Computational Analysis of Machining Induced Stress Distribution during Dry and Cryogenic Orthogonal Cutting of 7075 Aluminium Closed Cell Syntactic Foams.

The addition of hollow aluminium oxide bubbles to the 7075 aluminium matrix results in a lightweight syntactic foam with a reduced density and an increased peak compression strength. The presence of ceramic bubbles also aids in a reduced coefficient of thermal expansion and thermal conductivity in comparison to aluminium alloys. In spite of their enhanced material properties, the inclusion of hollow aluminium oxide bubbles presents the challenge of poor machinability. In order to elucidate the problem of poor surface machinability, an attempt has been made to develop a thermo-mechanical finite element machining model using AdvantEdgeTM software with which surface quality and machined syntactic foam material can be analyzed. If the novel model developed is combined with virtual reality technology, CNC technicians can observe the machining results to evaluate and optimize the machining program. The main novelty behind this software is that the material foam is assumed as a homogeneous material model for simplifying the material model as a complex heterogeneous material system. The input parameters used in this study are cutting speed, feed, average size and volume fraction of hollow aluminium oxide bubbles, and coolant. For the output parameters, the numerical analysis showed a 6.24% increase in peak tensile machining induced stress as well as a 51.49% increase in peak cutting temperature as cutting speed (25 m/min to 100 m/min) and uncut chip thickness (0.07 mm to 0.2 mm) were increased. The average size and volume fraction of hollow aluminium oxide bubbles showed a significant impact on the magnitude of cutting forces and the depth of tensile induced stress distribution. It was observed on the machined surface that, as the average size of hollow aluminium oxide bubbles became coarser, the peak machining induced tensile stress on the cut surface reduced by 4.47%. It was also noted that an increase in the volume fraction of hollow aluminium oxide bubbles led to an increase in both the peak machining induced tensile stress and the peak cutting temperature by 29.36% and 20.11%, respectively. This study also showed the influence of the ceramic hollow bubbles on plastic deformation behavior in 7075 aluminium matrix; the machining conditions for obtaining a favorable stress distribution in the machined surface and sub-surface of 7075 closed cell syntactic foam are also presented.

Neuropsychiatric Consequences of COVID-19 Pandemic: A Synthetic Review from a Global Perspective.

Some research suggests that distress, secondary to isolation and fear following COVID-19 infection, can negatively affect the long-term more than the COVID-19 infection itself. This narrative review aims to provide a global view on the neuropsychiatric consequences of COVID-19 that can be ascribed to several factors, ranging from the direct effect of infection, to the body's responses against the infection, or to the psychological sequelae of social isolation, unemployment, and fear for one's health and livelihood. Current findings show that the more severe the respiratory infection, the more likely are central nervous system (CNS) complications regarding the infection itself. The immune reactions to the infection may result in symptoms similar to chronic fatigue as well as neurocognitive deficits, which last long after the infection is gone. An increase in symptoms of depression, anxiety, and trauma-related stress may also follow upon economic fears and isolation from friends and family. The consequences of the pandemic are not limited to adults; children learning remotely and away from classmates and routine activities may develop adjustment disorders, acute stress disorder, and a variety of manifestations of grief. A summary of case reports suggests that COVID-19-related stress, economic recession, and political unrest increase the risk of suicidal behaviors and acts of violence. However, it is unknown whether manifestations of mental disorders result from social causes or whether CNS complications may be responsible.

Sustainable Machining of Mg-9Al-1.4Zn Foam Used for Temporary Biomedical Implant Using Cryogenic Cooling.

In this study, the drilling performance of biodegradable grade Mg-9Al-1.4Zn alloy reinforced with hollow thin-walled Al2O3 microspheres is inspected under different coolant environments such as dry, Almag® mineral oil, and liquid nitrogen. Drilling experiments were carried out using titanium aluminum nitride PVD coated and uncoated K10 tools on varying volume fractions of magnesium syntactic foams (5%, 10%, and 15%) reinforced with hollow Al2O3 microspheres. Test results showed a 30-60% higher thrust force generated with liquid nitrogen drilling in comparison to dry and oil-based drilling while cutting higher volume fraction foams. Higher microsphere volume fractions of syntactic foam recorded higher machining forces, which is roughly a 200% increase as the volume fraction raised to 15%. The performance of TiAlN PVD tool coating is reflected through a reduction in thrust forces by 20% during cryogenic drilling. Scanning electron microscope (SEM) investigation of cryogenic-machined bore surfaces showed minimal drilling-induced surface defects compared to dry and Almag® mineral oil conditions. A three-dimensional, thermo-mechanical finite element-based model for drilling Mg-9Al-1.4Zn syntactic foam using AdvantEdgeTM is developed for different sustainable lubrication conditions. Surface finish (Ra) showed a 45-55% improvement during cryogenic drilling of 15% syntactic foams with minimized subsurface damages compared to dry and wet cutting conditions. The higher the volume fraction, the higher the surface roughness (Ra) and thrust force under cryogenic machining.

