Miracle-dz/UniFAR-FTUs huggingface dataset:
The incidence of parental obesity in overweight individuals.

OBJECTIVE The purpose of this study was to ascertain the incidence of parental obesity in overweight individuals. METHOD The records of 3,227 adult (age 18 or older) obese (body mass index [BMI] higher than 27) outpatients seen at the Cathedral Hill Obesity Clinic over the past approximate three decades were reviewed. The incidence of parental and grandparental obesity was determined from patient histories. RESULTS A far higher prevalence of obese female parents than obese male parents was found in this overweight population. This excess is greater in blacks than in whites, and in females than in males. BMI is greater in earlier than later age of obesity onset. A higher incidence of obese grandmothers than grandfathers was also found in this sample. DISCUSSION The findings of a higher maternal and grandmaternal obesity incidence are discussed in terms of environmental and genetic factors.
Blind matched filtering for multiple input multiple output transceivers

Because of its linearity needs, the direct implementation of the cost effective blind matched filtering technique to multiple input multiple output communication channels was not possible. In this paper we show how to perform the cost effective blind matched filtering technique for these types of communication channels assuming a two-way transmission scenario. For this reason, the blind matched filter and the adaptive filtering blocks, which are required by the so called technique, are adapted for multiple input multiple output case. Besides its structural simplicity, such adaptation does also enable the use of no higher than second order statistics of the received signal for the matched filter identification purposes. Moreover, with the use of the novel receiver, the equalization of the multiple input multiple output channel is performed alongside the matched filter identification stage.
Calculation of the total electrostatic energy of a macromolecular system: Solvation energies, binding energies, and conformational analysis

In this report we describe an accurate numerical method for calculating the total electrostatic energy of molecules of arbitrary shape and charge distribution, accounting for both Coulombic and solvent polarization terms. In addition to the solvation energies of individual molecules, the method can be used to calculate the electrostatic energy associated with conformational changes in proteins as well as changes in solvation energy that accompany the binding of charged substrates. The validity of the method is examined by calculating the hydration energies of acetate, methyl ammonium, ammonium, and methanol. The method is then used to study the relationship between the depth of a charge within a protein and its interaction with the solvent. Calculations of the relative electrostatic energies of crystal and misfolded conformations of Themiste dyscritum hemerythrin and the VL domain of an antibody are also presented. The results indicate that electrostatic charge‐solvent interactions strongly favor the crystal structures. More generally, it is found that charge‐solvent interactions, which are frequently neglected in protein structure analysis, can make large contributions to the total energy of a macromolecular system.
Deregulation of Poly(A) Polymerase Interferes with Cell Growth

ABSTRACT Vertebrate poly(A) polymerase (PAP) contains a catalytic domain and a C-terminal Ser-Thr-rich regulatory region. Consensus and nonconsensus cyclin-dependent kinase (cdk) sites are conserved in the Ser-Thr-rich region in vertebrate PAPs. PAP is phosphorylated by cdc2-cyclin B on these sites in vitro and in vivo and is inactivated by hyperphosphorylation in M-phase cells, when cdc2-cyclin B is active. In the experiments described here, we undertook a genetic approach in chicken DT40 cells to study the function of PAP phosphorylation. We found that PAP is highly conserved in chicken and is essential in DT40 cells. While cells could tolerate reduced levels of PAP, even modest overexpression of either wild-type PAP or a mutant PAP with two consensus cdk sites mutated (cdk− PAP) was highly deleterious and at a minimum resulted in reduced growth rates. Importantly, cells that expressed cdk− PAP had a significantly lower growth rate than did cells that expressed similar levels of wild-type PAP, which was reflected in increased accumulation of cells in the G0-G1 phase of the cell cycle. We propose that the lower growth rate is due to the failure of hyperphosphorylation and thus M-phase inactivation of cdk−PAP.
Tumor and Stem Cell Biology A Tumorigenic MLL-Homeobox Network in Human Glioblastoma Stem Cells

