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This crossover trial aimed to investigate whether additional loading of unilateral Nordic hamstring exercise on a sloped platform would increase the biceps femoris long head electromyographic activity. Participants were randomly allocated to unilateral Nordic hamstring exercise under three conditions: bodyweight only (BW) or BW with an added weighted ball of 3 kg (BW + 3 kg) or 6 kg (BW + 6 kg), respectively. The biceps femoris long head electromyographic activity was significantly higher for BW + 6 kg (p p

AIMS Hepatocellular carcinoma (HCC) can still occur in hepatitis C virus (HCV) patients who have achieved a sustained virologic response (SVR), which remains an important clinical issue in the direct-acting antivirals era. The current study investigated the clinical utility of the aMAP score (consisting of age, male, albumin-bilirubin, and platelets) for predicting HCC occurrence in HCV patients achieving an SVR by direct-acting antivirals. METHODS A total of 1113 HCV patients without HCC history, all of whom achieved an SVR, were enrolled for clinical comparisons. RESULTS Hepatocellular carcinoma was recorded in 50 patients during a median follow-up period of 3.7 years. The aMAP score was significantly higher in the HCC occurrence group than in the HCC-free group (53 vs. 47, p

O artigo visa a analisar o direito à privacidade na contemporaneidade, momento em que as tecnologias de informação permitem o rastreamento constante dos indivíduos a partir de práticas onipresentes de coleta, processamento e mineração de dados pessoais. Sustenta-se que, se outrora a visão da privacidade como direito de ser deixado a sós era suficiente para garantir a sua tutela, o desenvolvimento tecnológico torna necessária a adoção de novos instrumentos jurídicos, na medida em que a proteção do direito à privacidade se torna progressivamente mais complexa. Adota-se a teoria da multifuncionalidade dos direitos fundamentais para explicar tal complexidade, a qual afirma que esses direitos abrangem um feixe de posições jurídicas jusfundamentais, impondo tanto deveres negativos de abstenção como deveres positivos de prestação, sendo que estes se subdividem em prestações fáticas e normativas, o que pode ser observado no contexto da Lei Geral de Proteção de Dados (Lei nº 13.709/2018). Conclui-se que proteger o direito à privacidade na era digital não significa pleitear o fim da coleta de dados pessoais, mas defender que tais práticas sejam realizadas em prol da transparência e da accountability, a fim de diminuir a assimetria entre os polos da relação informacional.

Background & Aims Natural killer (NK) cells are key participants in the innate immune response. Killer cell immunoglobulin-like receptors (KIRs) are involved in the activation and inhibition of NK cells through the recognition of human leukocyte antigen (HLA) class I molecules. We investigated the impact of KIR/HLA combinations on susceptibility and long-term clinical outcome in Japanese patients with type 1 autoimmune hepatitis (AIH). Methods A total of 154 cases of AIH were recruited at Shinshu University Hospital between 1974 and 2018. KIR genes and HLA class I and II alleles were genotyped in all patients along with 201 healthy individuals. Associations between KIR/HLA pairs and clinical outcomes (liver decompensation and liver-related death) were evaluated using the Cox proportional hazards model with stepwise method. Results After a median follow-up period of 11.1 years, 12% of patients experienced liver decompensation and 8% died from liver disease. KIR3DL1/HLA-B Bw4-80Ile (p = 0.0062) and the HLA-DRB1*04:05-DQB1*04:01 haplotype (p ≪0.001) were significantly associated with AIH. Conversely, significant protective associations were found for KIR3DL1/HLA-B Bw4-80Thr (p = 0.0092) and KIR2DL1/HLA-C2 (p = 0.0025). The KIR3DL1/HLA-B Bw4-positive phenotype was strongly associated with a favorable clinical outcome (liver decompensation: hazard ratio [HR] 0.37, p = 0.037; liver-related death: HR 0.26, p = 0.038). Cirrhosis was detected in 16 (10%) patients at diagnosis and was significantly related to poor survival (HR 17.87, p ≪0.001) and progression to liver decompensation (HR 9.00, p ≪0.001). Conclusions This study revealed the impact of specific KIR/HLA pairs in AIH susceptibility and progression in Japanese patients. KIR3DL1/HLA-B Bw4-negative patients with AIH and cirrhosis at diagnosis are at high risk of adverse outcomes and require careful surveillance. Lay summary Autoimmune hepatitis (AIH) is a disease of the liver that can present in acute or chronic hepatitis. We examined whether KIR/HLA pairs were associated with AIH susceptibility or disease progression. KIR3DL1/HLA-B Bw4 was a novel KIR/HLA pair related to a favorable clinical outcome, while cirrhosis at the initial diagnosis was a risk factor for poor prognosis. Thus, frequent and careful surveillance is advised for KIR3DL1/HLA-B Bw4-negative patients with AIH and cirrhosis., Graphical abstract Unlabelled Image, Highlights • KIR3DL1/HLA-B Bw4-80Ile is significantly associated with autoimmune hepatitis. • KIR2DL1/HLA-C2 and KIR3DL1/HLA-B Bw4-80Thr have protective associations with autoimmune hepatitis. • KIR3DL1/HLA-B Bw4 is a novel KIR/HLA pair related to a favorable outcome in autoimmune hepatitis. • Combined KIR3DL1/HLA-B Bw4 and cirrhosis at diagnosis relate to autoimmune hepatitis progression.

