Miracle-dz/UniFAR-FTUs huggingface dataset:
The Oral Iron Chelator Deferiprone Protects Against Retinal Degeneration Induced through Diverse Mechanisms.

PURPOSE To investigate the effect of the iron chelator deferiprone (DFP) on sodium iodate (NaIO3)-induced retinal degeneration and on the hereditary retinal degeneration caused by the rd6 mutation. METHODS Retinas from NaIO3-treated C57BL/6J mice, with or without DFP cotreatment, were analyzed by histology, immunofluorescence, and quantitative PCR to investigate the effect of DFP on retinal degeneration. To facilitate photoreceptor quantification, we developed a new function of MATLAB to perform this task in a semiautomated fashion. Additionally, rd6 mice treated with or without DFP were analyzed by histology to assess possible protection. RESULTS In NaIO3-treated mice, DFP protected against retinal degeneration and significantly decreased expression of the oxidative stress-related gene heme oxygenase-1 and the complement gene C3. DFP treatment partially protected against NaIO3-induced reduction in the levels of mRNAs encoded by visual cycle genes rhodopsin (Rho) and retinal pigment epithelium-specific 65 kDa protein (Rpe65), consistent with the morphological data indicating preservation of photoreceptors and RPE, respectively. DFP treatment also protected photoreceptors in rd6 mice. CONCLUSIONS The oral iron chelator DFP provides significant protection against retinal degeneration induced through different modalities. This suggests that iron chelation could be useful as a treatment for retinal degeneration even when the main etiology does not appear to be iron dysregulation. TRANSLATIONAL RELEVANCE These data provide proof of principle that the oral iron chelator DFP can protect the retina against diverse insults. Further testing of DFP in additional animal retinal degeneration models at a range of doses is warranted.
High-dimensional change-point estimation: Combining filtering with convex optimization

We consider change-point estimation in a sequence of high-dimensional signals given noisy observations. Classical approaches to this problem such as the filtered derivative method are useful for sequences of scalar-valued signals, but they have undesirable scaling behavior in the high-dimensional setting. However, many high-dimensional signals encountered in practice frequently possess latent low-dimensional structure. Motivated by this observation, we propose a technique for high-dimensional change-point estimation that combines the filtered derivative approach from previous work with convex optimization methods based on atomic norm regularization, which are useful for exploiting structure in high-dimensional data. Our algorithm is applicable in online settings as it operates on small portions of the sequence of observations at a time, and it is well-suited to the high-dimensional setting both in terms of computational scalability and of statistical efficiency. The main result of this paper shows that our method performs change-point estimation reliably as long as the product of the smallest-sized change (the Euclidean-norm-squared of the difference between signals at a change-point) and the smallest distance between change-points (number of time instances) is larger than a Gaussian width parameter that characterizes the low-dimensional complexity of the underlying signal sequence. A full version of this paper is available online [1].
“New Balls, Please!”—The Prosody of Tennis Scores

Tennis scores represent a natural language domain that offers the unique opportunity to study the effects of discourse constraints on prosody with strict control over syntactic and lexical variation. This study analyzed a set of tennis scores, such as 30–15, from live recordings of several Wimbledon and Davis Cup matches. The objective was to uncover how the prosody of these scores depended on three factors: (a) the local discourse context, which varied because, after every point, either the first or the second number was different than it had been in the score reported just previously; (b) the global situation, which varied because either the serving player or the receiving player had the lead in the current game; and (c) the speaker role, which varied as the umpire or a radio reporter uttered the scores. This study excised 96 tennis scores (spoken in English) by 2 umpires and 2 live radio reporters. These scores were labelled and perceptually evaluated in terms of perceived prominence and acoustically analyzed in terms of three prosodic characteristics: loudness, speech rate, and pitch. The perceptual and acoustic analyses both showed that the prominence patterns were affected by the global situation and speaker role, but not by the local context. For both speaker roles, prosodic prominence patterns correlated with whether the game, so far, was proceeding favorably for the serving player. In the umpire data, a favorable situation correlated with extra emphasis on the first word in a score, whereas in the reporter data, an unfavorable situation correlated with more emphasis on the second word.
Cetuximab and chemoradiation for rectal cancer–is the water getting muddy?

