Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of aprepitant, the first neurokinin‐1 receptor antagonist for the prevention of chemotherapy‐induced nausea and vomiting

Chemotherapy can be a life‐prolonging treatment for many cancer patients, but it is often associated with profound nausea and vomiting that is so distressing that patients may delay or decline treatment to avoid these side effects. EMEND™ (aprepitant) is the first and only neurokinin‐1 (NK‐1) receptor antagonist available on the market for the prevention of acute and delayed chemotherapy‐induced nausea and vomiting (CINV). Aprepitant acts centrally at NK‐1 receptors in vomiting centers within the central nervous system to block their activation by substance P released as an unwanted consequence of chemotherapy. By controlling nausea and vomiting, EMEND helps improve patients’ daily living and their ability to complete multiple cycles of chemotherapy. The development of aprepitant included a novel nanoparticle formulation to optimize oral absorption and innovative chemistry to discover a prodrug form suitable for intravenous administration to improve compliance and convenience for healthcare professionals and cancer patients.
Probing Single Molecules and Single Nanoparticles by Surface-Enhanced Raman Scattering

Optical detection and spectroscopy of single molecules and single nanoparticles have been achieved at room temperature with the use of surface-enhanced Raman scattering. Individual silver colloidal nanoparticles were screened from a large heterogeneous population for special size-dependent properties and were then used to amplify the spectroscopic signatures of adsorbed molecules. For single rhodamine 6G molecules adsorbed on the selected nanoparticles, the intrinsic Raman enhancement factors were on the order of 1014 to 1015, much larger than the ensemble-averaged values derived from conventional measurements. This enormous enhancement leads to vibrational Raman signals that are more intense and more stable than single-molecule fluorescence.
The Effect of Long-term, Daily Contact Lens Wear on Corneal Sensitivity

Purpose. To assess the effect of long-term, daily-wear soft contact lenses and rigid gas permeable (RGP) contact lenses on corneal sensitivity using a noninvasive, air-pulse stimulus. Methods. The central and peripheral (temporal, medial, inferior) corneal sensation thresholds of 40 non-lens wearers, 40 soft lens wearers, and 40 RGP lens wearers were assessed using the Non-Contact Corneal Aesthesiometer (NCCA). The individuals who wore contact lenses were grouped according to the number of years of lens wear (10 years or less, 11–20 years, and 21 years or more). Results. Although a significant reduction in corneal sensitivity was found between the contact lens wearers and non-lens wearers (p = 0.000), no difference was found between the two lens-type subgroups (p = 0.939). This pattern of significance was repeated at each of the peripheral test locations. No relationship between corneal sensitivity and years of lens wear was found centrally (r2= 0.004) or at any of the peripheral test locations. No significant difference was found between the central corneal sensation thresholds for the different subgroups of lens wear duration (p = 0.469) or for any of the peripheral test locations. Conclusions. Both soft and RGP lens wear produce a similar type of corneal sensitivity loss, although the mechanism for this loss is different for the two lens types. The extent of sensitivity loss is not related to the duration of lens wear and appears to plateau after the first few months of wear. No topographical variation in sensitivity loss was found with lens type or with the duration of lens wear.
No Female Disadvantage in Anthropometric Status among Children in India

