Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of quisqualate receptor desensitization in cultured postnatal rat hippocampal neurons

The quisqualate class of glutamate receptors is thought to play an important role in excitatory synaptic transmission, synaptic plasticity, and neuronal death. Since desensitization is a prominent feature of the responses mediated by this class of receptors, we have characterized the rapidly desensitizing quisqualate response in cultured postnatal rat hippocampal neurons using the whole-cell patch- clamp technique. Quisqualate and its structural analogs elicit a peak current that rapidly decays to a steady-state level. In contrast, currents induced by kainate, NMDA, and their structural analogs exhibit either no decay or a much slower decay. The biophysical and pharmacological properties of the peak and steady-state quisqualate currents indicate that both are mediated by an ionotropic quisqualate receptor. Quisqualate currents desensitized monoexponentially by approximately 70% with a time constant near 80 msec. Both the rate and percentage of desensitization showed slight voltage dependence and were concentration dependent, reaching maximal values at saturation. Additionally, the overlap of the dose-response curves for activation of the steady-state current and desensitization of the peak current by a conditioning dose suggests that the two processes are related. Furthermore, desensitizing quisqualate currents were observed when Ca2+, Mg2+, Na+, K+, and Cl- were removed from the extracellular solution or their concentrations greatly reduced. These results suggest that the decline in the response is not caused by a simple open channel block mechanism. Despite the lack of desensitization by kainate, our observations are consistent with the hypothesis that quisqualate and kainate act at a single receptor-channel complex. Kainate and quisqualate appeared to interact competitively when applied simultaneously and noncompetitively when quisqualate was applied first. In addition, saturating doses of quisqualate and kainate gave steady- state currents of equal amplitude in neurons treated with the lectin WGA, an inhibitor of quisqualate receptor desensitization.
A FcγRIII-engaging bispecific antibody expands the range of HER2-expressing breast tumors eligible to antibody therapy

Trastuzumab is established as treatment of HER2high metastatic breast cancers but many limitations impair its efficacy. Here, we report the design of a Fab-like bispecific antibody (HER2bsFab) that displays a moderate affinity for HER2 and a unique, specific and high affinity for FcγRIII. In vitro characterization showed that ADCC was the major mechanism of action of HER2bsFab as no significant HER2-driven effect was observed. HER2bsFab mediated ADCC at picomolar concentration against HER2high, HER2low as well as trastuzumab-refractive cell lines. In vivo HER2bsFab potently inhibited HER2high tumor growth by recruitment of mouse FcγRIII and IV-positive resident effector cells and more importantly, exhibited a net superiority over trastuzumab at inhibiting HER2low tumor growth. Moreover, FcγRIIIA-engagement by HER2bsFab was independent of V/F158 polymorphism and induced a stronger NK cells activation in response to target cell recognition. Thus, taking advantage of its epitope specificity and affinity for HER2 and FcγRIIIA, HER2bsFab exhibits potent anti-tumor activity against HER2low tumors while evading most of trastuzumab Fc-linked limitations thereby potentially enlarging the number of patients eligible for breast cancer immunotherapy.
Serum levels of the carboxy-terminal propeptide of type I procollagen and the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen as markers of bone metastases in patients with prostate carcinoma.

OBJECTIVES To evaluate serum levels of the carboxy-terminal propeptide of type I procollagen (PICP) and the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) as possible markers of bone metastases in patients with prostate carcinoma (PCA) patients. METHODS Levels of PICP and ICTP were measured by radioimmunoassay of serum from 29 patients with benign prostatic hyperplasia (BPH), 17 patients with PCA without bone metastases and 29 patients with PCA and bone metastases. RESULTS Serum levels of PICP in patients with PCA and bone metastases (mean +/- SD 304.3 +/- 365.9 ng/ml) were significantly higher than those in patients with BPH (95.6 +/- 27.1 ng/ml) and in patients with PCA without bone metastases (111.1 +/- 44.6 ng/ml). No significant difference was observed between the BPH and the PCA without bone metastases groups. Serum levels of ICTP were significantly higher in the PCA with (10.4 +/- 10.3 ng/ml) and without bone metastases groups (7.7 +/- 6.0 ng/ml) than in the BPH group (3.7 +/- 2.0 ng/ml). There was no significant difference between the PCA groups with and without bone metastases. CONCLUSION Serum PICP levels correlate well with results of bone scans, while serum ICTP levels increase in patients with PCA regardless of the presence of bone metastases.
The mouse Snrpn minimal promoter and its human orthologue: activity and imprinting

