Miracle-dz/UniFAR-FTUs huggingface dataset:
PTEN Represses RNA Polymerase III-Dependent Transcription by Targeting the TFIIIB Complex

ABSTRACT PTEN, a tumor suppressor whose function is frequently lost in human cancers, possesses a lipid phosphatase activity that represses phosphatidylinositol 3-kinase (PI3K) signaling, controlling cell growth, proliferation, and survival. The potential for PTEN to regulate the synthesis of RNA polymerase (Pol) III transcription products, including tRNAs and 5S rRNAs, was evaluated. The expression of PTEN in PTEN-deficient cells repressed RNA Pol III transcription, whereas decreased PTEN expression enhanced transcription. Transcription repression by PTEN was uncoupled from PTEN-mediated effects on the cell cycle and was independent of p53. PTEN acts through its lipid phosphatase activity, inhibiting the PI3K/Akt/mTOR/S6K pathway to decrease transcription. PTEN, through the inactivation of mTOR, targets the TFIIIB complex, disrupting the association between TATA-binding protein and Brf1. Kinetic analysis revealed that PTEN initially induces a decrease in the serine phosphorylation of Brf1, leading to a selective reduction in the occupancy of all TFIIIB subunits on tRNALeu genes, whereas prolonged PTEN expression results in the enhanced serine phosphorylation of Bdp1. Together, these results demonstrate a new class of genes regulated by PTEN through its ability to repress the activation of PI3K/Akt/mTOR/S6K signaling.
Cellular Uptake Mechanisms of an Antitumor Ruthenium Compound: The Endosomal/Lysosomal System as a Target for Anticancer Metal-Based Drugs

Abstract Previous studies have described promising antitumor activity of an organometallic Ru(II) complex, η5-Cyclopentadienyl(2,2′-bipyridyl)(triphenylphosphane) Ruthenium(II) triflate ([(η5-C5H5)Ru(2,2′-bipyridyl)(PPh3)][CF3SO3]) herein designated as TM34. Its broad spectrum of activity against a panel of human tumor cell lines and high antiproliferative efficiency prompted us to focus on its mode of action. We present herein results obtained with two human tumor cell lines A2780 and MDAMB231 on the compound distribution within the cell, the mechanism of its activity, and its cellular targets. The prospective metallodrug TM34 revealed: (a) fast antiproliferative effects even at short incubation times for both cell lines; (b) preferential localization at the cell membrane and cytosol; (c) cellular activity by a temperature-dependent process, probably macropinocytosis; (d) inhibition of a lysosomal enzyme, acid phosphatase, in a dose-dependent mode; and (e) disruption and vesiculation of the Golgi apparatus, which suggest the involvement of the endosomal/lysosomal system in its mode of action. These results are essential to elucidate the basis for the cytotoxic activity and mechanism of action of this RuII(η5-cyclopentadienyl) complex.
The Promises and Perils of “Scientifically Based” Research for Urban Schools

In this age of high-stakes testing and calls for more stringent measures of accountability, urban schools face a great deal of scrutiny. In fact, the direct benefactors of school reform remain the students most at risk for not reaping the benefits of reform rhetoric. Current legislation that propels the notion of “scientifically based research” to the forefront of debate on what constitutes a high-quality education fails to contextualize the teaching and learning process in urban settings and promises to do more harm than good. This article will examine the challenges and opportunities inherent in scientifically based research and the implications for urban schools.
Equine meniscal degeneration is associated with medial femorotibial osteoarthritis

