Frequency sweep rate dependence on the dielectrophoretic response of polystyrene beads and red blood cells.
Alternating current (AC) dielectrophoresis (DEP) experiments for biological particles in microdevices are typically done at a fixed frequency. Reconstructing the DEP response curve from static frequency experiments is laborious, but essential to ascertain differences in dielectric properties of biological particles. Our lab explored the concept of sweeping the frequency as a function of time to rapidly determine the DEP response curve from fewer experiments. For the purpose of determining an ideal sweep rate, homogeneous 6.08 μm polystyrene (PS) beads were used as a model system. Translatability of the sweep rate approach to ∼7 μm red blood cells (RBC) was then verified. An Au/Ti quadrapole electrode microfluidic device was used to separately subject particles and cells to 10Vpp AC electric fields at frequencies ranging from 0.010 to 2.0 MHz over sweep rates from 0.00080 to 0.17 MHz/s. PS beads exhibited negative DEP assembly over the frequencies explored due to Maxwell-Wagner interfacial polarizations. Results demonstrate that frequency sweep rates must be slower than particle polarization timescales to achieve reliable incremental polarizations; sweep rates near 0.00080 MHz/s yielded DEP behaviors very consistent with static frequency DEP responses for both PS beads and RBCs.


[Discussing the current situation of tuberculosis case-finding by mass miniature radiography in Japan].
The system of tuberculosis (TB) case-finding by mass miniature radiography (MMR) was established and expanded for almost all Japanese citizens in the 1950s. And, as stipulated by the TB Prevention Law, periodic mass screenings for schools, inhabitants, employees and institutions have been carried out. Among those aged over 25 years, the proportion of people screened by MMR was estimated to be 60.3%. This means that about 54 million people aged over 25 years are receiving medical service with MMR every year. However, the detection rates of TB cases by MMR have declined markedly compared with those in 1950s. As of 1998, the detection rate was 0.03 per 1,000 for school children and students, 0.06 per 1,000 for employees, and 0.16 per 1,000 for inhabitants. The proportion of cases detected by MMR among newly notified TB cases was 12.8% in 1998, and this ratio has been almost constant for the last 10 years. This ratio was greater among young adult TB cases. Approximately 20% of notified TB cases aged 20-39 years were detected by MMR for employees. Although the purpose of MMR is to find the cases before discharging TB bacilli, 35.1% of the cases were bacteriologically confirmed, and this proportion was greater among elderly TB cases. The Japan Anti-Tuberculosis Association (JATA) has been carrying out MMR for a long time. Eight selected branches of JATA that has been doing high quality case-finding reported 228 TB cases out of 965,440 inhabitants aged over 40 years examined by MMR in 1996. Based on these results, the cost per TB case detected by MMR was calculated. The cost was 4.4 millions yen (yen) per case for all forms of TB, yen 2.3 millions for male, yen 8.4 millions for female, yen 7.3 millions for those aged 40-49 years and yen 1.8 millions for those aged over 80 years. TB detection rate by MMR for inhabitants was correlated with TB incidence rate in various areas, and based on this correlation, the cost was calculated for various incidence rates. For all forms of TB, the cost was yen 4.0 millions per case for an incidence rate of 30 per 100,000, and yen 6.7 millions for an incidence rate of 20 per 100,000. MMR is not economically cost-effective even among elderly people and in areas with incidence rate less than 50 per 100,000, because the medical expense for a TB patient treated under hospitalization for 2 months and outpatient's clinic for 4 months is approximately yen 0.9 millions in 1996. The decision making in continuation or abolition or limitation of MMR should be discussed from a wide range of cost-effectiveness analyses as well as from the view of public health service and willingness of people. For the purpose of decision making, this study provides the detection rates; the costs stratified by sex, age and incidence; and the proportion of cases detected by MMR among newly notified TB cases by age-group and bacteriological status.


About the relationship between basic numerical processing and arithmetics in early Alzheimer's disease--a follow-up study.
We studied the relationship between basic numerical knowledge and arithmetics (facts and procedures) in early Alzheimer's Disease (AD). In most patients, basic numerical knowledge was found to be preserved, as reflected by low error rates, distance effect in number comparison, and subitizing in naming numerosities. However, within arithmetics, AD patients exhibited decreased fact and procedural knowledge. Interestingly, double dissociations were found not only between facts and procedures but also between basic numerical knowledge and arithmetics. Thus, our results suggest that basic numerical knowledge need not be a prerequisite for the maintenance of arithmetics, but rather corroborate calculation models that postulate the functional independence of its components. Further, we found patient specific error types which might serve to identify early AD. The follow-up about one year later indicated significant qualitative, but only marginal quantitative performance changes.


Protein utilization during energy undernutrition in sheep sustained by intragastric infusion: effects of protein infusion level, with or without sub-maintenance amounts of energy from volatile fatty acids, on energy and protein metabolism.
Utilization of endogenous and exogenous energy for protein accretion during energy undernutrition has been studied. Nine lambs nourished by intragastric infusion were given either progressively increasing or decreasing amounts of casein-N up to 2550 mg/kg metabolic weight (W0.75), with or without 250 kJ/kg W0.75 of volatile fatty acids daily. Energy balance (respiration calorimetry) and N balance were measured. While all experimental animals were in negative energy balance, N balance increased curve-linearly with the increase in casein-N infusion and attained positive N balance. Endogenous energy (presumably body fat) was found to meet the energy needs for protein accretion during energy undernutrition. It is concluded that body fat can be effectively utilized to support lean-tissue growth during energy undernutrition, so that the classical nutritional concept of dietary energy:protein ratio is only meaningful when both endogenous and exogenous energy are considered.


Atypical Presentation of Juvenile Hyaline Fibromatosis of Hands.
Juvenile hyaline fibromatosis is a rare disorder characterized by an extracellular accumulation of hyaline deposit. In the extremities, lesions may remain quiescent or gradually increase in size, eventually resulting in skin ulceration. There is no curative treatment. Surgery may allow some recovery of function, but recurrence is possible. We report a case of juvenile hyaline fibromatosis in both hands of a 25-year-old man who required multiple surgical procedures to address problems with function, pain, and appearance.


Computerized tomographic demonstration of a retroperitoneal hematoma causing femoral neuropathy. Report of two cases.
To the previously reported 28 cases of femoral neuropathy caused by a retroperitoneal hematoma in patients on anticoagulant drugs are added two cases in which the diagnosis was made by direct visualization of hematoma of the iliacus muscle by computerized tomography of the abdomen.


Fine structure mapping of the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene region of the human X chromosome (Xq26).
The Xq26-q27 region of the X chromosome is interesting, as an unusually large number of genes and anonymous RFLP probes have been mapped in this area. A number of studies have used classical linkage analysis in families to map this region. Here, we use mutant human T-lymphocyte clones known to be deleted for all or part of the hypoxanthine-guanine phosphoribosyltransferase (hprt) gene, to order anonymous probes known to map to Xq26. Fifty-seven T-cell clones were studied, including 44 derived from in vivo mutation and 13 from in vitro irradiated T-lymphocyte cultures. Twenty anonymous probes (DXS10, DXS11, DXS19, DXS37, DXS42, DXS51, DXS53, DXS59, DXS79, DXS86, DXS92, DXS99, DXS100d, DXS102, DXS107, DXS144, DXS172, DXS174, DXS177, and DNF1) were tested for codeletion with the hprt gene by Southern blotting methods. Five of these probes (DXS10, DXS53, DXS79, DXS86 and DXS177) showed codeletion with hprt in some mutants. The mutants established the following unambiguous ordering of the probes relative to the hprt gene: DXS53-DXS79-5'hprt3'-DXS86-DXS10-DXS177 . The centromere appears to map proximal to DXS53. These mappings order several closely linked but previously unordered probes. In addition, these studies indicate that rather large deletions of the functionally haploid X chromosome can occur while still retaining T-cell viability.


Systematic screening for the detection of atrial fibrillation.
Atrial fibrillation (AF), the most common arrhythmia in clinical practice, is a leading cause of morbidity and mortality. Screening for AF in asymptomatic patients has been proposed as a way of reducing the burden of the disease by detecting people who would benefit from prophylactic anticoagulation therapy before the onset of symptoms. However, for screening to be an effective intervention, it must improve the detection of AF and provide benefit for those detected earlier as a result of screening. This review aims to answer the following questions.Does systematic screening increase the detection of AF compared with routine practice? Which combination of screening population, strategy and test is most effective for detecting AF compared with routine practice? What safety issues and adverse events may be associated with individual screening programmes? How acceptable is the intervention to the target population? What costs are associated with systematic screening for AF? We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid) and EMBASE (Ovid) up to 11 November 2015. We searched other relevant research databases, trials registries and websites up to December 2015. We also searched reference lists of identified studies for potentially relevant studies, and we contacted corresponding authors for information about additional published or unpublished studies that may be relevant. We applied no language restrictions. Randomised controlled trials comparing screening for AF with routine practice in people 40 years of age and older were eligible. Two review authors (PM and CT) independently selected trials for inclusion. Two review authors (PM and CT) independently assessed risk of bias and extracted data. We used odds ratios (ORs) and 95% confidence intervals (CIs) to present results for the primary outcome, which is a dichotomous variable. As we identified only one study for inclusion, we performed no meta-analysis. We used the GRADE (Grades of Recommendation, Assessment, Development and Evaluation Working Group) method to assess the quality of the evidence and GRADEPro to create a 'Summary of findings' table. One cluster-randomised controlled trial met the inclusion criteria for this review. This study compared systematic screening (by invitation to have an electrocardiogram (ECG)) and opportunistic screening (pulse palpation during a general practitioner (GP) consultation for any reason, followed by an ECG if pulse was irregular) versus routine practice (normal case finding on the basis of clinical presentation) in people 65 years of age or older.Results show that both systematic screening and opportunistic screening of people over 65 years of age are more effective than routine practice (OR 1.57, 95% CI 1.08 to 2.26; and OR 1.58, 95% CI 1.10 to 2.29, respectively; both moderate-quality evidence). We found no difference in the effectiveness of systematic screening and opportunistic screening (OR 0.99, 95% CI 0.72 to 1.37; low-quality evidence). A subgroup analysis found that systematic screening and opportunistic screening were more effective in men (OR 2.68, 95% CI 1.51 to 4.76; and OR 2.33, 95% CI 1.29 to 4.19, respectively) than in women (OR 0.98, 95% CI 0.59 to 1.62; and OR 1.2, 95% CI 0.74 to 1.93, respectively). No adverse events associated with screening were reported.The incremental cost per additional case detected by opportunistic screening was GBP 337, compared with GBP 1514 for systematic screening. All cost estimates were based on data from the single included trial, which was conducted in the UK between 2001 and 2003. Evidence suggests that systematic screening and opportunistic screening for AF increase the rate of detection of new cases compared with routine practice. Although these approaches have comparable effects on the overall AF diagnosis rate, the cost of systematic screening is significantly greater than the cost of opportunistic screening from the perspective of the health service provider. Few studies have investigated effects of screening in other health systems and in younger age groups; therefore, caution needs to be exercised in relation to transferability of these results beyond the setting and population in which the included study was conducted.Additional research is needed to examine the effectiveness of alternative screening strategies and to investigate the effects of the intervention on risk of stroke for screened versus non-screened populations.


