Search

Presents information on a study which aimed to investigate carrier transport in hydrogenated amorphous silicon by applying the modulated photoconductivity (MPC) technique. Fundamental property of amorphous semiconductors; Theory for drift mobility measurements that characterize MPC behavior; Experimental details; Results of the study.

The Skyrme-Faddeev model has planar soliton solutions with the target space ℂPN. An Abelian Chern-Simons term (the Hopf term) in the Lagrangian of the model plays a crucial role for the statistical properties of the solutions. Because П3(ℂP1) = ℤ, the term becomes an integer for N = 1. On the other hand, for N > 1, it becomes perturbative because П3(ℂPN) is trivial. The prefactor Θ of the Hopf term is not quantized, and its value depends on the physical system. We study the spectral flow of normalizable fermions coupled with the baby-Skyrme model (ℂPN Skyrme-Faddeev model). We discuss whether the statistical nature of solitons can be explained using their constituents, i.e., quarks. [ABSTRACT FROM AUTHOR]

We consider a type of singular limit problem called the fast reaction limit . The problem of the fast reaction limit involves studying the behaviour of solutions of reaction–diffusion systems when the reaction speeds are very fast. Fast reaction limits of two-component systems have been studied in recent decades. In most of these systems, the fast reaction terms of each component are represented by the same function. Fast reaction limits of systems with different fast reaction terms are still far from being well understood. In this paper, we focus on a reaction–diffusion system for which the reaction terms consist of monomial functions of various powers. The behaviour of interfaces arising in the fast reaction limit of this system is studied. Depending on the powers, three types of behaviour are observed: (i) the initial interface vanishes instantaneously, (ii) the interface propagates at a finite speed, and (iii) the interface does not move. [ABSTRACT FROM AUTHOR]

Magnetic resonance wireless power transfer is expected to be one of the prevalent schemes because of its high efficiency and long transmission range. However, in this scheme, there is a problem that the characteristics of a transmission channel changes in according with the distance between coil antennas. This paper investigates the performance of data transmission with an array antenna in a wireless power transfer system. In the assumed system, the same antennas for wireless power transfer are used for data transmission. The assumed system uses multiple transmit antennas and beamforming is realized by shifting the phases of signals in a transmitter. Numerical results obtained through computer simulation show that the proposed scheme can mitigate the dependently of a bit error rate (BER) to the distance between the antenna coils. The variation of the performance is suppressed within 1-3 dB at the BER of $$10^{-5}$$ in the case of two transmit antennas. In addition, the system with two transmit antennas achieves 2 dB or more improvement in term of the BER performance than that with a single antenna at specific antenna distances. [ABSTRACT FROM AUTHOR]

The epidermal growth factor receptor (EGFR) is a central regulator of tumor progression in human cancers. Cetuximab is an anti-EGFR antibody that has been approved for use in oncology. Previously we investigated mechanisms of resistance to cetuximab using a model derived from the non-small cell lung cancer line NCI-H226. We demonstrated that cetuximab-resistant clones (CtxR) had increased nuclear localization of the EGFR. This process was mediated by Src family kinases (SFKs), and nuclear EGFR had a role in resistance to cetuximab. To better understand SFK-mediated nuclear translocation of EGFR, we investigated which SFK member(s) controlled this process as well as the EGFR tyrosine residues that are involved. Analyses of mRNA and protein expression indicated upregulation of the SFK members Yes (v-Yes-1 yamaguchi sarcoma viral oncogene) and Lyn (v-yes-1 Yamaguchi sarcoma viral-related oncogene homolog) in all CtxR clones. Further, immunoprecipitation analysis revealed that EGFR interacts with Yes and Lyn in CtxR clones, but not in cetuximab-sensitive (CtxS) parental cells. Using RNAi interference, we found that knockdown of either Yes or Lyn led to loss of EGFR translocation to the nucleus. Conversely, overexpression of Yes or Lyn in low nuclear EGFR-expressing CtxS parental cells led to increased nuclear EGFR. Chromatin immunoprecipitation (ChIP) assays confirmed nuclear EGFR complexes associated with the promoter of the known EGFR target genes B-Myb and iNOS. Further, all CtxR clones exhibited upregulation of B-Myb and iNOS at the mRNA and protein levels. siRNAs directed at Yes or Lyn led to decreased binding of EGFR complexes to the B-Myb and iNOS promoters based on ChIP analyses. SFKs have been shown to phosphorylate EGFR on tyrosines 845 and 1101 (Y845 and Y1101), and mutation of Y1101, but not Y845, impaired nuclear entry of the EGFR. Taken together, our findings demonstrate that Yes and Lyn phosphorylate EGFR at Y1101, which influences EGFR nuclear translocation in this model of cetuximab resistance. [ABSTRACT FROM AUTHOR]

When a compression wave generated by a high-speed train entering a tunnel propagates through the tunnel and arrives at the tunnel exit, an impulsive pressure wave (micro-pressure wave) is radiated from the tunnel exit. Improving the train nose shape is one of the techniques for suppressing the micro-pressure wave. Furthermore, tunnel entrance hoods are required for long concrete slab tunnels in order to suppress the micro-pressure wave. The effect of the tunnel entrance hood on the compression wave generated by the train can be evaluated by means of a rapid computational scheme devised and validated experimentally by Howe et al. In this study, the optimal longitudinal distribution of the cross-sectional area of the train nose shape was determined by using the rapid computational scheme and a genetic algorithm. The effect of the nose shape optimization was confirmed through experiments using scale models. [ABSTRACT FROM AUTHOR]