Female disadvantage in child mortality, intra-household allocation of food and coverage of health interventions has been shown to exist in India. At the same time, there has been limited examination of female disadvantage in nutritional status. Using measures of anthropometry and anthropometric failure, we study female disadvantage in child nutritional status from the data collected from the Indian National Family Health Survey (NFHS) undertaken in 1992–1993 and 2005–2006. Height and/or weight measurements were available on 70,148 children aged 0–47 months in both survey periods. Child anthropometry (height/length-for-age [HAZ], weight-for-age [WAZ], weight-for-height/length [WHZ]) and anthropometric failure (defined according to the 2006 WHO growth standards as stunting, wasting and underweight) were analysed using linear and logistic regression models. In pooled regression models, boys were more likely to have lower anthropometric scores and higher rates of anthropometric failure. Across survey periods, the change in anthropometric status was greater for boys compared to girls for WAZ/underweight and WHZ/wasting, but was similar for HAZ/stunting. Boy–girl differences in anthropometry (with boys doing worse) were greater at less than 24 months of age and narrowed over time particularly in the 0–5 and 6–11 month age groups, resulting in no gender differences in anthropometric status. Declines in anthropometric status in HAZ/stunting and WAZ/underweight were found among third or higher birth order boys and girls, especially within families with two preceding children of the same sex but also in households with preceding children of mixed genders, suggesting a birth order effect as opposed to a birth order and gender effect. In 1992–1993 and 2005–2006, levels of anthropometric failure were higher among boys compared to girls in a majority of states. Although girls had lower levels of anthropometric failure, the magnitude of the between survey period decline was higher in girls in fewer states compared to boys (5/20, 7/25 and 10/20 states for stunting, underweight and wasting, respectively). In summary, in the most recently available data, using measures of anthropometric status, we did not find consistent evidence for female disadvantage in nutritional status among girls in India.
Acetylation Polymorphism and Prevalence of Colorectal Adenomas 1

Polymorphic W-acetyltransferase (NAT2), an enzyme present in the colon, may affect incidence of colon cancer. Individuals with NAT2 fast acetylator genotypes may have higher colon cancer risks due to faster conversion of certain carcinogens to mutagens. We determined NAT2 genotypes in 447 subjects with distal colon adenomas and in 487 controls. No significant increase in adenoma prevalence among fast acetylators was observed. However, there was a suggestion of ethnic differences in NAT2 effects. For example, white fast acetylators potentially had slightly in creased risks for adenomas (odds ratio, 1.29; 95% confidence interval, 0.90-1.84), whereas fast acetylation was potentially protective among blacks (odds ratio, 0.64; 95% confidence interval, 0.32-1.28). The appar ent difference between blacks and whites may simply reflect random variation around an overall null effect, or it could represent a real difference. There was preliminary evidence for a possible interaction between NAT2 and the glutathione transferase Ml null genotype. Smok ers1 adenoma prevalence was 10-fold higher for fast acetylators with the null genotype compared to slow acetylators without the null genotype. Large, multiethnic populations and analysis of combinations of genes for carcinogen metabolism may be needed to further assess the role of NAT2 in colorectal tumorigenesis.
Improving the Performance of Dual Linear Polarization Antennas with Metamaterial Structures

In this dissertation, the operation of dual-linear polarized antennas is considered in order to provide ideal performance suited for several applications including polarimetric synthetic aperture radar (SAR), wireless and satellite communications. The underlying objectives realized in this work are reported as design realizations of dual-linear polarized antennas with low cross polarization patterns and high isolation between ports that employ special properties of the electromagnetic metamaterial (MTM) structures. Some of these key properties appear as negative permittivity, negative permeability, negative refractive index, and antiparallel nature of the phase velocity and the group velocity. The antenna design is carried out at two frequencies, 5.5 GHz and 10 GHz, and key physical issues that affect the operation of dual-linear polarization operation antennas are treated in light of electromagnetic MTM properties. It’s well known that a dual linear polarized antenna poses a big challenges such as cross polarization patterns and high mutual coupling between two input ports. Therefore, these drawbacks are key topic that receive significant attention in literature which reports on how to mitigate these drawbacks, however, at the expense of complexity of the antenna structures. The MTM structures have received considerable coverage in antenna research for obtaining size reduction, directivity enhancement, and beam steering. For this purpose, different MTMs structures are chosen in this thesis for achieving additional improvements, while keeping the antenna design as simple as possible, something which is very difficult to accomplish using conventional design methods. As a stepping stone, the MTM unit cell performance can be realized based on the composite right left-hand transmission line (CRLH-TL) analysis. Therefore, the LCparameters are extracted using the pseudo-inverse method for any arbitrary unit cell shape for providing approximate results. Later on, genetic algorithms (GAs) are invoked to tune the LCparameters and achieve the balanced design. Moreover, two categories of the MTMs are utilized as explained in the following: The first is related to the double negative media which are exploited for the design of the dual linear polarized patch antennas based on the application of the CRLH-TL unit cell. The second one exploits single negative media that is beneficial for developing the new antenna
Regulatory Differences in the Approval of GMOs: Extent and Development over Time

