Miracle-dz/UniFAR-FTUs huggingface dataset:
BNP7787-Mediated Modulation of Paclitaxel- and Cisplatin-Induced Aberrant Microtubule Protein Polymerization In vitro

Taxane and platinum drugs are important agents in the treatment of cancer and have shown activity against a variety of tumors, including ovarian, breast, and lung cancer, either as single agents or in combination with other chemotherapy drugs. However, a serious and prevalent side effect of taxane (docetaxel and all formulations/derivatives of paclitaxel) and platinum (cisplatin, carboplatin, and oxaliplatin) agents is dose-limiting chemotherapy-induced peripheral neuropathy (CIPN). CIPN can result in treatment delays, dose modifications, and, in severe cases, discontinuation of chemotherapy. Consequently, effective treatments for CIPN are needed. Dimesna (BNP7787; Tavocept TM; disodium 2,2′-dithio-bis-ethanesulfonate) is an investigational drug that is undergoing international clinical development as a treatment that is coadministered with first-line taxane and platinum combination chemotherapy in patients with inoperable advanced primary adenocarcinoma of the lung. BNP7787 is currently being developed with the objective of increasing the survival of cancer patients receiving taxane- and/or cisplatin-based chemotherapy. Additional data indicate that BNP7787 may also protect against common and serious chemotherapy-induced toxicities, including chemotherapy-induced anemia, nausea, emesis, nephrotoxicity, and neuropathy, without interfering with antitumor activity of the chemotherapeutic agent(s). Studies herein show that BNP7787 prevents aberrant microtubule protein (MTP) polymerization that is caused by exposure of MTP to paclitaxel or cisplatin. BNP7787 modulates paclitaxel-induced hyperpolymerization of MTP in a dose-dependent manner, and mesna, an in vivo metabolite of BNP7787, protects against time-dependent cisplatin-induced inactivation of MTP. We propose that interactions between BNP7787 and MTP may play a role in BNP7787-mediated protection against CIPN. Mol Cancer Ther; 9(9); 2558–67. ©2010 AACR.
Issuer Operating Performance and IPO Price Formation

type="main"> We study the relation between issuer operating performance and initial public offering (IPO) price formation from the initial price range to the offer price to the closing price on the first trading day. For a post-bubble sample of 2001–2013 IPOs, we find that pre-IPO net income and, in particular, operating cash flow are strongly, positively associated with the revision from the mid-point of the initial price range to the offer price and that the “partial adjustment phenomenon” concentrates among issuers with the strongest operating performance. As for why publicly observable information helps predict changes in valuation from when the initial price range is set to when the offer price is set, our findings suggest that strong-performing issuers, especially those offering small slices of ownership, have lower bargaining incentives and are susceptible to the underwriter(s) low-balling the price range. Overall, our results suggest an important role for accounting information in understanding the pricing of book-built IPOs and are consistent with the presence of agency problems between issuers and underwriters.
Inflation and housing market in Shanghai

Purpose – This paper sets out to examine the inflation‐hedging ability of housing properties in Shanghai.Design/methodology/approach – This paper examines both the short‐term and long‐term hedging characteristics of Shanghai residential properties against three types of inflation: actual, expected, and unexpected in the test period of 1997‐2005 by using the OLS model. Two methods, the Autoregressive Integrated Moving Average (ARIMA) and the Hedrick‐Prescott Filter, are used to estimate the expected inflation.Findings – The results show that, while the Shanghai housing property market does not provide a hedge against actual expected and unexpected inflation during the period, a positive real rate of return is reported in all cases.Research limitations/implications – Data limitations are due to lack of complete market transaction records and it is necessary to rely on property indices produced by the private‐sector firms as a proxy for market movements.Originality/value – The paper shows that government pol.
Intra-household gender bias in child educational spending in rural Ethiopia: panel evidence

