Detection of the Metastable Ice Phase during Water Crystallization.

BACKGROUND: Under atmospheric pressure, the identifiable phases of ice crystals are hexagonal (stable) and cubic (metastable). OBJECTIVE: This study aimed to test the hypothesis that water crystallizes into the cubic phase at the beginning and then changes to the hexagonal phase. MATERIALS AND METHODS: Aqueous solutions of 40% (w/w) and 50% (w/w) glucose, and 40% (w/w) ammonium hydrogen sulfate, as well as emulsified water, were investigated. RESULTS: The cubic-to-hexagonal ice phase transition was detected in 40% (w/w) glucose solution within a 1 s integration interval, whereas the cubic ice formed in 50% (w/w) glucose solution did not transition to the hexagonal phase. The cubic phase was also confirmed in the 40% (w/w) ammonium hydrogen sulfate solution, but not in emulsified water. CONCLUSION: The cubic-to-hexagonal ice phase transition was detected in three aqueous solutions tested upon freezing. It was not possible to clearly capture the transition process in emulsified water under the study condition.

The Rho guanine nucleotide exchange factor ARHGEF5 promotes tumor malignancy via epithelial-mesenchymal transition.

Epithelial tumor cells often acquire malignant properties, such as invasion/metastasis and uncontrolled cell growth, by undergoing epithelial-mesenchymal transition (EMT). However, the mechanisms by which EMT contributes to malignant progression remain elusive. Here we show that the Rho guanine nucleotide exchange factor (GEF) ARHGEF5 promotes tumor malignancy in a manner dependent on EMT status. We previously identified ARHGEF5, a member of the Dbl family of GEFs, as a multifunctional mediator of Src-induced cell invasion and tumor growth. In the present study, ARHGEF5 was upregulated during tumor growth factor-ß-induced EMT in human epithelial MCF10A cells, and promoted cell migration by activating the Rho-ROCK pathway. ARHGEF5 was necessary for the invasive and in vivo metastatic activity of human colorectal cancer HCT116 cells. These findings underscore the crucial role of ARHGEF5 in cell migration and invasion/metastasis. An in vivo tumorigenesis assay revealed that ARHGEF5 had the potential to promote tumor growth via the phosphatidylinositol 3-kinase (PI3K) pathway. However, ARHGEF5 was not required for tumor growth in epithelial-like human colorectal cancer HCT116 and HT29 cells, whereas the growth of mesenchymal-like SW480 and SW620 cells depended on ARHGEF5. Induction of EMT by tumor necrosis factor-α or Slug in HCT116 cells resulted in the dependence of tumor growth on ARHGEF5. In these mesenchymal-like cells, Akt was activated via ARHGEF5 and its activity was required for tumor growth. Analysis of a transcriptome data set revealed that the combination of ARHGEF5 upregulation and E-cadherin downregulation or Snail upregulation was significantly correlated with poor prognosis in patients with colorectal cancers. Taken together, our findings suggest that EMT-induced ARHGEF5 activation contributes to the progression of tumor malignancy. ARHGEF5 may serve as a potential therapeutic target in a subset of malignant tumors that have undergone EMT.

Quasicrystal as a Catalyst for the Synthesis of Carbon Nanotubes.

The present report describes the catalytic activity of mechanically activated nano quasicrystalline Al65Cu20Fe15 and related nano crystalline Al50Cu28Fe22 for the synthesis of carbon nanotubes (CNTs). CNTs are synthesized by catalytic decomposition of ethanol through nano quasicrystalline Al65Cu20Fe15 and related crystalline Al50Cu28Fe22 alloys as a catalyst. The synthesized multi-walled CNTs exhibits tube diameter ranging from 5 to 25 nm. The synthesized CNTs are characterized by scanning and transmission electron microscopy. It is found that Al65Cu20Fe15 nanoquasicystal shows better catalytic behaviour as compared to nano-crystalline Al50Cu28Fe22 alloys for decomposition of ethanol during the synthesis of multi-walled CNTs.

Selective overexpression of Comt in prefrontal cortex rescues schizophrenia-like phenotypes in a mouse model of 22q11 deletion syndrome.

