Spinal muscular atrophy (SMA) is a congenital neuromuscular disorder characterized by motor neuron loss, resulting in progressive weakness. SMA is notable in the health care community because it ...accounts for the most common cause of infant death resulting from a genetic defect. SMA is caused by low levels of the survival motor neuron protein (SMN) resulting from
gene mutations or deletions. However, patients always harbor various copies of
, an almost identical but functionally deficient copy of the gene. A genotype-phenotype correlation suggests that
is a potent disease modifier for SMA, which also represents the primary target for potential therapies. Increasing comprehension of SMA pathophysiology, including the characterization of
and
genes and SMN protein functions, has led to the development of multiple therapeutic approaches. Until the end of 2016, no cure was available for SMA, and management consisted of supportive measures. Two breakthrough SMN-targeted treatments, either using antisense oligonucleotides (ASOs) or virus-mediated gene therapy, have recently been approved. These two novel therapeutics have a common objective: to increase the production of SMN protein in MNs and thereby improve motor function and survival. However, neither therapy currently provides a complete cure. Treating patients with SMA brings new responsibilities and unique dilemmas. As SMA is such a devastating disease, it is reasonable to assume that a unique therapeutic solution may not be sufficient. Current approaches under clinical investigation differ in administration routes, frequency of dosing, intrathecal versus systemic delivery, and mechanisms of action. Besides, emerging clinical trials evaluating the efficacy of either SMN-dependent or SMN-independent approaches are ongoing. This review aims to address the different knowledge gaps between genotype, phenotypes, and potential therapeutics.
A
bstract
In this note, we present an alternative representation of the conformal block with external scalars in general spacetime dimensions in terms of a
finite
summation over Appell fourth ...hypergeometric function
F
4. We also construct its generalization to the non-local primary exchange operator with continuous spin and its corresponding Mellin representation which are relevant for Lorentzian spacetime. Using these results we apply the Lorentzian inversion formula to compute the so-called crossing kernel in general spacetime dimensions, the resultant expression can be written as a double infinite summation over certain Kampé de Fériet hypergeometric functions with the correct double trace operator singularity structures. We also include some complementary computations in AdS space, demonstrating the orthogonality of conformal blocks and performing the decompositions.
Background
There are several studies comparing the difference between adenocarcinoma (AC) and squamous cell carcinoma (SqCC) of lung cancer. However, seldom studies compare the different overall ...survival (OS) between AC and SqCC at same clinical or pathological stage. The aim of the study was to investigate the 5-year OS between AC and SqCC groups.
Methods
Data were obtained from the Taiwan Society of Cancer Registry. There were 48,296 non-small cell lung cancer (NSCLC) patients analyzed between 2009 and 2014 in this retrospective study. We analyzed both the AC and SqCC groups by age, gender, smoking status, Charlson co-morbidity index (CCI) score, clinical TNM stage, pathological stage, tumor location, histologic grade, pleura invasion, performance status, treatment, stage-specific 5-year OS rate in each clinical stage I–IV and causes of death. We used propensity score matching to reduce the bias.
Results
The AC and SqCC groups are significantly different in age, gender, smoking status, CCI score, clinical TNM stage, pathological stage, tumor location, histologic grade, pleura invasion, performance status, treatment, stage-specific 5-year OS rate in each clinical stage and causes of death (
p
< 0.0001). The stage-specific 5-year OS rates between AC and SqCC were 79% vs. 47% in stage I; 50% vs. 32% in stage II; 27% vs. 13% in stage III; 6% vs. 2% in stage IV, respectively (all
p
values < 0.0001).
Conclusions
AC and SqCC have significantly different outcomes in lung cancer. We suggest that these two different cancers should be analyzed separately to provide more precise outcomes in the future.
Abstract
This study investigates lexical development in second language (L2) learning from the perspective of complex dynamic system theory (CDST) using a complex network method. Based on authentic ...written output texts from L2 Chinese learners of different proficiency levels and language backgrounds, we successfully differentiate between different proficiency levels using a bi-gram lexical network model at a corpus level. A more in-depth investigation reveals that when compared to traditional lexical complexity indices, such as average word length and hapax legomena percentage (though
Guiraud
proves to be a robust predictor), the lexical network indices, such as network density and network clusters, provide a more profound understanding of L2 proficiency distinctions and a more precise approximation of the target language. Moreover, our findings illuminate the consistent manifestation of complex network characteristics within L2 Chinese lexical networks across all proficiency levels. Additionally, word association features, encompassing more than just word frequency information, provide comprehensive properties of the interlanguage system, as supported by their information gain values. We argue that studies within the CDST framework should integrate both lexical frequency and lexical network features to gain a comprehensive understanding of L2 lexical development.
Along with the concept of circular economy growing worldwide, circular business models (CBMs) have been receiving ever greater attention in both the business sector and academia. However, the ...existing literature on the CBM is scattered and fragmented; this study offers an integrated firm‐level framework to link CBM typologies, the circular economy transition process, and relevant tools for CBM development and clarifies the positioning and roles of those tools in the process. In response to the fragmentation issue, results of this study are presented in three subtopics: (a) CBM typologies and archetypes, (b) transition guidelines, and (c) major analytical tools for CBM research. The roles and functions of CBM typologies and tools were integrated in different stages of the transition process, and the challenges and shortfalls for CBM research in the various stages were identified. This work lays the foundation for future operational studies.
