Failure Hypothesis Research Articles

Executive failure hypothesis explains the trait-level association between motivation and mind wandering

Mind wandering (MW) is commonly observable in daily life. Early studies established an association between motivation and MW at the trait level using a questionnaire survey. Considering that the mechanism of state-level association between them is known, this study was conducted to replicate the trait-level association and determine its possible mechanisms. Two independent samples were analysed using several questionnaires, which included motivation and MW. General one- and multi-dimensional scales were administered for both variables. Besides the successful replication of the significant association between motivation and MW at the trait level, we found that people with low levels of executive function experience high rates of spontaneous MW. This finding indicates that the underlying mechanism of trait-level association is the executive failure hypothesis, which postulates that a failure of executive control during task-related objectives evokes MW. Further, the motivation–MW relationship exhibits a different psychological basis at the state and trait levels.

Under Pressure: A Rare Case Of Right Ventricular Failure In Setting Of Large Mediastinal Mass

<h3>Introduction</h3> Large mediastinal tumors are rare and have a wide spectrum of presentations. Herein we present a case of right ventricular failure in the setting of a large anterior mediastinal chondrosarcoma. <h3>Case presentation</h3> 32 year old male with no known significant past medical history presented with one week of severe cough and chest pain. CT scan showed a large anterior mediastinal mass (9.3 × 12.4 × 13.6 cms), and biopsy was consistent with chondrosarcoma. Three weeks later, patient underwent complete surgical resection of mass along with partial chest wall, pericardium and diaphragm resection and reconstruction. Postoperative echocardiogram (TTE) showed severe right ventricular (RV) dysfunction and severe tricuspid regurgitation. Pulmonary Hypertension and Right heart failure service was consulted for further evaluation. <h3>Decision making</h3> Review of postoperative TTE showed no signs of pulmonary hypertension (systolic notching, septal flattening, RV hypertrophy). Review of preop TTE showed distal 2/3 of RV obscured by mediastinal mass and basal 1/3 RV hypokinetic. Review of chest CT from one month prior to surgery revealed large anterior mediastinal mass severely compressing distal third of RV along with significant right atrial enlargement. Two possible hypotheses for RV failure were contemplated at this point. 1. Chronic compression of right ventricle leading to severe geometric distortion/increased wall tension of non-compressed RV segments leading to myocardial dysfunction. 2. Acute surgical injury or chronic compression of right coronary artery leading to infarct and scar. Patient was diuresed and TTE done on postoperative day 5 showed significant improvement in RV size/function. Repeat TTE done on postoperative day 30 showed further improvement in RV size/function. These findings suggest direct myocardial compression as a more likely etiology of RV failure as opposed to infarct. <h3>Conclusion</h3> This case presents a rare case of large mediastinal mass causing right ventricular dysfunction by compression. This case also illustrates the importance of multimodality imaging (TTE and CT) in the evaluation of RV failure.

Grace Under Pressure.

Grace Under Pressure.

The Effects of Cooling and Shrinkage on the Life of Polymer 3D Printed Injection Moulds.

3D Printed Injection Moulds (3DIM), commonly used for low volume production and prototyping purposes, are known to fail abruptly and have a comparatively shorter life than conventional moulds. Investigating the underlying critical factors affecting failure may help in reducing the risk of abrupt failures and possibly prolong the 3DIM tool life. A hypothesis that the cooling time of the Injection Moulding (IM) process is a critical factor for 3DIM tool failure has been proposed. The failure hypothesis has been validated by theoretical calculations, FEA simulations and experimental investigations. Experiments were performed using two different materials for the 3DIM tool (Visijet M3-X and Digital ABS) and an engineering thermoplastic (Lexan 943-A) as the moulding material. Results showed that cooling time was a critical factor on tool life and managing the thermal loading on a 3DIM tool could lead to increased tool life. The paper identifies cooling time as the critical factor affecting 3DIM tool life and presents a cooling regime that could possibly lead to prolonged tool life.