BACKGROUND There is limited information available concerning normal equine meniscal morphology, its degeneration and role in osteoarthritis (OA). OBJECTIVES To characterise normal equine meniscal morphology and lesions and to explore the relationship between equine meniscal degeneration and femorotibial OA. STUDY DESIGN Ex vivo cadaveric study. METHODS Menisci were harvested from 7 normal joints (n = 14 menisci) and 15 joints with OA (n = 30 menisci). A macroscopic femorotibial OA score (cartilage degeneration and osteophytosis) was employed to measure disease severity in each compartment. The femoral and tibial meniscal surfaces were scored for macroscopic fibrillation and tears (1-4). Histological sections (regions: cranial and caudal horn; body) were also scored for microscopic fibrillation and tears (0-3) and inner border degeneration (0-3). RESULTS Partial meniscal tears were present on both femoral and tibial surfaces in all 3 regions and most frequently identified on the femoral surface of the cranial horn of the medial meniscus and body of the lateral meniscus. There was a significantly positive correlation between the global medial meniscal macroscopic scores and osteophyte (r = 0.7, P = 0.002) or cartilage degeneration (r = 0.5, P = 0.03) scores within the medial femorotibial joint. The global medial meniscal macroscopic score was greater (P = 0.004) in the advanced OA joints compared with control joints. MAIN LIMITATIONS The menisci were principally from abattoir specimens without a known clinical history because of the challenge in obtaining a large number of specimens with a clinical diagnosis of femorotibial OA. CONCLUSIONS This study is the first to describe normal equine meniscal morphology and lesions. Meniscal lesions were identified in all segments and on both articular surfaces. Meniscal degeneration significantly correlated with OA severity in the equine medial femorotibial joint. The relationship between OA and meniscal pathology remains to be elucidated.
Standardized sine-wave fitting algorithms, extensions and applications

The objective of this paper is to present the statistical properties of the IEEE-STD-1057/IEEE-STD-1241 sine-wave fitting algorithms. The proper Cramer-Rao bound is derived for both the three-parameter and four-parameter algorithms. Further, we investigate the residual, and derive its statistical properties, in both the three- and four-parameter fitting case. In a practical setup were the frequency is almost known, we derive an analytical expression for the mean of the residual. By analysis we compare the two methods and state in which case one should use one over the other. Finally, we present some numerical evaluations confirming our analytical findings.
A review of efficacious technology-based weight-loss interventions: five key components.

OBJECTIVE Obesity is highly prevalent among American adults and has negative health and psychosocial consequences. The purpose of this article was to qualitatively review studies that used technology-based interventions for weight loss and to identify specific components of these interventions that are effective in facilitating weight loss. MATERIALS AND METHODS We conducted a narrow, qualitative review, focusing on articles published in the last 10 years that used an experimental or pre/posttest design and used a technology-based intervention for weight loss. RESULTS Among the 21 studies reviewed, we identified the following five components that we consider to be crucial in technology-based weight-loss interventions that are successful in facilitating weight loss: self monitoring, counselor feedback and communication, social support, use of a structured program, and use of an individually tailored program. CONCLUSIONS Short-term results of technologically driven weight-loss interventions using these components have been promising, but long-term results have been mixed. Although more longitudinal studies are needed for interventions implementing these five components, the interface of technology and behavior change is an effective foundation of a successful, short-term weight-loss program and may prove to be the basis of long-term weight loss.
No need to abandon focused parathyroidectomy: a multicenter study of long-term outcome after surgery for primary hyperparathyroidism.

OBJECTIVE The aim of this study was to investigate long-term outcomes after focused parathyroidectomy (FPTX) and open 4-gland parathyroid exploration (OPTX) for primary hyperparathyroidism (pHPT). BACKGROUND Concerns about increased long-term recurrence rates after FPTX in conjunction with decreased operative times for OPTX have led some groups to abandon FPTX in favor of routine 4-gland exploration. METHODS This is a multicenter retrospective cohort study of patients undergoing parathyroidectomy for pHPT from 1990 to 2013. The patient cohort was divided into 2 groups, FPTX and OPTX, based on intention-to-treat analysis. The primary outcome measure was the persistence of pHPT. Secondary outcome measures were differences in the long-term recurrence rate of persisting pHPT and surgical complications. RESULTS A total of 4569 patients (3585 females) were included. The overall persistence and recurrence rates were 2.2% and 0.9%, respectively, after a median follow-up of 6.5 years. There were 2531 FPTX cases and 2038 OPTX cases. The initial persistence rate was higher for FPTX than for OPTX (2.7% vs 1.7%, P = 0.036); however, the long-term recurrence rate was not different (5-year 0.6% vs 0.4%, log-rank P = 0.08). Complications were more common in OPTX than in FPTX (7.6% vs 3.6%, P < 0.001). CONCLUSIONS FPTX was associated with fewer operative complications and an equivalent rate of long-term recurrence than with OPTX. Although initial persistence rates were higher after FPTX than after OPTX, most were readily resolved with subsequent early reoperation. FPTX should not be abandoned in patients with positive preoperative localization.
What Difference Does Day School Make? The Impact of Day School: A Comparative Analysis of Jewish College Students

