Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of backward walking training on postural balance in children with hemiparetic cerebral palsy: a randomized controlled study

Objective: To study the effect of additional backward walking training on postural control in children with hemiparetic cerebral palsy. Design: Randomized controlled study. Setting: Physical therapy clinics. Subjects: Thirty spastic hemiparetic cerebral palsied children of both sexes (10-14 years, 14 girls and 16 boys). Intervention: Children were randomly assigned into two equal groups: experimental and control groups. Both groups received a traditional physical therapy program for 12 weeks. Experimental group additionally received backward walking training which was provided 25 min/day, 3 days/week for 3 successive months. Outcome measures: Baseline and post-treatment assessment for overall, anteroposterior, and mediolateral stability indices were evaluated by using Biodex balance system. Results: After treatment; two way ANOVA revealed significant improvement in overall, anteroposterior and mediolateral stability indices of experimental group at the most stable level (level 12) and moderately unstable level (level 7) (1.40 ± 0.44 and 1.73 ± 0.51; 1.11 ± 0.34 and 2.13 ± 0.52; 1.93 ± 0.51 and 2.68 ± 0.52) respectively, than control group (1.77 ± 0.44 and 2.17 ± 0.56; 1.44 ± 0.44 and 2.54 ± 0.49; 2.39 ± 0.65 and 3.11 ± 0.49) respectively, (P < 0.05). There were significant improvement in all measured variables for both groups at both levels (P < 0.05). Conclusion: Additional backward walking training to traditional physical therapy program yields improvement in postural stability indices in children with spastic hemiparetic cerebral palsy than traditional physical therapy alone.
Truncation and Activation of Dual Specificity Tyrosine Phosphorylation-regulated Kinase 1A by Calpain I

Background: Dyrk1A regulates alternative splicing of exon 10 and phosphorylation of Tau. Results: Calpain I proteolyzes Dyrk1A and enhances its kinase activity, which promotes exon 10 exclusion and hyperphosphorylation of Tau. Conclusion: Truncation and activation of Dyrk1A may be responsible for Tau pathology in AD brains. Significance: These findings indicate a new mechanism linked to Tau pathology in AD. Hyperphosphorylation and dysregulation of exon 10 splicing of Tau are pivotally involved in pathogenesis of Alzheimer disease (AD) and/or other tauopathies. Alternative splicing of Tau exon 10, which encodes the second microtubule-binding repeat, generates Tau isoforms containing three and four microtubule-binding repeats, termed 3R-Taus and 4R-Taus, respectively. Dual specificity tyrosine-phosphorylation-regulated kinase 1A (Dyrk1A) lies at the Down syndrome critical region of chromosome 21. Overexpression of this kinase may contribute to the early Tau pathology in Down syndrome via phosphorylation of Tau and dysregulation of Tau exon 10. Here, we report that Dyrk1A was truncated at the C terminus and was associated with overactivation of calpain I in AD brain. Calpain I proteolyzed Dyrk1A in vitro first at the C terminus and further at the N terminus and enhanced its kinase activity toward Tau via increased Vmax but not Km. C-terminal truncation of Dyrk1A resulted in stronger activity than its full-length protein in promotion of exon 10 exclusion and phosphorylation of Tau. Dyrk1A was truncated in kainic acid-induced excitotoxic mouse brains and coincided with an increase in 3R-Tau expression and phosphorylation of Tau via calpain activation. Moreover, truncation of Dyrk1A was correlated with an increase in the ratio of 3R-Tau/4R-Tau and Tau hyperphosphorylation in AD brain. Collectively, these findings suggest that truncation/activation of Dyrk1A by Ca2+/calpain I might contribute to Tau pathology via promotion of exon 10 exclusion and hyperphosphorylation of Tau in AD brain.
Performance of an adaptive QAM scheme over correlated Rayleigh fading with non-zero delay

