A microfluidic approach for the detection of uric acid through electrical measurement using an atomically thin MoS2 field-effect transistor.

There is a demand for biosensors working under in vivo conditions, which requires significant device size and endurance miniaturization in solution environments. We demonstrated the detection of uric acid (UA) molecules, a marker of diseases like gout, whose continuous monitoring is required in medical diagnosis. We used a field effect transistor (FET) composed of an atomically thin transition metal dichalcogenide (TMD) channel. The sensor detection was carried out in a solution environment, for which we protected the electrodes of the source and drain from the solution. A microfluidic channel controls the solution flow that can realize evaporation-free conditions and provide an accurate concentration and precise measurement. We detected a systematic change of the drain current with the concentration of the UA in isopropyl alcohol (IPA) solvent with a detection limit of 60 nM. The sensor behavior is reversible, and the drain current returns to its original value when the channel is washed with pure solvent. The results demonstrate the feasibility of applying the MoS2-FET device to UA detection in solution, suggesting its possible use in the solution environment.

In situ study of sensor behavior of MoS2 field effect transistor for methyl orange molecule in ultra high vacuum condition.

We investigate the sensor behavior of the MoS2 field effect transistor (FET) device with the deposition of methyl orange (MO) molecule which is widely used as a chemical probe. The channel of the FET is made of the single layer of MoS2 which makes it highly sensitive to the molecule adsorption, but at the same time the behavior depends much on the surface conditions of the MoS2 channel. In order to make the channel-surface conditions more defined, we prepare an in situ experimental system in which the molecule deposition and the surface- and electrical-characterization of the MoS2 FET are executed in a single ultra-high vacuum chamber. This system makes it possible to examine the change of the FET properties with precise control of the molecule coverage in the sub-monolayer region without the effect of the atmosphere. We detected the shift of the I d-V g curve of the MoS2-FET device with the increase of the molecule coverage (θ) of the MO molecule, which is quantitatively analyzed by plotting the threshold voltage (V th) of the I d-V g curve as a function of θ. The V th shifts towards the negative direction and the initial change with θ can be expressed with an exponential function of θ, which can be accounted for with the Langmuir type adsorption of the molecule for the first layer and the charge transfer from the molecule to the substrate. The V th versus θ curve shows a kink at a certain θ, which is conserved as the starting of the second layer growth. We detected the adsorption of MO far less than monolayer and the phase change from the first layer to the second layer growth, which is realized by the benefit of the in situ UHV experimental condition.

Chemistry of the photoisomerization and thermal reset of nitro-spiropyran and merocyanine molecules on the channel of the MoS2 field effect transistor.

We have explored the chemical reaction of the photoisomerization and thermal reaction of the photochromic spiropyran (SP) 1',3'-Dihydro-1',3',3' trimethyl-6-nitrospiro[2H-1 benzopyran-2,2'-(2H)-indole] molecule deposited on the atomic thin channel of a MoS2 field-effect transistor (FET) through the analysis of the FET property. With four monolayers of SP molecules on the channel, we observed a clear shift of the threshold voltage in the drain-current vs gate-voltage plot with UV-light injection on the molecule, which was due to the change of the SP molecule to merocyanine (MC). A complete reset from MC to SP molecule was achieved by thermal annealing, while the injection of green light could revert the FET property to the original condition. In the process of change from MC to SP, two types of decay rates were confirmed. The quick- and slow-decay components corresponded to the molecules attached directly to the substrate and those in the upper layer, respectively. The activation energies for the conversion of MC to SP molecules were estimated as 71 kJ/mol and 90 kJ/mol for the former and latter, respectively. Combined with DFT calculations, we concluded that the Id-Vg shift with photoisomerization from SP to MC is due to the upper layer molecules and the dipole moment in the surface normal direction. Based on the estimated activation energy of 90 kJ/mol for the reset process, we calculated the conversion rate in a controllable temperature range. From these values, we consider that the chemical state of MC can be maintained and switched in a designated time period, which demonstrates the possibility of this system in logical operation applications.

