•Rotary ultrasonic machining (RUM) and grinding of CFRP were compared.•Effects of tool rotation speed and feed rate were investigated.•Theoretical explanations were provided for experimental ...results.•RUM showed better performance than grinding in five aspects.
Carbon fiber reinforced plastic (CFRP) composites have been intensively used in various industries due to their superior properties. In aircraft and aerospace industry, a large number of holes are required to be drilled into CFRP components at final stage for aircraft assembling. There are two major types of methods for hole making of CFRP composites in industry, twist drilling and its derived multi-points machining methods, and grinding and its related methods. The first type of methods are commonly used in hole making of CFRP composites. However, in recent years, rotary ultrasonic machining (RUM), a hybrid machining process combining ultrasonic machining and grinding, has also been successfully used in drilling of CFRP composites. It has been shown that RUM is superior to twist drilling in many aspects. However, there are no reported investigations on comparisons between RUM and grinding in drilling of CFRP. In this paper, these two drilling methods are compared in five aspects, including cutting force, torque, surface roughness, hole diameter, and material removal rate.
The suprachiasmatic nucleus (SCN) is the “master clock” of the mammalian brain. It coordinates the peripheral clocks in the body, including the pineal clock that receives SCN input via a ...multisynaptic noradrenergic pathway. Rhythmic pineal melatonin production is disrupted in Alzheimer's disease (AD). Here we show that the clock genes hBmal1, hCry1, and hPer1 were rhythmically expressed in the pineal of controls (Braak 0). Moreover, hPer1 and hβ1‐adrenergic receptor (hβ1‐ADR) mRNA were positively correlated and showed a similar daily pattern. In contrast, in both preclinical (Braak I‐II) and clinical AD patients (Braak V‐VI), the rhythmic expression of clock genes was lost as well as the correlation between hPer1 and hβ1‐ADR mRNA. Intriguingly, hCry1 mRNA was increased in clinical AD. These changes are probably due to a disruption of the SCN control, as they were mirrored in the rat pineal deprived of SCN control. Indeed, a functional disruption of the SCN was observed from the earliest AD stages onward, as shown by decreased vasopressin mRNA, a clock‐controlled major output of the SCN. Thus, a functional disconnection between the SCN and the pineal from the earliest AD stage onward could account for the pineal clock gene changes and underlie the circadian rhythm disturbances in AD.—Wu, Y‐H., Fischer, D. F., Kalsbeek, A., Garidou‐Boof, M‐L., van der Vliet, J., van Heijningen, C., Liu, R‐Y., Zhou, J‐N., Swaab, D. F. Pineal clock gene oscillation is disturbed in Alzheimer's disease, due to functional disconnection from the “master clock.” FASEB J. 20, E1171–E1180 (2006)
An integrated breakwater-WEC system, which comprises of an array of heaving Oscillating Buoy Wave Energy Converters (OB-WECs) attached at the weather side of a fixed breakwater, is proposed in this ...study. Detailed experiments have been undertaken to investigate the heave-response-amplitude operator (HRAO), the wave force on the WEC devices and the transmission coefficient of the breakwater-WEC system. The design of the experiment is validated by comparing the HRAO of the devices with the corresponding numerical results. The hydrodynamic performance of the breakwater-WEC system is compared with that of its isolated counterparts, i.e., the isolated WEC array and the isolated breakwater. Parametric studies are conducted to optimise the draft of the WEC devices and the breakwater-WEC spacing, i.e. the gap between the WEC devices and the breakwater. Results show that, compared with the case of isolated WEC devices, the wave force and HRAO of the WEC devices are amplified for a properly designed breakwater-WEC system. Even though the external damping (caused by viscous damping and the friction loss) plays an important role while evaluating the efficiency of the WECs, the existence of the breakwater significantly improves the performance of the WEC array. The HRAO is sensitive to the draft of the devices and breakwater-WEC spacing.
•The heave response and wave force on WEC devices can be amplified in the breakwater-WEC system.•The transmission coefficient of the breakwater-WEC system is not compromised by comparing with the original breakwater.•The RAO of WEC devices in heave mode is sensitive to the draft of WEC device and the pontoon-WEC spacing.