Tribological adaption of a failure hypothesis for fretting fatigue based on the local parameters slip amplitude and contact pressure

Fretting fatigue is a phenomenon that can lead to catastrophic damage. It can cause components designed in the classical way in relation to intrinsic material strengths to fail unexpectedly and prematurely. To solve this problem, a failure hypothesis is needed to assess fretting fatigue in a realistic way and thus predict the risk to the components. To this end, the specific fretting-fatigue strengths of the material pairing of 34CrNiMo6+QT vs. C45+N were determined for a permutation of the tribological parameters of slip amplitude and contact pressure. A double-actuated flat-pad test bench was used for this. This test bench can keep the aforementioned tribological parameters constant over the entire test period, regardless of the cyclical tensile load on the specimen. From these tests, an equation was developed that describes the fretting-fatigue strength as a function of slip amplitude and contact pressure. Additional experimental tests were then carried out on connecting-rod connections. The connecting rods failed due to fretting fatigue. The failure location and fatigue limits of the connecting rods were determined. By numerical analysis of the connecting rods, it was possible to determine the local value of mechanical stress, slip amplitude and contact pressure. This was followed by a comparison of equivalent stress and fretting-fatigue strength with the same parameter combination of slip amplitude and contact pressure for each point in the contact, whereby the equivalent stress was calculated using cutting-plane methods that can take the multiaxial stress state into account. The point with the highest degree of utilization is the calculated failure location. With this adapted failure hypothesis, the failure location could be determined with very good accuracy. However, the maximum error in determining the degree of utilization is about 25%.

Cerebral perfusion in posterior reversible encephalopathy syndrome measured with arterial spin labeling MRI

Background and purposeThe pathophysiologic basis of posterior reversible encephalopathy syndrome (PRES) remains controversial. Hypertension (HTN)-induced autoregulatory failure with subsequent hyperperfusion is the leading hypothesis, whereas alternative theories suggest vasoconstriction-induced hypoperfusion as the underlying mechanism. Studies using contrast-based CT and MR perfusion imaging have yielded contradictory results supporting both ideas. This work represents one of the first applications of arterial spin labeling (ASL) to evaluate cerebral blood flow (CBF) changes in PRES. Materials and methodsAfter obtaining Institutional Review Board approval, MRI reports at our institution from 07/2015 to 09/2020 were retrospectively searched and reviewed for mention of “PRES” and “posterior reversible encephalopathy syndrome.” Of the resulting 103 MRIs (performed on GE 1.5 Tesla or 3 Tesla scanners), 20 MRIs in 18 patients who met the inclusion criteria of clinical and imaging diagnosis of PRES and had diagnostic-quality pseudocontinuous ASL scans were included. Patients with a more likely alternative diagnosis, technically non-diagnostic ASL, or other intracranial abnormalities limiting assessment of underlying PRES features were excluded. Perfusion in FLAIR-affected brain regions was qualitatively assessed using ASL and characterized as hyperperfusion, normal, or hypoperfusion. Additional quantitative analysis was performed by measuring average gray matter CBF in abnormal versus normal brain regions. ResultsHTN was the most common PRES etiology (65%). ASL showed hyperperfusion in 13 cases and normal perfusion in 7 cases. A hypoperfusion pattern was not identified. Quantitative analysis of gray matter CBF among patients with visually apparent hyperperfusion showed statistically higher perfusion in affected versus normal appearing brain regions (median CBF 100.4 ml/100 g-min vs. 61.0 ml/ 100 g-min, p < 0.001). ConclusionElevated ASL CBF was seen in the majority (65%) of patients with PRES, favoring the autoregulatory failure hypothesis as a predominant mechanism. Our data support ASL as a practical way to assess and noninvasively monitor cerebral perfusion in PRES that could potentially alter management strategies.