KRAS mutation is a predictive biomarker for resistance to cetuximab (Erbitux) in metastatic colorectal cancer (mCRC). This study sought to determine if KRAS mutant CRC lines could be sensitized to cetuximab using dasatinib (BMS-354825, Sprycel), a potent, orally bioavailable inhibitor of several tyrosine kinases, including the Src family kinases (SFKs). We analyzed 16 CRC lines for: (1) KRAS mutation status, (2) dependence on mutant KRAS signaling and (3) expression level of epidermal growth factor receptor (EGFR) and SFKs. From these analyses, we selected three KRAS mutant (LS180, LoVo and HCT116) cell lines and two KRAS wild-type cell lines (SW48 and CaCo2). In vitro, using poly-D-lysine/laminin plates, KRAS mutant cell lines were resistant to cetuximab, whereas KRAS wild-type lines showed sensitivity to cetuximab. Treatment with cetuximab and dasatinib showed a greater antiproliferative effect on KRAS mutant lines when compared with either agent alone in vitro and in vivo. To investigate potential mechanisms for this antiproliferative response in the combinatorial therapy, we performed Human Phospho-Kinase Antibody Array analysis, measuring the relative phosphorylation levels of 39 intracellular proteins in untreated, cetuximab, dasatinib or the combinatorial treatment in the KRAS mutant lines LS180, LoVo and HCT116 cells. The results of this experiment showed a decrease in a broad spectrum of kinases centered on the β-catenin pathway, the mitogen-activated protein kinase (MAPK) pathway, AKT/mammalian target of rapamycin (mTOR) pathway and the family of signal transducers and activators of transcription (STATs) when compared with the untreated control or monotherapy treatments. Next, we analyzed tumor growth with cetuximab, dasatinib or their combination in vivo. KRAS mutant xenografts showed resistance to cetuximab therapy, whereas KRAS wild type demonstrated an antitumor response when treated with cetuximab. KRAS mutant tumors exhibited minimal response to dasatinib monotherapy. However, as in vitro, KRAS mutant lines exhibited a response to the combination of cetuximab and dasatinib. Combinatorial treatment of KRAS mutant xenografts resulted in decreased cell proliferation, as measured by Ki67, and higher rates of apoptosis, as measured by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling). The data presented in this study indicate that dasatinib can sensitize KRAS mutant CRC tumors to cetuximab and may do so by altering the activity of several key signaling pathways. Furthermore, these results suggest that signaling via EGFR and SFKs may be necessary for cell proliferation and survival of KRAS mutant CRC tumors. These data strengthen the rationale for clinical trials combining cetuximab and dasatinib in the KRAS mutant CRC genetic setting. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) is a ubiquitously expressed receptor tyrosine kinase involved in the etiology of several human cancers. Cetuximab is an EGFR-blocking antibody that has been approved for the treatment of patients with head and neck squamous cell carcinoma and metastatic colorectal cancer. Previous reports have shown that EGFR translocation to the nucleus is associated with cell proliferation. Here we investigated mechanisms of acquired resistance to cetuximab using a model derived from the non-small cell lung cancer line H226. We demonstrated that cetuximab-resistant cells overexpress HER family ligands including epidermal growth factor (EGF), amphiregulin, heparin-binding EGF and β-cellulin. Overexpression of these ligands is associated with the nuclear translocation of the EGFR and this process was mediated by the Src family kinases (SFK). Treatment of cetuximab-resistant cells with the SFK inhibitor, dasatinib, resulted in loss of nuclear EGFR, increased membrane expression of the EGFR and resensitization to cetuximab. In addition, expression of a nuclear localization sequence-tagged EGFR in cetuximab-sensitive cells increased resistance to cetuximab both in vitro and in mouse xenografts. Collectively, these data suggest that nuclear expression of EGFR may be an important molecular determinant of resistance to cetuximab therapy and provides a rationale for investigating nuclear EGFR as a biomarker for cetuximab response. Further, these data suggest a rationale for the design of clinical trials that examine the value of treating patients with cetuximab-resistant tumors with inhibitors of SFKs in combination with cetuximab. [ABSTRACT FROM AUTHOR]

Abstract: An analysis is made of the sound produced by vorticity generated as high pressure fluid is forced through an aperture in the wall of a duct in the presence of an exterior baffle plate. The aperture typically behaves as a ‘pressure release’ opening when the flow is ideal and irrotational, corresponding to the traditional interpretation of the action of a finger hole of a woodwind instrument, although theoretical predictions that neglect vorticity are irrelevant in practice except at very high frequencies. The theory of vortex sound is applied to derive an approximate nonlinear equation for the volume flux through the baffled aperture that generalises Cummings''s empirical equation for a jet exhausting through a fully open orifice in a large wall. The equation takes account of the impingement of the jet on the baffle and of the nonlinear ‘inertial blocking’ of the aperture flow. Application is made to the problem of compression wave generation by a high-speed train entering a tunnel fitted with an entrance hood whose windows are partially ‘closed’ by the presence of a side-wall of a railway cutting or embankment. Theoretical predictions are found to be in good agreement with measurements made at model scale at train speeds . [Copyright &y& Elsevier]

