Miracle-dz/UniFAR-FTUs huggingface dataset:
CSF N-Glycan Profiles to Investigate Biomarkers in Brain Developmental Disorders: Application to Leukodystrophies Related to eIF2B Mutations

Background Primary or secondary abnormalities of glycosylation have been reported in various brain diseases. Decreased asialotransferrin to sialotransferrin ratio in cerebrospinal fluid (CSF) is a diagnostic marker of leukodystrophies related to mutations of genes encoding translation initiation factor, EIF2B. We investigated the CSF glycome of eIF2B-mutated patients and age-matched normal individuals in order to further characterize the glycosylation defect for possible use as a biomarker. Methodology/Principal Findings We conducted a differential N-glycan analysis using MALDI-TOF/MS of permethylated N-glycans in CSF and plasma of controls and eIF2B-mutated patients. We found in control CSF that tri-antennary/bisecting and high mannose structures were highly represented in samples obtained between 1 to 5 years of age, whereas fucosylated, sialylated structures were predominant at later age. In CSF, but not in plasma, of eIF2B-mutated patient samples, we found increased relative intensity of bi-antennary structures and decreased tri-antennary/bisecting structures in N-glycan profiles. Four of these structures appeared to be biomarker candidates of glycomic profiles of eIF2B-related disorders. Conclusion Our results suggest a dynamic development of normal CSF N-glycan profiles from high mannose type structures to complex sialylated structures that could be correlated with postnatal brain maturation. CSF N-glycome analysis shows relevant quantitative changes associated with eIF2B related disorders. This approach could be applied to other neurological disorders involving developmental gliogenesis/synaptogenesis abnormalities.
Message From Fred Spilhaus to AGU Members

Two underground detectors, in Japan and Italy, are currently recording interactions of highly penetrating particles called geoneutrinos, which are naturally produced inside the Earth. By measuring the geoneutrino flux, these pioneering projects along with several other projects that are being planned are advancing constraints on the contribution of radioactive elements to Earth’s heat budget in a novel way. The detector in Japan, which has been in operation the longest, now measures the geoneutrino flux with precision better than a model prediction. Future projects dedicated to measuring and modeling the planet’s geoneutrino flux would define the amount and distribution of heat-producing elements in the Earth and provide transformative insights into the thermal history and dynamic processes of the mantle. Geoneutrino measurements provide experimental evidence for the quantity and distribution of radioactive elements internally heating Earth. Radiogenic heating helps power plate tectonics, hot spot volcanism, mantle convection, and possibly the geodynamo. Information on the extent and location of this heating better defines the thermal dynamics and chemical composition of Earth. Given the enormous technological challenges for directly sampling deepEarth reservoirs, remotely sensing radioactive elements with geoneutrinos may furnish the first access to this information. Geoneutrinos are electron antineutrinos emitted in the beta decay of longlived terrestrial isotopes and their daughters [Fiorentini et al., 2007]. Isotopes contributing significantly to terrestrial heating are Message From Fred Spilhaus to AGU Members
Foot and Ankle Reconstruction Using the Radial Forearm Flap: A Review of 25 Cases

&NA; Twenty‐five patients underwent soft‐tissue reconstruction of the different anatomic regions of the foot and ankle using the microvascular radial forearm free flap. The patients, 19 men and 6 women, ranged in age from 3 to 80 years (mean, 48.4 years). Indications for the surgery included diabetes and/or vascular insufficiency (10 patients), trauma (9 patients), tumor (3 patients), gunshot wound (2 patients), and burn (1 patient). Osteomyelitis occurred in patients with traumatic (3 patients) and diabetic (3 patients) wounds. The weight‐bearing surface of the foot was involved in eight patients. Defects ranged in size from 45 to 210 cm2 (mean, 100.4 cm2). The radial forearm flap was successful in 23 of 25 cases (92 percent). Flap complications included flap loss (two patients), infection (three patients), and minor wound dehiscence at the flap‐leg skin interface (two patients). Recurrent ulceration occurred in two patients; both were diabetics with weight‐bearing flaps. Donor site complications included partial skin graft loss with tendon exposure in two patients; both healed with conservative management. Recurrent or persistent osteomyelitis was not seen in any of the patients. Of the eight patients with weightbearing flaps, four were ambulatory, one had limited ambulation, one was nonambulatory, one had too short a follow‐up, and one suffered flap loss. Two patients required modified shoes. Debulking was performed in one patient. Follow‐up ranged from 2 to 72 months (mean, 24.9 months). The radial forearm flap meets most of the anatomic prerequisites for the ideal foot flap. It facilitates the restoration of normal foot contour by replacing “like‐withlike,” allowing patients to use normal shoes without the need for debulking (except in one patient); it provides a durable and stable weight‐bearing plantar surface during ambulation; it achieves excellent aesthetic results without the dryness or cracking of the hypertrophied skin‐grafted muscle; and it permits sensory reinnervation. We have found it especially useful for resurfacing the dorsum, ankle, and forefoot, moderate‐sized defects, weight‐bearing surfaces, and osteomyelitic wounds. (Plast. Reconstr. Surg. 102: 1999, 1998.)
EGILS consensus report. Gastric extranodal marginal zone B-cell lymphoma of MALT

