Anomalous Flexural Elasticities of Graphene Membranes Unveiled by Manipulating Topology.

Mechanical behavior of atomically thin membranes is governed by bending rigidity and the Gaussian modulus. However, owing to methodological drawbacks, these two parameters have not been investigated sufficiently. We employed atomic force microscopy to demonstrate that the bending rigidity can be extracted from a quadratic relationship of adhesion energy with monolayer curvatures of rolled and unrolled graphene. The tip-induced topological defects revealed the Gaussian modulus; to the best of our knowledge, this is the first study on these parameters. Our study may hold great significance because existing investigations have been performed only on flat graphene. The configurational (strain) energy was evaluated via changes in the surface geometry, with subatomic resolution, by three-dimensional analyses of attractive interatomic forces. The mechanical parameters, evaluated at the hollow sites of the honeycomb lattice, were consistent with the isotropic elastic attributes. The remarkably large negative Gaussian modulus, observed when a single carbon atom was located at the center of the tip-induced bump, revealed attractive interactions between the topological defects and geometric potentials of the Gaussian curvature. Our approach will aid in developing two-dimensional materials and understanding cell biology.

A novel cooling method using carbon dioxide-rich water after passive heating.

In the event of a marked rise in body temperature, it is often necessary to reduce the temperature quickly. One method to rapidly drop body temperature is cold water immersion. Because carbon dioxide (CO2)-rich water causes cutaneous vasodilation, it may be that CO2-rich water reduces body temperature faster than fresh water. To test that idea, I compared the effects of CO2-rich and tap water immersion on auditory canal temperature (Tac) after passive heating. Nine healthy male subjects participated in the study. Subjects were first immersed for 15 min in a tap water bath at 40 °C to raise body temperature. They then moved to a tap water or CO2-rich water bath at 30 °C to reduce body temperature. Immersion in 40 °C tap water caused Tac to rise 0.64 ± 0.11 °C in the tap water session and 0.71 ± 0.25 °C in the CO2-rich water session (P > 0.05). During the 30 °C water immersion, Tac declined and was significantly lower in CO2-rich water than in tap water. Cooling rates were 0.06 ± 0.04 °C/min in tap water and 0.11 ± 0.05 °C/min in CO2-rich water (P < 0.05). In addition, both thermal sensation (3.2 ± 1.0 vs. 2.1 ± 0.9; P < 0.01) and thermal comfort (1.2 ± 0.4 vs. 2.1 ± 0.8; P < 0.01) were significantly better in CO2-rich water than tap water. These results suggest that CO2-rich water immersion reduces Tac 1.7 times faster than tap water immersion, and that CO2-rich water immersion cools the body more comfortably than tap water immersion.

Response to the "letter to the editor" by Sani Rachman Soleman et al., "spatiotemporal association of low birth weight with Cs-137 deposition at the prefecture level in Japan after the Fukushima nuclear power plant accidents".

We thank Sani Rachman Soleman et al. for three specific points of criticism concerning our investigation of the ecological association between low birth weight (LBW) and radioactive contamination in Japan after the Fukushima Daiichi Nuclear Power Plant (FDNPP) accidents: 1. Ecological variables are not justified enough to adjust potential confounding. 2. The spatiotemporal regression model does not consider temporal reduction in radiation dose rate. 3. Dose-response plot between dose rates and odds ratios overestimates R2 and underestimates p-value. This criticism is a good starting point to explain some of the technical backgrounds of our approach in more detail.

Spatiotemporal association of low birth weight with Cs-137 deposition at the prefecture level in Japan after the Fukushima nuclear power plant accidents: an analytical-ecologic epidemiological study.

