Algorithms for the School Districting Problem

This paper presents two algorithms for finding solutions to the problem of school districting, which is the dividing of an administrative area into some school districts consisting of several population units. The problem is formulated as a set partitioning problem, after having enumerated the feasible districts satisfying all the given requirements. An algorithm for finding an exact optimal solution is first proposed. Using the population units as indivisible elements, the first phase enumerates all the feasible districts which satisfy the given requirements, such as contiguity, capacity, and so on. The second phase determines the optimal school districting that minimizes the sum of the distances traveled by all students. Since the computation time of the exact algorithm increases very quickly as the number of population units increases, an improved algorithm is derived for finding an optimal or near-optimal solution within a reasonable computation time. This algorithm constructs the core of each school district before enumerating the feasible districts. The core of each school district is composed of the population units which are assigned to the school, with the minimal distances traveled until the given bound on the population is satisfied. Computation results show that the improved algorithm can find an optimal or near-optimal solution for a problem having 122 units within one minute

Transcripts expressed using a bicistronic vector pIREShyg2 are sensitized to nonsense-mediated mRNA decay

<p>Abstract</p> <p>Background</p> <p>pIREShyg2 has been widely used as a bicistronic expression vector. However, it is not known if the vector would affect the expression of cloned genes via nonsense-mediated mRNA decay (NMD), an mRNA surveillance system that degrades mRNA with a premature termination codon (PTC). In mammalian cells, the induction of NMD requires either a long 3'UTR or the presence of an exon-junction complex downstream of a PTC. The efficiency of NMD is greater when a PTC generates longer 3'UTR. pIREShyg2 provides the first cistron gene with a long 3'UTR consisting of a downstream intervening sequence (IVS), an internal ribosomal entry site (IRES) and the second cistron. Therefore, we hypothesized that the first cistron genes in pIREShyg2 are sensitized to NMD, which affects their expression levels. To examine this hypothesis, cDNAs encoding human granulocyte-macrophage colony-stimulating factor receptor β chain (βc) and its splice variant (βc79), in which the retention of a 79-base intron caused a frameshift generating 18 PTCs, were cloned into pIREShyg2 and stably expressed in a murine cell line, Ba/F3.</p> <p>Results</p> <p>Compared with wild-type βc, the mRNA levels of βc79 were less than one tenth and decayed faster. Both translation inhibition and Upf1 knockdown led to significantly greater up-regulation of βc79 than wild-type βc. However, the use of a monocistronic pMT21 vector abolished the up-regulatory effects of translation inhibition and Upf1 knockdown on both wild-type βc and βc79, suggesting that the NMD is attributable to a structural determinant in pIREShyg2. The elimination of the intron and the proximal 3' 17 PTCs did not alter the greater effects of translation inhibition on βc79, suggesting that the first PTC, which determines 3'UTR length, was sufficient to enhance NMD efficiency. Thus, transcripts of PTC-harboring genes with longer 3'UTR are more efficiently degraded by the vector-dependent NMD than those of wild-type genes with relatively shorter 3'UTR, resulting in minimized expression of truncated mutants.</p> <p>Conclusions</p> <p>We conclude that pIREShyg2, which sensitizes its bicistronic transcripts to NMD, may be useful for studying NMD but should be avoided when maximum expressions of PTC-harboring genes are required.</p

In vivo contribution of Class III alcohol dehydrogenase (ADH3) to alcohol metabolism through activation by cytoplasmic solution hydrophobicity

AbstractAlcohol metabolism in vivo cannot be explained solely by the action of the classical alcohol dehydrogenase, Class I ADH (ADH1). Over the past three decades, attempts to identify the metabolizing enzymes responsible for the ADH1-independent pathway have focused on the microsomal ethanol oxidizing system (MEOS) and catalase, but have failed to clarify their roles in systemic alcohol metabolism. In this study, we used Adh3-null mutant mice to demonstrate that Class III ADH (ADH3), a ubiquitous enzyme of ancient origin, contributes to alcohol metabolism in vivo dose-dependently resulting in a diminution of acute alcohol intoxication. Although the ethanol oxidation activity of ADH3 in vitro is low due to its very high Km, it was found to exhibit a markedly enhanced catalytic efficiency (kcat/Km) toward ethanol when the solution hydrophobicity of the reaction medium was increased with a hydrophobic substance. Confocal laser scanning microscopy with Nile red as a hydrophobic probe revealed a cytoplasmic solution of mouse liver cells to be much more hydrophobic than the buffer solution used for in vitro experiments. So, the in vivo contribution of high-Km ADH3 to alcohol metabolism is likely to involve activation in a hydrophobic solution. Thus, the present study demonstrated that ADH3 plays an important role in systemic ethanol metabolism at higher levels of blood ethanol through activation by cytoplasmic solution hydrophobicity