Timing is everything: Circadian rhythms and their role in the control of sleep.

Sleep and the circadian clock are intertwined and have persisted throughout history. The suprachiasmatic nucleus (SCN) orchestrates sleep by controlling circadian (Process C) and homeostatic (Process S) activities. As a "hand" on the endogenous circadian clock, melatonin is critical for sleep regulation. Light serves as a cue for sleep/wake control by activating retino-recipient cells in the SCN and subsequently suppressing melatonin. Clock genes are the molecular timekeepers that keep the 24 h cycle in place. Two main sleep and behavioural disorder diagnostic manuals have now officially recognised the importance of these processes for human health and well-being. The body's ability to respond to daily demands with the least amount of effort is maximised by carefully timing and integrating all components of sleep and waking. In the brain, the organization of timing is essential for optimal brain physiology.

Disruption of Circadian Rhythms by Ambient Light during Neurodevelopment Leads to Autistic-like Molecular and Behavioral Alterations in Adult Mice.

Although circadian rhythms are thought to be essential for maintaining body health, the effects of chronic circadian disruption during neurodevelopment remain elusive. Here, using the "Short Day" (SD) mouse model, in which an 8 h/8 h light/dark (LD) cycle was applied from embryonic day 1 to postnatal day 42, we investigated the molecular and behavioral changes after circadian disruption in mice. Adult SD mice fully entrained to the 8 h/8 h LD cycle, and the circadian oscillations of the clock proteins, PERIOD1 and PERIOD2, were disrupted in the suprachiasmatic nucleus and the hippocampus of these mice. By RNA-seq widespread changes were identified in the hippocampal transcriptome, which are functionally associated with neurodevelopment, translational control, and autism. By western blotting and immunostaining hyperactivation of the mTOR and MAPK signaling pathways and enhanced global protein synthesis were found in the hippocampi of SD mice. Electrophysiological recording uncovered enhanced excitatory, but attenuated inhibitory, synaptic transmission in the hippocampal CA1 pyramidal neurons. These functional changes at synapses were corroborated by the immature morphology of the dendritic spines in these neurons. Lastly, autistic-like animal behavioral changes, including impaired social interaction and communication, increased repetitive behaviors, and impaired novel object recognition and location memory, were found in SD mice. Together, these results demonstrate molecular, cellular, and behavioral changes in SD mice, all of which resemble autistic-like phenotypes caused by circadian rhythm disruption. The findings highlight a critical role for circadian rhythms in neurodevelopment.

Digital Image Correlation of Tensile Properties for Monel 400/SS 316L Dissimilar Metal Welding Joints.

Dissimilar metal weld joints of Monel 400 and Stainless Steel 316L stainless steel were carried out using Gas Tungsten Arc Welding (GTAW). Conventional annealing and cryogenic treatment were performed on the welded joints. Weld joints of this combination of materials have enormous potential applications in power industry and the available related literature is limited. In the present study, the tensile properties of heat treated (HT), cryotreated (CT), and untreated (UT) specimens were studied. The engineering stress and strain were determined experimentally as per Standard Test Methods for Tension Testing of Metallic Materials (ASTM E8). The strain distribution was evaluated at different zones of weld joint was evaluated using Digital Image Correlation (DIC). Significant difference was noticed between the zones. Weld zone of all samples had less local stress and strain and SS 316L heat affected zone (HAZ) zone had more local stress and strain when compared to other zones. The local strain distribution along distance from weld center line and local stress-strain curves of different zones are also predicted. Scanning Electron Microscopy was used to analyze the fracture behavior of welded samples for HT, CT, and UT specimens.

Biological Timing and Neurodevelopmental Disorders: A Role for Circadian Dysfunction in Autism Spectrum Disorders.