BACKGROUND: Perinatal mortality increased in contaminated prefectures after the Fukushima Daichi Nuclear Power Plant (FDNPP) accidents in Japan in 2011. Elevated counts of surgeries for cryptorchidism and congenital heart malformations were observed throughout Japan from 2012 onward. The thyroid cancer detection rate (2011 to 2016) was associated with the dose-rate at the municipality level in the Fukushima prefecture. Since the birth weight is a simple and objective indicator for gestational development and pregnancy outcome, the question arises whether the annual birth weight distribution was distorted in a dose-rate-dependent manner across Japan after Fukushima. METHODS: The Japanese Ministry of Health, Labour, and Welfare provides prefecture-specific annual counts for 26.158 million live births from 1995 to 2018, of which 2.366 million births (9.04%) with weights < 2500 g. Prefecture-specific spatiotemporal trends of the low birth weight proportions were analyzed. Logistic regression allowing for level-shifts from 2012 onward was employed to test whether those level-shifts were proportional to the prefecture-specific dose-rates derived from Cs-137 deposition in the 47 Japanese prefectures. RESULTS: The overall trend of the low birth weight prevalence (LBWp) in Japan discloses a jump in 2012 with a jump odds ratio (OR) 1.020, 95%-confidence interval (1.003,1.037), p-value 0.0246. A logistic regression of LBWp on the additional dose-rate after the FDNPP accidents adjusted for prefecture-specific spatiotemporal base-line trends yields an OR per µSv/h of 1.098 (1.058, 1.139), p-value < 0.0001. Further adjusting the logistic regression for the annual population size and physician density of the prefectures, as well as for the counts of the dead, the missing, and the evacuees due to earthquake and tsunami (as surrogate measures for medical infrastructure and stress) yields an OR per µSv/h of 1.109 (1.032, 1.191), p-value 0.0046. CONCLUSIONS: This study shows increased low birth weight prevalence related to the Cs-137 deposition and the corresponding additional dose-rate in Japan from 2012 onward. Previous evidence suggesting compromised gestational development and pregnancy outcome under elevated environmental ionizing radiation exposure is corroborated.

Chronological shifts and changing causes of death after radiotherapy for early-stage oral cancer.

BACKGROUND: Following recent improvements in the curability of oral cancer, chronological shifts and changes in the causes of death after treatment have been observed. We conducted a review of the post-treatment causes of death following radiotherapy for oral cancers. MATERIALS AND METHODS: The medical records of 966 patients with early-stage (stage I and II) oral cancer treated at our institute between 1980 and 2001 were reviewed, and the chronological shifts and changes in the causes of death after radiotherapy were assessed. RESULTS: Of the 966 patients enrolled in this study, 365 have died to date. Two hundred and eleven patients died of their primary malignancy; 193 of these deaths occurred within 5 years of treatment for the primary oral cancer. The second most frequent cause of death was second primary cancer (n = 90). Twenty-three patients with head and neck cancers and 18 patients with esophageal cancers died within 10 years of radiotherapy, and six patients with lung cancers died after more than 10 years. CONCLUSION: Within the first 5 years following treatment, the major cause of death was the primary oral cancer. After 5-10 years, a second primary cancer, such as head and neck cancer or esophageal cancer, became the leading cause of death. Over a 10-year period, the proportion of deaths from a second primary cancer in the lung was significant. We have demonstrated that there are chronological shifts and changes in the causes of death following treatment for early-stage oral cancer.

Relationships between the extent of apnea-induced bradycardia and the vascular response in the arm and leg during dynamic two-legged knee extension exercise.

Our aim was to test the hypothesis that apnea-induced hemodynamic responses during dynamic exercise in humans differ between those who show strong bradycardia and those who show only mild bradycardia. After apnea-induced changes in heart rate (HR) were evaluated during dynamic exercise, 23 healthy subjects were selected and divided into a large response group (L group; n = 11) and a small response group (S group; n = 12). While subjects performed a two-legged dynamic knee extension exercise at a work load that increased HR by 30 beats/min, apnea-induced changes in HR, cardiac output (CO), mean arterial pressure (MAP), arterial O(2) saturation (Sa(O(2))), forearm blood flow (FBF), and leg blood flow (LBF) were measured. During apnea, HR in the L group (54 ± 2 beats/min) was lower than in the S group (92 ± 3 beats/min, P < 0.05). CO, Sa(O(2)), FBF, LBF, forearm vascular conductance (FVC), leg vascular conductance (LVC), and total vascular conductance (TVC) were all reduced, and MAP was increased in both groups, although the changes in CO, TVC, LBF, LVC, and MAP were larger in the L group than in the S group (P < 0.05). Moreover, there were significant positive linear relationships between the reduction in HR and the reductions in TVC, LVC, and FVC. We conclude that individuals who show greater apnea-induced bradycardia during exercise also show greater vasoconstriction in both active and inactive muscle regions.

