Unstable Expansion Research Articles

AntimiR treatment corrects myotonic dystrophy primary cell defects across several CTG repeat expansions with a dual mechanism of action.

This study evaluated therapeutic antimiRs in primary myoblasts from patients with myotonic dystrophy type 1 (DM1). DM1 results from unstable CTG repeat expansions in the DMPK gene, leading to variable clinical manifestations by depleting muscleblind-like splicing regulator protein MBNL1. AntimiRs targeting natural repressors miR-23b and miR-218 boost MBNL1 expression but must be optimized for a better pharmacological profile in humans. In untreated cells, miR-23b and miR-218 were up-regulated, which correlated with CTG repeat size, supporting that active MBNL1 protein repression synergizes with the sequestration by CUG expansions in DMPK. AntimiR treatment improved RNA toxicity readouts and corrected regulated exon inclusions and myoblast defects such as fusion index and myotube area across CTG expansions. Unexpectedly, the treatment also reduced DMPK transcripts and ribonuclear foci. A leading antimiR reversed 68% of dysregulated genes. This study highlights the potential of antimiRs to treat various DM1 forms across a range of repeat sizes and genetic backgrounds by mitigating MBNL1 sequestration and enhancing protein synthesis.

A multiple animal and cellular models approach to study frataxin deficiency in Friedreich Ataxia.

Friedreich's ataxia (FA) is one of the most frequent inherited recessive ataxias characterized by a progressive sensory and spinocerebellar ataxia. The main causative mutation is a GAA repeat expansion in the first intron of the frataxin (FXN) gene which leads to a transcriptional silencing of the gene resulting in a deficit in FXN protein. The nature of the mutation (an unstable GAA expansion), as well as the multi-systemic nature of the disease (with neural and non-neural sites affected) make the generation of models for Friedreich's ataxia quite challenging. Over the years, several cellular and animal models for FA have been developed. These models are all complementary and possess their own strengths to investigate different aspects of the disease, such as the epigenetics of the locus or the pathophysiology of the disease, as well as being used to developed novel therapeutic approaches. This review will explore the recent advancements in the different mammalian models developed for FA.

Investigating dilation response in PET FRP-confined reinforced concrete: Experimental study

In compression, concrete undergoes dilation due to the Poisson’s effect. Beyond the elastic limit, rapid crack propagation causes unstable expansion, leading to stiffness degradation, reduced strength, and ductility. External confinement with fiber-reinforced polymer (FRP) composites effectively manages this dilation, maintaining core integrity at high strength and deformation levels. However, internal steel reinforcement, especially when poorly detailed, can hinder FRP's efficacy by inducing stress concentrations from longitudinal bar buckling, resulting in premature FRP failure. This study addresses this challenge by utilizing polyethylene terephthalate (PET) FRP with a large rupture strain (LRS) capacity to delay premature rupture to high strain levels. Experimental results on poorly detailed reinforced concrete (RC) externally confined with PET FRP are presented, with variables including PET FRP layers, longitudinal bar buckling length, and cross-sectional aspect ratio. Detailed discussions on the effects of these variables on lateral to axial strain ratio, dilation rate, and volumetric response of confined concrete are provided. Test results have shown that PET FRP effectively managed the unstable dilation of confined concrete, even with internal steel reinforcement. Following the yielding of lateral ties and the buckling of longitudinal bars, PET FRP efficiently handled local stress concentrations and redistributed internal concrete damage. Despite PET FRP's low elastic modulus causing significant lateral expansion, its LRS capacity maintained the integrity of the entire column under high deformation.