Autism spectrum disorders (ASDs) are a spectrum of neurodevelopmental disorders characterized by impaired social interaction and communication, as well as stereotyped and repetitive behaviors. ASDs affect nearly 2% of the United States child population and the worldwide prevalence has dramatically increased in recent years. The etiology is not clear but ASD is thought to be caused by a combination of intrinsic and extrinsic factors. Circadian rhythms are the ∼24 h rhythms driven by the endogenous biological clock, and they are found in a variety of physiological processes. Growing evidence from basic and clinical studies suggest that the dysfunction of the circadian timing system may be associated with ASD and its pathogenesis. Here we review the findings that link circadian dysfunctions to ASD in both experimental and clinical studies. We first introduce the organization of the circadian system and ASD. Next, we review physiological indicators of circadian rhythms that are found disrupted in ASD individuals, including sleep-wake cycles, melatonin, cortisol, and serotonin. Finally, we review evidence in epidemiology, human genetics, and biochemistry that indicates underlying associations between circadian regulation and the pathogenesis of ASD. In conclusion, we propose that understanding the functional importance of the circadian clock in normal and aberrant neurodevelopmental processes may provide a novel perspective to tackle ASD, and clinical treatments for ASD individuals should comprise an integrative approach considering the dynamics of daily rhythms in physical, mental, and social processes.

Autism Spectrum Disorder patients may be susceptible to COVID-19 disease due to deficiency in melatonin.

Patients with Autism Spectrum Disorder (ASD) may be particularly prone to develop COVID-19. An unusual extended course of COVID-19 disease illness has been reported in one ASD patient and a group of patients have COVID-19 disease in a neurodevelopmental facility. It has been widely reported that many of those with ASD have substantial sleep disorders with low levels of melatonin and various genetic alterations related to melatonin production have been found. Several lines of evidence point to a substantial role of melatonin in the body's innate defense system including acting as a scavenger, an antioxidant and modulating the immune system. We therefore hypothesize that melatonin deficiency may predispose those ASD patients who have low melatonin output to COVID-19 disease. Potential implications for treatment are discussed.

Clarifying the role of sleep in depression: A narrative review.

It has been established that 4.4 to 20% of the general population suffers from a major depressive disorder (MDD), which is frequently associated with a dysregulation of normal sleep-wake mechanisms. Disturbances of circadian rhythms are a cardinal feature of psychiatric dysfunctions, including MDD, which tends to indicate that biological clocks may play a role in their pathophysiology. Thus, episodes of depression and mania or hypomania can arise as a consequence of the disruption of zeitgebers (time cues). In addition, the habit of sleeping at a time that is out of phase with the body's other biological rhythms is a common finding in depressed patients. In this review, we have covered a vast area, emerging from human and animal studies, which supports the link between sleep and depression. In doing so, this paper covers a broad range of distinct mechanisms that may underlie the link between sleep and depression. This review further highlights the mechanisms that may underlie such link (e.g. circadian rhythm alterations, melatonin, and neuroinflammatory dysregulation), as well as evidence for a link between sleep and depression (e.g. objective findings of sleep during depressive episodes, effects of pharmacotherapy, chronotherapy, comorbidity of obstructive sleep apnea and depression), are presented.

Understanding the role of sleep and its disturbances in Autism spectrum disorder.

BACKGROUND: Several studies have established a positive relationship between sleep difficulties and symptomatology in ASD children. The rationale for this review is to describe and discuss the sleep difficulties, which are one of the significant complications associated with autism spectrum disorder (ASD). PURPOSE: Many types of sleep disorders have been reported in ASD individuals, but still lack a comprehensive study and in-depth analysis. Despite the contribution of sleep problems to the overall symptoms of ASD, the symptoms of disturbed sleep experienced by many affected patients have only recently started to receive attention from clinicians and family members. MATERIALS AND METHODS: This narrative overview has been prepared based on searching standard research databases with specific keywords; b. Additional search was made using the bibliographies of the retrieved articles; and c. author's collection of relevant peer-reviewed articles. Once selected, manuscripts are then compared and summarized based on the author's perspective. Results are based on a qualitative rather than a quantitative level. RESULTS: This article highlights the role of sleep in the brain and neural development of children and emphasizes that the intensity of sleep problems is associated with an increased occurrence of ASD symptoms. It also suggests the significance of treating sleep problems in ASD individuals. CONCLUSIONS: The review provides broader perspectives and a better understanding of sleep problems in pathophysiology, mechanism, and management with respect to ASD individuals. Finally, the implications for clinical practice and future agendas have also been discussed.

Basic chronobiology: what do sleep physicians need to know?

