Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase II randomised controlled trial of a 6-month self-managed community exercise programme for people with Parkinson's disease

Background Evidence for longer term exercise delivery for people with Parkinson's disease (PwP) is deficient. Aim Evaluate safety and adherence to a minimally supported community exercise intervention and estimate effect sizes (ES). Methods 2-arm parallel phase II randomised controlled trial with blind assessment. PwP able to walk ≥100 m and with no contraindication to exercise were recruited from the Thames valley, UK, and randomised (1:1) to intervention (exercise) or control (handwriting) groups, via a concealed computer-generated list. Groups received a 6-month, twice weekly programme. Exercise was undertaken in community facilities (30 min aerobic and 30 min resistance) and handwriting at home, both were delivered through workbooks with monthly support visits. Primary outcome was a 2 min walk, with motor symptoms (Movement Disorder Society Unified Parkinson's Disease Rating Scale, MDS-UPDRS III), fitness, health and well-being measured. Results Between December 2011 and August 2013, n=53 (n=54 analysed) were allocated to exercise and n=52 (n=51 analysed) to handwriting. N=37 adhered to the exercise, most attending ≥1 session/week. Aerobic exercise was performed in 99% of attended sessions and resistance in 95%. Attrition and adverse events (AEs) were similar between groups, no serious AEs (n=2 exercise, n=3 handwriting) were related, exercise group-related AEs (n=2) did not discontinue intervention. Largest effects were for motor symptoms (2 min walk ES=0.20 (95% CI −0.44 to 0.45) and MDS-UPDRS III ES=−0.30 (95% CI 0.07 to 0.54)) in favour of exercise over the 12-month follow-up period. Some small effects were observed in fitness and well-being measures (ES>0.1). Conclusions PwP exercised safely and the possible long-term benefits observed support a substantive evaluation of this community programme. Trial registration number NCT01439022.
Are Aldehydes in Heat-Sterllized Peritoneal Dialysis Fluids Toxic in Vitro?

Objective Chemical analysis of several brands of peritoneal dialysis fluids (PD fluids) has revealed the presence of 2-furaldehyde, 5-HMF (5-hydroxymethylfuraldehyde), acetaldehyde, formaldehyde, glyoxal, and methylglyoxal. The aim of this study was to investigate if the in vitro side effects caused by glucose degradation products, mainly formed during heat sterilization, are due to any of these recently identified aldehydes. Design Cell growth media or sterile filtered PD fluids were spiked with different concentrations ofthealdehydes. Measurements In vitro side effects were determined as the inhibition of cell growth of cultured mouse fibro blasts or stimulated superoxide radical release from human peritoneal cells. Results Our results demonstrate that the occurrences of 2-furaldehyde, 5-HMF, acetaldehyde, formaldehyde, glyoxal, or methylglyoxal in heat-sterilized PD fluids are probably not the direct cause of in vitro side effects. In order to induce the same magnitude of cell growth inhibition as the heat-sterilized PD fluids, the concentrations of 2-furaldehyde, glyoxal, and 5-HMF had to be 50 to 350 times higher than those quantified in the PD fluids. The concentrations of acetaldehyde, formaldehyde, and methylglyoxal observed in the heat-sterilized PD fluids were closer to the cytotoxic concentrations although still 3 to 7 times lower. Conclusion Since none of these aldehydes caused in vitro toxicity at the tested concentrations, the toxicity found in PD fluids is likely to be due to another glucose degradation product, not yet identified. However, it is possible that these aldehydes may still have adverse effects for patients on peritoneal dialysis.
Effects of Acute or Chronic Ethanol Exposure during Adolescence on Behavioral Inhibition and Efficiency in a Modified Water Maze Task