Role of Galectins in Tumors and in Clinical Immunotherapy Chou, Feng-Cheng; Chen, Heng-Yi; Kuo, Chih-Chi ...
International journal of molecular sciences,
2018-Feb-01, 2018-02-01, 20180201, Letnik:
19, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Galectins are glycan-binding proteins that contain one or two carbohydrate domains and mediate multiple biological functions. By analyzing clinical tumor samples, the abnormal expression of galectins ...is known to be linked to the development, progression and metastasis of cancers. Galectins also have diverse functions on different immune cells that either promote inflammation or dampen T cell-mediated immune responses, depending on cognate receptors on target cells. Thus, tumor-derived galectins can have bifunctional effects on tumor and immune cells. This review focuses on the biological effects of galectin-1, galectin-3 and galectin-9 in various cancers and discusses anticancer therapies that target these molecules.
This paper presents a one‐pot approach for preparing highly fluorescent Au8 clusters by reacting the Au3+ precursor solution with lysozyme type VI (Lys VI) at pH 3. The fluorescence band of (Lys ...VI)‐stabilized Au8 clusters is centered at 455 nm on the excitation at 380 nm. Blue‐emitting Au8 clusters have a high quantum yield (∼56%), two fluorescence lifetimes, and a rare amount of Au+ on the surface of the Au core. When the pH of a solution of Au8 clusters increases suddenly to 12, the Au8 clusters gradually convert to Au25 clusters over time. This conversion is also observed in the case of (Lys VI)‐directed synthesis of Au25 clusters at pH 12. The pH‐induced conversion of Au8 to Au25 clusters suggests that the size of (Lys VI)‐stabilized gold nanoclusters (AuNCs) relies on the secondary structure of Lys VI, which is susceptible to pH change. Based on these results and previous literature, this paper proposes the possible mechanism for growing (Lys VI)‐stabilized Au8 and Au25 clusters. Additionally, (Lys VI)‐stabilized Au8 clusters could sense glutathione (GSH) through GSH‐induced core‐etching of Au8 clusters; the limit of detection at a signal‐to‐noise ratio of 3 for GSH is determined to be 20 nm. Except for cysteine, the selectivity of (Lys VI)‐stabilized Au8 clusters for GSH over amino acids is remarkably high. The practicality of using Au8 clusters to determine the concentration of GSH in a single drop of blood is also validated.
A straightforward, one‐pot route for the synthesis of highly fluorescent Au8 clusters with lysozyme type VI at pH 3, is demonstrated. Au8 clusters can be converted to Au25 clusters by adjusting the solution pH to 12 because of pH‐induced change in protein structure. The observation of Au8 clusters is helpful in understanding the (lysozyme type VI)‐mediated formation of Au25 clusters.
The use of ℓ p (p = 1,2) norms has largely dominated the measurement of loss in neural networks due to their simplicity and analytical properties. However, when used to assess the loss of visual ...information, these simple norms are not very consistent with human perception. Here, we describe a different "proximal" approach to optimize image analysis networks against quantitative perceptual models. Specifically, we construct a proxy network, broadly termed ProxIQA, which mimics the perceptual model while serving as a loss layer of the network. We experimentally demonstrate how this optimization framework can be applied to train an end-to-end optimized image compression network. By building on top of an existing deep image compression model, we are able to demonstrate a bitrate reduction of as much as 31% over MSE optimization, given a specified perceptual quality (VMAF) level.
Ammonia removal and recovery from wastewater have been a critical issue worldwide and a key to achieve a sustainable nitrogen cycle and circular economy. Conventional ammonia removal via air ...stripping needs pH adjustment pretreatment with chemical additives while electrokinetic technologies can provide electrochemically in-situ pH control without chemicals needed. The integration of electrokinetic and air stripping technologies is a potential process for the simultaneous removal/recovery of ammonia/ammonium from wastewater. This study consolidates research findings of the separate research domains of electrokinetic and air stripping technologies and aims to identify an integrated process for the simultaneous nitrogen removal/recovery from waste streams. Process integration involves research on improved ammonia removal efficiencies and liquid side mass transfer performances using innovative air stripping system designs and gas-liquid contactors, e.g., rotating packed beds and membrane contactors, compared with the conventional stripping tower process. Findings in the applications and performances of electrokinetic separation processes, including electrodialysis, electrodeionization, capacitive deionization, electrochemical cell, and bio-electrochemical systems, on the removal/recovery of ammonia/ammonium, are a crucial link to integration as well. Energy consumptions between 5–20.4 kWh/kg–NH4-N with a removal ratio of around 90% for electrokinetic processes are currently achievable, and some groups can be implemented on the biodegradable organic substrates from urine. Innovative hybrid technologies of ammonia nitrogen removal/recovery with energy production and co-product valorization that reduce the overall cost and energy consumption via integrated processes optimization, and discussions on the environmental impact assessment (via life cycle assessment) and economic benefit analysis (via techno-economic analysis) of ammonia recovery practices on waste streams are investigated.
•Advanced NH3 stripping processes enhance the gas-liquid mass transfer rate.•Energy-efficient electrokinetic processes facilitate NH4+/NH3 recovery.•Novel hybrid technology for NH4+/NH3 recovery and energy production was discussed.•Establishes a sustainable nitrogen cycle to promote environmental and economic benefits.
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