On inherent hyperelastic crease

We present analyses of the inherent hyperelastic crease that entails an unstable degenerative singular perturbation field over a uniformly compressed hyperelastic half-space. The analyses reveal asymptotic far-field characteristics of the singular field that bring out admissible incremental elastic deformation mechanisms of the inherent creasing instability typically observed at a compressive strain of ∼0.354 in neo-Hookean solids. The admissible singular perturbation field has an asymptotic leading-order incremental-stress singularity decaying 1/r2 as the distance from the crease tip r→∞. In general, asymptotic incremental-deformation fields of 1/r2 stress singularity can be introduced by surface flaws. We found that the singular field creates a far-field eigenmode of three energy-release angular sectors separated by two energy-elevating sectors of incremental deformation. The far-field eigenmode braces the near-tip energy-release field of the surface flaw against the transition to an unstable self-similar expansion field of creasing. Two asymptotic far-field parameters can characterize the braced-incremental-deformation (bid) and crease fields. One is the Burgers vector of a projected subsurface dislocation of the asymptotically singular far field. The other is a dimensionless shape factor representing the ratio of the subsurface depth of the dislocation to the Burgers vector. Our analyses show that the shape factor gauges the transition from the stable bid field to the unstable inherent crease field at the crease limit point as the compression increases. Two tangential-manifold conservation integrals are revealed to identify the two parameters. At the crease-limit point, matched asymptotes lead to the ratio between the two separate scaling parameters of the asymptotic solutions of the crease-tip folding field and the leading-order far field. To this end, we introduced a novel finite element method (FEM) for simulating the crease field nearly in a hyperelastic half-space with a finite-size simulation domain. Furthermore, we uncovered with the Gent model (1996) that strain-stiffening in hyperelasticity alters the dependence of the shape factor on the compressive strain, raising crease resistance. The new findings in hyperelastic crease mechanisms will help study ruga mechanics of self-organization and design soft-material structures and skin conditions for high crease resistance.

“Unraveling the Diagnostic Dilemma: Unusual Presentation of Huntington’s Disease with Predominant Psychiatric Symptoms and Late-Onset Motor Manifestations”

IntroductionHuntington’s Disease is a neurodegenerative disease inherited in an autosomal dominant fashion.The underlying genetic defect is unstable CAG trinucleotide repeat expansion with a repeat length longer than 36 resulting in pathological aggregation of abnormal protein causing cell death.The clinical symptoms encompass 3 main domains-motor,cognitive and psychiatric.The psychiatric symptoms often in atypical form appear decades before other symptoms causing significant impact on patient’s functioning and quality of life.Here, we discuss an unusual presentation of Huntington’s Disease causing diagnostic dilemma.ObjectivesCase report discussing the unusual presentation of Huntington’s Disease.MethodsCase: Mr X is a 61 year old Caucasian male.He had an uneventful birth and early childhood attaining milestones appropriately. He experienced childhood adversity in the form of sexual abuse between ages 2-14 years. His mental health difficulties started following sexual abuse when he attempted to end his life by hanging and overdosing at age 15. He got married twice, both of which broke down. There is a history of significant alcohol abuse between ages 40-50. Following this, he had a myocardial infarction and a stroke requiring stenting.He presented to Psychiatric Outpatient Services in 2011 with auditory hallucinations, social anxiety with panic attacks, OCD type rituals, claustrophobia and feeling hot all the time. He was started on an antipsychotic medication for psychosis ,but clinically deteriorated. He started having anger outbursts, marching on the spot ,and head banging. He was diagnosed with Huntington’s Chorea in 2021 after he had developed chorea. He currently has low mood and is head banging for hours.ResultsPsychiatric symptoms in HD can span a variety of domains but most common are symptoms of frontal lobe dysfunction-disinhibition, poor attention, irritability, impulsivity and personality change. Apathy, emotional blandness and social withdrawal are also prominent features.Mr X had strong family history of Paranoid Schizophrenia (aunt and cousin).There was no family history of HD. His mental health problems started early in life with DSH, Depression and Harmful use of Alcohol. He presented predominantly with psychotic symptoms like auditory hallucinations, social anxiety, paranoia. Motor symptoms started late which he incorporated into voluntary movements like head banging which made it difficult to differentiate from deliberate self harm.ConclusionsPsychiatric symptoms constitute the core of HD. Studies have shown that though depression and personality change are typical of HD, there are number of other psychiatric symptoms that can impair quality of life. Early diagnosis and treatment of these symptoms will help patients and families to cope better with severe symptoms of this progressive disease.Disclosure of InterestNone Declared