Mechanosensitive channels play an important role in the adaptation of cells to hypo-osmotic shock. Among members of this channel family in Escherichia coli, the exact function and physiological role of the mechanosensitive channel homolog YbdG remain unclear. Characterization of YbdG's physiological role has been hampered by its lack of measurable transport activity. Using a nitrosoguanidine mutagenesis-aided screen in combination with next-generation sequencing, here we isolated a mutant with a point mutation in ybdG. This mutation (resulting in a I167T change) conferred sensitivity to high osmotic stress, and the mutant cells differed from WT cells in morphology during hyperosmotic stress at alkaline pH. Interestingly, unlike the cells containing the I167T variant, a null-ybdG mutant did not exhibit this sensitivity and phenotype. Although I167T was located near the putative ion-conducting pore in a transmembrane region of YbdG, no change in ion channel activities of YbdG-I167T was detected. Of note, introduction of the WT C-terminal cytosolic region of YbdG into the I167T variant complemented the osmo-sensitive phenotype. Co-precipitation of proteins interacting with the C-terminal YbdG region led to the isolation of HldD and FbaA, whose overexpression in cells containing the YbdG-I167T variant partially rescued the osmo-sensitive phenotype. This study indicates that YbdG functions as a component of a mechanosensing system that transmits signals triggered by external osmotic changes to intracellular factors. The cellular role of YbdG uncovered here goes beyond its predicted function as an ion or solute transport protein.

Natural killer cells are partially mediated through the binding of killer cell immunoglobulin-like receptors (KIR) with human leukocyte antigen (HLA) class I ligands. This investigation examined the risk of hepatocellular carcinoma (HCC) in relation to KIR–HLA pairs in patients with compensated hepatitis C virus (HCV)-associated cirrhosis. A total of 211 Japanese compensated HCV cirrhotic cases were retrospectively enrolled. After KIR, HLA-A, HLA-Bw, and HLA-C typing, associations between HLA, KIR, and KIR–HLA combinations and HCC development were evaluated using the Cox proportional hazards model with the stepwise method. During a median follow-up period of 6.6 years, 69.7% of patients exhibited HCC. The proportions of HLA-Bw4 and the KIR3DL1 + HLA-Bw4 pair were significantly higher in patients with HCC than in those without (78.9% vs. 64.1%, odds ratio (OR)—2.10, 95% confidence interval (CI)—1.10–4.01, p = 0.023 and 76.2% vs. 60.9%, odds ratio—2.05, p = 0.024, respectively). Multivariate analysis revealed the factors of male gender (hazard ratio (HR)—1.56, 95% CI—1.12–2.17, p = 0.009), α-fetoprotein &gt, 5.6 ng/mL (HR—1.56, 95% CI—1.10–2.10, p = 0.011), and KIR3DL1 + HLA-Bw4 (HR—1.69, 95% CI—1.15–2.48, p = 0.007) as independent risk factors for developing HCC. Furthermore, the cumulative incidence of HCC was significantly higher in patients with KIR3DL1 + HLA-Bw4 than in those without (log-rank test, p = 0.013). The above findings suggest KIR3DL1 + HLA-Bw4, in addition to HLA-Bw4, as a novel KIR–HLA pair possibly associated with HCC development in HCV cirrhosis. HCV-associated cirrhotic patients with the risk factors of male gender, α-fetoprotein &gt, 5.6 ng/mL, and KIR3DL1 + HLA-Bw4 may require careful surveillance for HCC onset.