An integrated fuzzy AHP approach for optimisation of theory of failures of multi-directional composite laminates

Owing to their improved engineering characteristics, composite materials have been widely used in various engineering fields over the past several decades. But unlike metals, composite materials' failure is progressive and may be initiated in the form of breaking of fibres, micro-cracks in the matrix, etc. but their propagation and final failure modes may be considerably different. The anisotropic behaviour of composite laminates makes it extremely difficult to formulate a failure theory since it requires performing bi-axial tests and plotting the failure envelopes. The failure strength of multi-direction composite materials has been the subject of decades of research. Since the last few decades, different failure theories have been used and subsequently refined to provide predictions. An attempt has also been made to provide designers with a ranking of the overall efficacy of each failure hypothesis. Fuzzy linguistic variables are frequently used to supplement the traditional analytic hierarchy process in capturing the decision maker's subjectiveness and fuzziness. The fuzzy AHP method is used in this paper to identify the best theory of failure for composite materials as a decision-making problem. Because of their effectiveness and simplicity, triangular fuzzy numbers are used to demonstrate the strength of each component in the hierarchy structure.

The Nerve Growth Factor Metabolic Pathway Dysregulation as Cause of Alzheimer's Cholinergic Atrophy.

The cause of the loss of basal forebrain cholinergic neurons (BFCNs) and their terminal synapses in the cerebral cortex and hippocampus in Alzheimer’s disease (AD) has provoked a decades-long controversy. The cholinergic phenotype of this neuronal system, involved in numerous cognitive mechanisms, is tightly dependent on the target-derived nerve growth factor (NGF). Consequently, the loss of BFCNs cholinergic phenotype in AD was initially suspected to be due to an NGF trophic failure. However, in AD there is a normal NGF synthesis and abundance of the NGF precursor (proNGF), therefore the NGF trophic failure hypothesis for the atrophy of BCNs was abandoned. In this review, we discuss the history of NGF-dependency of BFCNs and the atrophy of these neurons in Alzheimer’s disease (AD). Further to it, we propose that trophic factor failure explains the BFCNs atrophy in AD. We discuss evidence of the occurrence of a brain NGF metabolic pathway, the dysregulation of which, in AD explains the severe deficiency of NGF trophic support for the maintenance of BFCNs cholinergic phenotype. Finally, we revise recent evidence that the NGF metabolic dysregulation in AD pathology starts at preclinical stages. We also propose that the alteration of NGF metabolism-related markers in body fluids might assist in the AD preclinical diagnosis.

Oxidative Stress in Takotsubo Syndrome-Is It Essential for an Acute Attack? Indirect Evidences Support Multisite Impact Including the Calcium Overload-Energy Failure Hypothesis.

Indirect evidences in reviews and case reports on Takotsubo syndrome (TTS) support the fact that the existence of oxidative stress (OS) might be its common feature in the pre-acute stage. The sources of OS are exogenous (environmental factors including pharmacological and toxic influences) and endogenous, the combination of both may be present, and they are being discussed in detail. OS is associated with several pathological conditions representing TTS comorbidities and triggers. The dominant source of OS electrones are mitochondria. Our analysis of drug therapy related to acute TTS shows many interactions, e.g., cytostatics and glucocorticoids with mitochondrial cytochrome P450 and other enzymes important for OS. One of the most frequently discussed mechanisms in TTS is the effect of catecholamines on myocardium. Yet, their metabolic influence is neglected. OS is associated with the oxidation of catecholamines leading to the synthesis of their oxidized forms – aminochromes. Under pathological conditions, this pathway may dominate. There are evidences of interference between OS, catecholamine/aminochrome effects, their metabolism and antioxidant protection. The OS offensive may cause fast depletion of antioxidant protection including the homocystein-methionine system, whose activity decreases with age. The alteration of effector subcellular structures (mitochondria, sarco/endoplasmic reticulum) and subsequent changes in cellular energetics and calcium turnover may also occur and lead to the disruption of cellular function, including neurons and cardiomyocytes. On the organ level (nervous system and heart), neurocardiogenic stunning may occur. The effects of OS correspond to the effect of high doses of catecholamines in the experiment. Intensive OS might represent “conditio sine qua non” for this acute clinical condition. TTS might be significantly more complex pathology than currently perceived so far.