Aortic valve sclerosis (AVS) may predispose to a prothrombotic state, as AVS is predictor of cardiovascular events in hypertensive populations. Thrombin exerts non-thrombotic effects such as vessel tone regulation, progression of atherosclerosis and stimulation of atrial natriuretic peptide (ANP) secretion. We hypothesized that hypertensive patients with AVS may have a persistently activated thrombin generation. We studied 234 asymptomatic never-treated hypertensive patients (73 of them with AVS). Prothrombin F1+2 (F1+2), as a marker of thrombin generation and fibrin D-dimer, as a marker of thrombus formation, ANP and brain natriuretic peptide (BNP) were measured. Presence of AVS, aortic jet velocity and left ventricular diameter at diastole were determined by echocardiography. Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease formula. F1+2 (median and interquartile range (IQR)=1.05, 0.87–1.38 nM vs 0.93, 0.72–1.16) and ANP (22, 14–37 pg ml−1 vs 17, 11–25) levels were greater, and glomerular filtration rate values (65±9 ml min−1/1.73 m2 vs 68±11) were lower in hypertensive patients with AVS than in those without AVS. F1+2 (odds ratio, 95% CI=2.94, 1.07–8.6) was independently associated with AVS after being adjusted for age, gender and the variables of cardiorenal functions measured. After 6 months of treatment using valsartan, F1+2 levels remained elevated in hypertensive patients with AVS (1.14, 0.83–1.42 nM vs 1.07, 0.84–1.5, n=19), but decreased in those without AVS (1.01, 0.85–1.31 vs 0.8, 0.84–1.78, n=27). Thrombin generation was associated with AVS in untreated hypertensive patients, and this association was persistent after blood-pressure-lowering treatment using valsartan.Journal of Human Hypertension (2008) 22, 781–787; doi:10.1038/jhh.2008.68; published online 17 July 2008 [ABSTRACT FROM AUTHOR]

Plasma levels of von Willebrand factor (vWF), a marker of endothelial dysfunction/damage, are elevated in high-risk hypertensive patients and in patients with severe aortic regurgitation (AR). Patients with mild-to-moderate AR, frequently detected in hypertensive elderly, have additional left ventricular morphological and functional dysfunctions. We hypothesized that hypertensive patients with mild-to-moderate AR may have enhanced endothelial and/or left ventricular dysfunctions that may lead to a deteriorated prognosis. We measured vWF, prothrombin F1+2 (F1+2) as a marker of thrombin generation, brain natriuretic peptide (BNP) in 104 hypertensive patients with mild-to-moderate AR and 66 hypertensive patients without AR. The left ventricular diameter at systole (LVDs) and left ventricular posterior wall thickness (LVWT) were determined by echocardiography and indexed by body surface area (LVDs/BSA and LVWT/BSA). VWF (median, interquartile range (IQR) 154, 120–196%) and BNP (34.7 pg ml−1, 15–65%) levels were greater in patients with AR than in those without AR (135, 98–175% and 20, 10.3–49 pg ml−1). All patients were prospectively followed up for cardiac events during the period of median 43 months (IQR 31–81). Patients with AR had an increased risk of cardiac events (regression ratio (RR) 1.87, 95% confidence interval 1.28–2.87) when compared to those without AR. A multivariate Cox hazard analysis indicated that log vWF (RR 4.93) and log BNP (RR 1.9) were independent predictors in patients with AR. VWF was an independent predictor of clinical outcome in hypertensive patients with mild-to-moderate AR.Journal of Human Hypertension (2008) 22, 275–281; doi:10.1038/sj.jhh.1002321; published online 13 December 2007 [ABSTRACT FROM AUTHOR]

Heart-type fatty acid-binding protein (H-FABP), a marker of acute myocardial infarction and a soluble cytosolic protein, may be released following left ventricular remodelling in cardiac overloaded hearts caused by hypertension, aortic regurgitation (AR) or aortic stenosis (AS). Our aim was to investigate if H-FABP levels are associated with left ventricular remodelling and clinical outcome in hypertensive patients with AR or AS. H-FABP and brain natriuretic peptide (BNP) were measured, glomerular filtration rate (GFR) was estimated using the modification of diet in renal disease (MDRD) equation, and left ventricular dimension at systole corrected for body surface area (LVDs/BSA) and relative wall thickness (RWT) were determined by echocardiography in hypertensive patients with mild-to-moderate AR (n=78), those with mild-to-moderate AS (n=73) and those without valvular heart diseases (HT) (n=50). H-FABP levels were significantly higher in AR (4.9±3 ng/ml) and in AS (4.5±3) than in HT (3.4±1) and BNP (65±73 pg/ml, 76±75, 35±22). H-FABP correlated with LVDs/BSA in AR (β=0.23, P<0.05), and RWT in AS (β=0.18, P<0.05) after adjustment for age, gender and all the other variables. AS and AR patients were prospectively followed up for cardiac events during 34±19 months. A multivariate Cox hazard analysis indicated H-FABP was an independent predictor of outcome both in AR (relative risk (RR)=7.61, 95% CI=2.39–25.3) and AS (RR=13.6, 95% CI=3.27–66.9). H-FABP, associated with left ventricular remodelling, is useful in predicting clinical outcome in hypertensive patients with mild-to-moderate aortic valve diseases.Journal of Human Hypertension (2007) 21, 551–557; doi:10.1038/sj.jhh.1002195; published online 29 March 2007 [ABSTRACT FROM AUTHOR]