The 22q11.2 microdeletion is one of the highest genetic risk factors for schizophrenia. It is not well understood which interactions of deleted genes in 22q11.2 regions are responsible for the pathogenesis of schizophrenia, but catechol-O-methytransferase (COMT) is among the candidates. Df1/+ mice are 22q11.2 deletion syndrome (22q11DS) model mice with a hemizygous deletion of 18 genes in the 22q11-related region. Df1/+ mice showed enhanced response to the dopamine D1 agonist, SKF38393, and the N-methyl-D-aspartate antagonist, MK801, which can be normalized by a GABA(A) receptor agonist, bretazenil, or a GABA(A) α2/α3 receptor agonist, SL651498. Here, we demonstrated the curing effects of virus-mediated reintroduction of Comt to the prefrontal cortex (PFC) in Df1/+ mice. In contrast, both Comt overexpression and Comt inhibition caused an abnormal responsiveness to Bretazenil, a GABA(A) receptor agonist in control mice. Comt overexpression increased MK801-induced interneuronal activation and GABA release in the PFC. The expression levels of GABA-related genes such as Gabrb2 (GABA(A)receptor ß2), Gad2 (glutamic acid decarboxylase 65 (Gad65)) and Reln (Reelin) correlate with a Comt expression level in PFC. Our data suggest that Comt-mediated regulation of GABAergic system might be involved in the behavioral pathogenesis of Df1/+ mice.

Supercooling and vitrification of aqueous glycerol solutions at normal and high pressures.

The supercooling and vitrification of aqueous glycerol solutions was studied at high pressures. Homogeneous ice nucleation temperatures (T(H)) were obtained for aqueous glycerol solutions of R=50, 30, 20, 12, and 10 (R: moles of water/moles of glycerol) up to 300MPa. The R=20 glycerol solution formed a glass above 200MPa at a cooling rate of 200°C/min, indicating that pressure enhances glass-formation of aqueous glycerol solutions. The (dT(g)/dP) values were obtained for vitrified aqueous glycerol solutions of R=3, 5, 10, and 20. These data can be used for the development of cryo-preservation liquids for living cells at high pressures.

Case of anti-glomerular basement membrane antibody-induced glomerulonephritis with cytomegalovirus-induced thrombotic microangiopathy.

Although the involvement of cytomegalovirus (CMV) infections in the development of thrombotic microangiopathy (TMA) in HIV patients and transplant recipients has been reported, it is still controversial whether CMV itself can cause TMA. We report herein a rare case with rapid improvement of TMA by ganciclovir treatment in a patient who is neither HIV-positive nor a transplant recipient, suggesting a pathogenic role for CMV in TMA.

High power millimeter wave experiment of ITER relevant electron cyclotron heating and current drive system.

High power, long pulse millimeter (mm) wave experiments of the RF test stand (RFTS) of Japan Atomic Energy Agency (JAEA) were performed. The system consists of a 1 MW/170 GHz gyrotron, a long and short distance transmission line (TL), and an equatorial launcher (EL) mock-up. The RFTS has an ITER-relevant configuration, i.e., consisted by a 1 MW-170 GHz gyrotron, a mm wave TL, and an EL mock-up. The TL is composed of a matching optics unit, evacuated circular corrugated waveguides, 6-miter bends, an in-line waveguide switch, and an isolation valve. The EL-mock-up is fabricated according to the current design of the ITER launcher. The Gaussian-like beam radiation with the steering capability of 20°-40° from the EL mock-up was also successfully proved. The high power, long pulse power transmission test was conducted with the metallic load replaced by the EL mock-up, and the transmission of 1 MW/800 s and 0.5 MW/1000 s was successfully demonstrated with no arcing and no damages. The transmission efficiency of the TL was 96%. The results prove the feasibility of the ITER electron cyclotron heating and current drive system.

Navigation-guided fence-post tube technique for resection of a brain tumor: technical note.

INTRODUCTION: A new technique using a navigation system to minimize the influence of brain shift and to perform precise resection of brain tumors is demonstrated. To determine the resection plane, one to six tubes were inserted around the tumor under the guidance of a navigation system before dural incision. RESULTS: This technique termed the "navigation-guided fence-post tube" (NGFP) procedure was used to treat 34 patients with intraaxial brain tumors including gliomas (23 cases), malignant lymphomas (4 cases) and metastatic tumors (7 cases). Tumors were removed totally in 23 cases (67.6%), subtotally (95% or more removal) in 6 cases (17.6%) and partially (less than 95% removal) in 5 cases (14.7%). The cases with subtotal or partial resection contained tumors that were close to or involved the eloquent area, or disseminated lesions. No complications due to tube insertion occurred. CONCLUSION: NGFP is a useful and safe technique for brain tumor surgery with no influence of brain shift during tumor resection.

Supercooling of aqueous dimethylsulfoxide solution at normal and high pressures: Evidence for the coexistence of phase-separated aqueous dimethylsulfoxide solutions of different water structures.