Glioblastoma growth is driven by cancer cells that have stem cell properties, but molecular determinants of their tumorigenic behavior are poorly defined. In cancer, altered activity of the epigeneticmodifiers Polycomband Trithorax complexes may contribute to the neoplastic phenotype. Here, we provide the first mechanistic insights into the role of the Trithorax protein mixed lineage leukemia (MLL) in maintaining cancer stem cell characteristics in human glioblastoma. We found that MLL directly activates the Homeobox gene HOXA10. In turn, HOXA10 activates a downstream Homeobox network and other genes previously characterized for their role in tumorigenesis. The MLL–Homeobox axis we identified significantly contributes to the tumorigenic potential of glioblastoma stem cells. Our studies suggest a role for MLL in contributing to the epigenetic heterogeneity between tumor-initiating and non–tumor-initiating cells in glioblastoma. Cancer Res; 73(1); 1–11. 2012 AACR.
Drop-Landing Performance and Knee-Extension Strength After Anterior Cruciate Ligament Reconstruction.

CONTEXT Individuals with a history of anterior cruciate ligament reconstruction (ACLR) are at greater risk of reinjury and developing early-onset osteoarthritis due to persistent abnormal joint loading. Real-time clinical assessment tools may help identify patients experiencing abnormal movement patterns after ACLR. OBJECTIVE To compare performance on the Landing Error Scoring System (LESS) between participants with ACLR and uninjured control participants and to determine the relationship between LESS score and knee-extension strength in these participants. DESIGN Controlled laboratory study. SETTING Research laboratory. PATIENTS OR OTHER PARTICIPANTS Forty-six recreationally active participants, consisting of 22 with ACLR (12 men, 10 women; age = 22.5 ± 5.0 years, height = 172.8 ± 7.2 cm, mass = 74.2 ± 15.6 kg, body mass index = 24.6 ± 4.0) and 24 healthy control participants (12 men, 12 women; age = 21.7 ± 3.6 years, height = 168.0 ± 8.8 cm, mass = 69.2 ± 13.6 kg, body mass index = 24.3 ± 3.2) were enrolled. MAIN OUTCOME MEASURE(S) Bilateral normalized knee-extension maximal voluntary isometric contraction (MVIC) torque (Nm/kg) and LESS scores were measured during a single testing session. We compared LESS scores between groups using a Mann-Whitney U test and the relationships between LESS scores and normalized knee-extension MVIC torque using Spearman ρ bivariate correlations. RESULTS The ACLR participants had a greater number of LESS errors (6.0 ± 3.6) than healthy control participants (2.8 ± 2.2; t44 = -3.73, P = .002). In ACLR participants, lower normalized knee-extension MVIC torque in the injured limb (ρ = -0.455, P = .03) was associated with a greater number of landing errors. CONCLUSIONS Participants with ACLR displayed more errors while landing. The occurrence of landing errors was negatively correlated with knee-extension strength, suggesting that weaker participants had more landing errors. Persistent quadriceps weakness commonly associated with ACLR may be related to a reduced quality of lower extremity movement during dynamic tasks.
Functional disability can deteriorate despite suppression of disease activity in patients with rheumatoid arthritis: a large observational cohort study

ObjectiveTo analyze the relationship between the progression of disability and disease activity in patients with rheumatoid arthritis (RA) in daily practice.MethodsPatients from an observational cohort, IORRA, who completed surveys during 2009–2011 were eligible. Linear regression of disease activity score 28 (DAS28), Japanese version of Health Assessment Questionnaire (J-HAQ), and EQ-5D from baseline were calculated, and the angles of the regression lines were designated DAS28 slope, J-HAQ slope, and EQ-5D slope, respectively, in each patient; averages were compared between treatment groups.ResultsA total of 5,038 patients [84.0 % female, mean age 59.4 (SD 13.1) years, disease duration 13.2 (9.6) years, DAS28 3.29 (1.14), and J-HAQ 0.715 (0.760)] were analyzed. The average DAS28 slope indicated improvement in all groups, whereas J-HAQ slopes were negative in patients on methotrexate (MTX), biologics, combination biologics/disease-modifying antirheumatic drugs (DMARDs), and combination biologics/MTX at baseline, but positive in patients on prednisolone >5 mg/day [0.010 (0.153)] and not on MTX at baseline [0.007 (0.122)], representing a worsening of disability.ConclusionThere is some disparity between improvement of disease activity and progression of disability, suggesting that quality of remission must be considered.
Circular Business Models : Defining a Concept and Framing an Emerging Research Field

