Research on the Relation between Cast Iron and Oxygen. I : The Mechanism of the Formation of White Cast Iron under the Influence of Oxygen

It has been known that oxygen in the melt gives rise to the tendency of forming white cast iron, but the mechanism of such a phenomenon is yet unknown. We have herein clarified this mechanism on the basis of the atomic arrangement of the melt of cast iron and the double diagram. In molten cast iron, oxygen atoms behave partly as free atoms and partly as Fe-C-O-Fe clusters, and the latter prevents the melt from solidifying at the eutectic point C\u27 (austenite-graphite) by unbalancing the lever relation of E\u27 C\u27 F\u27, with the result that the eutectic point drops from C\u27 to C of austenite-Fe_3C, inducing the formation of white cast iron. Theoretically, the oxygen, content effective for white cast iron formation was estimated to be about 0.01 per cent, an amount equivalent to the carbon percentage corresponding to E-E\u27

Cortical electrical activity changes in healthy aging using EEG-eLORETA analysis

Brain aging causes loss of synaptic spines, neuronal apoptosis, and a reduction in neurotransmitter levels. These aging phenomena disturb cortical electrical activity and its synchronization with connected regions. Previous electroencephalography (EEG) studies reported an age-related decrease in electrical activity in the alpha frequency band at occipital, parietal, and temporal areas as well as a decrease in occipital delta activity. However, there is an ongoing debate about whether there is an increase or decrease of the activity in other frequency bands with aging due to inconsistent study findings. In this study, we aimed to detect age-related changes of cortical electrical activities in all five frequency bands (delta, theta, alpha, beta, and gamma) in a large sample of healthy subjects for the first time. Using eLORETA (exact low-resolution brain electromagnetic tomography) analysis, we applied an eLORETA source estimation method to resting-state EEG data in 147 healthy subjects (median age 55, IQR 26.5–67.0) to obtain cortical electrical activity and assessed age-related changes in this activity using correlation analysis with multiple comparison correction. The combination of the eLORETA source estimation method and correlation analysis implemented in eLORETA software detected age-related changes in specific cortical regions for each frequency band: (1) delta and theta cortical electrical activities decreased at the occipital area with age, (2) alpha cortical electrical activity decreased at the occipitoparietotemporal areas with age, (3) beta cortical electrical activity increased at the insula, sensorimotor area, supplementary motor area, premotor area, and right temporal areas with age (most significant correlation at the right insula), (4) gamma cortical electrical activity increased at the frontoparietal and left temporal areas with age. These findings extend previous EEG study findings and provide valuable information related to mechanisms of healthy aging. Overall, our findings revealed that even healthy aging greatly affects cortical electrical activities in a region-specific way

Alpha lipoic acid selectively inhibits proliferation and adhesion to fibronectin of v-H-ras-transformed 3Y1 cells

Here, we focused on the effects of racemic α-lipoic acid on proliferation and adhesion properties of 3Y1 rat fibroblasts and the v-H-ras-transformed derivative, HR-3Y1-2 cells. Racemic α-lipoic acid inhibited proliferation of HR-3Y1-2 but not 3Y1 cells at 0.3 and 1.0 mM. R-(+)-α-lipoic acid also inhibited proliferation of HR-3Y1-2 cells equivalent to that of racemic α-lipoic acid. In addition, racemic α-lipoic acid decreased intracellular reactive oxygen species levels in HR-3Y1 cells but not 3Y1 cells. Next, we evaluated the effects of racemic α-lipoic acid on cell adhesion to fibronectin. The results indicated that racemic α-lipoic acid decreased adhesive ability of HR-3Y1-2 cells to fibronectin-coated plates. As blocking antibody experiment revealed that β1-integrin plays a key role in cell adhesion in this experimental system, the effects of racemic α-lipoic acid on the expression of β1-integrin were examined. The results indicated that racemic α-lipoic acid selectively downregulated the expression of cell surface β1-integrin expression in HR-3Y1-2 cells. Intriguingly, exogenous hydrogen peroxide upregulated cell surface β1-integrin expression in 3Y1 cells. Taken together, these data suggest that reduction of intracellular reactive oxygen species levels by α-lipoic acid could be an effective means of ameliorating abnormal growth and adhesive properties in v-H-ras transformed cells

EEG resting-state networks in Alzheimer’s disease associated with clinical symptoms