[Lifestyle and probabilty of dementia in the elderly].
there is evidence of a relationship between physical and cognitive activity and the development of dementia, although this hypothesis has not been tested in Mexican population. analyze the association between an increased participation in physical and cognitive activities and the probability of having dementia, using a Mexican open population sample. we made a cross sectional survey in open Mexican population of residents in urban and rural areas of 65 of age and older; we performed cognitive assessments to identify subjects with dementia, as well as questionnaires to assess the level of participation in physical and cognitive activities. We performed a binary logistic regression analysis to establish the association between participation and the probability of having dementia. we included 2003 subjects, 180 with diagnosis of dementia. Subjects with dementia were older, had less education and higher prevalence of some chronic diseases. The low participation in cognitive activities was associated with a higher probability of developing dementia. Patients with dementia had significantly lower scores on physical activity scales. this study supports the hypothesis of a relationship between low cognitive and physical activity and the presentation of dementia.


Dietary B vitamin needs of strains of pigs with high and moderate lean growth.
Ten sets of 5 littermate pigs from each of 2 genetic strains were utilized to determine the impact of the dietary concentration of 5 B vitamins (riboflavin, niacin, pantothenic acid, cobalamin, and folacin) on growth from 9 to 28 kg of BW in pigs with high or moderate capacity for lean growth. All pigs (penned individually) were reared via a segregated, early weaning scheme, so that the lean growth potential of each strain could be expressed. The basal diet provided the 5 test vitamins at concentrations of total and estimated bioavailability equivalent to a minimum of 100 and 70%, respectively, of their estimated requirements (NRC, 1998) for 5- to 10-kg pigs. At a BW of 9 +/- 0.9 kg, pigs within each litter were allotted to the basal diet supplemented with sources of the 5 test vitamins equivalent to an additional 0, 100, 200, 300, or 400% (bioavailable) of the NRC requirements. Pigs from the high lean strain consumed less feed (P < 0.05) and gained BW faster (P < 0.02) and more efficiently (P < 0.01) than pigs of the moderate lean strain. In both lean strains, the rate and efficiency of growth were improved (P < 0.01) as dietary B vitamin concentrations were increased. However, the dietary B vitamin concentrations needed to optimize G:F were greater (P < 0.03) in the high (>470% of NRC, 1998) vs. moderate (270%) lean strain. Based on these data, the dietary needs for 1 or more of the 5 B vitamins are greater than current NRC (1998) estimates, particularly in pigs expressing a high rate of lean tissue growth. The greater need for these vitamins is not associated with greater dietary energy intake or body energy accretion rate but is potentially due to shifts in the predominant metabolic pathways.


Applications of Gold Nanoparticles in Nanomedicine: Recent Advances in Vaccines.
Nowadays, gold is used in (nano-)medicine, usually in the form of nanoparticles, due to the solid proofs given of its therapeutic effects on several diseases. Gold also plays an important role in the vaccine field as an adjuvant and a carrier, reducing toxicity, enhancing immunogenic activity, and providing stability in storage. An even brighter golden future is expected for gold applications in this area.


Physiologically Based Pharmacokinetic Modeling and Simulation of Mavacamten Exposure with Drug-Drug Interactions from CYP Inducers and Inhibitors by CYP2C19 Phenotype.
Mavacamten is a first-in-class, oral, selective, allosteric, reversible cardiac myosin inhibitor approved by the US Food and Drug Administration for the treatment of adults with symptomatic New York Heart Association functional class II-III obstructive hypertrophic cardiomyopathy. Mavacamten is metabolized in the liver, predominantly via cytochrome P450 (CYP) enzymes CYP2C19 (74%), CYP3A4 (18%), and CYP2C9 (8%). A physiologically-based pharmacokinetic (PBPK) model was developed using Simcyp version 19 (Certara, Princeton, NJ). Following model verification, the PBPK model was used to explore the effects of strong CYP3A4 and CYP2C19 inducers, and strong, moderate, and weak CYP2C19 and CYP3A4 inhibitors on mavacamten pharmacokinetics (PK) in a healthy population, with the effect of CYP2C19 phenotype predicted for poor, intermediate, normal, and ultrarapid metabolizers. The PBPK model met the acceptance criteria for all verification simulations (> 80% of model-predicted PK parameters within 2-fold of those observed clinically). A weak induction effect was predicted when mavacamten was administered with a strong CYP3A4 inducer in poor metabolizers. Moderate reductions in mavacamten exposure were predicted with a strong CYP2C19/CYP3A4 inducer in all CYP2C19 phenotypes. Except for the effect of strong CYP2C19 inhibitors on ultrarapid metabolizers, steady-state area under plasma concentration-time curve and maximum plasma concentration values were weakly affected (< 2-fold) or not affected (< 1.25-fold), regardless of CYP2C19 phenotype. In conclusion, a fit-for-purpose PBPK model was developed and verified, which accurately predicted the available clinical data and was used to simulate the potential impact of CYP induction and inhibition on mavacamten PKs, stratified by CYP2C19 phenotype.


Carotid intima-media thickness is associated with allelic variants of stromelysin-1, interleukin-6, and hepatic lipase genes: the Northern Manhattan Prospective Cohort Study.
Atherosclerosis is a complex disorder with hereditary and environmental causes. Carotid artery intima-media wall thickness (IMT) is a useful measure of atherosclerosis. The objective of this study was to determine the association between carotid IMT and functional promoter variants of stromelysin-1 (MMP3: -1612 5A>6A), interleukin-6 (IL6: -174G>C), and hepatic lipase (HL: -480C>T) genes. B-mode carotid ultrasound was performed among 87 subjects (mean age, 70+/-12 years; 55% women; 60% Caribbean-Hispanic, 25% black, and 13% white) from the Northern Manhattan Prospective Cohort Study. Carotid IMT was calculated as a composite measure (mean of the maximum IMT in the bifurcation, the common carotid artery, and the internal carotid artery). For all polymorphisms, genotype distribution was not significantly different from Hardy-Weinberg equilibrium. The frequencies of the rare alleles were as follows: MMP3 -1612 5A>6A, 0.31 (95% CI, 0.25 to 0.39); IL6 -174 G>C, 0.20 (95% CI, 0.13 to 0.25); and HL -480 C>T, 0.45 (95% CI, 0.35 to 0.50). Carotid IMT in the sample was 0.78+/-0.18 mm. Subjects with the MMP3 genotype 6A6A had 8% greater mean carotid IMT than the other MMP3 genotypes combined (0.95+/-0.17 versus 0.87+/-0.15 mm; P=0.04). Subjects with the IL6 genotype GG had 11% greater IMT (0.85+/-0.17 versus 0.76+/-0.16 mm; P=0.03), and those with the HL genotype CC had 13% greater IMT (0.87+/-20 versus 0.76+/-0.18 mm; P=0.02) than the other genotypes combined. Adjustment for other risk factors did not change these associations. Carotid IMT is higher among subjects homozygous for functional variants in genes related to matrix deposition (MMP3 -16126A), inflammation (IL6 -174G), and lipid metabolism (HL -480C). These associations were independent of race-ethnicity and some environmental exposures. Further studies are needed to confirm these genotype-phenotype associations.


[The C677T polymorphism in the methylene tetrahydrofolate reductase gene among Tunisian population].
The 5,10 methylene tetrahydrofolate reductase (MTHFR) is an enzyme that catalyzes the irreversible reduction of 5,10 methylene tetrahydrofolate into 5 methyl tetrahydrofolate. It is coded by a gene where several polymorphisms have been identified. The most common is the C677T polymorphism described as presenting an heterogeneous worldwide distribution and associated with different disorders such as cardiovascular and cancerous diseases. The aim of this work was to determine the allelic and genotypic frequencies of the C677T polymorphism among a Tunisian healthy population. The study concerned 185 subjects apparently healthy. It was carried out by the PCR/RFLP method, using the restriction enzyme Hinf I. The results has showed an allelic frequency of 17.8% with a genotype frequency of 5.4%. These values are intermediate between those observed in Africa and those observed in Western countries. They must be considered in the evaluation of the clinic significance of a predisposition to diseases.


Changes in sleep disturbance among Chinese adolescents: A population-based online survey.
Sleep disturbance is prevalent among adolescents but little is known about the short-term changes among Chinese adolescents. The study aimed to explore the prevalence and change patterns of sleep disturbance and identify its risk and protective factors. Data were collected online from April 21st to May 12th, 2021 (Time 1, T1) and December 17th to 26th, 2021 (Time 2, T2). The final sample comprised 34,260 adolescents. Self-administrated questionnaires were used to assess socio-demographic variables, sleep disturbance, depression, anxiety, life events, family function, and resilience. The prevalence of sleep disturbance was 12.0% at T1 and 11.8% at T2, with higher rates in females than males. Four groups of sleep disturbance change patterns were identified: non-sleep disturbance group (80.4%), persistent group (4.2%), new-onset group (7.6%), and remission group (7.8%). Risk factors for new-onset sleep disturbance included being in junior high school (AOR = 1.26, 95%CI = 1.15-1.38), family history of mental disorders (AOR = 1.49, 95%CI = 1.03-2.15), and moderate (AOR = 1.24, 95%CI = 1.13-1.36) and severe (AOR = 1.48, 95%CI = 1.27-1.72) family dysfunction. Risk factors for persistent sleep disturbance included being in junior (AOR = 1.25, 95%CI = 1.08-1.45) and senior (AOR = 1.53, 95%CI = 1.15-2.03) high school, parental currently unmarried status (AOR = 1.34, 95%CI = 1.05-1.73), moderate (AOR = 1.19, 95%CI = 1.02-1.39) and severe (AOR = 1.28, 95%CI = 1.06-1.55) family dysfunction. Medium (AOR = 0.48, 95%CI = 0.43-0.53) and high (AOR = 0.34, 95%CI = 0.29-0.40) levels of resilience were protective factors against new-onset sleep disturbance, as well as against persistent sleep disturbance (medium level: AOR = 0.51, 95%CI = 0.43-0.60; high level: AOR = 0.32, 95%CI = 0.25-0.43). Interventions aimed at promoting family functions and enhancing resilience may improve sleep disturbance among adolescents.


