Remote Mesoscopic Signatures of Induced Magnetic Texture in Graphene.

Mesoscopic conductance fluctuations are a ubiquitous signature of phase-coherent transport in small conductors, exhibiting universal character independent of system details. In this Letter, however, we demonstrate a pronounced breakdown of this universality, due to the interplay of local and remote phenomena in transport. Our experiments are performed in a graphene-based interaction-detection geometry, in which an artificial magnetic texture is induced in the graphene layer by covering a portion of it with a micromagnet. When probing conduction at some distance from this region, the strong influence of remote factors is manifested through the appearance of giant conductance fluctuations, with amplitude much larger than e^{2}/h. This violation of one of the fundamental tenets of mesoscopic physics dramatically demonstrates how local considerations can be overwhelmed by remote signatures in phase-coherent conductors.

Routine Referral by Urologists Increase Opportunities for Corneal Donation.

BACKGROUND: The levels of corneal donation are insufficient to meet the demand for corneal transplantation in Japan. To overcome this problem, we started to routinely mention the possibility of corneal donation to the families of patients who died in our hospital's Urology Department in February 2008. In this study, we evaluated the effectiveness of this approach. METHODS: We retrospectively reviewed the medical records of the patients who died in the Department of Urology, St. Marianna University School of Medicine Hospital, and analyzed the patients' characteristics and information about corneal donation. RESULTS: In total, 211 patients died in our department between February 2008 and March 2017, and 155 patients were medically suitable corneal donors. We mentioned the possibility of corneal donation to 129 (83.2%) families, and 29 (18.7%) families agreed. Three families subsequently withdrew their consent. Finally, 26 (16.8%) of the families that were approached about corneal donation by urologists agreed to donate their relatives' corneas. Another 2 families voluntarily offered to donate their relatives' corneas. Thus, 28 (18.1%) of 155 medically suitable donors donated their corneas for transplantation. Twenty-six (92.8%) donors were 60 years or older and all donors were affected with malignant genitourinary tumors. Fifty-four (96.4%) corneas were successfully transplanted into recipients. CONCLUSIONS: Even elderly patients who die of solid carcinoma can be an important source of corneal donors. In this study, we showed that routine referral by urologists increased corneal donation. If this approach were adopted by other departments, it might further increase the number of corneal donations.

Evaluation of clinical coding data to determine causes of critical bleeding in patients receiving massive transfusion: a bi-national, multicentre, cross-sectional study.

OBJECTIVES: To evaluate the use of routinely collected data to determine the cause(s) of critical bleeding in patients who receive massive transfusion (MT). BACKGROUND: Routinely collected data are increasingly being used to describe and evaluate transfusion practice. MATERIALS/METHODS: Chart reviews were undertaken on 10 randomly selected MT patients at 48 hospitals across Australia and New Zealand to determine the cause(s) of critical bleeding. Diagnosis-related group (DRG) and International Classification of Diseases (ICD) codes were extracted separately and used to assign each patient a cause of critical bleeding. These were compared against chart review using percentage agreement and kappa statistics. RESULTS: A total of 427 MT patients were included with complete ICD and DRG data for 427 (100%) and 396 (93%), respectively. Good overall agreement was found between chart review and ICD codes (78·3%; κ = 0·74, 95% CI 0·70-0·79) and only fair overall agreement with DRG (51%; κ = 0·45, 95% CI 0·40-0·50). Both ICD and DRG were sensitive and accurate for classifying obstetric haemorrhage patients (98% sensitivity and κ > 0·94). However, compared with the ICD algorithm, DRGs were less sensitive and accurate in classifying bleeding as a result of gastrointestinal haemorrhage (74% vs 8%; κ = 0·75 vs 0·1), trauma (92% vs 62%; κ = 0·78 vs 0·67), cardiac (80% vs 57%; κ = 0·79 vs 0·60) and vascular surgery (64% vs 56%; κ = 0·69 vs 0·65). CONCLUSION: Algorithms using ICD codes can determine the cause of critical bleeding in patients requiring MT with good to excellent agreement with clinical history. DRG are less suitable to determine critical bleeding causes.