7-Aryl-7-deazapurine 3'-deoxyribonucleoside derivative as a novel lead for Chagas' disease therapy: in vitro and in vivo pharmacology.

BackgroundThe protozoan Trypanosoma cruzi is auxotrophic for purines and causes Chagas’ disease (CD), a neglected illness affecting >6 million people. Combining the 3-deoxyribofuranose part of cordycepin with the modified purine ring of a nucleoside ‘hit’ led to the discovery of 4-amino-5-(4-chlorophenyl)-N7-(3′-deoxy-β-d-ribofuranosyl)-pyrrolo[2,3-d]pyrimidine (Cpd1), revealing promising anti-T. cruzi activity.ObjectivesTo further evaluate Cpd1 in vitro and in vivo to fully assess its therapeutic potential against CD, covering cell culture sterilization through washout assays, drug combination with benznidazole and long-term administration in T. cruzi-infected mice.ResultsAlthough less susceptible to Cpd1 than amastigotes, trypomastigotes present an impaired capacity to successfully establish intracellular infection of cardiac cultures. Combination of benznidazole with Cpd1 indicated no interaction (additive effect) (FIC index = 0.72) while administration to mice at one-tenth of the optimal dose (2.5 mg/kg and 10 mg/kg for Cpd1 and benznidazole, respectively) suppressed parasitaemia but failed to avoid mortality. Long-term treatment (60 days) gave a rapid drop of the parasitaemia (>98% decline) and 100% mice survival but only 16% cure. In vitro washout experiments demonstrated that although parasite release into the supernatant of infected cardiac cultures was reduced by >94%, parasite recrudescence did occur after treatment.ConclusionsParasite recrudescence did occur after treatment corroborating the hypothesis of therapeutic failure due to subpopulations of dormant forms and/or genetic factors in persister parasites involved in natural drug resistance.

Antipsychotics withdrawal in adults with intellectual disability and challenging behaviour: study protocol for a multicentre double-blind placebo-controlled randomised trial

BackgroundIn people with intellectual disability (ID) and challenging behaviour, antipsychotics (AP) are often used off-label and for a long period. Despite a lack of evidence for efficacy for challenging behaviour and concerns about common and clinically relevant side effects, complete withdrawal often fails. We postulate three possible hypotheses for withdrawal failure: 1. Influence of subjective interpretation of behavioural symptoms by caregivers and family; 2. Beneficial effects from AP treatment on undiagnosed psychiatric illness, through improvement in sleep or a direct effect on behaviour; and 3. Misinterpretation of withdrawal symptoms as a recurrence of challenging behaviour.MethodsTo investigate our hypotheses, we have designed a multicentre double-blind, placebo-controlled randomised trial in which AP (pipamperone or risperidone) are withdrawn. In the withdrawal group, the AP dose is reduced by 25% every 4 weeks and in the control group the dose remains unaltered. Behaviour, sleep, psychiatric disorders, withdrawal symptoms and side effects will be measured and compared between the two groups. If drop-out from the protocol is similar in both groups (non-inferiority), the first hypothesis will be supported. If drop-out is higher in the withdrawal group and an increase is seen in psychiatric disorders, sleep problems and/or behavioural problems compared to the control group, this suggests effectiveness of AP, and indications for AP use should be reconsidered. If drop-out is higher in the withdrawal group and withdrawal symptoms and side effects are more common in the withdrawal group compared to the control group, this supports the hypothesis that withdrawal symptoms contribute to withdrawal failure.DiscussionIn order to develop AP withdrawal guidelines for people with ID, we need to understand why withdrawal of AP is not successful in the majority of people with ID and challenging behaviour. With this study, we will bridge the gap between the lack of available evidence on AP use and withdrawal on the one hand and the international policy drive to reduce prescription of AP in people with ID and challenging behaviour on the other hand.Trial registrationThis trial is registered in the Netherlands Trial Register (NTR 7232) on October 6, 2018 (www.trialregister.nl).

