Search

Purpose – The Kirkendall void had been a well-known issue for long-term reliability of semiconductor interconnects; while even the KVs exist at the interfaces of Cu and Sn, it may still be able to pass the condition of unbias long-term reliability testing, especially for 2,000 cycles of temperature cycling test and 2,000 h of high temperature storage. A large number of KVs were observed after 200 cycles of temperature cycling test at the intermetallic Cu3Sn layer which locate between the intermetallic Cu6Sn5 and Cu layers. These kinds of voids will grow proportional with the aging time at the initial stage. This paper aims to compare various IMC thickness as a function of stress test, the Cu3Sn and Cu6Sn5 do affected seriously by heat, but Ni3Sn4 is not affected by heat or moisture. Design/methodology/approach – The package is the design in the flip chip-chip scale package with bumping process and assembly. The package was put in reliability stress test that followed AEC-Q100 automotive criteria and recorded the IMC growing morphology. Findings – The Cu6Sn5 intermetallic compound is the most sensitive to continuous heat which grows from 3 to 10 μm at high temperature storage 2,000 h testing, and the second is Cu3Sn IMC. Cu6Sn5 IMC will convert to Cu3Sn IMC at initial stage, and then Kirkendall void will be found at the interface of Cu and Cu3Sn IMC, which has quality concerning issue if the void’s density grows up. The first phase to form and grow into observable thickness for Ni and lead-free interface is Ni3Sn4 IMC, and the thickness has little relationship to the environmental stress, as no IMC thickness variation between TCT, uHAST and HTSL stress test. The more the Sn exists, the thicker Ni3Sn4 IMC will be derived from this experimental finding compare the Cu/Ni/SnAg cell and Ni/SnAg cell. Research limitations/implications – The research found that FCCSP can pass automotive criteria that follow AEC-Q100, which give the confidence for upgrading the package type with higher efficiency and complexities of the pin design. Practical implications – This result will impact to the future automotive package, how to choose the best package methodology and what is the way to do the package. The authors can understand the tolerance for the kind of flip chip package, and the bump structure is then applied for high-end technology. Originality/value – The overall three kinds of bump structures, Cu/Ni/SnAg, Cu/SnAg and Ni/SnAg, were taken into consideration, and the IMC growing morphology had been recorded. Also, the IMC had changed during the environmental stress, and KV formation was reserved.

The state-of-the-art review of hybrid GFRP-concrete systems for bridge decks is presented in this study. Previous research on the experimental work, analytical modeling, and field application on hybrid GFRP-concrete deck systems are presented, along with a variety of deck systems are discussed. Then, seven typical types of connection technology between FRP and concrete are introduced and compared. Besides, the current progress on the performance of shear connections via beam tests, pushout tests, and pullout tests are probed, respectively. Finally, general conclusions are made, identifying the need for future research.

Abstract Given the insidious and high-fatality nature of cardiovascular diseases (CVDs), the emergence of fluoride as a newly identified risk factor demands serious consideration alongside traditional risk factors. While vascular smooth muscle cells (VSMCs) play a pivotal role in the progression of CVDs, the toxicological impact of fluoride on VSMCs remains largely uncharted. In this study, we constructed fluorosis model in SD rats and A7R5 aortic smooth muscle cell lines to confirm fluoride impaired VSMCs. Fluoride aggravated the pathological damage of rat aorta in vivo. Then A7R5 were exposed to fluoride with concentration ranging from 0 to 1200 μmol/L over a 24-h period, revealing a dose-dependent inhibition of cell proliferation and migration. The further metabolomic analysis showed alterations in metabolite profiles induced by fluoride exposure, notably decreasing organic acids and lipid molecules level. Additionally, gene network analysis underscored the frequency of fluoride's interference with amino acids metabolism, potentially impacting the tricarboxylic acid (TCA) cycle. Our results also highlighted the ATP-binding cassette (ABC) transporters pathway as a central element in VSMC impairment. Moreover, we observed a dose-dependent increase in osteopontin (OPN) and α-smooth muscle actin (α-SMA) mRNA level and a dose-dependent decrease in ABC subfamily C member 1 (ABCC1) and bestrophin 1 (BEST1) mRNA level. These findings advance our understanding of fluoride as a CVD risk factor and its influence on VSMCs and metabolic pathways, warranting further investigation into this emerging risk factor.

