Miracle-dz/UniFAR-FTUs huggingface dataset:
Estimating stem cell fractions in hierarchically organized tumors

Cancers arise as a result of genetic and epigenetic alterations. These accumulate in cells during the processes of tissue development, homeostasis and repair. Many tumor types are hierarchically organized and driven by a sub-population of cells often called cancer stem cells. Cancer stem cells are uniquely capable of recapitulating the tumor and can be highly resistant to radio-and chemotherapy treatment. We investigate tumor growth patterns from a theoretical standpoint and show how significant changes in pre-and post-therapy tumor dynamics are tied to the dynamics of cancer stem cells. We identify two characteristic growth regimes of a tumor population that can be leveraged to estimate cancer stem cell fractions in vivo using simple linear regression. Our method is a mathematically exact result, parameter free and does not require any microscopic knowledge of the tumor properties. A more accurate quantification of the direct link between the sub-population driving tumor growth and treatment response promises new ways to individualize treatment strategies. Significance Statement Under the cancer stem cell hypothesis a tumor population is driven by a fraction of self-renewing cancer stem cells. Absolute and relative size of this population in human cancers at any stage of the disease remains unknown. We formulate a mathematical model that describes the tumor cell population’s growth dynamics and response to therapy. This allows to estimate cancer stem cell fraction from longitudinal measurements of tumor size (often available from imaging). Such estimates are critical because treatment outcome and risk of relapse depend on the tumor’s capacity to self-renew. Ideally, by tailoring patient treatment strategies based on the relative abundance of cancer stem cells could lead to radically different therapeutic regime and to the successful eradication of the disease.
Integration and segregation of inputs to higher‐order neuropils of the crayfish brain

Information about the input and output pathways of higher‐order brain neuropils is essential for gaining an understanding of their functions. The present study examines the connectivity of two higher‐order neuropils in the central olfactory pathway of the crayfish: the accessory lobe and its target neuropil, the hemiellipsoid body. It is known that the two subregions of the accessory lobe, the cortex and medulla, receive different inputs; the medulla receives visual and tactile inputs, whereas the cortex receives neither (Sandeman et al. [1995] J Comp Neurol 352:263–279). By using dye injections into the olfactory lobe, we demonstrate that the accessory lobe cortex and medulla also have differing connections with the olfactory lobe. These injections show that local interneurons joining the olfactory and accessory lobes branch primarily within the cortex with only limited branching within the medulla. Injections of different dyes into the two subregions of the hemiellipsoid body, HBI and HBII, show that the accessory lobe cortex and medulla also have separate output pathways. HBI is innervated by the output pathway from the cortex while HBII is innervated by the output pathway from the medulla. These injections also show that HBI and HBII are innervated by separate populations of local interneurons with differing connections to higher‐order neuropils in the olfactory and visual pathways. These results suggest a segregation of olfactory and multimodal (including olfactory) inputs within both the accessory lobe and the hemiellipsoid body and provide evidence of important functional subdivisions within both neuropils. J. Comp. Neurol. 481:118–126, 2005. © 2004 Wiley‐Liss, Inc.
ATAZANAVIR: EFFECTS ON P-GLYCOPROTEIN TRANSPORT AND CYP3A METABOLISM IN VITRO

