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Highlights • A Gamma accelerated degradation model based on the principle of degradation mechanism invariance is proposed. • The existence of the maximum likelihood estimate of the parameters of the proposed model is proved. • The approximate confidence interval for the shape parameter based on Cornish–Fisher expansion is derived. • The generalized confidence intervals for other model parameters and some important quantities are developed. Abstract This paper proposes a Gamma constant-stress accelerated degradation model based on the principle of the degradation mechanism invariance. The maximum likelihood estimators of the parameters of the proposed model are derived. Based on Cornish–Fisher expansion, the approximate confidence interval for the shape parameter of the Gamma degradation process is developed. Since it is difficult to obtain the exact confidence intervals for other model parameters and some quantities such as the mean degradation in unit time, the quantile and the reliability function of the lifetime at the normal stress level, the generalized confidence intervals for these quantities are proposed. The percentiles of the proposed generalized pivotal quantities can be obtained by the simulation. The performances of the proposed confidence intervals are evaluated by the Monte Carlo simulation method. In the simulation study, the proposed confidence intervals are compared with the Wald and the bootstrap- p confidence intervals. The simulation results show that the proposed confidence intervals outperform the Wald and the bootstrap- p confidence intervals in terms of the coverage percentage. Finally, a real example is used to illustrate the proposed procedures. [ABSTRACT FROM AUTHOR]

This study develops inferential procedures for the generalized exponential stress-strength model. A generalized confidence interval for the stress-strength reliability is derived when the stress and strength variables follow the generalized exponential distributions with the common rate parameters. Moreover, based on the Fisher Z transformation, a modified generalized confidence interval for the stress-strength reliability with the unequal rate parameters is proposed. The performance of the proposed procedures is evaluated by Monte Carlo simulation. The simulation results show that the coverage percentages of the proposed generalized confidence intervals are quite close to the nominal coverage probabilities, even for small sample sizes. Finally, an example is used to illustrate the proposed procedures. [ABSTRACT FROM AUTHOR]

The presence of respirable dust in underground space causes serious health hazards for workers while in tunnel drilling, which could result in pneumoconiosis and silicosis. In order to control the dust dispersion and improve the environment quality of underground space while in tunnel drilling, an innovative drilling system with a reverse circulation (RC) air hammer is proposed. In addition, the structure of the RC air hammer with double-row suction nozzles is specially designed, which contributes to the improvement of suction capacity of the air hammer. Totally four structural parameters of the RC air hammer are optimized, and the effects of four structural parameters on suction capacity of the air hammer also have been investigated by means of Computational Fluid Dynamics (CFD) simulation method, which is crucial for the dust suppression performance of the RC air hammer drilling system. Simulation results have shown that the inclination angle ( θ s ) has the greatest influence on suction capacity among the four structural parameters, which is descendingly followed by the defection angle ( θ d ), the vertical space ( L ) and the horizontal space ( S ). Meanwhile, the optimal parameters configuration of the air hammer with double-row suction nozzles has been obtained. Additionally, the laboratory and field tests on the RC drilling system with optimal parameter configuration have been subsequently conducted, and no dust or rock cuttings were suspended in the underground space, which dramatically improves the internal working conditions of tunneling drilling. In conclusion, the suction capacity of the air hammer with optimized structural configuration is outstanding, and the dust suppression performance of the RC air hammer drilling system is excellent, which is applicable to eliminate the dust dispersion in underground tunnel drilling. [ABSTRACT FROM AUTHOR]

