Miracle-dz/UniFAR-FTUs huggingface dataset:
A phase I study of antisense oligonucleotide GTI-2040 given by continuous intravenous infusion in patients with advanced solid tumors.

BACKGROUND This study of GTI-2040, a 20-mer phosphorothioate oligonucleotide complementary to the messenger ribonucleic acid (mRNA) of the R2 subunit of ribonucleotide reductase (RNR), was conducted to determine the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of the agent in patients with advanced solid tumors or lymphoma. Plasma pharmacokinetics of GTI-2040 and suppression of RNR expression in peripheral blood mononuclear cells were also studied. PATIENTS AND METHODS GTI-2040 was administered as a continuous intravenous infusion for 21 days every 4 weeks. Dose escalation was performed using an accelerated, dose-doubling schedule until any drug related toxicity > or = grade 2 was observed; subsequent dose escalation followed a more conservative dose escalation scheme with three patients/cohort. RESULTS A total of 49 cycles of therapy were administered to 36 patients at GTI-2040 doses ranging from 18.5 mg/m(2)/day to 222 mg/m(2)/day. GTI-2040 was generally well tolerated. At the highest dose level examined, two patients experienced dose limiting reversible hepatic toxicity. Constitutional toxicities consisting of fatigue and anorexia were the most common toxicities. CONCLUSIONS The recommended dose of GTI-2040 given on this infusion schedule is 185 mg/m(2)/day. GTI-2040 appears to have a manageable toxicity profile and is generally well tolerated as a single agent.
Peer Field Placements with Preservice Teachers: Negotiating the Challenges of Professional Collaboration

Peer placements, pairing two preservice teachers with a cooperating teacher, have been shown to provide a more supportive and collaborative context for learning to teach than the traditional student-cooperating teacher, single placement model. In some cases, however, tensions existed. This qualitative study seeks to expand the extant research by identifying and analyzing the challenges 24 preservice teachers experienced in their peer placements. While virtually all preservice teachers viewed their peer placements positively, results indicate that all preservice teachers negotiated challenges that pertained to the act or perceived value of collaboration in practice. Specifically, preservice teachers’ prior experiences had not prepared them for in-depth collaboration, and their tendency to view teaching as an autonomous profession that one gains entry into by “sinking or swimming” influenced their perception of the role of collaboration in professional learning. Recommendations are provided to guide the development or refinement of peer placements.
Microcystin Biosynthesis and mcyA Expression in Geographically Distinct Microcystis Strains under Different Nitrogen, Phosphorus, and Boron Regimes

Roles of nutrients and other environmental variables in development of cyanobacterial bloom and its toxicity are complex and not well understood. We have monitored the photoautotrophic growth, total microcystin concentration, and microcystins synthetase gene (mcyA) expression in lab-grown strains of Microcystis NIES 843 (reference strain), KW (Wangsong Reservoir, South Korea), and Durgakund (Varanasi, India) under different nutrient regimes (nitrogen, phosphorus, and boron). Higher level of nitrogen and boron resulted in increased growth (avg. 5 and 6.5 Chl a mg/L, resp.), total microcystin concentrations (avg. 1.185 and 7.153 mg/L, resp.), and mcyA transcript but its expression was not directly correlated with total microcystin concentrations in the target strains. Interestingly, Durgakund strain had much lower microcystin content and lacked microcystin-YR variant over NIES 843 and KW. It is inferred that microcystin concentration and its variants are strain specific. We have also examined the heterotrophic bacteria associated with cyanobacterial bloom in Durgakund Pond and Wangsong Reservoir which were found to be enriched in Alpha-, Beta-, and Gammaproteobacteria and that could influence the bloom dynamics.
The Wilson-Bappu Effect: a tool to determine stellar distances.

Wilson & Bappu (1957) have shown the existence of a remarkable correlation between the width of the emission in the core of the K line of CaII and the absolute visual magnitude of late-type stars. Here we present a new calibration of the Wilson-Bappu eect based on a sample of 119 nearby stars. We use, for the first time, width measurements based on high resolution and high signal to noise ratio CCD spectra and absolute visual magnitudes from the Hipparcos database. Our primary goal is to investigate the possibility of using the Wilson-Bappu eect to determine accurate distances to single stars and groups. The result of our calibration fitting of the Wilson-Bappu relationship is MV = 33:2 18: 0l ogW0, and the determination seems free of systematic eects. The root mean square error of the fitting is 0.6 mag. This error is mostly accounted for by measurement errors and intrinsic variability of W0, but in addition a possible dependence on the metallicity is found, which becomes clearly noticeable for metallicities below (Fe=H) 0:4. This detection is possible because in our sample (Fe/H) ranges from 1:5 to 0.4. The Wilson-Bappu eect can be used confidently for all metallicities not lower than 0:4, including the LMC. While it does not provide accurate distances to single stars, it is a useful tool to determine accurate distances to clusters and aggregates, where as ucient number of stars can be observed. We apply the Wilson-Bappu eect to published data of the open cluster M 67; the retrieved distance modulus is of 9.65 mag, in very good agreement with the best distance estimations for this cluster, based on main sequence fitting.
Genome-scale analysis of interaction dynamics reveals organization of biological networks