Microfluidic tank assisted nicotine sensing property of field effect transistor composed of an atomically thin MoS2 channel.

We investigated the sensor behavior of a field effect transistor, the channel of which is made of atomically thin MoS2 layers, focusing on the interaction of the MoS2 channel with the solution containing target molecules. For this purpose, we made a newly designed device in which the mask covered the electrodes of the source and the drain in order to make the solution contact only with the channel. In addition, a micro-fluid tank was fabricated above the channel as a solution reservoir. We examined the FET properties of this device for the sensing of the nicotine molecule for the development of a detection system for this molecule in the human body under in vivo conditions. We detected the sensor behavior both for the drop-cast process and for the condition where the channel contacts with the solution. The drain-current vs. gate-voltage variation of the MoS2-FET with the attachment of the nicotine molecule was clearly observed for both cases. For the latter case, the threshold voltage shifted in the negative gate-voltage direction with the increase of the concentration of the nicotine in the solution. This can be explained by the electron transfer from the molecule to the MoS2 channel, which was further confirmed by analyzing the X-ray photoemission spectroscopy and Raman spectroscopy together with the DFT calculation. The sensor can detect the variation of the nicotine concentration in the IPA solution by detecting the Vth change of the MoS2-FET.

Relationship between hematotoxicity and serum albumin level in the treatment of head and neck cancers with concurrent chemoradiotherapy using cisplatin.

OBJECTIVE: Patients with locally advanced head and neck cancer were treated with concurrent chemoradiotherapy using three courses of cisplatin. However, many patients were unable to complete the scheduled cisplatin treatment due to adverse effects. The objective of this study was to retrospectively elucidate the source of the low completion rate of cisplatin courses. METHODS: Between November 2007 and 28 May 2010, patients with head and neck cancer were treated with curative intent according to the concurrent chemoradiotherapy protocol (66-70 Gy at 2 Gy/day with cisplatin 80 mg/m(2) on Days 1, 22 and 43). Treatment courses, hematological data and other parameters were investigated, and the treatment completion rates and reasons for treatment failure were analyzed. RESULTS: Among the 28 patients, cisplatin was administered during the period of radiotherapy a total of 3 times in 9 (32%) patients, 2 times in 15 (54%) patients and only 1 time in 4 (14%) patients. Multiple regression analysis of the development of neutropenia at 3 weeks after the first cisplatin administration revealed that the serum albumin level was a significant explanatory variable (R(2)= 0.664, ß = 0.517, P< 0.01). Pearson's product-moment correlation coefficient showed a strong correlation between the serum albumin level and the neutrophil count after 3 weeks (r = 0.605, P< 0.01). CONCLUSIONS: The treatment completion rate by this protocol was low in head and neck cancer patients even when the cisplatin dose was reduced to 80 mg/m(2). This tendency was seen in patients with a low serum albumin level.

Sensor behavior of MoS2 field-effect transistor with light injection toward chemical recognition.

The application of field-effect transistor (FET) devices with atomically thin channels as sensors has attracted significant attention, where the adsorption of atoms/molecules on the channels can be detected by the change in the properties of FET. Thus, to further enhance the chemical sensitivity of FETs, we developed a method to distinguish the chemical properties of adsorbates from the electric behavior of FET devices. Herein, we explored the variation in the FET properties of an MoS2-FET upon visible light injection and the effect of molecule adsorption for chemical recognition. By injecting light, the drain current (I d) increased from the light-off state, which is defined as (ΔI d)ph. We examined this effect using CuPc molecules deposited on the channel. The (ΔI d)ph vs. wavelength continuous spectrum in the visible region showed a peak at the energy for the excitation from the highest occupied orbital (HOMO) to the molecule-induced state (MIS). The energy position and the intensity of this feature showed a sensitive variation with the adsorption of the CuPc molecule and are in good agreement with previously reported photo-absorption spectroscopy data, indicating that this technique can be employed for chemical recognition.

Geographic variation of Sr and S isotope ratios in bottled waters in Japan and sources of Sr and S.