Inicialmente concebido como o direito de ser deixado a sós, o direito à privacidade teve seu âmbito de proteção consideravelmente expandido ao longo das últimas décadas, na medida em que passou a ter profundas relações com o desenvolvimento tecnológico e, por conseguinte, com a proteção de dados pessoais. No contexto de crescente digitalização da vida cotidiana, os dados pessoais se tornaram um dos insumos de maior importância econômica do século XXI, o que faz com que o cidadão esteja em posição de vulnerabilidade dentro da relação informacional. Desta maneira, a devida tutela da privacidade e dos dados pessoais não mais se limita ao reconhecimento de um dever de abstenção por parte de terceiros, mas requer igualmente prestações positivas por parte do Estado. Isso pode ser observado mesmo anteriormente à promulgação da Lei Geral de Proteção de Dados (Lei nº 13.709/2018), com a discussão sobre temas como o habeas data e o direito ao esquecimento. A proliferação da internet, dos smartphones e das novas tecnologias disruptivas apenas exacerbou os desafios para a proteção dos dados pessoais, com a aceleração das técnicas de vigilância e de monitoramento dos indivíduos. Portanto, uma adequada reflexão sobre como diminuir a assimetria entre os polos da relação informacional necessariamente requer compreender que os direitos à privacidade e à proteção de dados não se encontram em um vácuo, mas possuem profundas ligações com outros direitos fundamentais, tais como a liberdade e a dignidade humana.

Background Strong eosinophil infiltration in chronic rhinosinusitis with nasal polyp (CRSwNP) is highly associated with recalcitrance and higher nasal polyp recurrence rate after surgery. The prevalence of eosinophilic CRSwNP (ECRS) is increasing in Asian countries including Japan. Benralizumab is a humanized anti-IL-5R alpha monoclonal antibody that depletes eosinophils by antibody-dependent cell-mediated cytotoxicity. Objective To assess the efficacy and safety of benralizumab in patients with ECRS. Methods This phase II, randomized, double-blind, placebo-controlled study was conducted in Japan. Patients were randomized 1:2:2 to placebo, a single administration of benralizumab 30 mg, or benralizumab 30 mg every 4 weeks (q4w) for a total of three doses. The primary endpoint was the change in nasal polyp score from baseline at Week 12. Results Overall, 56 patients were enrolled (placebo, n = 11; benralizumab single dose, n = 22; benralizumab q4w, n = 23). Although the mean total nasal polyp score began to decrease after the initiation of benralizumab treatment, there were no statistically significant differences in change in nasal polyp score from baseline at Week 12 between benralizumab and placebo (placebo, −0.5 ± 0.8; benralizumab single, −0.3 ± 0.8; benralizumab q4w, −0.5 ± 1.5). Post-hoc analysis showed that the administration of benralizumab decreased nasal polyp scores ≥2 points in 42.2% of ECRS patients and that patients with high blood eosinophil levels had a greater tendency to respond to benralizumab treatment. The safety profile was similar to that in previous studies and no unexpected adverse events were noted. Conclusion Although benralizumab did not meet the primary efficacy endpoint, reductions of nasal polyp scores were seen in the benralizumab group compared with the placebo group over the whole study period, especially in patients with high levels of blood eosinophils.