The relation between standing balance and cognitive information processing performance in elderly persons. Examination by the dual-task assessment

先行研究によれば,バランス障害を有する高齢者は,立位保持と計算,数字の復唱などの認知課題とを同時に行った場合,バランス障害のない高齢者と比較して,有意に重心動揺が増加するとされている.本研究では,高齢者に,立位保持課題と認知課題(ストループテスト)を同時に行わせた場合と,それらを単一に処理した場合とで,立位保持課題と認知課題それぞれの処理能力にどのような変化がみられるのかを比較,検討した.対象は,65歳以上の高齢者であり,Berg Balance Scaleの得点により,彼らをバランス良好群(14名)とバランス不良群(9名)の2群に編成した.立位保持能力と認知課題処理能力の指標として,足圧中心変位の総軌跡長(Length: LNG)とストループテストの処理時間を用いた.バランス不良群では通常立位でのLNGとストループカラーテストを処理しながらのLNGの間に有意差が認められ,また,座位におけるストループカラーテストの処理時間と,立位におけるストループカラーテストの処理時間との間にも有意差が認められた.バランス良好群では,二重課題を行なってもLNGとストループテストの処理時間のどちらも影響を受けなかった.結果から,バランスの不良な高齢者は,立位保持と比較的複雑な認知課題を同時に行なうと,双方の処理能力が低下することが示唆され,これには,立位を保持するのに注意を必要とするかしないかが関係すると考えられた.Antecedent research indicates that elderly persons with a balance disorder have significantly moreshifts in their body center of gravity than those with no balance disorder, while they simultaneouslyperform a task to maintain a standing position and a cognitive task such as calculation and repetition ofnumbers. In this research, a comparative study was made to identify what differences can be observed withrespect to elderly persons' abilities to deal with a task to maintain a standing position and a cognitive taskrespectively, in the following two cases: (1) when an elderly person performs both a task to maintain astanding position and a cognitive task (based on a the Stroop Test) simultaneously, and (2) when theelderly person performs the above tasks individually. Subjects were elderly persons of 65 years old or overand were organized into two groups based on scores of the Berg Balance Scale: the first group wascomposed of those who had good balance (14 persons); and the second group, poor balance (9persons).As an index to measure the ability to maintain a standing position and to perform a cognitive task,total excursion length (Length: LNG) of the shift in the center of pressure and the performance time forthe Stroop Test were used. Among the group with poor balance, differences in LNG were recognizedsignificantly between the two cases: when the subjects were in an ordinary standing position, and when thesubjects were performing the Stroop Color Test. Significant differences were also found in theperformance time for the Stroop Color Test between the two cases: when the subjects were in a sittingposition and when the subjects were in a standing position. Among the group with good balance, neitherLNG nor performance time for the Stroop Test were affected by performing both tasks simultaneously.The findings suggest that when elderly persons with bad balance deal with a task to maintain a standingposition and a cognitive task with a relative complexity simultaneously, the performance ability for bothtasks decreased. Thus, it is considered that whether or not a person needs to pay attention to maintain astanding position is involved in the decreased performance ability

Neutron Irradiation Effects in Al-Li and Al-Mg-Li Alloys

Al-2.3wt%Li and Al-4.1wt%Mg-1.1wt%Li alloys were neutron-irradiated in JOYO, JMTR and RTNS-II with different types of energy spectra. The changes of He production by different neutron sources and of precipitates due to the isothermal annealing at 400℃ were investigated by transmission electron microscopy (TEM). It was confirmed from TEM observations that He production by transmutation and the coagulation of He atoms after the annealing depend on neutron energy spectra used for the irradiation. It was also found that the addition of Mg to Al-Li alloy strongly suppresses the growth of He bubbles. Interrelations among precipitates, vacancies, He atoms and Li atoms were investigated, obtaining a reasonable coincidence between mutual amounts