Antenatal three-dimensional sonographic features of Roberts syndrome.

INTRODUCTION: We present a fetus whose characteristics most likely represent Roberts syndrome. CASE REPORT: Prenatal diagnosis at 21 weeks and 1 day age of gestation was made employing conventional two-dimensional (2D) sonography, showing shortened upper and lower extremities. An umbilical cord cyst was also noted. Three-dimensional (3D) sonography revealed additional abnormalities which included bilateral hypoplastic and proximal implantation of the thumb, exophthalmic eyes, and suspected cleft lip. Shortened upper extremities, contracted legs, and an umbilical cord cyst were also clearly confirmed. Transparent X-ray mode uncovered the absence of radial and ulnar bones. Subtle fetal structures were readily discernible with 3D sonography so that the family could understand the fetal condition in utero. They underwent counseling, and opted for termination of the pregnancy. The sonographic findings were confirmed after delivery, supported by a 3D computed tomographic skeletal survey. CONCLUSION: To the best of our knowledge, this is the first report of Roberts syndrome employing antenatal 3D sonographic imaging.

Comparison of low-concentration carbon dioxide-enriched and tap water immersion on body temperature after passive heating.

BACKGROUND: Because carbon dioxide (CO2)-enriched water causes cutaneous vasodilation, immersion in CO2-enriched water facilitates heat transfer from the body to the water or from the water to the body. Consequently, immersion in CO2-enriched water raises or reduces body temperature faster than immersion in fresh water. However, it takes time to dissolve CO2 in tap water and because the dissolved CO2 concentration decreases over time, the actual CO2 concentration is likely lower than the stated target concentration. However, it is unclear whether water containing a lower CO2 concentration would also cool the body faster than fresh water after body temperature had been increased. METHODS: Ten healthy males (mean age = 20 ± 1 years) participated in the study. Participants were first immersed for 15 min in a tap water bath at 40 °C to raise body temperature. They then moved to a tap water or CO2-enriched water bath at 30 °C to reduce body temperature. The CO2 concentration was set at 500 ppm. The present study measured cooling time and cooling rate (slope of the regression line relating auditory canal temperature (Tac) to cooling time) to assess the cooling effect of CO2-enriched water immersion. RESULTS: Immersion in 40 °C tap water caused Tac to rise 0.64 ± 0.25 °C in the tap water session and 0.62 ± 0.27 °C in the CO2-enriched water session (P > 0.05). During the 30 °C water immersion, Tac declined to the baseline within 13 ± 6 min in tap water and 10 ± 6 min in CO2-enriched water (P > 0.05). Cooling rates were 0.08 ± 0.06 °C/min in tap water and 0.08 ± 0.04 °C/min in CO2-enriched water (P > 0.05). CONCLUSIONS: CO2-enriched water containing 500 ppm CO2 did not cool faster than tap water immersion. This suggests that when the water temperature is 30 °C, a CO2 concentration of 500 ppm is insufficient to obtain the advantageous cooling effect during water immersion after body temperature has been increased.

An apical expression signal of the renal type IIc Na+-dependent phosphate cotransporter in renal epithelial cells.