Improving outcomes for hospital patients with critical bleeding requiring massive transfusion: the Australian and New Zealand Massive Transfusion Registry study methodology.

BACKGROUND: The Australian and New Zealand (ANZ) Massive Transfusion (MT) Registry (MTR) has been established to improve the quality of care of patients with critical bleeding (CB) requiring MT (≥ 5 units red blood cells (RBC) over 4 h). The MTR is providing data to: (1) improve the evidence base for transfusion practice by systematically collecting data on transfusion practice and clinical outcomes; (2) monitor variations in practice and provide an opportunity for benchmarking, and feedback on practice/blood product use; (3) inform blood supply planning, inventory management and development of future clinical trials; and (4) measure and enhance translation of evidence into policy and patient blood management guidelines. The MTR commenced in 2011. At each participating site, all eligible patients aged ≥18 years with CB from any clinical context receiving MT are included using a waived consent model. Patient information and clinical coding, transfusion history, and laboratory test results are extracted for each patient's hospital admission at the episode level. RESULTS: Thirty-two hospitals have enrolled and 3566 MT patients have been identified across Australia and New Zealand between 2011 and 2015. The majority of CB contexts are surgical, followed by trauma and gastrointestinal haemorrhage. Validation studies have verified that the definition of MT used in the registry correctly identifies 94 % of CB events, and that the median time of transfusion for the majority of fresh products is the 'product event issue time' from the hospital blood bank plus 20 min. Data linkage between the MTR and mortality databases in Australia and New Zealand will allow comparisons of risk-adjusted mortality estimates across different bleeding contexts, and between countries. Data extracts will be examined to determine if there are differences in patient outcomes according to transfusion practice. The ratios of blood components (e.g. FFP:RBC) used in different types of critical bleeding will also be investigated. CONCLUSIONS: The MTR is generating data with the potential to have an impact on management and policy decision-making in CB and MT and provide benchmarking and monitoring tools for immediate application.

Thermally Assisted Nonvolatile Memory in Monolayer MoS2 Transistors.

We demonstrate a novel form of thermally-assisted hysteresis in the transfer curves of monolayer MoS2 FETs, characterized by the appearance of a large gate-voltage window and distinct current levels that differ by a factor of ∼102. The hysteresis emerges for temperatures in excess of 400 K and, from studies in which the gate-voltage sweep parameters are varied, appears to be related to charge injection into the SiO2 gate dielectric. The thermally-assisted memory is strongly suppressed in equivalent measurements performed on bilayer transistors, suggesting that weak screening in the monolayer system plays a vital role in generating its strongly sensitive response to the charge-injection process. By exploiting the full features of the hysteretic transfer curves, programmable memory operation is demonstrated. The essential principles demonstrated here point the way to a new class of thermally assisted memories based on atomically thin two-dimensional semiconductors.

Conductance fluctuations in high mobility monolayer graphene: Nonergodicity, lack of determinism and chaotic behavior.

We have fabricated a high mobility device, composed of a monolayer graphene flake sandwiched between two sheets of hexagonal boron nitride. Conductance fluctuations as functions of a back gate voltage and magnetic field were obtained to check for ergodicity. Non-linear dynamics concepts were used to study the nature of these fluctuations. The distribution of eigenvalues was estimated from the conductance fluctuations with Gaussian kernels and it indicates that the carrier motion is chaotic at low temperatures. We argue that a two-phase dynamical fluid model best describes the transport in this system and can be used to explain the violation of the so-called ergodic hypothesis found in graphene.

Characteristics of meso-particles formed in coagulation process causing irreversible membrane fouling in the coagulation-microfiltration water treatment.