Qualitative and quantitative evidence reveals pervasive gender discrimination in many social and economic aspects in least developing countries, including Ethiopia. Investment in child schooling is an important dimension of this discrimination, which has a lasting consequence on both the child and the country’s economic development as a whole. The main objective of this study is to uncover if there is any intrahousehold gender-bias in the decision to enrollment and allocation of resources to child education. Using a panel data set from Ethiopian Rural Household Survey (ERHS), spanning from 1994-2004, we applied a panel hurdle models consisting of random effects probit for the initial decision in enrollment and conditional linear autoregressive model for the proportion spent. We found statistically significant gender-bias during the initial decision to enrollment against girls, especially those corresponding to secondary school cycle. Since the bias occurs inside the household, public investments should not only focus on facilitating access to school but also work towards altering the demand side as parents have differential preference towards siblings’ education. Policies that increase returns to girl’s education, increasing intrahousehold productivity, legislations that prohibit early marriage, etc. could mitigate the observed level of intra-household gender-bias against girls aged 15-19 years.
Identification of the PTPN22 functional variant R620W as susceptibility genetic factor for giant cell arteritis

Objective To analyse the role of the PTPN22 and CSK genes, previously associated with autoimmunity, in the predisposition and clinical phenotypes of giant cell arteritis (GCA). Methods Our study population was composed of 911 patients diagnosed with biopsy-proven GCA and 8136 unaffected controls from a Spanish discovery cohort and three additional independent replication cohorts from Germany, Norway and the UK. Two functional PTPN22 polymorphisms (rs2476601/R620W and rs33996649/R263Q) and two variants of the CSK gene (rs1378942 and rs34933034) were genotyped using predesigned TaqMan assays. Results The analysis of the discovery cohort provided evidence of association of PTPN22 rs2476601/R620W with GCA (PFDR=1.06E-04, OR=1.62, CI 95% 1.29 to 2.04). The association did not appear to follow a specific GCA subphenotype. No statistically significant differences between allele frequencies for the other PTPN22 and CSK genetic variants were evident either in the case/control or in stratified case analysis. To confirm the detected PTPN22 association, three replication cohorts were genotyped, and a consistent association between the PTPN22 rs2476601/R620W variant and GCA was evident in the overall meta-analysis (PMH=2.00E-06, OR=1.51, CI 95% 1.28 to 1.79). Conclusions Our results suggest that the PTPN22 polymorphism rs2476601/R620W plays an important role in the genetic risk to GCA.
Grafting response to excess boron and expression analysis of genes coding boron transporters in tomato.

Boron (B) is essential for plant growth, however its excess in soil and/or in irrigation water can severely compromise plant growth and yield. The goal of this work was to determine whether grafting onto 'Arnold', a commercial interspecific hybrid (Solanum lycopersicum × S. habrochaites) rootstock, which in a previous study was found to be tolerant to salt stress, could improve tomato (S. lycopersicum L. 'Ikram') tolerance to excess B, and whether this effect is associated with an exclusion mechanism. Non-grafted, self-grafted and grafted plants were hydroponically grown in a greenhouse with B concentration in the nutrient solution of 0.27 (control), 5, 10 and 15 mg·l-1 . A transcription analysis was carried out on SlNIP5 and SlBOR1 genes, which encode putative B transporters. Grafting 'Ikram' onto 'Arnold' rootstock reduced B concentration in leaf tissue of plants exposed to B concentrations of 10-15 mg·l-1 . At high B levels, SlNIP5 was down-regulated in all grafting combinations, while SlBOR1 was down-regulated only in the roots of plants grafted onto 'Arnold'. We conclude that grafting the susceptible tomato cultivar 'Ikram' onto the commercial rootstock 'Arnold' improved tolerance to excess B by reducing expression of genes encoding for B transporters at the root level, thus partially reducing the root uptake of B and its accumulation in the shoot.
Homeownership Returns, Tenure Choice and Inflation

This paper empirically investigates the impact of inflation on homeownership returns and tenure choice when the assumptions underlying the user cost of housing are modified to reflect separately the effects of unanticipated and anticipated inflation. The analysis demonstrates that when the user cost model is specified to reflect the impact of anticipated inflation on house prices, the mortgage interest rate and the capitalization rate, the returns to homeownership are lower than determined by previous user cost studies and are consistent with a reasonably efficient market. Copyright American Real Estate and Urban Economics Association.
Rare Event Risk and Emerging Market Debt with Heterogeneous Beliefs