Flocculation has been recognized for hundreds of years as an important phenomenon in brewing and wastewater treatment. However, the underlying molecular mechanisms remain elusive. The lack of a distinct phenotype to differentiate between slow-growing mutants and floc-forming mutants prevents the isolation of floc-related gene by conventional mutant screening. To overcome this, we performed a two-step Escherichia coli mutant screen. The initial screen of E. coli for mutants conferring floc production during high salt treatment yielded a mutant containing point mutations in 61 genes. The following screen of the corresponding single-gene mutants identified two genes, mrcB, encoding a peptidoglycan-synthesizing enzyme and cpxA, encoding a histidine kinase of a two-component signal transduction system that contributed to salt tolerance and flocculation prevention. Both single mutants formed flocs during high salt shock, these flocs contained cytosolic proteins. ΔcpxA exhibited decreased growth with increasing floc production and addition of magnesium to ΔcpxA suppressed floc production effectively. In contrast, the growth of ΔmrcB was inconsistent under high salt conditions. In both strains, flocculation was accompanied by the release of membrane vesicles containing inner and outer membrane proteins. Of 25 histidine kinase mutants tested, ΔcpxA produced the highest amount of proteins in floc. Expression of cpxP was up-regulated by high salt in ΔcpxA, suggesting that high salinity and activation of CpxR might promote floc formation. The finding that ΔmrcB or ΔcpxA conferred floc production indicates that cell envelope stress triggered by unfavorable environmental conditions cause the initiation of flocculation in E. coli.

Evolutionary strategies in growth improvement can be classified into r- or K-strategies. The former strategy corresponds to an evolutionary increase in growth rate, whereas the latter corresponds to an increase in the maximum amount of organisms or carrying capacity. What determines the strategies to be adopted during evolution? Spatial structures that compartmentalize the population into small patches are key to inducing the K-strategy. Interestingly, previous evolution experiments using Escherichia coli in a glucose-limited batch culture showed that carrying capacity could improve evolutionally even in the absence of spatial structures. However, it is unclear if the lack of spatial structures can direct evolution toward high carrying capacity for utilization of other resources. To address this question, we established a simplified evolution experiment using histidine-requiring E. coli grown under histidine limitation in a container with compartments. We confirmed the importance of spatial structures in K-strategy evolution in histidine utilization. Whole genome sequencing of the K-adapted strains showed functional variety of the mutated genes during the fitness-increasing period. These results validate the importance of spatial structures and imply that restriction of K-strategy evolution on a sort of nutrients is attributable to a paucity of appropriate selection rather than a paucity of causal mutation.

Killer cell immunoglobulin-like receptors (KIRs) are involved in the activation and inhibition of natural killer cells. Although combinations of KIRs and HLA have been associated with spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection, their roles are not fully understood in the context of hepatocellular carcinoma (HCC) development. We enrolled 787 consecutive patients with chronic HCV infection, which included 174 cases of HCC, and 325 healthy subjects to clarify the involvement of HLA-Bw and C, KIRs, and major histocompatibility complex class I chain-related gene A (MICA) gene polymorphisms (rs2596542 and rs1051792) in chronic HCV infection and HCV-related HCC. We observed a significant association with chronic hepatitis C susceptibility for HLA-Bw4 (P = 0.00012; odds ratio [OR] = 1.66) and significant protective associations for HLA-C2 and KIR2DL1-HLA-C2 (both P = 0.00099; OR = 0.57). When HCC patients were stratified into younger (

Our understanding of the source of methane (CH4) in freshwater ecosystems is being revised because CH4 production in oxic water columns, a hitherto inconceivable process of methanogenesis, has been discovered for lake ecosystems. The present study surveyed nine Japanese deep freshwater lakes to show the pattern and mechanisms of such aerobic CH4 production and subsurface methane maximum (SMM) formation. The field survey observed the development of SMM around the metalimnion in all the study lakes. Generalized linear model (GLM) analyses showed a strong negative nonlinear relationship between dissolved organic carbon (DOC) and dissolved inorganic nitrogen (DIN), as well as a similar curvilinear relationship between DIN and dissolved CH4, suggesting that the availability of organic carbon controls N accumulation in lake waters thereby influences the CH4 production process. The microbial community analyses revealed that the distribution of picocyanobacteria (i.e., Synechococcus), which produce CH4 in oxic conditions, was closely related to the vertical distribution of dissolved CH4 and SMM formation. Moreover, a cross-lake comparison showed that lakes with a more abundant Synechococcus population exhibited a greater development of the SMM, suggesting that these microorganisms are the most likely cause of methane production. Thus, we conclude that the stoichiometric balance between DOC and DIN might cause the cascading responses of biogeochemical processes, from N depletion to picocyanobacterial domination, and subsequently influence SMM formation in lake ecosystems.