Pain and gain of predictive genetic testing: Particular case of fragile X syndrome

IntroductionThe purpose of predictive genetic tests is to identify carriers or the onset of a disease in pre-symptomatic individuals. Prediction is linked to a negative psychological impact (anxiety, depression, etc.), depending on the perception of risk, the severity of the disease, and the availability and effectiveness of treatments.ObjectivesHere, we report on genetic counselling during predictive genetic testing offered to an Arab family affected by fragile X condition (FXS) caused by the unstable expansion of a CGG repeat (CGGR) in the FMR1 gene.MethodsA 10-year-old boy who harbored a mental retardation was referred to our genetic counselling for genetic testing as he was suspected to be affected by FXS. Screening of FMR1 gene mutations was conducted for the index case and his mother. A predictive genetic testing for the family members (brothers, sisters and others) was offered, focusing on knowledge of genetics and medical risks of FXS.ResultsFMR1 molecular analysis showed a full mutation (300 to 2000 CGGR) for the boy and a large premutation (100 CGGR) for the mother. During genetic counselling, the family was informed about the significance of the genetic results. In FXS initiated by an expansion of over 200 CGGR. While mental retarded males usually harbor the full mutation, the mother carry a premutation (70 to 200 CGGR). The deficiency of FMR protein (FMRP) in the neurons of affected males leads to brain developmental abnormalities. Some pre-mutated children may show signs of the autism spectrum disorder and females may develop FMR1-related premature ovarian insufficiency. An increased risk of a late onset fragile X tremor ataxia syndrome is identified in pre-mutated men (55 to 200 CGGR) and less in women.ConclusionsThe reduction or loss of FMRP leads to multisystem damage. Neuropsychiatric disorders such as mental retardation, speech and language delay, autism spectrum disorder, sensory hyperexcitation, social anxiety, abnormal eye contact, shyness and aggressive behaviour are common in individuals with the mutation. Affected women are often under-diagnosed because mental retardation is not constant, but minor disorders including a borderline IQ with learning difficulties and emotional disturbances have been reported. Conditions associated with fragile X premutation, a term proposed by the European Fragile X Network (FXPAC), seem to be characterized by many physical and psychological health symptoms. Anxiety, depression, sleep disorders and mood disorders are more common in permutated individuals. However, new reports suggested that FXS patients could be at unusually low risk of cancers, because FMRP is over-expressed in multiple cancer tissues.Disclosure of InterestNone Declared

Experimental Study on the Pre-Peak Mechanical and Seepage Characteristics of Granite

The Sanshandao Gold Mine is currently in the deep mining stage. The ground pressure on the surrounding rocks is gradually becoming more considerable, and at the same time, threatened by the overlying seawater, the possibility of mine water inrush accidents is increasing. In this study, the MTS815 rock triaxial seepage test system was employed for the triaxial compression testing and stress–seepage coupled testing of granite under different confining pressures. The results show that granite’s pre-peak mechanical evolution under different confining pressures is divided into four stages (the crack closure stage, linear elasticity stage, stable crack expansion stage, and unstable crack expansion stage). With the increase in the confining pressure, the crack initiation threshold, crack damage threshold, and peak threshold gradually increased, but the closure threshold had no corresponding change. Moreover, in the loading process, the permeability curve first decreased and then increased, and the confining pressure suppressed the peak permeability of granite. Finally, based on the test results, stress sensitivity analysis was carried out, and it was found that polynomials fit the relationship between permeability and effective stress better. Granite’s permeability showed strong stress sensitivity at medium confining pressures. The stress sensitivity of the permeability of granite decreased with increasing effective stress at medium and high confining pressures, while it tended to increase at low confining pressures.

A model for the dynamics of expanded CAG repeat alleles: ATXN2 and ATXN3 as prototypes.

Background: Spinocerebellar ataxia types 2 (SCA2) and 3 (SCA3/MJD) are diseases due to dominant unstable expansions of CAG repeats (CAGexp). Age of onset of symptoms (AO) correlates with the CAGexp length. Repeat instability leads to increases in the expanded repeats, to important AO anticipations and to the eventual extinction of lineages. Because of that, compensatory forces are expected to act on the maintenance of expanded alleles, but they are poorly understood. Objectives: we described the CAGexp dynamics, adapting a classical equation and aiming to estimate for how many generations will the descendants of a de novo expansion last. Methods: A mathematical model was adapted to encompass anticipation, fitness, and allelic segregation; and empirical data fed the model. The arbitrated ancestral mutations included in the model had the lowest CAGexp and the highest AO described in the literature. One thousand generations were simulated until the alleles were eliminated, fixed, or 650 generations had passed. Results: All SCA2 lineages were eliminated in a median of 10 generations. In SCA3/MJD lineages, 593 were eliminated in a median of 29 generations. The other ones were eliminated due to anticipation after the 650th generation or remained indefinitely with CAG repeats transitioning between expanded and unexpanded ranges. Discussion: the model predicted outcomes compatible with empirical data - the very old ancestral SCA3/MJD haplotype, and the de novo SCA2 expansions -, which previously seemed to be contradictory. This model accommodates these data into understandable dynamics and might be useful for other CAGexp disorders.

Study on flame propagation and inherent instability of hydrogen/ammonia/air mixture

To improve the safety and reliability of hydrogen energy, this paper studied the flame propagation and instability characteristics of hydrogen/ammonia/air mixture under different hydrogen contents, equivalence ratios and initial pressures. The results show that three typical phenomena are observed in the premixed hydrogen/ammonia/air flame propagation process under different experimental conditions. In a stable flame, the roughness of the flame surface does not increase, while during unstable flame expansion, the cracking of the flame surface splits and increases. In addition, under the condition of low equivalence ratio and hydrogen content, significant flame uplift is observed. With the increase in hydrogen content, the flame thickness and critical instability radius of the hydrogen/ammonia/air mixture decrease monotonously. The increase of hydrogen content mainly strengthens the hydrodynamic instability, leading to the weakening of flame stability. With the increase of the equivalence ratio, the Markstein length and the critical instability radius increase monotonically. The minimum value of flame thickness appears at the equivalence ratio of 1.0. The Lewis number is always less than 1 for poor combustion and greater than 1 for rich combustion. An increase in the hydrogen content only moves the Lewis number further away from 1. In rich burn, the thermal-diffusion is beneficial to flame stability, and the flame thickness increases with the increasing equivalence ratio. Under the combined effect of thermal-diffusion and hydrodynamic instability, the overall stability of the hydrogen/ammonia/air flame gradually increases with the increasing equivalence ratio. With the increase of initial pressure, the flame thickness decreases gradually. The critical instability radius and Markstein length both decrease rapidly with the increase of initial pressure.

Unstable Expansion: The Development of the Military Medical Evacuation Chain in Korea, 1948-1953.

This research examines the expansion and characteristics of the Korean Army's chain of medical evacuation in 1948-1953. The most important goal of the chain of medical evacuation was to conserve fighting strength, which cannot be achieved only by sending the sick and wounded to the rear for treatment. It was more important to maintain as many mission-capable wounded soldiers on the frontline. Therefore, triage for conserving strength was the priority in the evacuation process, and military doctors conducting triage played a significant role. Focusing on military doctors, this article studies the instability of the Korean Army's medical evacuation chain. Although Korea was liberated from Japanese colonial rule in August 1945, Korea had no army or army medical services. With the support of KMAG, the Korean Army was able to build a nationwide evacuation chain during the Korean War. However, the expansion of the medical evacuation chain resulted in instability. At the heart of the instability was manpower, rather than organization and transportation. Koreans had almost no experience with the military medical services before 1948, and during the Korean War, most doctors, who had been conscripted after the outbreak of the war, were not trained as military doctors. Therefore, the Korean Army had no other choice but to conduct medical evacuations using mobilized civilian doctors who were not sufficiently trained as military doctors. The escalating war revealed the problems of civilian doctors in military uniforms. Unlike the goal of the chain of medical evacuation, they easily evacuated patients and were reluctant to release patients to return to their duties. Korean Army doctors who were not sufficiently trained as military doctors struggled between the goals of military medical services and those of medical care. Consequently, the military doctors and the instability of the medical evacuation chain during the Korean War reflect the fundamental tension between war and medicine.