In a setting where the lender and the borrower have heterogeneous beliefs about the likelihood of a disastrous shock to the borrower's economy, we study the debt contract that defaults at the occurrence of that shock, as proposed by Barro (2006). We find that a higher belief by the lender compared to the borrower can lead to countercyclical interest rates and credit spreads in non-default times, and to an increase in the borrower's indebtedness in default times, as often observed in emerging market economies. When calibrating the model to prices in the credit default swap market, we show that heterogeneous beliefs can account for more than 40% of the variation in CDS spreads associated with shocks to the borrower's economy in non-default times.
Allied Breweries and the Development of the Area Manager in British Brewing, 1950–1984

Brewing in the United Kingdom in the years following 1950 saw a shift from a production to a retailing orientation. As part of this shift, the role of the area manager started to move from production and sales discipline to retail development. This article explores the job of the area manager during the period, seeking to demonstrate the weakness in recent accounts that suggest that area managers serve only as an “information relay” between senior managers and unit managers. Although the evidence is limited, because of problems with the survival of records, it suggests a more complex picture, which has implications for area managers in retail and service industries more generally.
Bone density phenotypes in mice aneuploid for the Down syndrome critical region

Down syndrome (trisomy 21) is associated with reduced bone density in humans, but it is unclear whether this is due to specific effects of chromosome 21 genes or lifestyle factors. Mouse models with aneuploidy of segments of mouse chromosome 16 that are homologous to human chromosome 21 can be used to elucidate the mechanism by which Down syndrome phenotypes arise. Ts1Rhr and Ms1Rhr mice are trisomic and monosomic, respectively, for the hypothesized “Down syndrome critical region” containing approximately 33 genes. We assessed the skeletons of these mice from 3 to 16 weeks of age using dual X‐ray absorptiometry. Ts1Rhr mice were unexpectedly similar to normal controls, showing that a larger region of trisomy is necessary to recapitulate the Down syndrome phenotype. Ms1Rhr mice, in contrast, showed decreases in weight, bone mineral content, bone mineral density, and bone area from weaning to adulthood. Regional bone density was also decreased in the femur, tibia, and lower lumbar spine. The microarchitecture of 3 week old Ms1Rhr femurs was then analyzed using µCT. Volumetric density, total tissue volume, bone volume, and bone fraction were all reduced in both cortical and trabecular bone. Ms1Rhr trabeculae were thinner and had decreased connectivity. A 31.5% reduction in the level of insulin‐like growth factor I in the serum was found, and we hypothesize that this is responsible for the bone density phenotype. We discuss bone‐related genes in the region and propose that humans with distal chromosome 21 deletions may exhibit reduced bone density. Published 2011. This article is a U.S. Government work and is in the public domain in the USA.
Understanding How People Use Natural Language to Ask for Recommendations

The technical barriers for conversing with recommender systems using natural language are vanishing. Already, there are commercial systems that facilitate interactions with an AI agent. For instance, it is possible to say "what should I watch" to an Apple TV remote to get recommendations. In this research, we investigate how users initially interact with a new natural language recommender to deepen our understanding of the range of inputs that these technologies can expect. We deploy a natural language interface to a recommender system, we observe users' first interactions and follow-up queries, and we measure the differences between speaking- and typing-based interfaces. We employ qualitative methods to derive a categorization of users' first queries (objective, subjective, and navigation) and follow-up queries (refine, reformulate, start over). We employ quantitative methods to determine the differences between speech and text, finding that speech inputs are typically longer and more conversational.
Convincing the toilers?

