continuous change combines with solutions to other problems in temporal reasoning, like indeterministic eeects of actions, and how it can be used not only for temporal projection, but also to solve planning and diagnosis problems or any combination thereof.
BRIT1/MCPH1 Is Essential for Mitotic and Meiotic Recombination DNA Repair and Maintaining Genomic Stability in Mice

BRIT1 protein (also known as MCPH1) contains 3 BRCT domains which are conserved in BRCA1, BRCA2, and other important molecules involved in DNA damage signaling, DNA repair, and tumor suppression. BRIT1 mutations or aberrant expression are found in primary microcephaly patients as well as in cancer patients. Recent in vitro studies suggest that BRIT1/MCPH1 functions as a novel key regulator in the DNA damage response pathways. To investigate its physiological role and dissect the underlying mechanisms, we generated BRIT1 −/− mice and identified its essential roles in mitotic and meiotic recombination DNA repair and in maintaining genomic stability. Both BRIT1 −/− mice and mouse embryonic fibroblasts (MEFs) were hypersensitive to γ-irradiation. BRIT1 −/− MEFs and T lymphocytes exhibited severe chromatid breaks and reduced RAD51 foci formation after irradiation. Notably, BRIT1 −/− mice were infertile and meiotic homologous recombination was impaired. BRIT1-deficient spermatocytes exhibited a failure of chromosomal synapsis, and meiosis was arrested at late zygotene of prophase I accompanied by apoptosis. In mutant spermatocytes, DNA double-strand breaks (DSBs) were formed, but localization of RAD51 or BRCA2 to meiotic chromosomes was severely impaired. In addition, we found that BRIT1 could bind to RAD51/BRCA2 complexes and that, in the absence of BRIT1, recruitment of RAD51 and BRCA2 to chromatin was reduced while their protein levels were not altered, indicating that BRIT1 is involved in mediating recruitment of RAD51/BRCA2 to the damage site. Collectively, our BRIT1-null mouse model demonstrates that BRIT1 is essential for maintaining genomic stability in vivo to protect the hosts from both programmed and irradiation-induced DNA damages, and its depletion causes a failure in both mitotic and meiotic recombination DNA repair via impairing RAD51/BRCA2's function and as a result leads to infertility and genomic instability in mice.
The Grapevine Expression Atlas Reveals a Deep Transcriptome Shift Driving the Entire Plant into a Maturation Program[W][OA]

The authors developed a comprehensive transcriptome atlas in grapevine by comparing the genes expressed in 54 diverse samples accounting for ∼91% of all known grapevine genes. Using a panel of different statistical techniques, they found that the whole plant undergoes transcriptomic reprogramming, driving it towards maturity. We developed a genome-wide transcriptomic atlas of grapevine (Vitis vinifera) based on 54 samples representing green and woody tissues and organs at different developmental stages as well as specialized tissues such as pollen and senescent leaves. Together, these samples expressed ∼91% of the predicted grapevine genes. Pollen and senescent leaves had unique transcriptomes reflecting their specialized functions and physiological status. However, microarray and RNA-seq analysis grouped all the other samples into two major classes based on maturity rather than organ identity, namely, the vegetative/green and mature/woody categories. This division represents a fundamental transcriptomic reprogramming during the maturation process and was highlighted by three statistical approaches identifying the transcriptional relationships among samples (correlation analysis), putative biomarkers (O2PLS-DA approach), and sets of strongly and consistently expressed genes that define groups (topics) of similar samples (biclustering analysis). Gene coexpression analysis indicated that the mature/woody developmental program results from the reiterative coactivation of pathways that are largely inactive in vegetative/green tissues, often involving the coregulation of clusters of neighboring genes and global regulation based on codon preference. This global transcriptomic reprogramming during maturation has not been observed in herbaceous annual species and may be a defining characteristic of perennial woody plants.
Clickers and Online Homework in the Criminal Justice Classroom: A Test Study

Abstract The criminal justice discipline has few studies that explore the use of technology as a supplement to traditional face-to-face instruction. Using a sample of criminal justice students enrolled in two sections of the same 300-level foundational criminal justice course, this study examines the impact of clickers and online homework on student performance in the course, as well as observes student perceptions of the integrated technology. Results reveal that while students perceived the technologies as helpful to their learning, the addition of technologies to the one section of the course had little impact on student performance indicators such as test scores and final letter grades. Potential explanations for these findings and directions for future research are discussed; and suggestions on how to potentially make these supplemental tools more useful are provided.
PRIS at TREC 2013 Microblog Track