The effect of atazanavir on P-glycoprotein (P-gp) expression and activity, as well as its inhibitory potency against CYP3A activity, was evaluated in vitro. Induction of P-gp activity and expression was studied using LS180V cells. P-gp inhibition was studied using both LS180V cells and Caco-2 cells. P-gp activity was assessed by measuring P-gp-mediated rhodamine 123 (Rh123) transport, and P-gp expression was determined using SDS-polyacrylamide gel electrophoresis/Western blot analysis. CYP3A inhibition was tested using triazolam hydroxylation in human liver microsomes (HLM). Extended (3-day) exposure of LS180V cells to 30 μM atazanavir caused a 2.5-fold increase in immunoreactive P-gp expression as well as a concentration-dependent decrease of intracellular Rh123 to a mean 45% (S.D. 5.2%) of control. Acute exposure (2 h) of LS180V cells to atazanavir increased intracellular Rh123 concentrations up to 300% of control at 100 μM atazanavir. At 30 μM and above, acute atazanavir exposure reversed P-gp induction caused by 3-day pretreatment with 10 μM ritonavir. P-gp inhibition was also observed in Caco-2 cells, causing an effect comparable to that observed for the known P-gp inhibitor verapamil (50% of control). In HLM, atazanavir was an inhibitor of triazolam hydroxylation, with inhibitory potency greatly increased by preincubation. IC50 values with and without preincubation were 0.31 μM (S.D. 0.13) and 5.7 μM (S.D. 4.1), respectively. Thus, atazanavir is an inhibitor and inducer of P-gp as well as a potent inhibitor of CYP3A in vitro, suggesting a potential for atazanavir to cause drug-drug interactions in vivo.
Independent state health surveys: responding to the need for local population health data.

CONTEXT There is high demand for local-level population health data. A national system of state and local data collection would help improve both population health and health care delivery. The primary source of state-level population health data for adults is the Behavioral Risk Factor Surveillance System. However, many states need data on children and adolescents, racial and ethnic subpopulations, consistent estimates for localities, or more in-depth information on key topics than the Behavioral Risk Factor Surveillance System provides. Eleven state health surveys (SHSs) have emerged in an effort to address these gaps. DESIGN Semistructured telephone interviews were conducted in 2009 with representatives of 9 SHSs. The interviews were recorded, and data were transcribed, organized, and analyzed according to the query structure. This analysis identified (1) the core elements of SHS that have been successful in meeting needs for local data and (2) the processes and strategies used by state officials in creating these surveys. RESULTS Key findings include the following: (1) SHSs provide concrete data on local health issues that meet the needs of policy makers who wish to adopt evidence-based public health policies; (2) data from SHSs allow researchers to identify issues, apply for grants, and evaluate, assess, and track health indicators; (3) a "champion" is required to build the case for a survey and push through barriers to obtain funding and stakeholder buy-in; and (4) SHSs face challenges such as inconsistent funding and lack of uniform standards. CONCLUSION Opportunities to support SHSs include (1) identifying sustained funding sources; (2) providing technical assistance and facilitating training to foster best practices, quality standards, and comparability across states; and (3) supporting an organization for SHS researchers to share resources, information, and experiences.
Direct Power Control of a Three-Phase Inverter for Grid Input Current Shaping of a Single-Phase Diode Rectifier With a Small DC-Link Capacitor

This paper describes motor drive system fed by a single-phase diode rectifier without power factor correction (PFC) circuit or the input filter. The system considered in this paper consists of a single-phase diode rectifier, a three-phase inverter, and a small dc-link capacitor. Since dc-link capacitance of the proposed system is few microfarads, the shape of the grid input current is directly affected by electrical output power of the inverter. Using this aspect, two goals of the drive system, controlling torque of the motor and suppressing the grid input current harmonics, can be simultaneously achieved by controlling the output power of the inverter. The proposed method includes the motor current reference generation and the direct output power regulation by modifying the output voltage reference. With the proposed method, the harmonic components of the grid input current can be reduced under the limits of the regulation IEC61000-3-2, lower than those in the conventional method. Also, the cost and size of the inverter system can be significantly reduced by removing electrolytic dc-link capacitor and input filter from the system. The performance of the proposed shaping method was validated by the experimental results using the motor drive system with a 5μF film capacitor at dc link.
Conceptual simulation modeling: The structure of domain specific simulation environment

This study focuses on the development of a conceptual simulation modeling tool that can be used to structure a domain specific simulation environment. The issues in software engineering and knowledge engineering such as object-oriented concepts and knowledge representations are addressed to identify and analyze modeling frameworks and patterns of a specific problem domain. Thus, its structural and behavioral characteristics can be conceptualized and described in terms of simulation architecture and context. Moreover, symbols, notations, and diagrams are developed as a communication tool that creates a blueprint to be seen and recognized by both domain experts and simulation developers, which leads to the effectiveness and efficiency in the simulation development of any specific domains.
Introduction: Rethinking Child Care Research