In this paper, the prediction intervals of the off-line and online remaining useful lifetimes for the k -out-of- n load-sharing system is studied under the equal load-sharing rule. When the lifetime of each component follows the Weibull distribution, the maximum likelihood estimators and two-stage estimators of the model parameters, system reliability and mean lifetime are proposed. The Wald and bootstrap-type confidence intervals for the model parameters are developed. The performance of the proposed prediction intervals is assessed by using Monte Carlo simulation. The simulation results indicate that the coverage probabilities of the proposed bootstrap-type prediction intervals are close to the nominal confidence levels even if the sample size is small. A real example is utilized to illustrate the proposed bootstrap-type prediction interval methods. • Distributions of off-line and online remaining useful life are derived. • Existence of maximum likelihood estimates is discussed. • Two-stage estimators of model parameters are provided. • Prediction intervals of off-line and online remaining useful life are obtained. [ABSTRACT FROM AUTHOR]

Abstract: This paper derives the exact confidence intervals for the exponential step-stress accelerated life-testing model as well as the approximate confidence intervals for the k-step exponential step-stress accelerated life-testing model under progressive Type-II censoring. A Monte Carlo simulation study is carried out to examine the performance of these confidence intervals. Finally, an example is given to illustrate the proposed procedures. [Copyright &y& Elsevier]

Background: Adolescence is considered a critical time of life for emotional development in humans. During this period the amygdala, which regulates emotions, undergoes structural reorganization. Auditory fear conditioning, a form of amygdala-dependent emotional learning, occurs differently in juvenile and adult rodents. Because this learning is mediated by plastic changes in the thalamic and cortical inputs to lateral amygdala (LA), we investigated changes in synaptic properties of these inputs during juvenile-to-adult transition. Methods: Whole-cell patch clamp recording in amygdala slices from juvenile and young adult mice was conducted to investigate long-term potentiation and basal synaptic transmission in the thalamic and cortical inputs to LA. Results: We show that physiological differences develop between thalamic and cortical afferents to LA during the juvenile-to-adult transition. Although in juvenile mice the two pathways have similar properties, in young adult mice the thalamic pathway has reduced plasticity, increased number of quanta released by a single action potential, and decreased proportion of silent synapses. Conclusions: Changes in thalamic but not cortical inputs to amygdala take place during late development and might contribute to differences in auditory fear conditioning between juveniles and adults. [Copyright &y& Elsevier]

Abstract: Polypropylene-based nanocomposites filled with polypropylene-grafted multiwalled carbon nanotubes (PP-g-MWNT) were compared to PP samples filled with pristine MWNT. The effect of such additives on the structure and morphology of the polymer matrix was studied by small angle X-ray scattering (SAXS), wide angle X-ray diffraction (WAXD), polarized light optical microscopy (PLOM) and differential scanning calorimetry (DSC). PP-g-MWNT allowed a more efficient and unhindered crystallization at a lamellar level, while MWNT disrupted the order of lamellar stacks, probably because of their tendency to aggregate. A common trend of tensile properties and lamellar morphology as a function of filler content was noted in the series filled with functionalized carbon nanotubes. [Copyright &y& Elsevier]

Abstract: A small amount of cyano groups in poly(styrene-co-acrylonitrile) (SAN) was converted to oxazoline groups through reaction with 2-aminoethanol. Reactive melt blending of oxazoline-containing SAN and acidified multiwalled carbon nanotubes (MWCNTs) leads to the grafting of polymer chains onto MWCNTs arising from reactions between oxazoline and carboxylic acid groups. Spectroscopic, thermal and microscopic techniques confirmed the successful grafting of SAN onto MWCNTs. This method is comparatively simpler and greener than a previously reported method, and can be adopted to graft other acrylonitrile-containing polymers onto MWCNTs. [Copyright &y& Elsevier]

Abstract: Polypropylene (PP) was grafted onto multiwalled carbon nanotubes (MWNTs) by melt blending PP containing 0.6wt% of maleic anhydride and amine-functionalized MWNTs. The mechanical properties of PP/PP-g-MWNTs composites were evaluated. When PP was reinforced with pristine MWNTs, its Young’s modulus and tensile strength were increased, but its ultimate strain and toughness were reduced. On the other hand, the Young’s modulus, tensile strength, ultimate strain and toughness of PP were improved by 108, 141, 49 and 287%, respectively, by the addition of PP-g-MWNTs with an effective MWNTs content of 1.5wt%. PP-g-MWNTs are more effective than organoclay in enhancing the mechanical properties of PP. [Copyright &y& Elsevier]