: This paper described the real-time search system we built for TREC 2013 microblog track. We focused on query expansion and ranking algorithm and employed different strategies. For query expansion, we implied pseudo-relevance feedback using WAF algorithms and a refined 𝑡𝑓 ∗ 𝑖𝑑𝑓 formula. For re-ranking part, our system makes use of various tweets’ features, such as expansion terms, URL information, and incorporate them in a learning–to-rank framework to improve the final ranking results.
On the Extension of the Minimum Cost Flow Algorithm for Phase Unwrapping of Multitemporal Differential SAR Interferograms

In this paper, an extension of the minimum cost flow (MCF) algorithm dealing with a sparse data grid, which allows the unwrapping of multitemporal differential synthetic aperture radar (SAR) interferograms for the generation of deformation time series, is presented. The proposed approach exploits both the spatial characteristics and the temporal relationships among multiple interferograms relevant to a properly chosen sequence. In particular, the presented solution involves two main steps: first of all, for each arc connecting neighboring pixels on the interferometric azimuth/range grid, the unwrapped phase gradients are estimated via the MCF technique applied in the temporal/perpendicular baseline plane. Following this step, these estimates are used as a starting point for the spatial-unwrapping operation implemented again via the MCF approach but carried out in the azimuth/range plane. The presented results, achieved on simulated and real European Remote Sensing satellite SAR data, confirm the effectiveness of the extended MCF unwrapping algorithm
The importance of studying prosody in the comprehension of spontaneous spoken discourse

The study of the role of prosodic breaks and pitch accents in comprehension has usually focused on sentence processing, through the use of laboratory speech produced by both trained and untrained speakers. In comparison, little attention has been paid to their role in the comprehension and production of spontaneous discourse, or to the interplay between prosodic cues and pitch accents and the generation of inferences. This article describes studies which have focused on the effects of prosodic boundaries and pitch accents in sentence comprehension. Their results suggest that prosody has an early influence in the parsing of sentences as well as the processing of the information structure of a statement. It also presents a new model of spontaneous discourse comprehension that can accommodate paralinguistic factors, like pitch and prosody, and other communication channels and their relation to cognitive processes. Stemming from the model presented, future research directions are suggested as well as the importance of including spontaneous spoken discourse materials and examining the role of prosodic cues and pitch accents in the establishment of connections among spoken statements is highlighted.
Cardiovascular disease and subsequent kidney disease.

BACKGROUND Chronic kidney disease is a risk factor for cardiovascular disease (CVD); however, it is uncertain if CVD is a risk factor for progression or development of kidney disease. METHODS Individual patient data were pooled from 2 longitudinal, community-based, limited-access studies, the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study. Baseline CVD was defined by stroke, angina, claudication, transient ischemic attack, coronary angioplasty or bypass, and recognized or silent myocardial infarction. Study outcomes included kidney function decline, defined by an increase in serum creatinine level of at least 0.4 mg/dL (>or=35.4 micromol/L), and development of kidney disease, defined by an increase in serum creatinine level of at least 0.4 mg/dL (>or=35.4 micromol/L) in which the baseline serum creatinine level was less than 1.4 mg/dL (<123.8 micromol/L) in men and less than 1.2 mg/dL (<106.1 micromol/L) in women and the final serum creatinine levels exceeded these levels. Secondarily, kidney function decline was defined by an estimated glomerular filtration rate (eGFR) reduction of at least 15 mL/min per 1.73 m(2), and development of kidney disease was defined by an eGFR reduction of at least 15 mL/min per 1.73 m(2) in which the baseline eGFR was at least 60 mL/min per 1.73 m(2) and the final eGFR was below these levels. Multivariate logistic regression analysis was used to determine the association between CVD and outcomes. RESULTS Among 13 826 individuals, the mean +/- SD baseline serum creatinine level was 0.9 +/- 0.2 mg/dL (79.6 +/- 17.7 micromol/L), and the mean +/- SD baseline eGFR was 89.8 +/- 20.1 mL/min per 1.73 m(2). In serum creatinine level-based models, 520 individuals (3.8%) experienced kidney function decline, and 314 individuals (2.3%) developed kidney disease during a mean +/- SD of 9.3 +/- 0.9 years of follow-up. Baseline CVD, present in 1787 individuals (12.9%), was associated with an increased risk of all outcomes (odds ratio, 1.70; 95% confidence interval, 1.36-2.13), an odds ratio of 1.75 (95% confidence interval, 1.32-2.32) for serum creatinine level, and odds ratios of 1.28 (95% confidence interval, 1.13-1.45) and 1.54 (95% confidence interval, 1.26-1.89) for eGFR for kidney function decline and development of kidney disease, respectively. CONCLUSION Cardiovascular disease is independently associated with kidney function decline and with the development of kidney disease.
The relationship between resilience and age in a large cross-sectional Japanese adult sample

