Miracle-dz/UniFAR-FTUs huggingface dataset:
CHARGE STABILITY AND CONDUCTANCE ANALYSIS OF ANTHRACENE-BASED SINGLE ELECTRON TRANSISTOR

The present paper discusses the investigation of electronic properties of anthracene-based single electron transistor (SET) operating in coulomb blockade region using Density Functional Theory (DFT) based Atomistix toolkit-Virtual nanolab. The charging energies of anthracene molecule in isolated as well as electrostatic SET environments have been calculated for analyzing the stability of the molecule for different charge states. Study also includes the analysis of SET conductance dependence on source/drain and gate potentials in reference to the charge stability diagram. Our computed charging energies for anthracene in isolated environment are in good agreement with the experimental values and the proposed anthracene SET shows good switching properties in comparison to other acene series SETs.
A genetic inference on cancer immune responsiveness

A cancer immune signature implicating good prognosis and responsiveness to immunotherapy was described that is observed also in other aspects of immune-mediated, tissue-specific destruction (TSD). Its determinism remains, however, elusive. Based on limited but unique clinical observations, we propose a multifactorial genetic model of human cancer immune responsiveness.
Rosiglitazone Inhibits Adrenocortical Cancer Cell Proliferation by Interfering with the IGF-IR Intracellular Signaling

Rosiglitazone (RGZ), a thiazolidinedione ligand of the peroxisome proliferator-activated receptor (PPAR)-γ, has been recently described as possessing antitumoral properties. We investigated RGZ effect on cell proliferation in two cell line models (SW13 and H295R) of human adrenocortical carcinoma (ACC) and its interaction with the signaling pathways of the activated IGF-I receptor (IGF-IR). We demonstrate a high expression of IGF-IR in the two cell lines and in ACC. Cell proliferation is stimulated by IGF-I in a dose- and time-dependent manner and is inhibited by RGZ. The analysis of the main intracellular signaling pathways downstream of the activated IGF-IR, phosphatidyl inositol 3-kinase (PI3K)-Akt, and extracellular signal-regulated kinase (ERK1/2) cascades reveals that RGZ rapidly interferes with the Akt and ERK1/2 phosphorylation/activation which mediates IGF-I stimulated proliferation. In conclusion, our results suggest that RGZ exerts an inhibitory effect on human ACC cell proliferation by interfering with the PI3K/Akt and ERK1/2 signaling pathways downstream of the activated IGF-IR.
Association of the Mouse Infertility Factor DAZL1 with Actively Translating Polyribosomes1

Abstract The DAZ (Deleted in AZoospermia) gene family was isolated from a region of the human Y chromosome long arm that is deleted in about 10% of infertile men with idiopathic azoospermia. DAZ and an autosomal DAZ-like gene, DAZL1, are expressed in germ cells only. They encode proteins with an RNA recognition motif and with either a single copy (in DAZL1) or multiple copies (in DAZ) of a DAZ repeat. A role for DAZL1 and DAZ in spermatogenesis is supported by their homology to a Drosophila male infertility protein Boule and by sterility of Dazl1 knock-out mice. The biological function of these proteins remains unknown. We found that DAZL1 and DAZ bound similarly to various RNA homopolymers in vitro. We also used an antibody against the human DAZL1 to determine the subcellular localization of DAZL1 in mouse testis. The sedimentation profiles of DAZL1 in sucrose gradients indicate that DAZL1 is associated with polyribosomes, and further capture of DAZL1 on oligo(dT) beads demonstrates that the association is mediated through the binding of DAZL1 to poly(A) RNA. Our results suggest that DAZL1 is involved in germ-cell specific regulation of mRNA translation.
Benefit, Risk, and Outcomes in Drug Development: A Systematic Review of Sunitinib.

