Miracle-dz/UniFAR-FTUs huggingface dataset:
Dual Role of Topoisomerase II in Centromere Resolution and Aurora B Activity

Chromosome segregation requires sister chromatid resolution. Condensins are essential for this process since they organize an axial structure where topoisomerase II can work. How sister chromatid separation is coordinated with chromosome condensation and decatenation activity remains unknown. We combined four-dimensional (4D) microscopy, RNA interference (RNAi), and biochemical analyses to show that topoisomerase II plays an essential role in this process. Either depletion of topoisomerase II or exposure to specific anti-topoisomerase II inhibitors causes centromere nondisjunction, associated with syntelic chromosome attachments. However, cells degrade cohesins and timely exit mitosis after satisfying the spindle assembly checkpoint. Moreover, in topoisomerase II–depleted cells, Aurora B and INCENP fail to transfer to the central spindle in late mitosis and remain tightly associated with centromeres of nondisjoined sister chromatids. Also, in topoisomerase II–depleted cells, Aurora B shows significantly reduced kinase activity both in S2 and HeLa cells. Codepletion of BubR1 in S2 cells restores Aurora B kinase activity, and consequently, most syntelic attachments are released. Taken together, our results support that topoisomerase II ensures proper sister chromatid separation through a direct role in centromere resolution and prevents incorrect microtubule–kinetochore attachments by allowing proper activation of Aurora B kinase.
Race and Time from Diagnosis to Radical Prostatectomy: Does Equal Access Mean Equal Timely Access to the Operating Room?—Results from the SEARCH Database

Background: African American men with prostate cancer are at higher risk for cancer-specific death than Caucasian men. We determine whether significant delays in management contribute to this disparity. We hypothesize that in an equal-access health care system, time interval from diagnosis to treatment would not differ by race. Methods: We identified 1,532 African American and Caucasian men who underwent radical prostatectomy (RP) from 1988 to 2007 at one of four Veterans Affairs Medical Centers that comprise the Shared Equal-Access Regional Cancer Hospital (SEARCH) database with known biopsy date. We compared time from biopsy to RP between racial groups using linear regression adjusting for demographic and clinical variables. We analyzed risk of potential clinically relevant delays by determining odds of delays >90 and >180 days. Results: Median time interval from diagnosis to RP was 76 and 68 days for African Americans and Caucasian men, respectively (P = 0.004). After controlling for demographic and clinical variables, race was not associated with the time interval between diagnosis and RP (P = 0.09). Furthermore, race was not associated with increased risk of delays >90 (P = 0.45) or >180 days (P = 0.31). Conclusions: In a cohort of men undergoing RP in an equal-access setting, there was no significant difference between racial groups with regard to time interval from diagnosis to RP. Thus, equal-access includes equal timely access to the operating room. Given our previous finding of poorer outcomes among African Americans, treatment delays do not seem to explain these observations. Our findings need to be confirmed in patients electing other treatment modalities and in other practice settings. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1208–12)
Ssy1p and Ptr3p Are Plasma Membrane Components of a Yeast System That Senses Extracellular Amino Acids

ABSTRACT Mutations in SSY1 and PTR3 were identified in a genetic selection for components required for the proper uptake and compartmentalization of histidine in Saccharomyces cerevisiae. Ssy1p is a unique member of the amino acid permease gene family, and Ptr3p is predicted to be a hydrophilic protein that lacks known functional homologs. Both Ssy1p and Ptr3p have previously been implicated in relaying signals regarding the presence of extracellular amino acids. We have found that ssy1 andptr3 mutants belong to the same epistasis group; single andssy1 ptr3 double-mutant strains exhibit indistinguishable phenotypes. Mutations in these genes cause the nitrogen-regulated general amino acid permease gene (GAP1) to be abnormally expressed and block the nonspecific induction of arginase (CAR1) and the peptide transporter (PTR2). ssy1 and ptr3 mutations manifest identical differential effects on the functional expression of multiple specific amino acid transporters. ssy1 and ptr3 mutants have increased vacuolar pools of histidine and arginine and exhibit altered cell growth morphologies accompanied by exaggerated invasive growth. Subcellular fractionation experiments reveal that both Ssy1p and Ptr3p are localized to the plasma membrane (PM). Ssy1p requires the endoplasmic reticulum protein Shr3p, the amino acid permease-specific packaging chaperonin, to reach the PM, whereas Ptr3p does not. These findings suggest that Ssy1p and Ptr3p function in the PM as components of a sensor of extracellular amino acids.
Development of oculomotor axon projections in the chick embryo