患患者は約 350万人を超えると報告されており(厚生 労働省 , 2015),従来のような発症後の治療的対応だ けでなく,精神疾患につながる可能性の高い不適応状 態からの回復や,再発予防に対する心的準備性の形成 などの総合的なアプローチが求められている(上野・ 飯村・雨宮・嘉瀬, 2017)。 その中で,心理概念の 1 つとしてレジリエンス(resilience)が注目されている。 レジリエンスとは「困難で脅威的な状況にもかかわら ず,うまく適応する過程・能力・結果」とされ(Masten, Best, & Garmezy, 1990),誰もが獲得でき身につけられ る能力である(Grotberg, 2003)。 レジリエンスは重篤 かつ深刻なリスク(例えば戦争や児童虐待など)を伴 う場面から派生した概念である(Garmezy & Rutter, 1985)。 現在までにレジリエンスを測定するため,国内外で 多くの尺度が開発されてきた(井隼, 2017; Windle, Bennett, & Noyes, 2011)。 海外の代表的な尺度として, Connor & Davidson(2003)の Connor-Davidson Resilience Scaleや, Wagnild & Young (1993) の Resilience Scaleなど があるが,国内においては翻訳版が使用されることは 少なく,独自に開発された尺度が用いられることが多 い。 国内でよく使用される尺度としては小塩・中谷・ 金子・長峰(2002)の精神的回復力尺度が挙げられ, 否定的なライフイベントを経験したにもかかわらず精 神的に健康な者は得点が高いことが報告されている 日本人成人におけるレジリエンスと年齢の関連 1, 2
Interaction of ataxin-2 and ataxin-3 in Machado-Joseph disease

Machado-Joseph disease also known as Spinocerebellar ataxia type 3 (MJD/SCA3) is a hereditary neurodegenerative disease first described among Portuguese immigrants from Azores. Is the most common autossomal dominant spinocerebellar ataxia worldwide and it presents severe clinical features with a fatal outcome. This disease is caused by an unstable expansion of the trinucleotide CAG in the coding region of the MJD1 gene, the mutation is translated into an expanded polyglutamine tract in the protein ataxin-3. The mutant ataxin-3 acquires toxic properties and leads to a downstream of pathogenic mechanisms that make MJD a very heterogeneous disease. Although the polyglutamine expansion in ataxin-3 is sufficient for the pathogenesis of the disease and for the number of repeats is correlated inversely with the age of onset, clinical observations suggest that the polyQ expansion does not account for all the diversity in the age of onset and clinical manifestations. Interactions between different proteins may affect the age of onset as well as the disease progression. In a screen for modifiers of neurodegeneration in MJD, previous studies found ataxin-2, a protein involved in the spinocerebellar ataxia type 2 (SCA2) which interacts with poly (A)-binding protein (PABP) and may potentiate the neurodegeneration in MJD. The main goal of our research was to investigate the relation between ataxin-2, PABP and ataxin-3 in MJD. Recurring to human material (brain tissue and fibroblasts), transgenic mice for MJD, a lentiviral-based MJD mouse model and a cellular model of the disease, we observed that levels of ataxin-2 and PABP suffer alterations in MJD. The ataxin-2 immunoreactivity is increased in the human tissue of MJD patients, which also occurred in the transgenic rodents. In the lentiviral model we observed both proteins’ recruitment into the nucleus with the progression of the disease. The cellular model revealed a positive feedback between ataxin-2 and PABP that may to be responsible for their capacity in reducing mutant ataxin-3 levels in the disease. Attesting that the levels of the three proteins seem to be interdependent, remaining only the question whether this interaction occurs direct or indirectly. These studies indicate that the levels and the consequent toxicity of a polyglutamine disease protein can be modulated by the normal activity of another. This synergicall relation may be critical for the pathogenesis of the disease and therefore be a potential therapeutic target.
Application of instruction analysis/scheduling techniques to resource allocation of superscalar processors