Relationships between anthropometric and body composition characteristics and age in Polish women over 60 as affected by their socioeconomic and health status and physical activity levels.
Background: Little is known about changes in anthropometric and body composition (A&BC) characteristics during the aging process. Research indicates that body composition can be linked with socioeconomic status (SES), health status (HS), and physical activity (PA) levels. Aim: The aim of this study was to evaluate age-related changes in A&BC characteristics in female seniors aged 60+ in view of their SES, HS, and PA levels. Methods: The survey was conducted in November and December 2022 on a total of 661 female seniors. A questionnaire survey was conducted to obtain information about the participants' socioeconomic status (chronic diseases, health status, marital status, membership in social organizations, financial status, place of residence, education). The respondents' PA levels were assessed with the International Physical Activity Questionnaire (IPAQ), and their A&BC characteristics were determined in a bioelectrical impedance analysis with the InBody 270 body composition analyzer. The relationships between A&BC characteristics and age were evaluated based on the values of the Pearson correlation coefficient (r). Results: The mean values of Percent Body Fat (PBF), Body Mass Index (BMI), and the waist-hip ratio (WHR) were relatively high (37.2%, 28.5 kg/m2, and 0.8, respectively) and indicative of overweight and gynoid obesity. A higher number of significant negative correlations between A&BC characteristics and age were observed in seniors with lower values of SES, HS, and PA, which points to more rapid involutional changes in this group of respondents. A segmental analysis also revealed significantly lower values of fat-free mass (FFM) and body fat mass (BFM) (both indicators were calculated in percentage and kg), in particular in the upper limbs, in women with lower SES, HS, and PA levels. Conclusion: Environmental factors, including biological, physiological, environmental, psychological, behavioral, and social factors, are significantly associated with aging in women. Age-related changes in A&BC characteristics tend to proceed more rapidly in female seniors with low values of SES and HE and insufficient PA levels.


Robust Eye Center Localization through Face Alignment and Invariant Isocentric Patterns.
The localization of eye centers is a very useful cue for numerous applications like face recognition, facial expression recognition, and the early screening of neurological pathologies. Several methods relying on available light for accurate eye-center localization have been exploited. However, despite the considerable improvements that eye-center localization systems have undergone in recent years, only few of these developments deal with the challenges posed by the profile (non-frontal face). In this paper, we first use the explicit shape regression method to obtain the rough location of the eye centers. Because this method extracts global information from the human face, it is robust against any changes in the eye region. We exploit this robustness and utilize it as a constraint. To locate the eye centers accurately, we employ isophote curvature features, the accuracy of which has been demonstrated in a previous study. By applying these features, we obtain a series of eye-center locations which are candidates for the actual position of the eye-center. Among these locations, the estimated locations which minimize the reconstruction error between the two methods mentioned above are taken as the closest approximation for the eye centers locations. Therefore, we combine explicit shape regression and isophote curvature feature analysis to achieve robustness and accuracy, respectively. In practical experiments, we use BioID and FERET datasets to test our approach to obtaining an accurate eye-center location while retaining robustness against changes in scale and pose. In addition, we apply our method to non-frontal faces to test its robustness and accuracy, which are essential in gaze estimation but have seldom been mentioned in previous works. Through extensive experimentation, we show that the proposed method can achieve a significant improvement in accuracy and robustness over state-of-the-art techniques, with our method ranking second in terms of accuracy. According to our implementation on a PC with a Xeon 2.5Ghz CPU, the frame rate of the eye tracking process can achieve 38 Hz.


Understanding coronary arterial anatomy in the congenitally malformed heart.
With the development of three-dimensional techniques for imaging, such as computed tomography and magnetic resonance imaging, it is now possible to demonstrate the precise sinusal origin and epicardial course of the coronary arteries with just as much accuracy as can be achieved by the morphologist holding the heart in his or her hands. At present, however, there is no universally accepted convention for categorising the various patterns found when the heart is congenitally malformed. In this review, we show how, to provide such a convention, it is necessary to take note not only of the sinusal origin of the three major coronary arteries, but also the relationship of the aortic root relative to the cardiac base. We summarise the evidence showing how the proximal portions of the developing coronary arteries grow into the aortic valvar sinuses subsequent to the separation of the aortic root from the subpulmonary infundibulum. We also discuss the evidence showing that the subpulmonary myocardium is impervious to the passage of epicardial coronary arteries, and suggest that the process of septation itself plays an integral role in guiding the arteries into the two aortic sinuses that are adjacent to the pulmonary root. We then show how marriage of convenience between the epicardial coronary arteries and the aortic valvar sinuses provides a good explanation for the known variations found in the setting of transposition. We point out that it is the absence of septation that likely governs the patterns seen in the setting of a common arterial trunk.


Investigating Possible Reciprocal Relations Between Depressive and Problem Gambling Symptoms in Emerging Adults.
Previous cross-sectional research has shown that depression and problem gambling co-occur. Longitudinal research, however, allows for a better determination of directionality, as behavioural changes in gambling involvement can be more reliably studied over time. Our study assesses symptoms of depression and problem gambling across 4 waves and addresses whether their relation is directional (with one reliably preceding the other), bidirectional, or pathoplastic. As part of the Manitoba Longitudinal Study of Young Adults, prospective data were collected on Canadian young adults' (Wave 1: n = 679, 51.8% female, aged 18 to 20 years) depressive symptoms, involvement in gambling, and risky gambling behaviour. Recruitment and the first cycle of data collection (Wave 1) took place in fall 2007. Three additional waves of data collection then occurred in 12- to 18-month intervals: fall 2008, spring 2010, and spring 2011. The Problem Gambling Severity Index and the Composite International Diagnostic Interview-Short Form were administered through telephone interview at each wave. Bivariate growth curves showed that depressive and problem gambling symptoms were positively correlated at Wave 1, Wave 2, and Wave 4. Neither disorder was found to be a risk factor for the other, and depression and problem gambling were not pathoplastically related (that is, increases in one did not result in increases in the other over time, and vice versa). While depression and problem gambling are related, their co-occurrence may be better explained not by depressive- or gambling-related risk, but by the presence of a common underlying factor (such as substance abuse).


Length and end group dependence of the electronic transport properties in carbon atomic molecular wires.
Carrying out theoretical calculations using the nonequilibrium Green's function method combined with the density functional theory, the transport properties of functionalized atomic chains of carbon atoms with different lengths are investigated. The results show that the I-V evolution and rectifying performance can be affected by the length of wire when both ends of it is capped with the benzene-thiol attached with an amino group and the pyridine attached with nitro group. But when capped with the benzene-thiol attached with an amino group and the nitro group, we can observe a surprised result that different systems show similar I-V characteristics and their transport properties are almost independent of molecular length, which suggests that this is a favorable way to design more ideal molecular interconnecting wires with a high length-independent conductance behavior.


Inbreeding influences herbivory in Cucurbita pepo ssp. texana (Cucurbitaceae).
In a series of field experiments Diabrotica beetle herbivory was found to influence the magnitude of inbreeding depression in Cucurbita pepo ssp. texana, an annual monoecious vine. Beetles damage flowers and fruits and chew dime-sized holes in leaf tissue between major veins. Inbred plants were found to be more likely to be damaged by beetles and to have more leaves damaged per plant than outcrossed plants. A positive linear association was found between the coefficient of inbreeding and the magnitude of leaf damage, whereas a negative association was found between coefficient of inbreeding and several male and female fitness traits. When pesticides were used to control beetle herbivory, the interaction between coefficient of inbreeding and pesticide treatment was significant for fruit production and marginally significant for pollen quantity per anther. Therefore, the magnitude of inbreeding depression in C. pepo ssp. texana varies depending on the severity of beetle herbivory.


Update of human and mouse matrix metalloproteinase families.
Matrix metalloproteinases (MMPs) are a family of zinc proteases that degrade most of the components of the extracellular matrix (ECM). MMPs also have a number of non-traditional roles in processing factors related to cell growth/proliferation, inflammation and more. There are 23 human MMPs and 23 mouse MMPs, most of which share orthology among most vertebrates; other examples have been found in invertebrates and plants. MMPs are named in order of discovery, but also have been grouped by domain structure or by phylogenetic analysis. MMPs are multi-domain proteins which generally contain a signal sequence; propeptide (which keeps the protein inactive until cleaved); catalytic domain; and a hemopexin-like domain (which provides substrate specificity). MMPs are thought to play a role in many disease states, including arthritis, vascular disease, lung injury, wound repair, cancer and various neurodegenerative disorders. Although there has been much clinical interest in MMP inhibitors (MMPIs), few trials have been successful - often due to the broad nature of inhibition and the complex role of different MMPs in a given disease state.


One-time graded doses of vitamin A to weanling piglets enhance hepatic retinol but do not always prevent vitamin A deficiency.
Vitamin A supplements are administered to infants in developing countries at immunization contacts; doses of 50000 IU vitamin A are recommended. Doses of 100000 IU are given to children aged 0.5-1 y. The efficacy of these doses has not been adequately determined. We aimed to quantify liver vitamin A after the administration of vitamin A doses to piglets. Piglets are a good model for infants because of their similar size, gastrointestinal anatomy, and vitamin A requirements. Castrated male piglets born to sows fed a vitamin A-depleted diet throughout 1 (parity A) or 3 (parity B) pregnancy and lactation cycles were randomly assigned to receive 1 of 4 oral vitamin A doses (ie, 0, 25000, 50000, or 100000 IU) at weaning (days 9-14). A vitamin A-depleted diet was fed until the piglets were killed on day 10. Serum retinol was measured on days 1, 2, 4, 7, and 10. The modified relative dose response was measured before supplementation and at the time of killing, and liver vitamin A concentration was measured. In both parities, 25000 IU did not result in a mean liver retinol reserve > 0.07 micromol/g liver (the deficiency cutoff). The 50000-IU dose increased mean reserves above 0.07 micromol/g only in parity A. Liver vitamin A reserves with the 100000-IU treatment were only 5% above those with the 50000-IU treatment. The modified relative dose-response test reflected differences in liver vitamin A stores in parity B, and the 0-IU group differed significantly from the 100000-IU group (P = 0.011). This piglet model suggests that, for supplementation to infants <6 mo old, a 50000-IU dose is likely to be more efficacious in mitigating deficiency than is a 25000-IU dose.