This report describes the first national study specifically designed to determine the near-term effects of day schools on the academic, social, and Jewish trajectories of former students during their college years. The study considers the impact of day schooling in a variety of areas including Jewish identity and connections to Jewish communal life, as well as social and academic integration into college. The study contextualizes the experiences of students from day schools through comparison with Jewish undergraduates from private and public school backgrounds. Although the findings suggest that day schools can do more to improve math and science learning and to address the needs of diverse learners, the report also validates that day schools provide top-notch preparation for a broad range of colleges and universities, including those that are the most selective. the video from the 5/14/2007 symposium is available at http://cmjs.org/pejesymp.cfm.
Accounting for Recent Declines in Employment Rates among Working-Aged Men and Women with Disabilities.

During the 1990s, while overall employment rates for working-aged men and women either remained roughly constant (men) or rose (women), employment rates for people with disabilities fell. During the same period the fraction of the working-aged population receiving Social Security Disability Insurance (DI) benefits increased quite dramatically. We present simple time series and cross-state evidence suggesting that the growth in the DI program can account for much of the decline in the relative employment position of men and women with disabilities.
The Effect of Child Work on School Enrollment in Egypt

The main objective of this paper is to determine the causal relationship between child work and school enrollment in Egypt while taking into account the simultaneous nature of family (or child) decisions regarding school and work activities. We also assess how a broader definition of work, including domestic work, affects conclusions about the impact of work on schooling for girls. Finally, we examine how children's vulnerability to work and lack of schooling relates to characteristics of their parents and households. We show that child work does not reduce the probability of schooling for boys, but that it does for girls, using either a traditional or broader definition of work. Although policy measures that succeeded in reducing girls? work would increase enrollment, it is hard to formulate such measures since most girls work within the confines of their own homes.
Utilizing Dredged Sediment for Enhancing Growth of Eelgrass in Artificially Prepared Substrates

Dredged sediment (DS) was utilized as source of silt-clay and organic matter in artificially prepared eelgrass substrates with mountain sand (MS) as the sand media. Addition of DS showed improved growth of eelgrass in the mixed substrates. Increase in added DS up to 15% silt-clay showed increased shoot growth but additional DS in 20% silt-clay mixture didn’t result to further increase in eelgrass growth. Improved root establishment were also found for plants in pots with added DS as shown by the increased resistance to uprooting, increased number of rhizome nodes and longer roots. Results demonstrated that addition of DS may be beneficial to eelgrass up to a certain extent only and too much of it might be harmful to eelgrass plants. Keywords—dredged sediment, eelgrass, eelgrass bed restoration, mountain sand, Zostera marina.
Optimizing the Michaelis Complex of Trimethylamine Dehydrogenase

Recent evidence from isotope studies supports the view that catalysis by trimethylamine dehydrogenase (TMADH) proceeds from a Michaelis complex involving trimethylamine base and not, as thought previously, trimethylammonium cation. In native TMADH reduction of the flavin by substrate (perdeuterated trimethylamine) is influenced by two ionizations in the Michaelis complex with pK a values of 6.5 and 8.4; maximal activity is realized in the alkaline region. The latter ionization has been attributed to residue His-172 and, more recently, the former to the ionization of substrate itself. In the Michaelis complex, the ionization of substrate (pK a ∼ 6.5 for perdeuterated substrate) is perturbed by ∼−3.3 to −3.6 pH units compared with that of free trimethylamine (pK a = 9.8) and free perdeuterated trimethylamine (pK a = 10.1), respectively, thus stabilizing trimethylamine base by ∼2 kJ mol−1. We show, by targeted mutagenesis and stopped-flow studies that this reduction of the pK a is a consequence of electronic interaction with residues Tyr-60 and His-172, thus these two residues are key for optimizing catalysis in the physiological pH range. We also show that residue Tyr-174, the remaining ionizable group in the active site that we have not targeted previously by mutagenesis, is not implicated in the pH dependence of flavin reduction. Formation of a Michaelis complex with trimethylamine base is consistent with a mechanism of amine oxidation that we advanced in our previous computational and kinetic studies which involves nucleophilic attack by the substrate nitrogen atom on the electrophilic C4a atom of the flavin isoalloxazine ring. Stabilization of trimethylamine base in the Michaelis complex over that in free solution is key to optimizing catalysis at physiological pH in TMADH, and may be of general importance in the mechanism of other amine dehydrogenases that require the unprotonated form of the substrate for catalysis.
Heterogeneity, not randomness, sets challenges for quantitative genetics and epidemiology: A response to Davey Smith’s “gloomy prospect”