This paper presents the development of instruction analysis/scheduling CAD techniques to measure the distribution of functional-unit usage and the microoperation level parallelism (MLP), which together determine the proper functional-unit allocation for superscalar microprocessors, such as the x86 microprocessors. The proposed techniques fit in the early design exploration phase in which the trace or microarchitecture simulator has not been available. The techniques have been applied to analyze several popular Windows95 applications such as Word, Excel, Communicator, etc., for their MLP and distribution of functional-unit usage. The results are used to evaluate the resource allocation of several existing x86 superscalar microprocessors and suggest future extension.
An image-analysis system based on support vector machines for automatic grade diagnosis of brain-tumour astrocytomas in clinical routine

An image-analysis system based on the concept of Support Vector Machines (SVM) was developed to assist in grade diagnosis of brain tumour astrocytomas in clinical routine. One hundred and forty biopsies of astrocytomas were characterized according to the WHO system as grade II, III and IV. Images from biopsies were digitized, and cell nuclei regions were automatically detected by encoding texture variations in a set of wavelet, autocorrelation and parzen estimated descriptors and using an unsupervised SVM clustering methodology. Based on morphological and textural nuclear features, a decision-tree classification scheme distinguished between different grades of tumours employing an SVM classifier. The system was validated for clinical material collected from two different hospitals. On average, the SVM clustering algorithm correctly identified and accurately delineated 95% of all nuclei. Low-grade tumours were distinguished from high-grade tumours with an accuracy of 90.2% and grade III from grade IV with an accuracy of 88.3% The system was tested in a new clinical data set, and the classification rates were 87.5 and 83.8%, respectively. Segmentation and classification results are very encouraging, considering that the method was developed based on every-day clinical standards. The proposed methodology might be used in parallel with conventional grading to support the regular diagnostic procedure and reduce subjectivity in astrocytomas grading.
The Relationship Between Students’ Reading Comprehension and Their Achievement in English

This study aimed at investigating the relationship between students’ reading comprehension and their achievement in English at Yarmouk University. The sample consisted of 150 female and male students. It was chosen randomly from all English101 students at Yarmouk University in the second semester of the academic year 2016-2017. To answer the questions of the study, the researcher used a reading comprehension test which consisted of 20 multiple-choice items and an achievement test which consisted of 40 multiple-choice items. The findings revealed that students’ reading comprehension was of a medium degree and their achievement in English was of a medium degree, too. Besides, there were no statistically significant differences in students’ reading comprehension or in their achievement due to gender. On the other hand, there were statistically significant differences in students’ reading comprehension and in their achievement due to college in favor of the college of science. Moreover, there was a statistically significant relationship between students’ reading comprehension and their achievement in English since reading comprehension positively affects students’ achievement. Finally, the researcher recommended conducting further research to investigate the link between students’ reading comprehension and their achievement in English since research in this area is rare.
Increasing the Problem-Solving Skills of Students with Developmental Disabilities Participating in General Education

Although skill in problem solving is critical to success in school and the community, as well as to promoting student self-determination, problem solving remains a neglected curriculum area for students with developmental disabilities. Using the self-determined learning model, 4 students with mental retardation or developmental disabilities were taught problem-solving skills to achieve self-set goals. A multiple-baseline-across-participants design was used, and the instruction was provided in general education content classes. Target behaviors included increasing appropriate touching, increasing contributions to class discussion, and increasing direction following. Data revealed immediate and dramatic changes for all participants, with performance levels maintained at 100%. Anecdotal social validation data supported the findings. The implications of these findings in respect to promoting self-determination and inclusive practice are discussed.
Gaussian-based edge-detection methods - a survey

The Gaussian filter has been used extensively in image processing and computer vision for many years. We discuss the various features of this operator that make it the filter of choice in the area of edge detection. Despite these desirable features of the Gaussian filter, edge detection algorithms which use it suffer from many problems. We review several linear and nonlinear Gaussian-based edge detection methods.