Analyzing large-scale interaction networks has generated numerous insights in systems biology. However, such studies have primarily been focused on highly co-expressed, stable interactions. Most transient interactions that carry out equally important functions, especially in signal transduction pathways, are yet to be elucidated and are often wrongly discarded as false positives. Here, we revisit a previously described Smith-Waterman-like dynamic programming algorithm and use it to distinguish stable and transient interactions on a genomic scale in human and yeast. We find that in biological networks, transient interactions are key links topologically connecting tightly regulated functional modules formed by stable interactions and are essential to maintaining the integrity of cellular networks. We also perform a systematic analysis of interaction dynamics across different technologies and find that high-throughput yeast two-hybrid is the only available technology for detecting transient interactions on a large scale.
Airflow in stop-vowel sequences of German

This study reports on the results of an airflow experiment that measured the duration of airflow and the amount of air from release of a stop to the beginning of a following vowel in stop vowel-sequences of German. The sequences involved coronal, labial and velar voiced and voiceless stops followed by the vocoids /j, i:, , , , a/. The experiment tested the influence of the three factors voicing of stop, place of stop articulation, and the following vocoid context on the duration and amount of air as possible explanation for assibilation processes. The results show that the voiceless stops are related to a longer duration and more air in the release phase than voiced ones. For the influence of the vocoids, a significant difference could be established between /j/ and all other vocoids for the duration of the release phase. This difference could not be found for the amount of air over this duration. The place of articulation had only restricted influence. Velars resulted in significantly longer duration of the release phase compared to non-velars. A significant difference in amount of air between the places of articulation could not be found.
Service users' views of a self-help pack for anxiety

Background: Despite some evidence for the effectiveness of self-help approaches and their recommended use in recent NICE guidance for anxiety and depression, more research is needed into service users' views of self-help materials and their effectiveness in different service settings, including self-help groups. Aim: To obtain the views of a group of mental health service users who attended a self-help organization of (a) a self-help anxiety pack, (b) the impact it had on their coping, and (c) the impact on them of the user consultation exercise. Method: The views were obtained through focus groups using a semi-structured interview schedule and were then subject to qualitative template analysis. Results: The emergent themes included recommendations for improving the pack by making it briefer, more readable and less technical. Other clear themes were the value of working with the pack as a group and concerns about individuals being able to make use of the pack without support and guidance. The implications of these findings for the development and implementation of self-help approaches for mental health problems and research with community-based self-help groups are discussed. Conclusions: Service user views of self-help approaches can inform the development of accessible and acceptable materials and clarify the support required to make effective use of the material. Declaration of interest: This study was funded by the University of Huddersfield.
An Improved Observation Model for Super-Resolution Under Affine Motion

Super-resolution (SR) techniques make use of subpixel shifts between frames in an image sequence to yield higher resolution images. We propose an original observation model devoted to the case of nonisometric inter-frame motion as required, for instance, in the context of airborne imaging sensors. First, we describe how the main observation models used in the SR literature deal with motion, and we explain why they are not suited for nonisometric motion. Then, we propose an extension of the observation model by Elad and Feuer adapted to affine motion. This model is based on a decomposition of affine transforms into successive shear transforms, each one efficiently implemented by row-by-row or column-by-column one-dimensional affine transforms. We demonstrate on synthetic and real sequences that our observation model incorporated in a SR reconstruction technique leads to better results in the case of variable scale motions and it provides equivalent results in the case of isometric motions
Evaluation of the Induction of Immune Memory following Infant Immunisation with Serogroup C Neisseria meningitidis Conjugate Vaccines – Exploratory Analyses within a Randomised Controlled Trial