The pattern of innervation of the extraocular muscles is highly conserved across higher vertebrate species and mediates sophisticated visuomotor processes. Defects in oculomotor development often lead to strabismus, a misalignment of the eyes that can cause partial blindness. Although it has been intensively studied from a clinical perspective, relatively little is known about how the system develops embryonically. We have therefore mapped the development of the oculomotor nerve (OMN) in chick embryos by using confocal microscopy. We show that OMN development follows a series of stereotyped steps that are tightly regulated in space and time. The OMN initially grows past three of its targets to innervate its distal target, the ventral oblique muscle, only later forming branches to the more proximal muscles. We have also investigated spatiotemporal aspects of the unusual contralateral migration of a subpopulation of oculomotor neurons by using molecular markers and have found the semaphorin axon guidance molecules and their receptors, the neuropilins, to be expressed in discrete subnuclei during this migration. Finally, we have created an embryological model of Duane retraction syndrome (DRS), a form of strabismus in which the OMN is believed to innervate aberrantly the lateral rectus, the normal target of the abducens nerve. By ablating rhombomeres 5 and 6 and hence the abducens, we have mimicked a proposed oculomotor deficit occurring in DRS. We find that the absence of the abducens nerve is not sufficient to produce this inappropriate innervation, so other factors are required to explain DRS. J. Comp. Neurol. 472:308–317, 2004. © 2004 Wiley‐Liss, Inc.
Internationalisation of publicly traded family firms: a transaction cost theory perspective and longitudinal analysis

There has been a prominent stream of research investigating internationalisation of organisations. While the importance of transaction costs in the governance decisions of firms has been well established in the literature, transaction cost theory (TCT) in family firms remains underutilised. We examine the impact of family governance (i.e. family ownership and involvement in management and the board of directors) on internationalisation within the domain of TCT using 386 S%P 500 firms. Our findings indicate an inverted U-shaped relationship between family ownership and internationalisation and a U-shaped relationship between family's involvement in management and the board and internationalisation. This illustrates the interesting differential impact of the components of family involvement on internationalisation. We conclude by discussing future research and implications for practice.
Predictive Value of Molecular Drug Resistance Testing of Mycobacterium tuberculosis Isolates in Valle del Cauca, Colombia

ABSTRACT Previous evaluations of the molecular GenoType tests have promoted their use to detect resistance to first- and second-line antituberculosis drugs in different geographical regions. However, there are known geographic variations in the mutations associated with drug resistance in Mycobacterium tuberculosis, and especially in South America, there is a paucity of information regarding the frequencies and types of mutations associated with resistance to first- and second-line antituberculosis drugs. We therefore evaluated the performance of the GenoType kits in this region by testing 228 M. tuberculosis isolates in Colombia, including 134 resistant and 94 pansusceptible strains. Overall, the sensitivity and specificity of the GenoType MTBDRplus test ranged from 92 to 96% and 97 to 100%, respectively; the agreement index was optimal (Cohen's kappa, >0.8). The sensitivity of the GenoType MTBDRsl test ranged from 84 to 100% and the specificity from 88 to 100%. The most common mutations were katG S315T1, rpoB S531L, embB M306V, gyrA D94G, and rrs A1401G. Our results reflect the utility of the GenoType tests in Colombia; however, as some discordance still exists between the conventional and molecular approaches in resistance testing, we adhere to the recommendation that the GenoType tests serve as early guides for therapy, followed by phenotypic drug susceptibility testing for all cases.
Improved Inverted Organic Solar Cells With a Sol–Gel Derived Indium-Doped Zinc Oxide Buffer Layer