Supercooling behavior of aqueous dimethylsulfoxide (DMSO) solution was investigated as a function of DMSO concentration and at high pressures. A linear relationship was observed for T(H) (homogeneous ice nucleation temperature) and T(m) (melting temperature) for the supercooling of aqueous DMSO solution at normal pressure. Analysis of the DTA (differential thermal analysis) traces for homogeneous ice crystallization in the bottom region of the T(H) curve for a DMSO solution of R=20 (R: moles of water/moles of DMSO) at high pressures supported the contention that the second critical point (SCP) of liquid water should exist at P(c2)= approximately 200 MPa and at T(c2)<-100 degrees C (P(c2): pressure of SCP, T(c2): temperature of SCP). The presence of two T(H) peaks for DMSO solutions (R=15, 12, and 10) suggests that phase separation occurs in aqueous DMSO solution (R

Transvenous embolization for dural arteriovenous shunt of the cavernous sinus. Comparison of multi-staged transvenous embolization and transvenous embolization with sinus packing.

SUMMARY: We describe the treatment and follow-up clinical symptoms and angiographic results in patients with dural arteriovenous fistula of the cavernous sinus treated by transvenous embolization (TVE). We have treated eight cases of dural arteriovenous fistula of the cavernous sinus by multi-staged TVE in two cases and TVE with sinus packing in six and three of six cases were treated with a combination of transarterial embolization. Multi-staged TVE was performed by occlusion from dangerous drainage veins to the cavernous sinus on several occasions. Angiographical results showed disappearance or reduction of the arteriovenous shunt in all cases. Six patients presented with ophthalmic symptoms and two had tinnitus. Six cases had complete disappearance of clinical symptoms after treatment. There was a deterioration of ocular movement in one patient treated by TVE with sinus packing. Multi-staged TVE was performed to reduce the coil volume for the packing of the cavernous sinus in two cases without cranial nerve palsy. Embolization, especially multi-staged TVE, was considered a good treatment to occlude arteriovenous shunts at the cavernous sinus without cranial nerve complications.

Function of surfactants in hair dyeing by oxidation dyes 2. Effect on formation of oxidation dyes by p-aminophenol and 5-amino-o-cresol in dye bath(1).

The effect of surfactants on an oxidation-hair-dye-formation reaction in a dye bath was studied in order to learn the mechanism of the effect of surfactants on the dyeability of hair by the oxidation dye. The dye-formation behaviours for the p-aminophenol and 5-amino-o-cresol system with the surfactants, of which the hydrophilic parts have different charges, were compared changing the concentration of surfactants. It was found that the same dyes are produced, regardless of the charge of surfactants added, and the rate of dye produced in the dyebath is increased in the presence of surfactants. The order of the production rate is, with an anionic surfactant > with non-ionic surfactant > with cationic surfactant > without surfactant. The relation between the dyeability of hair and the rate of dye produced in the dyebath in the presence of surfactants is not found. The major factor governing the dyeability of hair is different from the mechanism of the increased dye in the solution. It was also found that the dye-formation rate is increased by immersing hair into the reaction solution, and hair works as an accelerator for the dye-formation reaction.

The role of cyberknife radiosurgery/radiotherapy for brain metastases of multiple or large-size tumors.

OBJECTIVE: Focused, highly targeted radiosurgery and fractionated radiotherapy using the Cyberknife are useful treatments for multiple or large metastases. Here we present our results of Cyberknife radiosurgery for 71 patients with 148 metastatic brain lesions. METHODS: There were 32 women and 39 men with a median age of 63 (range: 30-88) years. Radiographic follow-up was available for 60 patients with 104 lesions. The mean and median initial volumes of the tumor per lesion were 6.6 and 2.9 cm(3) (range: 0.1-53.2 cm(3)), respectively, at the time of the initial Cyberknife treatment. Forty patients (56%) had a single lesion, and 31 (44%) had multiple lesions (range: 2-7) at initial treatment. The number of fractions ranged from 1 to 3, and forty (27%) of 148 lesions were treated by a fractionated course of Cyberknife therapy. The mean marginal dose was 20.2 Gy (range 7.8-30.1 Gy, median: 20.7 Gy). RESULTS: At 44 weeks of median follow-up, there were no permanent symptoms resulting from radiation necrosis. Overall 6-month and 1-year survival rates were 74% and 47%, respectively, and the median survival time was 56 weeks. The Karnofsky performance score and extracranial metastasis were significant prognostic factors at 6 months and 1 year, respectively, in both univariate and multivariate analyses. Age or multiple metastases did not influence prognosis at 6 months and 1 year. Local control was achieved in 83% (86 lesions). After additional radiosurgical or surgical salvage, no patient died as a result of intracranial disease. Twenty-five patients developed 92 new metastases (range 1-13) outside of the treated lesions with 22.4 weeks of median follow-up. Among them, 21 patients (84 lesions) were treated by salvage Cyberknife. CONCLUSION: Despite the inclusion of an unfavorable group of patients with large tumors, our results for survival and tumor control rates are comparable to those of published series. The Cyberknife provides the advantage of allowing for fractionated treatment to multiple or large-size tumors.