General pediatric care for a patient after heart transplant: what the practitioner needs to know.
The scope of this review is to discuss aspects of general pediatric care which significantly impact the outcome of children after heart transplant. The general practitioner (GP) often serves as the frontline for prevention and early detection of common problems after heart transplant. Multiple studies in the literature show the negative impact of preventable illness in immune compromised patients, including the appropriateness of vaccine administration. Except for live vaccines, pediatric heart transplant recipients generally follow standard childhood vaccine schedules. In addition, diagnosis of cardiac and noncardiac conditions by the practitioner can lead to earlier treatment by subspecialists. While rejection and infection are such conditions the practitioner may identify, psychological and neurocognitive conditions are common and impact both adherence to medications and quality of life. These issues are addressed in this review of the recent literature. Through knowledge, detection, and collaboration of care, the practitioner can greatly improve the well being of pediatric heart transplant recipients.


Atlantooccipital subluxation in a neonate with Down's syndrome. Case report and review of the literature.
Atlantooccipital subluxation (AOS) occurs in up to 63% of patients with Down's syndrome. However, presenting symptoms and the age at which preoperative screening becomes necessary have not been clearly delineated. Recently, a 16-day-old female with Down's syndrome and AOS presented to our institution. Following patent ductus arteriosus ligation, her neurological examination revealed trace movement, few spontaneous respirations, and left lower extremity clonus. Cervical spine radiographs revealed significant AOS. She was reduced and underwent a fusion from the occiput to C2. She gradually regained full strength and sensation. This case is the youngest example of AOS related to Down's syndrome described. It emphasizes the need for preoperative screening of all patients with Down's syndrome.


The effect of a short-term low-carbohydrate, high-fat diet with or without postmeal walks on glycemic control and inflammation in type 2 diabetes: a randomized trial.
Lowering carbohydrate consumption effectively lowers glucose, but impacts on inflammation are unclear. The objectives of this study were to: 1) determine whether reducing hyperglycemia by following a low-carbohydrate, high-fat (LC) diet could lower markers of innate immune cell activation in type 2 diabetes (T2D) and 2) examine if the combination of an LC diet with strategically timed postmeal walking was superior to an LC diet alone. Participants with T2D ( n = 11) completed a randomized crossover study involving three 4-day diet interventions: 1) low-fat low-glycemic index (GL), 2) and 3) LC with 15-min postmeal walks (LC+Ex). Four-day mean glucose was significantly lower in the LC+Ex group as compared with LC (-5%, P < 0.05), whereas both LC+Ex (-16%, P < 0.001) and LC (-12%, P < 0.001) conditions were lower than GL. A significant main effect of time was observed for peripheral blood mononuclear cells phosphorylated c-Jun N-terminal kinase ( P < 0.001), with decreases in all three conditions (GL: -32%, LC: -45%, and LC+Ex: -44%). A significant condition by time interaction was observed for monocyte microparticles ( P = 0.040) with a significant decrease in GL (-76%, P = 0.035) and a tendency for a reduction in LC (-70%, P = 0.064), whereas there was no significant change in LC+Ex (0.5%, P = 0.990). Both LC (-27%, P = 0.001) and LC+Ex (-35%, P = 0.005) also led to significant reductions in circulating proinsulin. An LC diet improved 4-day glycemic control and fasting proinsulin levels when compared with GL, with added glucose-lowering benefits when LC was combined with postmeal walking.


Proximal pedicled anterolateral thigh flap for reconstruction of trochanteric defect.
We describe our experience using the proximal pedicled anterolateral thigh (ALT) flap for the reconstruction of trochanteric defects. Seven ALT island flap procedures were performed in 6 patients between September 2006 and May 2007. Four of the 7 patients had trochanteric pressure sores because of paraplegia. In these patients, intramuscular perforators were dissected to raise a fasciocutaneous flap. Three myocutaneous flaps of the vastus lateralis muscle were used to treat osteomyelitis of the trochanter with implant extrusion. The mean follow-up was 7 months (range, 2-12 months), and all flaps survived. Trochanteric coverage with the proximal pedicled ALT flap gave excellent results. We conclude that the ALT flap is a reliable flap for trochanteric coverage.


Cognitive remediation in severe mental illness.
Cognitive enhancement has received substantial recent attention because of multiple recent successes. We review the current research literature on cognitive enhancement, focusing on new developments that separate previous less successful efforts from recent successes. These innovations include increased understanding of the dosing and spacing of sessions, the need for titration of difficulty of individual sessions, and the importance of concurrent interventions. We also review the domains of functioning shown to be improved by cognitive remediation and the possibility that some biomarkers improve as well. We close by noting that current societal factors may impose limitations on the benefits accrued from cognitive remediation and also note that some pharmacological treatments, such as anticholinergic medications, may reduce or eliminate the potential benefits from cognitive remediation.


ODVBA-C: Optimally-Discriminative Voxel-Based Analysis of Continuous Variables.
In this paper, we propose a new method that utilizes a novel spatially adaptive scheme for detection of multivariate neuroimaging patterns relating to a continuous subject-level variable, aiming to effectively determine the optimal spatially adaptive filtering of neuroimaging data from the persepective of finding relationships between imaging and continues (e.g. clinical and cognitive) variables. Analyses employ local pattern analysis using regularized least square regression with nonnegativity constraints within a spatial neighborhood around each voxel. Within each neighborhood, we determine the optimal regression coefficients that relate local patterns to the continuous variable of interest. As each voxel belongs to multiple overlapping neighborhoods, the statistic for a given voxel is determined by combining weights from all neighborhoods to which the voxel participates. Finally, nonparametric permutation testing is used to obtain a voxelwise significance map. Using both simulated and real fMRI data, we demonstrate the effectiveness of the proposed method.


Communication skills training in a hospice volunteer training program.
As hospice services have expanded, patient care volunteers have become increasingly important in providing support to the dying and their families. Fundamental to the success of hospice volunteers is the quality of interaction among the volunteer, the dying patient, and his or her family. This article examines the extent to which a specific hospice program provided communication skills training for its volunteers. Results indicate that, while listening, empathy, and nonverbal communication were touched upon, broader communication skills were not addressed and specific communication skills training was not provided. The implications for this lack of communication training are noted and methods of increasing active empathetic listening skills are proposed. The article concludes with a discussion of potential theoretical and pragmatic research contributions that the field of communication studies can make to hospice training programs.


Preventive effect of diabegon, a polyherbal preparation, during progression of diabetes induced by high-fructose feeding in rats.
In the present study, the polyherbal preparation diabegon, containing 18 plant extracts with hypoglycemic activity, was evaluated for its preventive effect during progression of type 2 diabetes in high-fructose-diet-fed rats. Oral administration of diabegon (100 mg/kg body weight) delayed development of glucose intolerance for 4 weeks in comparison with the diabetic control group, and the effect of diabegon was compared to that of the standard insulin sensitizer drug rosiglitazone. Diabegon treatment also ameliorated the elevation of glycosylated haemoglobin, liver glycogen content, plasma insulin, homeostasis model assessment, free fatty acids, triglycerides, total cholesterol, LDL-cholesterol, and VLDL-cholesterol, whereas it increased HDL-cholesterol after 56 days of treatment (P<0.05). The mechanism of action by which diabegon attenuates insulin resistance and dyslipidemia may be through induction of peroxisome proliferator-activated receptor-gamma and lipoprotein lipase activity in peripheral tissues (muscles). Moreover, diabegon administration for 56 days also produced no alteration in liver and kidney function tests, which seems to indicate its non-toxicity during treatment. Our present results suggest that diabegon may be included in diabetes mellitus treatment regimens, as a drug with good antidiabetic actions but no toxic manifestations.


The naturally occurring flavolignan, deoxypodophyllotoxin, inhibits lipopolysaccharide-induced iNOS expression through the NF-kappaB activation in RAW264.7 macrophage cells.
Deoxypodophyllotoxin (DPT), a naturally occurring flavolignan with anti-inflammatory activity, was isolated from Anthriscus sylvestris HOFFM., and we examined its effects on the expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated, murine macrophage-like RAW264.7 cells. Western blot analysis performed with specific anti-iNOS antibodies showed that a decrease in nitric oxide (NO) was accompanied by a decrease in the iNOS protein level. To clarify the mechanistic basis for DPT's ability to inhibit iNOS induction, we examined the effect of DPT on nuclear factor (NF)-kappaB transcriptional activity and DNA binding activity. DPT potently suppressed both reporter gene activity and DNA binding activity. These findings suggest that DPT in RAW264.7 cells abolished LPS-induced iNOS expression by inhibiting the transcription factor, NF-kappaB.


Targeted metabolomics study of serum bile acid profile in patients with end-stage renal disease undergoing hemodialysis.
Bile acids are important metabolites of intestinal microbiota, which have profound effects on host health. However, whether metabolism of bile acids is involved in the metabolic complications of end-stage renal disease (ESRD), and the effects of bile acids on the prognosis of ESRD remain obscure. Therefore, this study investigated the relationship between altered bile acid profile and the prognosis of ESRD patients. A targeted metabolomics approach based on ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine the changes in serum bile acids between ESRD patients (n = 77) and healthy controls (n = 30). Univariate and multivariate statistical analyses were performed to screen the differential proportions of bile acids between the two groups. Six differentially expressed bile acids were identified as potential biomarkers for differentiating ESRD patients from healthy subjects. The decreased concentrations of chenodeoxycholic acid, deoxycholic acid and cholic acid were significantly associated with dyslipidemia in ESRD patients. Subgroup analyses revealed that the significantly increased concentrations of taurocholic acid, taurochenodeoxycholic acid, taurohyocholic acid and tauro α-muricholic acid were correlated to the poor prognosis of ESRD patients. The serum bile acid profile of ESRD patients differed significantly from that of healthy controls. In addition, the altered serum bile acid profile might contribute to the poor prognosis and metabolic complications of ESRD patients.