Oxidative stress (OS) induces osteoblast apoptosis, which plays a crucial role in the initiation and progression of osteoporosis. Although OS is closely associated with mitochondrial dysfunction, ...detailed mitochondrial mechanisms underlying OS-induced osteoblast apoptosis have not been thoroughly elucidated to date. In the present study, we found that mitochondrial abnormalities largely contributed to OS-induced osteoblast apoptosis, as evidenced by enhanced production of mitochondrial reactive oxygen species; considerable reduction in mitochondrial respiratory chain complex activity, mitochondrial membrane potential, and adenosine triphosphate production; abnormality in mitochondrial morphology; and alteration of mitochondrial dynamics. These mitochondrial abnormalities were primarily mediated by an imbalance in mitochondrial fusion and fission through a protein kinase B- (AKT-) glycogen synthase kinase 3β- (GSK3β-) optic atrophy 1- (OPA1-) dependent mechanism. Hydroxytyrosol (3,4-dihydroxyphenylethanol (HT)), an important compound in virgin olive oil, significantly prevented OS-induced osteoblast apoptosis. Specifically, HT inhibited OS-induced mitochondrial dysfunction by decreasing OPA1 cleavage and by increasing AKT and GSK3β phosphorylation. Together, our results indicate that the AKT-GSK3β signaling pathway regulates mitochondrial dysfunction-associated OPA1 cleavage, which may contribute to OS-induced osteoblast apoptosis. Moreover, our results suggest that HT could be an effective nutrient for preventing osteoporosis development.
: Neuropathology is the most reliable criterion for diagnosing Alzheimer's disease (AD). A well‐established system for staging the spread of neuropathological changes in AD is available. The clinical ...use of a biomarker that reflects the neuropathological change occurring in brain tissue has not yet been established. Melatonin is a product that plays not only a major role in the regulation of the circadian rhythms but may also exert neuroprotective effects in AD. Melatonin levels were determined in ventricular postmortem cerebrospinal fluid (CSF) of 121 subjects. Braak staging and a modified Braak staging for cortex (MBSC) were used to evaluate the severity of AD neuropathology. The present study revealed that not only the Braak stages of AD, but also the MBSC were negatively correlated with CSF melatonin levels. By using MBSC, we now demonstrate for the first time that CSF melatonin levels were significantly decreased in the aged individuals with early neuropathological changes in the temporal cortex, where the AD process starts. Those individuals that did not have any neurofibrillary tangle (NFT) or neuritic plaque (NP) in the temporal cortex, had much higher melatonin levels (287 ± 68 and 280 ± 64 pg/mL, respectively) than those individuals that had a few NFTs and NPs (82 ± 4 and 39 ± 8 pg/mL, respectively) in the temporal cortex. These results suggest that the decrease in CSF melatonin levels may be an early event in the development of AD possibly occurring even before the clinical symptoms.
A disturbed sleep-wake rhythm is common in Alzheimer disease (AD) patients and correlated with decreased melatonin levels and a disrupted circadian melatonin rhythm. Melatonin levels in the ...cerebrospinal fluid are decreased during the progression of AD neuropathology (as determined by the Braak stages), already in cognitively intact subjects with the earliest AD neuropathology (Braak stages I-II) (preclinical AD). To investigate the molecular mechanisms behind the decreased melatonin levels, we measured monoamines and mRNA levels of enzymes of the melatonin synthesis and its noradrenergic regulation in pineal glands from 18 controls, 33 preclinical AD subjects, and 25 definite AD patients. Pineal melatonin levels were highly correlated with cerebrospinal fluid melatonin levels. The circadian melatonin rhythm disappeared because of decreased nocturnal melatonin levels in both the preclinical AD and AD patients. Also the circadian rhythm of β1-adrenergic receptor mRNA disappeared in both patient groups. The precursor of melatonin, serotonin was stepwise depleted during the course of AD, as indicated by the up-regulated monoamine oxidase A mRNA and activity (5-hydroxyindoleacetic acid:serotonin ratio). We conclude that a dysfunction of noradrenergic regulation and the depletion of serotonin by increased monoamine oxidase A result in the loss of melatonin rhythm already in preclinical AD.