Evaluation of Clinical, Gram Stain, and Microbiological Cure Outcomes in Men Receiving Azithromycin for Acute Nongonococcal Urethritis: Discordant Cures Are Associated With Mycoplasma genitalium Infection.

In men with nongonococcal urethritis (NGU), clinicians and patients rely on clinical cure to guide the need for additional testing/treatment and when to resume sex, respectively; however, discordant clinical and microbiological cure outcomes do occur. How accurately clinical cure reflects microbiological cure in specific sexually transmitted infections (STIs) is unclear. Men with NGU were tested for Neisseria gonorrhoeae, Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Trichomonas vaginalis, urethrotropic Neisseria meningitidis ST-11 clade strains, and Ureaplasma urealyticum (UU). Men received azithromycin 1 g and returned for a 1-month test-of-cure visit. In MG infections, we evaluated for the presence of macrolide resistance-mediating mutations (MRMs) and investigated alternate hypotheses for microbiological treatment failure using in situ shotgun metagenomic sequencing, phylogenetic analysis, multilocus sequence typing analyses, and quantitative PCR. Of 280 men with NGU, 121 were included in this analysis. In the monoinfection group, 52 had CT, 16 had MG, 7 had UU, 10 had mixed infection, and 36 men had idiopathic NGU. Clinical cure rates were 85% for CT, 100% for UU, 50% for MG, and 67% for idiopathic NGU. Clinical cure accurately predicted microbiological cure for all STIs, except MG. Discordant results were significantly associated with MG-NGU and predominantly reflected microbiological failure in men with clinical cure. Mycoplasma genitalium MRMs, but not MG load or strain, were strongly associated with microbiological failure. In azithromycin-treated NGU, clinical cure predicts microbiological cure for all STIs, except MG. Nongonococcal urethritis management should include MG testing and confirmation of microbiological cure in azithromycin-treated MG-NGU when MRM testing is unavailable.

Understanding the dynamics of resource curse in G7 countries: The role of natural resource rents and the three facets of financial development

In this study, we aim to reinvestigate the resource curse hypothesis with a special emphasis on the institutional failure hypothesis. Our sample is based on G7 countries, known to have a high degree of institutional strength, for four decades from 1980 to 2018. We first evaluate the presence or absence of resource curse by exploring the linkages between natural resources rents and financial development in G7 countries and then look at the two channels of this resource curse, i.e., Financial Markets or Financial Institutions, by utilizing the financial development index and its sub-indices proposed by (Svirydzenka, 2016). Our results refute the presence of resource curse in the long run for G7 economies; however, we clearly identify that this blessing is routed only through the development of Financial markets. There is strong evidence of hemorrhaging in financial institutions led by the abundance and utilization of natural resources. Our findings offer new insights on the linkages of the institutional failure hypothesis with the resource curse hypothesis and help countries develop short-term and long-term strategies to utilize their natural resources endowment optimally.

Influence of High Electrical Currents on WEC Formation in Rolling Bearings

Premature bearing failures due to white etching cracks (WECs) occur when the rolling contact is subjected to a so-called additional load such as an electrical current flow through the bearing in addition to the pure rolling load. Tests with oil-lubricated roller bearings and greased ball bearings showed that high electrical currents are a very critical WEC trigger. The influence of current intensity, electrical polarity, and load type (stationary ring load or rotating ring load) on WEC formation was proven by the performed bearing tests, whereas the influence of lubricant was relatively low. Based on the findings, the failure hypothesis “energetic WEC fatigue” was extended for high electrical currents.

