Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential action of the bisphosphonates (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) and disodium dichloromethylidene bisphosphonate (Cl2MDP) on rat macrophage-mediated bone resorption in vitro.

The bisphosphonates (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) and disodium dichloromethylidene bisphosphonate (Cl(2)MDP) effectively inhibit the accelerated bone resorption associated with some skeletal disorders, e.g., Paget's disease. However, it has not been established whether these compounds exert their inhibitory effect by rendering the bone mineral more resistant to degradation, by diminishing the activity of resorbing cells, or through some combination of both activities. In this study, we have tested these possibilities using an in vitro resorption assay system consisting of elicited rat peritoneal macrophages co-cultured with particles of (45)Ca-labeled, devitalized rat bone. This assay system permits the quantitative assessment of the action of APD and Cl(2)MDP on the two major phases of bone resorption (cell-substrate attachment and osteolysis) under circumstances where the drugs are present continuously or, most importantly for the issues in question, after the separate pretreatment of the particles or the resorbing cells. Our data indicate that (a) Both APD and Cl(2)MDP at concentrations >/=5 x 10(-6) M diminish macrophage-mediated (45)Ca release (i.e., bone resorption) in a log dose-dependent fashion. (b) A 10-min pretreatment of bone particles with either bisphosphonate (P-C-P) similarly inhibits resorptive activity, but is most pronounced with Cl(2)MDP. However, only APD is effective in reducing resorption when cells are preincubated (for 24 h) with P-C-P. (c) In cultures containing both labeled and unlabeled bone, significant inhibition occurs only when the labeled particles are coated with P-C-P (indicating that the action of P-C-P-treated bone is highly localized). (d) P-C-P does not diminish cell-bone particle attachment, an essential step in the resorptive process. On the other hand, delaying the addition of P-C-P until after cell-bone attachment is completed significantly reduces the resorption-inhibiting effect of these compounds. (e) Cl(2)MDP reduces culture DNA content in proportion to its inhibitory effect on resorption, and both the inhibitory and cytotoxic actions of this P-C-P are dependent upon the presence of bone. On the other hand, APD is cytotoxic only at very high concentrations (10(-4) M), acts independently of the presence of bone, and inhibits resorption without killing cells. We conclude that the mechanisms of action of APD and Cl(2)MDP are markedly different. Cl(2)MDP is a potent cytotoxin in the presence of bone and apparently exerts its inhibitory effect in this manner. APD is noncytotoxic at levels adequate to suppress resorption and, therefore, must inhibit macrophage activity by some other mechanism. Neither P-C-P appears to limit resorption by decreasing the solubility of mineralized bone matrix.
Transgenerational Variation in Metabolism and Life-History Traits Induced by Maternal Hypoxia in Daphnia magna*

Hypoxic stress can alter conspecific phenotype and additionally alter phenotypes of the filial generation, for example, via maternal or epigenetic processes. Lasting effects can also be seen across development and generations even after stressors have been removed. This study utilized the model of rapidly developing, parthenogenetic Daphnia to examine the intraspecific variability of response of exposure of a parental generation to hypoxia (4 kPa) within a single clone line across development, across broods, and across generations. Body mass across development and reproductive output were monitored in the parental generation and the first three broods of the first filial generation (which were not directly exposed to hypoxia). O2 consumption across a wide Po2 range (normoxia to anoxia) was assessed to determine whether exposure of the parental generation to hypoxia conferred hypoxia tolerance on the offspring and whether this transgenerational, epigenetic phenomenon varied intraspecifically. Differences in mass occurred in both the parental generation (hypoxia-exposed smaller during brood 1 and brood 2 neonate production) and the filial generation (e.g., brood 1 and 2 neonates from hypoxic mothers were initially smaller than control neonates). However, differences in mass were not accompanied by changes in reproductive output (assessed by brood number and neonate size). At day 0, first filial generation brood 1 neonates from hypoxia-exposed mothers had a higher metabolic rate than control neonates. However, this effect, like that of body mass, dissipated with development within a brood but also with subsequent broods. An isometric scaling exponent for was repeatedly observed across a wide Po2 range (21–2 kPa) throughout neonatal development.
Adjuvant Chemotherapy for Patients with Stage III Colon Cancer: Results from a CDC-NPCR Patterns of Care Study