Designing novel pH-sensitive non-phospholipid vesicle: characterization and cell interaction.

In this work, we report the preparation, the characterization and interaction with cells of novel pH-sensitive non-phospholipid vesicle formulations, from a non-ionic surfactant mixed with cholesterol (CHOL) and his derivative cholesteryl hemisuccinate (CHEMS), as pH-sensitive molecule. This molecule, can destabilize the vesicle lipid bilayer when exposed to an acidic environment, with a subsequent release of vesicular content, enhancing the cytoplasmatic delivery of drugs to target cells. Vesicles were characterized by static and dynamic light scattering, in order to evaluate their dimensions, bilayer thickness and vesicle stability. Membrane permeability changes were determined by the release of entrapped hydroxypyrene-1,3,6-trisulfonic acid (HPTS). Also diphenylhesatriene (DPH) fluorescence anisotropy and zeta potential measurements were used to evidence the pH sensitivity. Furthermore vesicles were characterized by means of electronic microscopy after freeze-fracture. The interaction of non-lipid vesicles containing different fluorescent dyes with Raw 264.7, mouse monocite macrophage, were analyzed by flow cytometric analysis. The obtained results indicate that the pH-sensitive vesicular structures show good plasma stability and relevant pH-sensitivity. Moreover this formulation was able to interact with target membranes (i.e. plasma or endosomal membrane) and to release the encapsulated material into the cytoplasm.

CyberKnife stereotactic radiotherapy for patients with malignant glioma.

OBJECTIVE: The CyberKnife is a new frameless image-guided radiosurgical modality. The authors report on their experience using the CyberKnife in 25 patients with malignant gliomas. METHODS: Twenty-five patients with histologically proven malignant gliomas (18 glioblastoma: GB, 7 anaplastic astrocytoma: AA) were treated with the CyberKnife at Konan St. Hill Hospital between June 1998 and November 2002. CyberKnife therapy was performed on 44 lesions (31 GB lesions, 13 AA lesions) in the 25 patients. The median target volume was 19.1 mL (range: 0.3 - 90.2). The median prescribed dose was 20.3 Gy (range: 13.9 - 26.4). Patient-, tumor-, and treatment-related variables were analyzed by univariate analysis, and survival curves were generated by the Kaplan-Meier product limit. RESULTS: In the 18 GB patients, the median survival after diagnosis was 20.7 months (82.6 weeks) with a mean follow-up of 85.7 weeks. Of the 7 AA patients, 6 were alive at the time of analysis with follow-up periods ranging from 11.4 to 52.8 months. Patients younger than 70 years had a median survival after diagnosis of 37.1 months, compared to 12.4 months for older patients (p = 0.003). Similarly, patients with well-controlled lesions had a median survival after diagnosis of 39.8 months compared to 16.0 months for those with uncontrolled lesions (p = 0.031). Late delayed radiation necrosis was seen in 1 GB patient. No other patient suffered acute or delayed neurological morbidity after CyberKnife therapy. CONCLUSION: This is the first report of CyberKnife stereotactic radiotherapy applied to the treatment of malignant gliomas. The frameless and painless CyberKnife stereotactic radiotherapy has the potential to be as useful for treatment of malignant glioma as other radiosurgical modalities.

Image-guided stereotactic radiosurgery with the CyberKnife for pituitary adenomas.