We studied sol-gel derived indium-doped zinc oxide (IZO) with various indium contents as a functional buffer layer in inverted polymer:fullerene bulk-heterojunction solar cell. The short-circuit current density was observed to increase by doping indium in pure ZnO buffer layer. The maximum current density was obtained with a 1 at. % indium doping. Although the open-circuit voltage and fill factor reduced slightly, the inverted organic solar cell with 1 at. % IZO buffer layer showed a power conversion efficiency of 3.3%, which is higher compared to that (2.94%) of the device with undoped ZnO buffer layer under illumination of AM1.5G. The better performance is due to combined effects of improvement in charge collection and higher optical transmittance of electrode/buffer layer stack.
Should fimbriae be included in pertussis vaccines? Studies on ELISA IgG anti‐Fim2/3 antibodies after vaccination and infection

The anti‐Fim response and long‐term persistence after vaccination and infection may be of importance in understanding population immunity. Longitudinal serum samples (n = 1330) from 542 non‐infected children related to a Swedish vaccine trial showed that the post vaccination (DTPa5) antibody decay curve for pertussis ELISA IgG anti‐fimbriae2/3 (anti‐Fim2/3) was bi‐phasic. A slower one followed an initial rapid decay approximately 5–6 months after the third dose at 12 months of age. After 71 months, however, 60% still had concentrations above ≥5 EU/ml, a level that had been shown to correlate with decreased risk of disease. Booster responses after re‐vaccination with DTPa5 at 4, 5 and 6 years of age were strong and appeared within 1 week after vaccination, indicating immune memory. Ninety‐six young children with verified pertussis infection, for whom we had serum samples both before, during and after the infection, showed a high response if they had been primed with fimbriae (either DTPa5 or DTPwc). In contrast, 76% of infected children not primed with fimbriae (a DTPa2 or DT group) only had concentrations below the minimum level of detection in all samples taken during and after the infection. In two Swedish seroepidemiological surveys, one from 1997 just after reintroduction of universal childhood vaccination against pertussis and one from 2007, the proportion of children 2–3 years with anti‐Fim2/3 concentrations <5 EU/ml was similar and above 90%. This reflects that the two‐ or three‐component pertussis vaccines (DTPa2 and DTPa3) that were introduced in Sweden in 1996 do not induce anti‐Fim2/3 antibodies. In previous studies it was shown in multivariate analyses that levels of IgG anti‐Fim2/3 ≥5 EU/ml reduced short‐term risk of pertussis in small children. As the antibody response to Fim2/3 after infection is poor in children who have not been primed earlier in life, inclusion of immunogenic Fim2/3 in future pertussis vaccines should be considered.
Acute human stroke studied by whole brain echo planar diffusion‐weighted magnetic resonance imaging

Our purpose was to use whole brain echo planar magnetic resonance imaging (MRI) to identify and characterize diffusion abnormalities in acute cerebral ischemia. We studied 40 patients as early as 3 hours after onset of signs and symptoms of cerebral ischemia. Diffusion‐weighted imaging (DWI) of the entire brain could be completed in 3 seconds or, using seven different diffusion sensitivities (maximum b=1,271 sec/2), in 48 seconds. Measurements and synthetic maps were made of apparent diffusion coefficients (ADC), a physiological parameter that characterizes the self‐diffusion of water in tissue. Early ischemic lesions were identified with DWI as hyperintense regions of decreased ADC in all patients who subsequently developed infarction, before changes were evident on conventional MRI in cases studied earlier than 6 hours after onset of ischemic symptoms. Lesions as small as 4 mm in diameter were identified. The extent of lesions within white matter was best defined by controlling for the anisotropic effect of axonal orientation. The mean ADC (± SD) for control regions in the 36 patients was 9.15 (± 2.91) × 10−4 mm2/sec. Mean ADC of ischemic regions was 56% of control values at 6 hours or less and stayed significantly reduced for 3 to 4 days after onset of ischemia. The relative ADC increased progressively over time to be pseudonormalized at 5 to 10 days and elevated in the chronic state, making the distinction of acute lesions adjacent to chronic infarcts readily apparent. DWI with echo planar imaging measures a unique physiological parameter that is sensitive to ischemic changes before conventional MRI. Its potential role in the quantitative study of human stroke pathophysiology and therapeutics is the subject of further investigation.
Human Salivary Sugar Clearance after Sugar Rinses and Intake of Foodstuffs