The type IIc Na(+)-dependent phosphate cotransporter (NaPi-IIc) is specifically targeted to, and expressed on, the apical membrane of renal proximal tubular cells and mediates phosphate transport. In the present study, we investigated the signals that determine apical expression of NaPi-IIc with a focus on the role of the N- and the C-terminal tails of mouse NaPi-IIc in renal epithelial cells [opossum kidney (OK) and Madin-Darby canine kidney cells]. Wild-type NaPi-IIc, the cotransporter NaPi-IIa, as well as several IIa-IIc chimeras and deletion mutants, were fused to enhanced green fluorescent protein (EGFP), and their cellular localization was analyzed in polarized renal epithelial cells by confocal microscopy and by cell-surface biotinylation. Fluorescent EGFP-fused NaPi-IIc transporter proteins are correctly expressed in the apical membrane of OK cells. The apical expression of N-terminal deletion mutants (deletion of N-terminal 25, 50, or 69 amino acids) was not affected by truncation. In contrast, C-terminal deletion mutants (deletion of C-terminal 45, 50, or 62 amino acids) did not have correct apical expression. A more detailed mutational analysis indicated that a domain (amino acids WLHSL) in the cytoplasmic C terminus is required for apical expression of NaPi-IIc in renal epithelial cells. We conclude that targeting of NaPi-IIc to the apical cell surface is regulated by a unique amino acid motif in the cytoplasmic C-terminal domain.

Therapeutic results of computed-tomography-guided transcatheter arterial chemoembolization for local recurrence of hepatocellular carcinoma after initial transcatheter arterial chemoembolization: the results of 85 recurrent tumors in 35 patients.

The aim of this study was to retrospectively evaluate the long-term results of transcatheter arterial chemoembolization (TACE) for the treatment of local recurrence of hepatocellular carcinoma (HCC) after the first TACE. Between September 1992 and October 2004, 85 recurrent HCC nodules of 35 patients were treated by TACE. During the median follow-up period of 15.5 months (range 1.9-58.6 months), 58 of the 85 treated tumors developed local recurrence again after the second TACE. The overall 6-, 12-, and 36-month recurrence-free rates of these tumors after the second TACE were 47.0%, 36.2%, and 25.8%, respectively. Local recurrence of HCC after the first TACE was treated by a second TACE with equivalent efficacy as that of the initial TACE, if segmental chemoembolization was achieved. We regard TACE as the treatment of choice for the management of local recurrence of HCC.

The cross-sectional relationships among hyperthermia-induced hyperventilation, peak oxygen consumption, and the cutaneous vasodilatory response during exercise.

To test the hypothesis that the hyperthermia-induced ventilatory response relates to aerobic power and/or the cutaneous vasodilatory response during exercise, we asked 18 subjects to perform 3 kinds of exercise: an incremental exercise to determine peak oxygen consumption (V(O)(2peak)), a steady state exercise at 50% of V(O)(2peak) to determine the ventilatory response to increasing body temperature, and a steady state exercise at 60% of V(O)(2peak) to determine the cutaneous vasodilatory response to increasing body temperature. The ventilatory and cutaneous vasodilatory responses were evaluated by plotting the increase in minute ventilation or in forearm vascular conductance against the increase in oesophageal temperature. Regression analysis revealed that: (1) there was a negative relationship between the hyperthermic ventilatory response and cutaneous vasodilatory response, (2) there was a negative relationship between the hyperthermic ventilatory response and V(O)(2peak), and (3) there was a positive relationship between the cutaneous vasodilatory response and V(O)(2peak). These results support our hypothesis and suggest that exercise training suppresses the hyperthermic ventilatory response and improves the thermoregulatory response.

Electron therapy for orbital and periorbital lesions using customized lead eye shields.

PURPOSE: To establish the protective efficacy against late complications of electron therapy using customized lead eye shields in cases with orbital and periorbital lesions. METHODS: Between 1982 and 2006, 16 patients with 22 orbital and periorbital lesions were treated by electron therapy. Customized lead eye shields were prepared and placed in the respective patients' eyes during each fraction of electron therapy. The toxicity and local control rates were analyzed. RESULTS: The preparation period for the customized lead eye shields was 2 days. The shields could be used throughout the treatment period in all the patients. No evidence of radiation cataract was observed in 15 of the 16 patients. None of the patients developed corneal ulceration or evidence of lead poisoning. CONCLUSION: Customized lead eye shields could be made relatively quickly, and electron therapy for orbital and periorbital lesions could be undertaken safely without any late complication.

