Miracle-dz/UniFAR-FTUs huggingface dataset:
Splice-Switching Therapy for Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a genetic disorder with severity ranging from premature death in infants to restricted motor function in adult life. Despite the genetic cause of this disease being known for over twenty years, only recently has a therapy been approved to treat the most severe form of this disease. Here we discuss the genetic basis of SMA and the subsequent studies that led to the utilization of splice switching oligonucleotides to enhance production of SMN protein, which is absent in patients, through a mechanism of exon inclusion into the mature mRNA. Whilst approval of oligonucleotide-based therapies for SMA should be celebrated, we also discuss some of the limitations of this approach and alternate genetic strategies that are currently underway in clinical trials.
Scaling Laws of Sampled Data and Many-to-One Capacity of Sensor Networks on Closed Surfaces

In this paper, we study the feasibility of sensing a bandlimited random field on a closed surface using a dense sensor network of inexpensive sensor nodes. The goal is to periodically gather quantized samples from the field and communicate it to a central collector, where this data is used to reconstruct the field. We show that under an arbitrary irregular placement of sensors that is uniformly discrete, the fie ld can be reconstructed with a pointwise distortion of O( 1 N ) when the sensors are equipped with logN -bit quantizers. This irregular sampling result allows us, using a recent result in oversampled A/D conversion, to trade-off one logN -bit sensor toN one-bit sensors, and still obtain a pointwise distortion ofO( 1 N ). The total data generated in the network also remains Θ(logN). We then study the capacity of the many-to-one wireless network through which the sensor nodes communicate their data to a central collector. We find that, upto a constant, the capacity has the same scaling law in the number of nodes as the total data rate of the network. Hence such a network for both sensing and communicating is indeed feasible.
Folate, Vitamin B6, and Vitamin B12 Intake and the Risk of Breast Cancer Among Mexican Women

Background: High intake of folate, vitamin B6, and vitamin B12 have been hypothesized to lower the risk for breast cancer. We conducted a population-based case-control study to evaluate the risk for breast cancer among Mexican women with relatively low vitamin intakes. Methods: We included 475 women (median age, 53 years; range, 23-87 years) diagnosed with incident breast cancer through six hospitals in Mexico City and interviewed them to obtain data on breast cancer risk factors and their usual diet using a food frequency questionnaire. We selected 1,391 (median age, 49 years; range, 18-82 years) controls from the Mexico City population using a national sampling frame. Results: Compared with women in the lowest quartile, the odds ratio for breast cancer for women in the highest quartile of folate intake was 0.64 [95% confidence intervals (CI), 0.45-0.90; P, test for trend = 0.009] and 0.32 (95% CI, 0.22-0.49; P, test for trend < 0.0001) for vitamin B12 intake. Among postmenopausal women, intakes of folate and vitamin B12 were associated with a lower risk of breast cancer and those associations were stronger than among premenopausal women. The inverse association of folate and breast cancer was stronger among women who consumed a high level of vitamin B12 as compared with women consuming diets low in vitamin B12. No association was observed for vitamin B6 intake. Conclusions: In this population, high intakes of folate and vitamin B12 were independently associated with decreased breast cancer risk, particularly among postmenopausal women. (Cancer Epidemiol Biomarkers Prev 2006;15(3):443–8)
Altered irinotecan pharmacokinetics in pediatric high-grade glioma patients receiving enzyme-inducing anticonvulsant therapy.

PURPOSE The purpose of this study was to determine the effect of enzyme-inducing anticonvulsants (EIAs) on the disposition of irinotecan and metabolites in pediatric patients with high-grade glioma. EXPERIMENTAL DESIGN Pediatric patients with newly diagnosed high-grade glioma were enrolled on this study between March 1999 and February 2001. During course 1, irinotecan was administered as a 60-min i.v. infusion at a dosage of 20 mg/m(2)/day for 5 days of 2 consecutive weeks. On days 1 and 12 of course 1, we collected serial plasma samples to measure the concentrations of the lactone and total forms of irinotecan and its metabolites SN-38 (7-ethyl-10-hydroxycamptothecin), SN-38 glucuronide (7-ethyl-10-[3,4,5-trihydroxy-pyran-2-carboxylic acid]camptothecin), and 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxycamptothecin. RESULTS Thirty-one patients were enrolled. In patients receiving EIAs, the area under the concentration versus time curve (AUC) of irinotecan lactone and SN-38 lactone was significantly lower (P = 0.01 and P = 0.002, respectively), and the irinotecan lactone clearance was significantly higher (P = 0.0003), as compared with those in patients who received no EIAs. The glucuronidation ratio was higher (P = 0.0009), and the ratio of SN-38 AUC to irinotecan AUC was lower (P = 0.02) in patients who received EIAs. Two patients receiving EIAs tolerated increased irinotecan dosages of 30 and 40 mg/m(2)/day without toxicity. One patient receiving EIAs experienced grade 3 diarrhea when the dosage of irinotecan was increased to 60 mg/m(2)/day. CONCLUSIONS EIAs increase the clearance of irinotecan and cause a decrease in systemic exposure to the active metabolite SN-38. Patients who are receiving irinotecan and who require anticonvulsants should be placed on non-EIA therapy, when possible.
The Herschel Gould Belt Survey in Chamaeleon II - Properties of cold dust in disks around young stellar objects