Transiently local release of Ca2+ from the sarcoplasmic reticulum (SR) activates nearby Ca2+-activated K+ channels to produce spontaneous transient outward currents (STOCs) in smooth muscle cells. The purpose of the present study was to investigate the possible effect of peroxynitrite (ONOO−) on STOCs in mesenteric arteriolar smooth muscle cells (ASMCs) and decide whether Ca2+ mobilization was involved in STOCs alteration by ONOO−. STOCs were recorded and characterized using the perforated whole-cell patch-clamp configuration. The results demonstrated that STOCs activity was greatly suppressed by removal of extracellular Ca2+; by addition of nifedipine, a specific inhibitor of L-type voltage-gated Ca2+ channels (VGCCs); or by addition of ryanodine, a SR ryanodine receptors (RyRs) blocker. In contrast, both caffeine, a RyR activator, and 2-aminoethoxydiphenylborate (2-APB), a membrane-permeable inositol 1,4,5-trisphosphate receptors, (IP3R) antagonist, increased STOCs activity. 3-morpholinosydnonimine (SIN-1), an ONOO− donor, at concentrations of 20–200 μM, induced a dose-dependent enhancement of STOCs in ASMCs and led to conspicuous increases in STOCs frequency and amplitude, which were prevented by prior exposure to low external Ca2+ (200 nM), ryanodine (10 μM), or nifedipine (10 μM). In contrast, caffeine (0.5 mM) did not further stimulate STOCs in ASMCs preincubated with SIN-1, and pretreatment with 2-APB (50 μM) had little effect on ONOO−-induced STOCs activation. These findings suggest that complex Ca2+-mobilizing pathways, including external Ca2+ influx through VGCCs activation and subsequent internal Ca2+ release through RyRs but not IP3Rs, are involved in ONOO−-mediated STOCs enhancement in ASMCs. [Copyright &y& Elsevier]

Peroxynitrite (ONOO−) has been recently known to act as a potent cytotoxin during pathogenesis of various diseases. This study aimed to investigate the possible effect of ONOO− on the cremaster muscle arteriolar reactivity in response to noradrenaline and subsequently determined whether membrane hyperpolarization and potassium channel activation were involved in ONOO−-induced alteration of arteriolar reactivity. The results demonstrated that 1) ONOO− could decrease arteriolar reactivity in a time- and concentration-dependent manner with no significant alteration of arteriolar diameter; 2) Superfusion with 20 μM ONOO− over 40 minutes showed slight but not significant influence on the resting potential (Em) of arteriolar smooth muscle cells (ASMCs). However, ASMCs subjected to 50 or 100 μM ONOO− administration were significantly hyperpolarized. As control, treatment with 50 μM decomposed ONOO− or Kreb''s solution had little effect on the Em of ASMCs; 3) ONOO−-induced arteriolar hyporeactivity could be greatly reversed by co-administration of KCl and partially by TEA. The above results indicated that membrane hyperpolarization and potassium channel activation were preferentially responsible for the reduction of cremaster muscle arteriolar reactivity after exposure to ONOO−. [Copyright &y& Elsevier]