This consensus report of the EGILS (European Gastro-Intestinal Lymphoma Study) group includes recommendations on the management of gastric extranodal marginal zone B-cell lymphoma of MALT. They are based on data from the literature and on intensive discussions and votings of the experts during their annual meetings.
Does elimination of placebo responders in a placebo run‐in increase the treatment effect in randomized clinical trials? A meta‐analytic evaluation

The use of a placebo run‐in phase, in which placebo responders are withdrawn from a study before random assignment to treatment condition, has been criticized as favoring the active treatment in clinical trials. We compared the effect size of randomized, placebo‐controlled clinical trials (in the treatment of depression with selective serotonin reuptake inhibitors [SSRIs]) that include a placebo run‐in phase with those that do not, using a meta‐analytic approach. This study differed from earlier meta‐analytic studies in that it considered only SSRIs and included only studies using continuous measures of depression, allowing for a more refined assessment of effect size. An extensive literature search identified 43 datasets published between 1980 and 2000 comparing placebo with SSRI and using a continuous measure of depression (usually the Hamilton Depression Rating Scale). We included only studies of at least 6 weeks' duration focusing on treatment for primary acute major depression in adults 18–65 years of age. Studies focusing on depression in specific medical illnesses were not included. Analysis of efficacy was based on 3,047 subjects treated with an SSRI antidepressant and 3,740 subjects treated with a placebo. There was no statistically significant difference in effect size between the clinical trials that had a placebo run‐in phase followed by withdrawal of placebo responders and those trials that did not. Despite the lack of a statistically significant difference between studies of withdrawing early placebo responders and those not using this procedure, this approach is likely to continue to be used widely because it produces large absolute effect sizes. It is recommended that future studies clearly describe these procedures and report the number of subjects dropped from the study for early placebo response and other reasons. Depression and Anxiety 19:10–19, 2004. 2004 Wiley‐Liss, Inc.
Weibull distributions for continuous-carcinogenesis experiments.

In 1966, Pike suggested that continuous-carcinogenesis experiments be analyzed by fitting appropriate Weibull distributions. Unfortunately, the Weibull distribution seems nearly degenerate with respect to the two of its three parameters which do not depend on treatment, and one of these may therefore have to be fixed arbitrarily. Since both degenerate parameters have definite physical meaning, the choice of a sensible pair of values is possible. When this is done, Pike's method is excellent for separating quantitative carcinogenic response from intercurrent mortality. In this paper we also give details of how regression-type arguments can be used in a multi-group experiment to find simple relationships between the treatment applied to each group and the value of the third (treatment dependent) Weibull coefficient for that group.
Results on Optimal Tuning of Fuzzy Models of Magnetic Levitation Systems

This paper presents some results related to the optimal tuning of fuzzy models of magnetic levitation systems as widely used nonlinear processes. A modeling approach is given. The Takagi-Sugeno fuzzy models of the process (which is first stabilized) are obtained by the modal equivalence principle, where the rule consequents contain the state-space models of the stabilized process linearized at important operating points. The optimization problems are focused on the minimization of objective functions defined as the mean square modeling error (i.e., the difference between the real-world process output and the fuzzy model output). The vector variables of the objective functions consist of a part of the parameters of the input membership functions of the fuzzy models. An operating point selection algorithm is inserted in the initial phase of the modeling approach. Several nature-inspired optimization algorithms are employed to solve the optimization problems that result in optimal fuzzy models, and Particle Swarm Optimization, Simulated Annealing and Gravitational Search Algorithms are exemplified.
The evolution of an interface for choreographers

This paper describes the evolution of the interface to Life Forms, a compositional tool for the creation of dance choreography, and highlights some of the important lessons we have learned during a six year design and implementation period. The lessons learned can be grouped into two categories: 1) Process, and 2) Architecture of the Interface. Our goal in developing a tool for choreography has been to provide computer-based creative design support for the conception and development of dance. The evolution was driven by feedback from the choreographers and users who were members of the development team, combined with our knowledge of current thinking on design and composition. Although the interface evolved in a relatively unconstrained way, the resulting system has many of the features that theoretical discussion in human interface design has projected necessary. The Life Forms interface has evolved incrementally with one major discontinuity where adoption of a new compositional primitive required a completely new version.
Central nervous system prophylaxis in adults with acute lymphoblastic leukemia

Central nervous system (CNS) recurrence continues to be a significant complication in the treatment of adult patients with acute lymphoblastic leukemia (ALL). Preventing CNS recurrence has been a therapeutic challenge and has not been addressed critically in many clinical trials. Adult studies modeled on childhood ALL studies have used multiple treatment modalities, including radiation therapy, systemic therapy, intrathecal therapy, and combinations thereof. Cranial irradiation is effective but is offset by substantial toxicity, including neurologic sequelae. Systemic chemotherapy, especially with cytarabine (AraC) and methotrexate, has demonstrated promise in decreasing CNS recurrence, but therapeutic levels of drugs in the cerebrospinal fluid (CSF) are not maintained. Intrathecal chemotherapy with or without high‐dose systemic therapy is the most common approach to CNS prophylaxis. Liposomal AraC recently has become available and confers prolonged levels of free AraC in the CSF, a critical requirement for CNS prophylactic therapy. This review discusses the various modalities used for CNS prophylaxis in patients with ALL and the emerging trends, with specific emphasis on the outcome in terms of event‐free survival and toxicity. Cancer 2010. © 2010 American Cancer Society.
Recombination associated with replication of malarial mitochondrial DNA.

Mitochondrial DNA of the malarial parasite Plasmodium falciparum comprises approximately 20 copies per cell of a 6 kb genome, arranged mainly as polydisperse linear concatemers. In synchronous blood cultures, initiation of mtDNA replication coincides with the start of the 4–5 doublings in nuclear DNA that mark the reproductive phase of the erythrocytic cycle. We show that mtDNA replication coincides with a recombination process reminiscent of the replication mechanism used by certain bacteriophages and plasmids. The few circular forms of mtDNA which are also present do not replicate by a theta mechanism, but are themselves the product of recombination, and we propose they undergo rolling circle activity to generate the linear concatemers.
Low-Quality Structural and Interaction Data Improves Binding Affinity Prediction via Random Forest

Docking scoring functions can be used to predict the strength of protein-ligand binding. It is widely believed that training a scoring function with low-quality data is detrimental for its predictive performance. Nevertheless, there is a surprising lack of systematic validation experiments in support of this hypothesis. In this study, we investigated to which extent training a scoring function with data containing low-quality structural and binding data is detrimental for predictive performance. We actually found that low-quality data is not only non-detrimental, but beneficial for the predictive performance of machine-learning scoring functions, though the improvement is less important than that coming from high-quality data. Furthermore, we observed that classical scoring functions are not able to effectively exploit data beyond an early threshold, regardless of its quality. This demonstrates that exploiting a larger data volume is more important for the performance of machine-learning scoring functions than restricting to a smaller set of higher data quality.
ISSUES IN MEASUREMENT AND INTERNATIONAL COMPARISON ISSUES OF PRODUCTIVITY – AN OVERVIEW by

At the beginning of the 1970s OECD countries entered a phase of much slower growth compared to the “golden age” of early post-World War II growth. Table 1 shows that average growth rates of labour productivity since 1973 are down by more than 2 percentage points compared to the period 1950 to 1973. At first, the slowdown was ascribed to “shocks” in the world economy, including the breakdown of the Bretton Woods arrangements and the oil shocks of 1973 and 1979. However, productivity growth continued to slow down during the 1980s, at only 2.2 per cent per year on average since 1987. The search for explanations has shifted to more structural factors inhibiting growth in the long term. Compared to the period 1973-87, the growth experiences of individual countries have been more diverse since 1987, as is shown by the strong increase in the coefficient of variation of growth rates.
Continous Head Pose Estimation using Random Regression Forests

Head pose is a rich visual cue that finds great interest in the field of human robot interaction (HRI) and for video surveillance applications. Previous attempts at solving this problem have often proposed solutions formulated in a classification setting. Furthermore, strong assumptions on illumination and scale in an occlusion-free environment have usually been made. We propose a regression solution to head pose estimation based on random regression forests trained over SURF features. We believe that slight improvements would suffice to make it even more robust under unconstrained environments.
Music Information Behaviors and System Preferences of University Students in Hong Kong

T his paper presents a user study on music information needs and behaviors of university students in Hong Kong. A mix of quantitative and qualitative methods was used. A survey was completed by 101 participants and supplemental interviews were conducted in order to investigate users’ music information related activities. We found that university students in Hong Kong listened to music frequently and mainly for the purposes of entertainment, singing and playing instruments, and stress reduction. This user group often searches for music with multiple methods, but common access points like genre and time period were rarely used. Sharing music with people in their online social networks such as Facebook and Weibo was a common activity. Furthermore, the popularity of smartphones prompted the need for streaming music and mobile music applications. We also examined users’ preferences on music services available in Hong Kong such as YouTube and KKBox, as well as the characteristics liked and disliked by the users. The results not only offer insights into non-Western users’ music behaviors but also for designing online music services for young music listeners in Hong Kong.
Increased sexual activity reduces male immune function in Drosophila melanogaster

