Juvenile amyotrophic lateral sclerosis (JALS) occurs at an age of onset below 25 years with a heterogeneous disease onset location, variable progression and survival time. To investigate whether an ...ALS gene profile could resolve any aspects of clinical symptom heterogeneity, we have used targeted sequencing technology in a cohort of 12 JALS patients of Chinese descent. We detected 5 likely pathogenic mutations, 2 in familial probands and 3 in sporadic patients. One was a known TARDBP mutation (p.G348V) and 4 were FUS frameshift mutations including a known p.Gln519Ilefs*9 mutation and 3 novel mutations, p.Gly515Valfs*14, p.Gly486Profs*30, and p.Arg498Alafs*32. Of the 4 FUS mutations, 2 were able to be confirmed as de novo mutations. The TARDBP mutation carrier showed a classic ALS phenotype. All patients with FUS mutations experienced limb weakness at an early age and developed bulbar symptoms during the disease course. FUS mutations have previously been associated with increased JALS disease progression, however, we found a large range 12 to 84 months in disease survival (mean 58.2 months). Our results justify future screening for variants in FUS as it remains the most frequent genetic determinant of early onset, JALS (found in 30% of our patients).
Abstract
Recently, FRB 190520B, which has the largest extragalactic dispersion measure (DM), was discovered by the Five-hundred-meter Aperture Spherical radio Telescope (FAST). The DM excess over the ...intergalactic medium and Galactic contributions is estimated as ∼900 pc cm
−3
, which is nearly ten times higher than that of other fast-radio-burst (FRB) host galaxies. The DM decreases with the rate ∼0.1 pc cm
−3
per day. It is the second FRB associated with a compact persistent radio source (PRS). The rotation measure (RM) is found to be larger than 1.8 × 10
5
rad m
−2
. In this Letter, we argue that FRB 190520B is powered by a young magentar formed by core collapse of massive stars, embedded in a composite of a magnetar wind nebula (MWN) and supernova remnant (SNR). The energy injection of the magnetar drives the MWN and SN ejecta to evolve together and the PRS is generated by the synchrotron radiation of the MWN. The magnetar has an interior magnetic field
B
int
∼ (2–4) × 10
16
G and an age
t
age
∼ 14–22 yr. The dense SN ejecta and the shocked shell contribute a large fraction of the observed DM and RM. Our model can naturally and simultaneously explain the luminous PRS, decreasing DM, and extreme RM of FRB 190520B.
This paper proposes a model of an integrated energy based direct district water-heating system, which makes joint use of wind energy, solar energy, natural gas and electric energy. The model includes ...a stand-alone wind turbine generator, heat producers, a water supply network and heating load. This research also investigates an optimal operating strategy in which the fossil fuel consumption of the system in daily operation is optimized. Based on the model, an objective function used to obtain the optimal control strategy is constructed with complex operating constraints. GSO (Group Search Optimizer) is used to trace the optimal set-point temperature of boilers and the optimal water flow of pumps to minimize fuels consumption while satisfying variable constraints. In order to verify the model and optimal operating strategy, simulation studies have been undertaken. The optimal operating strategy is evaluated in comparison with an unoptimized control strategy. The simulation results prove the validity of the model and show that the optimal operating strategy is able to make the system operation more energy efficient. The proposed system is also evaluated in comparison with a conventional natural gas heating system. The comparative results demonstrate the investment feasibility, the significant energy saving and cost reduction achieved in daily operation.
Context.
We investigate the use of saliency-map analysis to aid in searches for transient signals, such as fast radio bursts and individual pulses from radio pulsars.
Aims.
Our aim is to demonstrate ...that saliency maps provide the means to understand predictions from machine learning algorithms and can be implemented in pipelines used to search for transient events.
Methods.
We implemented a new deep learning methodology to predict whether any segment of the data contains a transient event. The algorithm was trained using real and simulated data sets. We demonstrate that the algorithm is able to identify such events. The output results are visually analysed via the use of saliency maps.
Results.
We find that saliency maps can produce an enhanced image of any transient feature without the need for de-dispersion or removal of radio frequency interference. The maps can be used to understand which features in the image were used in making the machine learning decision and to visualise the transient event. Even though the algorithm reported here was developed to demonstrate saliency-map analysis, we have detected a single burst event, in archival data, with dispersion measure of 41 cm
−3
pc that is not associated with any currently known pulsar.