Australians work comparatively long hours and, in recent years, most of the growth in per capita working hours has come from workers already employed full time.Yet, despite the problems long working hours can cause, this trend has not attracted political attention. Increasingly, the Australian working time regime is a weak regulator of working hours and promotes only limited equality between the working hours of men and women. This article uses responses from the Australian Survey of Social Attitudes 2003 to investigate whether workers' preferences are in accord with regime institutions. We find that people who work long hours are no less inclined than those who work standard hours or part time to see working hours as a choice and they do this despite more often reporting that their work interferes with family life and that employers expect long hours from them. We contend that seeing long working hours as a choice may be the product of the ‘liberal’ working time regime itself. Multivariate analysis of the responses suggest that structural pressures work to strengthen perceptions that there is a problem with long working hours and prompt the belief that long hours are not freely chosen. Implications of these findings tell us something about possible future regulation.
Differentiation antigens on rhesus monkey lymphocytes I. Identification of T cells bearing CD3 and CD8, and of a subset of CD8‐bearing cells

Rhesus monkeys provide an excellent preclinical model to test the effect of monoclonal antibodies (mAb) in vitro and in vivo. So far, mostly mAb have been used which were originally raised against human cell surface antigens but cross‐reacted reasonably well with homologous antigens on rhesus monkey cells. However, to optimize the model, it was necessary to produce mAb which react specifically with subsets of rhesus monkey lymphocytes. In this report, three mouse anti‐rhesus monkey mAb are described, specific for different subsets of rhesus monkey T lymphocytes. None of the reagents cross‐reacts with human lymphocytes. Characterization of these mAb was based upon indirect immunofluorescence, using a simultaneous staining technique, and immunoprecipitation of the specific target antigens. One antibody (GM9) reacts with the same subset as is recognized by mAb specific for human CD8+cells. The second mAb (GM13) is specific for a subset of CD8+ cells. A third mAb (FN18) was of particular interest: it identifies a cell surface complex, RhT3, expressed on mature T lymphocytes, of which the polypeptide chains have a molecular mass of 22 and 27 kDa. The data strongly suggest that RhT3 is a CD3‐like determinant, so far unidentified in the rhesus monkey.
User-generated Destination Image through Weblogs: A Comparison of Pre- and Post-visit Images

Despite the increase in use of user-generated electronic content as an information source by tourists, its influence in destination image formation is not yet fully understood. This research aimed to explore the communicated destination image held by tourists to Zanzibar Island (Tanzania) by utilizing communications in Lonely Planet. Content analysis of 214 posts using TextSTAT yielded 13 destination attributes. Comparatively, functional attributes were dominant in potential tourists whereas post-travel image perception was dominated by psychological attributes. Those who have visited tended to have a positive image of the island compared with those who are planning to visit the island. The results necessitate the differential use of the functional- and psychological-based information in communicating with tourists at different information-search stages. Studies to capture communications in another language are recommended as well as the employment of methodologies that might reveal hidden images held by tourists.
Choice Experiments to Assess Farmers' Willingness to Participate in a Water Quality Trading Market

Interest has grown in Water Quality Trading (WQT) as a means to achieve water quality goals, with more than 70 such programs now in operation in the United States. Substantial evidence exists that nonpoint sources can reduce nutrient loading at a much lower cost than point sources, implying the existence of gains from trade. Despite the potential gains, however, the most commonly noted feature of existing WQT markets is low trading volume, with many markets resulting in zero trades. This paper evaluates one explanation for the lack of participation from agricultural nonpoint sources. We test for and quantify the intangible costs' that may deter farmers from trading even if the monetary benefits from doing so outweigh the observable out-of-pocket costs. We do so by designing and implementing a series of choice experiments to elicit WQT trading behavior of Great Plains crop producers in different situations. Attributes of the choice experiment included market rules and features (e.g., application time and effort, penalties for violations, means of monitoring compliance) that may affect farmers' willingness to trade. The choice experiments were conducted with a total of 135 producers at four locations in the state of Kansas between August 2006 and January 2007. A Random Parameters Logit model is appropriate to analyze the resulting data, revealing diversity in the way that the attributes affect farmers' choices.
Polycomb complexes in X chromosome inactivation