Link adaptation techniques have recently been proposed as a spectrally efficient method of obtaining high quality service for mobile communication systems. These schemes aim to utilise channel capacity better than fixed transmission schemes, by adapting signal transmission parameters, such as modulation constellation and transmit power. Adaptive modulation schemes, which adapt the modulation constellation, have gained considerable favour for exploiting time-varying channel conditions without increasing the level of cochannel interference. However, the traditional adaptive modulation schemes are designed assuming zero delay between the channel estimation and the modulation mode adaptation. In the case of non-zero delay, the transmitter would update the modulation mode based on outdated channel state information from the receiver. We investigate an adaptive quadrature amplitude modulation (AQAM) scheme, which, by way of retransmissions, allows a targeted reliability level to be met, even in the presence of non-zero delay. The effect of non-zero delay on performance is then investigated. Closed form expressions for the average number of bits per symbol (BPS) throughput and the average bit error rate (BER) of the proposed scheme are derived.
A feasibility study on tension control of Bowden-cable based on a dual-wire scheme

A critical issue for Bowden-cable transmission is bending-dependent hysteresis that degrades control performance and limits the application. The relationship between input and output of the Bowden-cable varies with the changing bending angle of the cable. This paper proposes a novel method that can compensate the varying hysteresis of the Bowden-cable using an embedded auxiliary wire, called a sensing wire. The accumulated bend angle of the Bowden-cable can be estimated by measuring the displacement change of the sensing wire and the input tension of the actuation wire. The estimated bending angle of the sheath can be used to compensate the hysteresis of the Bowden-cable with a feedforward control scheme, even though it is subject to the varying shape of the Bowden-cable. The proposed system has a simple and fully embedded design inside the sheath and does not require any external shape sensor or output tension sensor, which keeps the size and complexity of the system low. The results show that the control error of output tension decreased from 4.22 N to 0.69 N when the bend angle of the Bowden-cable changes from 0° to 560°.
Feasibility of Ultra-High-Throughput Functional Screening of Melanoma Biopsies for Discovery of Novel Cancer Drug Combinations

Purpose: Successful development of targeted therapy combinations for cancer patients depends on first discovering such combinations in predictive preclinical models. Stable cell lines and mouse xenograft models can have genetic and phenotypic drift and may take too long to generate to be useful as a personalized medicine tool. Experimental Design: To overcome these limitations, we have used a platform of ultra-high-throughput functional screening of primary biopsies preserving both cancer and stroma cell populations from melanoma patients to nominate such novel combinations from a library of thousands of drug combinations in a patient-specific manner within days of biopsy. In parallel, patient-derived xenograft (PDX) mouse models were created and novel combinations tested for their ability to shrink matched PDXs. Results: The screening method identifies specific drug combinations in tumor cells with patterns that are distinct from those obtained from stable cell lines. Screening results were highly specific to individual patients. For patients with matched PDX models, we confirmed that individualized novel targeted therapy combinations could inhibit tumor growth. In particular, a combination of multi-kinase and PI3K/Akt inhibitors was effective in some BRAF–wild-type melanomas, and the addition of cediranib to the BRAF inhibitor PLX4720 was effective in a PDX model with BRAF mutation. Conclusions: This proof-of-concept study demonstrates the feasibility of using primary biopsies directly for combinatorial drug discovery, complementing stable cell lines and xenografts, but with much greater speed and efficiency. This process could potentially be used in a clinical setting to rapidly identify therapeutic strategies for individual patients. Clin Cancer Res; 23(16); 4680–92. ©2017 AACR.
A prospective randomized trial of 5-fluorouracil versus 5-fluorouracil and high-dose leucovorin versus 5-fluorouracil and methotrexate in previously untreated patients with advanced colorectal carcinoma.