Sleep is an essential physiological process, which profoundly affects a wide range of biological activities. It is now known that sleep supports myriad vital functions in the central nervous system. This includes neural plasticity, learning, memory, cognition and emotional regulation. Additionally, it affects basic processes such as cardiovascular, immunological and metabolic activity. Evidence from multiple lines of research has thus shown that good quality of sleep is essential for both survival and optimal functioning of life. Considerable evidence also supports the conclusion that even minimal dysfunctions in circadian regulation can significantly disrupt sleep and broadly affect body physiology. As a consequence, it is now appreciated that the therapy of sleep disorders is more complex than was once thought. At present, several clinical disciplines have recognized the significance of the biological clock in health and illness, and are incorporating this knowledge into treatment programs. Recent decades have seen the emergence of chronotherapies, i.e., treatment strategies that are aimed at producing adjustments in the circadian clock. The final objective of these approaches is to affect basic cellular and physiological processes, which in turn may be at the root of disorders such as physiological aging, immune functioning, metabolic activity, and psychiatric disturbance. It is suggested that the integration of chronobiological perspectives into many mainstream medical disciplines would be of significant benefit, both for the reduction of the prevalence of diseases and their treatment. This review considers the physiology of sleep and the importance of timekeeping mechanisms in the regulation of overall health.

The eIF2α Kinase GCN2 Modulates Period and Rhythmicity of the Circadian Clock by Translational Control of Atf4.

The integrated stress response (ISR) is activated in response to diverse stress stimuli to maintain homeostasis in neurons. Central to this process is the phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). Here, we report a critical role for ISR in regulating the mammalian circadian clock. The eIF2α kinase GCN2 rhythmically phosphorylates eIF2α in the suprachiasmatic circadian clock. Increased eIF2α phosphorylation shortens the circadian period in both fibroblasts and mice, whereas reduced eIF2α phosphorylation lengthens the circadian period and impairs circadian rhythmicity in animals. Mechanistically, phosphorylation of eIF2α promotes mRNA translation of Atf4. ATF4 binding motifs are identified in multiple clock genes, including Per2, Per3, Cry1, Cry2, and Clock. ATF4 binds to the TTGCAGCA motif in the Per2 promoter and activates its transcription. Together, these results demonstrate a significant role for ISR in circadian physiology and provide a potential link between dysregulated ISR and circadian dysfunction in brain diseases.

The contribution of modern 24-hour society to the development of type 2 diabetes mellitus: the role of insufficient sleep.

Epidemiological studies since 1980 have shown significant increases in the incidence of type 2 diabetes mellitus (T2DM). The public health burden generated by the growing prevalence of T2DM, which, in its fully developed form, is a lifelong illness, has been associated with further social and economic costs in affected countries. Recent studies have suggested that chronic sleep insufficiency or disrupted or poor quality sleep could contribute to the development of T2DM. Although many research findings have now shown that sleep plays a key role in glucose metabolism, the full implications of these findings have not been translated into clinical programs for improving patients' sleep quality as a means for addressing the treatment of T2DM. The purpose of this brief overview is to focus on the clinical significance of sleep in the onset and treatment of T2DM. We suggest here that physician education should emphasize the importance of sufficient sleep for overall health, including the management of T2DM, and that steps should be taken to incorporate this perspective into clinical practice. The promotion of sleep hygiene techniques as a clinical intervention could improve the regulation of glucose metabolism and thus the longevity of T2DM patients. Moreover, it may prevent secondary complications accruing from the illness and consequently reduce the significant medical costs of treating T2DM patients.

Are Type 2 Diabetes Mellitus and Depression Part of a Common Clock Genes Network?

In recent years, there has been an increased prevalence of type 2 diabetes mellitus (T2DM) and depression across the world. This growing public health problem has produced an increasing socioeconomic burden to the populations of all affected countries. Despite an awareness by public health officials and medical researchers of the costs associated with these diseases, there still remain many aspects of how they develop that are not understood. In this article, we propose that the circadian clock could be a factor that coordinates both the neurobehavioral and metabolic processes that underlie depression and T2DM. We propose further that this perspective, one which emphasizes the regulatory effects of clock gene activity, may provide insights into how T2DM and depression interact with one another, and may thus open a new pathway for managing and treating these disorders.

Rotavirus Infection and Disease in a Multisite Birth Cohort: Results From the MAL-ED Study.