This introduction summarizes the articles in this collection. It describes how the articles address one or more of the key elements of the child care research model: (a) selecting and measuring the independent variablesto determine the characteristics (“qualities”) of the child care environment (and, in some studies, the characteristics of parents and family), (b) selecting and measuring the dependent variablesto determine the child's physical and developmental status after a period of time in a particular child care arrangement (usually a school year) compared with that of children in other arrangements (or simply the same child before spending time in the arrangement), (c) establishing causal linksbetween the independent and dependent variables that are either assumed in randomized experiments or estimated through statistical controls in nonexperimental studies, and (d) assessing impacts across subgroups to see whether the program benefits one particular group more (or less) than others. The collection closes with a proposal to develop a systematic federal research program to pursue improvements in child care and early childhood education programs.
Bidirectional Single Power-Conversion DC–AC Converter With Noncomplementary Active-Clamp Circuits

This paper presents a bidirectional single power-conversion dc-ac converter with noncomplementary active-clamp circuits. The proposed converter comprises a bidirectional flyback converter and an unfolding bridge. In order to interface the grid with a low-voltage energy storage through only single power-conversion, the bidirectional flyback converter transforms the low voltage directly into the folded grid voltage and regulates the folded grid current. The proposed converter adopts noncomplementary operation strategy for the active-clamp circuits. By using this strategy, the bidirectional flyback converter not only avoids the voltage spike but also minimizes the power losses by the circulating energy. Thus, with single power-conversion and noncomplementary active-clamp circuits, the proposed converter obtains high power efficiency. To facilitate the bidirectional single power-conversion, a novel control algorithm is developed. With this control algorithm, the proposed converter ensures high grid power quality and seamless mode transition. The proposed bidirectional dc-ac converter is theoretically analyzed in detail. The experimental results based on a 250-W prototype are provided to evaluate its performance.
An Online Learning Algorithm for Bilinear Models

We investigate the bilinear model, which is a matrix form linear model with the rank 1 constraint. A new online learning algorithm is proposed to train the model parameters. Our algorithm runs in the manner of online mirror descent, and gradients are computed by the power iteration. To analyze it, we give a new second order approximation of the squared spectral norm, which helps us to get a regret bound. Experiments on two sequential labelling tasks give positive results.
HLA Class II Polymorphism in Egyptian Children with Lymphomas

Abstract The major histocompatibility complex (MHC) is a set of closely-linked genes encoded on the short arm of chromosome 6. It is important for understanding human immunological diseases, transplantation and in host defense against infection. The membrane proteins are two types; class I MHC proteins and class II MHC proteins. Strong arguments supporting genetic linkage between susceptibility to lymphomas and human leukocyte antigens (HLA)-class II are reported and give a clue about susceptibility or protection from the disease. Aim: To evaluate the possible changes of HLA class II (DR, DQ) alleles in children with lymphoma. Methods: Thirty cases were included in this limited study. Nineteen cases of non Hodgkin's lymphoma (NHL) and eleven patients with Hodgkin's lymphoma (HD). Their ages ranged from 1.5 to 15 years. The control group consisted of 121 unrelated healthy subjects for DRB1 alleles and 59 unrelated healthy subjects for DQB1 alleles (only 59 subjects were typed for both DRB1 and DQB1). All cases in the study were assessed by thorough history taking, physical examination and laboratory investigations that included complete blood count, renal function tests, liver function tests, serum uric acid and HLA typing. Patients and controls were typed for HLA class II DRB1 and DQB1 alleles using INNO-LIPA reverse hybridization line probe assay (Innogenetic, Belgium). Results: HLA-DRB1 *0403 and *1301 and HLA-DQB1 *0501,* 0201 and *0301 were significantly increased in patients with NHL when compared with control; whereas HLA-DRB1 *1302 and HLA-DQB1 *0502 and *0602 were significantly decreased when compared with control. In patients with HD, HLA-DRB1 *0403 and *1202 and HLA-DQB1 *0604, *0201 and *0203 were significantly increased when compared with control. Conclusions: (1) The susceptibility to NHL is related to HLA-DRB1 *0403 and *1301 and HLA-DQB1 *0501,* 0201 and *0301. (2) The susceptibility to HD is related to HLA-DRB1 *0403 and *1202 and HLA-DQB1 *0604, *0201 and *0203. (3) HLA-DRB1 *1302 and HLA-DQB1 *0502 and *0602 may confer protection to NHL. (4) Different HLA alleles may have a role in patients with both groups of lymphoma and further study is needed to better define the possible prognostic value of different HLA associations in patients with lymphomas regarding increased risk in the presence of certain HLA alleles and the possibility for treatment modifications in the future based on the presence or absence of certain HLA alleles.
Asymptomatic skin sensitization to birch predicts later development of birch pollen allergy in adults: a 3-year follow-up study.