AbstractIn this study, an experimental investigation of the thermal effect of welding on the mechanical behavior of thermomechanical control process (TMCP) high-strength steel (HSS) Q690CFD is ...carried out. Twenty-four specimens in four groups with different welding heat input, strength mismatch ratio of weld filler and base material, heat treatment condition preheating (PH) and postweld heat treatment (PWHT), as well as mechanical boundary condition during the welding process are designed and tested. The thermal history and cooling rate are monitored and analyzed. The welding residual stress near the weld toe and the microstructure of the heat-affected zone (HAZ), as well as Vickers hardness, are respectively examined with the ASTM hole-drilling method, metallurgical microscope observation, and Vickers hardness tests. The effect of heat input (q), mismatch ratio (r), heat treatment, and mechanical boundary conditions on welding residual stress, microstructure, and hardness of the HAZ is investigated. The effect of welding heat input on the tensile behavior of the TMCP HSS is studied. Results indict that different heat inputs could have varied cooling times and cooling rates and hence could produce different distributions of residual stress. When the same PH and PWHT is applied, the heat treatment could have better stress-relief effect for the specimens without mismatching. In addition, the width of the HAZ increases steadily with the increase in heat input. A good yield and ultimate strength prediction from hardness can be observed for base steel and welded connections.
The interactive effects of salicylic acid (SA) and nitric oxide (NO) on alleviating cadmium (Cd) toxicity in peanut (Arachis hypogaea L.) were studied. Seedlings of two cultivars (Huayu 22 — a big ...seed type, and Xiaobaisha — a small seed type) were treated with 200 μM CdCl₂without or with 0.1 mM SA or 0.25 mM sodium nitroprusside (SNP, an NO donor). Results show that the Cd exposure depressed the plant growth of both the cultivars but more of Huayu 22 than of Xiaobaisha. Exogenous SA and NO alleviated Cd toxicity in both the peanut cultivars: they improved growth, chlorophyll content, photosynthesis, and mineral nutrition. Furthermore, exogenous SA or NO decreased oxidative stress by increasing activities of antioxidant enzymes and content of non-enzymatic antioxidants. Besides, in roots and leaves of both the cultivars, exogenous SA and NO increased Cd accumulation in the cell wall and decreased Cd distribution to organelles. In particular, the effect of SA+SNP was most obvious.
Abstract Background Gastric cancer is one of most common malignancies in the world. Currently the prognostic prediction is entirely based on the TNM staging system. In this study, we evaluated ...whether metastatic lymph node ratio (rN) at the time of surgery would improve the prognostic prediction in conjunction with the TNM staging system. Methods This retrospective study includes 745 patients, who had been referred for surgery due to gastric cancer between 1995 and 2007 and had at least 15 lymph nodes examined at the time of surgery without preoperative treatment. Clinicopathologic features and overall survival were analyzed using univariate and multivariate modes to identify the risk factors for overall survival. Results Median overall survival of all patients analyzed is 57.8 months and 5-year overall survival is 49.5%. Tumor site, macroscopic type, pTNM stage, and rN stage are identified as independent prognostic factors. Increased positive lymph node ratio correlates with shorter survival in all patients and in each T and N stage. In stage III gastric cancer patients, rN stage shows additional prognostic value on overall survival ( p < 0.001). Conclusions rN stage is a simple and promising prognostic factor of gastric cancer after surgery in addition to the TNM stage system especially in stage III patients. But the independent prognostic value of rN stage in stage I, II and IV gastric cancer is yet to be determined.
We present observations of supernova (SN) 2017ens, discovered by the ATLAS survey and identified as a hot blue object through the GREAT program. The redshift z = 0.1086 implies a peak brightness of ...Mg = −21.1 mag, placing the object within the regime of superluminous supernovae. We observe a dramatic spectral evolution, from initially being blue and featureless, to later developing features similar to those of the broadlined Type Ic SN 1998bw, and finally showing ∼2000 km s−1 wide H and Hβ emission. Relatively narrow Balmer emission (reminiscent of a SN IIn) is present at all times. We also detect coronal lines, indicative of a dense circumstellar medium. We constrain the progenitor wind velocity to ∼50-60 km s−1 based on P-Cygni profiles, which is far slower than those present in Wolf-Rayet stars. This may suggest that the progenitor passed through a luminous blue variable phase, or that the wind is instead from a binary companion red supergiant star. At late times we see the ∼2000 km s−1 wide H emission persisting at high luminosity (∼3 × 1040 erg s−1) for at least 100 day, perhaps indicative of additional mass loss at high velocities that could have been ejected by a pulsational pair instability.