Abstract Considering the regulatory approval developments for cotton, maize, and soybean within the time period 2000–2013, this paper assesses the extent of asymmetry in the authorizations of new genetically modified organism (GMO) events between importing and exporting countries. The results show an increase in the asynchronous approval across the majority of country pairs. However, focusing only on commercialized events and considering only regulatory approval differences in which the importers are more stringent than the exporters, the asynchronous approval is considerably lower, and the result indicates that the major trade leaders have synchronized their approval status for GMOs over time. Some countries, such as Norway, Switzerland, Thailand, and Turkey seem to face the highest potential for trade disruption, while the opposite holds for Japan and South Korea.
Dissociation and reassembly of Escherichia coli type 1 pili

Escherichia coli type 1 pili, which mediate the mannose-sensitive adherence of the bacterium to eucaryotic cells, are comprised of very stable arrays of pilin protein subunits (molecular weight, approximately 17,000). Previous methods for the dissociation of pili caused their irreversible denaturation. We have found that incubation of pili in saturated guanidine hydrochloride at 37 degrees C led to their complete dissociation, as evidenced by nephelometry and electron microscopy. Gel chromatography of the dissociated pili on a Sepharose CL-6B column in the presence of saturated guanidine hydrochloride yielded a single protein peak with a molecular weight corresponding to that of pilin. Dialysis of this peak against 5 mM tris(hydroxymethyl)aminomethane hydrochloride (pH 8.0) and rechromatography in the same buffer afforded a major protein peak, probably consisting of pilin dimers. About 25% of the protein in this peak bound to a mannan-sepharose column and could be eluted with methyl alpha-D-mannoside. The pilin dimer gave a single protein band upon polyacrylamide gel electrophoresis in the presence of 0.1% sodium dodecyl sulfate (molecular weight, 16,600) or 10 M urea and penetrated completely into 7% gels in the absence of denaturants. Reassembly of the pilin dimers into pili was achieved upon dialysis against the tris(hydroxymethyl)aminomethane buffer containing 5 mM MgCl2, as observed by electron microscopy. Thus, the conditions used allow renaturation of the dissociated subunits and may aid in further studies of the structure-function relationship of pili.
Measuring Human Capital: Alternative Methods and International Evidence

Human capital is increasingly believed to play an important role in the growth process, however, adequately measuring its stock remains controversial. This paper identifies three general approaches to human capital measurement; cost-based, income-based and education-based, and presents a critical review of the theories and their applications to data from a range of countries. Emphasis on empirical evidence will be given to the case of New Zealand.
The relationship among human papilloma virus infection, survivin, and p53 gene in lung squamous carcinoma tissue.

OBJECTIVE To study the relationship between the infection of human papillomavirus (HPV) type 16, type 18, the expression of survivin, and the mutation of p53 gene in lung squamous carcinoma tissue for the research of pathogenesis of lung carcinoma. METHODS This study was carried out at the Laboratory of Molecular Biology, Xiangfan Central Hospital of Hubei Province, China from September 2008 to May 2010. Forty-five specimens of lung squamous carcinoma tissue confirmed by histopathology were the excisional specimens taken by the Thoracic Surgery of Xiangfan Central Hospital. Normal tissue, closely adjacent to the fresh carcinoma specimens, was used as the control group for p53 gene mutation analysis. Sixteen surgical excisional specimens of benign lung disease were used as a control group of non-carcinomatous diseases. Human papillomavirus DNA were detected by polymerase chain reaction (PCR), and we used the PCR-single-strand conformation polymorphism-ethidium bromide (PCR-SSCP-EB) method to detect the mutations of the p53 gene. The expression of the survivin gene was detected by immunohistochemistry methods. RESULTS Approximately 68.9% of 45 lung squamous carcinoma tissue had p53 gene mutations. The mutation rate of exon 5-8 p53 were 15.6%, 17.8%, 15.6% and 20%. Approximately 42.2% of lung squamous cell carcinoma samples were shown to be positive for HPV DNA expression and 62.2% were positive for survivin expression. There was an inverse correlation between the presence of HPV infections and mutations of p53 gene; and the mutations of p53 gene and expression of survivin had a positive relationship. CONCLUSION Mutation of p53 gene and HPV infection may facilitate each other in the generation of lung squamous cell carcinoma. Abnormal expression of the survivin gene may take part in the onset and progression of lung squamous cell carcinoma.
Both homodimeric isoforms of PDGF (AA and BB) have mitogenic and chemotactic activity and stimulate phosphoinositol turnover