Mechanosensitive channels play an important role in the adaptation of cells to hypo-osmotic shock. Among members of this channel family in Escherichia coli, the exact function and physiological role of the mechanosensitive channel homolog YbdG remain unclear. Characterization of YbdG's physiological role has been hampered by its lack of measurable transport activity. Using a nitrosoguanidine mutagenesis-aided screen in combination with next-generation sequencing, here we isolated a mutant with a point mutation in ybdG. This mutation (resulting in a I167T change) conferred sensitivity to high osmotic stress, and the mutant cells differed from WT cells in morphology during hyperosmotic stress at alkaline pH. Interestingly, unlike the cells containing the I167T variant, a null-ybdG mutant did not exhibit this sensitivity and phenotype. Although I167T was located near the putative ion-conducting pore in a transmembrane region of YbdG, no change in ion channel activities of YbdG-I167T was detected. Of note, introduction of the WT C-terminal cytosolic region of YbdG into the I167T variant complemented the osmo-sensitive phenotype. Co-precipitation of proteins interacting with the C-terminal YbdG region led to the isolation of HldD and FbaA, whose overexpression in cells containing the YbdG-I167T variant partially rescued the osmo-sensitive phenotype. This study indicates that YbdG functions as a component of a mechanosensing system that transmits signals triggered by external osmotic changes to intracellular factors. The cellular role of YbdG uncovered here goes beyond its predicted function as an ion or solute transport protein.

Thin film sensor that can measure the instantaneous temperature change on the wall surface of combustion chamber was developed in this study. This sensor was directly forms on combustion chamber surface by PVD(sputtering) method. In this study, with respect to the instantaneous temperature measurement accuracy using this thin film sensor, the optimum shape of the sensor was investigated by analysis, and additionally, an example of the measurement result by this sensor was shown in a rapid compression and expansion machine reported.

Article, PloS One. 13(4) :e0195778(2018)

Although it is now well known that some diseased areas, such as cancer nests, inflammation loci, and infarction areas, are acidified, little is known about cellular signal transduction, gene expression, and cellular functions under acidic conditions. Our group showed that different signal proteins were activated under acidic conditions compared with those observed in a typical medium of around pH 7.4 that has been used until now. Investigations of gene expression under acidic conditions may be crucial to our understanding of signal transduction in acidic diseased areas. In this study, we investigated gene expression in mesothelioma cells cultured at an acidic pH using a DNA microarray technique. After 24 h culture at pH 6.7, expressions of 379 genes were increased more than twofold compared with those in cells cultured at pH 7.5. Genes encoding receptors, signal proteins including transcription factors, and cytokines including growth factors numbered 35, 32, and 17 among the 379 genes, respectively. Since the functions of 78 genes are unknown, it can be argued that cells may have other genes for signaling under acidic conditions. The expressions of 37 of the 379 genes were observed to increase after as little as 2 h. After 24 h culture at pH 6.7, expressions of 412 genes were repressed more than twofold compared with those in cells cultured at pH 7.5, and the 412 genes contained 35, 76, and 7 genes encoding receptors, signal proteins including transcription factors, and cytokines including growth factors, respectively. These results suggest that the signal pathways in acidic diseased areas are different, at least in part, from those examined with cells cultured at a pH of around 7.4.