Effects of phosphodiesterase inhibitors on secretions of human monokines

ABSTRACTThe purpose of this study was to evaluate the effect of newly developed selective phosphodiesterase (PDE) inhibitors, KF19514 (type l/IV) and cilostazol (type III), and theophylline on the secretions of tumor necrosis factor a (TNFα) and interleukin-1β (IL-1 β) from human peripheral monocytes stimulated by lipopolysaccha- ride (LPS). Human blood monocytes were incubated with LPS in the absence or presence of KF19514, cilostazol or theophylline. TNFα and IL-1in the cell- free supernatants were measured with enzyme-linked immunosorbent assay. KF19514 showed significant inhibition on the release of TNFα (% inhibition ± SEM was 82.8 ± 7.4% at 1 nmol/L) and IL-1 β (34.4 ± 7.5% at 10 (μmol/L). In addition, KF19514 inhibited the expression of TNFa mRNA. Cilostazol inhibited the release of TNFa significantly (60.2 ± 8.9% at 30 μmol/L) but not IL-1 β. Theophylline inhibited slightly but significantly the release of TNFa at a therapeutic concentration (1 7.4 ± 5.1% at 100 μmol/L). These results suggest that theophylline may not only have a bronchodilating action but also an anti-inflammatory property in the treatment of bronchial asthma, and that KF19514 may have an anti-inflammatory action on at least the transcriptional level

μ-opioid Receptor-Mediated Alterations of Allergen-Induced Immune Responses of Bronchial Lymph Node Cells in a Murine Model of Stress Asthma

ABSTRACTBackgroundPsychological stress has a recognized association with asthma symptoms. Using a murine model of allergic asthma, we recently demonstrated the involvement of μ-opioid receptors (MORs) in the central nervous system in the stress-induced exacerbation of airway inflammation. However, the involvement of MORs on neurons and immunological alterations in the stress asthma model remain unclear.MethodsMOR-knockout (MORKO) mice that express MORs only on noradrenergic and adrenergic neurons (MORKO/Tg mice) were produced and characterized for stress responses. Sensitized mice inhaled antigen and were then subjected to restraint stress. After a second antigen inhalation, bronchoalveolar lavage cells were counted. Before the second inhalation, bronchial lymph node (BLN) cells and splenocytes from stressed and non-stressed mice were cultured with antigen, and cytokine levels and the proportions of T cell subsets were measured.ResultsStress-induced worsening of allergic airway inflammation was observed in wild-type and MORKO/Tg mice but not MORKO mice. In wild-type stressed mice, IFN-γ/IL-4 ratios in cell culture supernatants and the proportion of regulatory T cells in BLN cell populations were significantly lower than those in non-stressed mice. These differences in BLN cells were not observed between the stressed and non-stressed MORKO mice. Restraint stress had no effect on cytokine production or T cell subsets in splenocytes.ConclusionsRestraint stress aggravated allergic airway inflammation in association with alterations in local immunity characterized by greater Th2-associated cytokine production and a reduced development of regulatory T cells, mediated by MORs

Heart Disease Mortality in Cancer Survivors: A Population-Based Study in Japan

BACKGROUND: Data on the risk of cardiovascular-related mortality in patients with cancer are limited. METHODS AND RESULTS: This retrospective cohort study used data from the Osaka Cancer Registry and vital statistics in Japan between 1985 and 2013. The causes of death were investigated, and the risk of fatal heart disease was analyzed. Standardized mortality ratios were calculated to compare the risk of fatal heart disease between patients with cancer and the general population. Fine and Gray competing risk regression models were used to assess the risk of fatal heart disease among patients with cancer. In total, 682 886 patients with cancer were included in the analysis, and 335 635 patients died during the study period. Heart disease was the leading cause of noncancer deaths, with 10 686 deaths. Among the patients who died of heart disease, 5017 had ischemic heart disease, 3598 had heart failure, 356 had hypertensive disease, and 1715 had other heart diseases. The standardized mortality ratio for heart disease was 2.80 (95% CI, 2.74-2.85). The standardized mortality ratio for ischemic heart disease, heart failure, and hypertensive disease were 3.26 (95% CI, 3.17-3.35), 2.69 (95% CI, 2.60-2.78), and 5.97 (95% CI, 5.38-6.63), respectively. The risk of fatal heart disease increased over time after cancer diagnosis. Men were more likely to die of heart disease than women (subdistribution hazard ratio, 1.08 [95% CI, 1.02-1.16]). The risk of fatal heart disease among cancer survivors has decreased in recent years. CONCLUSIONS: Cancer survivors have a higher risk of fatal heart disease than the general population.Gon Y., Zha L., Sasaki T., et al. Heart Disease Mortality in Cancer Survivors: A Population-Based Study in Japan. Journal of the American Heart Association 12, e029967 (2023); https://doi.org/10.1161/JAHA.123.029967