The geographic distribution of the stable isotope ratio of Sr (87Sr/86Sr) is useful for identifying the provenance of drinking water, organisms, and agricultural products. To explore how environmental factors influence this ratio, we determined the 87Sr/86Sr, sulfur isotope ratio (δ34S), and elemental composition of 208 commercially available bottled waters in Japan, and compared them with the 87Sr/86Sr values of groundwater, rainwater, rocks, and vegetables from similar localities. We classified the bottled waters into seven categories based on the geology of their source aquifers. The 87Sr/86Sr and concentrations of several elements (Ca, K, Si, Rb, and Ba) of the bottled waters differed with the aquifer rock type and were well correlated with the 87Sr/86Sr of reported spring waters, indicating that bottled water, like other groundwater, reflects the lithology and chemistry of its aquifer. The 87Sr/86Sr of bottled water, taken as a proxy for groundwater, showed regional variations consistent with those of rocks and vegetables, demonstrating that an 87Sr/86Sr map of water and agricultural products has value for determining the production areas of these substances. However, the value and range of 87Sr/86Sr differed among these three materials, and the degree of the difference between groundwater and rock depended on the rock type. An analysis of geochemical data from rocks and rainwater suggests that groundwater contains Sr and additional S derived from atmospheric sources such as rainwater and sea salt aerosols. The atmospheric contribution of Sr to groundwater is greatest in areas of siliceous sedimentary rocks with low Sr concentrations and high resistance to weathering. A weak correlation of δ34S of bottled waters with 87Sr/86Sr indicates the usefulness of maps of combined Sr and S isotope ratios for groundwater provenance. This study shows that for accurate provenance determinations of groundwater, organisms, and agricultural products, it is essential to better quantify the contributions of Sr and S from the atmosphere as well as from rocks and human activities.

In Situ Study of Molecular Doping of Chlorine on MoS2 Field Effect Transistor Device in Ultrahigh Vacuum Conditions.

We report a precise measurement of the sensor behavior of the field effect transistor (FET) formed with the MoS2 channel when the channel part is exposed to Cl2 gas. The gas exposure and the electrical measurement of the MoS2 FET were executed with in situ ultrahigh-vacuum (UHV) conditions in which the surface analysis techniques were equipped. This makes it possible to detect how much sensitivity the MoS2 FET can provide and understand the surface properties. With the Cl2 gas exposure to the channel, the plot of the drain current versus the gate voltage (I d-V g curve) shifts monotonically toward the positive direction of V g, suggesting that the adsorbate acts as an electron acceptor. The I d-V g shifts are numerically estimated by measuring the onset of I d (threshold voltage, V th) and the mobility as a function of the dosing amounts of the Cl2 gas. The behaviors of both the V th shift and the mobility with the Cl2 dosing amount can be fitted with the Langmuir adsorption kinetics, which is typically seen in the uptake curve of molecule adsorption onto well-defined surfaces. This can be accounted for by a model where an impinging molecule occupies an empty site with a certain probability, and each adsorbate receives a certain amount of negative charge from the MoS2 surface up to the monolayer coverage. The charge transfer makes the V th shifts. In addition, the mobility is reduced by the enhancement of the Coulomb scattering for the electron flow in the MoS2 channel by the accumulated charge. From the thermal desorption spectroscopy (TDS) measurement and density functional theory (DFT) calculations, we concluded that the adsorbate that is responsible for the change of the FET property is the Cl atom that is dissociated from the Cl2 molecule. The monotonic shift of V th with the coverage suggests that the MoS2 device sensor has a good sensitivity to detect 10-3 monolayers (ML) of adsorption corresponding to the ppb level sensor with an activation time of 1 s.

Gas-Source CVD Growth of Atomic Layered WS2 from WF6 and H2S Precursors with High Grain Size Uniformity.