Although food hypersensitivity is a public health concern, its documentation among the elderly is limited. The current study aims to compare the prevalence and characteristics of food hypersensitivity among adolescent women between aged 18-24 with among older women50 years of age.660 female university students between the ages of 18 and 24 who volunteered were enrolled as adolescent subjects. 470 women50 years old who visited the Health Care Centre of Kyoto Katsura Hospital for health check-ups were enrolled as the older subjects. A questionnaire created by ourselves asking the presence of food hypersensitivity, symptoms, causative food, personal or family history of other allergic disorders was distributed.The prevalence of food hypersensitivity was statistically similar between adolescent (8.2%) and older women (8.9%). Among them, only 24.1% of the adolescent women and 26.2% of the older women had been diagnosed by physicians as having food allergy. The main causative foods (fruits, shellfish and fish) and the manifestations relating to food hypersensitivity were almost identical between adolescent and older women. In both adolescent and older women, food hypersensitivity positive group showed significantly higher prevalence of personal or family history of allergic disorders than that in food hypersensitivity negative group.These data indicate that food hypersensitivity in older women should be given more attention because the prevalence of this condition was as common as that in adolescent women.背景与目的：虽然食物过敏是一个公共健康问题，但在老年人中进行的研究有 限。本研究的目的是比较18-24 岁的青年女性和50 岁以上的老年女性食物过 敏的患病率和特点。方法与研究设计：纳入研究的青年研究对象是660 名年龄 在18-24 岁自愿参加的女大学生，老年研究对象是470 名到京都桂医院保健中 心进行健康体检的50 岁以上的女性。采用自编问卷询问研究对象食物过敏的 发生、症状、致敏食物、个人或家族其它过敏性疾病史。结果：青年女性和老 年女性食物过敏的患病率之间的差异无统计学意义，分别为8.2%和8.9%。她 们当中，只有24.1%的青年女性和26.2%的老年女性被医生诊断为食物过敏。 青年女性和老年女性的致敏食物（水果、贝类和鱼类）和食物过敏的表现几乎 相同。与食物过敏阴性组相比，青年女性和老年女性的食物过敏阳性组均显示 出较高的个人或家族过敏性疾病史。结论：这些数据表明，老年女性食物过敏 和年轻女性一样常见，应给予更多的关注。.

It is well understood that academic knowledge generated from basic research at university contribute to innovation in industrial sector. In order to demonstrate the degree to which academic knowledge contributes to innovation, we conducted multiple surveys on private corporations. Based on the results of our surveys, we have found the existence of a recognition gap between inventors and business managers with respect to contribution of academic knowledge to innovation. The reason for this gap is the potential disconnect in information between inventors and business managers concerning the application of academic knowledge.

With a focus on Japan, this paper empirically examines the stage in which drug development is abandoned. The time-consuming approval process for new drugs involves many stages and has low certainty. Based on pipeline data, we examine the stage in which drug development is completely abandoned or is “dead.” Using pipeline data on Japanese pharmaceutical companies, we investigate whether the abandonment of drug development depends on the drugs' characteristics. Through a review of the data, we find differences in the timing of drug development abandonment and the number of such abandonment by the disease and technology.

Clustering is a basic event for the initiation of immune cell responses, and simulation analyses of clustering of membrane proteins have been performed. It was claimed that a cluster is formed by the self-assembly induced by protein dimerization with a high binding speed (Woolf and Linderman, Biophys. Chem. 104, 217-227, 2003). We examined the cluster formation with Monte Carlo simulation using two algorithms. The first was that simulation processes were divided into two substeps. All proteins were subjected to movement in the first substep, followed by reaction in the second substep. The second algorithm was that proteins were first selected to react and proteins which did not react were subjected to movement. The self-assembly induced by dimerization was simulated only with the second algorithm. In this algorithm, monomers dissociated from dimers do not move because these monomers are not selected for movement, and a large proportion of such monomers are selected to form dimers in the next step. The self-assembly was again simulated with the first algorithm containing the conditions that monomers dissociated from dimers did not move in the next movement substep. This algorithm seems to be far removed from natural conditions. Thus, it is inferred that the self-assembly induced by dimerization is unlikely in situ, and that some interaction between proteins is required for cluster formation. In contrast to algorithms in previous simulations, our results suggest that it is more appropriate that proteins move to the same direction for a while and reflect when the collision occurs.

