60Fe and 244Pu deposited on Earth constrain the r-process yields of recent nearby supernovae.

Half of the chemical elements heavier than iron are produced by the rapid neutron capture process (r-process). The sites and yields of this process are disputed, with candidates including some types of supernovae (SNe) and mergers of neutron stars. We search for two isotopic signatures in a sample of Pacific Ocean crust-iron-60 (60Fe) (half-life, 2.6 million years), which is predominantly produced in massive stars and ejected in supernova explosions, and plutonium-244 (244Pu) (half-life, 80.6 million years), which is produced solely in r-process events. We detect two distinct influxes of 60Fe to Earth in the last 10 million years and accompanying lower quantities of 244Pu. The 244Pu/60Fe influx ratios are similar for both events. The 244Pu influx is lower than expected if SNe dominate r-process nucleosynthesis, which implies some contribution from other sources.

A preoperative prognostic nutritional index is a prognostic indicator in oral squamous cell carcinoma patients undergoing radical surgery.

The purpose of this study was to investigate the prognostic value of prognostic nutritional index (PNI) in oral squamous cell carcinoma (OSCC) patients and to undertake a comparative evaluation of the prognostic value of comparing PNI, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in terms of prognostic utility. A retrospective study was conducted involving 203 consecutive patients with OSCC who were treated with radical surgery with curative intent. The PNI and systemic inflammatory response were developed, and their prognostic utility was evaluated. Kaplan-Meier curve analysis and log-rank testing showed that PNI (P< 0.001), NLR (P=0.011), PLR (P=0.013), and LMR (P=0.014) were significantly associated with overall survival. Multivariate analysis identified PNI as an independent prognostic factor for OSCC patients (P=0.029). In time-dependent receiver operating characteristic curve analysis, PNI was continuously superior to that of NLR, PLR, and LMR. In conclusion, this study suggested that PNI offered an independent prognostic biomarker in OSCC patients undergoing radical surgery. However, this study was small and retrospective, thus further investigations are needed to clarify the utility of PNI for tailor-made treatments in clinical settings.

Iodine-129 for determining the origin of salinity in groundwater in Pampanga, Philippines.

Assessing groundwater vulnerability from salinity contamination is vital and relevant to meet the increasing demand for freshwater. Iodine-129 (129I, half-life = 15.7 million years), a radioisotope of iodine, was used as an environmental tracer for the possible origin of salinization in groundwater (e.g., natural rock weathering, evaporated water, seawater, brine fossil water, contamination). In July 2017 (wet season), thirty-two (32) water samples were taken from production wells of different localities in Pampanga, a province in the Philippines that relies heavily on groundwater for freshwater sources. Hydrogeochemical (mainly Cl) and stable water isotopes (δ2H and δ18O) were able to identify seven samples potentially affected by seawater intrusion. The salinity origin of these samples was investigated using iodine-129 and iodine-127 isotopes by generating two graphs: 129I vs. chloride and 129I/127I ratio vs. 1/127I. 129I vs. Cl graph was capable of showing a clear distinction between different salinity origins. Five out of the seven samples were being affected by evaporated water, one sample from possible wastewater, and one sample from brine fossil water. A conceptual model was produced to summarize the results. Compiled end-members (e.g., natural brine, seawater, modern rain) were plotted in the 129I/127I ratio vs. 1/127I graph to show the interaction between two recharge sources. The results of this study will be helpful to the government, civil society, and other organizations for monitoring, policymaking, and management of the groundwater and the subsurface formations that will be crucial to continuously supply the freshwater needs of the present and future generation.

Functional analysis of a novel G87V TNFRSF1A mutation in patients with TNF receptor-associated periodic syndrome.

Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is an autoinflammatory disease that is caused by heterozygous mutations in the TNFRSF1A gene. Although more than 150 TNFRSF1A mutations have been reported to be associated with TRAPS phenotypes only a few, such as p.Thr79Met (T79M) and cysteine mutations, have been functionally analyzed. We identified two TRAPS patients in one family harboring a novel p.Gly87Val (G87V) mutation in addition to a p.Thr90Ile (T90I) mutation in TNFRSF1A. In this study, we examined the functional features of this novel G87V mutation. In-vitro analyses using mutant TNF receptor 1 (TNF-R1)-over-expressing cells demonstrated that this mutation alters the expression and function of TNF-R1 similar to that with the previously identified pathogenic T79M mutation. Specifically, cell surface expression of the mutant TNF-R1 in transfected cells was inhibited with both G87V and T79M mutations, whereas the T90I mutation did not affect this. Moreover, peripheral blood mononuclear cells (PBMCs) from TRAPS patients harboring the G87V and T90I mutations showed increased mitochondrial reactive oxygen species (ROS). Furthermore, the effect of various Toll-like receptor (TLR) ligands on inflammatory responses was explored, revealing that PBMCs from TRAPS patients are hyper-responsive to TLR-2 and TLR-4 ligands and that interleukin (IL)-8 and granulocyte-macrophage colony-stimulating factor (GM-CSF) are likely to be involved in the pathogenesis of TRAPS. These findings suggest that the newly identified G87V mutation is one of the causative mutations of TRAPS. Our findings based on unique TRAPS-associated mutations provide novel insight for clearer understanding of inflammatory responses, which would be basic findings of developing a new therapeutic and prophylactic approach to TRAPS.

Experience of Quatro-Therapy With Everolimus to Minimize Calcineurin Inhibitor for Kidney Transplant Recipients.

BACKGROUND: This study was divided into three phases, on the occasion of the introduction of everolimus (EVR) in our hospital. METHODS: In the first phase, a study group of six maintenance patients (three living related donors, three deceased donors) who had a history of malignant disease with less than 500 mg/day of proteinuria were enrolled; a high serum creatinine and upper limit of duration after kidney transplant operation was not considered. EVR was discontinued in four of the six patients because of side effects or worsening renal function. The second phase comprised a study group of 12 maintenance patients (12 living related donors) who were more than 5 years after kidney transplant operation with serum creatinine <3 ng/mL and proteinuria <500 mg/day. In two patients, EVR was discontinued because of a skin rash or general fatigue, but EVR was continued in 10 cases. Calcineurin inhibitor (CNI) dosage was reduced and renal function improved, and mean estimated glomerular filtration rate recovered from 42.3 mL/min to 44.8 mL/min, with no rejections occurring. In the third phase, a study group of eight de novo transplant patients who were 2 to 3 weeks after transplant operation were examined. In one case, EVR was discontinued because of proteinuria but was restarted with a stepwise increasing method after 4 months and was continued without any side effects. RESULTS: Our study indicates that EVR was a useful drug for the maintenance of kidney transplant recipients for the optimal patients. CONCLUSIONS: In de novo cases, EVR plus a high dose of mizoribine and low CNI protocol was a useful regimen without serious adverse effects.

Recent near-Earth supernovae probed by global deposition of interstellar radioactive (60)Fe.

The rate of supernovae in our local Galactic neighbourhood within a distance of about 100 parsecs from Earth is estimated to be one every 2-4 million years, based on the total rate in the Milky Way (2.0 ± 0.7 per century). Recent massive-star and supernova activity in Earth's vicinity may be traced by radionuclides with half-lives of up to 100 million years, if trapped in interstellar dust grains that penetrate the Solar System. One such radionuclide is (60)Fe (with a half-life of 2.6 million years), which is ejected in supernova explosions and winds from massive stars. Here we report that the (60)Fe signal observed previously in deep-sea crusts is global, extended in time and of interstellar origin from multiple events. We analysed deep-sea archives from all major oceans for (60)Fe deposition via the accretion of interstellar dust particles. Our results reveal (60)Fe interstellar influxes onto Earth at 1.5-3.2 million years ago and at 6.5-8.7 million years ago. The signal measured implies that a few per cent of fresh (60)Fe was captured in dust and deposited on Earth. Our findings indicate multiple supernova and massive-star events during the last ten million years at distances of up to 100 parsecs.

Excitation-photon-energy selectivity of photoconversions in halogen-bridged Pd-chain compounds: Mott insulator to metal or charge-density-wave state.

Ultrafast photoinduced transitions of a one-dimensional Mott insulator into two distinct electronic phases, metal and charge-density-wave (CDW) state, were achieved in a bromine-bridged Pd-chain compound [Pd(en)2Br](C5-Y)2H2O (en=ethylenediamine and C5-Y=dialkylsulfosuccinate), by selecting the photon energy of a femtosecond excitation pulse. For the resonant excitation of the Mott-gap transition, excitonic states are generated and converted to one-dimensional CDW domains. For the higher-energy excitation, free electron and hole carriers are produced, giving rise to a transition of the Mott insulator to a metal. Such selectivity in photoconversions by the choice of initial photoexcited states opens a new possibility for the developments of advanced optical switching and memory functions.