Identifying the critical RNA binding proteins (RBPs) that elicit Xist mediated silencing has been a key goal in X inactivation research. Early studies implicated the Polycomb proteins, a family of factors linked to one of two major multiprotein complexes, PRC1 and PRC2 (Wang 2001 Nat. Genet. 28, 371–375 (doi:10.1038/ng574); Silva 2003 Dev. Cell 4, 481–495 (doi:10.1016/S1534-5807(03)00068-6); de Napoles 2004 Dev. Cell 7, 663–676 (doi:10.1016/j.devcel.2004.10.005); Plath 2003 Science 300, 131–135 (doi:10.1126/science.1084274)). PRC1 and PRC2 complexes catalyse specific histone post-translational modifications (PTMs), ubiquitylation of histone H2A at position lysine 119 (H2AK119u1) and methylation of histone H3 at position lysine 27 (H3K27me3), respectively, and accordingly, these modifications are highly enriched over the length of the inactive X chromosome (Xi). A key study proposed that PRC2 subunits bind directly to Xist RNA A-repeat element, a region located at the 5′ end of the transcript known to be required for Xist mediated silencing (Zhao 2008 Science 322, 750–756 (doi:10.1126/science.1163045)). Subsequent recruitment of PRC1 was assumed to occur via recognition of PRC2 mediated H3K27me3 by the CBX subunit of PRC1, as has been shown to be the case at other Polycomb target loci (Cao 2002 Science 298, 1039–1043 (doi:10.1126/science.1076997)). More recently, several reports have questioned aspects of the prevailing view, both in relation to the mechanism for Polycomb recruitment by Xist RNA and the contribution of the Polycomb pathway to Xist mediated silencing. In this article I provide an overview of our recent progress towards resolving these discrepancies. This article is part of the themed issue ‘X-chromosome inactivation: a tribute to Mary Lyon’.
Converting enzyme inhibitors cause pressure-independent resetting of baroreflex control of sympathetic outflow.

The current study was performed to determine whether baroreflex resetting after acute administration of converting enzyme inhibitors (CEIs) was dependent on the concomitant decrease in mean arterial pressure (MAP). Reflex changes in lumbar sympathetic nerve activity (LSNA) due to increases and decreases in MAP [i.v. phenylephrine (PE) and nitroprusside infusions] were determined in normotensive and renal hypertensive (1-kidney, 1-clip) anesthetized WKY rats 1) before (control), 2) 15 min after intravenous captopril (2 mg/kg) or enalaprilat (300 micrograms), and 3) 15 min after MAP was returned to pre-CEI levels with intravenous PE. CEIs decreased MAP and caused a leftward shift of the MAP-LSNA curve toward a lower operating pressure range in all hypertensive and in one group of normotensive rats. The baroreflex curve remained shifted to the left even after MAP was restored to pre-CEI levels by infusion of PE. Thus CEIs cause a pressure-independent resetting of baroreflex control of sympathetic outflow within 15 min. This effect of CEIs is most likely due to elimination of a central nervous system effect of circulating angiotensin II and could contribute to the antihypertensive actions of this class of compounds.
An 802.11p Cross-Layered Pilot Scheme for Time- and Frequency-Varying Channels and Its Hardware Implementation

Robust channel estimation in IEEE 802.11p systems in highly time- and frequency-varying vehicular channels, in combination with long data packets, is a challenging task due to the ill-suited pilot pattern. Solutions of increased receiver complexity that use decision feedback and iterative decoding have been proposed to overcome the difficulty in robust channel estimation. In this paper, a cross-layered method to introduce complementary training symbols into an 802.11p frame is proposed. In the proposed approach, known bits are multiplexed with the data in higher layers, and a modified receiver can utilize these bits as training data for improved channel estimation. A standard receiver treats these bits as data and passes them to the higher layers, where they can be removed, making the method compatible with standard 802.11p transceivers. A software/firmware update of the higher layers is needed in a standard receiver to remove the multiplexed bits. A modified receiver with low-complexity channel estimation schemes that utilizes the complementary training symbols is implemented in a field-programmable gate array (FPGA) platform. Frame error rate (FER) measurements have been performed by interfacing the hardware implementation with a channel emulator. The measurement results follow the computer simulation results, validating the hardware implementation. Moreover, measurement results show that the modified receiver follows the performance of an ideal receiver that has full knowledge of the channel (with only an offset in signal-to-noise ratio (SNR)) and significantly outperforms the commercial 802.11p transceiver we tested.