ATP participates in many cellular metabolic processes as a major substrate to supply energy. Many systems for acidic resistance (AR) under extremely acidic conditions have been reported, but the role of ATP has not been examined. To clarify whether or not ATP is necessary for the AR in Escherichia coli , the AR of mutants deficient in genes for ATP biosynthesis was investigated in this study. The deletion of purA or purB , each of which encodes enzymes to produce AMP from inosinate (IMP), markedly decreased the AR. The content of ATP in these mutants decreased rapidly at pH 2.5 compared to that of the wild type. The AR was again decreased significantly by the mutation of adk , which encoded an enzyme to produce ADP from AMP. The DNA damage in the purA and purB mutants was higher than that in the wild type. These results demonstrated that metabolic processes that require ATP participate in survival under extremely acidic conditions, and that one such system is the ATP-dependent DNA repair system.

The roles of OmpC and OmpF in acidic resistance (AR) were examined. When ompC and ompF were deleted, AR was decreased. The decreased level of AR seen in the mutant that was deficient in ompC and ompF was elevated by the addition of glutamate, but not by the addition of arginine or lysine. The expression levels of adiA and cadB were diminished by the deletion of ompC and ompF, and the conversion of arginine to agmatine and lysine to cadaverine by intact cells were reduced in the mutant. The expression of gadA/gadB was not affected by the deletion of ompC and ompF. These results suggest that the transport of arginine, lysine, and their decarboxylated products through OmpC and/or OmpF is essential for the survival of Escherichia coli cells under extremely acidic conditions.

Escherichia coli has three major K(+) uptake systems, Trk, Kup, and Kdp, which have been studied extensively at near neutral pH. However, the function of these transporters under acidic conditions is not well understood, although growth and survival under acidic conditions are important for bacterial pathogenesis. In this study, we examined the expression and activity of Kdp under acidic conditions and found that the transport activity of Kdp is decreased at low pH and that the expression of kdp is regulated by the internal K(+) concentration in a pH-independent manner. Consequently, the low activity of Kdp was compensated for by the induction of its elevated expression by low K(+) accumulation via Kdp at acidic pH.

To examine the efficacy of juvenile salmon research as a tool for forecasting adult returns, the results from a study on the early marine life stage of juvenile chum salmon, conducted in the Nemuro Strait during 1999–2002 (i.e., 1998–2001 brood years), were compared with the return rates of adult salmon. Among the four brood years, the 2000 brood year (i.e., salmon migrating to the sea in 2001) was previously reported as showing higher abundance, higher growth rate and better somatic condition during the coastal residency period. Consequently, we expected it to have the highest return rate, under a hypothesis that juvenile survival in coastal residency regulates brood-year strength. Contrary to this expectation, the 2000 brood year had almost the lowest return rate. Alternatively, a statistical model in which sea surface temperature during the first year of marine life and size at release were utilized as explanatory variables reconstructed the actual variability in return rates more accurately than that based on the early marine life stage. Possible reasons for the discrepancy between the results of the juvenile salmon research and adult returns are discussed, and we suggest improvements for future research on juvenile salmon.

In this paper, we empirically explain how scientific knowledge assimilated from academia affects corporate performance, particularly in the pharmaceutical industry of Japan. We use balanced panel data on 46 pharmaceutical firms in Japan for the period 1992–2005. Then, we introduce a new concept, propensity to capture basic research (PCBR), to index how much scientific knowledge firms have assimilated from universities and public research institutes. We use this index to verify whether absorption of such knowledge influences corporate performance. According to econometric analysis, PCBR is positively significant for patent applications and patent efficiency but not for number of approved drugs. This obviously implies that scientific knowledge assimilated from academia is effective for technological performance in firms. Moreover, the results suggest how R&D is structured in the organizational setup of Japanese pharmaceutical firms.

This study describes the effectiveness of ACT for people in Japan with severe mental disorders. The subjects were 21 schizophrenic patients and eight professionals. All consented to be a part of this study. Ten patients were in the ACT group and eleven were in the comparative group. The characteristics of the two groups were almost identical. Eight professionals were nurses, social workers, and psychiatrists. This study was implemented between December 2005 and February 2007. ACT intervention was conducted according to the ACT protocols of National ACT Standards with modifications by this research team. Evaluations were implemented by BPRS, GAF, LSP and CSQ questionnaires. These questionnaires were written by the primary psychiatrist and Certified Nurse Specialist or Head nurse.