The aetiology of dental caries is in part related to the retention time of dietary carbohydrates in the oral cavity and their subsequent metabolism by the oral bacteria. Salivary clearance of fermentable carbohydrates from three different foodstuffs was examined in 5 subjects and analyses performed by high–performance anion–exchange chromatography with pulsed amperometric detection. The clearance of glucose, fructose, sucrose, maltose and sorbitol rinses was studied as well as that of chocolate bars, white bread and bananas. Of the sugar rinses studied, sucrose was removed from saliva most rapidly whilst appreciable levels of sorbitol remained even after 1 h. Clearance of residual carbohydrates from bananas and chocolate bars seemed marginally faster than in the case of bread, but sucrose levels still tended to fall more quickly than other carbohydrates studied. Surprisingly, carbohydrate residues from the three foods studied were still present in the mouth even 1 h after ingestion, which is longer than has hitherto been reported.
Teacher Readiness Issues in Implementing School-based Assessment

School-based assessment (SBA) now viewed from a broader perspective. To ensure a quality education that leads to the development of human capital 'first class mentality', the examination system has now been reinforced by expanding the concept to pentaksiran. PBS is a form of assessment practices that are designed, built, managed, checked, recorded and reported systematically by teachers and school authorities. These assessments should follow the procedures established by the Examination Board. Accordingly, the practice assessment conducted by teachers expected to provide accurate and shows the real situation on the level of student learning. This article is a concept paper discussed issues relating to teachers willing to implement practices PBS. This article also highlighted the issue of readiness of teachers as well as its impact on the practice of PBS. Matters discussed in line with the Malaysian Education Blueprint (2013-2025), in the first wave (2013-2025), the Ministry of Education will focus on improving the quality of teaching by improving the quality of teachers and school leaders. The study also put forward some suggestions for the improvement of quality in the implementation of PBS.
In the Name of Managerialism: Reforming Organizations in the Swedish Public Sector

Abstract This paper focuses on the translation of managerialism in the Swedish public sector. A field study of the attempts by two large municipalities to launch a grand reform in the name of managerialism, that is, a purchasersupplier reform, shows the by now familiar difficulties of trying to change public organizations. Thus the actual consequences of actions taken in the name of managerialism are perhaps more complex than is often understood within new public management theory. The concept of translation could be a way of improving this understanding. By using this concept it is possible to grasp the complexity as well as the ambiguity and dynamism of change processes, a task that conventional concepts sometimes fail to fulfill. The overall analysis of the field study is held within the framework of institutional organization theory. By applying the notion of translation, a theoretical link can be constructed between organizational and institutional change.
Unique BK virus non‐coding control region (NCCR) variants in hematopoietic stem cell transplant recipients with and without hemorrhagic cystitis

Hematopoietic stem cell transplant recipients frequently develop BK virus (BKV)‐associated hemorrhagic cystitis, which coincides with BK viruria. However, the precise role of BKV in the etiology of hemorrhagic cystitis in hematopoietic stem cell transplant recipients remains unclear, since approximately 50% of all such adult transplant recipients excrete BKV, yet do not develop this clinical condition. In the present study, BKV were analyzed to determine if mutations in the non‐coding control region (NCCR), and specific BKV sub‐types defined by sequence analysis of major capsid protein VP1, were associated with development of hemorrhagic cystitis in hematopoietic stem cell transplant recipients. The regions encoding VP1 and NCCRs of BKV in urine samples collected from 15 hematopoietic stem cell transplant recipients with hemorrhagic cystitis and 20 without this illness were amplified and sequenced. Sequence variations in the NCCRs of BKV were identified in urine samples from those with and without hemorrhagic cystitis. Furthermore, five unique sequence variations within transcription factor binding sites in the canonical NCCR, O–P–Q–R–S, were identified, representing new BKV variants from a population of cloned quasi‐species obtained from patients with and without hemorrhagic cystitis. Thirty‐five BKV VP1 sequences were analyzed by phylogenetic analysis but no specific BKV sub‐type was associated with hemorrhagic cystitis. Five previously unrecognized naturally occurring variants of the BKV are described which involve amplifications, deletions, and rearrangements of the archetypal BKV NCCRs in individuals with and without hemorrhagic cystitis. Architectural rearrangements in the NCCRs of BKV did not appear to be a prerequisite for development of hemorrhagic cystitis in hematopoietic stem cell transplant recipients. J. Med. Virol. 78:485–493, 2006. © 2006 Wiley‐Liss, Inc.
Influence of dietary quality on the growth of highland and coastal Ecuadorian children