To aid companies in transitioning towards a circular economy and adopting strategies such as reuse, repair, and remanufacturing, the concept of circular business models has been developed. Although the concept draws on contributions from various academic disciplines, and despite its increasingly frequent use, few scholars clearly define what a circular business model is. Understanding about what makes a business model circular is diverse, hampering the theoretical development and practical application of circular business models. This study aims to help frame the field of circular business model research, by clarifying the fundamentals of the concept from the perspectives of resource efficiency and business model innovation. Expanding on these findings, a review of how the concept is used in recent academic literature is provided. It shows that a coherent view is lacking on which resource efficiency strategies classify a business model as circular. This study clarifies which resource efficiency strategies can be deemed as relevant key strategies for circular business models, and suggests a new definition of the concept. With the definition grounded in analysis of the fundamentals in terms of resource efficiency and business models, the study contributes to theoretical advancement and effective implementation of circular business models.
A Research Agenda for Trust in Online Environments

We present an agenda for the future research that has the potential to extend the conceptual foundations of trust in online environments and to improve the practice in the domain. The agenda draws on the previous work on trust, the papers included in this Special Issue, and our perspective on the state of the literature. This agenda is structured into four components-nature and role of trust, moderators of trust, antecedents of trust, and empirical methods for examining trust.
Energy resource management in the virtual data center

The virtual data center (VDC) is a truly evolutionary computing model, presenting the data center as a service view to a single computer, which virtualizes all hardware and software behind it. Recent variations of the VDC model include grid, autonomic, modular, fabric, and utility center, each with a focus on total cost of ownership benefits. A VDC, which satisfies quality of service (QoS) at guaranteed resource costs, can be extended to manage energy as a first class resource and guarantees energy at predictable costs. This article describes how virtual data centers differ from traditional data centers for energy management and surveys the ecological benefits of this emerging model. Emphasis is on dynamic extensions to VDC virtualization that leverage real-time migration of live, stateful applications.
Model-based leakage localization in drinking water distribution networks using structured residuals

In this paper, a new model based approach to leakage localization in drinking water networks is proposed based on generating a set of structured residuals. The residual evaluation is based on a numerical method based on an enhanced Newton-Raphson algorithm. The proposed method is suitable for water network systems because the non-linearities of the model make impossible to derive analytical residuals. Furthermore, the computed residuals are designed so that leaks are decoupled, which improves the localization of leaks with respect to other existing methods. Finally, the Hanoi water network benchmark is used to illustrate the results of the proposed approach.
Inducible but not endothelial nitric oxide synthase polymorphism is associated with susceptibility to rheumatoid arthritis in northwest Spain.

OBJECTIVE To assess the influence of inducible and endothelial nitric oxide synthase (iNOS and eNOS) polymorphisms in susceptibility to rheumatoid arthritis (RA). METHODS Two hundred RA patients fulfilling the 1987 American College of Rheumatology classification criteria followed at the out-patient rheumatology clinic of the Hospital Xeral-Calde (Lugo, Spain) and 251 ethnically matched controls were studied. Patients and controls were genotyped by PCR-based techniques for a multiallelic (CCTTT)(n) repeat in the promoter region of the iNOS gene and for a T/C polymorphism at position -786 in the promoter region and a polymorphism in exon 7 (298Glu/Asp or 5557G/T) of the eNOS gene. RESULTS No significant difference in allele or genotype frequencies for either polymorphism in the eNOS gene was observed between RA patients and controls. The overall iNOS CCTTT(n) allelic or genotypic distribution did not show statistical significant differences between RA patients and controls. Interestingly, when we stratified the iNOS alleles into short (8-11) and long (12-16) repeats, significant differences were observed between RA patients and controls (P = 0.021; odds ratio = 1.37, 95% confidence interval 1.04-1.81). Of note, individuals carrying two alleles with a repeat number less than 12 (fewer than 196 base pairs) exhibited a double risk of developing RA (P = 0.005, odds ratio 2.26, 95% confidence interval 1.25-4.08). CONCLUSIONS Significant differences in the iNOS promoter polymorphism genotype frequency between northwest Spanish RA patients and controls suggest a potential role for this polymorphism in susceptibility to RA.
Prevalence and Correlates of Heroin-Methamphetamine Co-Injection Among Persons Who Inject Drugs in San Diego, California, and Tijuana, Baja California, Mexico.

