Miracle-dz/UniFAR-FTUs huggingface dataset:
Intrinsic disorder and coiled coil formation in prostate apoptosis response factor-4 (Par-4) : submitted in fulfilment of the requirements of the degree of Doctor of Philosphy, Institute of Fundamental Sciences, Massey University, New Zealand

Prostate apoptosis response factor-4 (Par-4) is a ubiquitously expressed pro-apoptotic and tumour suppressive protein. Par-4 contains a highly conserved coiled coil (CC) region at the Cterminus, particularly the distal 40 residues fulfil the criteria for a leucine zipper (LZ). This Cterminal domain serves as the primary recognition domain for a large number of binding partners. Par-4 is tightly regulated by the aforementioned binding partners and also by posttranslational modifications. Biophysical data presented here describe Par-4 as primarily an intrinsically disordered protein (IDP). Bioinformatic analysis of the highly conserved Par-4 reveals low sequence complexity and enrichment in polar and charged amino acids. High proteolytic susceptibility and increased hydrodynamic radii are consistent with largely extended structures in solution. Spectroscopic measurements using circular dichroism (CD) and nuclear magnetic resonance (NMR) also reveal characteristic features of intrinsic disorder. Under physiological conditions, data show that Par-4 self-associates via the C-terminal domain possibly through coiled coil formation. Analysis of various constructs comprising the Par-4 LZ domain by NMR, CD, light scattering and other techniques reveals an environment-dependent conformational equilibrium between primarily disordered monomers and predominantly coiled coil dimers. Whereas the disordered monomers are easily observed by NMR, the coiled coil fraction is not amenable to NMR studies possibly due to intermediate exchange processes. Mutational approaches that stabilise the coiled coil fraction result in NMR spectra of lower quality compared to the wild-type form. The high degree of sequence conservation suggest that coiled coil formation and intrinsic disorder are essential for Par-4 to function as an effective regulator of apoptosis.
Allergen immunotherapy for asthma.

BACKGROUND Allergen specific immunotherapy has long been a controversial treatment for asthma. Although beneficial effects upon clinically relevant outcomes have been demonstrated in randomised controlled trials, there remains a risk of severe and sometimes fatal anaphylaxis. The recommendations of professional bodies have ranged from cautious acceptance to outright dismissal. With increasing interest in new allergen preparations and new methods of delivery, it was time to conduct a systematic review of allergen specific immunotherapy for asthma. OBJECTIVES Allergen specific immunotherapy involves injecting an extract of the allergen under the skin. It is also known as hyposensitisation or desensitisation, and carries a risk of potentially fatal anaphylaxis. The objective of this review was to assess the effects of allergen specific immunotherapy for asthma. SEARCH STRATEGY We searched the Cochrane Airways Group trials register up to 1997, Dissertation Abstracts, WorldCat and ArticleFirst. SELECTION CRITERIA Randomised trials using various forms of allergen specific immunotherapy to treat asthma. DATA COLLECTION AND ANALYSIS Eligibility of studies for inclusion was decided by three reviewers independently. Quality assessment of studies was performed by two reviewers independently. MAIN RESULTS Fifty-four trials were included. There were 25 trials of immunotherapy for house mite allergy; 13 pollen allergy trials; eight animal dander allergy trials; two Cladosporium mould allergy and six trials looking at multiple allergens. Concealment of allocation was assessed as clearly adequate in only 11 of these trials. Significant heterogeneity was present in a number of comparisons. Overall, there was a significant reduction in asthma symptoms and medication following immunotherapy. There was also a significant improvement in asthma symptom scores (standardised mean difference -0.52, 95% confidence interval -0.70 to -0.35). People receiving immunotherapy were less likely to report a worsening of asthma symptoms than those randomised to placebo (odds ratio 0.27, 95% confidence interval 0.21 to 0.35). People randomised to immunotherapy were less likely to require medication than those randomised to placebo (odds ratio 0.28, 95% confidence interval 0.19 to 0.42). Allergen immunotherapy reduced allergen specific bronchial hyper-reactivity, with some reduction in non-specific bronchial hyper-reactivity as well. There was no consistent effect on lung function. REVIEWER'S CONCLUSIONS Immunotherapy may reduce asthma symptoms and use of asthma medications, but the size of the benefit compared to other therapies is not known. The possibility of adverse effects (such as anaphylaxis) must be considered.
378PDISEASE PROGRESSION PATTERN IN METASTATIC BREAST CANCER PATIENTS (MBC) TREATED WITH ANTI-HER2 THERAPIES.