BACKGROUND Little is known about the total patient burden associated with clinical development and where burdens fall most heavily during a drug development program. Our goal was to quantify the total patient burden/benefit in developing a new drug. METHODS We measured risk using drug-related adverse events that were grade 3 or higher, benefit by objective response rate, and trial outcomes by whether studies met their primary endpoint with acceptable safety. The differences in risk (death rate) and benefit (overall response rate) between industry and nonindustry trials were analyzed with an inverse-variance weighted fixed effects meta-analysis implemented as a weighted regression analysis. All statistical tests were two-sided. RESULTS We identified 103 primary publications of sunitinib monotherapy, representing 9092 patients and 3991 patient-years of involvement over 10 years and 32 different malignancies. In total, 1052 patients receiving sunitinib monotherapy experienced objective tumor response (15.7% of intent-to-treat population, 95% confidence interval [CI] = 15.3% to 16.0%), 98 died from drug-related toxicities (1.08%, 95% CI = 1.02% to 1.14%), and at least 1245 experienced grade 3-4 drug-related toxicities (13.7%, 95% CI = 13.3% to 14.1%). Risk/benefit worsened as the development program matured, with several instances of replicated negative studies and almost no positive trials after the first responding malignancies were discovered. CONCLUSIONS Even for a successful drug, the risk/benefit balance of trials was similar to phase I cancer trials in general. Sunitinib monotherapy development showed worsening risk/benefit, and the testing of new indications responded slowly to evidence that sunitinib monotherapy would not extend to new malignancies. Research decision-making should draw on evidence from whole research programs rather than a narrow band of studies in the same indication.
Persistence of psychiatric disorders in pediatric settings.

OBJECTIVE To examine the longitudinal course of subthreshold and full-criteria child psychiatric disorders. METHOD Nine hundred ninety-six children, aged 4 to 9 years, from a representative sample of pediatric primary care practices participated in a 1-year follow-up in 1989-1990. Parent interviews included the Diagnostic Interview Schedule for Children, measures of psychosocial problems, stress, social support, possible child abuse, and sociodemographics. RESULTS The initial prevalence of full and subthreshold disorders was 18.8% and 14.0%, respectively. Full and subthreshold disorders were associated with impairment. Approximately 37% of children with full disorders had persistent disorders. Persistence was more common among boys than girls, particularly when comorbidity was present. Children with initial subthreshold disorders only were five times more likely than those without disorder to develop a full disorder. Persistence of full disorders was associated with high initial symptoms. Among boys, persistence was linked to possible child abuse, whereas among girls it was associated with full externalizing disorders that were accompanied by subthreshold internalizing disorders. CONCLUSIONS Intervention may be particularly crucial when a high number of symptoms and/or both internalizing and externalizing problems are present. Underscoring the importance of family-centered rather than child-centered interventions, boys whose parents reported possible child abuse were more likely to have persistent disorders.
Introducing Trigger Support for XML Database Systems ∗ c ©

There is a growing number of XML database systems of different kinds now on the market. XML DBMS vendors rushed to enrich their products with more flexible and advanced features to make them satisfy the requirements of modern applications. And the time is ripe for the database research community to study the issues involved with extending XML DBMS with capabilities analogous to those that are popular in traditional DBMS, keeping in mind that XML databases now become a widespread means for storing and exchanging information on the Web, and increasingly used in dynamic applications such as e-commerce. In this paper, being bound for the issues, we provide a definition of triggers for XML based on XQuery and a previously defined update language, and methods to support triggers in XML database systems.
Maternal lipids in pre-eclampsia: innocent bystander or culprit?

Pre-eclampsia continues to be a challenge – to understand the underlying pathogenesis and to prevent or treat in the clinical setting. One area of potential therapies opening up is treatment of maternal lipids and clinical trials are underway using statins in early pre-eclampsia. At present, most potential therapies to treat lipids cannot be recommended for general use in pregnancy and if we were to target maternal lipids to reduce rates of pre-eclampsia, very large numbers of women may need to be treated. Prior to reaching that point, we first need to understand whether maternal lipids are pathogenic in the processes underlying pre-eclampsia. The aim of this review is to examine the role of lipids in the pathogenesis and outcomes of pre-eclampsia, how abnormal lipid genes may be implicated and consider whether treatment of hyperlipidemia has a more general place in the prevention or treatment of pre-eclampsia.
An Annotation Support System for Middle School Teachers and Students in the ICDL

