Endocytosis-Like Vesicle Fission Mediated by a Membrane-Expanding Molecular Machine Enables Virus Encapsulation for In Vivo Delivery.

Biological membranes are functionalized by membrane-associated protein machinery. Membrane-associated transport processes, such as endocytosis, represent a fundamental and universal function mediated by membrane-deforming protein machines, by which small biomolecules and even micrometer-size substances can be transported via encapsulation into membrane vesicles. Although synthetic molecules that induce dynamic membrane deformation have been reported, a molecular approach enabling membrane transport in which membrane deformation is coupled with substance binding and transport remains critically lacking. Here, we developed an amphiphilic molecular machine containing a photoresponsive diazocine core (AzoMEx) that localizes in a phospholipid membrane. Upon photoirradiation, AzoMEx expands the liposomal membrane to bias vesicles toward outside-in fission in the membrane deformation process. Cargo components, including micrometer-size M13 bacteriophages that interact with AzoMEx, are efficiently incorporated into the vesicles through the outside-in fission. Encapsulated M13 bacteriophages are transiently protected from the external environment and therefore retain biological activity during distribution throughout the body via the blood following administration. This research developed a molecular approach using synthetic molecular machinery for membrane functionalization to transport micrometer-size substances and objects via vesicle encapsulation. The molecular design demonstrated in this study to expand the membrane for deformation and binding to a cargo component can lead to the development of drug delivery materials and chemical tools for controlling cellular activities.

Coarse-grained molecular dynamics simulation of cation distribution profiles on negatively charged lipid membranes during phase separation.

Revealing the ion distributions on a charged lipid membrane in aqueous solution under the influence of long-range interactions is essential for understanding the origin of the stability of the bilayer structure and the interaction between biomembranes and various electrolytes. However, the ion distributions and their dynamics associated with the phase separation process of the lipid bilayer membrane are still unclear. We perform coarse-grained molecular dynamics simulations to reveal the Na+ and Cl- distributions on charged phospholipid bilayer membranes during phase separation. During the phase separation, cations closely follow the position of negatively charged lipids on a microsecond timescale and are rapidly redistributed parallel to the lipid bilayer. In the homogenous mixture of zwitterionic and negatively charged lipids, cations weakly follow negatively charged lipids, indicating the strong interaction between cations and negatively charged lipids. We also compare cation concentrations as a function of surface charge density obtained by our simulation with those obtained by a modified Poisson-Boltzmann theory. Including the ion finite size makes the statistical results consistent, suggesting the importance of the ion-ion interactions in aqueous solution. Our simulation results advance our understanding of ion distribution during phase separation.

Rotational Dynamics of Water at the Phospholipid Bilayer Depending on the Head Groups Studied by Molecular Dynamics Simulations.

Hydration states are a crucial factor that affect the self-assembly and properties of soft materials and biomolecules. Although previous experiments have revealed that the hydration state strongly depends on the chemical structure of lipid molecules, the mechanisms at the molecular level remain unknown. Classical and density-functional tight-binding (DFTB) molecular dynamics (MD) simulations are employed to determine the mechanisms underlying dissimilar water dynamics between lipid membranes with phosphatidylcholine (PC) and phosphatidylethanolamine (PE) head groups. The classical MD simulation shows that rotational relaxations of water are faster on the PE lipid than on the PC lipid, which is consistent with a previous experimental study using terahertz spectroscopy. Furthermore, DFTB-MD simulation of N(CH3)4+ and NH4+ ions, which correspond to the different head groups in PC and PE, respectively, shows qualitative agreement with the classical MD simulation. Remarkably, the PE lipids and the NH4+ ions break hydrogen bonds between water molecules in the secondary hydration shell. In contrast, the PC lipids and the N(CH3)4+ ions bind water molecules weakly in both the primary and secondary hydration shells and increase hydrogen bonds between water. Our atomistic simulations show that these changes in the hydrogen-bond network of water molecules cause the different rotational relaxation of water molecules between the two lipids.