Multiaxial elastic, yield and failure behaviour of bonded joints using a hot-curing epoxy film adhesive: analytical and experimental investigation

ABSTRACT Film adhesives provide an excellent method for joint manufacturing with minimum waste and highly accurate thickness. Here, the multiaxial behaviour in terms of elasticity, yielding and failure of a hot curing epoxy film adhesive was analytically and experimentally investigated. Butt, scarf and thick adherend shear test joints were tested under static conditions. The variation between normal and shear stress among the different joint types allowed the variation of the multiaxiality using the same experimental set-up with a uniaxial testing machine. A consistent set of elastic constants was obtained by carefully calibrated displacement sensors, proper consideration of adherend elasticity and of lateral strain restrictions. The presentation of the von Mises equivalent stress and the hydrostatic pressure at the point of yield and failure indicated that hydrostatic stresses have a large influence on the static strength of the film adhesive. Failure and yield conditions were formulated based on linear or exponential forms of Drucker-Prager type models. A strain-based failure hypothesis was formulated using the second invariant of the strain deviator, and the first invariant of the strain tensor. Results showed that high values of volumetric strain are detrimental to the strength of the adhesive joints.

Accounting asymmetries in the long-run nexus between globalization and environmental sustainability in the United States: An aggregated and disaggregated investigation

In recent years, the number of studies on the relationship between globalization and ecological footprint is steadily increasing, yet the literature lacks any formal consensus. Previous studies unveil beneficial as well as harmful effects of globalization on the environment. Furthermore, most of the scholars rely on linear methods to investigate this relationship, which can produce biased outcomes when non-linearities exist in data. Unquestionably, the United States played a leading role in increasing global connectivity; however, the present US administration has demonstrated not only a penchant for isolationism by keeping certain critical resources, technologies, and manufacturing capacities in the US but also the tendency to ignore environmental concerns both domestically and globally. On this backdrop, this study uses asymmetric ARDL, and asymmetric causality methods to investigate the asymmetric relationship between globalization and the ecological footprint of the US. Additionally, the disaggregated asymmetric impacts of social, economic, and political globalization on footprint are also ascertained. The results indicate non-linear cointegration among variables. The long-run estimations reveal that a 1% positive change in overall globalization and in economic globalization increases ecological footprint by 1.32 and 0.72%, respectively, while a similar 1% negative change alleviates footprint by 6.75 and 1.05%, respectively. The outcomes elucidate much more dominant effects associated with negative changes in total and economic globalization. In contrast, positive changes in social globalization improve the environment by mitigating ecological footprint. Interestingly, positive shocks to political globalization stimulate footprint, indicating the validity of the environmental governance failure hypothesis. Further, Granger causality from positive changes in globalization to the footprint is found. Lastly, this study is concluded by comprehensive policy implications, including policy regarding FDI, trade, and enhancing social globalization, among others.

Triheptanoin Mitigates Brain ATP Depletion and Mitochondrial Dysfunction in a Mouse Model of Alzheimer's Disease.

Brain energy failure is an early pathological event associated with synaptic dysfunction in Alzheimer's disease (AD). Thus, mitigation or enhancement of brain energy metabolism may offer a therapeutic avenue. However, there is uncertainty as to what metabolic process(es) may be more appropriate to support or augment since metabolism is a multiform process such that each of the various metabolic precursors available is utilized via a specific metabolic pathway. In the brain, these pathways sustain not only a robust rate of energy production but also of carbon replenishment. Triheptanoin, an edible odd-chain fatty acid triglyceride, is uncommon in that it replenishes metabolites in the tricarboxylic acid cycle (TCA) cycle via anaplerosis in addition to fueling the cycle via oxidation, thus potentially leading to both carbon replenishment and enhanced mitochondrial ATP production. To test the hypothesis that triheptanoin is protective in AD, we supplied mice with severe brain amyloidosis (5×FAD mice) with dietary triheptanoin for four and a half months, followed by biological and biochemical experiments to examine mice metabolic as well as synaptic function. Triheptanoin treatment had minimal impact on systemic metabolism and brain amyloidosis as well as tauopathy while attenuating brain ATP deficiency and mitochondrial dysfunction including respiration and redox balance in 5×FAD mice. Synaptic density, a disease hallmark, was also preserved in hippocampus and neocortex despite profound amyloid deposition. None of these effects took place in treated control mice. These findings support the energy failure hypothesis of AD and justify investigating the mechanisms in greater depth with ultimate therapeutic intent.