The major histone-like Escherichia coli protein, HU, is composed of alpha and beta subunits respectively encoded by hupA and hupB in Escherichia coli. A mutant deficient in both hupA and hupB grew at a slightly slower rate than the wild type at pH 7.5. Growth of the mutant diminished with a decrease in pH, and no growth was observed at pH 4.6. Mutants of either hupA or hupB grew at all pH levels tested. The arginine-dependent survival at pH 2.5 was diminished approximately 60-fold by the deletion of both hupA and hupB, whereas the survival was slightly affected by the deletion of either hupA or hupB. The mRNA levels of adiA and adiC, which respectively encode arginine decarboxylase and arginine/agmatine antiporter, were low in the mutant deficient in both hupA and hupB. The deletion of both hupA and hupB had little effect on survival at pH 2.5 in the presence of glutamate or lysine, and expression of the genes for glutamate and lysine decarboxylases was not impaired by the deletion of the HU genes. These results suggest that HU regulates expression of the specific set of genes required for growth and survival in acidic environments.

Background Previous studies have described a role of oxidative stress in the pathogenesis of various pediatric disorders, but investigation into oxidative stress status in patients with severe disability remains limited. The aim of the present study was therefore to clarify the oxidative stress status in patients with severe disability, focusing specifically on intake of three major nutrients and micronutrients with antioxidant activities. Methods Thirty-one patients with severe disability (mean age, 14.1 ± 7.8 years) were enrolled. Three in vivo biomarkers, plasma biological antioxidant potential (BAP), plasma reactive oxygen metabolite-derived compounds (d-ROM), and urinary 8-hydroxydeoxyguanosine (8-OHdG), were determined for evaluating oxidative status. The dietary intake of three major nutrients and various micronutrients was estimated from dietary records over a 3 day period. Results In patients with severe disability, BAP was significantly lower and d-ROM and 8-OHdG significantly higher than in historical controls. Among these markers, a significant positive correlation was found in BAP versus d-ROM and d-ROM versus 8-OHdG. On multiple regression analysis, a significant inverse association between 8-OHdG and carotenoid intake was seen. Conclusion The oxidative/antioxidative balance shifts towards oxidative status dominance in patients with severe disability. More research is needed on nutritional intake of antioxidative nutrients to determine whether they can be used to reduce oxidative stress.

To uncover possible barriers to effective communication and learning, this study explored how college-level Japanese English language learners in English-as-a-second-language (ESL) and English-as-a-foreign-language (EFL) contexts viewed their English teachers and classroom activities. Analysis of 100 questionnaires incorporating quantitative and qualitative questions revealed that most Japanese students positively viewed teachers who were open, respectful of other cultures, and willing to adjust classroom content to meet students' needs. Among the differences between ESL and EFL students were ESL students' greater comfort with active participation in class, more time spent in class, physical proximity to teachers, and appreciation of student-centered behavior. On the other hand, EFL students appreciated teachers who provided native language support and avoided possible loss of face entailed by challenging and unexpected questions.

A simple and reliable method using liquid chromatography–electrospray ionization‐mass spectrometry (LC/ESI‐MS) has been developed for the determination of aminoglycoside antibiotics, streptomycin (SM), and dihydrostreptomycin (DSM) in honey. The LC separation was performed on a TSK‐gel Super ODS column (100 × 2 mm i.d.) using 5 mM heptafluoro‐n‐butyric acid (HFBA)–acetonitrile (88:12) as the mobile phase at a flow rate of 0.18 mL/min. The positive ionization produced the typical (M + H)+ molecular ions of both drugs (SM m/z 582.3; DSM m/z 584.3). The calibration graphs for SM and DSM were rectilinear from 0.05 to 10 ng with selected ion monitoring (SIM). The drugs were extracted with water, and the extracts were cleaned up on an Oasis HLB cartridge (60 mg). The recoveries of both drugs from honey fortified at a level of 0.1 µg/g was 85.8–89.1%, with high precision. The limits of quantification of the drugs in honey were 0.01 µg/g (signal‐to‐noise ratio >10).