Observation of Collider Muon Neutrinos with the SND@LHC Experiment.

We report the direct observation of muon neutrino interactions with the SND@LHC detector at the Large Hadron Collider. A dataset of proton-proton collisions at sqrt[s]=13.6 TeV collected by SND@LHC in 2022 is used, corresponding to an integrated luminosity of 36.8 fb^{-1}. The search is based on information from the active electronic components of the SND@LHC detector, which covers the pseudorapidity region of 7.2<η<8.4, inaccessible to the other experiments at the collider. Muon neutrino candidates are identified through their charged-current interaction topology, with a track propagating through the entire length of the muon detector. After selection cuts, 8 ν_{µ} interaction candidate events remain with an estimated background of 0.086 events, yielding a significance of about 7 standard deviations for the observed ν_{µ} signal.

Plasma natriuretic peptide levels in fetuses with congenital heart defect and/or arrhythmia.

OBJECTIVE: Diagnosing fetal heart failure remains challenging because it is difficult to know how well the fetal myocardium will perform as loading conditions change. In adult cardiology, natriuretic peptides (NPs) are established markers of heart failure. However, the number of studies investigating NP levels in fetuses is quite limited. The aim of this study was to evaluate the significance of plasma NP levels in the assessment of heart failure in fetuses with a congenital heart defect (CHD) and/or arrhythmia. METHODS: This was a prospective observational study conducted at a tertiary pediatric cardiac center. A total of 129 singletons with CHD and/or arrhythmia and 127 controls were analyzed between 2012 and 2015. Umbilical cord plasma atrial NP, brain NP and N-terminal pro-brain NP levels at birth were compared with ultrasonography findings indicating fetal heart failure, such as cardiovascular profile (CVP) score and morphological characteristics. RESULTS: Fetuses with CHD and/or arrhythmia had higher NP levels than did controls (P < 0.01). NP levels of fetuses with CHD and/or arrhythmia were correlated inversely with CVP score (P for trend < 0.01). No differences in NP levels were found in fetuses with CHD and/or arrhythmia and a CVP score of ≥ 8 in comparison to controls. Multivariate analysis showed that a CVP score of ≤ 5, tachy- or bradyarrhythmia at birth, preterm birth and umbilical artery pH < 7.15 were associated independently with high NP levels (P < 0.01). Among fetuses with a CVP score of ≤ 7, abnormal venous Doppler sonography findings were significantly more common and more severe in fetuses with tachy- or bradyarrhythmia than in those with CHD, and those with tachy- or bradyarrhythmia had higher NP levels than did those with CHD (P = 0.01). Fetuses with right-heart defect and moderate or severe tricuspid valve regurgitation had significantly higher NP levels than did fetuses with other types of CHD (P < 0.01). CONCLUSIONS: Plasma NP levels in fetuses with CHD and/or arrhythmia are correlated with the severity of fetal heart failure. Elevated NP levels are attributed mainly to an increase in central venous pressure secondary to arrhythmia or atrioventricular valve regurgitation due to CHD, rather than to the morphological abnormality itself. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Radon Anomaly: A Possible Precursor of the 1978 Izu-Oshima-kinkai Earthquake.

Precursory changes in the radon concentration of groundwater were observed prior to the Izu-Oshima-kinkai earthquake (magnitude 7.0) 14 January 1978. The distance from the epicenter to a continuous radon-monitoring station at Nakaizu was about 25 kilometers. A sudden drop and a subsequent increase in the radon concentration recorded on 9 January 1978 were significant. The size of the spike-like change was about 15 percent. After the earthquake, a remarkable increase in the radon concentration occurred.

Asymmetrical interhemispheric fiber tracts in patients with hemimegalencephaly on diffusion tensor magnetic resonance imaging.