In coagulation-membrane filtration water treatment processes, it is still difficult to determine the optimal coagulation condition to minimize irreversible membrane fouling. In microfiltration (MF), meso-particles (i.e., 20 nm-0.5 µm) are thought to play an important role in irreversible membrane fouling, especially their characteristics of particle number (PN) and zeta potential (ZP). In this study, a new nanoparticle tracker combined a high-output violet laser with a microscope was developed to identify the physicochemical characteristics of these microscopic and widely dispersed meso-particles. The effects of pH and coagulant dose on ZP and PN of micro-particles (i.e., >0.5 µm) and meso-particles were investigated, and then coagulation-MF tests were conducted. As the result, irreversible membrane fouling was best controlled for both types of membranes, while meso-particle ZP approached zero at around pH 5.5 for both types of natural water. Since PN was greatest under these conditions, ZP is more important in determining the extent of irreversible membrane fouling than PN. However, the acidic condition to neutralize meso-particles is not suitable for actual operation, as considering residual aluminum concentration, pipe corrosion, and chlorination efficiency. It is therefore necessary to investigate coagulants or other methods for the appropriate modification of meso-particle characteristics.

Probing weak localization in chemical vapor deposition graphene wide constriction using scanning gate microscopy.

Low-temperature scanning gate microscopy (LT-SGM) studies of graphene allow one to obtain important spatial information regarding coherent transport such as weak localization (WL) and universal conductance fluctuations. Although fascinating LT-SGM results on pristine graphene prepared by mechanical exfoliation have been reported in the literature, there appears to be a dearth of LT-SGM results on chemical vapor deposition (CVD)-grown graphene whose large scale and flexible substrate transferability make it an ideal candidate for coherent electronic applications. To this end, we have performed LT-SGM studies on CVD-grown graphene wide constriction (0.8 µm), which can be readily prepared by cost-effective optical lithography fully compatible with those in wafer foundry, in the WL regime. We find that the movable local gate can sensitively modulate the total conductance of the CVD graphene constriction possibly due to the intrinsic grain boundaries and merged domains, a great advantage for applications in coherent electronics. Moreover, such a conductance modulation by LT-SGM provides an additional, approximately magnetic-field-independent probe for studying coherent transport such as WL in graphene and spatial conductance variation.

Tuning surface grafting density of CeO2 nanocrystals with near- and supercritical solvent characteristics.

In this work, the solvent effect on the synthesis of CeO2 nanocrystals synthesized in near- and supercritical alcohols is discussed. The materials prepared displayed a unique morphology of small nanocrystals (<10 nm) aggregated into larger nanospheres (∼100-200 nm). In such syntheses, alcohol molecules directly interact with the nanocrystal surface through alkoxide and carboxylate bondings. The grafting density was quantified from the weight loss measured using thermogravimetric analysis. A direct correlation between the grafting density and the alcohol chain length can be established. It was demonstrated that the shorter the alcohol chain length (i.e. methanol), the higher the surface coverage is. This trend is independent of the synthesis mode (batch or continuous). Additionally, an influence of the grafting density on the resulting nanocrystal size was established. It is suggested that the surface coverage has a high influence on the early stages of the nucleation and growth. Indeed, when high surface coverages are reached, all surface active sites are blocked, limiting the growth step and therefore leading to smaller particles. This effect was noticed with the materials prepared in the continuous mode where shorter reaction time was performed.

Critical role of the neural pathway from the intermediate medial mesopallium to the intermediate hyperpallium apicale in filial imprinting of domestic chicks (Gallus gallus domesticus).

Filial imprinting in precocial birds is a useful model for studying early learning and cognitive development, as it is characterized by a well-defined sensitive or critical period. We recently showed that the thyroid hormone 3,5,3'-triiodothyronine (T3) determines the onset of the sensitive period. Moreover, exogenous injection of T3 into the intermediate medial mesopallium (IMM) region (analogous to the associative cortex in mammals) enables imprinting even on post-hatch day 4 or 6 when the sensitive period has been terminated. However, the neural mechanisms downstream from T3 action in the IMM region remain elusive. Here, we analyzed the functional involvement of the intermediate hyperpallium apicale (IMHA) in T3 action. Bilateral excitotoxic ablation of the IMHA prevented imprinting in newly hatched chicks, and also suppressed the recovery of the sensitive period by systemic intra-venous or localized intra-IMM injection of T3 in day-4 chicks. In contrast to the effect in the IMM, direct injection of T3 into the IMHA did not enable imprinting in day-4 chicks. Moreover, bilateral ablation of IMHA after imprinting training impaired recall. These results suggest that the IMHA is critical for memory acquisition downstream following T3 action in the IMM and further, that it receives and retains information stored in the IMM for recall. Furthermore, both an avian adeno-associated viral construct containing an anterograde tracer (wheat-germ agglutinin) and a retrograde tracer (cholera toxin subunit B) revealed neural connections from the IMM to the IMHA. Taken together, our findings suggest that hierarchical processes from the primary area (IMM) to the secondary area (IMHA) are required for imprinting.