Ethanol is well known to adversely affect frontal executive functioning, which continues to develop throughout adolescence and into young adulthood. This is also a developmental window in which ethanol is misused by a significant number of adolescents. We examined the effects of acute and chronic ethanol exposure during adolescence on behavioral inhibition and efficiency using a modified water maze task. During acquisition, rats were trained to find a stable visible platform onto which they could escape. During the test phase, the stable platform was converted to a visible floating platform (providing no escape) and a new hidden platform was added in the opposite quadrant. The hidden platform was the only means of escape during the test phase. In experiment 1, adolescent animals received ethanol (1.0g/kg) 30min before each session during the test phase. In experiment 2, adolescent animals received chronic intermittent ethanol (5.0g/kg) for 16 days (PND30 To PND46) prior to any training in the maze. At PND72, training was initiated in the same modified water maze task. Results from experiment 1 indicated that acute ethanol promoted behavioral disinhibition and inefficiency. Experiment 2 showed that chronic intermittent ethanol during adolescence appeared to have no lasting effect on behavioral disinhibition or new spatial learning during adulthood. However, chronic ethanol did promote behavioral inefficiency. In summary, results indicate that ethanol-induced promotion of perseverative behavior may contribute to the many adverse behavioral sequelae of alcohol intoxication in adolescents and young adults. Moreover, the long-term effect of adolescent chronic ethanol exposure on behavioral efficiency is similar to that observed after chronic exposure in humans.
A Novel Delivery System Using Chitosan Glycerophosphate to Deliver Bone Morphogenetic Protein Type-2 to Enhance Anterior Cruciate Ligament Graft Integration

There are over 100, 000 anterior cruciate ligament (ACL) reconstructions performed a year in the U.S. alone and this number is on the rise. Augmenting these reconstructions with bone morphogenetic protein (BMP) has proven successful in the past. Using a new delivery method for the BMP was anticipated to yield similar beneficial results on ACL graft healing, with a delivery method that was more amenable to arthroscopic surgery. The release kinetics of the chitosan gel used for protein delivery in this study showed a release pattern consistent with that required for local BMP delivery. Histology revealed a slow degradation of the gel over time, however imaging and biomechanical testing revealed its weakness. Those specimens treated with the gel (with or without BMP) had less bone growth (p<0.0001) and weaker grafts (p<0.0001) than internal controls. Ultimately, this new delivery system inhibited the normal healing process and negated the enhancing effect of the bone morphogenetic protein.
Photodynamic therapy of non‐melanoma malignant tumours of the skin using topical δ‐amino levulinic acid sensitization and laser irradiation

Eighty basal cell carcinomas (BCCs) in 21 patients, 10 lesions of Bowen's disease in three patients, and four lesions of cutaneous T‐cell lymphoma in two patients, were treated with photodynamic laser therapy (PDT), using topical application of the haem precursor δ‐amino levulinic acid (ALA). The diagnoses were confirmed histologically prior to treatment. Fifty‐five of the BCCs were superficial lesions, and 25 were nodular. Of the 80 BCCs, 39 (49%) were located on the trunk, 36 (45%) on the head and neck region, four (15%) on the leg and one on the arm. The two principal locations of the 10 Bowen's disease lesions were the leg (50%) and the trunk (40%). The T‐cell lymphoma lesions were located on the shoulder and on the arm. A water‐in‐oil based cream containing 20% ALA was applied to the lesions, with a margin of about 10–20 mm beyond the visible tumour border, 4–6 h before the laser procedure. During this period of time the highly fluorescent and photodynamically active substance protoporphyrin IX (Pp IX) is synthesized via the haem cycle. Laser‐induced fluorescence (LJF) was used for real‐time monitoring of the Pp IX distribution in the tumour and in the normal surrounding skin, before and after treatment in all patients. Before laser treatment the Pp IX distribution demonstrated by LJF showed a demarcation between tumour and normal skin of about 15:1 for BCC and Bowen's disease, and 5:1 for T‐cell lymphomas. Laser light from a pulsed frequency‐ doubled Nd: YAG laser pumping a dye laser with light emission at 630 nm was used for the therapy. The power density in the irradiation was kept below 110 mW/cm2, in order to avoid hyperthermal effects. A total energy of 60 J/cm2 was delivered for 10–20 min, depending on the tumour size. A complete response rate of 100% in superficial BCCs and 64% in nodular BCCs occurred after a single laser treatment, and a response rate of 100% was achieved after one additional treatment in the nodular BCCs. In the Bowen's disease lesions a complete response of 90% was obtained with a single treatment. Two of the four T‐cell lymphomas resolved completely. The follow‐up time was between 6 and 14 months.
Transient behavior of cache memories