Context. We report on the Herschel Gould Belt survey (HGBS) of the Chamaeleon II (Cha II) star-forming region, focusing on the detection of Class I to III young stellar objects (YSOs). Aims. We aim at characterizing the circumstellar material around these YSOs and at understanding which disk parameters are most likely constrained by the new HGBS data, which are expected to be crucial for studying the transition from optically thick disks to evolved debris-type disks. Methods. We recovered 29 of the 63 known YSOs in Cha II with a detection in at least one of the PACS/SPIRE pass-bands: 3 Class I YSOs (i.e.,100%), 1 flat source (i.e., 50%), 21 Class II objects (i.e., 55%), 3 Class III objects (i.e, 16%), and the unclassified far-infrared source IRAS 12522-7640. We explored PACS/SPIRE colors of this sample and modeled their spectral energy distributions (SEDs) from the optical to Herschel’s wavelengths with the RADMC-2D radiative transfer code. Results. We find that YSO colors are typically confined to the following ranges: −0.7 ≲ log (F_(70)/F_(160)) ≲ 0.5, −0.5 ≲ log (F_(160)/F_(250)) ≲ 0.6, 0.05 ≲ log (F_(250)/F_(350)) ≲ 0.25 and −0.1 ≲ log (F_(350)/F_(500)) ≲ 0.5. These color ranges are expected to be only marginally contaminated by extragalactic sources and field stars and, hence, provide a useful YSO selection tool when applied together. We were able to model the SED of 26 of the 29 detected YSOs. We discuss the degeneracy/limitations of our SED fitting results and adopted the Bayesian method to estimate the probability of different values for the derived disk parameters. The Cha II YSOs present typical disk inner radii ≲0.1 AU, as previously estimated in the literature on the basis of Spitzer data. Our probability analysis shows that, thanks to the new Herschel data, the lower limits to the disk mass (M_(disk)) and characteristic radius (R_C) are well constrained, while the flaring angle (1 + φ) is only marginally constrained. The lower limit to R_C is typically around 50 AU. The lower limits to M_(disk) are proportional to the stellar masses with a typical 0.3% ratio, i.e., in the range estimated in the literature for young Class II stars and brown dwarfs across a broad range of stellar masses. The estimated flaring angles, although very uncertain, point toward very flat disks (1 + φ ≲ 1.2), as found for low-mass M-type YSO samples in other star-forming regions. Thus, our results support the idea that disk properties show a dependence on stellar properties.
Elevated expression of hypoxia inducible factor‐2α in terminally differentiating growth plate chondrocytes

Growth plate chondrocytes exist in a hypoxic environment where it is recognized that hypoxia‐inducible factor‐1α (HIF‐1α) is essential for their survival. Its regulation of chondrocyte viability may be mediated by the increased expression of vascular endothelial growth factor (VEGF) and glycolytic enzymes. However, the full chondrocyte response to hypoxia and the molecular control of VEGF expression in relation to growth plate differentiation and vascularization remains poorly understood. Using Percoll density gradient centrifugation, chick chondrocytes were separated into populations of different maturational phenotype. A differential display analysis of the populations showed highly upregulated expression of HIF‐2α mRNA during chondrocyte differentiation. HIF‐2α is a homologue of the HIF‐1α transcription factor, both of which play a role in the activation of a number of hypoxia responsive genes. HIF‐1α mRNA was also found to be expressed, although levels of expression were found to be similar in all of the chondrocyte fractions. The elevated expression of HIF‐2α during chondrocyte differentiation was accompanied by increased VEGF expression. Analysis of the murine chondrocyte cell line, ATDC5, which undergoes ordered maturation indicated that HIF‐2α, VEGF, placental growth factor, and glucose transporter‐1 expression all increased in parallel with chondrocyte differentiation. This observation was supported by immunohistochemistry on sections of mouse bone which showed staining corresponding to the presence of HIF‐2α in hypertrophic growth plate chondrocytes. The presence of HIF‐2α was also observed in articular chondrocytes but was restricted to the superficial tangential zone. HIF‐2α is, therefore, likely to be involved in the initiation of blood vessel formation and a metabolic shift in the growth plate, processes crucial for endochondral ossification. J. Cell. Physiol. 206: 435–440, 2006. © 2005 Wiley‐Liss, Inc.
Gender effects on cortical thickness and the influence of scaling