Three-Phase Coexistence in Binary Charged Lipid Membranes in a Hypotonic Solution.

We investigated the phase separation of dioleoylphosphatidylserine (DOPS) and dipalmitoylphosphatidylcholine (DPPC) in giant unilamellar vesicles in a hypotonic solution using fluorescence and confocal laser scanning microscopy. Although phase separation in charged lipid membranes is generally suppressed by the electrostatic repulsion between the charged headgroups, osmotic stress can promote the formation of charged lipid domains. Interestingly, we observed a three-phase coexistence even in the DOPS/DPPC binary lipid mixtures. The three phases were DPPC-rich, dissociated DOPS-rich, and nondissociated DOPS-rich phases. The two forms of DOPS were found to coexist owing to the ionization of the DOPS headgroup, such that the system could be regarded as quasi-ternary. The three formed phases with differently ionized DOPS domains were successfully identified experimentally by monitoring the adsorption of positively charged particles. In addition, coarse-grained molecular dynamics simulations confirmed the stability of the three-phase coexistence. Attraction mediated by hydrogen bonding between protonated DOPS molecules and reduction of the electrostatic interactions at the domain boundaries stabilized the three-phase coexistence.

Role of OH Termination in Mitigating Friction of Diamond-like Carbon under High Load: A Joint Simulation and Experimental Study.

Diamond-like carbon (DLC) has recently attracted much attention as a promising solid-state lubricant because it exhibits low friction, low abrasion, and high wear resistance. Although we previously reported the reason why H-terminated DLC exhibits low friction based on a tight-binding quantum chemical molecular dynamics (TB-QCMD) simulation, experimentally, the low-friction state of H-terminated DLC is not stable, limiting its application. In the present work, our TB-QCMD simulations suggest that H/OH-terminated DLC could give low friction even under high loads, whereas H-terminated DLC could not. By using gas-phase friction experiments, we confirm that OH termination can indeed provide much more stable lubricity than H termination, validating the predictions from simulations. We conclude that H/OH-terminated DLC is a new low-friction material with high load capacity and high stable lubricity that may be suitable for practical use in industrial applications.

Cancer care for people with mental disorders: A qualitative survey among cancer care and psychiatric care professionals in Japan.

OBJECTIVE: It is widely assumed that there are multiple levels (from individual to policy level) of problems involving disparities in cancer care for people with mental disorders. However, few studies have comprehensively investigated issues as perceived by medical professionals. The purpose of the present study was to identify a wide range of issues in cancer care for people with mental disorders and offer corresponding solutions for both cancer care professionals and psychiatric care professionals. METHODS: We distributed open-ended questionnaires to 754 healthcare professionals in various medical facilities, including designated cancer hospitals, psychiatric hospitals, and other local healthcare/welfare facilities. Participants were asked to describe issues in cancer care for people with mental disorders. RESULTS: Of the 754 recruited professionals, 439 (58.2%) responded to the questionnaire. Sixty-one issues were extracted and categorized into 10 categories: patient factors; isolation and lack of support; obstacles to transport; socioeconomic factors; attitudes of psychiatric professionals; medical system of psychiatric hospitals; attitudes of cancer care professionals; medical system of designated cancer hospitals; regional cancer medical systems; and lack of coordination among multidisciplinary healthcare professionals. Forty-eight specific solutions were summarized into 12 goals. CONCLUSIONS: The present study widely identified issues causing disparities in cancer care for patients with mental disorders. We found that the issues extended from the patient level to the public-policy level. Our findings suggest the need for a multidisciplinary approach that includes both cancer and psychiatric care professionals to address the gap in cancer care for people with mental disorders.

Cooperative roles of chemical reactions and mechanical friction in chemical mechanical polishing of gallium nitride assisted by OH radicals: tight-binding quantum chemical molecular dynamics simulations.

