Comparison Between Movement-Based and Task-Based Mirror Therapies on Improving Upper Limb Functions in Patients With Stroke: A Pilot Randomized Controlled Trial

Objective: The aim of this trial was to compare the effect of movement-based mirror therapy (MMT) and task-based mirror therapy (TMT) on improving upper limb functions in patients with stroke.Methods: A total of 34 patients with sub-acute stroke with mildly to moderately impaired upper limb motor functions. The participants were randomly allocated to one of three groups: MMT, TMT, and conventional treatment (CT). The MMT group underwent movement-based mirror therapy for around 30 min/day, 5 days/week, for 4 weeks, whereas the TMT group underwent dose-matched TMT. The CT group underwent only conventional rehabilitation. The MMT and TMT groups underwent CT in addition to their mirror therapy. Blinded assessments were administered at baseline and immediately after the intervention. Upper limb motor functions, measured using Fugl-Meyer Assessment-upper extremity (FMA-UE), Wolf Motor Function Test (WMFT), and hand grip strength; upper limb spasticity, measured using the modified Ashworth scale (MAS); and activities of daily living, measured using the modified Barthel index (MBI).Results: A significant time-by-group interaction effect was noted in FMA-UE. Post-hoc analysis of change scores showed that MMT yielded a better effect on improving FMA-UE than the other two therapies, at a marginally significant level (P = 0.050 and 0.022, respectively). No significant interaction effect was noted in WMFT, hand grip strength, MAS, and MBI.Conclusion: Both MMT and TMT are effective in improving the upper limb function of patients with mild to moderate hemiplegia due to stroke. Nevertheless, MMT seems to be superior to TMT in improving hemiplegic upper extremity impairment. Further studies with larger stroke cohorts are expected to be inspired by this pilot trial.Trial registration number: No. ChiCTR1800019043 (http://www.chictr.org.cn/index.aspx

An evolution strategy of GAN for the generation of high impedance fault samples based on Reptile algorithm

In a distribution system, sparse reliable samples and inconsistent fault characteristics always appear in the dataset of neural network fault detection models because of high impedance fault (HIF) and system structural changes. In this paper, we present an algorithm called Generative Adversarial Networks (GAN) based on the Reptile Algorithm (GANRA) for generating fault data and propose an evolution strategy based on GANRA to assist the fault detection of neural networks. First, the GANRA generates enough high-quality analogous fault data to solve a shortage of realistic fault data for the fault detection model’s training. Second, an evolution strategy is proposed to help the GANRA improve the fault detection neural network’s accuracy and generalization by searching for GAN’s initial parameters. Finally, Convolutional Neural Network (CNN) is considered as the identification fault model in simulation experiments to verify the validity of the evolution strategy and the GANRA under the HIF environment. The results show that the GANRA can optimize the initial parameters of GAN and effectively reduce the calculation time, the sample size, and the number of learning iterations needed for dataset generation in the new grid structures

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

The biological principles and advanced applications of DSB repair in CRISPR-mediated yeast genome editing

To improve the performance of yeast cell factories for industrial production, extensive CRISPR-mediated genome editing systems have been applied by artificially creating double-strand breaks (DSBs) to introduce mutations with the assistance of intracellular DSB repair. Diverse strategies of DSB repair are required to meet various demands, including precise editing or random editing with customized gRNAs or a gRNA library. Although most yeasts remodeling techniques have shown rewarding performance in laboratory verification, industrial yeast strain manipulation relies only on very limited strategies. Here, we comprehensively reviewed the molecular mechanisms underlying recent industrial applications to provide new insights into DSB cleavage and repair pathways in both Saccharomyces cerevisiae and other unconventional yeast species. The discussion of DSB repair covers the most frequently used homologous recombination (HR) and nonhomologous end joining (NHEJ) strategies to the less well-studied illegitimate recombination (IR) pathways, such as single-strand annealing (SSA) and microhomology-mediated end joining (MMEJ). Various CRISPR-based genome editing tools and corresponding gene editing efficiencies are described. Finally, we summarize recently developed CRISPR-based strategies that use optimized DSB repair for genome-scale editing, providing a direction for further development of yeast genome editing

Doping the Buckminsterfullerene by Substitution: Density Functional Theory Studies of C59X (X = B, N, Al, Si, P, Ga, Ge, and As)

The heterofullerenes C59X (X = B, N, Al, Si, P, Ga, Ge, and As) were investigated by quantum chemistry calculations based on density functional theory. These hybrid cages can be seen as doping the buckminsterfullerene by heteroatom substitution. The geometrical structures, relative stabilities, electronic properties, vibrational frequencies, dielectric constants, and aromaticities of the doped cages were studied systemically and compared with those of the pristine C60 cage. It is found that the doped cages with different heteroatoms exhibit various electronic, vibrational, and aromatic properties. These results imply the possibility to modulate the physical properties of these fullerene-based materials by tuning substitution elements