A cache is a small, fast associative memory located between a central processor and primary memory and used to hold copies of the contents of primary memory locations. A key performance measure of a cache is the miss ratio: the fraction of processor references which are not satisfied by the cache and result in primary memory references. The miss ratio is sometimes measured by running a single program to completion; however, in real systems rarely does such uninterrupted execution occur. In this paper a mathematical model is developed which predicts the effect on the miss ratio of running a program in a sequence of interrupted execution intervals. Results from the model are compared to measured miss ratios of real programs executing in an interrupted execution environment.
On the Vulnerabilities of the Virtual Force Approach to Mobile Sensor Deployment

The virtual force approach is at the basis of many solutions proposed for deploying mobile sensors. In this paper we study the vulnerabilities of this approach. We show that by compromising a few mobile sensors, an attacker can influence the movement of other sensors and prevent the achievement of the network coverage goals. We introduce an attack, called opportunistic movement, and give an analytical study of its efficacy. We show that in a typical scenario this attack can reduce coverage by more than 50 percent, by only compromising a 7 percent of the nodes. We propose two algorithms to counteract the above mentioned attack, DRM and SecureVF. DRM is a light-weight algorithm which randomly repositions sensors from overcrowded areas. SecureVF requires a more complex coordination among sensors but, unlike DRM, it enables detection and identification of malicious sensors. We investigate the performance of DRM and SecureVF through simulations. We show that DRM can significantly reduce the effects of the attack, at the expense of an increase in the energy consumption due to additional movements. By contrast, SecureVF completely neutralizes the attack and allows the achievement of the coverage goals of the network even in the presence of localization inaccuracies.
Ectopic bone formation facilitated by human mesenchymal stem cells and osteogenic cytokines via nutrient vessel injection in a nude rat model

In vivo studies using bone marrow‐derived mesenchymal stem cells are still uncommon. Applications for bone defect replacement in undesirable clinical circumstances such as large defects, bacterial or other pathogen‐contaminated fields, and irradiated surgical wound bed necessitate vascularized bone regeneration. Use of a fascial flap including regenerated bone would be a very powerful tool for treatment. It would be especially beneficial in cases where normal bone regeneration is not expected due to a lack of sufficient blood supply, extensive surgical scaring, or bacterial contamination. In this study, we used nude rats in which the superficial epigastric flap of the experimental group was used to wrap around a mixture of human mesenchymal stem cells, bone morphogenetic protein‐2, and basic fibroblast growth factor cytokines in a gelatin carrier. These rats showed significantly higher bone mineral density at 4 weeks compared to the other experimental groups containing phosphate buffered saline, human mesenchymal stem cells alone, or the two cytokines alone (p < 0.01). There were no remarkable histologic differences up to 7 days. At 2 weeks, more progressive vascularity and perivascular tissue deposits were seen in the experimental group. Basophilic mineral structure surrounded the fibroblast‐like mesenchymal stem cells at 4 weeks, presumably osteoblastic or osteoclastic cell lining. Bone marker immunohistochemistry against alkaline phosphatase and osteocalcin revealed diffuse and distinct immunoreactivity in osteoblastic cells in the experimental group at 4 weeks. Further transcriptional expression of polyomavirus enhancer binding protein 2αA suggested that the human transplanted cells proceeded to osteogenic lineage in 4 weeks. These results may be useful as a new approach for bone regeneration.
CirCNN: Accelerating and Compressing Deep Neural Networks Using Block-Circulant Weight Matrices