OBJECTIVE: The internal structures of cerebral white matter in patients with hemimegalencephaly have not yet been investigated except for one, which evaluated aberrant fibers. We examined interhemispheric fiber tracts (FT) passing through the corpus callosum using magnetic resonance (MR) diffusion tensor imaging (DTI). METHODS: MR studies, including DTI, were performed in nine consecutive patients with hemimegalencephaly and in 11 patients with West syndrome as disease controls. The interhemispheric FT passing through the corpus callosum were evaluated in six regional geometric subdivisions in every hemimegalencephaly and West syndrome patient (54 and 66 subregions, respectively), and the distribution and volume differences between affected and unaffected hemispheres were all compared. RESULTS: In patients with hemimegalencephaly, interhemispheric FT were symmetrically distributed in 27 (50%) of the 54 corpus callosum subregions. However, the FT were distributed to different areas in the same lobes in 22 (40%) subregions, and to different lobes in five (9%) subregions. FT volumes were symmetrical in 35 (65%) subregions, while FT volumes on the affected side were greater, but less than those on the unaffected side, in 14 (26%) and five (9%) subregions, respectively. In contrast, in the West syndrome patients, interhemispheric FT showed symmetrical distributions and volumes in all regions. CONCLUSION: Asymmetrical interhemispheric FT are often observed in patients with hemimegalencephaly, and DTI was a useful means of elucidating the internal structures of white matter.

Prevention of corticosteroid-induced osteonecrosis in rabbits by intra-bone marrow injection of autologous bone marrow cells.

OBJECTIVES: Femoral head osteonecrosis (ON) is a serious complication of steroid administration. We evaluated bone marrow transplantation (BMT) for preventing corticosteroid-induced ON. METHODS: Rabbits, injected with methylprednisolone (MPSL; 20 mg/kg), were divided into four groups: (i) MPSL alone; MPSL injection only, (ii) MPSL+needling; 2 days after MPSL injection, a hole (1.2 mm diameter) was drilled from the outer cortex 2.5 cm distal to the proximal end of the greater trochanter, (iii) MPSL+saline; 2 days after MPSL injection, 2 ml saline was injected directly into the bone marrow cavity, and (iv) MPSL+BMT; 2 days after MPSL injection, 1 x 10(7)/2 ml bone marrow cells (BMCs) were injected directly into the bone marrow cavity. Platelets, fibrinogen, prothrombin time and total cholesterol in peripheral blood were measured before and after treatment. Tissues were stained with haematoxylin and eosion and terminal deoxynucleotidyl-mediated deoxyuridine triphosphate nick-end labelling stain and immunostained for VEGF, while cell proliferation and viability of whole BMCs in the femur were analysed by cell cycle analysis and [(3)H]-thymidine uptake. RESULTS: The ON incidence in rabbits treated with MPSL alone, MPSL+needling and MPSL+saline was 72.7, 70.0 and 66.7%, respectively, while in the MPSL+BMT group, the incidence was 0%. Serological findings in the MPSL+BMT group were almost normalized. VEGF and TUNEL staining were reduced in the MPSL+BMT group compared with all other groups. There were significantly fewer BMCs in G1 phase from the MPSL+BMT group than the other groups, while uptake of [(3)H]-thymidine was significantly increased. CONCLUSION: Direct injection of autologous BMCs into femurs prevents corticosteroid-induced ON following treatment with high-dose, short-term steroids.

CLOCK gene T3111C polymorphism is associated with Japanese schizophrenics: a preliminary study.

The CLOCK gene has attracted attention due to its influence on the circadian rhythm, as well as its impacts on the dopaminergic system. We conducted a preliminary study to examine whether the T3111C single nucleotide polymorphism of the CLOCK gene is associated with the development of schizophrenia by examining samples from schizophrenics (n=145) and normal controls (n=128). Both genotype and allele frequencies were significantly different between schizophrenics and controls (p=0.022, p=0.015, respectively). Schizophrenics had a significantly higher frequency of the C allele compared to controls (odds ratio 1.76, 95% CI 1.12-2.75). In particular, disorganized and residual type schizophrenics had significantly higher C allele frequencies than controls (p=0.004 and p=0.037, respectively). Our results suggest that the T3111C polymorphism of the CLOCK gene is associated with schizophrenia. It is important to explore the association between CLOCK and dopamine function, and to examine the impact of CLOCK on phenotypes such as symptoms and drug response in patients with schizophrenia.

Mice overexpressing human caspase 3 appear phenotypically normal but exhibit increased apoptosis and larger lesion volumes in response to transient focal cerebral ischaemia.