Comparative In Vitro and In Vivo Studies of Porcine Rotavirus G9P[13] and Human Rotavirus Wa G1P[8].
The changing epidemiology of group A rotavirus (RV) strains in humans and swine, including emerging G9 strains, poses new challenges to current vaccines. In this study, we comparatively assessed the pathogenesis of porcine RV (PRV) G9P[13] and evaluated the short-term cross-protection between this strain and human RV (HRV) Wa G1P[8] in gnotobiotic pigs. Complete genome sequencing demonstrated that PRV G9P[13] possessed a human-like G9 VP7 genotype but shared higher overall nucleotide identity with historic PRV strains. PRV G9P[13] induced longer rectal virus shedding and RV RNAemia in pigs than HRV Wa G1P[8] and generated complete short-term cross-protection in pigs challenged with HRV or PRV, whereas HRV Wa G1P[8] induced only partial protection against PRV challenge. Moreover, PRV G9P[13] replicated more extensively in porcine monocyte-derived dendritic cells (MoDCs) than did HRV Wa G1P[8]. Cross-protection was likely not dependent on serum virus-neutralizing (VN) antibodies, as the heterologous VN antibody titers in the sera of G9P[13]-inoculated pigs were low. Thus, our results suggest that heterologous protection by the current monovalent G1P[8] HRV vaccine against emerging G9 strains should be evaluated in clinical and experimental studies to prevent further dissemination of G9 strains. Differences in the pathogenesis of these two strains may be partially attributable to their variable abilities to replicate and persist in porcine immune cells, including dendritic cells (DCs). Additional studies are needed to evaluate the emerging G9 strains as potential vaccine candidates and to test the susceptibility of various immune cells to infection by G9 and other common HRV/PRV genotypes. The changing epidemiology of porcine and human group A rotaviruses (RVs), including emerging G9 strains, may compromise the efficacy of current vaccines. An understanding of the pathogenesis and genetic, immunological, and biological features of the new emerging RV strains will contribute to the development of new surveillance and prevention tools. Additionally, studies of cross-protection between the newly identified emerging G9 porcine RV strains and a human G1 RV vaccine strain in a susceptible host (swine) will allow evaluation of G9 strains as potential novel vaccine candidates to be included in porcine or human vaccines.


On the error in the nucleus-centered multipolar expansion of molecular electron density and its topology: A direct-space computational study.
The convergence of nucleus-centered multipolar expansion of the quantum-chemical electron density (QC-ED), gradient, and Laplacian is investigated in terms of numerical radial functions derived by projecting stockholder atoms onto real spherical harmonics at each center. The partial sums of this exact one-center expansion are compared with the corresponding Hansen-Coppens pseudoatom (HC-PA) formalism [Hansen, N. K. and Coppens, P., "Testing aspherical atom refinements on small-molecule data sets," Acta Crystallogr., Sect. A 34, 909-921 (1978)] commonly utilized in experimental electron density studies. It is found that the latter model, due to its inadequate radial part, lacks pointwise convergence and fails to reproduce the local topology of the target QC-ED even at a high-order expansion. The significance of the quantitative agreement often found between HC-PA-based (quadrupolar-level) experimental and extended-basis QC-EDs can thus be challenged.


Novel high-pressure windows made of glass-like carbon for x-ray analysis.
Original high-pressure glass-like carbon windows developed for x-ray spectroscopy applications are presented. The scientific and technological background of this new technical development is exposed, in particular the limitations of our existing beryllium windows in the context of x-ray absorption spectroscopy (XAS) measurements of solutions with very low solute concentrations at hydrothermal conditions (0.1-200 MPa, 30-600 °C). The benefits of glass-like carbon are exposed, notably its non-crystalline character, the absence of impurities which has been verified by micro-fluorescence laboratory measurements, and its non-toxicity which makes its machining safer. Finite elements mechanical calculations and experimental pressure tests were conducted to determine the pressure limits of windows with two different geometries: cylindrical (thickness 0.5 mm) and inversed-dome shape (thickness 0.5 mm at the tip of the dome). The former break at 150 MPa and the latter show no sign of rupture at 400 MPa. Recent XAS measurements conducted with the new dome shaped windows are presented to show the advantages of the design that allow for the detection of very low concentrations in the transmission mode (down to 30 ppm) and the acquisition of fluorescence XAS spectra in diluted solutions at high pressure. Eventually the perspectives of this original development are discussed.


Lipoma-Like Bronchogenic Cyst in the Right Chest Sidewall: A Case Report and Literature Review.
Bronchogenic cyst most commonly occurs in the mediastinum, followed by the lung. We admitted a 59-year female patient with bronchogenic cyst being uniquely located on the right chest wall of the parietal pleura. Preoperative CT scan showed a local low-density lesion on the right chest wall. The lesion was removed by the thoracoscopic surgery. During the surgical resection, the lesion was observed to be located on the right chest wall. The lesion was surrounded by adipose tissue and covered with entire parietal pleura, which looks like lipoma. Pathological examination demonstrated that the lesion was bronchogenic cyst. In addition, previously reported cases of bronchogenic cyst were reviewed, and the relevant clinical knowledge was discussed.


Effects of Age and Hearing Loss on the Discrimination of Amplitude and Frequency Modulation for 2- and 10-Hz Rates.
Detection of frequency modulation (FM) with rate = 10 Hz may depend on conversion of FM to amplitude modulation (AM) in the cochlea, while detection of 2-Hz FM may depend on the use of temporal fine structure (TFS) information. TFS processing may worsen with greater age and hearing loss while AM processing probably does not. A two-stage experiment was conducted to test these ideas while controlling for the effects of detection efficiency. Stage 1 measured psychometric functions for the detection of AM alone and FM alone imposed on a 1-kHz carrier, using 2- and 10-Hz rates. Stage 2 assessed the discrimination of AM from FM at the same modulation rate when the detectability of the AM alone and FM alone was equated. Discrimination was better for the 2-Hz than for the 10-Hz rate for all young normal-hearing subjects and for some older subjects with normal hearing at 1 kHz. Other older subjects with normal hearing showed no clear difference in AM-FM discrimination for the 2- and 10-Hz rates, as was the case for most older hearing-impaired subjects. The results suggest that the ability to use TFS cues is reduced for some older people and most hearing-impaired people.


Is hyaluronan deposition in the stroma of pancreatic ductal adenocarcinoma of prognostic significance?
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis and the number of PDAC-related deaths is rising. Recently the tumour stroma and in particular one of its main components, hyaluronan (HA), have attracted considerable attention as intravenous hyaluronidase treatment together with conventional chemotherapy considerably prolonged survival in HA-rich PDA patients. We therefore wanted to investigate the prognostic significance of HA deposition in PDA using both antibodies to HA and hyaluronan binding protein (HABP). Tissue microarrays of PDAs of 184 patients and pancreatic xenografts tumours were immunohistochemically (IHC) stained for HA using either biotinylated hyaluronic acid binding protein (HABP) or anti-HA antibody. The pattern of staining with HABP differed significantly from that with antibody IHC. Antibody staining was found both within cancer cells and in the extracellular matrix and staining could not be eliminated by hyaluronidase predigestion of the tissue sections. In contrast, HABP staining was generally confined to the extracellular matrix and was completely abolished by hyaluronidase pretreatment. HA positivity as determined by HABP was associated with larger primary tumours (p = 0.046). There were no correlations between overall survival, disease-free survival and HA expression. Presence of HA alone is not of prognostic importance in PDAC, and IHC with utilization of antibody detection shows no reliable staining pattern and should not be applied for HA IHC.


Update on monoclonal antibody therapy in chronic lymphocytic leukemia.
Monoclonal antibodies are an evolving treatment modality in chronic lymphocytic leukemia that has the potential to provide more effective and safer targeted therapy. This review provides historical context and detailed analysis of current developments, as well as an outline for future prospects and expectations in this exciting new arena of therapeutics.


Growth and clonogenic assays compared for irradiated MCF-7 and Colo-205 cell lines.
Clonogenic assays have been the golden standard for the assessment of cytotoxic injury from irradiation or drugs. Since such assays are time consuming, growth assays, often with automatic quantifying equipment, are frequently used. Since these procedures do not immediately reflect loss of clonogenic capacity, it was considered important to validate the two procedures using gamma-irradiation (0, 2 and 4 Gy) of two human cell lines (MCF-7 and Colo-205). The cells were growing exponentially in 96-well plates and crystal violet staining resulted in optical densities proportional to cell number. The homogeneity of optical densities within the plates was optimal if the wells to be measured were surrounded by liquid-containing ones. The slopes of the exponential growth curves were decreased upon irradiation. An "apparent cell survival", the mean of the three lowest ratios between irradiated and control cells, was defined. It was compared with the SF2 and SF4 as found in parallel Courtenay-Mills assays. In this work we found a modest underestimation of cell survival using the growth assay, ranging from 0 to 17 per cent in absolute terms.


Antagonistic and Synergistic Activation of Cardiovascular Vagal and Sympathetic Motor Outflows in Trigeminal Reflexes.
The trigeminal nerve and heart are strongly related through somato-autonomic nervous reflexes that induce rapid changes in cardiovascular function. Several trigeminal reflexes have been described, but the diving and trigeminocardiac reflexes are the most studied. The heart is a target organ dually innervated by the sympathetic and parasympathetic systems. Thus, how cardiac function is regulated during the trigeminal reflexes is the result of the combination of an increased parasympathetic response and increased, decreased, or unaltered sympathetic activity. Various hemodynamic changes occur as a consequence of these alterations in autonomic tone. Often in the oxygen-conserving physiological reflexes such as the diving reflex, sympathetic/parasympathetic co-activation reduces the heart rate and either maintains or increases blood pressure. Conversely, in the trigeminocardiac reflex, bradycardia and hypotension due to parasympathetic activation and sympathetic inactivation tend to be observed. These sudden cardiac innervation disturbances may promote the generation of arrhythmias or myocardial ischemia during surgeries in the trigeminal territory. However, the function and mechanisms involved in the trigeminal reflexes remain to be fully elucidated. The current review provides a brief update and analysis of the features of these reflexes, with special focus on how the autonomic nervous system interacts with cardiovascular function.


Nitroxyl (HNO) suppresses vascular Nox2 oxidase activity.
Nox2 oxidase activity underlies the oxidative stress and vascular dysfunction associated with several vascular-related diseases. We have reported that nitric oxide (NO) decreases reactive oxygen species production by endothelial Nox2. This study tested the hypothesis that nitroxyl (HNO), the redox sibling of NO, also suppresses vascular Nox2 oxidase activity. Specifically, we examined the influence of two well-characterized HNO donors, Angeli's salt and isopropylamine NONOate (IPA/NO), on Nox2-dependent responses to angiotensin II (reactive oxygen species production and vasoconstriction) in mouse cerebral arteries. Angiotensin II (0.1μmol/L)-stimulated superoxide (measured by lucigenin-enhanced chemiluminescence) and hydrogen peroxide (Amplex red fluorescence) levels in cerebral arteries (pooled basilar and middle cerebral (MCA)) from wild-type (WT) mice were ~60% lower (P<0.05) in the presence of either Angeli's salt (1μmol/L) or IPA/NO (1μmol/L). Similarly, phorbyl 12,13-dibutyrate (10μmol/L; Nox2 activator)-stimulated hydrogen peroxide levels were ~40% lower in the presence of IPA/NO (1μmol/L; P<0.05). The ability of IPA/NO to decrease superoxide levels was reversible and abolished by the HNO scavenger l-cysteine (3mmol/L; P<0.05), but was unaffected by hydroxocobalamin (100μmol/L; NO scavenger), ODQ (10μmol/L; soluble guanylyl cyclase (sGC) inhibitor), or Rp-8-pCPT-cGMPS (10μmol/L; cyclic guanosine monophosphate (cGMP)-dependent protein kinase inhibitor). Angiotensin II-stimulated superoxide was substantially less in arteries from Nox2-deficient (Nox2(-/y)) versus WT mice (P<0.05). In contrast to WT, IPA/NO (1μmol/L) had no effect on superoxide levels in arteries from Nox2(-/y) mice. Finally, angiotensin II (1-1000μmol/L)-induced constriction of WT MCA was virtually abolished by IPA/NO (1μmol/L), whereas constrictor responses to either the thromboxane A2 mimetic U46619 (1-100 nmol/L) or high potassium (122.7mmol/L) were unaffected. In conclusion, HNO suppresses vascular Nox2 oxidase activity via a sGC-cGMP-independent pathway. Thus, HNO donors might be useful therapeutic agents to limit and/or prevent Nox2-dependent vascular dysfunction.