Two-dimensional (2D) transition-metal dichalcogenides have attracted a considerable amount of attention because of their potential for post-silicon device applications, as well as for exploring fundamental physics in an ideal 2D system. We tested the chemical vapour deposition (CVD) of WS2 using the gaseous precursors WF6 and H2S, augmented by the Na-assistance method. When Na was present during growth, the process created triangle-shaped WS2 crystals that were 10 µm in size and exhibited semiconducting characteristics. By contrast, the Na-free growth of WS2 resulted in a continuous film with metallic behaviour. These results clearly demonstrate that alkali-metal assistance is valid even in applications of gas-source CVD without oxygen-containing species, where intermediates comprising Na, W, and S can play an important role. We observed that the WS2 crystals grown by gas-source CVD exhibited a narrow size distribution when compared with crystals grown by conventional solid-source CVD, indicating that the crystal nucleation occurred almost simultaneously across the substrate, and that uniform lateral growth was dominant afterwards. This phenomenon was attributed to the suppression of inhomogeneous nucleation through the fast and uniform diffusion of the gas-phase precursors, supported by the Na-assisted suppression of the fast reactions between WF6 and H2S.

Effect of agriculture on water quality of Lake Biwa tributaries, Japan.

We investigated the effects of natural environments and human activity on Lake Biwa, central Japan. We determined the concentrations of 19 elements and the compositions of stable S and Sr isotopes in the main tributaries of the lake and compared them with the corresponding values obtained from the lake water during the circulation period. Results of a principal component analysis indicated that the components dissolved in the lower reaches of the tributaries can be divided into group 1 (HCO(3), SO(4), NO(3), Ca, Mg, Sr) and group 2 components (Cl, Br, Na, K, Ba, Rb, Cs). The concentrations of group 1 components were high in the rivers of the southern area, which is urbanized and densely populated, and the eastern area, which consists of plains where agriculture predominates, compared with the rivers of the northern and western areas, which are mostly mountainous and sparsely populated. The concentrations of group 2 components tended to be high in the river water of industrial areas. The delta(34)S values of SO(4) in the river water converged to 0+/-2 per thousand as the SO(4) concentration increased and, excluding the areas where limestone is extensively distributed, as the HCO(3) concentration increased. In particular, both the delta(34)S values (0+/-2 per thousand) and the (87)Sr/(86)Sr ratios (0.7117+/-0.0005) fell within narrow ranges in the small and medium rivers of the eastern plain area, where rice is widely grown. These values agreed respectively with the delta(34)S values of the fertilizers used in the Lake Biwa basin and the soil-exchangeable (87)Sr/(86)Sr in the eastern plain. The characteristics of water quality in the small and medium rivers of the eastern area can be explained by a model in which sulfuric, nitric, and bicarbonic acids generated by the decomposition of agricultural fertilizer and paddy rice selectively leached out alkaline-earth elements adsorbed on the soil and sediments of the plain or dissolved calcium carbonate enriched with Mg and Sr. Compared with tributary waters, the lake water was depleted in NO(3), owing to denitrification, and in Mn, owing to mineralization, which occur under the redox condition of bottom sediments. Excluding NO(3) and Mn, the compositions of both the dissolved elements and the Sr and S isotopes in the water of Lake Biwa can be approximately reproduced by simple mixing of the tributary water, indicating that these components provide effective indices for evaluating the relationship between the waters of the lake and its tributaries.

Swallowing function following extensive resection of oral or oropharyngeal cancer with laryngeal suspension and cricopharyngeal myotomy.

OBJECTIVE: To investigate factors that influence postoperative swallowing function in patients who underwent tongue and oropharynx resection. METHODS: Sixty-two subjects who had undergone extensive resection of oral or oropharyngeal cancer between 1993 and 2005 participated in this study. All surgical procedures involved excision of the bilateral suprahyoid muscles or of >or=50% of the tongue base. Laryngeal suspension and cricopharyngeal myotomy were performed on all subjects. A multivariate analysis of the effects of extensive tongue and oropharynx resection on swallowing function was performed. RESULTS: A total of 53 (85.5%) of the 62 subjects achieved independent oral intake and no longer required tube feeding. Six months after surgery, better eating capabilities had been attained by younger patients as compared with older patients; patients with less extensive tongue base resections; patients who had not undergone radiotherapy; and patients reconstructed with free flaps rather than pedicled flaps. CONCLUSIONS: Age was found to be the most important factor in determining whether a patient could achieve independent oral intake after extensive oral or oropharyngeal resection. The main factors in determining the quality of diet attained by the patient were found to be age, the percentage of tongue base resection, and the method of postoperative reconstruction.