Caspase 3 activation has been implicated in cell death following a number of neurodegenerative insults. To determine whether caspase genes can affect the susceptibility of cells to neurodegeneration, a transgenic mouse line was created, expressing human caspase 3 under control of its own promoter. The human gene was regulated by the murine homeostatic machinery and human procaspase 3 was expressed in the same tissues as mouse caspase 3. These novel transgenic mice appeared phenotypically and developmentally normal and survived in excess of 2 years. Behavioural assessment using the 5-choice serial reaction time task found no differences from wild-type littermates. Caspase activity was found to be tightly regulated under physiological conditions, however, significantly larger lesions were obtained when transgenic mice were subjected to focal cerebral ischaemia/reperfusion injury compared to wild-type littermates. These data demonstrate that mice overexpressing human caspase 3 are essentially normal, however, they have increased susceptibility to degenerative insults.

Plasma membrane-associated actin in bright yellow 2 tobacco cells. Evidence for interaction with microtubules

Plasma membrane ghosts form when plant protoplasts attached to a substrate are lysed to leave a small patch of plasma membrane. We have identified several factors, including the use of a mildly acidic actin stabilization buffer and the inclusion of glutaraldehyde in the fixative, that allow immunofluorescent visualization of extensive cortical actin arrays retained on membrane ghosts made from tobacco (Nicotiana tabacum L.) suspension-cultured cells (line Bright Yellow 2). Normal microtubule arrays were also retained using these conditions. Membrane-associated actin is random; it exhibits only limited coalignment with the microtubules, and microtubule depolymerization in whole cells before wall digestion and ghost formation has little effect on actin retention. Actin and microtubules also exhibit different sensitivities to the pH and K+ and Ca2+ concentrations of the lysis buffer. There is, however, strong evidence for interactions between actin and the microtubules at or near the plasma membrane, because both ghosts and protoplasts prepared from taxol-pretreated cells have microtubules arranged in parallel arrays and an increased amount of actin coaligned with the microtubules. These experiments suggest that the organization of the cortical actin arrays may be dependent on the localization and organization of the microtubules.

Analysis system of submicron particle tracks in the fine-grained nuclear emulsion by a combination of hard x-ray and optical microscopy.

Analyses of nuclear emulsion detectors that can detect and identify charged particles or radiation as tracks have typically utilized optical microscope systems because the targets have lengths from several µm to more than 1000 µm. For recent new nuclear emulsion detectors that can detect tracks of submicron length or less, the current readout systems are insufficient due to their poor resolution. In this study, we developed a new system and method using an optical microscope system for rough candidate selection and the hard X-ray microscope system at SPring-8 for high-precision analysis with a resolution of better than 70 nm resolution. Furthermore, we demonstrated the analysis of submicron-length tracks with a matching efficiency of more than 99% and position accuracy of better than 5 µm. This system is now running semi-automatically.

Genetic risk factors in Japanese Alzheimer's disease patients: alpha1-ACT, VLDLR, and ApoE.

We studied the polymorphism of alpha1-antichymotrypsin (ACT), very low density lipoprotein receptor (VLDLR) and apolipoprotein E (ApoE) genes in 200 control subjects and 65 patients with Alzheimer's disease (AD) in Japanese. The subjects consisted of 30 patients with early onset familial Alzheimer's disease (FAD), a patient with late onset FAD, 29 patients with an early onset isolated form of AD, and 5 patients with late onset AD. ApoE genotypes were significantly different between controls and FAD (p < 0.0005) or AD (p < 0.05), and patients carrying at least one ApoE epsilon4 allele were found in 44% of FAD and 34.3% of AD; both were significantly different (p < 0.001) from the controls (12.5%). ACT genotypes and allele frequencies were not different among these groups except for genotypes between ApoE epsilon4 FAD and ApoE epsilon4 controls (p = 0.019). There was a slight but significant increase of the 5 repeat allele of VLDLR in AD (p = 0.014), but the difference was rather diminished in the presence of an ApoE epsilon4 allele. None of combinations of ACT and VLDLR genotypes in the presence or absence of an ApoE epsilon4 allele gave significant difference. Thus, we conclude that among the reported genetic risk factors, ApoE epsilon4 is the only definite risk factor for both FAD and AD, and the VLDLR polymorphism might be associated with AD cases in Japanese.