OBJECTIVE Although persons who inject drugs (PWID) in the western United States-Mexico border region are known to inject both heroin and methamphetamine, little is known about the prevalence and risks associated with co-injection of this depressant-stimulant combination (also known as "goofball" and "Mexican speedball"). METHOD Baseline data from parallel cohort studies of PWID conducted concurrently in San Diego, CA, and Tijuana, Mexico, were used to estimate the prevalence and identify correlates of heroin-methamphetamine co-injection. PWID older than 18 years of age who reported injecting illicit drugs in the past month (N = 1,311; 32.7% female) were recruited in San Diego (n = 576) and Tijuana (n = 735) and completed interviewer-administered questionnaires. Bivariate and multivariable logistic regression analyses were used to identify correlates of heroin-meth-amphetamine co-injection. RESULTS The prevalence of co-injection in the past 6 months was 39.9% overall and was higher in Tijuana (55.8%) than in San Diego (19.8%). In multivariable analyses adjusting for study cohort, distributive syringe sharing, purchasing syringes prefilled with drugs, finding it hard to get new syringes, reporting great or urgent need for treatment, and younger age were independently associated with co-injection. Past-6-month overdose was significantly associated with higher odds of co-injection in San Diego than in Tijuana. CONCLUSIONS These findings indicate that heroin-methamphetamine co-injection is more common in Tijuana than in San Diego, yet this practice was only associated with overdose in San Diego. Heroin-methamphetamine coinjection was also independently associated with HIV-associated injection risk behaviors. Overdose-prevention interventions should address co-injection of depressants and stimulants.
Neuropathy Target Esterase Biosensor

Neuropathy Target Esterase (NTE), is a membrane-bound protein found in neurons of vertebrates (Glynn, 1999; Atkins & Glynn, 2000; van Tienhoven et al., 2002; Li et al., 2003; Makhaeva et al., 2003; Kropp et al., 2004), has been shown to be necessary for embryonic development in mice, and is believed to be involved in cell-signaling pathways and lipid trafficking (Glynn, 1999). NTE has serine esterase activity and can hydrolyze ester, peptide, and amide bonds. The nucleophilic serine residue (active site) of NTE attacks the carbonyl carbon atom of the substrate, forming a covalent acyl-enzyme intermediate, which is subsequently hydrolyzed. A consequence of this reaction mechanism is that the esterase activity of NTE is susceptible to covalent inhibition by organophosphorus esters (OPs) with which it forms an analogous phosphyl-enzyme intermediate. Irreversible binding of some OP compounds to the active serine site results in a debilitating neural disease known as OP-induced delayed neuropathy (OPIDN) (Glynn, 1999). Signs of OPIDN include flaccid paralysis of the lower limbs, which becomes evident two to three weeks after exposure to neuropathic OPs. Recovery from this disease is usually poor, and there is no specific treatment. In addition, mutations in the NTE gene have been linked to motor neuron disease (Rainier et al., 2008). Because NTE plays a central role in both chemically induced and spontaneously occurring neurological diseases, approaches that can help measure its esterase activity and inhibition are of tremendous scientific and commercial importance. Because NTE is difficult to produce for research purposes, research to study its esterase activity is typically done using a fragment of the NTE protein that contains the esterase activity and can be more easily produced. One such fragment, known as NEST, (Atkins & Glynn, 2000; Forshaw et al., 2001; Kropp et al., 2004) reacts with esters and inhibitors in a manner very similar to NTE. Conventionally, the esterase activity of NTE (or NEST) is measured using two distinct steps. In the first step, a solution containing phenyl valerate is brought into contact with NEST or NTE protein solution, whose esterase activity reacts with a portion of the artificial substrate phenyl valerate to form phenol. In the second step, the concentration of phenol in the solution is determined either colorimetrically, in the presence of 4-amino antipyrine
Rapid Quantitation of Neuraminidase Inhibitor Drug Resistance in Influenza virus Quasispecies