Abstract: A practical analytical scheme is proposed for making rapid numerical predictions of the compression wave generated when a high-speed train enters a tunnel fitted with a vented entrance hood. The method synthesises results from several analytical procedures developed during the past few years for treating different aspects of the tunnel-entry problem, including the effects of change in cross-sectional area at the hood-tunnel junction, high-speed jet flows from windows distributed along the length of the hood, frictional losses associated with separated turbulent flow between the tunnel and hood walls and the train, and the influence of train nose shape. Details are given in this paper for the simplest case of circular cylindrical tunnels and hoods of the type used in model scale testing and design studies. Typical predictions can be made in a few seconds on a personal computer (in contrast to the tens or hundreds of hours required for simulations using the Euler or Navier–Stokes equations on a high performance supercomputer). A summary is given of selected predictions and their comparisons with experiments performed at the Railway Technical Research Institute in Tokyo at train Mach numbers as large as . [Copyright &y& Elsevier]

Effective thermal conductivity of fireworks raw materials and their mixture have been measured by the temperature modulated DSC and the hot wire method, in order to predict spontaneous ignition properties precisely. As a result, an excellent linear correlation has been obtained between the density and the λe by the TMDSC method. Moreover, the low-density data by the hot wire method lie on the extrapolated point of the linear correlation. Thus, the λe within the ordinary limit of fireworks composition can be measured by the TMDSC method. Krupiczka’s estimation method shows a good agreement with the experimental values. [ABSTRACT FROM AUTHOR]

In order to determine the actual circumstances of wayside low-frequency noise and infrasound generated by high-speed trains (Shinkansen), field measurements were performed at two sites, one near a tunnel portal and the other in a fully open section. The measurements were based upon the manual issued by the Ministry of the Environment of Japan in October 2000 and conducted to obtain G-weighted SPL, 1/3-octave band spectra, velocity dependence and distance attenuation of SPL. The measured results show that major components of the low-frequency noise from the tunnel portal are impulsive micro-pressure waves and continuous pressure waves, while those in the open section are near-field hydrodynamic pressure variations and far-field acoustic pressure waves. [ABSTRACT FROM AUTHOR]

Abstract: Carboxymethylcellulose (CMC) is well known as a safe and biodegradable material, which is widely used as food additives, wash paste, etc., in our daily life. Aiming at the environmental purification of this eco-friendly substance, the authors have investigated Cu2+ absorption property of CMC gel that was crosslinked by irradiating with γ-rays without toxic crosslinker. The CMC gel has revealed to capture Cu2+ of which number depends on the γ-ray dose as well as the CMC concentration, indicating the chelation by carboxyl group at the end of the side chain. [Copyright &y& Elsevier]

A theoretical and experimental study is made of the compression wave generated when a train enters a nominally uniform tunnel with a long, unvented entrance hood. The purpose of the hood is to reduce as much as practicable the maximum gradient of the compression wave front. The pressure gradient can increase in a long tunnel as a result of nonlinear wave steepening, and thereby increase the impact on residential dwellings of the acoustic ‘boom’ (or micro-pressure wave) radiated from the far end of the tunnel when the compression wave arrives. Our experiments are conducted at model scale using axisymmetric ‘trains’ projected at speeds up to 350 kph along the axis of a cylindrical tunnel fitted with a cylindrical entrance hood. Theoretical predictions of the compression wave are made using the equation of aerodynamic sound containing a slender body approximation to the effective source representing the moving train, coupled with a small correction that accounts for the ‘vortex’ sources in the free shear layers in the exit flows from the hood and tunnel of the air displaced by the train. The compression wave is generated by the two successive interactions of the train nose with the hood portal and with the junction between the hood and tunnel. The interactions produce a system of compression and expansion waves, each having characteristic wavelengths that are much smaller than the hood length; the waves are temporarily reflected back and forth within the hood prior to transmission into the tunnel, and are resolved analytically by use of an approximate Green''s function determined by the hood geometry. Theoretical predictions are found to be in excellent agreement with experiment, including in particular a detailed correspondence between measured and predicted interference patterns produced by the multiple reflections of waves in the hood. [Copyright &y& Elsevier]

Investigates the characteristics of homogeneous charge compression ignition (HCCI) combustion. Definition of the boundaries of the operational range of HCCI; General properties of HCCI; Description of engine speed dependence; Effects of the intake air temperature and compression ratio.

Sewage and treated water can be a heat source in urban area due to large heat capacity, thus recovery and reuse of its energy is one of the most desirable plans for the sewerage system. In this paper, characteristics of heat energy in wastewater, reuse plans, and some experiences in Japan are presented. Full-scale reuse projects for heating and cooling in the Tokyo Metropolitan Districts and project for melting snow in Sapporo City are discussed. The key factors found in experience of Tokyo were setting the heat pumps near the demand points and the technical developments of equipment to prevent system from clogging, corrosion, and decrease in the heat transfer efficiency. It was also found through the project for melting snow in Sapporo that the key factor in public acceptance was the multi-purpose use of the sewerage system both for melting snow in winter and retaining rain water in summer. [ABSTRACT FROM AUTHOR]

Mitogen-activated protein (MAP) kinases act as transducers of extracellular signaling via tyrosine kinase-growth factor receptors and G-protein-linked receptors to transcription factors. Constitutive activation of MAP kinase has been observed in a variety of solid tumors including renal cancer and breast cancer. Recently, we have reported that constitutively activated MAP kinase was observed in 50% of human primary acute myeloid leukemia (AML) cells. Ras is one of the components of G-proteins and transduces the signal from cytokine receptors to raf-1 theoretically resulting in the activation of MAP kinase pathway. In the present study, we have examined the correlation of Ras mutations and the activation of MAP kinase pathway in patients with AML. Twenty out of 22 AML cases with activating N-Ras mutations showed no phosphorylated forms of ERK2. ERK2 phosphorylation was tightly correlated with ERK1 phosphorylation and MAP kinase activity detected by in vitro kinase assay. Three samples with N-Ras mutations were stimulated with IL-3, GM-CSF and G-CSF separately but ERK2 activation was induced in none of these samples stimulated with these cytokines. In contrast, ERK2 was constitutively activated in all of four pancreatic carcinoma cases with K-Ras mutation at codon 12. These results suggest that function of the Ras mutations may be different between solid tumors, such as pancreatic carcinoma and colorectal carcinoma, and AML. Mutated Ras does not always stimulate MAP kinase pathway constitutively and may rather inhibit classical MAP kinase cascade in AML blasts from leukemia patients. [ABSTRACT FROM AUTHOR]

Clinical and endoscopic manifestations of 18 gastric inflammatory fibroid polyps (IFP) in 16 patients who underwent endoscopic or surgical removal were retrospectively analyzed. All of the lesions were located within the pyloric antrum, and the sizes varied from 0.8 to 7.0 cm. On endoscopy, six polyps which measured 1.0 cm or less uniformly seemed to be sessile or intramural tumors, whereas four of the nine polyps between 1.1 and 2.0 cm in size were additionally accompanied by a central depression. The remaining three, which measured more than 2.0 cm, showed characteristic polypoid growth with ulcerations. Three polyps more than 1.0 cm in size occasionally prolapsed into the duodenal bulb. Three patients with these prolapsing polyps and two with polyps accompanied by ulcerations experienced abdominal pain, nausea, or severe anemia. Two polyps (11%) were precisely diagnosed as IFP by means of conventional forceps biopsy. Histological examinations revealed that all of the polyps proliferated within the submucosa. Therefore, this type of polyp may be subject to endoscopic removal to enable a precise diagnosis and treatment. [ABSTRACT FROM AUTHOR]

The serine/threonine kinase AKT, also known as protein kinase B (PKB), is the major substrate to phosphoinositide 3-kinase (PI3K) and consists of three paralogs: AKT1 (PKBα), AKT2 (PKBβ) and AKT3 (PKBγ). The PI3K/AKT pathway is normally activated by binding of ligands to membrane-bound receptor tyrosine kinases (RTKs) as well as downstream to G-protein coupled receptors and integrin-linked kinase. Through multiple downstream substrates, activated AKT controls a wide variety of cellular functions including cell proliferation, survival, metabolism, and angiogenesis in both normal and malignant cells. In human cancers, the PI3K/AKT pathway is most frequently hyperactivated due to mutations and/or overexpression of upstream components. Aberrant expression of RTKs, gain of function mutations in PIK3CA , RAS , PDPK1 , and AKT itself, as well as loss of function mutation in AKT phosphatases are genetic lesions that confer hyperactivation of AKT. Activated AKT stimulates DNA repair, e.g. double strand break repair after radiotherapy. Likewise, AKT attenuates chemotherapy-induced apoptosis. These observations suggest that a crucial link exists between AKT and DNA damage. Thus, AKT could be a major predictive marker of conventional cancer therapy, molecularly targeted therapy, and immunotherapy for solid tumors. In this review, we summarize the current understanding by which activated AKT mediates resistance to cancer treatment modalities, i.e. radiotherapy, chemotherapy, and RTK targeted therapy. Next, the effect of AKT on response of tumor cells to RTK targeted strategies will be discussed. Finally, we will provide a brief summary on the clinical trials of AKT inhibitors in combination with radiochemotherapy, RTK targeted therapy, and immunotherapy. [ABSTRACT FROM AUTHOR]