• Presents accurate reliability inference for degradation with small samples. • Proposes exact test for the population heterogeneity under Wiener process. • Derives general pivotal quantities for parameters and important quantities. The Wiener process is often used to fit degradation data in reliability modeling. Though there is an abundant literature covering the inference procedures for the Wiener model, their performance may not be satisfactory when the sample size is small, which is often the case in degradation data analysis. In this paper, we focus on the accurate reliability inference based on the Wiener process with random drift parameter for degradation data. We propose an exact procedure to test whether there is population heterogeneity. An exact confidence interval (CI) procedure for the diffusion parameter of the Wiener process is also obtained. Generalized confidence intervals (GCIs) are proposed for model parameters and some commonly used reliability metrics such as the quantile, the reliability function, etc. Furthermore, a generalized prediction interval (GPI) for the future degradation levels is obtained. The performance of the proposed GCIs and GPI is assessed by the Monte Carlo simulation. The simulation results show that the proposed interval procedures outperform existing method such as the Wald, the bootstrap- p and the likelihood-ratio-based CIs in terms of the coverage probability, and our proposed procedures have desirable properties even under small sample sizes. Finally, an example is used to illustrate the proposed procedures. [ABSTRACT FROM AUTHOR]

Abstract: This study investigated whether adenosine A1 receptors could modulate respiratory rhythm in mammals. Experiments were performed in in vitro brainstem slice preparations from neonatal rats. These preparations included the medial region of Nucleus Retrofacialis (mNRF) with the hypoglossal nerve (XII nerve) rootlets retained. The rhythmical discharges of the biphasic expiratory (biphasic E) neurons/inspiratory neurons (I neurons) and activities of the XII nerve rootlets were simultaneously recorded by using extracellular microelectrodes and suction electrodes, respectively. Roles of adenosine A1 receptors in modulation of respiratory rhythm were investigated by administration of the adenosine A1 receptor agonist R-phenylisopropyl-adenosine (R-PIA, 10μM) and its specific antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 2μM). DPCPX decreased the respiratory period (27.19%) and expiratory duration (28.27%) of biphasic E neurons and at the same time increased the peak discharge frequency (48.13%). By contrast, R-PIA produced opposite effects. On the other hand, the effects of DPCPX and R-PIA on the I neurons were similar to that on the biphasic E neurons except that R-PIA shortened the discharge duration of I neurons (34.12%) and decreased the peak discharge frequency (37.75%) in the middle phase of inspiration, but not in the initial and terminal phases. These results suggest that adenosine A1 receptors are involved in the phase-switching between expiration and inspiration by affecting biphasic E neurons. Activation of adenosine A1 receptors may modulate the inhibitory synaptic inputs from I neurons to biphasic E neurons. [Copyright &y& Elsevier]

Brain systems that promote maintenance of homeostasis in the face of stress have significant adaptive value. A growing body of work across species demonstrates a critical role for the amygdala in promoting homeostasis by regulating physiological and behavioral responses to stress. This review focuses on an emerging body of evidence that has begun to delineate the contribution of specific long-range amygdala circuits in mediating the effects of stress. After summarizing the major anatomical features of the amygdala and its connectivity to other limbic structures, we discuss recent findings from rodents showing how stress causes structural and functional remodeling of amygdala neuronal outputs to defined cortical and subcortical target regions. We also consider some of the environmental and genetic factors that have been found to moderate how the amygdala responds to stress and relate the emerging preclinical literature to the current understanding of the pathophysiology and treatment of stress-related neuropsychiatric disorders. Future effort to translate these findings to clinics may help to develop valuable tools for prevention, diagnosis, and treatment of these diseases. [ABSTRACT FROM AUTHOR]