Purpose Over the last decade a dramatic improvement in the treatment and prognosis of human epidermal growth factor receptor-2 (HER2) positive metastatic breast cancer (MBC) has been achieved. This study aimed to describe pattern, timing of metastases, and time to progression (TTP) of MBC patients (pts) treated with multiple lines of therapy with trastuzumab and/or lapatinib.
Over 200 years of drainage practices and lake level drawdown in the Uściwierskie Lowering (Łęczna-Włodawa Lakeland)

Abstract Meliorations of the Łęczna-Włodawa Lakeland have considerably determined its water relations within the last more than 200 years. The analysis of the map by Anton Mayer von Heldensfeld, so far not applied in studies on the drainage network of this lakeland, executed in the years 1801-04, revealed the drainage of the Uściwierskie Lowering already at the turn of the 18th and 19th century. This shifts the commencement of strong anthropogenic impact on this area to a considerably earlier period than was previously assumed. The lakes subject to analysis (Rotcze, Uściwierz, Bikcze, and Lakes Piaseczno and Łukie neighbouring with the Lowering) were incorporated into the drainage system in various periods. Such incorporation of a water body involved water level drawdown. The water level decreased first in Lake Bikcze, and the latest in Lake Rotcze. More detailed information on changes in the water level in the lakes of the Uściwierskie Lowering since 1882 was obtained based on calculation and on comparison with current data of measurements conducted by Rostworowski. The analysis revealed that the water level in Lakes Bikcze and Piaseczno, although fluctuating, has not changed within the last 130 years, whereas the water level in Lake Uściwierz decreased by 33 cm, and in Lake Rotcze by 90 cm.
The geomorphological effectiveness of floods—a contribution stimulated by two recent events in mid-wales

The occurrence of two ‘rare’ floods (August 1973, August 1977) in the Plynlimon experimental catchments has confirmed the susceptibility of small upland catchments to summer flooding and provided clues to complications in the geomorphological interpretation of floods in terms of their magnitude and frequency. Magnitude may be treated both in terms of work and effectiveness; the emphasis here is on effectiveness, as revealed by simple surveys. The first Plynlimon flood was more effective on slopes and the second in channels, despite peak discharges of similar return periods and almost identical rates of work revealed by bedload trapping. Effectiveness/frequency studies are likely to require a much more detailed approach, subdividing both the characteristics of the flood and the spatial elements of the affected catchments; a simple slope/channel subdivision is found to be suitable for accounts of effectiveness found in the literature on British floods this century. Effectiveness studies also require regular surveys throughout the recovery period following major flooding; in upland catchments these surveys should concentrate on identifying threshold phenomena and illustrating the relationship between effectiveness and work assessments of magnitude.
Coccolithophorids and related nannoplankton of the early Tertiary in California

Evidence of the stratigraphic value of the fossil remains of an abundant and varied calcareous nannoplankton has been limited by little published data. Description of the species and tabulated distributions in 86 samples from a continuous sequence of Paleocene and Eocene strata of California permit recognition of 6 distinct biostratigraphic units. Available evidence on their extension as zones elsewhere and relations to type areas of some European stages are presented.
Migrations and Management of the Jackson Elk Herd.

Abstract : From April 1978 to April 1982,85 adult (> minus 2.7 years-old) elk (Cervus elaphus nelsoni) were captured and radio-collared on the National Elk Refuge in northwestern Wyoming. Relocations with biotelemetry from 1978 to 1984 showed that the radio-collared elk occupied four distinct summer ranges: 48% summered in Grand Teton National Park, 28% in Yellowstone National Park, 12% in the Teton Wilderness, and 12% in the Gros Ventre drainage.
Temporal Trends in Percutaneous Coronary Intervention Associated Acute Cerebrovascular Accident (From the 1998– 2008 Nationwide Inpatient Sample [NIS] Database)

Acute cerebrovascular accident (CVA) after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) and coronary artery disease (CAD) is associated with high morbidity and mortality. Nationwide Inpatient Sample from 1998 to 2008 was utilized to identify 1,552,602 PCIs performed for ACS and CAD. We assessed temporal trends in the incidence, predictors and prognostic impact of CVA in a broad range of patients undergoing PCI. The overall incidence of CVA was 0.56% (95% confidence interval (CI), 0.55%–0.57%). The incidence of CVA remained unchanged over the study period (adjusted p for trend = 0.2271). The overall mortality in the CVA group was 10.76% (95% CI, 10.1%–11.4%). The adjusted odds ratio (OR) of CVA for in-hospital mortality was 7.74 (95% CI, 7.00–8.57; p<0.0001); this remained high but decreased over the study period (adjusted p for trend <0.0001). Independent predictors of CVA included older age (OR, 1.03, 95% CI, 1.02–1.03; p<0.0001), disorder of lipid metabolism (OR, 1.31, 95% CI, 1.24– 1.38; p<0.001), history of tobacco use (OR, 1.21, 95% CI, 1.10–1.34; p=0.0002), coronary atherosclerosis (OR 1.56, 95% CI, 1.43–1.71; p<0.0001), and IABP use (OR 1.39, 95% CI, 1.09– 1.77; p=0.0073). A nomogram for predicting the probability of CVA achieved a concordance index of 0.73 and was well calibrated. In conclusion, the incidence of CVA associated with PCI has remained unchanged from 1998–2008 in face of improved equipment, techniques and adjunctive pharmacology. The risk of CVA associated in-hospital mortality is high; however, this risk has declined over the study period.
Statistical and case studies of radio emissions observed near 2ƒce and 3ƒce in the auroral zone