Cetuximab, an approved anti-EGFR receptor monoclonal antibody, is used for the treatment of metastatic cancer, often in conjunction with cytotoxic chemotherapy. It is also employed as a radiosensitizer in the context of definitive radiation therapy for locally advanced cases. However, overcoming resistance to cetuximab, whether intrinsic or acquired, represents a significant challenge in clinical practice. In preclinical studies, the identification of tyrosine 821 (Y821) on the C-terminal of AXL has been linked to resistance to both cetuximab and radiation therapy via signaling through the tyrosine kinase c-Abl. Blocking c-Abl signaling with the tyrosine kinase inhibitor imatinib restored sensitivity to cetuximab and radiotherapy, ultimately resulting in complete tumor regression without recurrence in models of head and neck cancer. In this clinical trial, we aim to translate these promising preclinical findings into clinical practice through a window-of-opportunity trial that evaluates the effects of combining cetuximab with imatinib in head and neck cancer patients. This is a window-of-opportunity study conducted at a single center, involving patients diagnosed with head and neck squamous cell carcinoma who are undergoing treatment with surgery, radiation, or chemoradiation. A total of 15 patients will be recruited for this study. Participants will initially undergo a medical history review and physical examination and provide written informed consent. To be eligible, subjects must have sufficient tumor volume to allow for a minimum of two core research biopsies. The first research biopsy will be performed at baseline prior to therapy to analyze Ki67 and potential markers of sensitivity to cetuximab and imatinib. Simultaneously with the first research biopsy, research-related blood samples will be collected to assess circulating tumor cells through the course of the trial. Subjects will receive two doses of cetuximab as follows: a loading dose of 400 mg/m2 on Day 1 and 250 mg/m2 on Day 8. In addition, they will take 400 mg of imatinib orally daily for a period ranging from a minimum of 8 days to a maximum of 14 days before undergoing definitive surgery or definitive radiation/chemoradiation. Following the combined treatment with imatinib and cetuximab, subjects will undergo a second research blood draw and a research biopsy. The administration of imatinib will be discontinued 1-3 days prior to the second research biopsy. For patients undergoing surgical resection, this second research biopsy will be obtained during the surgical procedure. Patients will return for follow-up visits at 1, 3, and 12 months after completing definitive therapy to assess toxicities, monitor adverse events, and collect blood samples. Enrollment in the study is ongoing. NCT05816785 TBD TBD [ABSTRACT FROM AUTHOR]

We describe a successful surgical technique of abdominal trachelectomy and re‐vaginoplasty for cervico‐vaginal stenosis following unsuccessful uterovaginal anastomosis and vaginoplasty in a patient with congenital cervical and vaginal aplasia. After the surgical procedure, cervico‐vaginal stenosis was resolved and periodic menstruation without dysmenorrhoea resumed. While long‐term follow‐up is essential to ensure successful pregnancy and delivery, we conclude that this novel surgical procedure is a promising alternative for improvement of the quality of life and normal sexual function, and for preservation of fertility in patients with cervical and vaginal aplasia. [ABSTRACT FROM AUTHOR]

A case of familial adenomatosis coli with villous adenoma of the third portion of the duodenum, which falls in the category of a Gardner's syndrome, is described. The patient, who had complained of an abdominal mass which had been diagnosed as a desmoid tumor after surgical resection, had numerous adenomatous polyps throughout the colon confirmed by colonoscopy with biopsy. Endoscopic examination of the upper gastrointestinal tract revealed fundic gland polyposis in the stomach and numerous small adenomas in the duodenum. In addition, there was a pedunculated polyp in the third portion of his duodenum, measuring 30 mm in diameter, the surface of which had a cauliflowerlike appearance. The polyp was removed with the electrocautery snare and was histologically diagnosed as villous adenoma. Our case report supports the concept that villous adenoma, which possesses a high malignant potential, may occur in the upper gastrointestinal tract in patients with familial adenomatosis coli, and careful examination of the upper gastrointestinal tract including the distal duodenum seems to be necessary in the follow-up patients with this disease. [ABSTRACT FROM AUTHOR]

Responds to a comment on an article in 'Gut' about the classification of mucosa associated lymphoid tissue lymphomas. Classification from the World Health Organization.

Sewage and treated water can be a heat source in urban area due to large heat capacity, thus recovery and reuse of its energy is one of the most desirable plans for the sewerage system. In this paper, characteristics of heat energy in wastewater, reuse plans, and some experiences in Japan are presented. Full-scale reuse projects for heating and cooling in the Tokyo Metropolitan Districts and project for melting snow in Sapporo City are discussed. The key factors found in experience of Tokyo were setting the heat pumps near the demand points and the technical developments of equipment to prevent system from clogging, corrosion, and decrease in the heat transfer efficiency. It was also found through the project for melting snow in Sapporo that the key factor in public acceptance was the multi-purpose use of the sewerage system both for melting snow in winter and retaining rain water insummer. [ABSTRACT FROM AUTHOR]

Objective: To estimate the incidence and survival rates of total and cause specific dementia in a general Japanese population.Methods: A total of 828 subjects without dementia, aged 65 years or over, were followed-up prospectively for 17 years. Dementia was subdivided into cause specific subtypes: namely, Alzheimer's disease (AD), vascular dementia (VD), dementia with Lewy bodies (DLB), combined dementia and other types of dementia. During the follow-up, 275 subjects developed dementia; of these, 251 (91.2%) were evaluated morphologically, with 164 subjected to brain autopsy examination and the remaining 87 to neuroimaging.Results: The incidences of total dementia, AD, VD, DLB, combined dementia and other types of dementia were 32.3 (n = 275), 14.6 (124), 9.5 (81), 1.4 (12), 3.8 (33), and 3.1 (16) per 1000 person years, respectively. The incidences of AD, combined dementia and other types of dementia rose with increasing age, particularly after the age of 85 years, but this tendency was not observed for VD or DLB. The survival curve of dementia cases aged 65-89 years was significantly lower than that of age and sex matched controls (10 year survival rate, 13.6% vs 29.3%; hazard ratio 1.67; 95% confidence interval 1.31 to 2.13). The 10 year survival rates were not significantly different among dementia subtypes.Conclusions: Our findings suggest that the Japanese elderly population has a high risk for the development of dementia, specifically AD and VD, and once dementia is established, the risk of death is considerable. [ABSTRACT FROM AUTHOR]