Neuroimmune Response in Natural Preclinical Scrapie after Dexamethasone Treatment.

A recently published report on chronic dexamethasone treatment for natural scrapie supported the hypothesis of the potential failure of astroglia in the advanced stage of disease. Herein, we aimed to extend the aforementioned study on the effect of this anti-inflammatory therapy to the initial phase of scrapie, with the aim of elucidating the natural neuroinflammatory process occurring in this neurodegenerative disorder. The administration of this glucocorticoid resulted in an outstanding reduction in vacuolation and aberrant protein deposition (nearly null), and an increase in glial activation. Furthermore, evident suppression of IL-1R and IL-6 and the exacerbation of IL-1α, IL-2R, IL-10R and IFNγR were also demonstrated. Consequently, the early stage of the disease is characterized by an intact neuroglial response similar to that of healthy individuals attempting to re-establish homeostasis. A complex network of neuroinflammatory markers is involved from the very early stages of this prion disease, which probably becomes impaired in the more advanced stages. The in vivo animal model used herein provides essential observations on the pathogenesis of natural scrapie, as well as the possibility of establishing neuroglia as potential target cells for anti-inflammatory therapy.

A mechanistic hypothesis for the impairment of synaptic plasticity by soluble Aβ oligomers from Alzheimer's brain.

It is increasingly accepted that early cognitive impairment in Alzheimer's disease results in considerable part from synaptic dysfunction caused by the accumulation of a range of oligomeric assemblies of amyloid β-protein (Aβ). Most studies have used synthetic Aβ peptides to explore the mechanisms of memory deficits in rodent models, but recent work suggests that Aβ assemblies isolated from human (AD) brain tissue are far more potent and disease-relevant. Although reductionist experiments show Aβ oligomers to impair synaptic plasticity and neuronal viability, the responsible mechanisms are only partly understood. Glutamatergic receptors, GABAergic receptors, nicotinic receptors, insulin receptors, the cellular prion protein, inflammatory mediators, and diverse signaling pathways have all been suggested. Studies using AD brain-derived soluble Aβ oligomers suggest that only certain bioactive forms (principally small, diffusible oligomers) can disrupt synaptic plasticity, including by binding to plasma membranes and changing excitatory-inhibitory balance, perturbing mGluR, PrP, and other neuronal surface proteins, down-regulating glutamate transporters, causing glutamate spillover, and activating extrasynaptic GluN2B-containing NMDA receptors. We synthesize these emerging data into a mechanistic hypothesis for synaptic failure in Alzheimer's disease that can be modified as new knowledge is added and specific therapeutics are developed.

Effect of Rock Stress Evolution on Failure Under Transverse Plain Water Jet

The subject of this investigation is the stress evolution characteristics of rock impacted by transverse plain water jet (PWJ), including the application of stress evolution in the interpretation of the laws of breaking rocks (including artificial rock). Based on the semi-infinite plane theory, an analytical solution of the stress evolution of rock subjected to transverse jet loading is obtained, and the evolution of the stress state variable F of the rock microelement based on the Mohr–Coulomb criterion is also obtained. Then, elastic brittle failure and elastic-brittle damage of rock microelements are analyzed. Besides, an expression of the damage variable D based on elastic-brittle failure assumption is proposed. The analysis shows that the peak values of the F evolution curve determines the failure of the rock microelement based on the elastic-brittle failure hypothesis. The area SF surrounded by the evolution curve F and the line (F = F0) is positively correlated with the damage variable D, which can be used to qualitatively explain the time dependence of breaking rock using a transverse PWJ. In addition, the method based on damage variable D presented in this paper shows great potential in quantitative analysis of time dependence of rock failure.