Chemical mechanical polishing (CMP) is a key manufacturing process for applying gallium nitride (GaN), especially the Ga-face GaN, to semiconductor devices such as laser diodes. However, the CMP efficiency for GaN is very low due to its high hardness and chemical stability. Experimentally, OH radicals appear able to improve the CMP efficiency of GaN polished by a SiO2 abrasive grain, whereas the mechanisms of the OH-radical-assisted CMP process remain unclear because experimental elucidation of the complex chemical reactions occurring among GaN substrate, abrasive grain, and OH radicals is difficult. In this work, we used our previously developed tight-binding quantum chemical molecular dynamics simulator to study the OH-radical-assisted CMP process of the widely employed Ga-face GaN substrate polished by an amorphous SiO2 abrasive grain in an effort to understand how OH radicals assist the CMP process and then aid the development of next-generation CMP techniques. Our simulations revealed that the OH-radical-assisted CMP process of GaN occurs via the following three basic reaction steps: (i) first, all hydrogen terminations on the GaN surface are replaced by OH terminations through continuous reactions with OH radicals; (ii) after the substrate is fully terminated by OH, the hydrogen atoms of these OH terminations are removed by reacting with newly added OH radicals, which forms H2O molecules and leaves energetic oxygen atoms with dangling bonds on the surface; and (iii) finally, these energetic oxygen atoms intrude inside the substrate with concomitant dissociation of Ga-N bonds and the generation of N2 and gallium hydroxide molecules, which accumulatively lead to the removal of N and Ga atoms from the substrate.

Validity and Reliability of the Japanese Version of the 12-item Self-administered World Health Organization Disability Assessment Schedule (WHODAS) 2.0 in Patients with Schizophrenia.

It is necessary to assess functional impairment when treating schizophrenia. The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) has been adopted as a measure of functional disability in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. This study was a secondary analysis from a cross-sectional study of health-related behaviors among patients with schizophrenia. We examined the validity and reliability of the Japanese version of the 12-item WHODAS 2.0 when self-administered by such patients. Participants were 350 outpatients with schizophrenia from a psychiatric hospital. The standard six-factor structure of the WHODAS 2.0 showed a good fit for these participants. The Cronbach's alpha coefficient was 0.858, showing good internal consistency. The WHODAS 2.0 showed moderate correlations with the modified Global Assessment of Functioning and Kessler 6 scales (r=-0.434 and 0.555, respectively). The results of this study show that the Japanese version of the 12-item self-administered WHODAS 2.0 has good internal consistency and convergent validity among patients with schizophrenia. Further exploration of the usefulness of WHODAS 2.0 in clinical settings is needed.

Supramolecular Biocomposite Hydrogels Formed by Cellulose and Host-Guest Polymers Assisted by Calcium Ion Complexes.

Hydrogels are biocompatible polymer networks; however, they have the disadvantage of having poor mechanical properties. Herein, the mechanical properties of host-guest hydrogels were increased by adding a filler and incorporating other noncovalent interactions. Cellulose was added as a filler to the hydrogels to afford a composite. Citric acid-modified cellulose (CAC) with many carboxyl groups was used instead of conventional cellulose. The preparation began with mixing an acrylamide-based αCD host polymer (p-αCD) and a dodecanoic acid guest polymer (p-AADA) to form supramolecular hydrogels (p-αCD/p-AADA). However, when CAC was directly added to p-αCD/p-AADA to form biocomposite hydrogels (p-αCD/p-AADA/CAC), it showed weaker mechanical properties than p-αCD/p-AADA itself. This was caused by the strong intramolecular hydrogen bonding (H-bonding) within the CAC, which prevented the CAC reinforcing p-αCD/p-AADA in p-αCD/p-AADA/CAC. Then, calcium chloride solution (CaCl2) was used to form calcium ion (Ca2+) complexes between the CAC and p-αCD/p-AADA. This approach successfully created supramolecular biocomposite hydrogels assisted by Ca2+ complexes (p-αCD/p-AADA/CAC/Ca2+) with improved mechanical properties relative to p-αCD/p-AADA hydrogels; the toughness was increased 6-fold, from 1 to 6 MJ/m3. The mechanical properties were improved because of the disruption of the intramolecular H-bonding within the CAC by Ca2+ and subsequent complex formation between the carboxyl groups of CAC and p-AADA. This mechanism is a new approach for improving the mechanical properties of hydrogels that can be broadly applied as biomaterials.