The role of the amygdala in mediating stress coping has been long appreciated. However, basolateral amygdala (BLA) projection neurons (PNs) are organized into discrete output circuits, and it remains unclear whether stress differentially impacts these circuits. Mice were exposed to acute restraint stress or chronic restraint stress (CRS), and c-fos expression was measured as a proxy for neuronal activation in Retrobead retrogradely labeled dorsomedial prefrontal cortex–targeting PNs (BLA→dmPFC) and non-dmPFC-targeting PNs (BLA↛dmPFC). Next, the effects of CRS on neuronal firing and membrane potassium channel current were examined via ex vivo electrophysiology in these neuronal populations and correlated with anxiety-like behavior, as measured in the elevated plus maze and novel open field tests. Lastly, the ability of virus-mediated overexpression of subtype 2 of small-conductance, calcium-activated potassium (SK2) channel in BLA↛dmPFC PNs to negate the anxiety-related effects of CRS was assessed. BLA→dmPFC PNs were transiently activated after CRS, whereas BLA↛dmPFC showed sustained c-fos expression and augmented firing to external input. CRS led to a loss of SK2 channel–mediated currents in BLA↛dmPFC PNs, which correlated with heightened anxiety-like behavior. Virus-mediated maintenance of SK2 channel currents in BLA↛dmPFC PNs prevented CRS-induced anxiety-like behavior. Finally, CRS produced persistent activation of BLA PNs targeting the ventral hippocampus, and virally overexpressing SK2 channels in this projection population were sufficient to prevent CRS-induced anxiety-like behavior. The current data reveal that chronic stress produces projection-specific functional adaptations in BLA PNs. These findings offer new insight into the neural circuits that contribute to stress-induced psychopathology. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic stress exposure increases the risk of developing various neuropsychiatric illnesses. The behavioral sequelae of stress correlate with dendritic hypertrophy and glutamate-related synaptic remodeling at basolateral amygdala projection neurons (BLA PNs). Yet, though BLA PNs are functionally heterogeneous with diverse corticolimbic targets, it remains unclear whether stress differentially impacts specific output circuits. Methods Confocal imaging was used to reconstruct the morphology of mouse BLA PNs with the aid of retrograde tracing and biocytin staining. The synaptic activity in these neurons was measured with in vitro electrophysiology, and anxiety-like behavior of the mice was assessed with the elevated plus maze and open field test. Results Chronic restraint stress (CRS) produced dendritic hypertrophy across mouse BLA PNs, regardless of whether they did (BLA→dorsomedial prefrontal cortex [dmPFC]) or did not (BLA↛dmPFC) target dmPFC. However, CRS increased the size of dendritic spine heads and the number of mature, mushroom-shaped spines only in BLA↛dmPFC PNs, sparing neighboring BLA→dmPFC PNs. Moreover, the excitatory glutamatergic transmission was also selectively increased in BLA↛dmPFC PNs, and this effect correlated with CRS-induced increases in anxiety-like behavior. Segregating BLA↛dmPFC PNs based on their targeting of ventral hippocampus (BLA→ventral hippocampus) or nucleus accumbens (BLA→nucleus accumbens) revealed that CRS increased spine density and glutamatergic signaling in BLA→ventral hippocampus PNs in a manner that correlated with anxiety-like behavior. Conclusions Chronic stress caused BLA PN neuronal remodeling with a previously unrecognized degree of circuit specificity, offering new insight into the pathophysiological basis of depression, anxiety disorders, and other stress-related conditions. [ABSTRACT FROM AUTHOR]

Emerging evidence indicates that loss of inhibitory tone in amygdala with its subsequent overactivation contributes to the development of multiple mental disorders such as anxiety disorders and post-traumatic stress disorder (PTSD). Harmine is a member of natural β-carboline alkaloids which can readily cross the blood brain barrier and displays significant antidepressant and anxiolytic effects in rodents. However, the underlying neurobiological mechanisms are largely unknown. Here, by using whole-cell patch clamp recordings in in vitro amygdala slices, we examined the effect of harmine on glutamatergic and GABAergic transmission onto basal amygdala (BA) projection neurons (PNs). Our results showed that harmine affected neither the amplitude nor the frequency of spontaneous and miniature excitatory postsynaptic currents (sEPSCs/mEPSCs) of PNs. By contrast, it markedly increased both the amplitude and frequency of the spontaneous inhibitory postsynaptic currents (sIPSCs). For mIPSCs, only an increase of their frequency but not amplitude was observed following harmine perfusion, suggesting that harmine might act through presynaptic mechanism. In parallel, a reduction of paired-pulse ratio of evoked IPSCs emerged in the presence of harmine. Furthermore, the intrinsic excitability of PNs was dramatically decreased upon harmine treatment. Together, our study suggests that harmine selectively potentiates the inhibitory but not excitatory transmission onto BA PNs, which may contribute to its antidepressant and anxiolytic influence. [ABSTRACT FROM AUTHOR]