31P NMR study of the interactions between oligodeoxynucleotides containing (6-4) photoproduct and Fab fragments of monoclonal antibodies specific for (6-4) photoproduct.

A 31P nuclear magnetic resonance (NMR) study of the interactions between oligonucleotides containing the (6-4) photoproduct and the Fab fragments of monoclonal antibodies (64M3 and 64M5) recognizing the (6-4) photoproduct is reported. The 31P chemical shift data indicate that backbone conformation of (64) adduct is affected by the presence of flanking oligodeoxynucleotides, and (6-4) adducts with different backbone conformations are accommodated in the antigen binding sites of these antibodies. It was also revealed that epitopes for these antibodies consist of not only the (6-4) adduct but the flanking di- or tri-deoxynucleotides on both the 5' and 3' sides as well.

Plasma sulfhydryl-containing amino acids in patients with cerebral infarction and in hypertensive subjects.

It has been postulated that an accumulation of a sulfhydryl-containing amino acid, homocysteine in plasma may induce arteriosclerosis. In order to explore a possible contribution of homocysteine to the development of cerebral infarction in middle-aged and elderly patients, plasma sulfhydryl-containing amino acid profiles of 45 patients with cerebral infarction (CI) were compared with those of 45 normotensive and 45 hypertensive controls, and 20 patients with cerebral bleeding (CB), of similar ages and sex. The concentrations of both free and total homocysteine in plasma were highest in patients with CI among the 4 groups, while plasma free and total cysteinylglycine levels were similar. Although both free and total cysteine levels were also higher in patients with CI than in normotensive controls, the total homocysteine/total cysteine ratio was highest in patients with CI among the four groups. The hypertensive controls had higher plasma free and total concentrations than normotensive controls, but the levels did not differ between the 21 normotensive and 24 hypertensive CI patients. Our results suggest that high levels of plasma homocysteine in conjunction with hypertension could be one of the risk factors for arteriosclerotic CI.

Donepezil hydrochloride preserves regional cerebral blood flow in patients with Alzheimer's disease.

UNLABELLED: The aim of this SPECT study was to investigate the effects of donepezil on regional cerebral blood flow (rCBF) in patients with mild to moderate Alzheimer's disease (AD) using statistical parametric mapping. METHODS: rCBF was noninvasively measured using (99m)Tc-ethyl cysteinate dimer in 35 AD patients with a Mini-Mental State Examination score > 16 on initial evaluation. Baseline and follow-up SPECT studies with a mean interval of 12 mo were performed on these patients. We used the adjusted rCBF images in the relative flow distribution (normalization of global cerebral blood flow for each patient to 50 mL/100 g/min with proportional scaling) to compare these groups through statistical parametric mapping. RESULTS: In the follow-up study, the adjusted rCBF was significantly preserved in the right and left anterior cingulate gyri, right middle temporal gyrus, right inferior parietal lobules, and prefrontal cortex of donepezil-treated AD patients, compared with placebo-treated AD patients. CONCLUSION: Treatment with donepezil for 1 y appears to reduce the decline in rCBF, suggesting preservation of functional brain activity.

Longitudinal evaluation of early Alzheimer's disease using brain perfusion SPECT.