Objective To evaluate adjuvant chemotherapy use for Stage III colon cancer. Methods This analysis included 973 patients with surgically treated stage III colon cancer. Socioeconomic information from the 2000 census was linked to patients’ residential census tracts. Vital status through 12/31/02 was obtained from medical records and linkage to state vital statistics files and the National Death Index. Results Adjuvant chemotherapy was received by 67%. Treatment varied by state of residence, with Colorado, Rhode Island and New York residents more likely to receive chemotherapy than Louisiana residents. Older age, increasing comorbidities, divorced/widowed marital status, and residence in lower education areas or non-working class neighborhoods were associated with lower chemotherapy use. Survival varied by state but after adjustment for sex, sociodemographic and health factors, was significantly higher only for California and Rhode Island. Older age and lower educational attainment were associated with lower survival. Chemotherapy was protective for all comorbidity groups. Conclusion Although adjuvant chemotherapy for Stage III colon cancer improves survival, some patients did not receive standard of care, demonstrating the need for cancer treatment surveillance. Interstate differences likely resulted from differences in local practice patterns, acceptance of treatment, and access.
Accuracy of Alcohol Use Disorders Identification Test for detecting problem drinking in 18-35 year-olds in England: method comparison study.

AIMS To assess the accuracy of Alcohol Use Disorders Identification Test (AUDIT) scores for problem drinking in males and females aged 18-35 in England. METHODS A method comparison study with 420 primary care patients aged 18-35. Test measures were AUDIT and AUDIT-C. Reference standard measures were (a) Time-Line Follow-Back interview for hazardous drinking; World Mental Health Composite International Diagnostic Interview for (b) DSM-IV alcohol abuse, (c) DSM-IV alcohol dependence, (d) DSM-5 alcohol use disorders. RESULTS Area under the curve (AUC) was (a) 0.79 (95% CI 0.73-0.85; males) and 0.84 (0.79-0.88; females); (b) 0.62 (0.54-0.72; males) and 0.65 (0.57-0.72; females); (c) 0.77 (0.65-0.87; males) and 0.76 (0.67-0.74; females); (d) 0.70 (0.60-0.78; males) and 0.73 (CI 0.67-0.78; females). Identification of threshold cut-point scores from the AUC was not straightforward. Youden J statistic optimal cut-point scores varied by 4-6 AUDIT scale points for each outcome according to whether sensitivity or specificity were prioritized. Using Bayes' Theorem, the post-test probability of drinking problems changed as AUDIT score increased, according to the slope of the probability curve. CONCLUSION The full AUDIT scale showed good or very good accuracy for all outcome measures for males and females, except for alcohol abuse which had sufficient accuracy. In a screening scenario where sensitivity might be prioritized, the optimal cut-point is lower than established AUDIT cut-points of 8+ for men and 6+ for women. Bayes' Theorem to calculate individual probabilities for problem drinking offers an alternative to arbitrary cut-point threshold scores in screening and brief intervention programmes.
Evolution of upper airway resistance syndrome