Platelet‐derived growth factor (PDGF) occurs as three dimeric isoforms, AA, BB, and AB, which were previously shown to bind to two receptors with different isoform‐specificity, the A/B‐type (binds all three isoforms) and the B‐type (binds only PDGF‐BB). Results from competition binding experiments with Swiss 3T3 cells suggest the existence of a third receptor type, which recognizes PDGF‐AB and PDGF‐BB. Furthermore, Swiss 3T3 cells and human dermal fibroblasts express different relative and absolute levels of these receptor types. In particular, Swiss 3T3 cells express 90,000 PDGF‐AA binding sites (A/B‐receptors) per cell, whereas human fibroblasts express only 20,000 A/B‐receptors per cell. All three PDGF isoforms were tested in either cell type for their effect on DNA synthesis. PDGF‐BB and PDGF‐AA were also tested in Swiss 3T3 cells for their effect on inositol phospholipid metabolism and chemotaxis. Each isoform promoted all three processes dose‐dependently, but there were differences in the maximum cellular responses elicited. These responses reflect the capacity of the cells to bind the individual isoforms. These results demonstrate that the previous distinctions in responsiveness to the different PDGF isoforms are primarily a consequence of the differences in the levels of surface expression of the various isoform‐specific receptor types, rather than of the differences in the intrinsic activity of these isoforms. Furthermore, these results suggest that all types of PDGF receptors are capable of responding to their respective ligands by mediating phosphoinositide breakdown, chemotactic responses, and DNA synthesis. Whether they exhibit other functional differences remains to be seen.
Validation of Dual-Source Single-Tube Reconstruction as a Method to Obtain Half-Dose Images to Evaluate Radiation Dose and Noise Reduction: Phantom and Human Assessment Using CT Colonography and Sinogram-Affirmed Iterative Reconstruction (SAFIRE)

Objective To evaluate a method for obtaining half-dose CT images for observer studies evaluating lower-dose CT. Methods Phantoms of varying sizes were scanned at multiple tube potentials using dose-matched dual-source (DS) and single-source (SS) protocols. Images from single-tube reconstruction of DS data were compared with SS images acquired at half-original CTDIvol. Thirty patients underwent supine SS and dose-matched prone DS CT colonography (CTC). Half-dose prone images were reconstructed with sinogram-affirmed iterative reconstruction (SAFIRE). Two radiologists scored image quality on 2-dimensional (2D) and 3D images. Results Image noise was similar between half-dose SS images and DS images reconstructed from one tube only with tube potential of 120 kV or more for phantoms 40 cm or smaller (P < 0.05). For both readers, the patients’ CTC image quality scores were more than 84% concordant between SS or DS CTC images, and half-dose–prone CTC images with SAFIRE had 84% or more concordance with routine-dose CTC except for 3D image noise. Conclusions In appropriately sized patients, DS acquisition with single-tube reconstruction can create half-dose images, permitting comparison to full-dose images. For CTC, there is comparable image quality for colonic evaluation between full-dose and half-dose images reconstructed with SAFIRE.
Burg Matrix Divergence-Based Hierarchical Distance Metric Learning for Binary Classification