The altered drivers of evapotranspiration trends around the recent warming hiatus in China

This study focuses on the trends and the causes of variation in actual evapotranspiration (AET) around the warming hiatus over China by a comprehensive analysis applying various temporal–spatial methods. It is observed that the annual AET showed a different trend around 2000 for China as a whole. By employing segmented regression analysis for detecting warming hiatus points, high temporal inconsistency can be found in eight climatic regions of China. The impacts of meteorological variables on AET were further identified by affecting the intensity and relative change of meteorological factors. AET was highly correlated (p <.01) with solar radiation in the southeast (R = 0.80) and air specific humidity in the northwest areas (R = 0.83). AET changes presented the highest sensitivity to specific humidity in Northwest before 2006 and in north central China after 2003, with sensitivity coefficients of 1.48 and 1.74, respectively. Three variables, including air specific humidity (with an average contribution rate of ~17% in the northwest), short-wave radiation and air temperature, can be the main factors that lead to the changes in AET. The specific meteorological factors varied from region to region: the changes in AET can be ascribed to the increased wind and short-wave radiation in north central China and east China, the decreased air temperature in Tibetan Plateau, the increased specific humidity in southeast China during warming hiatus, and so on. After the warming hiatus occurred, the dominant factor of AET trends changed from air specific humidity to short-wave radiation and other factors. Generally, air specific humidity and air temperature have played leading roles in AET trends during the past 30 years

Drivers of the water use efficiency changes in China during 1982–2015

This study investigates the drivers of water use efficiency (WUE), a key metric of water resources management, and its changes over eight regions across China from 1982 to 2015 based on gross primary production (GPP) and actual evapotranspiration (AET) datasets. The order of seasonal change of WUE from large to small is autumn, summer, spring and winter. The drivers include seven variables, air temperature, specific humidity, precipitation, short-wave radiation, Normalized Difference Vegetation Index (NDVI), soil moisture and CO2. Our analysis suggests that the sensitivity of annual average NDVI to WUE changes was high nationwide, but there were some differences in seasonal scales. The annual average contribution of air temperature and CO2 affecting WUE change was relatively high in China's largest area (SW, SE, E, NP). Other influencing factors were only relatively high in the local area. Seasonally, NDVI is the driving factor with the highest contribution rate in summer and autumn for NC and NW region. The seasonal contribution rates of driving factors in other regions are significantly different. For the study period (1982–2015), the shrubland ecosystem had the highest annual WUE followed by forest and cropland. The WUE of the farmland ecosystem was higher than that of the grassland ecosystem in most areas

UCST-Type Thermoresponsive Polymers in Synthetic Lubricating Oil Polyalphaolefin (PAO)

This Article reports a family of UCST-type thermoresponsive polymers, poly­(alkyl methacrylate)­s with an appropriate alkyl pendant length in an industrially important nonvolatile organic liquid polyalphaolefin (PAO). The cloud point (CP) can be readily tuned over a wide temperature range by changing the alkyl pendant length; at a concentration of 1 wt % and similar polymer molecular weights, the CP varies linearly with the (average) number of carbon atoms in the alkyl pendant. PAO solutions of ABA triblock copolymers, composed of a PAO-philic middle block and thermoresponsive outer blocks with appropriate block lengths, undergo thermoreversible sol–gel transitions at sufficiently high concentrations. The discovery of thermoresponsive polymers in PAO makes it possible to explore new applications by utilizing PAO’s unique characteristics such as thermal stability, nonvolatility, superior lubrication properties, and so on. Two examples are presented: thermoresponsive physical gels for control of optical transmittance and injectable gel lubricants

Multiplex genome editing targeting soybean with ultra-low anti-nutritive oligosaccharides

Soybean is the primary source of plant protein for humans. Owing to the indigestibility of the raffinose family of oligosaccharides (RFO), raffinose and stachyose are considered anti-nutritive factors in soybean seeds. Low-RFO soybean cultivars are generated by mutagenesis of RFO biosynthesis genes, but the carbohydrate profiles invite further modification to lower RFOs. This study employed a pooled multiplex genome editing approach to target four seed-specifically expressed genes mediating RFO biosynthesis, encoding three raffinose synthases (RS2, RS3, and RS4) and one stachyose synthase. In T1 progeny, rs2/rs3 and rs4/sts homozygous double mutants and a rs2/rs3/rs4/sts quadruple mutant (rfo-4m) were characterized. The rs2/rs3 mutant showed reduced raffinose and stachyose contents, but the rs4/sts mutant showed only reduced stachyose in seeds. The RFO contents in the rfo-4m mutant were almost eliminated. Metabolomic analysis showed that the mutation of four RFO biosynthesis genes led to a shift of metabolic profile in the seeds, including the accumulation of several oligosaccharides-related metabolites. These mutants could contribute to precision breeding of soybean cultivars for soy food production