Conduction Mechanisms in CVD-Grown Monolayer MoS2 Transistors: From Variable-Range Hopping to Velocity Saturation.

We fabricate transistors from chemical vapor deposition-grown monolayer MoS2 crystals and demonstrate excellent current saturation at large drain voltages (Vd). The low-field characteristics of these devices indicate that the electron mobility is likely limited by scattering from charged impurities. The current-voltage characteristics exhibit variable range hopping at low Vd and evidence of velocity saturation at higher Vd. This work confirms the excellent potential of MoS2 as a possible channel-replacement material and highlights the role of multiple transport phenomena in governing its transistor action.

Metal-insulator transition in the quasi-one-dimensional transport of fractional quantum Hall states.

We investigate edge state transmission in quantum point contacts (QPCs) in the fractional quantum-Hall regime, finding behavior reminiscent of a metal-insulator transition. The transition is suggested by an unusual behavior of the differential conductance in the fractional-quantum-Hall regime, and by the presence of a fixed point and universal scaling in the temperature dependence of the linear conductance. Noting that the 0.7 feature evolves continuously into a last fractional plateau at high magnetic fields, we suggest that this still unresolved feature may itself be viewed as a manifestation of a local, microscopic, metal-insulator transition.

Scanning gate imaging of a disordered quantum point contact.

Scanning gate microscopy (SGM) is a novel technique that has been used to image characteristic features related to the coherent electron flow in mesoscopic structures. For instance, SGM has successfully been applied to study peculiar electron transport properties that arise due to small levels of disorder in a system. The particular case of an InGaAs quantum well layer in a heterostructure, which is dominated by a quasi-ballistic regime, was analyzed. A quantum point contact fabricated onto this material exhibits conduction fluctuations that are not expected in typical high-mobility heterostructures such as AlGaAs/GaAs. SGM revealed not only interference patterns corresponding to specific conductance fluctuations but also mode-dependent resistance peaks corresponding to the first and second quantum levels of conductance (2e(2)/h) at zero magnetic field. On the other hand, clear conductance plateaus originating from the integer quantum Hall effect were observed at high magnetic fields. The physical size of incompressible edge channels was estimated from cross-sectional analysis of these images.

On the zero-bias anomaly and Kondo physics in quantum point contacts near pinch-off.

We investigate the linear and non-linear conductance of quantum point contacts (QPCs), in the region near pinch-off where Kondo physics has previously been connected to the appearance of the 0.7 feature. In studies of seven different QPCs, fabricated in the same high-mobility GaAs/AlGaAs heterojunction, the linear conductance is widely found to show the presence of the 0.7 feature. The differential conductance, on the other hand, does not generally exhibit the zero-bias anomaly (ZBA) that has been proposed to indicate the Kondo effect. Indeed, even in the small subset of QPCs found to exhibit such an anomaly, the linear conductance does not always follow the universal temperature-dependent scaling behavior expected for the Kondo effect. Taken collectively, our observations demonstrate that, unlike the 0.7 feature, the ZBA is not a generic feature of low-temperature QPC conduction. We furthermore conclude that the mere observation of the ZBA alone is insufficient evidence for concluding that Kondo physics is active. While we do not rule out the possibility that the Kondo effect may occur in QPCs, our results appear to indicate that its observation requires a very strict set of conditions to be satisfied. This should be contrasted with the case of the 0.7 feature, which has been apparent since the earliest experimental investigations of QPC transport.