Abstract: A numerical procedure for the rapid prediction of the compression wave generated by a high-speed train entering a tunnel was presented and validated by Howe et al. [Rapid calculation of the compression wave generated by a train entering a tunnel with a vented hood, Journal of Sound and Vibration 297 (2006) 267–292]. The method was devised to deal principally with compression wave generation in long hoods typically of length times the tunnel height and ‘vented’ by means of a series of windows distributed along the hood walls. Hoods of this kind will be needed to control wave generation by newer trains operating at speeds U exceeding about 350km/h. In this paper experimental results are presented and compared with predictions in order to extend the range of applicability of the numerical method of Howe et al. (2006) to include short hoods with lengths as small as just twice the tunnel height (the situation for most hoods currently deployed on the Japanese Shinkansen) and for U as large as 400km/h. [Copyright &y& Elsevier]

An optimally designed entrance portal must be capable of minimizing the maximum growth rate of the compression wave generated when a high-speed train enters a tunnel. A theoretical and experimental investigation has been made to determine the changes in compression wave characteristics produced when the portal is 'scarfed' with tapering side walls. It is concluded that portal modifications of this type are unlikely to produce a significant reduction in the maximum compression wave growth rate. Small decreases in growth rate are possible (up to about 15%) for scarf walls extending a distance beyond the tunnel entrance of the order of the tunnel height, but little or no additional improvement is achieved with longer walls. [ABSTRACT FROM AUTHOR]

Abstract: High-performance superconducting quadrupole magnets, MQXA, for the LHC low-beta insertions have been designed, manufactured in series and tested. The design field gradient of the quadrupole, which has a coil aperture of diameter 70mm, was 240T/m at 1.9K; its effective length is 6.37m, and it is required to operate reliably at up to 215T/m when subjected to radiation heat deposit in the coils of up to 5W/m. The series of 20 magnets has been produced in industry, and tested at KEK. The magnet design is explained, and the construction and performance of the series units, in terms of training, field quality and geometry, are presented. [Copyright &y& Elsevier]

Self-induced sloshing was found to occur in a cylindrical tank when an upward round jet on the tank axis created a surface swell at the impingement point. The conditions under which the sloshing occurred were investigated experimentally, together with the sloshing modes and frequencies. The sloshing was found to appear when the inlet velocity exceeded a certain value, which depends on the inlet-surface distance. The mode always had one diametrical node, and a lower mode appeared at increased inlet-surface distance and velocity. A feedback model was proposed in order to explain the energy supply mechanism to the sloshing, which was composed of a jet deflection process caused by a lateral pressure gradient and a pressure imbalance generation process caused by jet movement. The lateral pressure gradient deflects the jet, resulting in the displacement of the surface impingement point. When the jet moves, transformation of the jet-induced swell does not follow the movement immediately, generating an imbalance of pressure. The imbalance caused by the motion of the swell is considered to supply energy to the sloshing. The calculated jet deflection caused by the lateral pressure gradient was found to agree with the experimental findings. The measured lateral pressure gradient was calculated as the sum of the lateral pressures caused by the sloshing motion and by the jet impingement point movement. The calculated oscillating region in the water-depth jet-velocity map was found to agree fairly well with the experimental findings, which suggests the validity of the model. [Copyright &y& Elsevier]

Summary A porcine bacterial artificial chromosome (BAC) library consisting of 103 488 clones has been constructed. The average insert size in the BAC vector was calculated to be 133 kb based on the examination of 189 randomly selected clones, indicating that the library contained 4.4 genome equivalents. The library can be screened by two-step PCR. The first screening step is performed on 22 superpools, each containing 4704 clones (49×96 well plates). In the second screening step, 49 plates comprising a superpool are arrayed in a 7×7 matrix and 4D-PCR is performed. Screening of the library superpools by PCR for 125 marker sequences selected from different regions of swine genome revealed 123 sequences, indicating that the library is not biased. Subsequent screenings (4D-PCR) were successfully applied for identification of clones containing each marker sequence. This porcine BAC library and the PCR screening system are useful for isolation of genomic DNA fragments containing desired sequences. [ABSTRACT FROM AUTHOR]

A total of 263 gastric hyperplastic polyps, which had been removed endoscopically from 202 patients, were clinicopathologically analyzed. Among these polyps, there were nine polyps with neoplastic components (3.4%), corresponding to adenoma in five lesions and mucosal adenocarcinoma in four lesions. Comparing the neoplastic transformed polyps with the pure hyperplastic polyps, there was no significant difference according to age, gender, location, gross appearance, or size. However, the transformed polyps which were located in the lower third of the stomach were larger in size (mean, 20.8 mm) and were more likely to be found among older patients (mean, 75.8 years) than were the pure hyperplastic polyps (mean size and age: 14.5 mm and 61.8 years). These results may indicate the possibility of a different carcinogenesis belonging to gastric hyperplastic polyps by location, and this finding seems to be significant in the application of endoscopic polypectomy. [ABSTRACT FROM AUTHOR]