Abstract The epidermal growth factor receptor (EGFR) inhibitor cetuximab has been successfully combined with radical radiotherapy in head and neck cancer. In colorectal cancer, increased response rates are achieved by cetuximab and panitumumab within standard chemotherapy schedules, but not in chemoradiation regimens. This review examines the clinical evidence and potential mechanisms for an interaction when EGFR inhibitors are added to fluoropyrimidine-based chemoradiation in rectal adenocarcinoma. Methods. This review was compiled by searching PubMed and Medline for English language articles published until 2009 with established search strategies, supplemented by hand searching of abstracts from the proceedings of relevant international meetings. The primary outcome measure was pathological complete response (pCR). Results. Only 13 publications and three presentations in abstract of 13 phase I/II trials of preoperative chemoradiation with cetuximab in rectal cancer were identified. A total of 316 patients were identified who received cetuximab in combination with radiotherapy and 5-fluorouracil or capecitabine preoperatively. One hundred and thirty eight of these patients received either additional irinotecan or oxaliplatin. One study with panitumumab with safety but no efficacy results was identified, and two studies with gefinitib. The pCR rate ranged from 0–20%. The overall pooled pCR for cetuximab based chemoradiation was 9.1% (29/316). The rate of G3/G4 gastrointestinal toxicity, in terms of diarrhoea, varied from 5–30%, with an overall pooled rate of 47/313 (15%). Discussion. Potential reasons for the disappointing results of EGFR inhibition with fluoropyrimidine-based preoperative chemoradiation include a less critical role of repopulation in rectal adenocarcinoma using a non-curative radiation dose; or antagonistic effects on 5FU-based chemoradiation and oxaliplatin, if some cells arrest in G1 or G2-M and fail to pass through S phase. Conclusion. Cetuximab combined with fluoropyrimidine-based chemoradiation is not currently recommended. A better understanding of the mechanisms involved in combinations of chemotherapy and radiotherapy might allow more effective future scheduling of biological and chemical agents in combination with radiation.
MicroRNAs modulated by local mIGF-1 expression in mdx dystrophic mice

Duchenne muscular dystrophy (DMD) is a X-linked genetic disease in which the absence of dystrophin leads to progressive lethal skeletal muscle degeneration. It has been demonstrated that among genes which are important for proper muscle development and function, micro-RNAs (miRNAs) play a crucial role. Moreover, altered levels of miRNAs were found in several muscular disorders, including DMD. A specific group of miRNAs, whose expression depends on dystrophin levels and whose deregulation explains several DMD pathogenetic traits, has been identified. Here, we addressed whether the anabolic activity of mIGF-1 on dystrophic muscle is associated with modulation of microRNAs expression. We demonstrated that some microRNAs are strictly linked to the dystrophin expression and are not modulated by mIGF-1 expression. In contrast, local expression of mIGF-1 promotes the modulation of other microRNAs, such as miR-206 and miR-24, along with the modulation of muscle specific genes, which are associated with maturation of regenerating fibers and with the stabilization of the differentiated muscle phenotype. These data suggest that mIGF-1, modifying the expression of some of the active players of muscle homeostasis, is able, even in absence of dystrophin expression, to activate circuitries that confer robustness to dystrophic muscle.
Drosophila comes of age as a model system for understanding the function of cytoskeletal proteins in cells, tissues, and organisms

For the last 100 years, Drosophila melanogaster has been a powerhouse genetic system for understanding mechanisms of inheritance, development, and behavior in animals. In recent years, advances in imaging and genetic tools have led to Drosophila becoming one of the most effective systems for unlocking the subcellular functions of proteins (and particularly cytoskeletal proteins) in complex developmental settings. In this review, written for non‐Drosophila experts, we will discuss critical technical advances that have enabled these cell biological insights, highlighting three examples of cytoskeletal discoveries that have arisen as a result: (1) regulation of Arp2/3 complex in myoblast fusion, (2) cooperation of the actin filament nucleators Spire and Cappuccino in establishment of oocyte polarity, and (3) coordination of supracellular myosin cables. These specific examples illustrate the unique power of Drosophila both to uncover new cytoskeletal structures and functions, and to place these discoveries in a broader in vivo context, providing insights that would have been impossible in a cell culture model or in vitro. Many of the cellular structures identified in Drosophila have clear counterparts in mammalian cells and tissues, and therefore elucidating cytoskeletal functions in Drosophila will be broadly applicable to other organisms. © 2015 Wiley Periodicals, Inc.
Type 2C protein phosphatases directly regulate abscisic acid-activated protein kinases in Arabidopsis

Abscisic acid (ABA) signaling is important for stress responses and developmental processes in plants. A subgroup of protein phosphatase 2C (group A PP2C) or SNF1-related protein kinase 2 (subclass III SnRK2) have been known as major negative or positive regulators of ABA signaling, respectively. Here, we demonstrate the physical and functional linkage between these two major signaling factors. Group A PP2Cs interacted physically with SnRK2s in various combinations, and efficiently inactivated ABA-activated SnRK2s via dephosphorylation of multiple Ser/Thr residues in the activation loop. This step was suppressed by the RCAR/PYR ABA receptors in response to ABA. However the abi1–1 mutated PP2C did not respond to the receptors and constitutively inactivated SnRK2. Our results demonstrate that group A PP2Cs act as ‘gatekeepers’ of subclass III SnRK2s, unraveling an important regulatory mechanism of ABA signaling.
Evaluating the Performance Potential of Function Level Parallelism