Tuning the Fano resonance with an intruder continuum.

Through a combination of experiment and theory we establish the possibility of achieving strong tuning of Fano resonances (FRs), by allowing their usual two-path geometry to interfere with an additional, "intruder", continuum. As the coupling strength to this intruder is varied, we predict strong modulations of the resonance line shape that, in principle at least, may exceed the amplitude of the original FR itself. For a proof-of-concept demonstration of this phenomenon, we construct a nanoscale interferometer from nonlocally coupled quantum point contacts and utilize the unique features of their density of states to realize the intruder. External control of the intruder coupling is enabled by means of an applied magnetic field, in the presence of which we demonstrate the predicted distortions of the FR. This general scheme for resonant control should be broadly applicable to a variety of wave-based systems, opening up the possibility of new applications in areas such as chemical and biological sensing and secure communications.

Pulmonary M. tuberculosis infection delays Th1 immunity via immunoadaptor DAP12-regulated IRAK-M and IL-10 expression in antigen-presenting cells.

Interaction of mycobacteria with the host leads to retarded expression of T helper cell type 1 (Th1) immunity in the lung. However, the immune mechanisms remain poorly understood. Using in vivo and in vitro models of Mycobacterium tuberculosis (M. tb) infection, we find the immunoadaptor DAP12 (DNAX-activating protein of 12 kDa) in antigen-presenting cells (APCs) to be critically involved in this process. Upon infection of APCs, DAP12 is required for IRAK-M (interleukin-1 receptor-associated kinase M) expression, which in turn induces interleukin-10 (IL-10) and an immune-suppressed phenotype of APCs, thus leading to suppressed Th1 cell activation. Lack of DAP12 reduces APC IL-10 production and increases their Th1 cell-activating capability, resulting in expedited Th1 responses and enhanced protection. On the other hand, adoptively transferred DAP12-competent APCs suppress Th1 cell activation within DAP12-deficient hosts, and blockade of IL-10 aborts the ability of DAP12-competent APCs to suppress Th1 activation. Our study identifies the DAP12/IRAK-M/IL-10 to be a novel molecular pathway in APCs exploited by mycobacterial pathogens, allowing infection a foothold in the lung.

Cervicofacial subcutaneous emphysema associated with dental laser treatment.

Cervicofacial subcutaneous emphysema is a rare complication of dental procedures. Although most cases of emphysema occur incidentally with the use of a high-speed air turbine handpiece, there have been some reports over the past decade of cases caused by dental laser treatment. Emphysema as a complication caused by the air cooling spray of a dental laser is not well known, even though dental lasers utilize compressed air just as air turbines and syringes do. In this study, we comprehensively reviewed cases of emphysema attributed to dental laser treatment that appeared in the literature between January 2001 and September 2012, and we included three such cases referred to us. Among 13 cases identified in total, nine had cervicofacial subcutaneous and mediastinal emphysema. Compared with past reviews, the incidence of mediastinal emphysema caused by dental laser treatment was higher than emphysema caused by dental procedure without dental laser use. Eight patients underwent CO2 laser treatment and two underwent Er:YAG laser treatment. Nine patients had emphysema following laser irradiation for soft tissue incision. Dentists and oral surgeons should be cognizant of the potential risk for iatrogenic emphysema caused by the air cooling spray during dental laser treatment and ensure proper usage of lasers.