UNLABELLED: The aim of this SPECT study was to determine the initial abnormality and longitudinal changes in regional cerebral blood flow (rCBF) in early Alzheimer's disease (AD) using statistical parametric mapping (SPM). METHODS: rCBF was noninvasively measured using (99m)Tc-ethyl cysteinate dimer SPECT in 32 patients complaining of mild cognitive impairment, with a Mini-Mental State Examination score more than 24 at the initial study, and 45 age-matched healthy volunteers. All patients satisfied the diagnostic criteria of AD during the follow-up period of at least 2 y. Follow-up SPECT studies were performed on the patients at a mean interval of 15 mo. We used the raw data (absolute rCBF parametric maps) and the adjusted rCBF images of relative flow distribution (normalization of global cerebral blood flow [CBF] for each subject to 50 mL/100 g/min with proportional scaling) to compare these groups with SPM. RESULTS: In the baseline study, the adjusted rCBF was significantly and bilaterally decreased in the posterior cingulate gyri and precunei of patients compared with healthy volunteers. In the follow-up study, selected reduction of the adjusted rCBF was observed in the left hippocampus and parahippocampal gyrus. These areas showed the most prominent reduction in absolute rCBF on each occasion. Moreover, further decline of the absolute rCBF was longitudinally observed in extensive areas of the cerebral association cortex. CONCLUSION: SPM analysis showed the characteristic early-AD rCBF pattern of selective decrease and longitudinal decline, which may be overlooked by a conventional region-of-interest technique with observer a priori choice and hypothesis. This alteration in rCBF may closely relate to the pathophysiologic process of this disease.

Associations between retrospectively recalled napping behavior and later development of Alzheimer's disease: association with APOE genotypes.

To evaluate putative risk factors for Alzheimer's disease (AD), we conducted a case-control study with exposure assessment performed after disease onset. In this study, we evaluated the effect of recalled habitual napping according to its duration and examined whether APOE genotype modifies the effect. The subjects were 337 patients (144 men, 193 women, age at onset and the time of study (years): 69+/-10, 73+/-9) with a diagnosis of probable AD based on the NINCDS-ADRDA criteria. Two hundred and sixty spouses of the subjects (94 men, 166 women, age at the time of study: 69+/-9) served as controls. We asked retrospectively about habitual (3 or more days per week) napping and its duration observed between 5 and 10 years before the onset of AD for cases, and between 5 and 10 years before the time of the study for controls. The analysis revealed that limited napping for up to 60 min had an apparently protective effect against the development of AD, especially for carriers of the APOEepsilon 4 allele. By contrast, napping for more than 60 min increased the risk of AD morbidity among the carriers of the allele. Habitual napping may modulate or disturb the physiological functions of sleep and circadian time-keeping according to its duration, and this might be associated with some mechanism that leads to the development of AD.

Severe hypoxia due to ventilation-perfusion mismatch caused by aortic arch aneurysm.

We report a very rare case of hugh aortic arch aneurysm associated with aortic restenosis, which caused severe hypoxia due to ventilation-perfusion mismatch by compression of the left main bronchus and the right pulmonary artery. Aortic arch replacement was performed under circulatory arrest and deep hypothermia in addition to aortic valve replacement as a redo operation, and consequently such hypoxia was relieved.

Prevalence of dementia and distribution of ApoE alleles in Japanese centenarians: an almost-complete survey in Yamanashi Prefecture, Japan.

OBJECTIVE: To determine the prevalence and types of dementia in centenarians and to examine whether the ApoE epsilon 4 allele has significant impact on the development of Alzheimer's disease (AD) in the population. DESIGN: Cross-sectional study and a 6-month prospective study. SETTING: Yamanashi Prefecture, Japan. PARTICIPANTS: Forty-seven centenarians participated in the study to determine the prevalence and types of dementia. Thirty-three of the 47 participated in the study of ApoE genotyping. As controls, 224 demented older adults participated in the genetic study. Their age at onset was < 90 years. OUTCOMES: Prevalence of dementia based on DSM-III-R; types of dementia based on NINCDS-ADRDA and ICD-10; distribution on ApoE alleles in the centenarians and in the controls; and the 6-month mortality rate of the subjects. MAIN RESULTS: Of 47 centenarians, 70.2% had dementia, and AD accounted for the majority (75.8%) of the dementia cases. The distribution of ApoE alleles in all the subjects and the AD subjects was epsilon 2: 4.6% vs. 0%; epsilon 3: 90.1% vs. 94.1%; epsilon 4: 4.6% vs. 5.9%. The frequency of the epsilon 4 allele in the AD patients showed a tendency to decrease with increasing age, ranging from 38% for those with an age at onset of < 60 years to 22% for those with an age at onset of ranging from 80 to 89 years. The 6-month mortality rate was 27% (9/33) for the demented centenarians, whereas none of the 14 nondemented centenarians died. CONCLUSION: This almost-complete survey, conducted in a prefecture of Japan, revealed a high prevalence of dementia in centenarians. The ApoE epsilon 4 allele does not have an impact on the development of AD in centenarians.