Lipid-Coated Nanobubbles in Plants.

One of the more surprising occurrences of bulk nanobubbles is in the sap inside the vascular transport system of flowering plants, the xylem. In plants, nanobubbles are subjected to negative pressure in the water and to large pressure fluctuations, sometimes encompassing pressure changes of several MPa over the course of a single day, as well as wide temperature fluctuations. Here, we review the evidence for nanobubbles in plants and for polar lipids that coat them, allowing nanobubbles to persist in this dynamic environment. The review addresses how the dynamic surface tension of polar lipid monolayers allows nanobubbles to avoid dissolution or unstable expansion under negative liquid pressure. In addition, we discuss theoretical considerations about the formation of lipid-coated nanobubbles in plants from gas-filled spaces in the xylem and the role of mesoporous fibrous pit membranes between xylem conduits in creating the bubbles, driven by the pressure gradient between the gas and liquid phase. We discuss the role of surface charges in preventing nanobubble coalescence, and conclude by addressing a number of open questions about nanobubbles in plants.

Radial impact fracture characteristics and crack initiation criterion of concentric perforated granite after high temperature-water cycle

In this study, the radial impact fracture characteristics and crack initiation criterion of concentric perforated granite after high temperature-water cycle were evaluated based on the engineering environment such as high temperature, water encounter and dynamic disturbance experienced by the wellbore surrounding rock in the energy storage area during deep geothermal energy mining. And the combination of mechanical test, numerical simulation and theoretical analysis was used. The results revealed that the concentric perforated granite treated with high temperature and water soaking under radial impact load successively underwent three stages: transient elastic deformation, stable and unstable expansion of internal cracks. Finally, the tensile failure was produced and the granite was split into four pieces of approximately symmetrical. The main fracture direction of the rock sample was the impact direction revealed by the strain, fracture history and lateral strain clouds of the inner bore wall of the sample. Meanwhile, the tensile cracks firstly sprouted from the inner bore wall of the sample in the impact direction and expanded to the outer wall, and then from the outer wall in the vertical direction to the inner bore wall. Then, based on the test results, the damage variables were defined according to the proportion of damage degree caused by single factor and the law of crack germination inside the rock sample. It was calculated that the damage accumulation rate of concentric perforated granite under radial impact load after high temperature and water immersion experienced three typical stages: “slow-fast-slow”. Finally, the energy structure relationship of the micro-element of concentric perforated granite was constructed. The crack initiation criterion of the rock sample with concentric perforated structure under radial impact load was established by considering the initial damage caused by heating and water immersion and using the parameters such as the energy storage limit of the rock sample and the energy required for crack initiation. In addition, the rationality was also verified. The research can provide a theoretical reference for the formation of heat transfer channel caused by fracture of stored rock mass and the stability control of surrounding rock of geothermal wellbore, which have great engineering practice and scientific significance.

Experimental Study on the Influence of Humidity on Double-K Fracture Toughness and Fracture Energy of Concrete under Water Environment

Saturated concrete is significantly different from dry concrete in fracture mechanical properties. Using the wedge-splitting tensile method to research the rule of change in moisture content, double-K fracture toughness and fracture energy of three strength grades (C20, C30, and C40) of concrete immersed in a free water environment for 0 h, 2 h, 5 h, 24 h, and 120 h were studied in order to provide support for the safety evaluation of concrete structures in a water environment. The initial cracking fracture toughness of C20, C30, and C40 concrete in saturated state were, respectively, 29.6%, 23.2%, and 33.4% lower than that in dry state. The unstable fracture toughness of C20, C30, and C40 concrete in saturated state were, respectively, 22.7%, 23.9% and 33.8% lower than that in dry state. The fracture energy of C20, C30, and C40 concrete in saturated state are only 71.99%, 70.29%, and 66.11% of that in dry state, respectively. The initial cracking fracture toughness and unstable fracture toughness of concrete all show a linear, decreasing trend with an increase in moisture content. Before the crack initiation, the measured P–CMOD curve had an obvious linear elastic stage, stable expansion stage, and unstable expansion stage. The critical crack opening displacement gradually decreases with an increase in moisture content; the deformation capacity and toughness of concrete are shown to decrease. The humidity state should be fully considered when evaluating the fracture mechanical properties of concrete.