Background Microdeletions in chromosome 15q13‐15 of Prader‐Willi (PWS) and Angelman Syndrome (AS) patients suggested that SNRPN promoter/exon 1, together with a short sequence located approximately 35 kb upstream, constitute an imprinting control centre that regulates the entire 2 Mb PWS/AS imprinted domain. We have recently shown that a minitransgene composed of the human upstream sequence and mouse Snrpn promoter/exon 1 harbours all the elements necessary for establishing and maintaining an imprinted state.
Use of sire referencing schemes to select for improved carcass composition in sheep.

Objective genetic improvement in specialized meat breeds of sheep in Britain is based largely on the performance recording and genetic evaluation service provided by Signet and the Meat and Livestock Commission. This includes the use of ultrasonic scanning and a selection index to identify animals with high genetic merit for lean growth. More than 20 sire referencing schemes (SRS) have been established in Britain during the last 12 yr. About half of the performance-recorded flocks in Britain now belong to SRS.
Alterations in circadian and meal-induced gut peptide levels in lean and obese rats

Alterations in gut hormone signaling are a likely contributing factor to the metabolic disturbances associated with overweight/obesity as they coordinate the timing of feeding behavior, absorption, and utilization of nutrients. These hormones are released in response to food intake, or follow a circadian or anticipatory pattern of secretion that is independent of nutrient stimulation. The aim of this study was to identify the degree to which high-fat diet-induced obesity would alter the daily rhythm of gut peptide plasma levels (glucagon-like peptide-1 [GLP-1], peptide YY [PYY], insulin or amylin [AMY]) or meal-induced levels in the middle of the light or dark cycle. Male Sprague-Dawley rats were fed a high-fat diet (OBESE) or chow (LEAN), implanted with jugular catheters, and blood samples were taken every 2 h throughout the light/dark cycle while freely feeding or after an Ensure liquid meal. We found that even when OBESE and LEAN animals ate the same kcals and have a similar pattern of food intake, there is a difference in both the levels and rhythm of plasma gut peptides. GLP-1 and PYY are higher during the light cycle in LEAN animals and AMY is higher in the OBESE group throughout the light/dark cycle. There was also a differential response of plasma gut signals after the Ensure meal, even though the composition and amount of intake of the meal were the same in both groups. These changes occur prior to the high-fat diet induced loss of glycemic control and may be a target for early intervention. Impact statement The aim of this study was to test if obesity would alter the daily rhythm of gut peptides or meal-induced levels in the middle of the light or dark cycle. We found that even when animals are eating the same amount (in kcal) of food that the obese animals have altered daily rhythms and meal-induced gut peptide levels. In particular, we are the first to show that obesity induces increases in peptide YY levels during the light cycle and amylin remains high throughout the light and dark cycle in obese animals. These changes occurred prior to a loss of glycemic control. Thus, the rhythm of gut peptides could be used as an early indicator of later and more serious metabolic disturbances and may be a target for early intervention.
Comparison of Temporal Patterns and Meaningfulness of the Daily Activities of Schizophrenic and Normal Adults

Assessment of a patient's use of time and the meaningfulness of activities which make up that time is believed to provide occupational therapists with important diagnostic information. Temporal adaptation, although one of the profession's earliest concepts, remains relatively unexplored. Using a cross sectional survey, a pilot study of time use behaviors and perceived meaningfulnes (enjoyability, autonomy, and competency) of daily activities was conducted for a sample of normal and schizophrenic adults. This paper presents the significant differences and trends that were uncovered, suggesting a relationship between schizophrenia and temporal dysfunction does indeed exist.
Extracting More Data from LiDAR in Forested Areas by Analyzing Waveform Shape