Abstract Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of cells. Relevant studies have been constantly making inroads in our understanding of pathophysiology, and inspiring development of therapeutics. As a crucial component of epigenetics at post-transcription level, RNA modification significantly determines RNA fates, further affecting various biological processes and cellular phenotypes. To be noted, immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological contexts. In this review, we characterize the distribution features, modifying mechanisms and biological functions of 8 RNA modifications, including N6-methyladenosine (m6A), N6,2′-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N4-acetylcytosine (ac4C), N7-methylguanosine (m7G), Pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing, which are relatively the most studied types. Then regulatory roles of these RNA modification on metabolism in diverse health and disease contexts are comprehensively described, categorized as glucose, lipid, amino acid, and mitochondrial metabolism. And we highlight the regulation of RNA modifications on immunometabolism, further influencing immune responses. Above all, we provide a thorough discussion about clinical implications of RNA modification in metabolism-targeted therapy and immunotherapy, progression of RNA modification-targeted agents, and its potential in RNA-targeted therapeutics. Eventually, we give legitimate perspectives for future researches in this field from methodological requirements, mechanistic insights, to therapeutic applications.

Summary: Wide-apart double defect in head and neck region is rare and difficult to reconstruct at one time. Double free flaps are normally used for this scenario and often tedious and technically complicated. This study presented a technique using branch-based anterolateral thigh free flap to simultaneously reconstruct the 2 defects separated wide apart. The concept, indications, surgical technique, and anatomical variations are discussed. Branch-based anterolateral thigh flap is a safe technique and the dissection will be easy when the oblique branch is present.

AbstractBackground Venetoclax monotherapy is an effective option for patients with acute myeloid leukemia (AML). Venetoclax has also been used in non-myeloablative conditioning allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk AML with a tolerable toxicity profile. However, the efficacy and safety of a venetoclax-containing myeloablative conditioning (MAC) allo-HSCT regimen for high-risk AML have not been evaluated.Objective To evaluate the safety and efficacy of a MAC regimen containing venetoclax for high-risk AML.Study design From 25 February 2021 to 4 September 2022, a total of 31 patients with high-risk AML who underwent allo-HSCT and a MAC regimen with venetoclax were analyzed.Results At the time of transplantation, 21 patients were in first complete remission (CR1), 4 were in a second complete remission (CR2), and 6 in non-remission (NR). Twenty-four patients (77.4%) were minimal residual disease (MRD)-positive before transplant. The FLT3-ITD gene mutation was present in 51.6% of patients. NUP98 rearrangement, MLL rearrangement or MLL-PTD and DEK::CAN fusion genes were found in 5 (16.1%), 7(22.6%) and 2 (6.5%) patients, respectively. Twenty-nine (93.6%) patients underwent haploidentical allo-HSCT. The median follow-up time was 278 days (range: 52–632 days). The 100-day cumulative incidence of grade 3 to 4 acute graft-versus-host disease (aGVHD) was 16.1% (95%CI, 7.2–36.0%). The 180-day cumulative incidence of moderate to severe chronic graft-versus-host disease (cGVHD) was 7.1% (95%CI, 1.9–26.9%). Cumulative incidence of 100-day cytomegalovirus (CMV) viraemia and 100-day Epstein-Barr virus (EBV) viraemia was 61.6% (95%CI, 46.5–81.4%) and 3.2% (95%CI, 0.4–22.2%), respectively. The 600-day overall survival (OS) and leukemia-free survival (LFS) were 80.9% (95%CI, 63.5–93.6%) and 81.3% (95%CI, 64.2–93.7%), respectively. The 600-day relapse incidence (RI) and non-relapse mortality (NRM) was 6.9% (95%CI, 1.8–26.3%) and 11.7% (95%CI, 3.9–35.0%).Conclusion Our study shows that the addition of venetoclax to a MAC allo-HSCT was feasible, safe and effective for high-risk AML patients.