Study on cathode spot expansion process in vacuum arc with high di/dt

The study on cathode spot under high di/dt condition promotes the application of vacuum circuit breaker in DC transmission and aerospace technology. Cathode spot, as a source of microscopic particles, directly affects the breaking capacity of vacuum circuit breaker. In this paper, vacuum arc with high di/dt was generated in L-C oscillating circuit. The cathode spot behavior was obtained by a high-speed camera. There are two types of cathode spots with different size, different expansion velocity and brightness. The difference in the size of different types of cathode spots leads to the difference in the thermal diffusion velocity of the spots, which is also the main reason for the difference in the expansion velocity of the two types of spots. The influence of spot current density on temperature and electric field is discussed. With the increase of di/dt, the phenomenon of unstable expansion of cathode spots is observed. A new cathode spot is generated in the cold electrode area far away from the previous cathode spot area, resulting in a significant increase in the arc voltage. The expansion characteristics of cathode spot under different current amplitude, frequency and di/dt conditions are obtained.

Advances in Nucleotide Repeat Expansion Diseases: Transcription Gets in Phase.

Unstable DNA repeat expansions and insertions have been found to cause more than 50 neurodevelopmental, neurodegenerative, and neuromuscular disorders. One of the main hallmarks of repeat expansion diseases is the formation of abnormal RNA or protein aggregates in the neuronal cells of affected individuals. Recent evidence indicates that alterations of the dynamic or material properties of biomolecular condensates assembled by liquid/liquid phase separation are critical for the formation of these aggregates. This is a thermodynamically-driven and reversible local phenomenon that condenses macromolecules into liquid-like compartments responsible for compartmentalizing molecules required for vital cellular processes. Disease-associated repeat expansions modulate the phase separation properties of RNAs and proteins, interfering with the composition and/or the material properties of biomolecular condensates and resulting in the formation of abnormal aggregates. Since several repeat expansions have arisen in genes encoding crucial players in transcription, this raises the hypothesis that wide gene expression dysregulation is common to multiple repeat expansion diseases. This review will cover the impact of these mutations in the formation of aberrant aggregates and how they modify gene transcription.

Fluid Biomarkers of Central Nervous System (CNS) Involvement in Myotonic Dystrophy Type 1 (DM1).

Myotonic dystrophy type 1 (DM1), commonly known as Steinert's disease (OMIM #160900), is the most common muscular dystrophy among adults, caused by an unstable expansion of a CTG trinucleotide repeat in the 3' untranslated region (UTR) of DMPK. Besides skeletal muscle, central nervous system (CNS) involvement is one of the core manifestations of DM1, whose relevant cognitive, behavioral, and affective symptoms deeply affect quality of life of DM1 patients, and that, together with muscle and heart, may profoundly influence the global disease burden and overall prognosis. Therefore, CNS should be also included among the main targets for future therapeutic developments in DM1, and, in this regard, identifying a cost-effective, easily accessible, and sensitive diagnostic and monitoring biomarker of CNS involvement in DM1 represents a relevant issue to be addressed. In this mini review, we will discuss all the papers so far published exploring the usefulness of both cerebrospinal fluid (CSF) and blood-based biomarkers of CNS involvement in DM1. Globally, the results of these studies are quite consistent on the value of CSF and blood Neurofilament Light Chain (NfL) as a biomarker of CNS involvement, with less robust results regarding levels of tau protein or amyloid-beta.