RAS/PI3K crosstalk and cetuximab resistance in head and neck squamous cell carcinoma.

PURPOSE: Cetuximab, an antibody directed against the EGF receptor, is an effective clinical therapy for patients with head and neck squamous cell cancer (HNSCC). Despite great clinical promise, intrinsic or acquired cetuximab resistance hinders successful treatment outcomes but little is known about the underlying mechanism. EXPERIMENTAL DESIGN: To study the role of oncogenic HRAS in cetuximab resistance in HNSCC, the frequency of oncogenic HRAS mutations was determined in a cohort of 180 genomic DNAs from head and neck cancer specimens. We also used a combination of cetuximab-resistant cell lines and a transgenic mouse model of RAS-driven oral cancer to identify an oncogenic RAS-specific gene expression signature that promotes cetuximab resistance. RESULTS: Here, we show that activation of RAS signaling leads to persistent extracellular signal-regulated kinase 1/2 signaling and consequently to cetuximab resistance. HRAS depletion in cells containing oncogenic HRAS or PIK3CA restored cetuximab sensitivity. In our study, the gene expression signature of c-MYC, BCL-2, BCL-XL, and cyclin D1 upon activation of MAPK signaling was not altered by cetuximab treatment, suggesting that this signature may have a pivotal role in cetuximab resistance of RAS-activated HNSCC. Finally, a subset of patients with head and neck cancer with oncogenic HRAS mutations was found to exhibit de novo resistance to cetuximab-based therapy. CONCLUSIONS: Collectively, these findings identify a distinct cetuximab resistance mechanism. Oncogenic HRAS in HNSCC promotes activation of ERK signaling, which in turn mediates cetuximab resistance through a specific gene expression signature. Clin Cancer Res; 20(11); 2933-46. ©2014 AACR.

Diagnostic value of MRI for odontogenic tumours.

OBJECTIVES: To evaluate the diagnostic value of MRI for odontogenic tumours. MATERIALS AND METHODS: 51 patients with odontogenic tumours were subjected to pre-operative MRI examinations. For tumours with liquid components, i.e. ameloblastomas and keratocystic odontogenic tumours (KCOTs), the signal intensity (SI) uniformity of their cystic components (UΣ) was calculated and then their UΣ values were compared. For tumours with solid components that had been examined using dynamic contrast-enhanced MRI (DCE-MRI), their CImax (maximum contrast index), Tmax (the time when CImax occurred), CIpeak (CImax × 0.90), Tpeak (the time when CIpeak occurred) and CI300 (i.e. the CI observed at 300 s after contrast medium injection) values were determined from CI curves. We then classified the odontogenic tumours according to their DCE-MRI parameters. RESULTS: Significant differences between the UΣ values of the ameloblastomas and KCOT were observed on T1 weighted images, T2 weighted images and short TI inversion recovery images. Depending on their DCE-MRI parameters, we classified the odontogenic tumours into the following five types: Type A, CIpeak > 2.0 and Tpeak < 200 s; Type B, CIpeak < 2.0 and Tpeak < 200 s; Type C, CI300 > 2.0 and Tmax < 600 s; Type D, CI300 > 2.0 and Tmax > 600 s; Type E, CI300 < 2.0 and Tmax > 600 s. CONCLUSION: Cystic component SI uniformity was found to be useful for differentiating between ameloblastomas and KCOT. However, the DCE-MRI parameters of odontogenic tumours, except for odontogenic fibromas and odontogenic myxomas, contributed little to their differential diagnosis.

Absence of age-related prefrontal NAA change in adults with autism spectrum disorders.

Atypical trajectory of brain growth in autism spectrum disorders (ASDs) has been recognized as a potential etiology of an atypical course of behavioral development. Numerous neuroimaging studies have focused on childhood to investigate atypical age-related change of brain structure and function, because it is a period of neuron and synapse maturation. Recent studies, however, have shown that the atypical age-related structural change of autistic brain expands beyond childhood and constitutes neural underpinnings for lifelong difficulty to behavioral adaptation. Thus, we examined effects of aging on neurochemical aspects of brain maturation using 3-T proton magnetic resonance spectroscopy ((1)H-MRS) with single voxel in the medial prefrontal cortex (PFC) in 24 adult men with non-medicated high-functioning ASDs and 25 age-, IQ- and parental-socioeconomic-background-matched men with typical development (TD). Multivariate analyses of covariance demonstrated significantly high N-acetylaspartate (NAA) level in the ASD subjects compared with the TD subjects (F=4.83, P=0.033). The low NAA level showed a significant positive correlation with advanced age in the TD group (r=-0.618, P=0.001), but was not evident among the ASD individuals (r=0.258, P=0.223). Fisher's r-to-z transformation showed a significant difference in the correlations between the ASD and TD groups (Z=-3.23, P=0.001), which indicated that the age-NAA relationship was significantly specific to people with TD. The current (1)H-MRS study provided new evidence that atypical age-related change of neurochemical aspects of brain maturation in ASD individuals expands beyond childhood and persists during adulthood.