Background: Incidence rates of papillary thyroid cancer (PTC) have increased rapidly, with incidentally detected cancers contributing a large proportion. We aimed to explore the impact of incidental detection on thyroid cancer-specific and competing mortality among PTC patients. Methods: We conducted a retrospective cohort study of PTC patients at a cancer center in Guangzhou. Baseline information on detection route and other covariates were collected between 2010 and 2018, and death outcome was followed up for each patient. Cumulative incidence functions were used to estimate the mortality risk of thyroid cancer and competing risk. Cause-specific hazard models were the n utilized to explore the association between detection routes and PTC-specific and competing mortality. Results: Of the 2874 patients included, 2011 (70.0%) were detected incidentally, and the proportion increased from 36.9% in 2011 to 82.3% in 2018. During a median follow-up of 5.6 years, 42 deaths occurred, with 60% of them due to competing causes. The probability of competing mortality at 5 years in the non-incidental group and incidental group was 1.4% and 0.4%, respectively, and PTC-specific mortality in the non-incidental group and incidental group was 1.0% and 0.1%, respectively. After adjusting for covariates, the HRs of incidental detection were 0.13 (95% CI: 0.04–0.46; P = 0.01) and 0.47 (95% CI: 0.20–1.10; P = 0.10) on PTC-specific mortality and competing mortality, respectively. Conclusions: Incidental detection is associated with a lower risk of PTC-specific and competing mortality. Under the context of increasing magnitude of overdiagnosis, incorporation of detection route in clinical decision-making might be helpful to identify patients who might benefit from more extensive or conservative therapeutic strategies.

[Purpose/Significance] Multi-modal feature analysis and service efficiency improvement of digital community consumers will help to provide a new vision for the construction of digital intelligent online communities and provide new impetus for relevant departments to make decisions. In addition, although the current research on digital consumption includes the relevant content of user analysis, it mainly aims at the formulation of detailed operation plans, and lacks the analysis of service efficiency improvement of digital communities. On the other hand, the research on user value orientation for online service quality optimization is mostly based on profile technology, which only considers the difference characteristics of a single target user, and lacks the horizontal comparison and difference attribution research of multi-modal features among groups. Based on this, this paper, from the perspective of value discovery, achieves clustering by aggregating user profiles, analyzes the multi-modal characteristics of consumer groups in digital communities, and proposes a service efficiency improvement scheme. [Method/process] First, this paper analyzed the target consumers in the digital community and established a cluster indicator system. Then, users were grouped, and the multi-modal information profile of the target group was restored based on group characteristics and inter-group interaction characteristics. Finally, it proposed the path to improve the efficiency of digital community services. In terms of technical implementation, the data related to consumer activities were extracted from the digital community, integrated, cleaned, and distributed to the storage bucket. The clustering indicator system was built through feature mining and existing indicators, and the indicators were mapped to aims, and DBSCAN clustering was carried out on the basis of using AP to realize the image. After grouping and naming, the characteristics analysis, interaction analysis, and drift and penetration phenomenon analysis were carried out according to the characteristics of various groups. We extracted various parameters of the design of digital community consumption activities, and built a decision variable function to find the optimal behavior equilibrium conditions of the digital product supplier, consumer and digital community. Based on this, we built an efficiency improvement tree, and proposed community service efficiency improvement strategies at the initial, middle and later stages of consumption activities. [Results/Conclusions] The empirical analysis results show that the model in this paper can first generate reasonable and effective clustering results, and then realize the classification of group characteristics and the analysis of inter-group infiltration and drift. The clustering results show six types of consumer groups: focus, center, special, sleeping, loss and general groups. Most groups will have user penetration, and only general user groups will have inter-group drift. The service efficiency improvement model shows that the most valued group is the center and key group. The inadequacy of this study is that the applicability of the model to multi-source heterogeneous data needs to be tested and there is still room for improvement in clustering granularity.