Despite the benefits of resistance, susceptibility to infectious disease is commonplace. Although specific susceptibility may be considered an inevitable consequence of the co-evolutionary arms race between parasite and host, a more general constraint may arise from the cost of an immune response. This “cost” hypothesis predicts a tradeoff between immune defense and other components of fitness. In particular, a tradeoff between immunity and sexually selected male behavior has been proposed. Here we provide experimental support for the direct phenotypic tradeoff between sexual activity and immunity by studying the antibacterial immune response in Drosophila melanogaster. Males exposed to more females showed a reduced ability to clear a bacterial infection, an effect that we experimentally link to changes in sexual activity. Our results suggest immunosuppression is an important cost of reproduction and that immune function and levels of disease susceptibility will be influenced by sexual selection.
Disparities in Peaks, Plateaus, and Declines in Prevalence of High BMI Among Adolescents

OBJECTIVES: The objective of this study was to investigate trends in prevalence of high BMI from 2001 to 2008 and examine racial/ethnic disparities. METHODS: Records for a total of 8 283 718 fifth-, seventh-, and ninth-grade students who underwent California's school-based BMI screening between 2001 and 2008 were included. Logistic regression identified trends in prevalence of high BMI (≥85th, ≥95th, ≥97th, and ≥99th percentiles). RESULTS: For 3 of 4 BMI cut points, prevalence continued to increase for black and American Indian girls through 2008, Hispanic girls plateaued after 2005, non-Hispanic white girls declined to 2001 prevalence levels after peaking in 2005, and Asian girls showed no increases. Non-Hispanic white boys peaked in 2005, then declined to 2001 prevalence levels for all BMI cut points; Hispanic and Asian boys declined after 2005 (for 3 lowest BMI cut points only) but remained above 2001 levels; and American Indian boys peaked later (2007) and declined only for BMI ≥95th. No girls and few boys showed a decline after peaking in prevalence of BMI ≥99th percentile. In 2008, disparities in prevalence were greatest for BMI ≥99th percentile, with prevalence of 4.9% for American Indian girls and 4.6% for black girls versus 1.3% for non-Hispanic white girls. CONCLUSIONS: On the basis of statewide California data, prevalence of high BMI is declining for some groups but has not declined for American Indian and black girls. These trends portend greater disparities over time, particularly in severe obesity. Interventions and policies that are tailored to the highest risk groups should be pursued.
Evidence That Does Not Support Pyruvate Kinase M2 (PKM2)-catalyzed Reaction as a Rate-limiting Step in Cancer Cell Glycolysis*

It has been recognized that the rate-limiting function of pyruvate kinase M2 (PKM2) in glycolysis plays an important role in distributing glycolytic intermediates for anabolic and catabolic purposes in cancer cells. However, after analysis of the catalytic capacity of PKM2 relative to other glycolytic enzymes, the regulation range of PKM2 activity, metabolic flux control, and thermodynamics, we suggest that the PKM2-catalyzed reaction is not a rate-limiting step in cancer cell glycolysis. Hexokinase and phosphofructokinase 1 (PFK1), the first and third enzyme along the pathway, are rate-limiting enzymes that limit the overall glycolytic rate, whereas PKM2 and lactate dehydrogenase, the last two enzymes in the pathway, are for the fast removal of upstream intermediates to prevent the obstruction of the pathway. The argument is in accordance with the catalytic capacity of glycolytic enzymes, regulation range of enzyme activities, metabolic flux control, and thermodynamics.
Working memory abilities in children with special educational needs

This study investigates the distinctive working memory profiles of children with learning difficulties. A sample of 64 children aged 7 to 11 years with recognised special educational needs at varying stages participated in this study. They were tested on measures of the central executive, phonological loop and visuospatial skills. The children in all three special needs subgroups performed below the expected attainment levels for their age in central executive and visuo-spatial tasks, but not in measures of the phonological loop. Very low levels of working memory performance were many times more common in the special needs sample than in a large sample of children without special educational needs. Deficits in working memory performance were more marked in children with statements of special needs than those at earlier stages of recognition of the need for educational support, particularly in measures of the central executive. These children struggle to meet the demands of complex tasks that require them to process, maintain, and store information simultaneously. It is suggested that this difficulty may underpin their failures to make normal educational progress.