Using magnetic resonance imaging and well‐validated computational cortical pattern matching methods in a large and well‐matched sample of healthy subjects (n = 60), we analyzed the regional specificity of gender‐related cortical thickness differences across the lateral and medial cortices at submillimeter resolution. To establish the influences of brain size correction on gender effects, comparisons were performed with and without applying affine transformations to scale each image volume to a template. We revealed significantly greater cortical thickness in women compared to men, after correcting for individual differences in brain size, while no significant regional thickness increases were observed in males. The pattern and direction of the results were similar without brain size correction, although effects were less pronounced and a small cortical region in the lateral temporal lobes showed greater thickness in males. Our gender‐specific findings support a dimorphic organization in male and female brains that appears to involve the architecture of the cortical mantle and that manifests as increased thickness in female brains. This sexual dimorphism favoring women, even without correcting for brain size, may have functional significance and possibly account for gender‐specific abilities and/or behavioral differences between sexes. Hum Brain Mapp, 2005. © 2005 Wiley‐Liss, Inc.
Recognition of Off-Line Handwritten Arabic Words Using Neural Network

Neural network (NN) has been used with some success in recognizing printed Arabic words. In this paper, a complete scheme for unconstrained Arabic handwritten word recognition based on a neural network is proposed and discussed. The overall engine of this combination of a global feature scheme with a NN is a system able to classify Arabic-handwritten words of one hundred different writers. The system first attempts to remove some of the variation in the images that do not affect the identity of the handwritten word. Next, the system codes the skeleton and edge of the word so that feature information about the strokes in the skeleton is extracted. Then, a classification process based on the artificial NN classifier is used as global recognition engine, to classify the Arabic words. The output is a word in the dictionary. A detailed experiment is carried out, and successful recognition results are reported
Managing an Epidemic of Swiss Needle Cast in the Douglas-Fir Region of Oregon: The Role of the Swiss Needle Cast Cooperative

Swiss needle cast (SNC) is a foliage disease specific to Douglas-fir (Pseudotsuga menziesii) caused by the Ascomycete fungus Phaeocryptopus gaeumannii. Currently, it is causing an epidemic west of the Oregon Coast Range from Coos Bay to Astoria: 2010 aerial survey estimate of almost 400,000 ac of plantations with visible symptoms. General symptoms include chlorotic needles, decreased needle retention resulting in sparse crowns, and growth reductions. Growth losses in the epidemic area have been in the range of 20‐55%, although mortality from the disease is rare. The SNC Cooperative (SNCC) was established in January 1997 at Oregon State University with private, state, and federal partners. The mission of the SNCC is to conduct research on enhancing Douglas-fir productivity and health in the presence of SNC. We present an integrated pest management framework for SNC on the Oregon Coast based on research sponsored by the SNCC.
Friction of possible solid lubricants with various crystal structures

Report presenting a number of possible solid lubricants with various crystal structures tested in a low-speed, high-load, friction apparatus under conditions of continuous sliding. None of the solids tested were as effective as MoS2 but were at least as effective as zinc stearate and graphite in these tests. Results regarding common lubricants, layer-lattice structure, and low-shear-strength solids without layer-lattice structure are provided.
Schizophrenia and cortical blindness: protective effects and implications for language

The repeatedly noted absence of case-reports of individuals with schizophrenia and congenital/early developed blindness has led several authors to argue that the latter can confer protective effects against the former. In this work, we present a number of relevant case-reports from different syndromes that show comorbidity of congenital and early blindness with schizophrenia. On the basis of these reports, we argue that a distinction between different types of blindness in terms of the origin of the visual deficit, cortical or peripheral, is crucial for understanding the observed patterns of comorbidity. We discuss the genetic underpinnings and the brain structures involved in schizophrenia and blindness, with insights from language processing, laying emphasis on the three structures that particularly stand out: the occipital cortex, the lateral geniculate nucleus (LGN), and the pulvinar. Last, we build on previous literature on the nature of the protective effects in order to offer novel insights into the nature of the protection mechanism from the perspective of the brain structures involved in each type of blindness.
Fault Dictionary Size Reduction for Million-Gate Large Circuits

In general, fault dictionary is prevented from practical applications for its extremely large size. Several previous works are proposed for the fault dictionary size reduction. However, they might not be able to handle today's million-gate circuits due to the high time and space complexity. In this paper, we propose an algorithm to significantly reduce the size of fault dictionary while still preserving high diagnostic resolution. The proposed algorithm possesses extremely low time and space complexity by avoiding constructing the huge distinguishability table, which inevitably boosts up the required computation complexity. Experimental results demonstrate that the proposed algorithm is fully capable of handling industrial million-gate large circuits in a reasonable amount of runtime and memory.
Wrist Circumference Is a Clinical Marker of Insulin Resistance in Overweight and Obese Children and Adolescents