Abstract Marvelous advancements have been made in cancer therapies to improve clinical outcomes over the years. However, therapeutic resistance has always been a major difficulty in cancer therapy, with extremely complicated mechanisms remain elusive. N6-methyladenosine (m6A) RNA modification, a hotspot in epigenetics, has gained growing attention as a potential determinant of therapeutic resistance. As the most prevalent RNA modification, m6A is involved in every links of RNA metabolism, including RNA splicing, nuclear export, translation and stability. Three kinds of regulators, “writer” (methyltransferase), “eraser” (demethylase) and “reader” (m6A binding proteins), together orchestrate the dynamic and reversible process of m6A modification. Herein, we primarily reviewed the regulatory mechanisms of m6A in therapeutic resistance, including chemotherapy, targeted therapy, radiotherapy and immunotherapy. Then we discussed the clinical potential of m6A modification to overcome resistance and optimize cancer therapy. Additionally, we proposed existing problems in current research and prospects for future research.

ABSTRACT Petroleum-source and black carbon-source aromatic compounds are present in the cold seep environments, where ANaerobic MEthanotrophic (ANME) archaea as the dominant microbial community mediates the anaerobic oxidation of methane to produce inorganic and organic carbon. Here, by predicting the aromatics catabolic pathways in ANME metagenome-assembled genomes, we provide genomic and biochemical evidences that ANME have the potential of metabolizing aromatics via the strategy of CoA activation of the benzene ring using phenylacetic acid and benzoate as the substrates. Two ring-activating enzymes phenylacetate-CoA ligase (PaaKANME) and benzoate-CoA ligase (BadAANME) are able to convert phenylacetate to phenylacetyl-CoA and benzoate to benzoyl-CoA in vitro, respectively. They are mesophilic, alkali resistance, and with broad substrate spectra showing different affinity with various substrates. An exploration of the relative gene abundance in ANME genomes and cold seep environments indicates that about 50% of ANME genomes contain PCL genes, and various bacteria and archaea contain PCL and BCL genes. The results provide evidences for the capability of heterotrophic metabolism of aromatic compounds by ANME. This has not only enhanced our understanding of the nutrient range of ANME but also helped to explore the additional ecological and biogeochemical significance of this ubiquitous sedimentary archaea in the carbon flow in the cold seep environments. IMPORTANCE ANaerobic MEthanotrophic (ANME) archaea is the dominant microbial community mediating the anaerobic oxidation of methane in the cold seep environments, where aromatic compounds are present. Then it is hypothesized that ANME may be involved in the metabolism of aromatics. Here, we provide genomic and biochemical evidences for the heterotrophic metabolism of aromatic compounds by ANME, enhancing our understanding of their nutrient range and also shedding light on the ecological and biogeochemical significance of these ubiquitous sedimentary archaea in carbon flow within cold seep environments. Overall, this study offers valuable insights into the metabolic capabilities of ANME and their potential contributions to the global carbon cycle.

Summary: Marine group II (MGII) is the most abundant planktonic heterotrophic archaea in the ocean. The evolutionary history of MGII archaea is elusive. In this study, 13 new MGII metagenome-assembled genomes were recovered from surface to the hadal zone in Challenger Deep of the Mariana Trench; four of them from the deep ocean represent a novel group. The optimal growth temperature (OGT) of the common ancestor of MGII has been estimated to be at about 60°C and OGTs of MGIIc, MGIIb, and MGIIa at 47°C–50ºC, 37°C–44ºC, and 30°C–37ºC, respectively, suggesting the adaptation of these species to different temperatures during evolution. The estimated OGT range of MGIIc was supported by experimental measurements of cloned β-galactosidase that showed optimal enzyme activity around 50°C. These results indicate that MGIIc may have originated from a common ancestor that lived in warm or even hot marine environment, such as hydrothermal vents.

As a specific type of asthenoteratozoospermia, multiple morphological abnormalities of the sperm flagella (MMAF) is characterized by composite abnormalities, including absent, short, coiled, angulation, and irregular-caliber flagella. Mutations in cilia- and flagella-associated protein 43 (CFAP43) are one of the main causative factors of MMAF established to date. To identify whether there are other CFAP43 mutations related to MMAF and to determine the clinical outcomes of assisted reproductive technology for patients with MMAF harboring different mutations, we recruited and screened 30 MMAF-affected Chinese men using a 22-gene next-generation sequencing panel. After systematic analysis, seven mutations in CFAP43, including five novel mutations and two previously reported mutations, were identified from four families and related to MMAF in an autosomal recessive pattern. Papanicolaou staining, immunofluorescence, and electronic microscopy further clarified the semen characteristics and abnormal sperm morphologies, including disorganized axonemal and peri-axonemal structures, of the CFAP43-deficient men. The female partners of two patients were pregnant after undergoing assisted reproductive technology through intracytoplasmic sperm injection, and one of them successfully gave birth to a healthy boy. This study significantly expands the mutant spectrum of CFAP43, and together with the available information regarding male infertility and MMAF, provides new information for the genetic diagnosis and counseling of MMAF in the future.