Light Detection And Ranging (LiDAR) in forested areas is used for constructing Digital Terrain Models (DTMs), estimating biomass carbon and timber volume and estimating foliage distribution as an indicator of tree growth and health. All of these purposes are hindered by the inability to distinguish the source of returns as foliage, stems, understorey and the ground except by their relative positions. The ability to separate these returns would improve all analyses significantly. Furthermore, waveform metrics providing information on foliage density could improve forest health and growth estimates. In this study, the potential to use waveform LiDAR was investigated. Aerial waveform LiDAR data were acquired for a New Zealand radiata pine plantation forest, and Leaf Area Density (LAD) was measured in the field. Waveform peaks with a good signal-to-noise ratio were analyzed and each described with a Gaussian peak height, half-height width, and an exponential decay constant. All parameters varied substantially across all surface types, ruling out the potential to determine source characteristics for individual returns, particularly those with a lower signal-to-noise ratio. However, pulses on the ground on average had a greater intensity, decay constant and a narrower peak than returns from coniferous foliage. When spatially averaged, canopy foliage density (measured as LAD) varied significantly, and was found to be most highly correlated with the volume-average exponential decay rate. A simple model based on the Beer-Lambert law is proposed to explain this relationship, and proposes waveform decay rates as a new metric that is less affected by shadowing than intensity-based metrics. This correlation began to fail when peaks with poorer curve fits were included.
Microstructural Evolution in a CeO2-Gd2O3 System

Abstract Microstructural evolution in a CeO2-Gd2O3 system at atomic and nanoscale levels with increasing Gd concentration has been comprehensively investigated by transmission electron microscopy. When the Gd concentration was increased from 10 to 80 at. %, the phase transformation from ceria with fluorite structure to solid solution with C-type structure was not a sudden change but an evolution in the sequence of clusters, domains, and precipitates with C-type structure in the fluorite-structured matrix. Moreover, the ordering of aggregated Gd cations and oxygen vacancies in these microstructural inhomogeneities developed continuously with increasing Gd concentration. This microstructural evolution can be further described based on the development of defect clusters containing Gd cations and oxygen vacancies.
Dynamics of Consumer Demand for New Durable Goods

Most new consumer durable goods experience rapid prices declines and quality improvements, suggesting the importance of modeling dynamics. This paper specifies a dynamic model of consumer preferences for new durable goods with persistently heterogeneous consumer tastes, rational expectations, and repeat purchases over time. We estimate the model on the digital camcorder industry using panel data on prices, sales, and characteristics. We find that the 1-year elasticity in response to a transitory industrywide price shock is about 25 percent less than the 1-month elasticity. Standard cost-of-living indices overstate welfare gain in later periods due to a changing composition of buyers.
Increased health care utilization among long‐term cancer survivors compared to the average Dutch population: A population‐based study

In the present study, self‐reported health care utilization of cancer survivors is compared with those of an age‐ and gender‐matched normative population and predictors of health care utilization are identified. A population‐based, cross‐sectional survey among 1893 long‐term survivors of endometrial and prostate cancer and malignant lymphomas (Hodgkin's and non‐Hodgkin's) diagnosed between 1989 and 1998 was conducted using the cancer registry of the Comprehensive Cancer Centre South. Cancer survivors visited their general practitioner somewhat more often compared to the age and gender‐matched general Dutch population but this effect was not always statistically significant. In addition, they visited their medical specialist significantly more often. Survivors only sporadically (0–3%) visited or required a dietician, sexologist, oncology nurse, pastor, creative therapy or recovery program. Contact with a psychologist, physiotherapist and other cancer survivors took place somewhat more often. Patients visited a medical specialist less often if they were diagnosed with endometrial cancer (OR = 0.2; 95% CI = 0.1–0.5), if they were diagnosed between 10–15 years ago (OR = 0.6; 95% CI = 0.1–0.5) and if they were not married or divorced (OR = 0.5; 95% CI = 0.3–0.9). Contact with a psychologist was related to having a university or college degree (OR = 3.6; 95% CI = 1.3–9.4). Cancer survivors visited their specialist more often compared to the normative population. Changes in health care, such as less administrative work for the specialist and more efficiency, are probably necessary in order to cope adequately with the increasing demand on the system. © 2007 Wiley‐Liss, Inc.
Measuring Mobile Users' Concerns for Information Privacy