This study examines variation in dietary patterns and its influence on physical growth among children under 60 months of age from rural households of highland and coastal Ecuador. Differences in subsistence ecology between the regions appear to influence infant and early childhood feeding patterns. Coastal children are weaned significantly earlier than their highland counterparts (median ± SE = 15.9 ± 1.7 vs. 24.7 ± 3.4 months) and have a weaning/supplemental diet that contains significantly more animal foods. In both regions, growth retardation is most severe among infants (<12 months), with growth rates being poorer in the highlands than on the coast. Linear growth rates among coastal infants are positively correlated with intakes of animal energy and animal protein, whereas among highland children energy intake from supplemental/weaning foods is negatively correlated with linear growth. These divergent patterns appear to be a consequence of the differences in nutrient density of the weaning/supplemental diets. Among the coastal infants, higher quality, nutrient dense foods augment breast milk and contribute to better growth rates. In contrast, among the highland infants the more filling, less nutrient dense foods appear to be replacing breast milk, and thus compromising growth status. In the older cohorts (i.e., “weaning age” children: 12.0–35.9 months, and completely weaned children: 36.0–59.9 months), linear growth rates stabilize with little evidence of “catch up” growth in either region. Improved weight gain, however, is seen among the highland children, and is correlated with the nutritional intake (i.e., energy, total protein, and animal protein) from weaning foods. Overall, marked growth stunting is seen in both regions, but is more pronounced in the highland children. These high levels of stunting are largely established in the first 12 months of life. Greater growth retardation among the highland children appears to reflect the influence of hypoxia as well as the lower nutrient density of weaning foods in that region. Am. J. Hum. Biol. 12:825–837, 2000. © 2000 Wiley‐Liss Inc.
Perceptual Color Space Representations in the Oculomotor System Are Modulated by Surround Suppression and Biased Selection

The oculomotor system utilizes color extensively for planning saccades. Therefore, we examined how the oculomotor system actually encodes color and several factors that modulate these representations: attention-based surround suppression and inherent biases in selecting and encoding color categories. We measured saccade trajectories while human participants performed a memory-guided saccade task with color targets and distractors and examined whether oculomotor target selection processing was functionally related to the CIE (x,y) color space distances between color stimuli and whether there were hierarchical differences between color categories in the strength and speed of encoding potential saccade goals. We observed that saccade planning was modulated by the CIE (x,y) distances between stimuli thus demonstrating that color is encoded in perceptual color space by the oculomotor system. Furthermore, these representations were modulated by (1) cueing attention to a particular color thereby eliciting surround suppression in oculomotor color space and (2) inherent selection and encoding biases based on color category independent of cueing and perceptual discriminability. Since surround suppression emerges from recurrent feedback attenuation of sensory projections, observing oculomotor surround suppression suggested that oculomotor encoding of behavioral relevance results from integrating sensory and cognitive signals that are pre-attenuated based on task demands and that the oculomotor system therefore does not functionally contribute to this process. Second, although perceptual discriminability did partially account for oculomotor processing differences between color categories, we also observed preferential processing of the red color category across various behavioral metrics. This is consistent with numerous previous studies and could not be simply explained by perceptual discriminability. Since we utilized a memory-guided saccade task, this indicates that the biased processing of the red color category does not rely on sustained sensory input and must therefore involve cortical areas associated with the highest levels of visual processing involved in visual working memory.