Osteoarthritis (OA) is a degenerative disease of the joints characterized by inflammation and cartilage degeneration. Zinc finger E-box binding homeobox 2 (ZEB2) contains various function domains ...that interact with multiple transcription factors involved in various cellular functions. However, the function of ZEB2 in OA has not been clearly illustrated.OBJECTIVEOsteoarthritis (OA) is a degenerative disease of the joints characterized by inflammation and cartilage degeneration. Zinc finger E-box binding homeobox 2 (ZEB2) contains various function domains that interact with multiple transcription factors involved in various cellular functions. However, the function of ZEB2 in OA has not been clearly illustrated.Interleukin-1β (IL-1β) was used to establish an OA model in vitro. We quantified the ZEB2 expression in cartilage tissues from OA patients and IL-1β-induced chondrocytes through reverse transcription-quantitative polymerase chain reaction and Western blot. We then used functional assays to explore the function of ZEB2 during OA progression.METHODInterleukin-1β (IL-1β) was used to establish an OA model in vitro. We quantified the ZEB2 expression in cartilage tissues from OA patients and IL-1β-induced chondrocytes through reverse transcription-quantitative polymerase chain reaction and Western blot. We then used functional assays to explore the function of ZEB2 during OA progression.ZEB2 expression was increased in OA cartilage tissues and chondrocytes. The silencing of ZEB2 increased aggrecan and collagen II levels, and reduced the content of matrix metalloproteinase-3 (MMP-3), MMP-9, and MMP-13. ZEB2 knockdown inhibited the effects of IL-1β on the production of nitric oxide and prostaglandin E2, and the expression of inducible nitric oxide synthase and cyclooxygenase-2. ZEB2 inhibition also suppressed the levels of IL-6 and tumour necrosis factor-α, and increased the IL-10 level in IL-1β-treated cells. Mechanically, ZEB2 knockdown blocked the activation of the Wnt/β-catenin pathway in chondrocytes.RESULTSZEB2 expression was increased in OA cartilage tissues and chondrocytes. The silencing of ZEB2 increased aggrecan and collagen II levels, and reduced the content of matrix metalloproteinase-3 (MMP-3), MMP-9, and MMP-13. ZEB2 knockdown inhibited the effects of IL-1β on the production of nitric oxide and prostaglandin E2, and the expression of inducible nitric oxide synthase and cyclooxygenase-2. ZEB2 inhibition also suppressed the levels of IL-6 and tumour necrosis factor-α, and increased the IL-10 level in IL-1β-treated cells. Mechanically, ZEB2 knockdown blocked the activation of the Wnt/β-catenin pathway in chondrocytes.Knockdown of ZEB2 alleviated IL-1β-induced cartilage degradation and the inflammatory response through the Wnt/β-catenin pathway in chondrocytes.CONCLUSIONKnockdown of ZEB2 alleviated IL-1β-induced cartilage degradation and the inflammatory response through the Wnt/β-catenin pathway in chondrocytes.
Abstract
In order to reduce the force transmitted from the upper carriage of a Truck-mounted howitzer to the lower carriage, the upper carriage is optimized for structural parameters under the ...premise that the position of the trunnion chamber is allowed to change. Based on the secondary development function of ABAQUS, established the parametric modeling script of the upper carriage structural, and built the ABAQUS computing environment through the integration of Simcode components of the ISIGHT platform. The position parameters of the trunnion chamber on the upper carriage were selected as the design variables, and the maximum support reaction force was minimized as the optimization objective. The multi-island genetic algorithm was used to optimize the structure parameters of the upper carriage under multiple working conditions, and the global optimal solution was obtained. The optimization results meet the rigidity and strength requirements, and the optimization effect is obvious. This optimization method can be used in the design of the upper carriage structure, reducing the force transmitted from the upper carriage of the artillery to the lower carriage, and can provide a certain optimization space for the weight reduction of the lower carriage, and has engineering application value.
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