The question of whether upper airway resistance syndrome (UARS) is a distinct disease or an initial feature of obstructive sleep apnoea syndrome is still a matter of debate. We evaluated a retrospective group of UARS patients to determine the evolution of UARS over time and the relationship between clinical evolution and subjects’ phenotype. Investigations were performed in 30 patients, in whom UARS was diagnosed between 1995 and 2000 by the use of full polysomnography (PSG) without oesophageal pressure (Pes) measurement. The time between initial and follow‐up investigations was 6.6 ± 2.6 years. All subjects had full PSG with Pes measurement and completed a sleep questionnaire, including the Epworth Sleepiness Scale. In 19 subjects, PSG results were compatible with UARS. In nine subjects, obstructive sleep apnoea–hypopnoea syndrome (OSAHS) was diagnosed. In two subjects, PSG did not demonstrate breathing abnormalities. The mean ± SD apnoea–hypopnoea index in the UARS group was 1.5 ± 1.7 h−1 and 25.2 ± 19 h−1 in the OSAHS group (P < 0.01). The increase in body mass index (BMI) between initial and follow‐up investigations in the UARS group was from 29.4 ± 4 to 31 ± 5.7 kg m−2 (P = 0.014) and in the OSAHS group from 30 ± 4.1 to 32.4 ± 4.7 kg m−2(P = 0.004). Amplitude of Pes swings during respiratory events was significantly higher in OSAHS than that in UARS (P = 0.014). Our results suggest that UARS is part of a clinical continuum from habitual snoring to OSAHS. Progression from UARS to OSAHS seems to be related to an increase in the BMI.
A Cognitive Science Approach to the Semantics of Spatial Gradation

This paper presents a new approach to the semantics of spatial degree and comparison (gradation) expressions (e.g., 2m less long than). Taking a broad cognitive science perspective, results of different research fields are combined into a cognitive framework for the ‘semantics of gradation’ (Bierwisch 1989). A distinction between implicitly and explicitly represented aspects of space will be made, and selective spatial attention will be proposed as a cognitive construct that is essential for the explanation of gradation phenomena.
Piezoelectric and dielectric properties of siloxane elastomers filled with bariumtitanate

Piezoelectric elastomers were prepared from suspensions of bariumtitanate (BaTiO 3 ) particles in a telechelic polydimethylsiloxane (t-PDMS) by crosslinking the t-PDMS under an electric field. Crosslinking reaction was monitored by measurement of complex dielectric constant e' - ie. Dielectric constant e' increased with increasing BaTiO 3 content, and agreed approximately with the theoretical e' calculated with the Maxwell-Wagner theory. Piezoelectric constant d 33 of the poled elastomers was measured by application of compressions in the direction of the poling field. It was found that d 33 was of the order of 10 -11 C/N and increased steeply with increasing content of BaTiO 3 but became almost independent of composition in the range of BaTiO 3 content from 3 to 14 vol %. To examine the effect of electric field on the aggregation structure of the particles, we observed light scattering of the suspension under an electric field, and found that the scattering pattern became anisotropic. This indicated that the particles are connected like a pearl necklace and are stretched in the direction of the poling field. The dependence of d 33 on the volume fraction of BaTiO 3 was explained by a model proposed by Banno.
The Signaling and Biological Implications of FAK Overexpression in Cancer

In this issue of Clinical Cancer Research , Canel et al. ([1][1]) describe a new study investigating the role of focal adhesion kinase (FAK) in head and neck squamous cell carcinoma (HNSCC). Using immunohistochemical analysis of >200 HNSCC clinical specimens, they show FAK overexpression in the
Mixed Finite Elements for Variational Surface Modeling

Many problems in geometric modeling can be described using variational formulations that define the smoothness of the shape and its behavior w.r. t. the posed modeling constraints. For example, high‐quality C2 surfaces that obey boundary conditions on positions, tangents and curvatures can be conveniently defined as solutions of high‐order geometric PDEs; the advantage of such a formulation is its conceptual representation‐independence. In practice, solving high‐order problems efficiently and accurately for surfaces approximated by meshes is notoriously difficult. For modeling applications, the preferred approach is to use discrete geometric schemes which are efficient and robust, but their convergence properties are less well understood compared to higher‐order FEM. In this paper, we explore discretizations of common geometric PDEs on meshes using mixed finite elements, where additional variables for the derivatives in the problem are introduced. Such formulations use first‐order derivatives only, allowing a discretization with simple linear elements. Various boundary conditions can be naturally discretized in this setting. We formalize continuous region constraints commonly used in modeling applications, and show that these seamlessly fit into the mixed framework. We demonstrate that some of the commonly used discrete geometric discretizations can be regarded as a particular case of mixed finite elements. We study the convergence behavior of our discretizations, and how they can be applied to implement common modeling tasks.
Conflict between Translation Initiation and Elongation in Vertebrate Mitochondrial Genomes