EGFR inhibitors augment antitumour helper T-cell responses of HER family-specific immunotherapy.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a major cause of cancer-related morbidity and mortality worldwide. Epidermal growth factor receptor (EGFR)-targeted therapy is an attractive strategy alternative to conventional cancer treatments for HNSCC, but its efficacy remains controversial. T-cell-based immunotherapy has been proposed as a novel therapeutic approach to improve the clinical outcome for HNSCC. In this study, we report human epidermal receptor (HER) family epitopes that induced CD4 T-cell responses to HNSCC. The results provide support for a novel strategy to treat HNSCC by combining EGFR-targeted therapy with T-cell-based immunotherapy. METHODS: We evaluated the capacity of predicted CD4 T-cell peptide epitopes from EGFR to induce antitumour immune responses in vitro. In addition, EGFR inhibitors were evaluated for their ability to augment tumour MHC class II expression in HNSCC cell lines and subsequently increase T-cell recognition. RESULTS: Among several predicted peptide epitopes, EGFR875-889 elicited CD4 T-cell responses that were restricted by HLA-DR4, DR15, or DR53 molecules, indicating that the peptide functions as a promiscuous T-cell epitope. The peptide-reactive T cells responded to autologous dendritic cells loaded with EGFR-expressing tumour cell lysates, indicating that these epitopes are naturally processed. In addition, the CD4 T cells were capable of directly recognising and killing HNSCC cells expressing EGFR and the appropriate HLA class II molecule. T cells reactive with the EGFR875-889 epitope could be detected in the blood of HNSCC patients. EGFR875-889-reactive CD4 T cells were also able to recognise several peptide analogues derived from homologous regions of EGFR family members, HER-2, HER-3 and c-MET. Finally, we examined the effects of EGFR tyrosine kinase inhibition or EGFR-blocking antibodies on CD4 T-cell tumour reactivity. Treatment of tumour cells with the EGFR inhibitors enhanced tumour recognition by EGFR875-889-reactive T cells presumably due to the upregulation of HLA-DR expression in the HNSCC cells. CONCLUSION: We identified novel CD4 T-cell EGFR epitopes and amongst these, EGFR875-889 functions as a promiscuous helper T-cell epitope that can elicit effective antitumour T-cell responses against tumours expressing HER family members and c-MET. These observations should facilitate the translation of T-cell-based immunotherapy into the clinic for the treatment of HNSCC and provide a rational basis for EGFR inhibition, immune-targeted combination therapy.

Fast energy relaxation of hot carriers near the Dirac point of graphene.

We investigate energy relaxation of hot carriers in monolayer and bilayer graphene devices, demonstrating that the relaxation rate increases significantly as the Dirac point is approached from either the conduction or valence band. This counterintuitive behavior appears consistent with ideas of charge puddling under disorder, suggesting that it becomes very difficult to excite carriers out of these localized regions. These results therefore demonstrate how the peculiar properties of graphene extend also to the behavior of its nonequilibrium carriers.

Biological clock dysfunction exacerbates contact hypersensitivity in mice.

BACKGROUND: Immediate-type skin allergic reactions, such as passive cutaneous anaphylactic reaction, are associated with circadian rhythm, but the role of circadian mechanisms on delayed-type skin allergic reactions, such as contact hypersensitivity (CHS), remains uncertain. In mice, CHS, a T-cell-mediated immune response, is a classic model of human allergic contact dermatitis. OBJECTIVES: We investigated whether biological clock dysfunction affects CHS pathogenesis in CLOCK mutant mice compared with wild-type (WT) mice. METHODS: Mice were treated with 2,4,6-trinitro-1-chlorobenzene (TNCB) on the abdominal skin on day 0 (sensitization) and then treated with TNCB on the ears on day 5 (challenge). RESULTS: We found that biological clock dysfunction resulted in severe inflammation. Ear swelling, serum immunoglobulin E level and mast cell number were significantly increased in CLOCK mutant mice compared with WT mice. These results provide evidence that CLOCK mutation promotes the T-helper type 2 immune response and exacerbates CHS. Corticosterone has a protective effect on CHS. The serum corticosterone level lost rhythmicity and showed a decreased daily level in CLOCK mutant mice compared with WT mice, supporting the exacerbating effect of CLOCK mutation on CHS. Adrenalectomy markedly worsened TNCB-induced CHS in WT mice but not in CLOCK mutant mice. In addition, dramatic dexamethasone-induced protection of CHS was observed in CLOCK mutant mice compared with WT mice. CONCLUSIONS: The present results suggest that circadian rhythm might be an important factor in the regulation of CHS via corticosterone rhythmicity and/or level.