Change in smoking cessation stage over 1 year in patients with schizophrenia: a follow up study in Japan.

BACKGROUND: We performed a follow up study about willingness and behaviors to quit smoking among smokers with schizophrenia in Japan. METHODS: Participants were outpatients with schizophrenia aged 20-69 years who had been visiting the hospital for ≥1 year as of April 1, 2016, and had visited the hospital more than once in the previous 6 months. A baseline survey on smoking behaviors including current smoking status and smoking cessation stage, was administered in 420 participants that were randomly extracted from a patient pool (n = 680) in 2016, and a follow-up survey was administered in 2017. We calculated the distribution and change in smoking cessation stage, number of smokers and nonsmokers after 1 year, and quitting rate from a naturalistic 1-year smoking-cessation follow up. RESULTS: The number of baseline respondents was 350; 113 current smokers and 68 former smokers. Among the 113 current smokers, 104 (92.0%) were followed for 1 year, 79 (70.0%) were interested in smoking cessation, and only 7 had received smoking cessation treatments at baseline. Among the tracked 104 participants, only 6 (5.8%) stopped smoking after 1 year. Among the 25 participants who had intentions to quit smoking within 6 months at baseline, 6 (24.0%) maintained their intention to quit smoking for 1 year, and 16 (64.0%) did not maintain their intention to quit smoking. CONCLUSIONS: Our findings showed that many smokers with schizophrenia were interested in quitting smoking, but few patients received treatment and actually quit smoking. Timely intervention, including the option to receive smoking cessation treatment, is necessary for those patients with schizophrenia who smoke. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN000023874, registered on August 31, 2016).

Confidence in communicating with patients with cancer mediates the relationship between rehabilitation therapists' autistic-like traits and perceived difficulty in communication.

OBJECTIVE: Recently, rehabilitation therapists have become involved in cancer rehabilitation; however, no communication skills training that increases the ability to provide emotional support for cancer patients has been developed for rehabilitation therapists. In addition, no study has examined associations between rehabilitation therapists' communication skills and their level of autistic-like traits (ALT), which are in-born characteristics including specific communication styles and difficulty communicating with patients. In this study, we aimed to investigate whether confidence in communicating with patients mitigates communication difficulties experienced by rehabilitation therapists who have high levels of ALT. METHOD: Rehabilitation therapists who treat patients with cancer completed self-administered postal questionnaires anonymously. Scores were obtained on the Autism-Spectrum Quotient short form, confidence in communication, and communication difficulties. We used covariance structure analyses to test hypothetical models, and confirmed that confidence in communication mediates the relationship between ALT and perceived communication difficulties. RESULTS: Participants included 1,343 respondents (49.6%). Autism-Spectrum Quotient scores were positively correlated with communication difficulties (r = 0.16, p < 0.001). The correlation was mitigated by confidence in communication in the fit model. However, higher confidence in creating a supportive atmosphere was associated with more difficulty in communication (r = 0.16, p < 0.001). SIGNIFICANCE OF RESULTS: Communication difficulty was linked to rehabilitation therapists' ALTs. By increasing confidence in areas of communication other than creation of a supportive atmosphere, ALT-related difficulties in communication may be ameliorated. Confidence to create supportive environments correlated positively with difficulty. Communication skills training to increase confidence in communication for rehabilitation therapists should be developed with vigilance regarding ALT levels.

Association between serious psychological distress and nonparticipation in cancer screening and the modifying effect of socioeconomic status: Analysis of anonymized data from a national cross-sectional survey in Japan.