The strand-biased mutation spectrum in vertebrate mitochondrial genomes results in an AC-rich L-strand and a GT-rich H-strand. Because the L-strand is the sense strand of 12 protein-coding genes out of the 13, the third codon position is overall strongly AC-biased. The wobble site of the anticodon of the 22 mitochondrial tRNAs is either U or G to pair with the most abundant synonymous codon, with only one exception. The wobble site of Met-tRNA is C instead of U, forming the Watson-Crick match with AUG instead of AUA, the latter being much more frequent than the former. This has been attributed to a compromise between translation initiation and elongation; i.e., AUG is not only a methionine codon, but also an initiation codon, and an anticodon matching AUG will increase the initiation rate. However, such an anticodon would impose selection against the use of AUA codons because AUA needs to be wobble-translated. According to this translation conflict hypothesis, AUA should be used relatively less frequently compared to UUA in the UUR codon family. A comprehensive analysis of mitochondrial genomes from a variety of vertebrate species revealed a general deficiency of AUA codons relative to UUA codons. In contrast, urochordate mitochondrial genomes with two tRNAMet genes with CAU and UAU anticodons exhibit increased AUA codon usage. Furthermore, six bivalve mitochondrial genomes with both of their tRNA-Met genes with a CAU anticodon have reduced AUA usage relative to three other bivalve mitochondrial genomes with one of their two tRNA-Met genes having a CAU anticodon and the other having a UAU anticodon. We conclude that the translation conflict hypothesis is empirically supported, and our results highlight the fine details of selection in shaping molecular evolution.
The Transcription Factor Prdm16 Marks a Single Retinal Ganglion Cell Subtype in the Mouse Retina

Purpose Retinal ganglion cells (RGC) can be categorized into roughly 30 distinct subtypes. How these subtypes develop is poorly understood, in part because few unique subtype markers have been characterized. We tested whether the Prdm16 transcription factor is expressed by RGCs as a class or within particular ganglion cell subtypes. Methods Embryonic and mature retinal sections and flatmount preparations were examined by immunohistochemistry for Prdm16 and several other cell type-specific markers. To visualize the morphology of Prdm16+ cells, we utilized Thy1-YFP-H transgenic mice, where a small random population of RGCs expresses yellow fluorescent protein (YFP) throughout the cytoplasm. Results Prdm16 was expressed in the retina starting late in embryogenesis. Prdm16+ cells coexpressed the RGC marker Brn3a. These cells were arranged in an evenly spaced pattern and accounted for 2% of all ganglion cells. Prdm16+ cells coexpressed parvalbumin, but not calretinin, melanopsin, Smi32, or CART. This combination of marker expression and morphology data from Thy1-YFP-H mice suggested that the Prdm16+ cells represented a single ganglion cell subtype. Prdm16 also marked vascular endothelial cells and mural cells of retinal arterioles. Conclusions A single subtype of ganglion cell appears to be uniquely marked by Prdm16 expression. While the precise identity of these ganglion cells is unclear, they most resemble the G9 subtype described by Völgyi and colleagues in 2009. Future studies are needed to determine the function of these ganglion cells and whether Prdm16 regulates their development.
Broadening the versatility of lentiviral vectors as a tool in nucleic acid research via genetic code expansion

With the aim of broadening the versatility of lentiviral vectors as a tool in nucleic acid research, we expanded the genetic code in the propagation of lentiviral vectors for site-specific incorporation of chemical moieties with unique properties. Through systematic exploration of the structure–function relationship of lentiviral VSVg envelope by site-specific mutagenesis and incorporation of residues displaying azide- and diazirine-moieties, the modifiable sites on the vector surface were identified, with most at the PH domain that neither affects the expression of envelope protein nor propagation or infectivity of the progeny virus. Furthermore, via the incorporation of such chemical moieties, a variety of fluorescence probes, ligands, PEG and other functional molecules are conjugated, orthogonally and stoichiometrically, to the lentiviral vector. Using this methodology, a facile platform is established that is useful for tracking virus movement, targeting gene delivery and detecting virus–host interactions. This study may provide a new direction for rational design of lentiviral vectors, with significant impact on both basic research and therapeutic applications.
Adult Active Transport in the Netherlands: An Analysis of Its Contribution to Physical Activity Requirements