BACKGROUND The skin prick test is the allergologic test of choice, but asymptomatic skin sensitization to aeroallergens is common. However, no data in the literature describe the clinical phenotype of asymptomatic sensitized adults. OBJECTIVE The purposes of this investigation were to provide a clinical characterization of skin test-positive subjects without symptoms and to ascertain the predictive values of common allergologic tests. METHODS Asymptomatic adults with positive skin prick test results for birch (n = 15), nonatopic control subjects (n = 25), and birch pollen-allergic patients (n = 6) were followed through use of daily diary cards during 3 consecutive birch pollen seasons. At inclusion and at the 3-year follow-up visit, conjunctival and nasal challenges, intradermal late-phase reaction evaluation, and measurement of specific IgE were performed. RESULTS Asymptomatic sensitized subjects defined a clinically significant phenotype between nonatopic and allergic subjects in terms of specific IgE levels and susceptibility to conjunctival provocation testing. Sixty percent (n = 9) of the asymptomatic sensitized subjects developed clinical allergy. This was associated with an initial birch skin prick test weal diameter of > or =4 mm, a positive conjunctival provocation test result, and specific IgE of > or =CAP class 2, as well as with the presence of other allergies. Specific IgE of > or =CAP class 2 was 87.5% predictive for allergy development, whereas a negative conjunctival provocation test result was 100% negatively predictive. Nasal provocation testing possessed no additional prognostic information. No changes in clinical phenotype were seen in nonatopic or birch-allergic subjects. CONCLUSION Asymptomatic skin sensitization is a risk factor for later allergy development. At risk is any subject with target organ sensitivity, an elevated specific IgE level, and/or a skin prick test weal diameter of >4 mm.
Adaptive model-based assistive control for pneumatic direct driven soft rehabilitation robots

Assistive behavior and inherent compliance are assumed to be the essential properties for effective robot-assisted therapy in neurological as well as in orthopedic rehabilitation. This paper presents two adaptive model-based assistive controllers for pneumatic direct driven soft rehabilitation robots that are based on separated models of the soft-robot and the patient's extremity, in order to take into account the individual patient's behavior, effort and ability during control, what is assumed to be essential to relearn lost motor functions in neurological and facilitate muscle reconstruction in orthopedic rehabilitation. The high inherent compliance of soft-actuators allows for a general human-robot interaction and provides the base for effective and dependable assistive control. An inverse model of the soft-robot with estimated parameters is used to achieve robot transparency during treatment and inverse adaptive models of the individual patient's extremity allow the controllers to learn on-line the individual patient's behavior and effort and react in a way that assist the patient only as much as needed. The effectiveness of the controllers is evaluated with unimpaired subjects using a first prototype of a soft-robot for elbow training. Advantages and disadvantages of both controllers are analyzed and discussed.
Innovation through knowledge codification