Relaxation dynamics of photoexcited excitons in rubrene single crystals using femtosecond absorption spectroscopy.

The relaxation dynamics of an exciton in rubrene was investigated by femtosecond absorption spectroscopy. Exciton relaxation to a self-trapped state occurs via the coherent oscillation with 78 cm(-1) due to a coupled mode of molecular deformations with phenyl-side-group motions and molecular displacements. From the temperature dependence of the decay time of excitons, the energy necessary for an exciton to escape from a self-trapped state is evaluated to be ~35 meV (~400 K). As a result, a self-trapped exciton is stable at low temperatures. At room temperature, excitons can escape from a self-trapped state and, subsequently, they are dissociated to charged species. The exciton dissociation mechanism is discussed on the basis of the results.

Serum levels of P-selectin in men with high-functioning autism.

Immune dysfunction has been proposed as a mechanism for the pathophysiology of autistic-spectrum disorders. The selectin family of adhesion molecules plays a prominent role in immune/inflammatory responses. We determined the serum levels of three types of soluble-form selectin (sP, sL and sE) in 15 men with high-functioning autism and 22 age-matched healthy controls by enzyme-linked immunosorbent assay. Levels of sP-selectin and sL-selectin were significantly lower in patients than in controls. Furthermore, sP-selectin levels were negatively correlated with impaired social development during early childhood.

Evaluation of panoramic radiographs taken at the initial visit at a department of paediatric dentistry.

OBJECTIVES: To examine oral and maxillofacial lesions other than those related to the chief complaint in panoramic radiographs taken at the department of paediatric dentistry at our hospital. METHODS: We retrospectively reviewed all 1092 patients who had visited the department of paediatric dentistry at our hospital and had a panoramic radiograph taken between August 1999 and October 2004. The following information was obtained from the patients' files and panoramic radiographs: gender, age, chief complaints and the presence or absence of lesions. RESULTS: Lesions were observed in 140 of the 1092 panoramic radiographs (12.8%). Among the 140 patients discovered to have lesions in the panoramic radiographs, 66 (47.1%, or 6.05% of the entire group of 1092 patients) had different lesions from those underlying the chief complaint. These 66 patients ages ranged from 3 years to 14 years and the lesions involved 39 (59.1%) missing teeth, 20 (30.3%) mesiodentes, 4 supernumerary teeth, 1 odontoma, 1 radicular cyst and 1 impacted tooth. The missing teeth were observed in the central and lateral incisor, canine, and first and second premolar positions of both jaws, especially in the lower lateral incisor and upper central incisor positions. CONCLUSIONS: We were able to detect incidental lesions at a rate of 6.05% (66 of 1092 patients) and at a relatively early age (mean 6.8 years) in the present study. Early treatment of these lesions could avoid maxillofacial deformity and other complications.

p53AIP1 expression can be a prognostic marker in non-small cell lung cancer.

AIMS: p53AIP1 is a potential mediator of p53-dependent apoptosis that is mutated in many kinds of carcinoma. To investigate the role of this gene for non-small cell lung cancer, we compared the relationship between p53AIP1 gene expression and clinicopathological status of lung cancer. MATERIALS AND METHODS: Seventy samples from non-small cell lung cancer patients were obtained between 1997 and 2003. For quantitative evaluation of RNA expression by polymerase chain reaction (PCR) we used the Taqman PCR methods. Exons 5-8 of the p53 gene were analysed using PCR-single-stranded conformation polymorphism and sequenced for mutation analysis. RESULTS: p53AIP1 gene expression levels in the lymph node metastasis-positive group were significantly lower than in the negative group (positive 35.1+/-83.9; negative 64.2+/-113.4; P=0.0486). The overall survival of the p53AIP1 low expression group was significantly worse than that of the p53AIP1 high expression group (P=0.0206). In the multivariate Cox proportional hazard model, p53AIP1 (P=0.0489) was the independent predictor for overall survival. When we investigated mutation analyses of the p53 gene, we could find several point mutations in 15.7% of all samples. However, there was no relationship between p53AIP1 expression and p53 status. CONCLUSIONS: These data suggest that the p53AIP1 gene is important for non-small cell lung cancer progression and may be a possible prognostic marker.