Seventy-four previously untreated patients with metastatic colorectal adenocarcinoma were prospectively randomized into one of three treatment regimens: (1) 5-fluorouracil (5-FU) 450 mg/m2 as an intravenous (IV) bolus daily for five days or toxicity, then 200 mg/m2 IV bolus every other day for six doses; (2) methotrexate (MTX) 50 mg/m2 in normal saline by IV infusion over four hours followed by an IV bolus of 5-FU 600 mg/m2. This was administered weekly for 4 weeks and then every 2 weeks. (3) Leucovorin 500 mg/m2 in a two-hour IV infusion of normal saline with 5-FU 600 mg/m2 as an IV bolus one hour after the Leucovorin began every week for 6 weeks. The combined complete and partial response rates in the three regimens were 11%, 5%, and 48%, respectively (P = .0009). The median duration of response in the 5-FU and Leucovorin regimen was 10 months. There was no statistically significant difference between the treatment regimens with respect to survival time (P = .6). Toxicity in the 5-FU and Leucovorin regimen was predominantly diarrhea (13 of 30 patients, 40%). In this regimen, eight of 13 patients (52%) who developed diarrhea not only required a dose reduction of 5-FU, but also hospitalization for IV hydration. The predominant toxicity in the 5-FU alone regimen and the 5-FU and MTX regimen was leukopenia. One drug-related death occurred in each regimen.
A semantic contribution to nonword recall? Evidence for intact phonological processes in semantic dementia

Patients with semantic dementia make numerous phonological errors in their immediate serial recall of words that they understand poorly. Previous studies have argued that these errors result from a reduction in the normal contribution made by semantics to the coherence of items in the phonological system. It is possible, however, that the errors might reflect additional subtle phonological deficits. Six patients with semantic dementia were tested on a variety of phonological processing and short-term memory tasks, in order to explore these possibilities. For the most part, the patients showed normal performance in phonological awareness and discrimination tasks and normal effects of phonological similarity and word length in immediate serial recall. The more severely impaired patients, however, showed some weakness on tests of nonword repetition and recall. Every patient showed better recall of words that were still relatively well understood, compared with words that were more semantically degraded. This difference extended to nonwords that were phonologically similar to the known and degraded words, suggesting that the patients' semantic deficits could account for their impairments in nonword recall. The recall advantage for semantically known over degraded items also extended to a nonverbal delayed picture copying task, suggesting that the patients' immediate serial recall impairments were underpinned by a central semantic deficit, and not by a separable lexical deficit. The first author, who is now at the University of Manchester, was supported by an ESRC studentship.
Primary and secondary metabolism, and post‐translational protein modifications, as portrayed by proteomic analysis of Streptomyces coelicolor

The newly sequenced genome of Streptomyces coelicolor is estimated to encode 7825 theoretical proteins. We have mapped approximately 10% of the theoretical proteome experimentally using two‐dimensional gel electrophoresis and matrix‐assisted laser desorption ionization time‐of‐flight (MALDI‐TOF) mass spectrometry. Products from 770 different genes were identified, and the types of proteins represented are discussed in terms of their anno‐tated functional classes. An average of 1.2 proteins per gene was observed, indicating extensive post‐translational regulation. Examples of modification by N‐acetylation, adenylylation and proteolytic processing were characterized using mass spectrometry. Proteins from both primary and certain secondary metabolic pathways are strongly represented on the map, and a number of these enzymes were identified at more than one two‐dimensional gel location. Post‐translational modification mechanisms may therefore play a significant role in the regulation of these pathways. Unexpectedly, one of the enzymes for synthesis of the actinorhodin polyketide antibiotic appears to be located outside the cytoplasmic compartment, within the cell wall matrix. Of 20 gene clusters encoding enzymes characteristic of secondary metabolism, eight are represented on the proteome map, including three that specify the production of novel metabolites. This information will be valuable in the characterization of the new metabolites.
Accumulation patterns of polychlorinated biphenyl congeners and organochlorine pesticides in Steller's sea eagles and white‐tailed sea eagles, threatened species, in Hokkaido, Japan