Social epidemiologist Davey Smith (2011) argues that epidemiologists should accept a gloomy prospect: considerable randomness at the individual level means that they should keep their focus on modifiable causes of disease at the population level. The difficulty epidemiology has had in moving from significant population-level risk factors to improved prediction of cases at an individual level is analogous to the lack of success in the search for systematic aspects of the non-shared environmental influences that human quantitative genetics claims overshadow common environmental influences (e.g., the family’s socioeconomic status which siblings have in common). This article responds to the argument and analogy, aiming to draw three audiences—social epidemiologists, human quantitative geneticists, and philosophers of science—into a shared discussion that centers not on randomness, but on heterogeneity in various forms. The first half undercuts the analogy, providing a critical account of human quantitative genetics that explains why its estimates are unreliable and typical interpretations, such as that of non-shared environmental influences, unjustified. In the process, attention is drawn to the possibility of underlying heterogeneity—when similar responses of different types in a species or of different groups of people are observed, it need not be assumed that similar conjunctions of genetic and environmental factors (or, in epidemiology, risk and protective factors) have been involved in producing those responses. The second half introduces several additional forms of heterogeneity and captures their potential significance for epidemiology in four conceptual themes. The themes complicate Davey Smith’s advice for epidemiologists not to seek improved prediction of cases at an individual level and his view of the limited prospects for personalized medicine.
Epidemiological characteristics and prediction of esophageal cancer mortality in China from 1991 to 2012.

BACKGROUND To analyze the mortality distribution of esophageal cancer in China from 1991 to 2012, to forecast the mortality in the future five years, and to provide evidence for prevention and treatment of esophageal cancer. MATERIALS AND METHODS Mortality data for esophageal cancer in China from 1991 to 2012 were used to describe its epidemiological characteristics, such as the change of the standardized mortality rate, urban-rural differences, sex and age differences. Trend-surface analysis was used to study the geographical distribution of the mortality. Curve estimation, time series, gray modeling, and joinpoint regression were used to predict the mortality for the next five years in the future. RESULTS In China, the incidence rate of esophageal cancer from 2007 and the mortality rate of esophageal cancer from 2008 increased yearly, with males at 8.72/105 being higher than females, and the countryside at 15.5/105 being higher than in the city. The mortality rate increased from age 45. Geographical analysis showed the mortality rate increased from southern to eastern China, and from northeast to central China. CONCLUSIONS The incidence rate and the standardized mortality rate of esophageal cancer are rising. The regional disease control for esophageal cancer should be focused on eastern, central and northern regions China, and the key targets for prevention and treatment are rural men more than 45 years old. The mortality of esophageal cancer will rise in the next five years.
Extensive cranial decompression in the treatment of severe lead encephalopathy.