In this paper we describe a system for middle school students and teachers that combines the affordances of paper with the affordances of digital books. Our teacher composer tool focuses on providing teachers with tools to annotate books with reading comprehension hints for their students. The student annotation tool focuses on providing students with highlighters, stamps and sticky notes to aid them in better understanding their reading. The Interactive Workbook provides not only the functionality of a freeform note-pad, but begins to incorporate structured reading activities that teachers create to help students further explore concepts in books. Our preliminary user study shows that (something like: this tool helps students better understand books they read and helps teachers compose more comprehensive lesson plans). The tools we have designed successfully make use of paper affordances in the digital domain, giving teacher and students a powerful alternative to paper-based worksheets and books.
Toxic Role of K+ Channel Oxidation in Mammalian Brain

Potassium (K+) channels are essential to neuronal signaling and survival. Here we show that these proteins are targets of reactive oxygen species in mammalian brain and that their oxidation contributes to neuropathy. Thus, the KCNB1 (Kv2.1) channel, which is abundantly expressed in cortex and hippocampus, formed oligomers upon exposure to oxidizing agents. These oligomers were ∼10-fold more abundant in the brain of old than young mice. Oxidant-induced oligomerization of wild-type KCNB1 enhanced apoptosis in neuronal cells subject to oxidative insults. Consequently, a KCNB1 variant resistant to oxidation, obtained by mutating a conserved cysteine to alanine, (C73A), was neuroprotective. The fact that oxidation of KCNB1 is toxic, argues that this mechanism may contribute to neuropathy in conditions characterized by high levels of oxidative stress, such as Alzheimer's disease (AD). Accordingly, oxidation of KCNB1 channels was exacerbated in the brain of a triple transgenic mouse model of AD (3xTg-AD). The C73A variant protected neuronal cells from apoptosis induced by incubation with β-amyloid peptide (Aβ1–42). In an invertebrate model (Caenorhabditis elegans) that mimics aspects of AD, a C73A-KCNB1 homolog (C113S-KVS-1) protected specific neurons from apoptotic death induced by ectopic expression of human Aβ1–42. Together, these data underscore a novel mechanism of toxicity in neurodegenerative disease.
Topical anaesthesia and intravenous cannulation success in paediatric patients: a randomized double-blind trial.

BACKGROUND It is not known whether the choice of topical anaesthetic influences the likelihood of successful i.v. cannulation in the paediatric population. The null hypothesis of this study was that no difference exists in the initial success rate of cannulation between two commonly used topical anaesthetics. METHODS A randomized double-blind trial conducted on patients between the age of 12 months and 12 yr presenting to a tertiary hospital emergency department. Patients requiring cannulation were randomized to either 4% amethocaine gel (AnGEL) or 5% lidocaine and prilocaine in a 1:1 emulsion (EMLA). The primary endpoint was success of initial attempt at i.v. cannulation. RESULTS One hundred and seventy-seven patients were analysed of 203 enrolled. The success rate of AnGEL (73/97, 75%) and EMLA (59/80, 74%) did not significantly differ (chi2(1) 0.05, P=0.82). CONCLUSIONS No difference exists in the cannulation success rates between the two anaesthetics. The choice of topical anaesthetic in paediatric cannulation should be based on other factors such as cost, time to anaesthesia, efficacy of the agent, and adverse effect profile.
Glial Cell Contributions to Auditory Brainstem Development