Background Maintaining gamma-aminobutyric acidergic (GABAergic) inhibition in the amygdala within a physiological range is critical for the appropriate expression of emotions such as fear and anxiety. The synaptic GABA type A receptor (GABA A R) is generally known to mediate the primary component of amygdala inhibition and prevent inappropriate expression of fear. However, little is known about the contribution of the extrasynaptic GABA A R to amygdala inhibition and fear. Methods By using mice expressing green fluorescent protein in interneurons (INs) and lacking the δ subunit-containing GABA A R (GABA A (δ)R), which is exclusively situated in the extrasynaptic membrane, we systematically investigated the role of GABA A (δ)R in regulating inhibition in the lateral amygdala (LA) and fear learning using the combined approaches of immunohistochemistry, electrophysiology, and behavior. Results In sharp contrast to the established role of synaptic GABA A R in mediating LA inhibition, we found that either pharmacological or physiological recruitment of GABA A (δ)R resulted in the weakening of GABAergic transmission onto projection neurons in LA while leaving the glutamatergic transmission unaltered, suggesting disinhibition by GABA A (δ)R. The disinhibition arose from IN-specific expression of GABA A (δ)R with its activation decreasing the input resistance of local INs and suppressing their activation. Genetic deletion of GABA A (δ)R attenuated its role in suppressing LA INs and disinhibiting LA. Importantly, the GABA A (δ)R facilitated long-term potentiation in sensory afferents to LA and permitted the expression of learned fear. Conclusions Our findings suggest that GABA A (δ)R serves as a brake rather than a mediator of GABAergic inhibition in LA. The disinhibition by GABA A (δ)R may help to prevent excessive suppression of amygdala activity and thus ensure the expression of emotion. [ABSTRACT FROM AUTHOR]

Objective: To explore possible reasons for the incidence of a pituitary abscess following transsphenoidal surgery and determine the most effective treatment. Methods: A series of 12 patients who had undergone transsphenoidal surgery in other hospitals before being treated at Peking Union Medical College Hospital were reviewed. The presence of a pituitary abscess was confirmed when pus was intraoperatively observed within the sella turcica. All patients were treated with debridement of the abscess, nine among whom through a transsphenoidal approach and the other three via a craniotomy, followed by antibiotic treatment and hormone replacement therapy. The mean follow-up time was 27.0 months (range from 3.0 to 79.0 months). Results: Headache (92%), panhypopituitarism (58%) and visual disturbance (50%) were the most common clinical indicators of a pituitary abscess. Imaging tests demonstrated a pituitary mass in all patients, with seven (58%) manifested with typical magnetic resonance features of an abscess. Ten patients (83%) were correctly diagnosed preoperatively. During surgical exploration, six presented with severe inflammation or an abscess within the sphenoidal sinus. Causative organisms were identified in five patients (42%). After surgical and antibiotic therapies, all patients fully recovered except for two presenting with severe visual impairment. Six patients (50%) required hormone replacement therapy. Conclusion: Retrograde infection from the sphenoid sinus may be a vital mechanism underlying the formation of a pituitary abscess following transsphenoidal surgery. Debridement of the abscess through surgical approaches combined with antibiotic treatment has been found to yield positive outcomes. [ABSTRACT FROM AUTHOR]

This article describes a case of confirmed adrenocorticotropic hormone (ACTH)-secreting macroadenoma in Addison's disease due to adrenal tuberculosis. The patient was a 58-year-old woman with Addison's disease who presented with headache and blurred vision over two months. Endocrine tests revealed elevated plasma ACTH. Lumbar spine X-ray showed fusion of the L4-S1 vertebrae, consistent with previous tuberculosis infection.