Association between the detection rate of thyroid cancer and the external radiation dose-rate after the nuclear power plant accidents in Fukushima, Japan.

A thyroid cancer ultrasonography screening for all residents 18 years old or younger living in the Fukushima prefecture started in October 2011 to investigate the possible effect of the radiological contamination after the Fukushima Daiichi Nuclear Power Plant accidents as of March 12 to 15, 2011. Thyroid cancer in 184 cases was reported by February 2017. The question arises to which extent those cancer cases are a biological consequence of the radiation exposure or an artefactual result of the intense screening of a large population.Experiences with the Chernobyl accident suggest that the external dose may be considered a valid surrogate for the internal dose of the thyroid gland. We, therefore, calculated the average external effective dose-rate (µSv/h) for the 59 municipalities of the Fukushima prefecture based on published data of air and soil radiation. We further determined the municipality-specific absolute numbers of thyroid cancers found by each of the two screening rounds in the corresponding municipality-specific exposed person-time observed. A possible association between the radiation exposure and the thyroid cancer detection rate was analyzed with Poisson regression assuming Poisson distributed thyroid cancer cases in the exposed person-time observed per municipality.The target populations consisted of 367,674 and 381,286 children and adolescents for the 1st and the 2nd screening rounds, respectively. In the 1st screening, 300,476 persons participated and 270,489 in the 2nd round. From October 2011 to March 2016, a total of 184 cancer cases were found in 1,079,786 person-years counted from the onset of the exposure to the corresponding examination periods in the municipalities. A significant association between the external effective dose-rate and the thyroid cancer detection rate exists: detection rate ratio (DRR) per µSv/h 1.065 (1.013, 1.119). Restricting the analysis to the 53 municipalities that received less than 2 µSv/h, and which represent 176 of the total 184 cancer cases, the association appears to be considerably stronger: DRR per µSv/h 1.555 (1.096, 2.206).The average radiation dose-rates in the 59 municipalities of the Fukushima prefecture in June 2011 and the corresponding thyroid cancer detection rates in the period October 2011 to March 2016 show statistically significant relationships.

Effect of food intake on respiratory chemosensitivity to CO2 in young adults.

BACKGROUND: Food intake augments CO2 production; however, minute ventilation is not augmented during exercise after food intake. Respiratory chemoreceptors respond to CO2 and influence respiration. We examined the effect of food intake on respiratory chemosensitivity to CO2 in young adults. METHODS: The hypercapnic ventilatory response was measured in eleven healthy individuals before and after food intake. To evaluate the respiratory chemoreflex response to CO2, minute ventilation was plotted against end-tidal PCO2 using data obtained with the rebreathing method. RESULTS: Sublingual temperature, CO2 output, minute ventilation, and end-tidal PCO2 were all significantly higher at baseline in the session after food intake than in the session before food intake. On the other hand, there was no significant difference in chemosensitivity to CO2 between the sessions before and after food intake (1.60 ± 0.62 vs. 1.53 ± 0.62 l min-1 mmHg-1). CONCLUSIONS: Food intake does not influence respiratory chemosensitivity to CO2 in young adults, which is different from infants. This suggests that control of respiration differs between young adults and infants and that the elevated minute ventilation after food intake in young adults is not caused by a change in respiratory chemosensitivity.

Effect of food intake on the ventilatory response to increasing core temperature during exercise.