Traditional cloud providers provide services solely for users,which has problems of insufficient local cloud resources and high expansion costs.While the emerging multi-cloud combines services of cloud providers with different geographical locations providing users with more choices and has gradually become a research hotspot.At the same time,workflow scheduling is one of the key problems in multi-cloud research.Therefore,this paper firstly makes a thorough investigation and analysis on workflow scheduling technology in multi-cloud environment,then compares and classifies the workflow scheduling method inclu-ded.This paper focuses on single objective workflow scheduling optimization problem for cost and completion time,multi-objective optimization workflow scheduling problem for cost and completion time,for response time and cost,for reliability,cost and completion time,and for other multi-objective optimization.Finally,the future research directions of workflow scheduling in the multi-cloud environment are discussed,including uncertain workflow scheduling,joint scheduling optimization of energy consumption and other objectives,scheduling optimization with edge servers,and hybrid scheduling of virtual machine and Serverless platform.

Abstract N6-methyladenosine (m6A), the most prevalent epigenetic modification of RNA in mammals, has become a hot topic throughout recent years. m6A is involved with every links of the RNA fate, including RNA splicing, nuclear export, translation and stability. Due to the reversible and dynamic regulatory network composed of ‘writers’ (methylase), ‘erasers’ (demethylase) and ‘readers’ (m6A binding proteins), m6A has been deemed as an essential modulator in vast physiological and pathological processes. Previous studies have shown that aberrant expression and dysfunction of these regulators are implicated in diverse tumors, exemplified by hematological malignancies. However, we should hold a dialectic perspective towards the influence of m6A modification on leukemogenesis. Given that m6A itself is neither pro-oncogenic nor anti-oncogenic, whether the modifications promote hematological homeostasis or malignancies occurrence and progression is dependent on the specific targets it regulates. Ample evidence supports the role of m6A in maintaining normal hematopoiesis and leukemogenesis, thereby highlighting the therapeutic potential of intervention in m6A modification process for battling leukemia. In this review, we introduce the advances of m6A modification and summarize the biological functions of m6A in RNA metabolism. Then we discuss the significance of several well-studied m6A regulators in modulating normal and malignant hematopoiesis, with focus on the therapeutic potentials of targeting these regulators for battling hematopoietic malignancies.

Objective To find the trends and regional differences of the resistance of Helicobacter pylori(Hp) to metronidazole, clarithromycin, levofloxacin, amoxicillin, furazolidone and tetracycline in recent years in the mainland of China. Methods By searching several databases, the literatures on the resistance of Hp to six commonly prescribed antibiotics in mainland of China were collected and analyzed with Stata15 software. The antibiotic resistance in Huaihe Hospital of Henan University was reviewed and compared. Results The investigation results from 2013 to 2020 showed that rate of Hp metronidazole resistance was the highest and the clarithromycin was the second, while the rate of resistance to amoxicillin was the lowest one. The amoxicillin resistance in the south of China was significantly higher than that in the north of China. The resistance to metronidazole, clarithromycin, levofloxacin and amoxicillin reached (or closed to) the highest level from 2019 to 2020. At present, the resistance to amoxicillin and furazolidone was low and the resistance to clarithromycin was the highest in Huaihe Hospital of Henan University. Conclusions The resistance of Hp to antibiotics in the mainland of China was at a relatively high level. The resistance rate to metronidazole and clarithromycin was high, while that to amoxicillin was low. The antibiotic resistance of HP was more popular in the south of China.