Background— Excess fat is one of the main determinants of insulin resistance, representing the metabolic basis for developing future cardiovascular disease. The aim of the current study was to find an easy-to-detect clinical marker of insulin resistance which can be used to identify young subjects at increased risk of cardiovascular disease. Methods and Results— Four-hundred and seventy-seven overweight/obese children and adolescents (mean age 10.31±2.80 years) were consecutively enrolled. Standard deviation score body mass index, fasting biochemical parameters, and homeostasis model assessment of insulin resistance were evaluated. Statistical differences were investigated using multiple linear regression analysis. Manual measure of wrist circumference was evaluated in all children and adolescents. Fifty-one subjects, randomly selected, underwent nuclear magnetic resonance imaging of the wrist to evaluate transversal wrist area at the Lister tubercle level. A statistically significant association was found between manual measure of wrist circumference and insulin levels or homeostasis model assessment of insulin resistance (&bgr;=0.34 and 0.35, respectively; P<10−5 for both comparisons). These associations were more significant than those between SD score body mass index and insulin levels or homeostasis model assessment of insulin resistance (&bgr;=0.12 and 0.10, respectively; P⩽0.02 for both comparisons). Nuclear magnetic resonance imaging acquisition clarified that the association between wrist circumference and insulin levels or homeostasis model assessment of insulin resistance reflected the association with bone tissue-related areas (P⩽0.01 for both) but not with the adipose tissue ones (P>0.05), explaining 20% and 17% of the variances of the 2 parameters. Conclusions— Our findings suggest a close relationship among wrist circumference, its bone component, and insulin resistance in overweight/obese children and adolescents, opening new perspectives in the prediction of cardiovascular disease.
The complete mitochondrial genome of Megophrys shapingensis (Amphibia, Anura, Megophryidae)

The complete mitochondrial genome sequence of the Shaping horned toad Megophrys shapingensis, the first complete mitogenome from the family Megophryidae, was determined. The total length of this complete mitogenome was 17,631 bp, containing 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and a control region (D-loop). The gene arrangement and composition of the mitogenome were similar to those of most amphibians. The base composition on light strand was 28.2% A, 31.5% T, 26.1% C, and 14.3% G. The D-loop region contained 10 copies of 97-bp tandem repeats. The complete mitogenome sequence of M. shapingensis provided fundamental data for resolving phylogenetic and genetic problems related to this species.
PTK 787 / ZK 222584 , a Specific Vascular Endothelial Growth Factor-Receptor Tyrosine Kinase Inhibitor , Affects the Anatomy of the Tumor Vascular Bed and the Functional Vascular Properties as Detected by Dynamic Enhanced Magnetic Resonance Imaging 1

Antiangiogenic therapy is a promising new strategy of inhibiting tumor growth and formation of metastases. Recently, a number of compounds with different effects on tumor endothelial cells have entered clinical trials and revealed the need for diagnostic methods to detect their biological activity. Dynamic enhanced magnetic resonance imaging (dyMRI) is used in most clinical trials with antiangiogenic active compounds. We evaluated this method by using PTK787/ZK 222584, a specific inhibitor of the VEGF-receptor tyrosine kinases, which showed antitumoral and antiangiogenic activity in a murine renal cell carcinoma (RENCA) model. After intrarenal application of RENCA cells, mice developed a primary tumor and metastases to the lung and abdominal lymph nodes. After daily oral therapy for 21 days with either PTK787/ZK 222584 at a dose of 50 mg/kg or vehicle, primary tumors of all animals were analyzed by dyMRI. Gadolinium-DOTA (Dotarem) was used as a contrast agent to detect vessel permeability and contrast agent extravasation, whereas intravascular iron oxide nanoparticles (Endorem) were used to detect partial tumor blood volume. Additionally, vessel density, architecture, diameter, and blood flow velocity were investigated by appropriate methods. Surprisingly, no changes in extravasation occurred under treatment with PTK787/ZK 222584 as compared with the control group, whereas a significant decrease in vessel permeability occurred. Furthermore, an increase in partial blood volume was found in the PTK787/ZK 222584treated group, although vessel density was reduced as seen by histology. Using the corrosion cast technique, reduction in vessel density was significant but not very pronounced and predominantly attributable to the loss of microvessels only. This finding correlated with a shift to large vessel diameters in the primary tumors of PTK787/ZK 222584-treated animals and with reduction of blood flow velocity in the tumor feeding renal artery. From these findings, we conclude that the treatment with PTK787/ZK 222584 primarily reduces the number of tumor microvessels, accompanied by a hemodynamic dilation of the remaining vessels. This dilation could influence the result of dyMRI such that no change in extravasation or even an increase in partial tumor blood volume could be observed.