Effects of microstructure heterogeneity on tensile properties and failure mechanism of GTAW joint of as-cast Ti2531

In this study, as-cast dual-phase titanium alloy Ti2531 was welded by Gas Tungsten Arc Welding, and the effects of microstructure heterogeneity on tensile properties and failure mechanism was analyzed. Tensile test results showed that the specimens fractured in the base metal region, and the tensile strength R m of the welded plate was 855 MPa ~ 859 MPa, which was almost the same as that of the base metal. It was found that, compared with the base metal region, the fine and basketweave phase in the weld zone and heat-affected zone resulted in higher hardness and yield strength. Therefore, plastic strain concentration occurred in the base metal region and a large number of kink bands were found, which accounts for the relatively good plasticity with the fracture strain of 0.073–0.09. In addition, by means of intergranular orientation analysis, it was demonstrated that [0001] α and [101] β were the rotation axes of kink bands in the α and β phases, respectively. Furthermore, by observing the high-resolution electron microscopy, it was found that these kink bands were formed by the arrangement of edge dislocations. As a consequence, when the lattice distortion was severe, the unstable expansion of kink bands occurred and cracks were formed in widmanstätten colonies, inducing the failure of the specimen in the base metal region and great tensile strength equivalent to that of base material. • The weld joint of Ti2531 had good tensile strength close to that of base material. • Plastic deformation was concentrated in base metal region rather than other regions. • Kink bands were formed to coordinate severe plastic deformation in base metal region. • The instable expansion of kink bands resulted in the fracture of the welded specimen.

Clinical practice guidelines for Fragile X syndrome

Fragile X syndrome (FXS) is the most common monogenic form of inherited intellectual disability and autism spectrum disorder (ASD). More than 99% of individuals with FXS are caused by the unstable expansion of CGG repeats located within the 5'-untranslated region of the FMR1 gene. The clinical features of FXS include various degrees of cognitive deficit, physical, behavioral and psychiatric problems. Early treatment and prevention from having further affected children can be guided by molecular genetic testing of the FMR1 gene. The following guideline has combined the relevant research, guidelines and consensus worldwide, and summarized the genetic knowledge and clinical treatment for FXS in order to achieve a standardized diagnosis, treatment and prevention for patients and families affected by this disease.

Rational Thinking on the Reform of Super-Ministry System in Colleges and Universities

The Super-Ministry System has been considered as the main direction of the reform in colleges and universities, but it can not avoid the limitations of traditional solidified organization, most colleges and universities still hold a wait-and-see attitude towards this innovation. The relevant theory and practice need rational thinking, overcome the three limitations of "change and invariance", so as to promote the reform in depth. Firstly, it should overcome the limitation of unstable and unlimited expansion of the functional boundary caused by "changing functions with remaining institutions", then establish dynamic adjustment mechanism and "overload" supervision mechanism for further improvement. Secondly, it should overcome the limitation that academic rights cannot be highlighted due to “changing institutions with remaining power”, fulfill the “addition and subtraction” of power, restructure the system of responsibility with certain adjustment. Thirdly, it should overcome the limitation of "changing environment with remaining institution", which can not meet the new requirements of discipline construction and governance modernization under the support of new platform and new technology.

Creep characteristics of muddy submarine channel slope instability

Creep is an important factor of muddy submarine channel slope instability. In this study, a sub-bottom profiler was used to monitor the continuous internal change of a muddy submarine channel slope in the laboratory to better understand the creep characteristics and mechanism of slope instability. The creep process was analyzed according to changes in the slope internal sound intensity. The results indicate a notable change of the creep characteristics during the slope instability process. Changes in the sound intensity time series decrease with increasing slope depth, and the fluctuation depth of the vertical sound intensity series varies during the slope creep process. The creep process of slope instability can be roughly divided into four stages based on the sub-bottom profile data: an expansion stage; an unstable expansion stage; a fracture stage; and a post-fracture development stage. An adjustment of the sediment microstructure in the slope is ascribed to slope creep deformation. This study highlights the prospects of high-resolution acoustic monitoring to detect and quantify the entire creep process of muddy submarine channel slope instability, which is of great significance for the evaluation and early warning prediction of channel slope instability.