BACKGROUND: It is unclear whether individuals who have serious psychological distress (SPD) are less likely to participate in screening tests for gastric cancer, lung cancer, and other types of cancer. Of the few studies that have examined the association between SPD and participation in cancer screening, none have reported modifying effects of educational, marital, or employment status. METHODS: The authors analyzed a national representative data set from the 2010 Comprehensive Survey of Living Conditions of Japan., including individuals aged <69 years who met the national program criteria for each type of cancer screening (colorectal, gastric, and lung cancers, n = 29,926; breast cancer, n = 15,423; and cervical cancer, n = 24,735). SPD was defined as a score of 13 or greater on the Kessler 6 scale. Logistic regression analyses were conducted to examine the association between SPD and participation in cancer screening, and multivariate analyses stratified by socioeconomic status also were conducted. RESULTS: SPD was significantly associated with a lower odds ratio (OR) for participation in screening for colorectal cancer (OR, 0.743; 95% confidence interval [CI], 0.638-0.866), gastric cancer (OR, 0.823; 95% CI, 0.717-0.946), and lung cancer (OR, 0.691; 95% CI, 0.592-0.807). Only educational status significantly modified the effect of SPD on participation in these 3 types of cancer screening (P < .05). CONCLUSIONS: Individuals with SPD, especially those with lower education levels, were less likely to participate in screening for colorectal, gastric, and lung cancers. Individuals with SPD should be encouraged and supported to participate in cancer screening tests. Cancer 2018;124:555-62. © 2017 American Cancer Society.

Low Cancer Screening Rates among Japanese People with Schizophrenia: A Cross-Sectional Study.

Health care disparities among people with schizophrenia is a global concern. Our previous study revealed cancer screening rates in Japanese people with schizophrenia lower than rates of approximately 40% of the general population. However, that study was based on self-reports, which can be inaccurate, and rates did not differentiate the types of cancer screening provider (i.e., municipal screening, collective opportunistic screening, and individual opportunistic screening). This study aimed to investigate records-based cancer screening rates, focusing on participation rates of people with schizophrenia who are subject to municipal cancer screening programs. We conducted a cross-sectional study at a psychiatric hospital outpatient clinic from September to November 2016. We randomly extracted 420 potential participants from among 680 eligible patients and asked them to participate. We then selected subgroups of participants living in Okayama city who were enrolled in the National Health Insurance or Public Assistance systems and were subject to colorectal, gastric, lung, breast, or cervical cancer screening provided by Okayama city (n = 97, 96, 97, 42, and 64, respectively). Participation in cancer screenings was assessed based on local government records. Municipal cancer screening rates were as follows: 13.4% (95% confidence interval: 6.6%-20.2%) for colorectal, 7.3% (2.1%-12.5%) for gastric, 16.5% (9.1%-23.9%) for lung, 21.4% (9.0%-33.8%) for breast, and 14.1% (5.6%-22.6%) for cervical cancers. The findings demonstrated extremely low cancer screening rates among people with schizophrenia subject to municipal cancer screenings in Japan. A strategy to promote municipal cancer screening for people with schizophrenia is needed.

Cancer screening participation in schizophrenic outpatients and the influence of their functional disability on the screening rate: A cross-sectional study in Japan.

AIM: The influence of schizophrenic patients' functional disability on cancer screening participation worldwide is unclear. There are few findings on the disparities in schizophrenic patients' participation in cancer screening programs in Asia. The aim of this study was to investigate the screening rate and the associations between screening and symptom severity/functional disability in patients with schizophrenia. METHODS: This cross-sectional study was conducted in a psychiatric hospital outpatient clinic in Japan. We recruited schizophrenic patients meeting the national program criteria for cancer screening for colorectal, gastric, lung, breast, and cervical cancer (n = 224, 223, 224, 110, and 175, respectively). Receipt of cancer screenings was assessed using a self-report questionnaire. Scores on the modified Global Assessment of Functioning (mGAF) were evaluated by participants' primary psychiatrists. RESULTS: Rates of cancer screenings were as follows: 24.1% for colorectal, 21.5% for gastric, 30.8% for lung, 25.5% for breast, and 19.4% for cervical cancer. A multivariable logistic analysis showed that a 1-point increase in severity/disability (100 minus mGAF score) was associated with significantly lower odds ratios (OR) for receipt of cancer screenings, except for breast cancer (OR, 0.95, 95% confidence interval [CI], 0.93-0.98 for colorectal; OR, 0.96, 95%CI, 0.93-0.98 for gastric; OR, 0.95, 95%CI, 0.93-0.97 for lung; OR, 0.97, 95%CI, 0.94-1.00 for breast; and OR, 0.95, 95%CI, 0.92-0.98 for cervical cancer). CONCLUSION: The findings demonstrated low rates of cancer screenings in schizophrenic patients in Japan. Our study suggests the need to encourage attendance at cancer screenings, especially in schizophrenic patients with severe symptoms/functional disability.