Background Emerging resistance of influenza viruses to neuraminidase inhibitors is a concern, both in surveillance of global circulating strains and in treatment of individual patients. Current methodologies to detect resistance rely on the use of cultured virus, thus taking time to complete or lacking the sensitivity to detect mutations in viral quasispecies. Methodology for rapid detection of clinically meaningful resistance is needed to assist individual patient management and to track the transmission of resistant viruses in the community. Methods We have developed a pyrosequencing methodology to detect and quantitate influenza neuraminidase inhibitor resistance mutations in cultured virus and directly in clinical material. Our assays target polymorphisms associated with drug resistance in the neuraminidase genes of human influenza A H1N1 as well as human and avian H5N1 viruses. Quantitation can be achieved using viral RNA extracted directly from respiratory or tissue samples, thus eliminating the need for virus culture and allowing the assay of highly pathogenic viruses such as H5N1 without high containment laboratory facilities. Results Antiviral-resistant quasispecies are detected and quantitated accurately when present in the total virus population at levels as low as 10%. Pyrosequencing is a real-time assay; therefore, results can be obtained within a clinically relevant timeframe and provide information capable of informing individual patient or outbreak management. Conclusions Pyrosequencing is ideally suited for early identification of emerging antiviral resistance in human and avian influenza infection and is a useful tool for laboratory surveillance and pandemic preparedness.
Caution warranted in extrapolating from Boston Naming Test item gradation construct

ABSTRACT The Boston Naming Test (BNT) was designed to present items in order of difficulty based on word frequency. Changes in word frequencies over time, however, would frustrate extrapolation in clinical and research settings based on the theoretical construct because performance on the BNT might reflect changes in ecological frequency of the test items, rather than performance across items of increasing difficulty. This study identifies the ecological frequency of BNT items at the time of publication using the American Heritage Word Frequency Book and determines changes in frequency over time based on the frequency distribution of BNT items across a current corpus, the Corpus of Contemporary American English. Findings reveal an uneven distribution of BNT items across 2 corpora and instances of negligible differentiation in relative word frequency across test items. As BNT items are not presented in order from least to most frequent, clinicians and researchers should exercise caution in relying on the BNT as presenting items in increasing order of difficulty. A method is proposed for distributing confrontation-naming items to be explicitly measured against test items that are normally distributed across the corpus of a given language.
Comparative genomic analysis of Vibrio cholerae: Genes that correlate with cholera endemic and pandemic disease

Historically, the first six recorded cholera pandemics occurred between 1817 and 1923 and were caused by Vibrio cholerae O1 serogroup strains of the classical biotype. Although strains of the El Tor biotype caused sporadic infections and cholera epidemics as early as 1910, it was not until 1961 that this biotype emerged to cause the 7th pandemic, eventually resulting in the global elimination of classical biotype strains as a cause of disease. The completed genome sequence of 7th pandemic El Tor O1 strain N16961 has provided an important tool to begin addressing questions about the evolution of V. cholerae as a human pathogen and environmental organism. To facilitate such studies, we constructed a V. cholerae genomic microarray that displays over 93% of the predicted genes of strain N16961 as spotted features. Hybridization of labeled genomic DNA from different strains to this microarray allowed us to compare the gene content of N16961 to that of other V. cholerae isolates. Surprisingly, the results reveal a high degree of conservation among the strains tested. However, genes unique to all pandemic strains as well as genes specific to 7th pandemic El Tor and related O139 serogroup strains were identified. These latter genes may encode gain-of-function traits specifically associated with displacement of the preexisting classical strains in South Asia and may also promote the establishment of endemic disease in previously cholera-free locations.