Food intake increases metabolism and body temperature, which may in turn influence ventilatory responses. Our aim was to assess the effect of food intake on ventilatory sensitivity to rising core temperature during exercise. Nine healthy male subjects exercised on a cycle ergometer at 50% of peak oxygen uptake in sessions with and without prior food intake. Ventilatory sensitivity to rising core temperature was defined by the slopes of regression lines relating ventilatory parameters to core temperature. Mean skin temperature, mean body temperature (calculated from esophageal temperature and mean skin temperature), oxygen uptake, carbon dioxide elimination, minute ventilation, alveolar ventilation, and tidal volume (VT) were all significantly higher at baseline in sessions with food intake than without food intake. During exercise, esophageal temperature, mean skin temperature, mean body temperature, carbon dioxide elimination, and end-tidal CO2 pressure were all significantly higher in sessions with food intake than without it. By contrast, ventilatory parameters did not differ between sessions with and without food intake, with the exception of VT during the first 5 min of exercise. The ventilatory sensitivities to rising core temperature also did not differ, with the exception of an early transient effect on VT. Food intake increases body temperature before and during exercise. Other than during the first 5 min of exercise, food intake does not affect ventilatory parameters during exercise, despite elevation of both body temperature and metabolism. Thus, with the exception of an early transient effect on VT, ventilatory sensitivity to rising core temperature is not affected by food intake.

Modulation of the control of muscle sympathetic nerve activity during incremental leg cycling.

We tested the hypotheses that arterial baroreflex (ABR) control over muscle sympathetic nerve activity (MSNA) in humans does not remain constant throughout a bout of leg cycling ranging in intensity from very mild to exhausting. ABR control over MSNA (burst incidence, burst strength and total MSNA) was evaluated by analysing the relationship between beat-to-beat spontaneous variations in diastolic arterial pressure (DAP) and MSNA in 15 healthy subjects at rest and during leg cycling in a seated position at five workloads: very mild (10 W), mild (82 +/- 5.0 W), moderate (126 +/- 10.2 W), heavy (156 +/- 14.3 W), and exhausting (190 +/- 21.2 W). The workload was incremented every 6 min. The linear relationships between DAP and MSNA variables were significantly shifted downward during very mild exercise, but then shifted progressively upward as exercise intensity increased. During heavy and exhausting exercise, moreover, the DAP-MSNA relationships were also significantly shifted rightward from the resting relationship. The sensitivity of ABR control over burst incidence and total MSNA was significantly lower during very mild exercise than during rest, and the sensitivity of the burst incidence control remained lower than the resting level at all higher exercise intensities. By contrast, the sensitivity of the total MSNA control recovered to the resting level during mild and moderate exercise, and was significantly increased during heavy and exhausting exercise (versus rest). We conclude that, in humans, ABR control over MSNA is not uniform throughout a leg cycling exercise protocol in which intensity was varied from very mild to exhausting. We suggest that this non-uniformity of ABR function is one of the mechanisms by which sympathetic and cardiovascular responses are matched to the exercise intensity.

Effect of hypohydration on hyperthermic hyperpnea and cutaneous vasodilation during exercise in men.

We tested the hypothesis that, in humans, hypohydration attenuates hyperthermic hyperpnea during exercise in the heat. On two separate occasions, thirteen male subjects performed a fluid replacement (FR) and a no-fluid replacement (NFR) trial in random order. The subjects performed two bouts of cycle exercise (Ex1 and Ex2, 30-60 min) at 50% peak oxygen uptake (Vo2 peak) in 35 degrees C separated by a 70- to 80-min rest period, during which they drank water containing 25 mosmol/l sodium in the FR trial but not the NFR trial. The drinking in the FR trial nearly restored the body fluid to the euhydrated condition, so that the body fluid status differed between the trials before Ex2 (the difference in plasma osmolality before Ex2 was 9.4 mosmol/kgH2O; plasma volume was 7.6%, and body weight was 2.5%). The slopes of the linear relationships between ventilatory variables (minute ventilation, ventilatory equivalents for oxygen uptake and carbon dioxide output, tidal volume, respiratory frequency, and end-tidal CO2 pressure) and esophageal temperature (Tes) did not significantly differ between Ex1 and Ex2, or between the FR and NFR trials. On the other hand, during Ex2 in the NFR trial, the Tes threshold for the onset of increased forearm vascular conductance (FVC) was higher, and the slope and peak values of the relationship between FVC and Tes were lower than during Ex1 in the NFR trial and during Ex2 in the FR trial. These findings suggest that hypohydration does not affect the hyperthermic hyperpnea during exercise, although it markedly attenuates the cutaneous vasodilatory response.