Receivers located at Two Rivers, Alaska (64.9°N, 146.9°W), and Circle Hot Springs, Alaska (65.5°N, 144.7°W), have been used to monitor the spectrum between 0.05-4.8 MHz for extended periods. Seasonal and diurnal effects of auroral roar, a weak narrow band radio emission near 2 and 3 times the ionospheric electron cyclotron frequency (ƒce), have been determined. Many individual auroral roar events correlate with magnetic activity, and superposed epoch analysis using planetary K indices shows a correlation between magnetic activity and auroral roar commencement. For a 3ƒce roar event on March 23, 1992, riometer, magnetometer, photometer, and all-sky camera data are available and show that individual bursts of 3ƒce auroral roar are associated with intensifications of the aurora, as was known previously for 2ƒce roar. Finally, two possible generation mechanisms are investigated in detail: nonlinear interaction between lower hybrid and electrostatic upper hybrid waves producing electromagnetic waves, and the feasibility of a lower ionospheric decameter maser for direct generation of X mode waves at harmonics of ƒce.
Title: The effect of levodopa on saccades – Oxford Quantification in Parkinsonism study

The evaluation of novel disease modifying drugs requires biomarkers that are simultaneously sensitive to disease state but resistant to the effects of background symptomatic treatment. Saccadic eye movement parameters have been proposed as a neurophysiological biomarker for Parkinson’s disease (PD) and so it is important to know how they are affected by dopaminergic medication. Studies to date are conflicting: some have concluded that medication prolongs saccadic latencies while others suggest they are shortened. We aimed to characterise the effects of antiparkinsonian medication on prosaccadic and antisaccadic parameters in a large cohort of PD patients and age matched healthy controls and to survey the current literature in comparison to the study findings. We studied saccades both off and on medication in 38 PD patients and 34 healthy controls (HC). Latencies, amplitudes, velocities, and directional errors were evaluated, using a published standardised protocol. We then combined this study and previously published literature in a meta-analysis of the effects of antiparkinsonian medication on prosaccadic latency (PSL).
Pyric Herbivory: Rewilding Landscapes through the Recoupling of Fire and Grazing

Abstract: Our understanding of fire and grazing is largely based on small‐scale experimental studies in which treatments are uniformly applied to experimental units that are considered homogenous. Any discussion of an interaction between fire and grazing is usually based on a statistical approach that ignores the spatial and temporal interactions on complex landscapes. We propose a new focus on the ecological interaction of fire and grazing in which each disturbance is spatially and temporally dependent on the other and results in a landscape where disturbance is best described as a shifting mosaic (a landscape with patches that vary with time since disturbance) that is critical to ecological structure and function of many ecosystems. We call this spatiotemporal interaction pyric herbivory (literal interpretation means grazing driven by fire). Pyric herbivory is the spatial and temporal interaction of fire and grazing, where positive and negative feedbacks promote a shifting pattern of disturbance across the landscape. We present data we collected from the Tallgrass Prairie Preserve in the southern Great Plains of North America that demonstrates that the interaction between free‐roaming bison (Bison bison) and random fires promotes heterogeneity and provides the foundation for biological diversity and ecosystem function of North American and African grasslands. This study is different from other studies of fire and grazing because the fires we examined were random and grazing animals were free to roam and select from burned and unburned patches. For ecosystems across the globe with a long history of fire and grazing, pyric herbivory with any grazing herbivore is likely more effective at restoring evolutionary disturbance patterns than a focus on restoring any large vertebrate while ignoring the interaction with fire and other disturbances.
Improved modeling of sea level patterns by incorporating self-attraction and loading