Detection of metallo-beta-lactamase producing Pseudomonas aeruginosa in intensive care units.
Metallo-beta-lactamase (MBL) producing Pseudomonas aeruginosa has emerged as a threat to hospital infection control, due to its multi-drug resistance, especially in intensive care units (ICUs). This study was carried out to detect MBL producing P. aeruginosa isolates from medical and surgical ICUs, to compare and evaluate different phenotypic methods currently in use and to determine antibiograms. A prospective study was undertaken to detect MBLs in P. aeruginosa isolates obtained from various clinical samples. A total of 49 strains were recovered from patients admitted in inpatient wards and ICUs, and screened for imipenem resistance by Kirby Bauer disk diffusion method. Detection of MBLs was further done by imipenem-EDTA disk synergy test and combined disk test. Out of 49 isolates, 11 isolates (22.4 per cent) were imipenem resistant. All 11 imipenem resistant P. aeruginosa strains, when further tested, were positive for MBL production by combined disk test, but, only eight showed positive results by imipenem-EDTA disk synergy test. MBL production was the main resistance mechanism in the 11 carbapenem resistant P. aeruginosa isolates collected, with multidrug resistance associating significantly with MBL production in P. aeruginosa from our institution.


Experimental and human brain neoplasms: detection with in vivo sodium MR imaging.
Elevations of intracellular sodium concentration have been observed in rapidly proliferating cells and malignant neoplasms. Sodium magnetic resonance (MR) imaging (with repetition times of 133 msec and echo times of 13, 26, 39, and 42 msec) was performed in ten patients and three dogs with central nervous system neoplasms. In all instances the neoplasms were associated with an increased sodium signal compared with that of normal brain. Unfortunately, the available echo times did not enable discrimination of intracellular sodium from extracellular sodium, which was present in high concentrations in adjacent vasogenic edema fluid. Further study is necessary to establish the utility of sodium MR imaging for the investigation of malignant neoplasms.


New sensor allowing continuous water activity measurement of submerged or solid-substrate fermentations.
Water activity of the substrate is an important and acute factor for growth as well as for metabolic production of microorganisms or for biocatalyst systems. A sensor has been designed in order to control this parameter on-line during submerged and solid-substrate fermentations. This sterilizable sensor allows the measurement of the relative humidity of the atmosphere in a small chamber by means of a capacitive element separated from the medium by a thin ethylenepolytetrafluoride membrane. For high a(w) values (>0.90) a sequential circulation of a dried gas prevents the sensor saturation. Measurements are rapid and accurate, and control of the water activity of a fermentation medium has been carried out for 5 days using this sensor.


Y-chromosome DNA haplotype XI in Eastern Europe.
Haplotype XI frequencies at the Y-chromosome-specific DNA polymorphism (p49-TaqI) were reported in 639 males originating from 13 different geographic locations in Eastern Europe, where haplotype XI represents the major haplotype. The highest frequencies were obtained from Ukraine (44%), Russia (43.9%), and Hungary (40.7%). Percentages of haplotype XI geographic distribution show a gradient of decreasing frequency from these areas of higher percentages toward southeastern and more western countries in Europe.


Association of pain in knee osteoarthritis with distinct patterns of synovitis.
To determine possible patterns of synovitis on contrast-enhanced magnetic resonance imaging (CE-MRI) and its relation to pain and severity in patients with radiographic knee osteoarthritis (OA). In total, 86 patients (mean age 62 years, 66% women, median body mass index 29 kg/m(2) ) with symptomatic knee OA (Kellgren/Lawrence radiographic score 3) were included. T1-weighted, gadolinium-chelate-enhanced MRI with fat suppression was used to semiquantitatively score the extent of synovitis at 11 knee sites (total score range 0-22). Self-reported pain was assessed with 3 standardized questionnaires. Principal components analysis (PCA) was used to investigate patterns (the location and severity) of synovitis. Subsequently, these patterns were assessed for associations with pain measures and radiographic severity in adjusted logistic regression models. Synovitis was observed in 86 patients and was found to be generally mild on CE-MRI (median total synovitis score 7, range 0-16). The median pain scores were 53 (range 0-96) on the visual analog scale for pain, 51.4 (range 2.8-97.2) on the Knee Injury and Osteoarthritis Outcome Score (KOOS) for pain, 35 (range 0-75) on the Intermittent and Constant Osteoarthritis Pain (ICOAP) score for constant pain, and 40.6 (range 0-87.5) on the ICOAP score for intermittent pain. PCA resulted in extraction of 3 components, explaining 53.4% of the variance. Component 1 was characterized by synovitis at 7 sites (mainly medial parapatellar involvement) and was associated with scores on the KOOS pain subscale and the ICOAP constant pain subscale. Component 2 was characterized by synovitis at 4 sites (mainly the site adjacent to the anterior cruciate ligament), but was not associated with pain measures or with radiographic severity. Component 3, characterized by synovitis at 3 sites (mainly at the loose body site), was associated with radiographic severity. Different patterns of synovitis in knee OA were observed. The pattern that included several patellar sites was associated with pain, whereas other patterns showed no association, suggesting that pain perception in patients with knee OA is a localized response.


A Fluorogenic Far Red-Emitting Molecular Viscometer for Ascertaining Lysosomal Stress in Live Cells and Caenorhabditis elegans.
The cellular physiochemical properties such as polarity, viscosity, and pH play a critical role in cellular homeostasis. The dynamic change of lysosomal viscosity in live cells associated with different environmental stress remains enigmatic and needs to be explored. We have developed a new class of Julolidine-based molecular viscometers with an extended π-conjugation to probe the lysosomal viscosity in live cells. High biocompatibility, pH tolerance, and the fluorogenic response with far red-emission (>600 nm) properties make these molecular viscometers suitable for live-cell fluorescence imaging in Caenorhabditis elegans. Among these probes, JIND-Mor is specifically designed to target lysosomes via simple modification. The real-time monitoring of lysosomal viscosity change under cellular stress was achieved. We believe that such a class of molecule viscometers has the potential to monitor lysosomal health in pathogenic conditions.


Effect of traditional Chinese cooking methods on fatty acid profiles of vegetable oils.
The effect of four frying processes (vegetable salad, stir frying, pan frying, and deep frying) on fatty acid composition of ten vegetable oils (peanut oil, soybean oil, rapeseed oil, corn oil, sunflower seed oil, rice bran oil, olive oil, sesame oil, linseed oil, and peony seed oil) was investigated using GC-MS. The result showed that trans-fatty acid (TFA) was produced during all processes. Rapeseed oil had the highest TFA content in vegetable salad oil with 2.88% of total fatty acid. The TFA content of sunflower seed oil was 0.00% in vegetable salad oil, however, after stir frying and pan frying, it increased to 1.53% and 1.29%, respectively. Peanut oil had the lowest TFA content after deep frying for 12h with 0.74mg/g. It was concluded that a healthy cooking process could be acquired by a scientific collocation.


Evidence that specific oligosaccharides block early events necessary for the expression of antigen-specific proliferation by human lymphocytes.
We have previously shown that monosaccharides and disaccharides will block the expression of spontneous monocyte-mediated cytotoxicity. Our data were consistent with the hypothesis that human mononuclear cells express lectin-like receptors that are capable of binding to a variety sugar moieties found on target cell membranes. In this communication, we will present evidence that monosaccharides and disaccharides are also capable of blocking the expression of T cell reactivity as measured by an in vitro antigen-specific proliferative assay. The majority of sugars that blocked monocyte-mediated cytotoxicity had no effect on antigen-specific proliferation. Those sugars that did suppress antigen-induced proliferation had no effect on PHA-induced proliferation. Furthermore, some of these sugars only inhibited if they were added at the initiation of the assay; they failed to inhibit if added 24 hr after the initiation of the assay. Antigen-pulsing experiments suggested that these sugars did not block antigen uptake by human monocytes. These data suggest that a variety of cellular interactions may be mediated by receptors with specificity for simple sugars. The ability to block these naturally occurring lectins specifically both in vitro and in vivo may prove to be a powerful tool for dissecting out various forms of cellular recognition and collaboration.


Universal scaling of higher-order spacing ratios in Gaussian random matrices.
Higher-order spacing ratios are investigated analytically using a Wigner-like surmise for Gaussian ensembles of random matrices. For a kth order spacing ratio (r^{(k)},k>1) the matrix of dimension 2k+1 is considered. A universal scaling relation for this ratio, known from earlier numerical studies, is proved in the asymptotic limits of r^{(k)}→0 and r^{(k)}→∞.


The resolution of acyclic P-stereogenic phosphine oxides via the formation of diastereomeric complexes: A case study on ethyl-(2-methylphenyl)-phenylphosphine oxide.
As an example of acyclic P-chiral phosphine oxides, the resolution of ethyl-(2-methylphenyl)-phenylphosphine oxide was elaborated with TADDOL derivatives, or with calcium salts of the tartaric acid derivatives. Besides the study on the resolving agents, several purification methods were developed in order to prepare enantiopure ethyl-(2-methylphenyl)-phenylphosphine oxide. It was found that the title phosphine oxide is a racemic crystal-forming compound, and the recrystallization of the enantiomeric mixtures could be used for the preparation of pure enantiomers. According to our best method, the (R)-ethyl-(2-methylphenyl)-phenylphosphine oxide could be obtained with an enantiomeric excess of 99% and in a yield of 47%. Complete racemization of the enantiomerically enriched phosphine oxide could be accomplished via the formation of a chlorophosphonium salt. Characterization of the crystal structures of the enantiopure phosphine oxide was complemented with that of the diastereomeric intermediate. X-ray analysis revealed the main nonbonding interactions responsible for enantiomeric recognition.


Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects.
Temporal lobe epilepsy is a common, chronic neurological disorder characterized by recurrent spontaneous seizures. MicroRNAs (miRNAs) are small, noncoding RNAs that regulate post-transcriptional expression of protein-coding mRNAs, which may have key roles in the pathogenesis of neurological disorders. In experimental models of prolonged, injurious seizures (status epilepticus) and in human epilepsy, we found upregulation of miR-134, a brain-specific, activity-regulated miRNA that has been implicated in the control of dendritic spine morphology. Silencing of miR-134 expression in vivo using antagomirs reduced hippocampal CA3 pyramidal neuron dendrite spine density by 21% and rendered mice refractory to seizures and hippocampal injury caused by status epilepticus. Depletion of miR-134 after status epilepticus in mice reduced the later occurrence of spontaneous seizures by over 90% and mitigated the attendant pathological features of temporal lobe epilepsy. Thus, silencing miR-134 exerts prolonged seizure-suppressant and neuroprotective actions; determining whether these are anticonvulsant effects or are truly antiepileptogenic effects requires additional experimentation.


Bone Marrow-Derived CD4+ T Cells Are Depleted in Simian Immunodeficiency Virus-Infected Macaques and Contribute to the Size of the Replication-Competent Reservoir.
The bone marrow (BM) is the key anatomic site for hematopoiesis and plays a significant role in the homeostasis of mature T cells. However, very little is known on the phenotype of BM-derived CD4+ T cells, their fate during simian immunodeficiency virus (SIV) infection, and their contribution to viral persistence during antiretroviral therapy (ART). In this study, we characterized the immunologic and virologic status of BM-derived CD4+ T cells in rhesus macaques prior to SIV infection, during the early chronic phase of infection, and during ART. We found that BM memory CD4+ T cells are significantly depleted following SIV infection, at levels that are similar to those measured in the peripheral blood (PB). In addition, BM-derived memory CD4+ T cells include a high frequency of cells that express the coinhibitory receptors CTLA-4 and PD-1, two subsets previously shown to be enriched in the viral reservoir; these cells express Ki-67 at levels similar to or higher than the same cells in PB. Finally, when we analyzed SIV-infected RMs in which viral replication was effectively suppressed by 12 months of ART, we found that BM CD4+ T cells harbor SIV DNA and SIV RNA at levels comparable to those of PB CD4+ T cells, including replication-competent SIV. Thus, BM is a largely understudied anatomic site of the latent reservoir which contributes to viral persistence during ART and needs to be further characterized and targeted when designing therapies for a functional or sterilizing cure to HIV.IMPORTANCE The latent viral reservoir is one of the major obstacles in purging the immune system of HIV. It is paramount that we elucidate which anatomic compartments harbor replication-competent virus, which upon ART interruption results in viral rebound and pathogenesis. In this study, using the rhesus macaque model of SIV infection and ART, we examined the immunologic status of the BM and its role as a potential sanctuary for latent virus. We found that the BM compartment undergoes a similar depletion of memory CD4+ T cells as PB, and during ART treatment the BM-derived memory CD4+ T cells contain high levels of cells expressing CTLA-4 and PD-1, as well as amounts of cell-associated SIV DNA, SIV RNA, and replication-competent virus comparable to those in PB. These results enrich our understanding of which anatomic compartments harbor replication virus and suggest that BM-derived CD4+ T cells need to be targeted by therapeutic strategies aimed at achieving an HIV cure.


Electrophysiological evaluation of the Wolff-Parkinson-White syndrome: problems in assessing antegrade and retrograde conduction over the accessory pathway.
The effect of atrial pacing and recording site and ventricular pacing site on assessment of conduction over the accessory pathway (AP) was examined in a group of patients with the Wolff-Parkinson-White syndrome. The importance of initial localization of the AP by recording the sequence of retrograde atrial activation during circus movement tachycardia is demonstrated. Inability to record or pace near the AP may lead to significant errors in the assessment of the antegrade and retograde conduction properties of the AP. During ventricular pacing, retrograde atrial fusion was consistently demonstrated with laterally located APs.


Cellular effects of heavy charged particles.
The human cell is rendered reproductively inactive by the passage of a single heavy ion through its nucleus when the heavy ion deposits energy at a rate greater than about 3500 MeV cm-1. This is demonstrated by the correlation of inactivation probability with nuclear area when cells having nuclei of different sizes are compared. This single-hit inactivation is irreversible and unmodifiable. The ion path length over which cells will be inactivated in this way is calculable from stopping power theory. Laboratory experiments in which three-dimensional human cell cultures were irradiated with high-energy nitrogen ions (3.9 GeV) at the Princeton Particle Accelerator confirm that cells are inactivated with maximum probability over the last 0.5 cm of the ion trajectory. This means that groups of adjacent cells in the ion path will be inactivated by a single ion with high probability. Organized systems of multiplying cells would be expected to amplify this spatially correlated effect of heavy ion irradiation. Abnormalities induced in Zea seedlings by heavy ion irradiation of seeds are consistent with the inactivation of embryonic cells in groups.


The Herpesvirus saimiri replication and transcription activator acts synergistically with CCAAT enhancer binding protein alpha to activate the DNA polymerase promoter.
The open reading frame (ORF) 50 gene product, also known as the replication and transcription activator (Rta), is an immediate-early gene which is well conserved among all gamma-2 herpesviruses and plays a pivotal role in regulating the latent-lytic switch. Herpesvirus saimiri (HVS) ORF 50a functions as a sequence-specific transactivator capable of activating delayed-early (DE) gene expression via binding directly to an ORF 50 response element (RE) within the respective promoter. Analysis of the ORF 50 REs have identified two distinct types within HVS gene promoters. The first comprises a consensus sequence motif, CCN(9)GG, the second an AT-rich sequence. Here we demonstrate that ORF 50a is capable of transactivating the DE ORF 9 promoter which encodes the DNA polymerase. Deletion analysis of the ORF 9 promoter mapped the ORF 50 RE to a 95-bp region situated 126 bp upstream of the initiation codon. Gel retardation analysis further mapped the RE to a 28-bp fragment, which was able to confer ORF 50 responsiveness on an enhancerless simian virus 40 minimal promoter. Furthermore, sequence analysis identified multiple CCAAT enhancer binding protein alpha (C/EBPalpha) binding sites within the ORF 9 promoter and specifically two within the close vicinity of the AT-rich ORF 50 RE. Analysis demonstrated that the HVS ORF 50a and C/EBPalpha proteins associate with the ORF 9 promoter in vivo, interact directly, and synergistically activate the ORF 9 promoter by binding to adjacent binding motifs. Overall, these data suggest a cooperative interaction between HVS ORF 50a and C/EBPalpha proteins to activate the DNA polymerase promoter during early stages of the lytic replication cycle.


Evaluation of integral membrane antigens of Mycobacterium habana for serodiagnosis of extrapulmonary tuberculosis: association between levels of antibodies and Mycobacterium tuberculosis antigens.
The performance of integral membrane antigens (IMAs) of Mycobacterium habana TMC 5135 in detecting antimycobacterial antibodies in serum and body fluids of patients mainly of extrapulmonary tuberculosis was evaluated. The IMAs were recovered from the detergent phase during Triton X-114 treatment of the plasma membrane of M. habana. Antimycobacterial antibodies were detected by ELISA using IMAs in serum and body fluids of 42 patients and 62 control subjects. As authentic adjunct Mycobacterium tuberculosis antigens were also detected (by ELISA) in body fluids and circulating immune complexes using anti-M. tuberculosis H37Ra antibodies. Anti-M. habana IMA antibody detection increased the positivity rate from 26.% (11/42) and 10% (4/42) obtained by culture and smear microscopy, respectively, to 86% (36/42). M. tuberculosis antigens were also found in 29 out of 36 anti-M. habana IMA antibody-positive cases. Interestingly, all 11 culture-positive cases were also positive for anti-M. habana IMA antibodies. The mean antigen titres in 23 cases, positive for antigens in body fluids, were 2.34 times higher in those who were also positive for anti-IMA antibodies in serum than in those negative for these antibodies. M. habana IMAs may be promising non-tubercular candidate antigens in ELISA-based serodiagnosis of extrapulmonary tuberculosis with substantial sensitivity, specificity and safety.


[Umbilical cord blood as a source of nerve and stem cells].
The aim of the study was to assess proliferative ability of the stem cells in the umbilical cord blood and their potential to differentiate in in vitro culture. The material consisted of 14 samples of umbilical cord blood collected from the umbilical cord vein. Mononuclear cells were isolated using the method of density gradient medium. Next, CD34 cells were isolated from the interphase with the use of the VarioMACS sorter and anti-CD34 antibodies. Long-term cultures were conducted on Iscove's modified Dulbecco medium (IMDM) with addition of granulocyte-macrophage colony stimulating factor (GM-CSF) and nerve growth factor (NGF). Qualitative identification was performed using the May-Grunwald-Giemsy staining method, taking photographs with a confocal microscope, and with the immunoenzymatic method. In our research, CD34+ stem cells constituted 1.16% of the mononuclear cells, and after centrifugation in medium 0.37% of leukocytes in whole umbilical cord blood. Even after 60 days of culture without addition of the growth factors, CD34+ cells were present in the fraction of adherent cells. After stimulation with GM-CSF and NGF a part of the umbilical cord blood cells were transformed into nerve cells (presence of neuron-specific enolase was shown) and into cells morphologically similar to fibroblast and dendritic cells. After stimulation with GM-CSF and NGF cytokines, the umbilical cord blood cells proliferate in long-term medium, transform into nerve cells and into cells similar to fibroblast and dendritic cells.


Pulse-spray thrombolysis in acute myocardial infarction caused by thrombotic occlusion of an ectatic coronary artery.
Pulse-spray thrombolysis was performed in 2 patients with acute myocardial infarction (AMI) caused by thrombotic occlusion of coronary artery ectasia. Case 1, a 66-year-old woman with an inferior AMI underwent emergency coronary arteriography, which revealed occlusion of an ectatic right coronary artery. Primary balloon angioplasty failed to reestablish distal flow. Urokinase was administered through the pulse-spray infusion catheter (UltraFuse) and intravenous recombinant tissue plasminogen activator was also administered. Angiographic disappearance of the thrombus was observed within 30 min of starting the infusion, and there was only mild irregularity in the ectatic coronary artery. Case 2, a 45-year-old man with an inferior AMI underwent emergency coronary arteriography, which revealed occlusion of an ectatic right coronary artery. TIMI-3 flow was soon obtained after administration of 480,000 units of urokinase through the pulse-spray infusion catheter. There was diffuse right coronary ectasia without angiographic evidence of coronary stenosis. Coronary ectasia sometimes develops into AMI without the coexistence of coronary stenosis. Because a massive thrombus plays a major role, pulse-spray thrombolysis is a possible treatment in coronary artery ectasia with thrombotic occlusion.