Polychlorinated biphenyls (PCBs), including coplanar congeners, hexachlorocyclohexane isomers, chlordane‐related compounds, and hexachlorobenzene, were found in the breast muscle of Steller's sea eagles (SSE) and white‐tailed sea eagles (WSE) threatened species, collected in Hokkaido, Japan, during the two years from 1998 to 1999. Both PCBs and DDTs were the most notable compounds, with concentrations one to two orders of magnitude higher than the other compounds, that is, from 120 to 39,000 and from 68 to 15,000 ng/g wet weight, respectively. Non‐ortho (International Union of Pure and Applied Chemistry [IUPAC] 77, 126, and 169) and mono‐ortho (IUPAC 105, 118, and 156)‐substituted coplanar PCB congeners amounted to 9.2 to 740 pg/g of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin toxic equivalents derived from the World Health Organization, Paris, France (WHO), toxic equivalent factors. The atmospheric PCBs and DDTs in eastern Siberian cities, such as Khabarovsk and Magadan, have been reported to be much higher than Hokkaido and the North Pacific. Thus, we speculated that the eagles might have been contaminated in these areas, where they spend most of the year except winter, which they spend in eastern Siberia. Adult eagles accumulated more PCBs and DDTs than younger ones. The patterns of PCB congeners were also found to change, depending on the age of the eagle examined; adult eagles showed relatively higher proportions of highly chlorinated PCBs than juvenile eagles did. This difference would be related to the efficiency of the excretion and the metabolism of each PCB congener in the eagles.
Uracil-Induced Down-Regulation of the Yeast Uracil Permease

ABSTRACT In Saccharomyces cerevisiae theFUR4-encoded uracil permease catalyzes the first step of the pyrimidine salvage pathway. The availability of uracil has a negative regulatory effect upon its own transport. Uracil causes a decrease in the level of uracil permease, partly by decreasing theFUR4 mRNA level in a promoter-independent fashion, probably by increasing its instability. Uracil entry also triggers more rapid degradation of the existing permease by promoting high efficiency of ubiquitination of the permease that signals its internalization. A direct binding of intracellular uracil to the permease is possibly involved in this feedback regulation, as the behavior of the permease is similar in mutant cells unable to convert intracellular uracil into UMP. We used cells impaired in the ubiquitination step to show that the addition of uracil produces rapid inhibition of uracil transport. This may be the first response prior to the removal of the permease from the plasma membrane. Similar down-regulation of uracil uptake, involving several processes, was observed under adverse conditions mainly corresponding to a decrease in the cellular content of ribosomes. These results suggest that uracil of exogenous or catabolic origin down-regulates the cognate permease to prevent buildup of excess intracellular uracil-derived nucleotides.
Control Replication: Compiling Implicit Parallelism to Efficient SPMD with Logical Regions

We present control replication, a technique for generating high-performance and scalable SPMD code from implicitly parallel programs. In contrast to traditional parallel programming models that require the programmer to explicitly manage threads and the communication and synchronization between them, implicitly parallel programs have sequential execution semantics and naturally avoid the pitfalls of explicitly parallel code. However, without optimizations to distribute control overhead, scalability is often poor. Performance on distributed-memory machines is especially sensitive to communication and synchronization in the program, and thus optimizations for these machines require an intimate understanding of a program’s memory accesses. Control replication achieves particularly effective and predictable results by leveraging language support for first-class data partitioning in the source programming model. We evaluate an implementation of control replication for Regent and show that it achieves up to 99% parallel efficiency at 1024 nodes with absolute performance comparable to hand-written MPI(+X) codes. CCS CONCEPTS • Software and its engineering → Parallel programming languages; Compilers;
Ultra‐long‐acting insulin degludec has a flat and stable glucose‐lowering effect in type 2 diabetes

Insulin degludec (IDeg) is a new‐generation, ultra‐long‐acting basal insulin that forms soluble multihexamers upon subcutaneous injection, resulting in a depot from which IDeg is absorbed slowly and continuously into circulation. This double‐blind, two‐period, incomplete block cross‐over trial investigated the pharmacodynamic and pharmacokinetic properties of IDeg at steady state (SS) in people with type 2 diabetes.
An SRF-PLL-Based Sensorless Vector Control Using the Predictive Deadbeat Algorithm for the Direct-Driven Permanent Magnet Synchronous Generator

