On an Optimum Allocation of Workplace and Residence

In this paper, we describe a process for obtaining an optimum allocation of workplace and residence to minimize the total commuting hours of workers. We do not consider the people whose workplaces and residences have already been determined, but try to minimize the total commuting hours for work journeys for people who will find a work place or a residence, in the future, by means of the optimum allocation of workplace and residence. Let us suppose that people who want to find work and whose residences have been determined will get a job in the area to which they can commute from their residences, in proportion to the amount of demand for workers. And also let us suppose that people whose residences have not been determined as yet will reside in the area from which they can commute to their workplaces, in proportion to the number of houses. Then, the problem of obtaining the optimum allocation of workplace and residence is amenable to a technique of linear programming. An optimum allocation of workplace and residence in Kyoto City obtained through the above procedure is presented

Establishment of testis-specific SOX9 activation requires high-glucose metabolism in mouse sex differentiation

AbstractIn mouse sex differentiation, SRY promotes Sertoli cell differentiation via SOX9 action, resulting in testis formation. SRY/SOX9 also initiates various testis-specific morphogenic events including glycogenesis in pre-Sertoli cells, suggesting the importance of glucose storage for certain SRY/SOX9-downstream events in gonadal sex determination. However, it remains unclear which cell types and what molecular/cellular events require sex-dimorphic high-energy metabolic rate. Here we show that the establishment of SOX9 activation itself is a metabolically active process with sex-dimorphic high-energy requirements in gonadal sex differentiation. The glucose-deprivation and metabolic rescue experiments using genital ridge cultures of the XY/XX-wildtype and XX/Sry transgenic embryos demonstrated that, among the various somatic cell types, pre-Sertoli cells are the most sensitive to glucose starvation despite the differences between XX/Sry and XY genotypes. Moreover, our data showed that, in developing pre-Sertoli cells, the high-glucose metabolic state is required for the establishment of SOX9 expression through an ECM (extracellular matrix)-mediated feed-forward pathway. In contrast, the expression of SRY, SF1/Ad4Bp, GATA4 and WT1, as well as initiation of early SOX9 expression, is properly maintained in the glucose-deprived condition. Therefore, our results imply the metabolic importance of the high-glucose condition for the establishment of SOX9 activation in testis differentiation

Characteristics of Grouped Discharge Waveforms Observed in Long-term Masseter Muscle Electromyographic Recording: A Preliminary Study

We investigated the characteristics of grouped discharge (GD) waveforms obtained from long-term masseter electromyogram (EMG) recording in 6 female temporomandibular disorder (TMD) patients with myofascial pain and 6 healthy females. The EMG measurement was performed from the morning of the experiment day until the subject woke up the next day. We observed a significantly larger number of GD waveforms in the TMD group compared to the control group (p=0.002). Our results indicate that the existence of GD waveforms in masseter EMGs might be a predictor of future TMD with myofascial pain

Mechanomyographic activity in the human lateral pterygoid muscle during mandibular movement

The activity of the lateral pterygoid muscle has been regarded to be related to the pathological condition of the temporomandibular joint (TMJ) in the craniomandibular disorders. Because the lateral pterygoid muscle is a deep muscle, a needle electrode is necessary for EMG recordings. The purpose of this study was to establish a non-invasive method for the evaluation of muscle activity of the lateral pterygoid muscle using mechanomyogram (MMG). In three male subjects, surface electromyogram (EMG) in the left masseter muscle, left anterior and posterior belly of the temporal muscle, left anterior belly of the digastric muscle and needle EMG of the inferior head of the lateral pterygoid were recorded during mandibular movement tasks simultaneously with the MMG derived from a condenser microphone in the external ear canal. There were significant positive correlations between the needle EMG signal of the lateral pterygoid muscle and the MMG signal for the tasks of static jaw opened position of 30 mm of interincisal distance (p = 0.000, R(2)=0.725), static jaw opened position of 40 mm of interincisal distance (p = 0.000, R(2) = 0.753), 5 mm protruded mandibular position (p = 0.000, R(2) = 0.653), the most protruded mandibular position (p = 0.000, R(2) = 0803). On the contrary, for the task of maximal clenching, there was no significant correlation between the EMG signal of the lateral pterygoid muscle and the MMG signal. These results suggest that the activity of the lateral pterygoid muscle could be evaluated by the MMG signals recorded in the external ear canal, unless jaw closing major muscles show active contraction

Association between Epstein-Barr virus serological reactivation and psychological distress: a cross-sectional study of Japanese community-dwelling older adults

Reactivation of Epstein-Barr virus (EBV) is associated with the etiopathogenesis of a broad spectrum of diseases. This study aimed to investigate the association between psychological distress and EBV serological reactivation among community-dwelling older people and assess the role of sex differences in this association. This population-based cross-sectional survey was conducted among individuals who underwent annual health checkups (N = 2,821; median age 72.4 years). EBV serological reactivation was defined as elevation of EBV early antigen immunoglobulin G titers, and psychological distress was defined as Kessler 6 scores ≥5. Multivariable logistic regression analysis was performed to calculate odds ratios (OR) and 95% confidence intervals (CI) for EBV serological reactivation and psychological distress. EBV serological reactivation and psychological distress were detected in 16.4% and 8.7% of participants, respectively. Women accounted for 71% (328/463) of those with EBV serological reactivation. Multivariable logistic regression analysis showed psychological distress was not significantly associated with EBV serological reactivation among all participants (OR 1.31, 95% CI: 0.95, 1.82; P = 0.102). A sex-stratified multivariable analysis showed a positive association among women (OR 1.45, 95% CI: 1.01, 2.08; P = 0.043), but no association among men. EBV serological reactivation was independently associated with psychological distress in community-dwelling older women. The sex difference in our results warrants further investigation to clarify the physiological mechanisms underlying the association

Highly organized DnaA–oriC complexes recruit the single-stranded DNA for replication initiation

In Escherichia coli, the replication origin oriC consists of two functional regions: the duplex unwinding element (DUE) and its flanking DnaA-assembly region (DAR). ATP-DnaA molecules multimerize on DAR, unwinding DUE for DnaB helicase loading. However, DUE-unwinding mechanisms and functional structures in DnaA–oriC complexes supporting those remain unclear. Here, using various in vitro reconstituted systems, we identify functionally distinct DnaA sub-complexes formed on DAR and reveal novel mechanisms in DUE unwinding. The DUE-flanking left-half DAR carrying high-affinity DnaA box R1 and the ATP-DnaA-preferential DnaA box R5, τ1-2 and I1-2 sites formed a DnaA sub-complex competent in DUE unwinding and ssDUE binding, thereby supporting basal DnaB loading activity. This sub-complex is further subdivided into two; the DUE-distal DnaA sub-complex formed on the ATP–DnaA-preferential sites binds ssDUE. Notably, the DUE-flanking, DnaA box R1–DnaA sub-complex recruits DUE to the DUE-distal DnaA sub-complex in concert with a DNA-bending nucleoid protein IHF, thereby promoting DUE unwinding and binding of ssDUE. The right-half DAR–DnaA sub-complex stimulated DnaB loading, consistent with in vivo analyses. Similar features are seen in DUE unwinding of the hyperthermophile, Thermotoga maritima, indicating evolutional conservation of those mechanisms

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts