Miracle-dz/UniFAR-FTUs huggingface dataset:
High-Mobility Group A2 Protein Modulates hTERT Transcription To Promote Tumorigenesis

ABSTRACT The high-mobility group A2 gene (HMGA2) is one of the most frequently amplified genes in human cancers. However, functions of HMGA2 in tumorigenesis are not fully understood due to limited knowledge of its targets in tumor cells. Our study reveals a novel link between HMGA2 and the regulation of human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, which offers critical insight into how HMGA2 contributes to tumorigenesis. The expression of HMGA2 modulates the expression of hTERT, resulting in cells with enhanced telomerase activities and increased telomere length. Treatment with suberoylanilide hydroxamide (SAHA), a histone deacetylase (HDAC) inhibitor, causes dose-dependent hTERT reporter activation, mimicking HMGA2 overexpression. By interacting with Sp1, HMGA2 interferes with the recruitment of HDAC2 to the hTERT proximal promoter, enhancing localized histone H3-K9 acetylation and thereby stimulating hTERT expression and telomerase activity. Moreover, HMGA2 knockdown by short hairpin HMGA2 in HepG2 cells leads to progressive telomere shortening and a concurrent decrease of steady-state hTERT mRNA levels, attenuating their ability to form colonies in soft agar. Importantly, HMGA2 partially replaces the function of hTERT during the tumorigenic transformation of normal human fibroblasts. These findings are potentially clinically relevant, because HMGA2 expression is reported to be upregulated in a number of human cancers as telomere maintenance is essential for tumorigenesis.
A preliminary study of the effect of external qigong on lymphoma growth in mice.

OBJECTIVE To examine the effectiveness of external qigong on the in vivo growth of transplantable murine lymphoma cells in mice. BACKGROUND Qigong is a traditional Chinese health practice that is believed by many to have special preventive and healing power. Underlying the system is the belief in the existence of a subtle energy (qi), which circulates throughout the body, and when strengthened or balanced, can improve health and ward off or slow the progress of disease. To date, much of the literature showing the effects of qi are presented in the non-Western literature, and as such are viewed with considerable skepticism. In an attempt to demonstrate qi in a controlled setting, the effect of external qigong emission from a qigong healer on the in vivo growth of transplantable murine lymphoma cells in mice was explored in two pilot studies. METHODS In study 1, 30 SJL/J mice were injected intravenously with lymphoma cells that localize and exhibit aggressive growth in the lymphoid tissues of untreated syngeneic recipients. These tumor-injected mice were divided into 3 groups: (1). qigong treatment (administered by a qigong healer); (2). sham treatment; and (3). no-treatment control. The sham group received the same number of treatments from a person without training in qigong, who imitated the motions of the qigong healer. The control group received no treatment at all. In study 1, the mice were sacrificed on the 9th or 11th days after tumor-cell injection, and in study 2, the mice were sacrificed on the 10th and 13th days. Tumor growth in lymph nodes (LN) was estimated by LN weight expressed as a percentage of total body weight. RESULTS In study 1, LNs from mice in the qigong-treated group were significantly smaller than LN from mice in either the control group or in the sham treatment group (p < 0.05), suggesting that there was less tumor growth in the qigong-treated mice. In study 2, using the same design as study 1, the same pattern of difference found in study 1 emerged: LN ratio from mice in the qigong-treated group was smaller than that in either the control group or in the sham group. However, these results did not reach statistical significance, partially as a result of larger variances in all groups in this study. CONCLUSIONS These preliminary results, while still inconclusive, suggest that qigong treatment from one particular qigong practitioner might influence the growth of lymphoma cells negatively. Further studies with different practitioners, more repeated trials, and/or different tumor models are needed to further investigate the effects of external qigong on tumor growth in mice.
Floating microspheres of valacyclovir HCl: Formulation, optimization, characterization, in vitro and in vivo floatability studies

Floating microspheres are multiple unit Gastroretentive drug delivery systems. Valacyclovir hydrochloride (VCH) is L-valyl ester prodrug of acyclovir. VCH degrades in intestinal fluid. The objective was to develop floating microspheres of VCH to localise the drug at upper part of GIT, for improved absorption. Floating microspheres were prepared by W/O emulsification solvent evaporation method using Ethylcellulose (EC) as polymer. Particle size and % EE were 550.021±0.241 μm, 79.88±2.236% respectively. in vitro and in vivo floatability studies confirmed floating behaviour of microspheres. VCH loaded floating microspheres can be a suitable alternative to the conventional formulation, by localizing the drug at upper GIT.
Democratization or Diversion? The Effect of Community Colleges on Educational Attainment

Throughout the late 1970s and the early 1980s, over 50% of all first-time first-year college students started in a junior college. Despite such a large role in higher education, we know relatively little about how well they serve their role of providing an education for all who want to attend college. Junior colleges affect educational attainment in two ways. First, the schools provide a place in higher education for those who might not have otherwise attended college, the democratization effect; however, they also draw away some students who might otherwise have attended a four-year college, the diversion effect. The democratization effect is nonnegative; however the effect of diversion on educational attainment is unclear, a priori, as some students might be better off starting in a four-year school. This paper attempts to sort out the overall impact of junior colleges on educational attainment. I use the natural experiment arising from variation in access to junior colleges across cities and states to address the problem of self-selection into types of colleges. This approach is implemented by an instrumental variables strategy in which distance to junior college and average state two-year college tuition are used to instrument for junior college attendance in an educational attainment equation. The results suggest that on net junior colleges increase total years of schooling, but do not change the likelihood of attaining a BA.
The cutworm Peridroma saucia (Lepidoptera: Noctuidae) supports growth and transport of pBR322-bearing bacteria

Variegated cutworms were exposed to bean plants in microcosms sprayed with pBR322-carrying strains of Enterobacter cloacae, Klebsiella planticola, and Erwinia herbicola. The three bacterial species exhibited differential survival on leaves, in soil, and in guts and fecal pellets (frass) of the insects. High numbers of Enterobacter cloacae(pBR322) were detected in all samples, while the other species were unable to establish residence in the insect. To assess the impact of this colonization on site-to-site transport of microorganisms, larvae were fed plants that had been sprayed with the bacteria and then were transferred to uninoculated plants. Cutworms were efficient carriers of Enterobacter cloacae(pBR322), as indicated by its rapid appearance on uninoculated leaves and continued persistence in the insects for 3 days after transfer. Few Erwinia herbicola(pBR322) and K. planticola(pBR322) were obtained from larvae after transfer, although up to 10(3) CFU/g were detected in soil and on plants. Differences in bacterial survival and growth were confirmed by incubating frass overnight and observing the change in population numbers. The proportion of total samples showing at least a 25-fold increase during incubation was 68% for Enterobacter cloacae(pBR322), 39% for K. planticola(pBR322), and 0% for Erwinia herbicola(pBR322). Our results emphasize the role that cutworms and possibly other insects have in persistence and growth of microorganisms in the environment.
Genetic fine structure of the leucine operon in Salmonella.

with the leucine biosynthetic pathway in Salmonella typhimurium. That the regulation of gene activity is basically determined by genetic controlling elements was first prominently suggested by the work of MCCLINTOCK with maize (MCCLINTOCK 1956, 1961). In bacteria, the evidence that in many cases the genes associated with a single biochemical pathway were clustered together on the bacterial chromosome (see DEMEREC and HARTMAN 1959) together with the evidence for coordinate control of the synthesis of enzymes involved in the pathway, has allowed the development of a model for the regulation of gene activity (JACOB and MONOD 1961a,b). As in the earlier model described by MCCLINTOCK for maize, there are three elements involved. The first is the ‘Lstructural gene” which determines the identities and order of amino acids in a polypeptide chain, thus determining enzyme structure. The second is the ‘Loperator” which, in the model of JACOB and MONOD (1961a,b), is a region of the chromosome closely linked to one end of a cluster of structural genes and may, in fact, be a part of the terminal structural gene which it adjoins. The operator directs the activities of the structural genes associated with it in response to the product of the third genetic element of the control system, the “regulator. ” The product of the regulator, in conjunction with an inducing substrate or repressing end product, determines whether the operator turns the structural genes on or off. The regulator may or may not be located close to the operon,” which is the term used by JACOB and MONOD to describe the conjoined operator and structural gene (or genes). In the system described in this report, the structural genes and operator responsible for leucine synthesis have been defined, but the regulator has not yet been identified. In a brief preliminary note, the presence of four complementation groups involved in leucine synthesis in Salmonella typhimurium had been previously reported ( MARGOLIN 1959). Initial evidence of the existence of operons was derived from genetic and CL
Morphology of single olivocerebellar axons labeled with biotinylated dextran amine in the rat

The morphology of olivocerebellar (OC) axons originating from the inferior olive (IO) was investigated in the rat by reconstructing the entire trajectories of single axons that had been labeled with biotinylated dextran amine. Virtually all of the OC axons entered the cerebellum through the inferior cerebellar peduncle (ICP) contralateral to the IO, with a few exceptions. Although most OC projection was contralateral, a few axons projected bilaterally by crossing the midline within the cerebellum. Collaterals of OC axons could be classified into thick branches and thin collaterals. Thick branches of each OC axon (6.1 ± 3.7/OC axon, mean ± SD for n = 16 axons) terminated as climbing fibers (CFs) on single Purkinje cells (PCs) in a one‐to‐one relationship. Besides terminal arborization around PC thick dendrites, CFs had terminals that surrounded a PC soma, fine branchlets that extended transversely in the molecular layer, and thin retrograde collaterals that re‐entered the PC and granular layers. Innervation of a single PC by two CFs originating from the same axon was seen, although infrequently. Concerning thin collaterals, about half of the OC axons had one or only a few collaterals terminating in the white matter of the ICP, most had 1 to 6 collaterals terminating in a single cerebellar nucleus, and all had 3 to 16 collaterals that terminated mainly in the granular layer, but occasionally in the cerebellar white matter and the PC layer. Some swellings of thin collaterals touched somata of presumed Golgi cells and PCs. No OC axons terminated solely in the ICP, cerebellar nucleus or granular layer without giving rise to CFs. J. Comp. Neurol. 414:131–148, 1999. © 1999 Wiley‐Liss, Inc.
Evaluating the MESSAGE Communication Strategies in Dementia training for use with community-based aged care staff working with people with dementia: a controlled pretest-post-test study.

AIMS AND OBJECTIVES The study aims to evaluate the effects of a communication skills training programme on community aged care staff's knowledge of communication support in dementia and on staff's care experience. BACKGROUND Dementia can lead to impairments in communication. Therefore, quality community-based dementia care requires that staff be skilled communicators, equipped to facilitate interactions with people with dementia. The current investigation evaluated the effectiveness of the MESSAGE Communication Strategies in Dementia for Care Staff training programme with respect to knowledge of communication support and the staff/caregiver experience. DESIGN A multi-centre controlled pretest/post-test design with randomised cohort allocation was used. Outcome measures were completed at baseline, immediately after training (training group only), and at three-month follow-up. METHODS Thirty-eight care staff working in community aged care participated and completed all outcome measures (training = 22; control = 16). Training and control groups completed the following outcome measures: knowledge of communication support strategies, self-efficacy, preparedness to provide care, strain in nursing care and attitude to dementia care. Staff in the training group provided written feedback on the training. RESULTS A significant improvement in knowledge scores from baseline was found for the training group both immediately after training and at three-month follow-up. There was also a significant training effect for self-efficacy and preparedness to provide care. No significant difference was found for the control group for any measure. No significant training effects were found for measures of strain or attitudes to dementia care. Feedback from staff suggests that the training was well received. CONCLUSIONS The MESSAGE training was positively received by staff and had a significant effect on care staff knowledge, and confidence to provide care for people with dementia. RELEVANCE TO CLINICAL PRACTICE The easily accessible multimedia training programme is well received by staff and has the potential to improve quality of care.
Drivers and Dynamics of Internal and International Remittances

Abstract This article analyses whether and how intra-household remittance volumes vary with the length of a migrant's absence, and whether the drivers and dynamics of remittance decay depend on the migrant's destination. We address these questions by using data from the 64th round of the Indian National Sample Survey, conducted between July 2007 and June 2008. We find that the average intra-household remittance function follows a curvilinear trajectory that is best approximated by a quartic (M-shaped) specification. The volatility of intra-household remittances is distinct across migration destinations, with international remittance flows being more volatile than internal intra-state or inter-state flows.
N-Terminal Pro-Brain Natriuretic Peptide and Heart Failure Risk Among Individuals With and Without Obesity: The Atherosclerosis Risk in Communities (ARIC) Study

Background— Obesity is a risk factor for heart failure (HF) but is associated with lower N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. It is unclear whether the prognostic value and implications of NT-proBNP levels for HF risk differ across body mass index (BMI) categories. Methods and Results— We followed up 12 230 ARIC participants free of prior HF at baseline (visit 2, 1990–1992) with BMI ≥18.5 kg/m2. We quantified and compared the relative and absolute risk associations of NT-proBNP with incident HF across BMI categories. There were 1861 HF events during a median 20.6 years of follow-up. Despite increased HF risk in obesity, a weak inverse association was seen between baseline BMI and NT-proBNP levels (r=−0.10). Nevertheless, higher baseline NT-proBNP was associated with increased HF risk in all BMI categories. NT-proBNP improved HF risk prediction overall, even among those with severe obesity (BMI ≥35 kg/m2; improvement in C statistic, 0.032; 95% confidence interval, 0.011–0.053). However, given the higher HF rates among those with obesity, at each NT-proBNP level, higher BMI was associated with greater absolute HF risk. Indeed, among those with NT-proBNP of 100 to <200 pg/mL, the average 10-year HF risk was <5% among normal-weight individuals but >10% among the severely obese. Conclusions— Despite its inverse relationship with BMI, NT-proBNP provides significant prognostic information on the risk of developing HF even among individuals with obesity. Given the higher baseline HF risk among persons with obesity, even slight elevations in NT-proBNP may have implications for increased absolute HF risk in this population.
Simulation of Execution Costs in the Global Institutional Spot FX Market

We discuss execution costs in the global spot FX market where only limit orders are permitted. In this work we expand our approach for simulations of maker loss (Schmidt [2008]) to large orders that might notably affect price dynamics if they were submitted in real life. We discern three types of orders: (1) Maker orders: bid (offer) orders submitted at best bid (offer) price until they are completely filled. (2) Auto - match orders: bid (offer) orders submitted at best offer (bid) price but their unfilled remainders are submitted as maker orders. (3) Taker orders: buy (sell) orders submitted at sufficiently high (low) price to be immediately filled. We used the EBS/ICAP market data for EUR/USD in February 2009 for calibrating our simulation model and estimating maker loss. Besides sequential runs upon historical market data, we used also several resampling techniques: bootstrap, Monte Carlo Markov Chain, and random entry. We found that the latter method is preferable for our simulations. Our main conclusion in the early work for one-million orders (the minimal order size in the EBS market) holds also for multi-million orders: expected maker loss is lower than the taker loss.
Structural and biochemical characterization of the GTPgammaS-, GDP.Pi-, and GDP-bound forms of a GTPase-deficient Gly42 --> Val mutant of Gialpha1.

The Gly42 --> Val mutant of Gialpha1 was characterized structurally and biochemically to elucidate two important features of Gialpha1-catalyzed GTP hydrolysis. The crystal structure of the GTPgammaS-bound G42VGialpha1 protein demonstrates that the steric bulk of Val42 pushes the Gln204 residue into a catalytically incompetent conformation, providing a rationale for the diminished GTPase activity of this mutant. The same phenomenon may also account for the diminished GTPase activity of the homologous transforming Gly42 --> Val mutation in p21(ras). Similarly, the steric bulk of the unique Ser42 residue in Gzalpha may account for the comparatively slower rate of GTP hydrolysis by this Galpha subunit. The G42VGialpha1 subunit was also characterized structurally in its GDP.Pi- and GDP-bound states, providing a unique opportunity to view three "snapshots" of GTP hydrolysis. Hydrolysis of GTP to a transient GDP.Pi-bound intermediate is associated with substantial conformational changes in the switch II segment of the protein. Eventual release of Pi results in further removal of switch I from the active site and a highly mobile switch II segment. Despite their disparate biochemical properties, the structural similarity of G42VGialpha1 to the G203AGialpha1 mutant in the GDP.Pi-bound form suggests that both mutations stabilize a conformation of the GDP. Pi-bound protein that occurs only transiently in the wild-type protein. The structures of the GDP-bound forms of the wild-type and mutant proteins are similar.
Varietal Intensities and Similarities of the World's Wine Regions*

Abstract This paper examines empirically two distinguishing aspects of the world's wine regions: their degree of specialization in certain varieties, as measured by a varietal intensity index; and their similarity with the varietal mix of other regions, as measured by a varietal-based regional similarity index. Twelve of the most important wine-producing countries, that together account for all but one-eighth of the world's winegrapes, are included in the analysis. The data refer to circa 2000 (or 1999 for EU member countries, since that is their most recent census data). These indexes provide a baseline against which to compare more recent and future vintages. They will be especially useful as producers and regulators respond at varying speeds to the impacts of climate changes, in addition to market developments, on the optimal location of production of different varieties around the world. (JEL Classifications: D24, L66, Q13, Q15)
The challenge of integrating innovation and quality management practice

Following in the footsteps of ‘New Public Management’, where quality management and quality control have become widely implemented concepts among public authorities, there is now a subsequent government demand to also be innovative. However, integrating and achieving a balance between improved quality and increased innovation is not an easy task. Previous research indicates a complex and ambiguous relation, raising questions as to how to optimally combine these two approaches organisationally, operationally, and culturally. Is there an ‘edge of chaos’ where there is maximal flexibility for innovation while maintaining sufficient order for quality? The purpose of this paper is to examine the potential integration of innovation and quality management practice within the public sector. The paper is based on a multiple case study design, confronted with existing literature, and shows that the current quality management practice is perceived as being related to standardisation, leading to a decrease in the space for innovation. Second, that there is an expectation and belief that innovation and quality management can be handled in parallel and reinforce each other instead of being mutually detrimental.
Percutaneous Vertebroplasty for Painful Compression Fractures in a Small Cohort of Patients with a Decreased Expectation-Related Placebo Effect due to Dementia

BACKGROUND AND PURPOSE: Although abundant literature has reported success with vertebroplasty for the treatment of painful compression fractures, none has accounted for a potential expectation-related placebo effect. We report the results of vertebroplasty for painful vertebral body compression fractures in a small cohort of patients with dementia with the assumption that this patient subgroup is subjected to a decreased placebo effect. MATERIALS AND METHODS: All patients with objective evidence of dementia (N = 10) who had undergone vertebroplasty at our institution were identified from a comprehensive prospectively constructed vertebroplasty data base. The patients’ pain at rest and activity, mobility, and pain-medication use were analyzed at 2 hours postprocedure, 1 week, 1 month, 6 months, and 1 year. RESULTS: Pain with activity decreased or resolved in 80%–100% of patients at each time point, whereas pain at rest decreased or resolved in 78%–100% of all patients at each time point. Improved mobility was reported in 80%–100% of patients at all time points. Pain medication was decreased or stopped in 67% of patients at 1 week and in 100% of patients at 6 months and 1 year. CONCLUSION: Treatment of painful compression fractures in patients with dementia demonstrates a high rate of success regarding pain relief and mobility. This study offers additional evidence that vertebroplasty has true benefit.