Glial cells, previously thought to have generally supporting roles in the central nervous system, are emerging as essential contributors to multiple aspects of neuronal circuit function and development. This review focuses on the contributions of glial cells to the development of auditory pathways in the brainstem. These pathways display specialized synapses and an unusually high degree of precision in circuitry that enables sound source localization. The development of these pathways thus requires highly coordinated molecular and cellular mechanisms. Several classes of glial cells, including astrocytes, oligodendrocytes and microglia, have now been explored in these circuits in both avian and mammalian brainstems. Distinct populations of astrocytes are found over the course of auditory brainstem maturation. Early appearing astrocytes are associated with spatial compartments in the avian auditory brainstem. Factors from late appearing astrocytes promote synaptogenesis and dendritic maturation, and astrocytes remain integral parts of specialized auditory synapses. Oligodendrocytes play a unique role in both birds and mammals in highly regulated myelination essential for proper timing to decipher interaural cues. Microglia arise early in brainstem development and may contribute to maturation of auditory pathways. Together these studies demonstrate the importance of non-neuronal cells in the assembly of specialized auditory brainstem circuits.
In Vivo Activity of a Phospholipase C Inhibitor, 1-(6-((17β-3-Methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122), in Acute and Chronic Inflammatory Reactions

To investigate the role of phospholipase C (PLC) in inflammatory processes, we tested 1-(6-((17β-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122), a widely used PLC inhibitor, in several in vitro and in vivo assays. We first examined the effects of U73122 on human phospholipase C-β (PLC-β) isozymes and found that U73122 significantly inhibited recombinant human PLC-β2, with an IC50 of ∼6 μM. U73122 had little effect on PLC-β1, PLC-β3, or PLC-β4. Consistent with its ability to inhibit PLC-β2 enzymatic activity, U73122 reduced interleukin-8 and leukotriene B4-induced Ca2+ flux and chemotaxis in human neutrophils in a concentration-dependent manner. In vivo, U73122 blocked carrageenan-induced hind paw edema in rats, carrageenan-induced macrophage and lymphocyte accumulation into subcutaneous chambers in dogs, lipopolysaccharide-induced macrophage, lymphocyte infiltration and prostaglandin E2 production in a mouse peritonitis model, and 12-O-tetradecanoylphorbol-13-acetate-induced ear edema in mice. These results implicate PLC-dependent signaling pathways in the development of acute and chronic inflammatory responses in vivo.
AC Loss Reduction of Superconducting Power Transmission Cables Composed of Coated Conductors

AC losses in power transmission cables composed of coated conductors could be potentially small. A strategy to approach their potentially small AC loss was studied. AC losses in mono-layer conductors for cables were calculated numerically in order to show the principle for AC loss reduction: use of narrower coated conductors and/or decrease in space between conductors reduce the magnetic field component perpendicular to the wide face of coated conductors, and they are effective for AC loss reduction. This principle was confirmed experimentally by using short mono-layer conductors. Based on the principle, 1 kArms-class three-layer conductors were fabricated, and AC loss of 0.054 W/m at 1 kArms was achieved in a three-layer conductor whose outer diameter is 19.6 mm. The influence of a magnetic substrate on the AC losses in a single coated conductor and a mono-layer conductor for a cable was studied numerically.
A POMDP formulation of preference elicitation problems

Preference elicitation is a key problem facing the deployment of intelligent systems that make or recommend decisions on the behalf of users. Since not all aspects of a utility function have the same impact on object-level decision quality, determining which information to extract from a user is itself a sequential decision problem, balancing the amount of elicitation effort and time with decision quality. We formulate this problem as a partially-observable Markov decision process (POMDP). Because of the continuous nature of the state and action spaces of this POMDP, standard techniques cannot be used to solve it. We describe methods that exploit the special structure of preference elicitation to deal with parameterized belief states over the continuous state space, and gradient techniques for optimizing parameterized actions. These methods can be used with a number of different belief state representations, including mixture models.
Solution structure and dynamics of linked cell attachment modules of mouse fibronectin containing the RGD and synergy regions: comparison with the human fibronectin crystal structure.