Aim We measured meningococcal serogroup C (MenC)-specific memory B-cell responses in infants by Enzyme-Linked Immunospot (ELISpot) following different MenC conjugate vaccine schedules to investigate the impact of priming on immune memory. Methods Infants aged 2 months were randomised to receive 1 or 2 doses of MenC-CRM197 at 3 or 3 and 4 months, 1 dose of MenC-TT at 3 months, or no primary MenC doses. All children received a Haemophilus influenzae type b (Hib)-MenC booster at 12 months. Blood was drawn at 5, 12, 12 months +6 days and 13 months of age. Results Results were available for 110, 103, 76 and 44 children from each group respectively. Following primary immunisations, and prior to the 12-month booster, there were no significant differences between 1- or 2-dose primed children in the number of MenC memory B-cells detected. One month following the booster, children primed with 1 dose MenC-TT had more memory B-cells than children primed with either 1-dose (p = 0.001) or 2-dose (p<0.0001) MenC-CRM197. There were no differences in MenC memory B-cells detected in children who received 1 or 2 doses of MenC-CRM197 in infancy and un-primed children. Conclusions MenC-specific memory B-cell production may be more dependent on the type of primary vaccine used than the number of doses administered. Although the mechanistic differences between MenC-CRM197 and MenC-TT priming are unclear, it is possible that structural differences, including the carrier proteins, may underlie differential interactions with B- and T-cell populations, and thus different effects on various memory B-cell subsets. A MenC-TT/Hib-MenC-TT combination for priming/boosting may offer an advantage in inducing more persistent antibody. Trial Registration EU Clinical Trials Register 2009-016579-31 ClinicalTrials.gov NCT01129518
Osteology Supports a Stem-Galliform Affinity for the Giant Extinct Flightless Bird Sylviornis neocaledoniae (Sylviornithidae, Galloanseres)

The giant flightless bird Sylviornis neocaledoniae (Aves: Sylviornithidae) existed on La Grande Terre and Ile des Pins, New Caledonia, until the late Holocene when it went extinct shortly after human arrival on these islands. The species was generally considered to be a megapode (Megapodiidae) until the family Sylviornithidae was erected for it in 2005 to reflect multiple cranial autapomorphies. However, despite thousands of bones having been reported for this unique and enigmatic taxon, the postcranial anatomy has remained largely unknown. We rectify this deficiency and describe the postcranial skeleton of S. neocaledoniae based on ~600 fossils and use data from this and its cranial anatomy to make a comprehensive assessment of its phylogenetic affinities. Sylviornis neocaledoniae is found to be a stem galliform, distant from megapodiids, and the sister taxon to the extinct flightless Megavitiornis altirostris from Fiji, which we transfer to the family Sylviornithidae. These two species form the sister group to extant crown-group galliforms. Several other fossil galloanseres also included in the phylogenetic analysis reveal novel hypotheses of their relationships as follows: Dromornis planei (Dromornithidae) is recovered as a stem galliform rather than a stem anseriform; Presbyornis pervetus (Presbyornithidae) is the sister group to Anseranatidae, not to Anatidae; Vegavis iaai is a crown anseriform but remains unresolved relative to Presbyornis pervetus, Anseranatidae and Anatidae. Sylviornis neocaledoniae was reconstructed herein to be 0.8 m tall in a resting stance and weigh 27–34 kg. The postcranial anatomy of S. neocaledoniae shows no indication of the specialised adaptation to digging seen in megapodiids, with for example, its ungual morphology differing little from that of chicken Gallus gallus. These observations and its phylogenetic placement as stem galliforms makes it improbable that this species employed ectothermic incubation or was a mound-builder. Sylviornis neocaledoniae can therefore be excluded as the constructor of tumuli in New Caledonia.
The role of APOE epsilon4 in modulating effects of other risk factors for cognitive decline in elderly persons.

CONTEXT Cognitive decline in elderly persons is often an early predictor of dementia. Subclinical cardiovascular disease (CVD) and diabetes mellitus may contribute to substantial decline in cognitive function in the elderly. These risks may be modified by gene-environment interactions between apolipoprotein E (APOE) genotype and CVD risk factors or subclinical CVD. OBJECTIVES To examine the association between subclinical CVD and decline in cognitive functioning in the elderly and to examine effect modification by the APOE genotype of the association between subclinical disease and cognitive decline. DESIGN The Cardiovascular Health Study, a population-based, prospective cohort study. SETTING AND POPULATION A total of 5888 randomly selected Medicare-eligible participants from Sacramento County, California; Forsyth County, North Carolina; Washington County, Maryland; and Pittsburgh, Pa, aged 65 years or older, who were recruited in 1989-1990 (n = 5201) and in 1992-1993 (n = 687) and who were followed up for 7 and 5 years, respectively. MAIN OUTCOME MEASURES Change over time in scores on the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test as a function of APOE genotype, subclinical CVD, and diabetes mellitus. RESULTS Seventy percent of participants had no significant decline on the Modified Mini-Mental State Examination. Systolic blood pressure, the ankle-arm brachial index, atherosclerosis of the internal carotid artery, diabetes mellitus, and several diagnoses of prevalent CVD were significantly associated with declines in scores on the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test. The rate of cognitive decline associated with peripheral vascular disease, atherosclerosis of the common and internal carotid arteries, or diabetes mellitus was increased by the presence of any APOE epsilon4 allele. CONCLUSIONS Most healthy elderly people did not experience cognitive decline. Measures of subclinical CVD were modest predictors of cognitive decline. Those with any APOE epsilon4 allele in combination with atherosclerosis, peripheral vascular disease, or diabetes mellitus were at substantially higher risk of cognitive decline than those without the APOE epsilon4 allele or subclinical CVD. High levels of atherosclerosis increased cognitive decline independently of APOE genotype.
Analysing Flexibility and Integration Needs in budgeting is Technologies