Past emergent phase of Shatsky Rise deep-marine igneous plateau.

The Cretaceous Period stands out in Earth's geologic history by ubiquitous and sustained massive eruption of lava, forming several enormous igneous plateaus in the ocean basins worldwide. It has been proposed that the subaerial phases of Cretaceous oceanic plateau formation spurred the global environmental deterioration, yet this view is supported by patchy fossil and/or rock evidence for uplifting of the plateau summits above the sea level. Reported here is by far the most comprehensive case of Cretaceous plateau emergence at northern Shatsky Rise, Northwest Pacific, based on the integration of unique micropalaeontological and seismic evidence. From just above the flat-topped igneous edifice, recent Integrated Ocean Drilling Program (at Site U1346) recovered early Cretaceous (Hauterivian) ostracod and foraminiferal assemblages showing marked shallow-marine preferences. Most intriguing discovery is an ostracod taxon with well-developed eye tubercles, which serves as compelling palaeobiological evidence for a very shallow, euphotic setting. By linking the nearshore biofacies (<20 m water depth) to the basement topography undoubtedly shaped by subaerial weathering and/or erosion, it is obvious that northern Shatsky Rise was remarkably emergent during its final emplacement phase. We suggest that early Cretaceous surface environments might have been affected, at least in part, by Shatsky Rise subaerial volcanism.

[A Phase I study of docetaxel and cisplatin for advanced squamous cell carcinoma of the head and neck].

A Phase I study of docetaxel (DOC) and cisplatin (CDDP) combination therapy was conducted as second-line treatment for advanced squamous cell carcinoma of the head and neck in order to determine the maximum tolerated dose (MTD), the dose-limiting toxicity (DLT) of DOC, and the recommended dose (RD) for this combination therapy. Twenty patients with recurrence for whom failed first-line chemotherapy with CDDP and 5-FU proved in-effective (17 male, 3 female; age range 38-74 years; performance status 0=7, 1 =8, 2=5) were included in this study. DOC at dose level I (40 mg/m2), level II (50 mg/m2), level III (60 mg/m2) and level IV (70 mg/m2) was used, followed by CDDP administration at a fixed dose of 80 mg/m2. Originally, chemotherapy was repeated every 3 weeks. In level I, grade 4 hypokalemia occurred in one patient. No DLT occurred at level II. At level III, one patient experienced grade 4 vomiting. At level IV, grade 2 creatinine clearance decrease occurred in a total of two patients. The maximum tolerated dose in this combination therapy was DOC 70 mg/m2, and CDDP 80 mg/m2. The recommended dose for this combination therapy is DOC 60 mg/m2, and CDDP 80 mg/ m2. A multicenter cooperative phase II study in this RD is recommended.

Craniofacial Resection for T4 Maxillary Sinus Carcinoma: Managing Cases with Involvement of the Skull Base.

OBJECTIVE: The objective of this study was to clarify the outcomes of craniofacial resection for locally advanced maxillary sinus carcinoma classified as T4 and to present methods for managing cases involving the skull base. STUDY DESIGN: Case series with chart review. SETTING: Tertiary university hospital. SUBJECTS AND METHODS: We performed anterolateral craniofacial resection in en bloc fashion for locally advanced maxillary sinus carcinoma at stage T4. Participants comprised 40 patients with T4 maxillary sinus carcinoma treated between 1992 and 2011. Surgical outcomes were analyzed retrospectively. RESULTS: Forty patients with stage T4a (n = 26) or stage T4b (n = 14) were included in this study. Five-year overall and disease-free survival rates for the 40 patients with T4 maxillary sinus carcinoma were 62.7% and 52.6%, respectively. Cavernous sinus involvement correlated significantly with worse prognosis (P = .012). In 35 cases without cavernous sinus involvement, previous treatment (P = .017) and positive margins (P = .019) correlated significantly with worse prognosis, and 5-year overall and disease-free survival rates were 72.4% and 55.3%, respectively. CONCLUSION: This study only included cases of locally advanced maxillary sinus carcinoma classified as T4. Considering the advanced stage, our study suggests relatively favorable outcomes and the importance of managing the cavernous sinus in en bloc resections of malignant skull base tumors. Craniofacial resection in en bloc fashion achieved good survival rates.