Calcium regulation in clam foot muscle. Calcium sensitivity of clam foot myosin.

1. The ATPase activity of clam foot myosin alone in the presence of 10 mM MgCl2 was activated approximately ten-fold by 10 muM free calcium ions. The calcium activation was observed in various concentrations of KCl (35-600 mM) and ATO (1 muM-1 mM), and at various pHs (pH 6-9.4). 2. The superprecipitation and ATPase activities of clam foot myosin B were studied by conducting experiments in two different ways. In one of these, the ATP concentration was varied at a fixed concentration of MgCl2, and in the other, the MgCl2 concentration was varied at a fixed concentration of ATP. The following was found: (a) The activities responded in a biphasic manner to change in either the ATP or MgCl2 concentration, giving a peak activity around 10 muM ATP or MgCl2. It is thus suggested that Mg-ATP complex is responsible for both activation and inhibition in the biphasic response. (b) When the ATP or MgCl2 concentration was higher than 100-300 muM, practically no superprecipitation occurred in either the presence or absence of calcium, whereas the ATPase activity was still strongly activated by calcium. 3. Similar results to those described above (a, b) were obtained by using rabbit skeletal actoclam foot myosin in place of clam foot myosin B. Moreover, it was found that as the ATP concentration increased from 1 muM to 1 mM, Mg-ATPase activity of clam foot myosin in the presence of calcium increased in a monophasic manner and that it was as active as actomyosin in the presence of calcium when the ATP concentration was higher than approximately 200 muM. In other words, actin-activation of myosin-ATPase was absent in the ATP concentration where no superprecipitation of actomyosin was observed. 4. Clam foot myosin contained two types of light chain subunits: LCl (17,000 daltons) and LC2 (16,000 daltons). Only LC1 was removed upon washing clam myosin with 10 mM EDTA, and removal of LC1 resulted in loss of the calcium sensitivity of actomyosin-ATPase. 5. In our previous report (J. Biochem. 85, 1543-1546, 1979), it was shown that removal of LC1 from clam foot myosin also resulted in loss of the superprecipitation activity of actomyosin reconstituted from "EDTA-washed" myosin. We now provide further evidence that removal of the regulatory light chain (LC1) results in a reversible uncoupling of ATPase reaction from superprecipitation reaction.

Calcium sensitivy of foot muscle myosin from clam (Meretrix lusoria).

1. It was found that Mg-ATPase of clam foot myosin is strongly activated by calcium or strontium ions and is as sensitive to those divalent cations as the Mg-ATPase and superprecipitation of rabbit skeletal acto-clam foot myosin are. 2. It was also found that desensitization and resensitization of clam foot myosin result in the loss of superprecipitation activity with acto-desensitized myosin and in its recovery with acto-resensitized myosin, respectively. However, the ATP-ASE activity in the absence of calcium ions rises with acto-desensitized myosin and falls again with acto-resensitized myosin. 3. It is thus proposed that the primary role of the EDTA-light chain component in calcium regulation is to inhibit myosin-ATPase rather than to inhibit the actin-myosin interaction.

Repetitive cocaine administration decreases neurogenesis in adult rat hippocampus.

Cocaine HCl (20 mg/kg) was administered to adult male rats to investigate the effects of cocaine on neurogenesis in the hippocampus. Proliferation of granule cells in the dentate gyrus was measured by in vivo labeling with 5-bromo-2'-deoxyuridine (BrdU). Rats that received repetitive cocaine treatment for 14 days showed 26% fewer BrdU-positive cells relative to control rats, while no difference was observed in the rats that received a single injection of cocaine. Differentiation of newly born cells was not influenced. The present experiment is the first to demonstrate the influence of cocaine on hippocampal neurogenesis. These data suggest that the regulation of hippocampal neurogenesis may be involved in the emergence of certain symptoms of cocaine addiction, such as cognitive impairment and behavioral sensitization.