Large-scale deep neural networks (DNNs) are both compute and memory intensive. As the size of DNNs continues to grow, it is critical to improve the energy efficiency and performance while maintaining accuracy. For DNNs, the model size is an important factor affecting performance, scalability and energy efficiency. Weight pruning achieves good compression ratios but suffers from three drawbacks: 1) the irregular network structure after pruning, which affects performance and throughput; 2) the increased training complexity; and 3) the lack of rigirous guarantee of compression ratio and inference accuracy.To overcome these limitations, this paper proposes CirCNN, a principled approach to represent weights and process neural networks using block-circulant matrices. CirCNN utilizes the Fast Fourier Transform (FFT)-based fast multiplication, simultaneously reducing the computational complexity (both in inference and training) from $\mathrm {O}(n^{2})$ to $\mathrm {O}(n$ log n) and the storage complexity from $\mathrm {O}(n^{2})$ to O(n), with negligible accuracy loss. Compared to other approaches, CirCNN is distinct due to its mathematical rigor: the DNNs based on CirCNN can converge to the same “effectiveness” as DNNs without compression. We propose the CirCNN architecture, a universal DNN inference engine that can be implemented in various hardware/software platforms with configurable network architecture (e.g., layer type, size, scales, etc In CirCNN architecture: 1) Due to the recursive property, FFT can be used as the key computing kernel which ensures universal and small-footprint implementations. 2) The compressed but regular network structure avoids the pitfalls of the network pruning and facilitates high performance and throughput with highly pipelined and parallel design. To demonstrate the performance and energy efficiency, we test CIR-CNN in FPGA, ASIC and embedded processors. Our results show that CirCNN architecture achieves very high energy efficiency and performance with a small hardware footprint. Based on the FPGA implementation and ASIC synthesis results, CirCNN achieves 6 - 102X energy efficiency improvements compared with the best state-of-the-art results.CCS Concepts• Computer systems organization$\rightarrow $ Embedded hardware;
A time and place for language comprehension: mapping the N400 and the P600 to a minimal cortical network

We propose a new functional-anatomical mapping of the N400 and the P600 to a minimal cortical network for language comprehension. Our work is an example of a recent research strategy in cognitive neuroscience, where researchers attempt to align data regarding the nature and time-course of cognitive processing (from ERPs) with data on the cortical organization underlying it (from fMRI). The success of this “alignment” approach critically depends on the functional interpretation of relevant ERP components. Models of language processing that have been proposed thus far do not agree on these interpretations, and present a variety of complicated functional architectures. We put forward a very basic functional-anatomical mapping based on the recently developed Retrieval-Integration account of language comprehension (Brouwer et al., 2012). In this mapping, the left posterior part of the Middle Temporal Gyrus (BA 21) serves as an epicenter (or hub) in a neurocognitive network for the retrieval of word meaning, the ease of which is reflected in N400 amplitude. The left Inferior Frontal Gyrus (BA 44/45/47), in turn, serves a network epicenter for the integration of this retrieved meaning with the word's preceding context, into a mental representation of what is being communicated; these semantic and pragmatic integrative processes are reflected in P600 amplitude. We propose that our mapping describes the core of the language comprehension network, a view that is parsimonious, has broad empirical coverage, and can serve as the starting point for a more focused investigation into the coupling of brain anatomy and electrophysiology.
Oral melatonin reduces blood coagulation activity: a placebo‐controlled study in healthy young men

Abstract: Melatonin has previously been suggested to affect hemostatic function but studies on the issue are scant. We hypothesized that, in humans, oral administration of melatonin is associated with decreased plasma levels of procoagulant hemostatic measures compared with placebo medication and that plasma melatonin concentration shows an inverse association with procoagulant measures. Forty‐six healthy men (mean age 25 ± 4 yr) were randomized, single‐blinded, to either 3 mg of oral melatonin (n = 25) or placebo medication (n = 21). One hour thereafter, levels of melatonin, fibrinogen, and D‐dimer as well as activities of coagulation factor VII (FVII:C) and VIII (FVIII:C) were measured in plasma. Multivariate analysis of covariance and regression analysis controlled for age, body mass index, mean arterial blood pressure, heart rate, and norepinephrine plasma level. Subjects on melatonin had significantly lower mean levels of FVIII:C (81%, 95% CI 71–92 versus 103%, 95% CI 90–119; P = 0.018) and of fibrinogen (1.92 g/L, 95% CI 1.76–2.08 versus 2.26 g/L, 95% CI 2.09–2.43; P = 0.007) than those on placebo explaining 14 and 17% of the respective variance. In all subjects, increased plasma melatonin concentration independently predicted lower levels of FVIII:C (P = 0.037) and fibrinogen (P = 0.022) explaining 9 and 11% of the respective variance. Melatonin medication and plasma concentration were not significantly associated with FVII:C and D‐dimer levels. A single dose of oral melatonin was associated with lower plasma levels of procoagulant factors 60 min later. There might be a dose–response relationship between the plasma concentration of melatonin and coagulation activity.
BWMK 1 , a Rice Mitogen-Activated Protein Kinase , Locates in the Nucleus and Mediates Pathogenesis-Related Gene Expression by Activation of a Transcription Factor 1