Alzheimer’s disease (AD) is a progressive neuropsychiatric disease affecting many elderly people and is characterized by progressive cognitive impairment of memory, visuospatial, and executive functions. As the elderly population is growing, the number of AD patients is increasing considerably. There is currently growing interest in determining AD’s cognitive dysfunction markers. We used exact low-resolution-brain-electromagnetic-tomography independent-component-analysis (eLORETA-ICA) to assess activities of five electroencephalography resting-state-networks (EEG-RSNs) in 90 drug-free AD patients and 11 drug-free patients with mild-cognitive-impairment due to AD (ADMCI). Compared to 147 healthy subjects, the AD/ADMCI patients showed significantly decreased activities in the memory network and occipital alpha activity, where the age difference between the AD/ADMCI and healthy groups was corrected by linear regression analysis. Furthermore, the age-corrected EEG-RSN activities showed correlations with cognitive function test scores in AD/ADMCI. In particular, decreased memory network activity showed correlations with worse total cognitive scores for both Mini-Mental-State-Examination (MMSE) and Alzheimer’s Disease-Assessment-Scale-cognitive-component-Japanese version (ADAS-J cog) including worse sub-scores for orientation, registration, repetition, word recognition and ideational praxis. Our results indicate that AD affects specific EEG-RSNs and deteriorated network activity causes symptoms. Overall, eLORETA-ICA is a useful, non-invasive tool for assessing EEG-functional-network activities and provides better understanding of the neurophysiological mechanisms underlying the disease

Novel Oral Derivative UD-017, a Highly Selective CDK7 Inhibitor, Exhibits Anticancer Activity by Inducing Cell-Cycle Arrest and Apoptosis in Human Colorectal Cancer

Objective: This study aimed to investigate the anticancer profile of a new cyclin-dependent kinase 7 (CDK7) inhibitor, UD-017, by examining its mechanism of action using HCT-116 colorectal cancer cells. Methods: The anticancer properties of UD-017 were assessed using several assays, including in vitro kinase, proliferation, and apoptosis assays, western blot analysis, and an in vivo xenograft mouse model. Results: UD-017 significantly inhibited CDK7 activity (IC50 = 16 nM) with high selectivity in an in vitro kinase assay testing a panel of over 300 proteins and lipid kinases. UD-017 also inhibited the growth of HCT-116 cells (GI50 = 19 nM) and inhibited the phosphorylation of various downstream mediators of CDK7 signaling. In cell cycle and apoptosis assays using HCT-116 cells, UD-017 increased the number of cells in both G1 and G2/M phases and induced apoptosis. In vivo, UD-017 inhibited tumor growth in an HCT-116 xenograft mouse model by 33%, 64%, and 88% at doses of 25, 50, and 100 mg/kg, respectively, with clear dose-dependency. Co-administration of 5-FU and 50 mg/kg UD-017 had a strong synergistic effect, as reflected in the complete inhibition of tumor growth. Conclusion: CDK7 may play a major role in colorectal cancer growth by regulating the cell cycle and apoptosis. UD-017 is a promising candidate therapeutic agent for the treatment of cancer involving CDK7 signaling

Noninvasive prediction of shunt operation outcome in idiopathic normal pressure hydrocephalus

Idiopathic normal pressure hydrocephalus (iNPH) is a syndrome characterized by gait disturbance, cognitive deterioration and urinary incontinence in elderly individuals. These symptoms can be improved by shunt operation in some but not all patients. Therefore, discovering predictive factors for the surgical outcome is of great clinical importance. We used normalized power variance (NPV) of electroencephalography (EEG) waves, a sensitive measure of the instability of cortical electrical activity, and found significantly higher NPV in beta frequency band at the right fronto-temporo-occipital electrodes (Fp2, T4 and O2) in shunt responders compared to non-responders. By utilizing these differences, we were able to correctly identify responders and non-responders to shunt operation with a positive predictive value of 80% and a negative predictive value of 88%. Our findings indicate that NPV can be useful in noninvasively predicting the clinical outcome of shunt operation in patients with iNPH

Different Characteristics of Cognitive Impairment in Elderly Schizophrenia and Alzheimer's Disease in the Mild Cognitive Impairment Stage

We compared indices of the revised version of the Wechsler Memory Scale (WMS-R) and scaled scores of the five subtests of the revised version of the Wechsler Adult Intelligence Scale (WAIS-R) in 30 elderly schizophrenia (ES) patients and 25 Alzheimer's disease (AD) patients in the amnestic mild cognitive impairment (aMCI) stage (AD-aMCI). In the WMS-R, attention/concentration was rated lower and delayed recall was rated higher in ES than in AD-aMCI, although general memory was comparable in the two groups. In WAIS-R, digit symbol substitution, similarity, picture completion, and block design scores were significantly lower in ES than in AD-aMCI, but the information scores were comparable between the two groups. Delayed recall and forgetfulness were less impaired, and attention, working memory and executive function were more impaired in ES than in AD-aMCI. These results should help clinicians to distinguish ES combined with AD-aMCI from ES alone