Seven patients are presented who were treated for severe lead encephalopathy by massive bilateral cranial decompression. Of the seven patients, five are alive. One of the fatalities resulted from gastrointestinal hemorrhage 1 week later although it is believed the encephalopathy was controlled. There is recognized significant mental retardation present in two of the surviving patients although the remaining patients cannot be accurately evaluated at the present age. One of the two showing definite retardation also had craniosynostosis which may itself be associated with cerebral dysfunction. A plea is made for more widespread use of decompression as a lifesaving measure and it is further suggested that the impairment of mental function following lead encephalopathy may be reduced if cerebral decompression is undertaken when it becomes apparent that the course of the disease is not being altered by medical agents.
Pediatric Emergency Department Discharge Prescriptions Requiring Pharmacy Clarification

Objectives The aims of the study were to analyze and classify reasons why retail pharmacies need to contact the pediatric emergency department (PED) for clarification on outpatient prescriptions generated using an electronic prescribing system and to categorize the severity of errors captured. Methods A retrospective chart review was conducted at a PED that cares for approximately 92,000 patients annually. All pharmacy callbacks documented in the electronic medical record between August 1, 2008 and July 31, 2009 were included. A datasheet was used to capture patient demographics (age, sex, race, insurance), prescriptions written, and reason for callback. Each call was then assigned a severity level, and time to respond to all calls was estimated. Frequencies were used to analyze the data. Results A total of 731 errors for 695 callbacks were analyzed from 49,583 prescriptions written at discharge. The most common errors included administrative/insurance issues 342/731 (47%) and prescription writing errors 298/731 (41%). The errors were classified as insignificant (340/729 [47%]), problematic (288/729 [40%]), significant (77/729 [11%]), serious (12/729 [1.64%]), and severe (12/729 [1.64%]). Almost 96% of errant prescriptions were not able to be filled as originally written and required a change by the prescriber. These calls required approximately 127 hours to complete. Conclusions Prescription errors requiring a pharmacy callback are typically insignificant. However, 13.8% of callbacks about an error were considered significant, serious, or severe. Automated dose checking and verifying insurance coverage of prescribed medications should be considered essential components of prescription writing in a PED.
MODELING PRIVATE EQUITY FUNDS AND PRIVATE EQUITY COLLATERALISED FUND OBLIGATIONS

The recent development of the securitisation of funds of private equity funds poses the question of the individual and joint modelling of the underlying funds. Private equity funds are different from other managed funds because of their particular bounded life cycle: when the fund starts, the investment partners make an initial capital commitment, the fund managers gradually draw down the committed capital into investments, returns and proceeds are distributed as the investments are realised and the fund is eventually liquidated as the final investment horizon is reached. Modelling private equity funds therefore requires three stages: the modelling of the commitment drawdowns, the modelling of the investment value and the modelling of the return repayments. A standard lognormal process is utilised for the dynamics of the investment value. Squared Bessel processes are utilised for the dynamics of the rates of drawdowns and repayments.Resume: Le recent developpement de la titrisation de fonds de fonds de placements prives pose la question de la modelisation individuelle et jointe des fonds sous-jacents. Les fonds de placements prives sont differents des autres societes d'investissement a cause de leur cycle de vie particulier et limite: au demarrage du fonds, les associes s'engagent sur un apport initial en capital; puis les gerants du fonds operent des tirages progressifs sur le capital apporte pour proceder a des investissements; les revenus et les profits sont distribues a mesure que les investissements sont realises; enfin, le fonds est liquide lorsque l'horizon d'investissement est atteint. La modelisation d'un fonds doit donc se faire en trois etapes: la modelisation des tirages sur l'apport en capital, la modelisation de la valeur des investissements et enfin la modelisation des paiements et remboursements des dividendes et retours sur investissements. Un processus lognormal standard est utilise pour la dynamique de la valeur des investissements. Des processus de Bessel carre sont utilises pour la dynamique des taux de tirage et de remboursement.
The maturation of the immune system.

31% NON-DIGESTIBLE OLIGOSACCHARIDES ARE THE THIRD MOST ABUNDANT COMPONENT OF HUMAN MILK after lactose and lipids2 L A C T O S E LIPIDS HUMAN MILK OLIGOSACCHARIDES were originally discovered as a PREBIOTIC “BIFIDUS FACTOR”3 LACTOSE LIPIDS NON-DIGESTIBLE OLIGOSACCHARIDES ARE ALMOST ABSENT IN COW MILK which is generally the basis for infant formulas2,3 LACTOSE Early infant nutrition the role of prebiotics