Tight-binding quantum chemical molecular dynamics simulations for the elucidation of chemical reaction dynamics in SiC etching with SF6/O2 plasma.

We used our etching simulator [H. Ito et al., J. Phys. Chem. C, 2014, 118, 21580-21588] based on tight-binding quantum chemical molecular dynamics (TB-QCMD) to elucidate SiC etching mechanisms. First, the SiC surface is irradiated with SF5 radicals, which are the dominant etchant species in experiments, with the irradiation energy of 300 eV. After SF5 radicals bombard the SiC surface, Si-C bonds dissociate, generating Si-F, C-F, Si-S, and C-S bonds. Then, etching products, such as SiS, CS, SiFx, and CFx (x = 1-4) molecules, are generated and evaporated. In particular, SiFx is the main generated species, and Si atoms are more likely to vaporize than C atoms. The remaining C atoms on SiC generate C-C bonds that may decrease the etching rate. Interestingly, far fewer Si-Si bonds than C-C bonds are generated. We also simulated SiC etching with SF3 radicals. Although the chemical reaction dynamics are similar to etching with SF5 radicals, the etching rate is lower. Next, to clarify the effect of O atom addition on the etching mechanism, we also simulated SiC etching with SF5 and O radicals/atoms. After bombardment with SF5 radicals, Si-C bonds dissociate in a similar way to the etching without O atoms. In addition, O atoms generate many C-O bonds and COy (y = 1-2) molecules, inhibiting the generation of C-C bonds. This indicates that O atom addition improves the removal of C atoms from SiC. However, for a high O concentration, many C-C and Si-Si bonds are generated. When the O atoms dissociate the Si-C bonds and generate dangling bonds, the O atoms terminate only one or two dangling bonds. Moreover, at high O concentrations there are fewer S and F atoms to terminate the dangling bonds than at low O concentration. Therefore, few dangling bonds of dissociated Si and C atoms are terminated, and they form many Si-Si and C-C bonds. Furthermore, we propose that the optimal O concentration is 50-60% because both Si and C atoms generate many etching products producing fewer C-C and Si-Si bonds are generated. Finally, we conclude that our TB-QCMD etching simulator is effective for designing the optimal conditions for etching processes in which chemical reactions play a significant role.

A cross-sectional study of psychological distress, burnout, and the associated risk factors in hospital pharmacists in Japan.