Post-traumatic stress disorder (PTSD) is a major problem among military veterans and civilians alike, yet its pathophysiology remains poorly understood. We performed a genome-wide association study ...and bioinformatic analyses, which included 146,660 European Americans and 19,983 African Americans in the US Million Veteran Program, to identify genetic risk factors relevant to intrusive reexperiencing of trauma, which is the most characteristic symptom cluster of PTSD. In European Americans, eight distinct significant regions were identified. Three regions had values of P < 5 × 10
: CAMKV; chromosome 17 closest to KANSL1, but within a large high linkage disequilibrium region that also includes CRHR1; and TCF4. Associations were enriched with respect to the transcriptomic profiles of striatal medium spiny neurons. No significant associations were observed in the African American cohort of the sample. Results in European Americans were replicated in the UK Biobank data. These results provide new insights into the biology of PTSD in a well-powered genome-wide association study.
Background: The extent to which sleep loss may predispose astronauts to a state of altered immunity during extended space travel prompts evaluation with ground-based models. Objective: We sought to ...measure plasma levels of selected cytokines and their receptors, including the putative sleep-regulation proteins soluble TNF-α receptor (sTNF-αR) I and IL-6, in human subjects undergoing 2 types of sleep deprivation during environmental confinement with performance demands. Methods: Healthy adult men (n = 42) were randomized to schedules that varied in severity of sleep loss: 4 days (88 hours) of partial sleep deprivation (PSD) involving two 2-hour naps per day or 4 days of total sleep deprivation (TSD). Plasma samples were obtained every 6 hours across 5 days and analyzed by using enzyme-linked immunoassays for sTNF-αRI, sTNF-αRII, IL-6, soluble IL-2 receptor, IL-10, and TNF-α. Results: Interactions between the effects of time and sleep deprivation level were detected for sTNF-αRI and IL-6 but not for sTNF-αRII, soluble IL-2 receptor, IL-10, and TNF-α. Relative to the PSD condition, subjects in the TSD condition had elevated plasma levels of sTNF-αRI on day 2 (P = .04), day 3 (P = .01), and across days 2 to 4 of sleep loss (P = .01) and elevated levels of IL-6 on day 4 (P = .04). Conclusions: Total sleep loss produced significant increases in plasma levels of sTNF-αRI and IL-6, messengers that connect the nervous, endocrine, and immune systems. These changes appeared to reflect elevations of the homeostatic drive for sleep because they occurred in TSD but not PSD, suggesting that naps may serve as the basis for a countermeasures approach to prolonged spaceflight. (J Allergy Clin Immunol 2001;107:165-70.)
Transsexuals have the strong feeling, often from childhood onwards, of having been born the wrong sex. The possible psychogenic or biological aetiology of transsexuality has been the subject of ...debate for many years. Here we show that the volume of the central subdivision of the bed nucleus of the stria terminals (BSTc), a brain area that is essential for sexual behaviour, is larger in men than in women. A female-sized BSTc was found in male-to-female transsexuals. The size of the BSTc was not influenced by sex hormones in adulthood and was independent of sexual orientation. Our study is the first to show a female brain structure in genetically male transsexuals and supports the hypothesis that gender identity develops as a result of an interaction between the developing brain and sex hormones.
Transsexuals experience themselves as being of the opposite sex,
despite having the biological characteristics of one sex. A crucial
question resulting from a previous brain study in male-to-female
...transsexuals was whether the reported difference according to gender
identity in the central part of the bed nucleus of the stria terminalis
(BSTc) was based on a neuronal difference in the BSTc itself or just a
reflection of a difference in vasoactive intestinal polypeptide
innervation from the amygdala, which was used as a marker. Therefore,
we determined in 42 subjects the number of somatostatin-expressing
neurons in the BSTc in relation to sex, sexual orientation, gender
identity, and past or present hormonal status. Regardless of sexual
orientation, men had almost twice as many somatostatin neurons as women
(P < 0.006). The number of neurons in the BSTc of
male-to-female transsexuals was similar to that of the females
(P = 0.83). In contrast, the neuron number of a
female-to-male transsexual was found to be in the male range. Hormone
treatment or sex hormone level variations in adulthood did not seem to
have influenced BSTc neuron numbers. The present findings of
somatostatin neuronal sex differences in the BSTc and its sex reversal
in the transsexual brain clearly support the paradigm that in
transsexuals sexual differentiation of the brain and genitals may go
into opposite directions and point to a neurobiological basis of gender
identity disorder.
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