Mitogen-activated protein kinase (MAPK) cascades are known to transduce plant defense signals, but the downstream components of the MAPK have as yet not been elucidated. Here, we report an MAPK from rice (Oryza sativa), BWMK1, and a transcription factor, OsEREBP1, phosphorylated by the kinase. The MAPK carries a TDY phosphorylation motif instead of the more common TEY motif in its kinase domain and has an unusually extended C-terminal domain that is essential to its kinase activity and translocation to the nucleus. The MAPK phosphorylates OsEREBP1 that binds to the GCC box element (AGCCGCC) of the several basic pathogenesis-related gene promoters, which in turn enhances DNA-binding activity of the factor to the cis element in vitro. Transient co-expression of the BWMK1 and OsEREBP1 in Arabidopsis protoplasts elevates the expression of the -glucuronidase reporter gene driven by the GCC box element. Furthermore, transgenic tobacco (Nicotiana tabacum) plants overexpressing BWMK1 expressed many pathogenesis-related genes at higher levels than wild-type plants with an enhanced resistance to pathogens. These findings suggest that MAPKs contribute to plant defense signal transduction by phosphorylating one or more transcription factors.
Noncanonical agonist PPARγ ligands modulate the response to DNA damage and sensitize cancer cells to cytotoxic chemotherapy

Significance Peroxisome proliferator-activated receptor-γ (PPARγ) is a transcription factor that plays a central role in the formation of adipose tissue. We show that phosphorylation of a single amino acid of PPARγ alters the response of cells to DNA damaging agents, including multiple types of chemotherapy. Noncanonical agonist PPARγ ligands that block PPARγ phosphorylation sensitize a variety of cancer cell types to these chemotherapeutic agents in vitro and in vivo. We show that PPARγ interacts with the tumor-suppressor p53 in a manner dependent on PPARγ phosphorylation at S273. These data strongly suggest that noncanonical agonist PPARγ ligands, which lack many of the known side effects of classic agonists, should be explored for clinical use in combination with traditional chemotherapy for a variety of malignancies. The peroxisome-proliferator receptor-γ (PPARγ) is expressed in multiple cancer types. Recently, our group has shown that PPARγ is phosphorylated on serine 273 (S273), which selectively modulates the transcriptional program controlled by this protein. PPARγ ligands, including thiazolidinediones (TZDs), block S273 phosphorylation. This activity is chemically separable from the canonical activation of the receptor by agonist ligands and, importantly, these noncanonical agonist ligands do not cause some of the known side effects of TZDs. Here, we show that phosphorylation of S273 of PPARγ occurs in cancer cells on exposure to DNA damaging agents. Blocking this phosphorylation genetically or pharmacologically increases accumulation of DNA damage, resulting in apoptotic cell death. A genetic signature of PPARγ phosphorylation is associated with worse outcomes in response to chemotherapy in human patients. Noncanonical agonist ligands sensitize lung cancer xenografts and genetically induced lung tumors to carboplatin therapy. Moreover, inhibition of this phosphorylation results in deregulation of p53 signaling, and biochemical studies show that PPARγ physically interacts with p53 in a manner dependent on S273 phosphorylation. These data implicate a role for PPARγ in modifying the p53 response to cytotoxic therapy, which can be modulated for therapeutic gain using these compounds.
3D shape scanning with a time-of-flight camera

We describe a method for 3D object scanning by aligning depth scans that were taken from around an object with a time-of-flight camera. These ToF cameras can measure depth scans at video rate. Due to comparably simple technology they bear potential for low cost production in big volumes. Our easy-to-use, cost-effective scanning solution based on such a sensor could make 3D scanning technology more accessible to everyday users. The algorithmic challenge we face is that the sensor's level of random noise is substantial and there is a non-trivial systematic bias. In this paper we show the surprising result that 3D scans of reasonable quality can also be obtained with a sensor of such low data quality. Established filtering and scan alignment techniques from the literature fail to achieve this goal. In contrast, our algorithm is based on a new combination of a 3D superresolution method with a probabilistic scan alignment approach that explicitly takes into account the sensor's noise characteristics.