The duality characteristics of budgeting between the flexibility driven decision making and the integration focused management control inspire the author to investigate how the flexibility and integration domains influence business controllers? choices of IS technologies used in budgeting. This includes the enterprise resource planning (ERP) system, business intelligent (BI), web tool and spreadsheets. Guided by the concept of human agency, twenty business controllers in eleven companies in Thailand are interviewed. The analysis shows that flexibility and integration in budgeting IS technologies can be viewed from four domains: organisation-in-focus, personal requirement, business requirement and reporting requirement. The analysis also shows that there are conflicts between these four domains based on the needs for flexibility and integration. It is found that spreadsheets are used when flexibility is needed especially for decision making at local unit level. However advanced IS technologies like the ERP system, BI and web tool, are employed for relatively stable management control tasks. The major implication is that business controllers apply budgeting IS technologies to fit the nature of the budgeting tasks at hand. Therefore there is clearly a need to employ a variety of IS technologies, and not to dominate any particular IS technologies for budgeting because each system is designed for its own respective purposes and intentions. (Less)
Endoscopic third ventriculostomy – effectiveness of the procedure for obstructive hydrocephalus with different etiology in adults

Introduction After a time of domination of shunt placement, endoscopic third ventriculostomy (ETV) has been increasingly applied in treatment of obstructive hydrocephalus. Aim To assess the effectiveness of ETV in treatment of adults with three-ventricle hydrocephalus of different etiology. Material and methods Ninety-six patients with obstructive hydrocephalus were studied: 24 with primary aqueductal stenosis, 61 with brain tumor, and 2 with basilar tip aneurysm. In 9 patients the etiology of hydrocephalus remained undetermined. The assessment of treatment results was based on clinical and radiological criteria. Results Clinical improvement was observed in 74 (77.1%) patients, and radiological improvement in 52 (54.2%). One patient died. Follow-up of 24 patients with primary aqueductal stenosis has shown that in 20 (83.3%) of them clinical improvement has been stable, and in 14 (58.3%) radiological improvement has been observed. Two patients required shunt placement due to hydrocephalus recurrence 12–24 months after the ETV procedure. Among 9 patients with undefined hydrocephalus, 3 required shunt placement within 6 months after ETV (2 shunted previously). Endoscopic third ventriculostomy treatment in a patient with hydrocephalus caused by basilar tip aneurysm succeeded. The assessment of ETV effectiveness in oncological patients has been indirect in view of the underlying disease. Conclusions The best results of ETV treatment have been demonstrated for patients with primary aqueductal stenosis. Ventricle size cannot determine the effectiveness of treatment as an individual requirement. Endoscopic third ventriculostomy is effective in previously shunted patients although the prediction of outcome should be cautious. Endoscopic third ventriculostomy enables preparation for further therapy and is palliative treatment in oncological patients with secondary hydrocephalus.
Distinct contributions of conduct and oppositional defiant symptoms to adult antisocial behavior: evidence from an adoption study.

BACKGROUND We conducted an exploratory multivariate analysis of juvenile behavior symptoms in an adoption data set. One goal was to see if a few DSM-interpretable symptom dimensions economically captured information within the data. A second goal was to study the relationships between any such dimensions, biological and environmental background, and eventual adult antisocial behavior. METHODS The data originated from a retrospective adoption study. Probands with a biological background for parental antisocial personality or alcoholism were heavily oversampled. Symptoms were ascertained by proband and adoptive parent interview. We performed, by gender, orthogonal rotated principal component analyses of juvenile behavior disturbance symptoms (females, n = 87; males, n = 88). We used structural equation modeling to examine the relationships hypothesized above. RESULTS For both genders, an oppositional defiant disorder (ODD) component and at least 1 conduct component emerged. Regardless of the conduct component scores, the ODD components were significant predictors of adult antisocial behavior. For males, the ODD component was predicted by an antisocial biological background, but not by scores on the Adverse Adoptive Environment Scale. The conduct components were predicted by adoptive environment alone. For females, biological background or biological-environmental interactions predicted each of the components. CONCLUSIONS There has been little previous distinction between conduct disorder and ODD in studies of genetic and environmental influences on juvenile behavior. The study suggests that adolescent ODD symptoms may be a distinct antecedent of adult antisocial personality. In males, adolescent ODD symptoms may represent early expression of genetic sociopathic personality traits.