We report the three-dimensional solution structure of the mouse fibronectin cell attachment domain consisting of the linked ninth and tenth type III modules, mFnFn3(9,10). Because the tenth module contains the RGD cell attachment sequence while the ninth contains the synergy region, mFnFn3(9,10) has the cell attachment activity of intact fibronectin. Essentially complete signal assignments and approximately 1800 distance and angle restraints were derived from multidimensional heteronuclear NMR spectra. These restraints were used with a hybrid distance geometry/simulated annealing protocol to generate an ensemble of 20 NMR structures having no distance or angle violations greater than 0.3 A or 3 degrees. Although the beta-sheet core domains of the individual modules are well-ordered structures, having backbone atom rmsd values from the mean structure of 0.51(+/-0.12) and 0.40(+/-0.07) A, respectively, the rmsd of the core atom coordinates increases to 3.63(+/-1.41) A when the core domains of both modules are used to align the coordinates. The latter result is a consequence of the fact that the relative orientation of the two modules is not highly constrained by the NMR restraints. Hence, while structures of the beta-sheet core domains of the NMR structures are very similar to the core domains of the crystal structure of hFnFn3(9,10), the ensemble of NMR structures suggests that the two modules form a less extended and more flexible structure than the fully extended rod-like crystal structure. The radius of gyration, Rg, of mFnFn3(9,10) derived from small-angle neutron scattering measurements, 20.5(+/-0.5) A, agrees with the average Rg calculated for the NMR structures, 20.4 A, and is ca 1 A less than the value of Rg calculated for the X-ray structure. The values of the rotational anisotropy, D ||/D perpendicular, derived from an analysis of 15N relaxation data, range from 1.7 to 2.1, and are significantly less than the anisotropy of 2.67 predicted by hydrodynamic modeling of the crystal coordinates. In contrast, hydrodynamic modeling of the NMR coordinates yields anisotropies in the range of 1.9 to 2.7 (average 2.4(+/-0.2)), with NMR structures bent by more than 20 degrees relative the crystal structure having calculated anisotropies in best agreement with experiment. In addition, the relaxation parameters indicate that several loops in mFnFn3(9,10), including the RGD loop, are flexible on the nanosecond to picosecond time-scale. Taken together, our results suggest that, in solution, the limited set of interactions between the mFnFn3(9,10) modules position the RGD and synergy regions to interact specifically with cell surface integrins, and at the same time permit sufficient flexibility that allows mFnFn3(9,10) to adjust for some variation in integrin structure or environment.
Formation of three-dimensional cell/polymer constructs for bone tissue engineering in a spinner flask and a rotating wall vessel bioreactor.

The aim of this study is to investigate the effect of the cell culture conditions of three-dimensional polymer scaffolds seeded with rat marrow stromal cells (MSCs) cultured in different bioreactors concerning the ability of these cells to proliferate, differentiate towards the osteoblastic lineage, and generate mineralized extracellular matrix. MSCs harvested from male Sprague-Dawley rats were culture expanded, seeded on three-dimensional porous 75:25 poly(D,L-lactic-co-glycolic acid) biodegradable scaffolds, and cultured for 21 days under static conditions or in two model bioreactors (a spinner flask and a rotating wall vessel) that enhance mixing of the media and provide better nutrient transport to the seeded cells. The spinner flask culture demonstrated a 60% enhanced proliferation at the end of the first week when compared to static culture. On day 14, all cell/polymer constructs exhibited their maximum alkaline phosphatase activity (AP). Cell/polymer constructs cultured in the spinner flask had 2.4 times higher AP activity than constructs cultured under static conditions on day 14. The total osteocalcin (OC) secretion in the spinner flask culture was 3.5 times higher than the static culture, with a peak OC secretion occurring on day 18. No considerable AP activity and OC secretion were detected in the rotating wall vessel culture throughout the 21-day culture period. The spinner flask culture had the highest calcium content at day 14. On day 21, the calcium deposition in the spinner flask culture was 6.6 times higher than the static cultured constructs and over 30 times higher than the rotating wall vessel culture. Histological sections showed concentration of cells and mineralization at the exterior of the foams at day 21. This phenomenon may arise from the potential existence of nutrient concentration gradients at the interior of the scaffolds. The better mixing provided in the spinner flask, external to the outer surface of the scaffolds, may explain the accelerated proliferation and differentiation of marrow stromal osteoblasts, and the localization of the enhanced mineralization on the external surface of the scaffolds.