Because of technology advances, current trend in processor architecture design focuses on placing multiple cores on single chip instead of increasing the complexity of single core processors. These upcoming processors are able to execute several threads in parallel, which make them a suitable platform for the application of automatic parallelization techniques. Most of the research efforts concerning automatic parallelization are in essence sophisticated translations from Instruction Level Parallelism (ILP) techniques working on loop parallelization, which apply speculation in both data and control prediction. Nevertheless, these techniques incur in a high overhead due to the additional instructions required to detect dependencies among iterations or to verify predictions. In order to avoid these shortcomings, in this paper, we devise a novel way to exploit Thread Level Parallelism (TLP) by means of a compiler-based technique, referred to as Function Level Parallelism (FLP), that looks for parallelism at a function level. This technique detects larger threads than other existing techniques like the loop-level based ones, which is a main concern when exploiting TLP. In addition, it also reduces the involved runtime overhead.
Glaciers Dominate Eustatic Sea-Level Rise in the 21st Century

Ice loss to the sea currently accounts for virtually all of the sea-level rise that is not attributable to ocean warming, and about 60% of the ice loss is from glaciers and ice caps rather than from the two ice sheets. The contribution of these smaller glaciers has accelerated over the past decade, in part due to marked thinning and retreat of marine-terminating glaciers associated with a dynamic instability that is generally not considered in mass-balance and climate modeling. This acceleration of glacier melt may cause 0.1 to 0.25 meter of additional sea-level rise by 2100.
Modeling and characterization of energy storage devices

The increasing production of energy from intermittent renewable sources (solar, wind) is also increasing the necessity of energy storage systems, which can provide a wide array of solutions to issues that affect electric power systems. This paper is aimed at summarizing the main characteristics of energy storage technologies, the factors that have to be considered for their selection, their main applications, and the type of models proposed for representing these technologies in economic and power system studies.
Different frequencies of angiotensin-converting enzyme genotypes in older hypertensive individuals.

The frequency of the D allele of an insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene has been reported to be elevated in myocardial infarction and other patients. We therefore hypothesized that death rate of DD individuals should be increased in the population as a whole and this should be evident as a decrease in DD frequency with age. This hypothesis was tested in 118 Caucasian subjects who were already at high risk of cardiovascular events by having severe, early onset, familial hypertension (HT). A group of 196 age-, sex- and body mass index-matched normotensives (NTs) was used as a control. In the NT group II, ID, and DD genotype frequencies were similar for different age groups. DD frequency was 0.42 in NTs, but in HTs was 0.28, 0.26, and 0.10 for the age groups < 50, 50-59, and > or = 60 yr, respectively. Corresponding D allele frequencies were 0.52, 0.46, and 0.40 in the respective age groups of HTs, compared with 0.61 in NTs (by chi 2-analysis, P = 0.1, 0.047, and 0.0006, respectively). In HTs aged > or = 60, DD frequency was only 14% of expected. Plasma ACE activity tracked similarly with I/D genotype in HTs (P = 0.027; n = 35) as in NTs (P = 0.0001; n = 94) and Michaelis constant was identical for DD and II. Neither blood pressure, body mass index, nor sex bore any relationship with I/D genotype. In conclusion, in a group of severely HT patients not selected for cardiac pathology, there appeared to be a marked, selective decrease, in subgroups of increasing age, in frequency of the ACE DD genotype. One possibility suggested by this data might be that DD increases risk of premature death, at least in HTs who have two HT parents.
Growing up with a Single Parent: What Hurts, What Helps

McLanahan, Sara, and Sandefur, Gary. (1994). Growing Up With a Single Parent: What Hurts, What Helps. Cambridge, MA: Harvard University Press. 196 pp. Hardcover ISBN 0-674-36407-4, price $19.95. Integrating their insights from more than a decade of research on single-parent families, McLanahan and Sandefur rekindle the debate concerning the consequences for children growing up in households where only one biological parent is present. Their news is not good. Based on extensive analyses of four national data sets, the authors conclude that the disadvantages for children living with single parents are substantial, they occur across several important life domains, and they persist long into adulthood. The authors fmd that regardless of parents' race or educational background, children spending some part of their childhood in a single-parent household earn lower grades in school and are less likely to graduate from high school, less likely to attend or graduate from college, and more likely to be unemployed during late adolescence and early adulthood. Young women from single-parent households are more likely to bear children outside of marriage. This research is made more significant by the fact that most studies have examined children's short-term adjustment to divorce and other single-parent arrangements, and very few have examined long-term effects. Attempting to establish linkages between childhood family structure and later success, the authors systematically explore the potential mediating influence of parenting practices, socioeconomic differences, and community involvement across family types. They document that, according to high school sophomores, divorced parents provide less supervision and less help with homework than married parents and that children from single-parent households are more likely than other children to be poor, to live in poor neighborhoods, to attend poorly funded schools with high dropout rates, and to have peers who do not value education. Importantly, when predivorce and postdivorce income are controlled in analyses of high school dropout risk and other outcomes, the differences between adolescents who experience parental divorce and those who do not diminish to 3 to 4 percentage points. Readers should be aware that the authors value the "standard package"the heterosexual, conjugal, nuclear, domestic unit headed by a male breadwinner and female caretaker. Most of these families are assumed to be happy and functional and when adverse circumstances arise, they should stay together because "the child would probably be better off" (p. 31). The authors argue that in single-mother families, "parental affection and warmth is . …
Efficiently compiling a functional language on AMD64: the HiPE experience