This study demonstrates the clinical usefulness of image-guided fractionated stereotactic radiosurgery with the CyberKnife system. Twenty-one patients with pituitary adenomas received image-guided stereotactic radiosurgery with the CyberKnife, and were followed up for more than 18 months. The patients consisted of 14 with non-functioning adenomas, 3 with prolactinomas, 2 with acromegaly, and 2 with ACTH-producing tumors. In 20 cases, fractionated radiosurgery was performed. The change in the tumor volume, visual acuity, hormonal function, and complications by this therapy were analyzed in each case. The volume of the tumors ranged from 0.2 cm (3) to 34.9 cm (3) (mean +/- SD: 11.3 +/- 9.2 cm (3)). The mean volumes of the non-functioning and functioning adenomas were 13.3 cm (3) and 7.5 cm (3), respectively. The marginal irradiation dose ranged from 6.4 Gy to 27.7 Gy (mean: non-functioning adenomas 12.6 Gy, functioning adenomas 17.5 Gy), as a dose of a single fraction. The follow-up periods ranged from 18 months to 59 months (mean +/- SD: 35.3 +/- 10.7 months). The tumor control rate was 95.2 %. In 1 case, visual acuity worsened due to cystic enlargement of the tumor. Hormonal function improved in all of the 7 functioning adenomas. The hormone level normalized in 1 prolactinoma, and decreased to less than normal in 1 ACTH-producing adenoma. In 2 cases, hypopituitarism occurred after the therapy. Image-guided stereotactic radiosurgery with the CyberKnife is effective and safe against relatively large pituitary adenomas. Careful long-term follow-up of the patients is necessary because of delayed cystic enlargement of the tumor in rare cases.

CyberKnife radiosurgery for vestibular schwannoma.

OBJECTIVE: The CyberKnife is newly developed equipment for radiosurgery and fractionated radiosurgery. The authors report on their experience using the CyberKnife in 38 patients with vestibular schwannoma who were treated between 1998 to 2002. METHODS: During this period, 38 patients with vestibular schwannoma were treated using CyberKnife fractionated radiosurgery. Before undergoing fractionated radiosurgery, 14 patients had Gardner Robertson classes I or II hearing (the serviceable hearing group), and 24 patients had classes III to V hearing (the non-serviceable hearing group). The treatment volumes of these two groups were 0.5 to 24.0 cm (3) (mean 4.7 cm (3)), and 0.5 to 41.6 cm (3) (mean 8.2 cm (3)). Target irradiation was administered in 1 - 3 fractions (mean 2.5 fractions). The total marginal radiation doses were 15.0 to 20.5 Gy (mean 17.0 Gy), and 11.9 to 20.1 Gy (mean 16.9 Gy), respectively. RESULTS: After a mean follow-up period of 31.9 months (range 12 to 59 months, median 27 months), 94 % of the tumors were controlled. Only one patient in the group with non-serviceable hearing underwent additional surgical resection for a presumed increase in tumor size. The hearing preservation rate was 93 %. Facial weakness did not develop in any of the patients in the serviceable hearing group. New trigeminal symptoms did not develop in any patients in either group. CONCLUSION: Although a longer and more extensive follow-up is needed, CyberKnife fractionated radiosurgery is considered to be safe and effective, even in patients with large tumors.

Identification of dislocations in large tetragonal hen egg-white lysozyme crystals by synchrotron white-beam topography.

Large tetragonal hen egg-white (HEW) lysozyme crystals have been grown by a salt concentration-gradient method. The grown crystals, of thicknesses greater than 1.5 mm, were observed by means of X-ray topography using white-beam synchrotron radiation. Line contrasts clearly appeared on the Laue topographs. Extinction of the line images was observed in specific reflections. These results mean that the observed lines correspond to dislocation images. From the extinction criterion it is shown that the predominant dislocations are of screw character with <110> Burgers vectors. In addition, dislocation loops with [001] Burgers vectors have been found in a tetragonal HEW lysozyme crystal including some cracks. These results are discussed in the light of dislocation elastic energy and slip systems in the crystals.

Image-guided transsphenoidal surgery for pituitary lesions using Mehrkoordinaten Manipulator (MKM) navigation system.

Twenty-five patients with pituitary lesions were operated on by image-guided transsphenoidal surgery (TSS) using the Mehrkoordinaten Manipulator (MKM) navigation system. The cases included 21 cases of pituitary adenomas, 2 cases of craniopharyngioma and 2 cases of Rathke's cleft cyst. All operations were performed through the sublabial approach under an operative microscope. In some cases, an endoscope was used for the observation of the residual tumor and surrounding structures. The tumors and surrounding important structures such as the internal carotid arteries, the basilar artery, and the optic nerves were precisely localized, and mechanical error was less than 2 mm in almost all cases. In 3 early cases of pituitary adenoma, the patient's head was moved slightly during the insertion of the nasal speculum; in these cases, the resulting error was more than 2 mm. In evaluating the procedures, we determined that the most useful benefit of the MKM system compared with other systems is that the navigation information is not only displayed on the monitor, but also presented in the operative field under the microscope. Therefore, the surgeon can obtain the navigation information without removing his eyes from the operative field under the microscope. The most important drawback to the system is its bulky size.