Distance metric learning is the foundation of many learning algorithms, and it has been widely used in many real-world applications. The basic idea of most distance metric learning methods is to find a space that can optimally separate data points that belong to different categories. However, current methods are mostly based on the single space that only learns one Mahalanobis distance for each data set, which actually fails to perfectly separate different categories in most real-world applications. To improve the accuracy of binary classification, a hierarchical method is proposed in this paper to completely separate different categories by sequentially learning subspace distance metrics. In the proposed method, a base-space distance metric is learned based on a similarity constraint first. Then, for binary classification problems, we formulate the subspace learning problem as a particular Burg Matrix optimization problem that minimizes the Burg Matrix divergence with distance constraints. Moreover, a cyclic projection algorithm is presented to solve the subspace learning problems. The experiments on five UCI data sets using different performance indices demonstrate the improved performance of the proposed method when compared with the state-of-the-art methods.
Where do hybrids come from? Entrepreneurial team heterogeneity as an avenue for the emergence of hybrid organizations

This conceptual article aims to respond to the poorly addressed question of the emergence of hybrid organizations; that is, organizations that embrace several institutional logics. It does so by developing a model and a set of propositions focusing on the heterogeneity of the entrepreneurial team as a possible driver for hybridity throughout the entrepreneurial process and up to the emergence of a hybrid organization. Contributing to the literatures on (collective) entrepreneurship, imprinting and hybrid organizations, we advance several avenues and conditions under which the heterogeneity of the entrepreneurial team may imprint the entrepreneurial process and lead to the creation of hybrid organizations. Our propositions connect the individual, team and organizational levels and thus, advance our understanding of how institutional logics can be combined across different levels of analysis and throughout the stages of an entrepreneurial process.
Kinesin Takes One 8-nm Step for Each ATP That It Hydrolyzes*

Conventional kinesin is a motor protein that moves stepwise along microtubules carrying membrane-bound organelles toward the periphery of cells. The steps are of amplitude 8.1 nm, the distance between adjacent tubulin binding sites, and are powered by the hydrolysis of ATP. We have asked: how many steps does kinesin take for each molecule of ATP that it hydrolyzes? To answer this question, the motility and ATP hydrolysis of recombinant, heterotetrameric and homodimeric conventional Drosophila kinesins adsorbed to 200-nm-diameter casein-coated silica beads were assayed under identical, single-molecule conditions. Division of the speed by the maximum microtubule-activated ATPase rate gave a stoichiometry of 1.08 ± 0.09 steps for each ATP hydrolyzed at 1 mmATP. Therefore, under low loads in which the drag force ≪ 1 pN, coupling between the chemical and mechanical cycles of kinesin is tight, consistent with conventional power stroke models. Our results rule out models that require two or more ATPs/step, such as some thermal ratchet models, or that propose multiple steps powered by single ATPs.
Socio-economic determinants of fertility

This study examined the effect of economic caste and income variations on fertility in India. It was hypothesized that the fertility differential among Indias caste groupings can be explained on the basis of economic status. The mean number of live births for the upper middle and lower caste women in the sample was 3.00 3.51 and 4.38 respectively. When the population was stratified according to income however the mean number of live births for the upper middle and lower income groups was 3.40 3.22 and 4.26 respectively showing that fertility does not decline uniformly with rising economic status. When the study sample was simultaneously stratified by caste and income the different income groups within castes did not follow a consistent pattern. The upper income group in the upper caste had the lowest mean number of births (2.17) compared with 3.18 for the upper income group in the middle caste and 4.85 for the upper income group in the lower caste. Overall the middle income group tended to demonstrate the lowest fertility and the low income group the highest fertility. Education was also found to lower fertility: women with no education averaged 4.45 births compared with 3.14 among women with less than a high school education and 2.50 among high school graduates. Respondents who claimed to participate in family decision making averaged 3.09 births whereas women who did not participate in this process averaged 4.17 births. Similarly women who reported a strong relationship with their husbands tended to have planned families (3 or fewer children) more often than women who reported an unsatisfactory relationship. These results indicate that fertility is affected by both the caste and economic status of the family with education affecting fertility directly by raising the age at marriage and indirectly through better knowledge of contraception and increased awareness of the costs of raising children.