Introduction Modern, urban lifestyles have engineered physical activity out of everyday life and this presents a major threat to human health. The Netherlands is a world leader in active travel, particularly cycling, but little research has sought to quantify the cumulative amount of physical activity through everyday walking and cycling. Methods Using data collected as part of the Dutch National Travel Survey (2010 – 2012), this paper determines the degree to which Dutch walking and cycling contributes to meeting minimum level of physical activity of 150 minutes of moderate intensity aerobic activity throughout the week. The sample includes 74,465 individuals who recorded at least some travel on the day surveyed. As physical activity benefits are cumulative, all walking and cycling trips are analysed, including those to and from public transport. These trips are then converted into an established measure of physical activity intensity, known as metabolic equivalents of tasks. Multivariate Tobit regression models were performed on a range of socio-demographic, transport resources, urban form and meteorological characteristics. Results The results reveal that Dutch men and women participate in 24 and 28 minutes of daily physical activity through walking and cycling, which is 41% and 55% more than the minimum recommended level. It should be noted however that some 57% of the entire sample failed to record any walking or cycling, and an investigation of this particular group serves as an important topic of future research. Active transport was positively related with age, income, bicycle ownership, urban density and air temperature. Car ownership had a strong negative relationship with physically active travel. Conclusion The results of this analysis demonstrate the significance of active transport to counter the emerging issue of sedentary lifestyle disease. The Dutch experience provides other countries with a highly relevant case study in the creation of environments and cultures that support healthy, active living.
Job Satisfaction of Nurses in a Regional Hospital in Oman: A Cross-Sectional Survey.

BACKGROUND Job satisfaction has become a critical issue for healthcare organizations, particularly in nursing, because of the shortage of nursing labor, the effect on patient care, and the associated costs. This study explores the factors that influence the level of job satisfaction of nurses working in one regional hospital in Oman. PURPOSE This study aims to measure the job satisfaction of nurses working at a regional hospital in Oman and to determine the factors that most significantly influence this satisfaction. Job satisfaction is measured using the McCloskey/Mueller Satisfaction Scale. In addition, the demographic characteristics of participants (age, gender, level of education, years of experience, marital status, work shift, work unit, and nationality) are obtained to assess potential correlations. METHODS A questionnaire survey was used to collect the data, and stratified random sampling was used to recruit potential participants. A cross-sectional survey was used to collect data from 155 participants who worked at one regional hospital in Oman, with survey data analyzed using SPSS version 19. One hundred forty-three valid responses were received (response rate: 92%). The study used descriptive data analysis to address the first research question and used analysis methods such as multiregression analyses, and one-way analysis of variance to identify the relationships between the other variables. RESULTS The overall mean score for satisfaction was 3.49, indicating that participants had a moderate level of job satisfaction. "Interaction with coworkers" and "extrinsic reward" earned, respectively, the highest and lowest job satisfaction ratings on the subscale of McCloskey/Mueller Satisfaction Scale. The results showed that age, work shift, and nationality each had a statistically significant effect on overall job satisfaction. A multiple regression analysis indicated that 21.8% of the total variance in the dependent variables was explained by being non-Omani in nationality, indicating that that overall job satisfaction was higher in non-Omani nurses than in Omani nurses. CONCLUSIONS The result suggests that professional opportunity and extrinsic reward are two important factors that affect the job satisfaction of nurses in Oman. Addressing these two factors effectively may help improve the quality of nursing care in Oman. Furthermore, this study may be conducted more widely in government hospitals in Oman to validate the identified factors and to identify additional factors that may affect job satisfaction.