Background: In a multicountry birth cohort study, we describe rotavirus infection in the first 2 years of life in sites with and without rotavirus vaccination programs. Methods: Children were recruited by 17 days of age and followed to 24 months with collection of monthly surveillance and diarrheal stools. Data on sociodemographics, feeding, and illness were collected at defined intervals. Stools were tested for rotavirus and sera for antirotavirus immunoglobulins by enzyme immunoassays. Results: A total of 1737 children contributed 22646 surveillance and 7440 diarrheal specimens. Overall, rotavirus was detected in 5.5% (408/7440) of diarrheal stools, and 344 (19.8%) children ever had rotavirus gastroenteritis. Household overcrowding and a high pathogen load were consistent risk factors for infection and disease. Three prior infections conferred 74% (P < .001) protection against subsequent infection in sites not using vaccine. In Peru, incidence of rotavirus disease was relatively higher during the second year of life despite high vaccination coverage. Conclusions: Rotavirus infection and disease were common, but with significant heterogeneity by site. Protection by vaccination may not be sustained in the second year of life in settings with high burdens of transmission and poor response to oral vaccines.

Association of Per3 length polymorphism with bipolar I disorder and schizophrenia.

BACKGROUND: Sleep-wake disturbances have frequently been reported in bipolar disorder and schizophrenia, and are considered to be caused by an underlying circadian rhythm disorder. The study presented here was designed to investigate the existence of Per3 polymorphism in bipolar disorder type I (BD-I) and schizophrenic patients in South India. METHODS: Blood samples were collected from 311 BD-I patients, 293 schizophrenia patients, and 346 age- and sex-matched normal controls. Per3 genotyping was performed on DNA by polymerase chain reaction using specific primers. RESULTS: An increased prevalence of five repeat homozygotes was seen in BD-I patients as compared with healthy controls (odds ratio =1.72 [95% confidence interval: 1.08-2.76, P=0.02]). In BD-I patients, the frequency of the five repeat allele was higher (allele frequency =0.41), and that of the four repeat allele lower (allele frequency =0.36) (χ (2)=4.634; P<0.03) than in the control group. No significant association was observed in the allele frequencies of four and five repeat alleles in schizophrenia patients when compared with controls. CONCLUSION: The occurrence of the five repeat allele of Per3 may be a risk factor for BD-I onset in this ethnic group.

Per3 length polymorphism in patients with type 2 diabetes mellitus.

BACKGROUND: A number of observations support the involvement of circadian clock genes in the regulation of metabolic processes. One of these circadian genes, Per3, exhibits a variable number tandem repeat length polymorphism, consisting of two alleles, namely four and five repeat alleles, in its exon 18. The objective of this study was to examine the existence of Per3 variants in patients with type 2 diabetes mellitus (T2DM) as compared to a non T2DM control group. METHODS: Intravenous blood samples were collected to obtain white blood cells from 302 T2DM patients and 330 non-diabetic, age- and sex-matched, individuals. Per3 genotyping was performed on DNA by polymerase chain reaction. RESULTS: Frequency of five repeat allele was higher, and that of four repeat allele lower, in T2DM patients as compared to non-diabetic controls (χ2=6.977, p=0.0082) CONCLUSIONS: The results indicate an association of Per3 five repeat allele with T2DM occurrence and suggest that individuals with five repeat allele may be at a greater risk for T2DM as compared to those carrying the four repeat allele.

Should we listen to our clock to prevent type 2 diabetes mellitus?

The circadian clock drives a number of metabolic processes including energy intake, storage and utilization coupled with the sleep/wake cycles. Globally, the increasing prevalence of type 2 diabetes (T2DM) has become a significant international public health concern. In view of the heavy societal burden caused by diabetes, and further, to reduce its growing incidence, it is clearly essential to understand the causes of this disease and to devise more effective strategies for its treatment. Although many factors cause T2DM, this article centers on the role of circadian regulation of metabolism. The correlation between the increased occurrence of T2DM and the ubiquity of modern social pressures such as 24/7 lifestyles as well as nocturnal lighting conditions point strongly to the hypothesis that malfunctioning of circadian controls may be involved in the etiology of the illness. Nocturnal light exposure, unusual timing of food, irregular sleep/wake schedules and traveling between different time zones are some of the factors responsible for improper entrainment of the clock. Recent reports have proposed that strengthening of circadian clock functioning and proper timing of food intake could stabilize glucose homeostasis. This strategy thus represents a chronotherapeutic option for non-pharmaceutical intervention in treating T2DM patients.