Photoinduced metallic state mediated by spin-charge separation in a one-dimensional organic Mott insulator.

Charge dynamics in a one-dimensional (1D) Mott insulator was investigated by fs pump-probe reflection spectroscopy on an organic charge-transfer compound, bis(ethylenedithio)tetrathiafulvalene-difluorotetracyanoquinodimethane (ET-F2TCNQ). The analyses of the transient reflectivity changes demonstrate that low-energy spectral weight induced by photocarrier doping is concentrated on a Drude component being independent of the doping density, and midgap state is never formed. Such phenomena can be explained by the concept of spin-charge separation characteristic of 1D correlated electron systems.

Osteopontin as biomarker in early invasion by squamous cell carcinoma in tongue.

BACKGROUND: Osteopontin (OPN) expression in squamous cell carcinoma (SCC) of the tongue has not been clearly elucidated. METHODS: We selected 46 cases of tongue SCC and investigated the expression of OPN by immunohistochemical staining. The immunopositive reaction and score for each case were semiquantitatively evaluated. RESULTS: Scores were significantly higher in carcinoma nests than in neighboring normal epithelium or epithelial dysplasia. The OPN was expressed clearly in the cytoplasm of carcinoma cells. In cases of early invasive carcinoma, in particular, expression of OPN showed a remarkable increase at the invasion front compared with the non-invaded regions. However, there was no significant correlation between expression of OPN in the primary tumor nest and lymphatic metastasis, recurrence, or survival rate. CONCLUSION: This suggests that OPN is a useful biomarker of early invasion by SCC in tongue.

Endoscopic carpal tunnel release in the elderly.

The present study is aimed to clarify the postoperative outcome of endoscopic carpal tunnel release in elderly patients with carpal tunnel syndrome. Endoscopic carpal tunnel release was performed on 37 hands of 27 patients (2 men, 25 women) who were aged 70 years or older and clinically and electrophysiologically diagnosed with carpal tunnel syndrome. Mean age at the time of surgery was 74.5 years (range: 70-85 years). Mean postoperative follow-up was 35.5 months (range: 12-114 months). Pain was present preoperatively in 20 hands, but quickly resolved postoperatively in all cases. Numbness completely disappeared in 13 of 37 hands (35.1%), but some degree of numbness remained in the remaining cases. Preoperative severity of thenar muscle atrophy was none in 4 hands, mild in 7 hands, moderate in 12 hands and severe in 14 hands. Postoperative severity of thenar muscle atrophy at final follow-up was none in 13 hands, mild in 16 hands, moderate in 2 hands and severe in 6 hands, confirming that thenar muscle atrophy improves even in elderly patients. However, moderate or severe thenar muscle atrophy remained in 8 hands (21.6%). Endoscopic carpal tunnel release should be considered in the elderly, even though clinical symptoms may not improve substantially in advanced cases.

Moderate magnesium-restricted diet affects bone formation and bone resorption in rats.

This study investigated the effects of moderate magnesium (Mg)-restricted diet on bone formation and bone resorption in rats. Weanling Wistar strain rats were randomly divided into three dietary groups of 6 rats each and fed their respective diets; a control diet containing 0.05% Mg (C), a half Mg diet containing 0.025% Mg (1/2Mg), or a one-fifth Mg diet containing 0.01% Mg (1/5Mg), for 21 days. Serum osteocalcin level was significantly reduced with decreasing dietary Mg level. Urinary excretion of C-terminal telopeptide of type 1 collagen was significantly higher in the 1/5Mg group than in the C group. Serum insulin-like growth factor-1 (IGF-1) level was significantly lower in the 1/2Mg and 1/5Mg groups than in the C group. Serum soluble receptor activator of nuclear factor-kappaB ligand (sRANKL) level was significantly higher in the 1/2Mg and 1/5Mg groups than in the C group. These results showed that a moderate Mg-restricted diet induced a decrease in bone formation and an increase in bone resorption. Furthermore, these changes of bone formation and bone resorption might be caused by serum IGF-1 and sRANKL levels, respectively.