Event sequences that would lead to an early radioactive release or a large radioactive release are required to be practically eliminated in HAF102—2016. But there are lack of specific acceptance criteria and demonstration method of practical elimination in China. Safety requirement of practical elimination was studied, and some insights, acceptance criteria and demonstration method of practical elimination were proposed in this paper. Demonstration of practical elimination for HPR1000 was evaluated. The main conclusions are as follows: 1) Practical elimination is a higher requirement for the safety design of nuclear power plants. It is not a requirement that accident conditions have no release, but the plant states that could lead to an early or a large radioactive release have been practically eliminated. And conditions that have not been practically eliminated should be fully considered in the design to ensure its radiological consequences limited. 2) With reference to international practice and the relevant requirements of emergency plans and preparations in China, it is the first time to propose the deterministic and probability acceptance criteria for practical elimination in China at this stage. The radiological release acceptance criteria at this stage are suggested that there is no evacuate action beyond 3 km from the site boundary, and no sheltering action beyond 5 km. It is recommended that the DEC�B design requirement is less than 100 TBq equivalent 137Cs. This criterion is also the criterion for large radioactive release in the level 2 PSA. 3) Demonstration method of practical elimination was proposed in this paper, and demonstration of practical elimination for HPR1000 was evaluated. In the final analysis, DBA is effectively mitigated by defence�in�depth, and severe accident prevention and mitigation measures are considered sufficiently for HPR1000. Even if severe accident considered in design is happened, the containment could be intact. Practical elimination is realized on HPR1000.

BackgroundThe aim of this study was to explore the risk factors for early spontaneous abortion (ESA) in fresh- and frozen-embryo transfers.MethodsThis retrospective cohort study comprised a total of 35,076 patients, including 15,557 women in the fresh-embryo transfer group and 19,519 women in the frozen-embryo transfer group from January 2016 to December 2020. The primary outcome of this study was ESA, which we defined as the termination of embryonic development before 12 weeks of pregnancy (i.e., an early abortion after artificial multi-fetal pregnancy reduction was excluded).ResultsIn the 35,076 ART transfer cycles, the incidence of ESA was 5.77% (2023/35,076), and the incidence rates for ESA in fresh and frozen cycles were 4.93% (767 of 15,557) and 6.43% (1,256 of 19,519), respectively. Using a multivariate logistic regression analysis model, maternal age, body mass index (BMI), and number of embryos transferred were independent predictors for ESA. In addition, frozen-thawed transfer was a risk factor for ESA as compared with fresh transfer (OR = 1.207; 95% CI, 1.094–1.331; P = 0.000), blastocyst transfer was risk factor for ESA as compared with cleavage transfer (OR =1.373; 95% CI, 1.186–1.591; P = 0.000 in the total group; OR = 1.291; 95% CI, 1.111–1.499; P = 0.001 in the frozen-transfer group), and unexplained infertility was a protective factor for ESA only in the frozen group (OR = 0.746; 95% CI, 0.565–0.984; P = 0.038).ConclusionsMaternal age, BMI, number of embryos transferred, and frozen-thawed transfer were independent risk factors for ESA in assisted reproductive technology treatment cycles.

The porosity of the micro-arc oxidation coating of pure titanium was assessed through the utilization of Mercury intrusion porosimetry (MIP). The porosity values were subsequently adjusted by accounting for the proportion of coating volume, resulting in a more precise determination of the coating’s porosity. Additionally, the fractal dimension of the pore structure was determined through the application of a linear regression equation utilizing the Mercury intrusion data. The findings indicate that the observed numerical dispersion from image metohd is substantial, with a range of 34.9% between the minimum and maximum values. This suggests that the precision and validity of the porosity outcomes derived from this approach are inadequate; The MIP is capable of determining both the porosity, average pore size and pore size distribution of the sample, while also mitigating the impact of the matrix through test result correction, thereby yielding precise porosity values. Additionally, the results of the verification experiment demonstrate a positive correlation between the porosity alteration of the MIP and oxidation duration, thereby affirming the reliability of the test outcomes; Through the analysis of pressure, pore size, cumulative Mercury intrude volume, and incremental Mercury intrude volume data obtained from MIP, the fractal dimension of the coating’s pore structure then be determined. Research showed that as the oxidation time increases, the pore fractal dimension of the MAO coating gradually expands within a narrow range, from 2.57 and finally stabilized at 2.77, indicating a gradual increase in pore structure complexity.