BACKGROUND: Opportunities for face-to-face communication with patients is increasing in modern hospital pharmacist practice. This may impose new burdens on hospital pharmacists. We performed a cross-sectional study to examine the prevalence of psychological distress, burnout, and compassion fatigue among hospital pharmacists. We also investigated possible relevant factors, such as sex, years of experience, hospital size, interpersonal work hours, and personality traits related to communication. METHODS: We mailed self-administered questionnaires to all pharmacists (n = 823) belonging to the prefectural society of hospital pharmacists in Japan. The questionnaires were the General Health Questionnaire (GHQ-12), Burnout (BO) and Compassion Fatigue and Secondary Traumatic Stress (CF/STS) subscales of the Professional Quality of Life Scale, the Autism Spectrum Quotient (AQ), and the Adult ADHD (attention deficit hyperactivity disorder) Self-Report Scale (ASRS). We examined associations between personality traits (AQ, ASRS) and psychological burden (GHQ-12, BO, CF/STS) using rank ANCOVA or multivariate logistic regression analyses. RESULTS: Complete responses were obtained from 380 pharmacists (46.2 % response rate). A substantial number of participants obtained scores that were higher than the cutoff points of the GHQ-12 (54.7 %), BO (49.2 %), and CF/STS (29.2 %). The GHQ-12 scores were negatively affected by years of experience (p < 0.001), and positively affected by AQ (p < 0.001) and ASRS (p < 0.001) scores. The BO scores was positively affected by AQ (p < 0.001) and ASRS (p = 0.001) scores, while the CF/STS (p = 0.023) score was negatively affected by years of experience, and positively affected by AQ (p < 0.001) and ASRS (p < 0.001) scores. CONCLUSIONS: There is a high prevalence of psychological distress and work-related burnout/CF among hospital pharmacists. Additionally, two common personality traits, such as autistic-like traits and ADHD-like symptoms, which might be related to communication style, could increase the risk of psychological distress and burnout/CF. Early risk assessment and preventive interventions that are specialized for these characteristics could protect individuals with these specific traits from burnout.

An Open-Label Feasibility Trial of Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Major Depressive Episodes.

Repetitive transcranial magnetic stimulation (rTMS) has been reported to be a new treatment option for treatment-resistant depression. In Japan, there has been limited research into its feasibility, efficacy, and tolerability. We have launched a trial of rTMS for treating medication-resistant major depressive disorder and bipolar depression. We are investigating low-frequency rTMS to the right dorsolateral prefrontal cortex and traditional high-frequency rTMS to the left dorsolateral prefrontal cortex, in 20 patients. The primary outcome of the study is the treatment completion rate. This study will provide new data on the usefulness of rTMS for treatment-resistant depression in Japan.

Communication: different behavior of Young's modulus and fracture strength of CeO2: density functional theory calculations.

In this Communication, we use density functional theory (DFT) to examine the fracture properties of ceria (CeO2), which is a promising electrolyte material for lowering the working temperature of solid oxide fuel cells. We estimate the stress-strain curve by fitting the energy density calculated by DFT. The calculated Young's modulus of 221.8 GPa is of the same order as the experimental value, whereas the fracture strength of 22.7 GPa is two orders of magnitude larger than the experimental value. Next, we combine DFT and Griffith theory to estimate the fracture strength as a function of a crack length. This method produces an estimated fracture strength of 0.467 GPa, which is of the same order as the experimental value. Therefore, the fracture strength is very sensitive to the crack length, whereas the Young's modulus is not.

Rotational Dynamics of Water near Osmolytes by Molecular Dynamics Simulations.

The behavior of water molecules around organic molecules has attracted considerable attention as a crucial factor influencing the properties and functions of soft matter and biomolecules. Recently, it has been suggested that the change in protein stability upon the addition of small organic molecules (osmolytes) is dominated by the change in the water dynamics caused by the osmolyte, where the dynamics of not only the directly interacting water molecules but also the long-range hydration layer affect the protein stability. However, the relation between the long-range structure of hydration water in various solutions and the water dynamics remains unclear at the molecular level. We performed density-functional tight-binding molecular dynamics simulations to elucidate the varying rotational dynamics of water molecules in 15 osmolyte solutions. A positive correlation was observed between the rotational relaxation time and our proposed normalized parameter obtained by dividing the number of hydrogen bonds between water molecules by the number of nearest-neighbor water molecules. For the 15 osmolyte solutions, an increase or a decrease in the value of the normalized parameter for the second hydration shell tended to result in water molecules with slow and fast rotational dynamics, respectively, thus illustrating the importance of the second hydration shell for the rotational dynamics of water molecules. Our simulation results are anticipated to advance the current understanding of water dynamics around organic molecules and the long-range structure of water molecules.