Leasing or Selling? Durable Goods Manufacturer Marketing Model Selection under a Mixed Carbon Trading-and-Tax Policy Scenario.
Many carbon reduction policies have been implemented to reduce carbon dioxide in the manufacturing process of products. However, many products emit more carbon dioxide in the consumption process. From the consumer's utility perspective, this paper firstly analyses the manufacturing and marketing model selection decisions of a monopoly manufacturer under the mixed carbon policy, and then a win-win result that can encourage the manufacturer to choose the marketing model with lower carbon emissions while at the same time obtaining the optimal profit is discussed. The results show that the production activity will proceed only when the carbon trading price is lower than a certain threshold. When the carbon trading price is lower than a certain threshold, leasing represents the manufacturer's optimal marketing model. When the carbon trading price is higher than the threshold, selling represents the manufacturer's optimal marketing model. For the carbon cap Q, there are equilibrium intervals in which the government can achieve the aim of controlling carbon emissions, while not overly affecting the manufacturer's enthusiasm for production. For the carbon trading price and the carbon tax rate, there are two different intervals in which leasing gains more profit for the manufacturer while emitting lower carbon emissions.


The assessment of array comparative genomic hybridization in complex karyotype analyses.
Molecular-cytogenetic methods were used to analyse and specify complex genome rearrangements in malignant cells. Twelve samples of bone marrow cells were collected from patients with myelodysplastic syndromes (MDS). The complex karyotypes were examined by multicolour fluorescence in situ hybridization (mFISH), high-resolution multicolour banding (mBAND) and array comparative genomic hybridization (aCGH). For aCGH, DNA was isolated from fixed bone marrow cells in methanol and acetic acid and amplified by whole-genome amplification. Three samples were analysed by the oligonucleotide array NimbleGen on the basis of full service. BAC-based Haematochips (BlueGnome) were used for the other nine samples. Sensitivity and detection limits of both methods were compared. The results obtained by mFISH/mBAND were in most cases confirmed by the microarray technique. aCGH detected 43 unbalanced chromosomal changes that were also identified by classical cytogenetics and FISH. Moreover, aCGH discovered 14 additional changes. Cryptic amplifications and deletions were characterized with a resolution of 0.5 Mb. In one bone marrow sample with suspected monosomy 5 detected by conventional cytogenetic analysis, aCGH revealed a 22.3 Mb region of chromosome 5 inserted in another autosome within the complex karyotype. Amplified DNA was successfully used for aCGH in 11 out of 12 cases, improving resolution of unbalanced chromosomal aberrations. The combination of both approaches brought more detailed description of complex karyotypes and is highly recommended.


Evaluation of the Combined Effect of Recombinant High-Density Lipoprotein Carrier and the Encapsulated Lovastatin in RAW264.7 Macrophage Cells Based on the Median-Effect Principle.
Recombinant high-density lipoprotein (rHDL) displays a similar anti-atherosclerotic effect with native HDL and could also be served as a carrier of cardiovascular drug for atherosclerotic plaque targeting. In our previous studies, rHDL has shown a more potent anti-atherosclerotic efficacy as compared to the other conventional nanoparticles with a payload of lovastatin (LS). Therefore, we hypothesized that a synergistic anti-atherosclerotic effect of the rHDL carrier and the encapsulated LS might exist. In this study, the dose-effect relationships and the combined effect of the rHDL and LS were quantitatively evaluated in RAW 264.7 macrophage cells using the median-effect analysis, in which the rHDL carrier was regarded as a drug combined. Median-effect analysis suggested that rHDL and LS exerted a desirable synergistic inhibition on the oxLDL internalization at a ratio of 6:1 ( Dm,LS: Dm,rHDL) in RAW 264.7 macrophage cells. About 50% of the reduction on the intracellular lipid contents was found when RAW264.7 cells were treated with LS-loaded rHDLs at their respective median-effect dose ( Dm) concentrations and a synergistic effect on the mediating cholesterol efflux was also observed, which verified the accuracy of the results obtained from the median-effect analysis. The mechanism underlying the synergistic effect of the rHDL carrier and the drug might be attributed to their potent inhibitory effects on SR-A expression. In conclusion, the median-effect analysis was proven to be a feasible method to quantitatively evaluate the synergistic effect of the biofunctional carrier and the drug encapsulated.


Lack of degradation in visuospatial perception of line orientation after one night of sleep loss.
Sleep deprivation impairs a variety of cognitive abilities including vigilance, attention, and executive function. Although sleep loss has been shown to impair tasks requiring visual attention and spatial perception, it is not clear whether these deficits are exclusively a function of reduced attention and vigilance or if there are also alterations in visuospatial perception. Visuospatial perception and sustained vigilance performance were therefore examined in 54 healthy volunteers at rested baseline and again after one night of sleep deprivation using the Judgment of Line Orientation Test and a computerized test of psychomotor vigilance. Whereas psychomotor vigilance declined significantly from baseline to sleep-deprived testing, scores on the Judgment of Line Orientation did not change significantly. Results suggest that documented performance deficits associated with sleep loss are unlikely to be the result of dysfunction within systems of the brain responsible for simple visuospatial perception and processing of line angles.


Identification and characterization of glycosyltransferases involved in the biosynthesis of soyasaponin I in Glycine max.
Triterpene saponins are a diverse group of compounds with a structure consisting of a triterpene aglycone and sugars. Identification of the sugar-transferase involved in triterpene saponin biosynthesis is difficult due to the structural complexity of triterpene saponin. Two glycosyltransferases from Glycine max, designated as GmSGT2 and GmSGT3, were identified and characterized. In vitro analysis revealed that GmSGT2 transfers a galactosyl group from UDP-galactose to soyasapogenol B monoglucuronide, and that GmSGT3 transfers a rhamnosyl group from UDP-rhamnose to soyasaponin III. These results suggest that soyasaponin I is biosynthesized from soyasapogenol B by successive sugar transfer reactions.


Iron and virulence in the family Enterobacteriaceae.
The ability of bacterial pathogens to acquire iron in the host is an essential component of the disease process. Pathogenic Enterobacteriaceae spp. may either scavenge host iron sources such as heme or induce high-affinity iron-transport systems to remove iron from host proteins. The ease with which iron is acquired from the host will be at least partially determined by the iron status of the host at the time of infection. In response to infection, mammalian hosts reduce serum iron levels and withhold iron from the invading microorganisms. Thus the competition for iron is an active process which influences the outcome of a host-bacterial interaction.


Isotype specific ELISAs to detect antibodies against swine vesicular disease virus and their use in epidemiology.
Isotype specific ELISAs to detect antibodies against swine vesicular disease, which may help to estimate the moment of infection, were developed and validated on sera from pigs experimentally infected with four different isolates of swine vesicular disease virus. Virus specific IgM antibodies could be detected from days 3-49 and occasionally up to day 91 after infection. IgG1 antibodies were first detected at day 8 and IgG2 at day 11. IgA antibodies coincided with IgG1 antibodies, but antibody titres varied widely. From the results obtained with the sera from the experimentally infected pigs, we calculated the day at which 50% of the pigs had become positive (D50). A D50 of 5, 4, 12, 12 and 24 days was calculated, respectively, for the appearance of antibodies in the virus neutralization test, the IgM, total IgG, IgG1 and IgG2 ELISA. A D50 of 49 days was calculated for the disappearance of IgM antibodies. The isotype specific ELISAs proved to be valuable tools to study the epidemiology of the disease.


Low energy levels in thiamine-deficient encephalopathy.
Pyrithiamine-induced acute thiamine-deficient encephalopathy was produced in adult male Wistar rats. Twenty-four hours before the onset of neurological signs the brain showed no morphological abnormalities. Encephalopathic rats had symmetrical lesions of edematous necrosis localized in the thalamus, mammillary body, and pontine tegmentum. Biochemically, encephalopathic rats had brain thiamine levels less than 20% of controls. For the assay of the concentrations of adenosine triphosphate (ATP) and phosphocreatine, the brains were fixed using 5 KW microwave irradiation and were divided into four parts: cerebral cortex, diencephalon, lower brainstem, and cerebellum. In the lower brainstem of the encephalopathic rats ATP concentrations were 89.5% of normal controls. Phosphocreatine levels were lowered to 70% of controls in the diencephalon and to 75% in the lower brainstem. Total high energy phosphate levels were decreased to 89% of controls in the diencephalon and 91% in the lower brainstem before the onset of neurological signs and to 76% and 79%, respectively, after the onset. In the cerebral cortex and cerebellum high energy phosphates were not significantly reduced. Lower high energy phosphate levels and the distribution of edematous lesions were coincident in the brain. These findings suggest that a low energy state is closely related to the formation of edematous lesions in thiamine-deficient encephalopathy.


An Improved Method for Accurate Radiation Measurement Based on Dark Output Noise Drift Compensation.
This paper verified through experiments that change in ambient temperature are the main cause of dark output noise drift. Additionally, the impact of dark output noise drift in fiber optic spectrometers on emissivity measurements has been investigated in this work. Based on an improved fiber optic spectrometer, two methods were proposed for characterizing and correcting the dark output noise offset in fiber optic spectrometers: the mean correction scheme and the linear fitting correction scheme. Compared to the mean correction scheme, the linear fitting correction scheme is more effective in solving the problem of dark output noise drift. When the wavelength is greater than 1600 nm, the calibration relative error of silicon carbide (SIC) emissivity is less than 0.8% by the mean correction scheme, while the calibration relative error of silicon carbide emissivity is less than 0.62% by the linear fitting correction scheme. This work solves the problem of dark output noise drift in prolonged measurement based on fiber optic spectrometers, improving the accuracy and reliability of emissivity and quantitative radiation measurement.


Curriculum considerations for correlating basic and clinical sciences.
An analysis of the problem of curriculum design for correlating basic and clinical sciences is presented. The analysis identifies six ways a dentist can profit from the basic sciences: (1) increased sensitivity to the environment, (2) improved judgement, (3) better explanations to patients, (4) enhanced ability to learn, (5) improved communication with health professionals, and (6) greater role diversity. Literature is reviewed related to four mental processes underlying functional knowledge: attending, associating with past learning, relation to future situations, and practicing mental applications. Implications are made for the design of dental curricula and instructional techniques based on factors that influence the recall and use of knowledge.