Experience with the use of salazosulfapyridine for intractable diarrhea after hematopoietic stem cell transplantation.

We encountered 2 children with intractable diarrhea after allogeneic hematopoietic stem cell transplantation (SCT). In both cases, salazosulfapyridine (SASP) was administered to treat the diarrhea. One patient was a 14-year-old male with acute myelogenous leukemia who received SCT from a related HLA-identical donor. The leukemia recurred early, and a second SCT from the same donor was performed approximately half a year later. Because intestinal graft-versus-host disease (GVHD) was observed, steroids and octreotide were administered, but the symptoms were not improved. Thereafter, SASP was administered, and the symptoms remitted 9 days later. The other patient was a 12-year-old male with chronic myelogenous leukemia who received SCT from an unrelated HLA-identical donor. Diarrhea and abdominal pain developed early after engraftment and did not respond to either steroids or tacrolimus. Oral administration of SASP was initiated on day 236, and the diarrhea remitted 4 days later without recurrence thereafter. SASP may be effective in children for the digestive system symptoms of chronic GVHD.

Phyllodes tumor metastasis to the tonsil with synchronous undifferentiated carcinoma.

INTRODUCTION: Breast tumor metastasis to the tonsil is extremely rare. PRESENTATION OF CASE: A 54-year-old woman underwent resection of a breast malignant phyllodes tumor and later presented with metastasis to the lung and the left tonsil. She underwent left lower lobectomy and resection of the left tonsillar tumor. She subsequently developed undifferentiated carcinoma of the right tonsil. She underwent resection of the right tonsillar tumor and chemotherapy was started. The central venous catheter became infected with methicillin-resistant Staphylococcus aureus. Finally, she died. DISCUSSION: To the best of our knowledge, this is the first reported case of a phyllodes tumor metastasizing to the tonsil. Furthermore, morphological and immunohistochemical study revealed that the right tonsillar tumor was irrelevant to the phyllodes tumors. CONCLUSION: We report a case of phyllodes tumor metastasis to the left tonsil which developed undifferentiated carcinoma in the other side of tonsil later. Breast tumor metastasis to the tonsil is rare but it should be considered as a possible diagnosis.

A boy with mitochondrial disease: asymptomatic proteinuria without neuromyopathy.

Mitochondrial disorder is a relatively rare disease during childhood. Previous studies concluded that renal complications in this disease most often occur in patients with mitochondrial encephalomyopathies. We describe a boy with mitochondrial disease who presented with proteinuria while lacking neuromyopathy. Proteinuria was detected at the age of 6 years, including large amounts of low-molecular-weight proteins such as beta(2)- and alpha1-microglobulin. Renal functions were normal. Proximal tubular dysfunction and other renal manifestations were absent. Episodic neurologic problems such as migraine and nervous system diseases including epilepsy, depression, schizophrenia and amytrophic lateral sclerosis (ALS) were found in the boy's family members. Renal tubular basement membrane atrophy and interstitial fibrosis with mononuclear cell infiltration were observed. Ultrastructural examination showed mitochondria, mainly in the proximal tubules, which varied in size and had disoriented cristae. Mutation analysis using mitochondrial DNA (mtDNA) extracted from renal tissues demonstrated a A-->G point mutation at nucleotide position 3243 in the tRNA(Leu(UUR)) gene, while there was no mutation found in mtDNA extracted from peripheral leukocytes. Awareness among pediatricians of mitochondrial disorders, detection of low-molecular-weight proteinuria, renal ultrastructural examination and mutation analysis of mtDNA obtained from renal tissues could be important for early diagnosis of this disease.