The evolution of mobile network technologies and smartphones has provided mobile consumers with unprecedented access to Internet and value-added services while on the move. Privacy issues in such context become critically important because vendors may access a large volume of personal information. Although several pioneering studies have examined general privacy risks, few systematic attempts have been made to provide a theory-driven framework on the specific nature of privacy concerns among mobile consumers. To fill the gap in the literature, this article introduced a 9-item scale, which was shown to reasonably represent the dimensionality of mobile users' information privacy concerns (MUIPC), categorized as perceived surveillance, perceived intrusion, and secondary use of personal information. Through a survey study (n=310), the three-factor structure of MUIPC as revealed in exploratory factor analysis was further confirmed through confirmatory factor analysis. Further analysis revealed that the second-order model of MUIPC performed better than its first-order model.
Implications of Frequency Control Bias Settings on Interconnected System Operation and Inadvertent Energy Accounting

This paper describes the adversities of present practices for inadvertent energy and time error correction from the interconnected system point of view by considering their constrained coupling effects between control areas. Partial implementations of decomposition theory are suggested as practical solutions to the iniquities and deficiencies of the present scheme. A scheme for phasing-in decomposition accounting, which can be voluntary by area, is suggested and explained. An argument is made for an official and essentially constant annual value of frequency bias to be used for decomposition. The frequency bias used in area control error (ACE) need not be constant, or necessarily equal to the decomposition parameter.
Atherosclerosis and vasomotor dysfunction in arteries of animals after exposure to combustion-derived particulate matter or nanomaterials

Abstract Exposure to particulate matter (PM) from traffic vehicles is hazardous to the vascular system, leading to clinical manifestations and mortality due to ischemic heart disease. By analogy, nanomaterials may also be associated with the same outcomes. Here, the effects of exposure to PM from ambient air, diesel exhaust and certain nanomaterials on atherosclerosis and vasomotor function in animals have been assessed. The majority of studies have used pulmonary exposure by inhalation or instillation, although there are some studies on non-pulmonary routes such as the gastrointestinal tract. Airway exposure to air pollution particles and nanomaterials is associated with similar effects on atherosclerosis progression, augmented vasoconstriction and blunted vasorelaxation responses in arteries, whereas exposure to diesel exhaust is associated with lower responses. At present, there is no convincing evidence of dose-dependent effects across studies. Oxidative stress and inflammation have been observed in the arterial wall of PM-exposed animals with vasomotor dysfunction or plaque progression. From the data, it is evident that pulmonary and systemic inflammation does not seem to be necessary for these vascular effects to occur. Furthermore, there is inconsistent evidence with regard to altered plasma lipid profile and systemic inflammation as a key step in vasomotor dysfunction and progression of atherosclerosis in PM-exposed animals. In summary, the results show that certain nanomaterials, including TiO2, carbon black and carbon nanotubes, have similar hazards to the vascular system as combustion-derived PM.
Assessing the cost-effectiveness of pharmacogenomics