Academics and business professionals are currently showing a significant interest in understanding the management of knowledge and the roles to be played therein by information and communication technology (ICT). This paper takes a closer look at one of the primary issues raised when supporting the management of knowledge: how to understand the role of knowledge classification and codification as means for further organizational learning and innovation. Two manufacturing cases are analysed using particular perspectives from current theories on classification, namely the management of knowledge and organizational innovation. It is concluded that a more complex understanding of the interplay between cognitive and community models for knowledge management as informed by research on the social processes of classification can inform our understanding of both the role of classification of knowledge for organizational innovation and the viability of providing ICT support based on codified knowledge.
Qualification of a Noninvasive Magnetic Resonance Imaging Biomarker to Assess Tumor Oxygenation

Purpose: Although hypoxia has been long recognized as a crucial factor impairing tumor response in many therapeutic schemes, atraumatic and reliable methods of individually quantifying tumor oxygenation are still lacking in day-to-day clinical practice. The aim of this work was to investigate the potentially quantitative properties of our recently described noninvasive magnetic resonance (MR) technique “MOBILE” (mapping of oxygen by imaging lipids relaxation enhancement) and to qualify this endogenous contrast as a tumor hypoxia marker. Experimental Design: The “MOBILE” technique, which assesses the longitudinal MR relaxation rate, R1, of lipid protons, was benchmarked with the parent technique which assesses the global (or water) R1, in response to a hyperoxic challenge (carbogen breathing) and to a hypoxic challenge (combretastatin A4) in MDA-MB-231 xenografts and in NT2 mammary tumors. Electron paramagnetic resonance (EPR) oximetry was used to quantitatively assess the tumor pO2 in matching tumors longitudinally. Results and Conclusion: Our study evidenced that (i) positive and negative changes in tumor oxygenation can be detected using MOBILE; (ii) a change in the R1 of lipids is positively correlated with a change in the tumor pO2 (P = 0.0217, r = 0.5097); (iii) measured lipid R1 values are positively correlated with absolute pO2 values in both tumor models (P = 0.0275, r = 0.3726); and (iv) changes in the R1 of lipids are more sensitive than changes in the global R1. As this technique presents unique translational properties, it seems promising for the individual longitudinal monitoring of tumor oxygenation in a clinical setting. Clin Cancer Res; 20(21); 5403–11. ©2014 AACR.
Stories Around You: Location-based Serendipitous Recommendation of News Articles

Existing studies in serendipitous recommendation mostly focus on extending the metrics of desired goals such as accuracy, novelty and serendipity with respect to the user preferences. This work aims at serendipity by exploiting the prevailing location (spatial) contexts of the recommendation. For this purpose, we propose a novel spatial context model and a number of recommendation techniques based on the model. A user study on a real news dataset shows that our approach outperforms the baseline distance-based approach and thereby improves the overall user satisfaction with the recommendation result in the absence of the user’s personal information.
Improving the process and outcome of care in COPD: development of a standardised assessment tool.

INTRODUCTION A major goal of COPD treatment is to reduce symptom burden and ensure that the patient's health is as good as possible. This goal requires regular systematic assessment of the patient's COPD with clear and efficient communication between the patient and clinician. AIM To explore patient and physician descriptions of COPD attributes, in order to inform content development of a patient-reported clinical assessment tool. METHODS Qualitative research methods (one-to-one interviews and patient focus groups) were used to elicit key characteristics to evaluate COPD health status and explore how patients with COPD experience their condition. ATLAS.ti version 5.0 was used to identify major themes and generate an item pool. RESULTS Fifty-eight patients with COPD (GOLD stages 1-4; MRC grades 2-5) and 10 clinicians participated in this research. Twenty-one items were generated, capturing patient assessment of breathlessness, wheeze, cough, sleep, activity limitation, energy/fatigue, social function, and anxiety. CONCLUSIONS This qualitative study identified a broad range of items that are potentially suitable for inclusion in a short, simple COPD assessment tool for use in routine clinical practice.