We describe and document our experience from developing an AMD64 backend for the HiPE (High Performance Erlang) native code compiler. We consider implementation alternatives and critically examine design choices for obtaining an efficient AMD64 backend. In particular, we consider in detail how other functional language implementors can migrate their existing x86 backends to the AMD64 architecture, a platform which is becoming increasingly important these days. We mention backend components that can be shared between x86 and AMD64, and those that better be different for achieving high performance on AMD64. Finally, we measure the performance of several different alternatives in the hope that this information can save development effort for others who intend to engage in a similar feat.
Typed cross-module compilation

Higher-order modules are very effective in structuring large programs and defining generic, reusable software components. Unfortunately, many compilation techniques for the core languages do not work across the module boundaries. As a result, few optimizing compilers support these module facilities well.This paper exploits the semantic property of ML-style modules to support efficient cross-module compilation. More specifically, we present a type-directed translation of the MacQueen-Tofte higher-order modules into a predicative variant of the polymorphic &lambda;-calculus F&omega;. Because modules can be compiled in the same way as ordinary polymorphic functions, standard type-based optimizations such as representation analysis immediately carry over to the module languages.We further show that the full-transparency property of the MacQueen-Tofte system yields a near optimal cross-module compilation framework. By propagating various static information through the module boundaries, many static program analyses for the core languages can be extended to work across higher-order modules.
A prospective study of intake of fish and marine fatty acids and prostate cancer.

Experimental studies suggest that marine fatty acids have an antitumor effect on prostate tumor cells. The aim of this study was to investigate whether high consumption of fish and marine fatty acids reduces the risk of prostate cancer in humans. We followed 47882 men participating in the Health Professionals Follow-up Study. Dietary intake was assessed in 1986, 1990, and 1994, using a validated food frequency questionnaire. During 12 years of follow-up, 2482 cases of prostate cancer were diagnosed, of which 617 were diagnosed as advanced prostate cancer including 278 metastatic prostate cancers. Eating fish more than three times per week was associated with a reduced risk of prostate cancer, and the strongest association was for metastatic cancer (multivariate relative risk, 0.56; 95% confidence interval, 0.37-0.86, compared with infrequent consumption, i.e., less than twice per month). Intake of marine fatty acids from food showed a similar but weaker association. Each additional daily intake of 0.5 g of marine fatty acid from food was associated with a 24% decreased risk of metastatic cancer. We found that men with high consumption of fish had a lower risk of prostate cancer, especially for metastatic cancer. Marine fatty acids may account for part of the effect, but other factors in fish may also play a role.
The equine periodic paralysis Na+ channel mutation alters molecular transitions between the open and inactivated states.

1. The Na+ channel mutation associated with equine hyperkalaemic periodic paralysis (HPP) affects a highly conserved phenylalanine residue in an unexplored region of the alpha‐subunit. This mutation was introduced into the rat skeletal muscle Na+ channel gene at the corresponding location (i.e. F1412L) for functional expression and characterization in Xenopus oocytes. 2. In comparison with wild‐type (WT) channels, equine HPP channels showed clear evidence for disruption of inactivation: increased time‐to‐peak current, slowed rates of whole‐cell current decay, significant increases in sustained current, rightward shifts in the steady‐state inactivation curve by 9.5 mV, a 6‐fold acceleration in the rate of recovery from inactivation at ‐80 mV, decreased number of blank single‐channel sweeps, repetitive opening of single channels throughout depolarizing steps, increased open probability per sweep, and an increased mean open time. 3. The observed disruption of inactivation in HPP occurred without measurable changes in steady‐state activation and first latency kinetics of channel opening. 4. Kinetic modelling demonstrates that the equine HPP phenotype can be simulated by altering the rate constants for transitions entering and leaving the inactivated states resulting from an energetic destabilization of the inactivated state. 5. These results suggest that the highly conserved cytoplasmic end of the third transmembrane segment (S3) in the fourth internal repeat domain (domain IV) plays a critical role in Na+ channel inactivation.