The field emission from an amorphous carbon (a-C) film grown by electrochemical deposition has been studied. The deposition of the a-C film was accomplished by applying a direct-current potential to a substrate that was immersed in methanol. Both scanning electron microscopy and Raman results indicate that smooth and homogeneous a-C films are grown on specific substrates such as Ti and Al. Field emission measurements demonstrate excellent emission properties such as threshold fields as low as 5 V/μm. Enhancement factors are estimated to be in the range of 1300-1500; these are attributed to local field enhancements around sp2 carbon clusters that are embedded in the a-C films. Emission properties of a-C films grown on Si exhibit a current saturation under higher applied fields. These saturation characteristics are explained by effects of a potential barrier at the interface between the a-C film and the substrate. The interface barrier is reduced by formation of the Ti interfacial layer, suggesting that the formation of TiC decreases the contact resistance between the substrate and the a-C film. Therefore, an approach to use carbide formation at the interface is verified as useful to improve the emission properties of a-C films. [ABSTRACT FROM AUTHOR]

A large aperture beam separation dipole (D1 magnet) is required to generate a field integral of 35 Tm at 12 kA and 1.9 K for the high luminosity upgrade of the large hadron collider (HL-LHC). High-energy accelerator Research Organization (KEK) fabricated the first 2 m model (MBXFS1) and a magnet test was performed in 2015-2016. Although the quench current reached the nominal operating current, training performance was not satisfactory. The measured azimuthal coil pre-stress was completely released below the nominal current, and this was suggested to be themain reason for the insufficient training performance. After the magnet test, MBXFS1 was disassembled and reassembled as MBXFS1b after increasing the coil pre-stress. In this paper, we report the reassembly of the magnet and test results focusing on the training performance. [ABSTRACT FROM AUTHOR]

Mechanisms of post-stroke recovery are still poorly understood. Recent evidence suggests that cortical reorganisation in the unaffected hemisphere plays an important role. A 59 year old man developed a small lacunar infarct in the left corona radiata, which then caused marked deterioration in a pre-existing left hemiparesis that had resulted from an earlier right putaminal haemorrhage. Functional magnetic resonance imaging showed that the paretic left hand grip activated the ipsilateral left motor areas, but not the right hemispheric motor areas. This suggests that partial recovery of the left hemiparesis had been brought about by cortical reorganisation of the left hemisphere and intensification of the uncrossed corticospinal tract. The subsequent small infarct may have damaged the uncrossed tract, thereby causing the pre-existing hemiparesis to deteriorate even further. [ABSTRACT FROM AUTHOR]

The palisade vessels present at the distal end of the esophagus are considered to be a landmark of the esophagogastric junction and indispensable for diagnosis of columnar-lined esophagus on the basis of the Japanese criteria. Here we clarified the features of normal palisade vessels at the esophagogastric junction using magnifying endoscopy. We prospectively studied palisade vessels in 15 patients undergoing upper gastrointestinal endoscopy using a GIF-H260Z instrument (Olympus Medical Systems Co., Tokyo, Japan). All views of the palisade vessels were obtained at the maximum magnification power in the narrow band imaging mode. We divided the area in which palisade vessels were present into three sections: the area from the squamocolumnar junction (SCJ) to about 1 cm orad within the esophagus (Section 1); the area between sections 1 and 3 (Section 2); and the area from the upper limit of the palisade vessels to about 1 cm distal within the esophagus (Section 3). In each section, we analyzed the vessel density, caliber of the palisade vessels, and their branching pattern. The vessel density in Sections 1, 2, and 3 was 9.1 ± 2.1, 8.0 ± 2.6, and 3.3 ± 1.3 per high-power field (mean ± standard deviation [SD]), respectively, and the differences were significant between Sections 1 and 2 ( P= 0.0086) and between Sections 2 and 3 ( P < 0.0001). The palisade vessel caliber in Sections 1, 2, and 3 was 127.6 ± 52.4 µm, 149.6 ± 58.6 µm, and 199.5 ± 75.1 µm (mean ± SD), respectively, and the differences between Sections 1 and 2, and between Sections 2 and 3, were significant ( P < 0.0001). With regard to branching form, the frequency of branching was highest in Section 1, and the 'normal Y' shape was observed more frequently than in Sections 2 and 3. Toward the oral side, the frequency of branching diminished, and the frequency of the 'upside down Y' shape increased. The differences in branching form were significant among the three sections ( P < 0.0001). These results indicate that the density of palisade vessels is highest near the SCJ, and that towards their upper limit they gradually become more confluent and show an increase of thickness. Within a limited area near the SCJ, observations of branching form suggest that palisade vessels merge abruptly on the distal side. We have demonstrated that palisade vessels are a useful marker for endoscopic recognition of the lower esophagus. [ABSTRACT FROM AUTHOR]

The superconducting magnet system for the J-PARC neutrino beam line for the T2K experiment has been served for the beam operation without serious disturbance since April 2009. Present most concern of the system is the operational current limit of superconducting corrector magnets for beam steering due to systematic quenches at lower currents. Operational experience of the magnet system and examples of troubleshoot including countermeasures against the corrector magnet quenches are presented. [ABSTRACT FROM AUTHOR]