[1] We implement the effects of gravitational self-attraction and loading (SAL) into a global baroclinic ocean circulation model and investigate effects on sea level patterns, ocean circulation, and density distributions. We compute SAL modifications as an additional force on the water masses at every time step by decomposing the field of ocean bottom pressure anomalies into spherical harmonic functions and then applying Love numbers to account for the elastic properties of the solid Earth. Considering SAL in the postprocessing turns out to be insufficient, especially in coastal waters and on subweekly time scales, where SAL modifies local sea level by around 0.6–0.8 cm on average; in the open ocean, changes mostly remain around 0.3 cm. Modifications of water velocities as well as of heat and salt distributions are modeled, yet they are small. Simple parameterizations of SAL effects currently used in a number of ocean circulation models suffer from the process's inhomogeneity in space and time. These parameterizations improve the modeled sea level patterns but fail to reproduce SAL impacts on circulation and density distributions. We therefore suggest to explicitly consider the full SAL effect in ocean circulation models, especially when investigating sea level variations faster than around 4 days.
The Parieto-Frontal Integration Theory (P-FIT) of intelligence: Converging neuroimaging evidence

Abstract “Is there a biology of intelligence which is characteristic of the normal human nervous system? ” Here we review 37 modern neuroimaging studies in an attempt to address this question posed by Halstead (1947) as he and other icons of the last century endeavored to understand how brain and behavior are linked through the expression of intelligence and reason. Reviewing studies from functional (i.e., functional magnetic resonance imaging, positron emission tomography) and structural (i.e., magnetic resonance spectroscopy, diffusion tensor imaging, voxel-based morphometry) neuroimaging paradigms, we report a striking consensus suggesting that variations in a distributed network predict individual differences found on intelligence and reasoning tasks. We describe this network as the Parieto-Frontal Integration Theory (P-FIT). The P-FIT model includes, by Brodmann areas (BAs): the dorsolateral prefrontal cortex (BAs 6, 9, 10, 45, 46, 47), the inferior (BAs 39, 40) and superior (BA 7) parietal lobule, the anterior cingulate (BA 32), and regions within the temporal (BAs 21, 37) and occipital (BAs 18, 19) lobes. White matter regions (i.e., arcuate fasciculus) are also implicated. The P-FIT is examined in light of findings from human lesion studies, including missile wounds, frontal lobotomy/leukotomy, temporal lobectomy, and lesions resulting in damage to the language network (e.g., aphasia), as well as findings from imaging research identifying brain regions under significant genetic control. Overall, we conclude that modern neuroimaging techniques are beginning to articulate a biology of intelligence. We propose that the P-FIT provides a parsimonious account for many of the empirical observations, to date, which relate individual differences in intelligence test scores to variations in brain structure and function. Moreover, the model provides a framework for testing new hypotheses in future experimental designs.
Alternative coordinate systems for analyzing cross-section shapes of glaciated valleys: a case study from the Dalijia Mountains, China

The morphometry of glaciated valleys has been of considerable significance in evaluating models and processes of valley form development, and is typically evaluated using a power law function fit to topographic data. Results of the power law method are sensitive to the location of the coordinate system origin, but most previous research has used a coordinate system centered on the valley midpoint and has not systematically assessed alternative approaches. Here, we test four options for selecting the coordinate system origin, using cross-section profiles from glacial, fluvial, and transitional valleys in the Dalijia Mountains, China: (A) the lowest elevation point, (B) the valley midpoint, (C) the lowest point on the valley side wall, and (D) the highest point on the valley side. Option A produces results that are most consistent with expected values and trends for shape parameters in the Dalijia Mountains. Over half of the values calculated using Option B overestimate key valley-shape parameters compared to Option A. Options C and D produce similar values to each other, but these values are very different from Option A and less useful for landform interpretation. In morphometric studies designed to evaluate impacts of glacial erosion using the power law approach, we recommend that alternate coordinate system origins be evaluated, including the lowest elevation point on a cross-profile.
Breeding of Black Swan in Tasmania

The breeding distribution of the Black Swan in Tasmania is given and the breeding history of the species over three years in the principal breeding area at Moulting Lagoon is described. The incubation period was found to be 39+ 2 days and cygnets fly 60 days after the appearance of juvenile plumage. Floods are the main source of egg mortality and other factors are relatively unimportant. Direct observation and statistical calculations were used to estimate the annual cygnet production. The statistical methods gave widely divergent estimates. Shooting over the breeding ground has an adverse effect upon breeding, upsetting pair formation. Restriction of this shooting has re1sulted in a greater cygnet production. Flooding and autodestruction of habitat are important factors in breeding success and recommendations for the management of the species are given.
An overlapping pattern of cerebral cortical thinning is associated with both positive symptoms and aggression in schizophrenia via the ENIGMA consortium

Abstract Background Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample. Method To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls. Results The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression. Conclusion These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.