The objective of this study was to investigate the effect of Mycobacterium vaccae on Jagged 1 and gamma delta T17 (γδT17) cells in asthmatic mice. An asthma mouse model was established through immunization with ovalbumin (OVA). Gamma-secretase inhibitor (DAPT) was used to block the Notch signaling pathway. M. vaccae was used to treat asthma, and related indicators were measured. Blocking Notch signaling inhibited the production of γδT17 cells and secretion of cytokine interleukin (IL)-17, which was accompanied by a decrease in Jagged1 mRNA and protein expression in the treated asthma group compared with the untreated asthma group. Similarly, treatment with M. vaccae inhibited Jagged1 expression and γδT17 cell production, which was associated with decreased airway inflammation and reactivity. The Notch signaling pathway may play a role in the pathogenesis of asthma through the induction of Jagged1 receptor. On the other hand, the inhibitory effect of M. vaccae on Jagged1 receptor in γδT17 cells could be used for the prevention and treatment of asthma.

A new method of controlling the residual stress in laser directed energy deposition additive manufacturing (DED AM) products proposed based on constraints used in manufacturing and the substrate design. The simulation results of the residual stress, which were validated with the experimental measured data, showed that weaker constraints on the substrate could greatly decrease the residual stress in the laser DED AM products. In addition, by designing local reduced thickness regions into the substrate, such as long strip holes or support legs, the residual stress in DED AM products could be further decreased. In this study, when long strip holes were designed in the substrate, the tensile residual stress was decreased by 28%. An even smaller amount of residual stress was achieved when the design structure was changed to support legs. The tensile residual stress decreased by more than 30%. The fewer support legs, the smaller the residual stress. The residual stress in DED AM products could be well-controlled by design, while the stiffness can be weakened with fewer constraints.

Abstract Recurrent neural networks (RNNs) have shown an ability to model temporal dependencies. However, the problem of exploding or vanishing gradients has limited their application. In recent years, long short-term memory RNNs (LSTM RNNs) have been proposed to solve this problem and have achieved excellent results. Bidirectional LSTM (BLSTM), which uses both preceding and following context, has shown particularly good performance. However, the computational requirements of BLSTM approaches are quite heavy, even when implemented efficiently with GPU-based high performance computers. In addition, because the output of LSTM units is bounded, there is often still a vanishing gradient issue over multiple layers. The large size of LSTM networks makes them susceptible to overfitting problems. In this work, we combine local bidirectional architecture, a new recurrent unit, gated recurrent units (GRU), and residual architectures to address the above problems. Experiments are conducted on the benchmark datasets released under the IARPA Babel Program. The proposed models achieve 3 to 10% relative improvements over their corresponding DNN or LSTM baselines across seven language collections. In addition, the new models accelerate learning speed by a factor of more than 1.6 compared to conventional BLSTM models. By using these approaches, we achieve good results in the IARPA Babel Program.

Abstract Background Congenital myasthenic syndrome caused by mutations in AGRN, a gene encoding a protein with a crucial function at the neuromuscular junction, is a rare disorder. There are few studies in this area. We here present two cases with novel mutations of AGRN of which we further investigated possible pathogenesis. Results Patient 1 had general limb weakness with fluctuation and deterioration in the afternoon and in hot weather. Patient 2 had early-onset weakness of lower extremities with suspected fluctuation in the early stages, which then progressed to the upper limbs. Both distal and proximal muscles were involved. Repetitive stimulation on EMG in both patients showed decrement in proximal and distal limbs. Patient 2 showed a marked response to salbutamol while Patient 1 did not. By targeted exome sequencing, two novel homozygous missense variants, p.L1176P and p.R1698C, in the SEA and LG2 domain of agrin were identified respectively. Further functional analysis revealed instability of the protein and impaired clustering of the acetylcholine receptor (AChR) by both mutations. Conclusions The mutations identified in AGRN in our study may cause congenital myasthenic syndrome by damaging protein stability and interfering with AChR clustering. These results broaden the understandings on the phenotype, genotype and pathogenesis of this rare disorder.