This paper proposes an enhanced sensorless vector control strategy using the predictive deadbeat algorithm for a direct-driven permanent magnet synchronous generator (PMSG). To derive favorable sensorless control performances, an enhanced predictive deadbeat algorithm is proposed. First, the estimated back electromotive force (EMF), corrected by a cascade compensator, was put into a deadbeat controller in order to improve the system stability, while realize the null-error tracking of the stator current at the same time. Subsequently, an advance prediction of the stator current based on the Luenberger algorithm was used to compensate the one-step-delay caused by digital control. Maintaining the system stability, parameters of the controller were optimized based on discrete models in order to improve the dynamic responses and robustness against changes in generator parameters. In such cases, the proposed methodology of synchronous rotating frame phase lock loop (SRF-PLL), which applies the estimated back EMF, can observe the rotor position angle and speed without encoders, realizing the flux orientation and speed feedback regulation. Finally, the simulation and experimental results, based on a 10-kW PMSG-based direct-driven power generation system, are both shown to verify the effectiveness and feasibility of the proposed sensorless vector control strategy.
Association of the dihydrolipoamide dehydrogenase gene with Alzheimer's disease in an Ashkenazi Jewish population

Abundant biochemical evidence links deficient activity of mitochondrial α‐ketoglutarate dehydrogenase with neuropathologically confirmed Alzheimer's disease (AD). Reduced α‐ketoglutarate dehydrogenase activity has also been associated with anti‐mortem measures of clinical disability. One of the genes encoding this complex, namely, DLD, lies within a chromosome 7 region that is in linkage disequilibrium with AD. We therefore examined the hypothesis that variation in DLD is associated with AD risk. Denaturing HPLC was used to search for sequence variations in the coding and flanking regions of all exons of DLD, but no abundant variants that alter protein sequence were found. However, four common SNPs were identified and genotyped in a case‐control series of 297 Caucasians from New York City, including 229 residents of a Jewish nursing home. Logistic regression analysis was performed for the four‐locus DLD genotype, sex, and ApoE4 status to determine the association of these independent variables with AD. Significant associations with AD were observed for ApoE4 (P < 10−6) and sex combined with DLD genotype (P = 0.013). The association with the DLD genotypes appears only in the male population in both the Caucasian series (P = 0.0009, n = 83) and the Ashkenazi Jewish subseries (P = 0.017, n = 49). The DLD genotype appears to operate independently of APOE in conferring AD risk. © 2004 Wiley‐Liss, Inc.
Adaptation and Validation of Turbogenerator Model Parameters Through On-Line Frequency Response Measurements

Turbogenerator models derived from standstill frequency response measurements may not be adequate for representing machine performance over a wide range of operating conditions, particularly if the machine rotor structure is complex due to the presence of a damper winding. This paper describes an identification technique which can be used to make such models more acceptable by modifying their parameters using measurements from on-line (on-load) frequency response test data. The identification technique is applied to the measurements made on two large turbogenerators.
Benzidine Stain for the Histochemical Detection of Hemoglobin in Splinter Hemorrhage (Subungual Hematoma) and Black Heel

&NA; Minor nail trauma may cause bluish discoloration of the nail, while tangential skin trauma on the heel can result in a so‐called black heel. To rule out melanoma in such clinical situations, a biopsy is needed to reveal homogeneous eosinophilic masses deposited under the nail plate or within it (transepidermal elimination). Most dermatopathologists attempt to demonstrate the presence of hemoglobin in these eosinophilic masses with Prussian blue stain, which typically remains negative. In our experience, these traumatically induced blood deposits are always situated in avascular spaces, devoid of degrading phagocytes. Consequently, a histochemical stain for these deposits should be directed specifically toward hemoglobin, not hemosiderin. In the dermatopathologic literature, the various techniques to detect hemoglobin deposits in tissue sections are not well‐known. We would like to emphasize benzidine stain, a highly selective and efficient method to demonstrate the presence of hemoglobin deposits in histologic sections. To date, benzidine stain has not been utilized to characterize splinter hemorrhage (subungual hematoma). Of concern, the use of benzidine in histopathology laboratories is restricted because this agent is a known carcinogen, while the nonmutagenic derivative, 3,3′,5,5′‐tetramethylbenzidine, does not stain histologic sections. Patent blue V, a completely different and less specific agent, stains hemoglobin an intense blue‐green.