The use of pharmacogenomics to individualize drug therapy offers the potential to improve drug effectiveness, reduce adverse side effects, and provide cost-effective pharmaceutical care. However, the combinations of disease, drug, and genetic test characteristics that will provide clinically useful and economically feasible therapeutic interventions have not been clearly elucidated. The purpose of this paper was to develop a framework for evaluating the potential cost-effectiveness of pharmacogenomic strategies that will help scientists better understand the strategic implications of their research assist in the design of clinical trials, and provide a guide for health care providers making reimbursement decisions. We reviewed concepts of cost-effectiveness analysis and pharmacogenomics and identified 5 primary characteristics that will enhance the cost-effectiveness of pharmacogenomics: 1) there are severe clinical or economic consequence that are avoided through the use of pharmacogenomics, 2) monitoring drug response using current methods is difficult, 3) a well-established association between genotype and clinical phenotype exists, 4) there is a rapid and relatively inexpensive genetic test, and 5) the variant gene is relatively common. We use this framework to evaluate several examples of pharmacogenomics. We found that pharmacogenomics offers great potential to improve patients' health in a cost-effective manner. However, pharmacogenomics will not be applied to all currently marketed drugs, and careful evaluations are needed on a case-by-case basis before investing resources in research and development of pharmacogenomic-based therapeutics and making reimbursement decisions.
Localized overexpression of alpha‐internexin within nodules in multinodular and vacuolating neuronal tumors

Multinodular and vacuolating neuronal tumors (MVNT) have been recently referred to as a distinctive neuronal tumor entity based on histopathological findings. They are characterized by multiple tumor nodules, vacuolar alteration and widespread immunolabeling for human neuronal protein HuC/HuD. Only 13 cases have been reported in the literature to date and little is known about the histopathology of these tumors. Herein, we report a case of MVNT with additional confirmation of immunohistochemical features. A 22‐year‐old woman presented with a continuous headache. MRI showed a subcortical white matter lesion with multiple satellite nodules in the frontal lobe appearing as T2/fluid‐attenuated inversion recovery (FLAIR) hyperintensities. Histological examination of the resected lesion revealed well‐defined multiple nodules composed of predominant vacuolating tumor cells. The tumor cells exhibited consistent immunolabeling for doublecortin, as well as HuC/HuD, both representative neuronal biomarkers associated with earlier stages of neuronal development. Immunopositivity for oligodendrocyte transcription factor 2 (Olig2) and S100 was also detected in tumor cells. Additionally, significant overexpression of alpha‐internexin was observed in the background neuropil limited to tumor nodules. Neuronal nuclear antigen (NeuN), synaptophysin and neurofilament, markers for mature neurons, were either negative or weakly positive. The expression profile of neuronal biomarkers can be distinguished from that of classic neuronal tumors and is the immunohistochemical hallmark of MVNT. In summary, we identified the characteristic tumoral expression of HuC/HuD and doublecortin and the presence of abundant neuropil localized in MVNT tumor nodules, which exhibited widespread alpha‐internexin expression. These results supported the presumption that MVNT is a distinct histopathological entity.
Validity of the American Sign Language Discrimination Test

American Sign Language (ASL) is one of the most commonly taught languages in North America. Yet, few assessment instruments for ASL proficiency have been developed, none of which have adequately demonstrated validity. We propose that the American Sign Language Discrimination Test (ASL-DT), a recently developed measure of learners’ ability to discriminate phonological and morphophonological contrasts in ASL, provides an objective overall measure of ASL proficiency. In this study, the ASL-DT was administered to 194 participants at beginning, intermediate, and high levels of ASL proficiency, a subset of which (N = 57) also was administered the Sign Language Proficiency Interview (SLPI), a widely used subjective proficiency measure. Using Rasch analysis to model ASL-DT item difficulty and person ability, we tested the ability of the ASL-DT Rasch measure to detect participant proficiency group mean differences and compared its discriminant performance to the SLPI ratings for classifying individuals into their pre-assigned proficiency groups using resource operating characteristic statistics. The ASL-DT Rasch measure outperformed the SLPI ratings, indicating that the ASL-DT may provide a valid objective measure of overall ASL proficiency. As such, the ASL-DT Rasch measure may provide a useful complement to measures such as the SLPI in comprehensive sign language assessment programs.