Miracle-dz/UniFAR-FTUs huggingface dataset:
Cystic Fibrosis Gene Therapy: Key Questions and Prospects

Cystic fibrosis is a monogenic disorder with significant morbidity and mortality, despite advances in conventional treatment. It is a good candidate for gene therapy and this field has progressed rapidly since the cystic fibrosis transmembrane conductance regulator gene was cloned. We will review the specific questions to address for successful cystic fibrosis gene therapy, such as the extraand intracellular barriers to airway gene transfer, the target cells and the endpoints to assess efficacy. We will discuss recent advances in viral and nonviral gene transfer agents, delivery techniques and novel strategies to enhance airway gene transfer and expression.
Carbidopa enhances antitumoral activity of bicalutamide on the androgen receptor‐axis in castration‐resistant prostate tumors

Response to bicalutamide after castration failure is not durable and treatment options at this stage are limited. Carbidopa, an L‐dopa decarboxylase (AR‐coactivator) inhibitor, has been shown to retard prostate tumor growth/PSA production in xenografts. Here, we hypothesize that pharmacological targeting of the AR‐axis by combination treatment with bicalutamide plus carbidopa significantly enhances antitumoral activity in vitro and in vivo compared to monotherapy with either drug.
Modern and Novel Radiotherapy Approaches for the Treatment of Uveal Melanoma.

Uveal melanoma (UM) is the most common primary malignant intraocular tumor in adults and comprises approximately 5% of all melanoma diagnoses in the United States each year. The overall longterm rate of metastasis for UM is approximately 50%, resulting in a 15year mortality rate that approaches 40% to 50%, as a result of metastatic disease. Historically, all UMs were treated by enucleation to prevent metastases and death. In the 1970s, Zimmerman et al challenged the traditional treatment of UMs by theorizing that enucleation may worsen prognosis by promoting dissemination of tumor cells—and therefore increasing metastases—during the act of enucleating the eye. The socalled ‘‘Zimmerman hypothesis’’ partly inspired the multicenter Collaborative Ocular Melanoma Study (COMS), which ultimately disproved this theory. As a result of the various findings of the COMS, most primary UMs are no longer enucleated, but are instead treated with radiotherapy. Plaque brachytherapy remains the most commonly used treatment for COMS medium-size tumors, with apical heights <10 mm. In this setting, the goal of treatment for UMs has shifted from enucleation to preservation of the eye and vision, whenever possible, by treating locally with radiotherapy. Enucleation is now reserved for larger tumors where radiation delivery would lead to excessive morbidity including injury to the normal tissues and/or significant visual morbidity. However, over the past few decades, alternative forms of radiation
From neoclassical theory to mainstream modelling : fifty years of moral hazard in perspective

Tony Lawson asks why and under what circumstances we should use the term ‘neoclassical’ to refer to a specific school of economics. His answer is both nuanced and strategic. It is nuanced in the sense that, though Lawson believes that a conception of neoclassicism can be salvaged, that conception differs significantly from accounts defended by neoclassical economists themselves and by prominent historians of economic thought. It is strategic in the sense that, following a careful reconstruction of how Veblen’s original conception of neoclassicism might be extended to strands of modern economics, Lawson eventually suggests that the term should be abandoned.
Differences in height explain gender differences in the response to the oral glucose tolerance test

Gender differences in 2 h-plasma glucose (2hPG; women > men) in the AusDiab Survey disappeared following adjustment for height, suggesting that the results of the oral glucose tolerance test (OGTT) may need adjustment for body height [1]. The aims of our study were (i) to determine whether these findings could be replicated in another population and (ii) to evaluate whether these sex differences could be alternatively explained by fat-free mass (kg) [FFM(kg)] as an indicator of muscle mass. All 1353 participants (697 men, 656 women) without known diabetes from the KORA Survey 2000, conducted in the area of Augsburg, were included {age: men 64.1 ± 5.6 years, women 63.9 ± 5.3 years, P = 0.46; weight: men 83.2 ± 11.4 kg, women 72.2 ± 12.0 kg, P < 0.001; height: men 171.8 ± 6.4 cm, women 159.0 ± 6.1 cm, P < 0.001; FFM: men 55.4 ± 6.7 kg, women 42.6 ± 4.7 kg, P < 0.001; newly diagnosed diabetes: men 10.5%, women 7.5%, P = 0.06; pre-diabetes [impaired fasting glucose (IFG)/impaired glucose tolerance (IGT)]: men 29.7%, women 22.2%, P = 0.02} [2]. FFM(kg) was determined by bioelectric impedance measurement as described elsewhere [3]. Men had significantly higher fasting plasma glucose (FPG) than women (5.8 ± 1.0 vs. 5.5 ± 0.8 mmol/l, P < 0.001, difference: 0.32; 95% confidence interval: 0.22; 0.42), but similar 2hPG (7.1 ± 2.9 vs. 6.9 ± 2.6 mmol/l, P = 0.18) and a similar 2hPG–FPG increment in the OGTT compared with women (1.3 ± 2.4 vs. 1.4 ± 2.1 mmol/l, P = 0.34). No significant sex difference was found for HbA 1c (5.6 ± 0.5 vs. 5.7 ± 0.5%, P = 0.08). The gender difference in FPG persisted after adjusting for height, FFM(kg) and body mass index (BMI) (Table 1). Because the observed 2hPG values of the (pre-)diabetic subjects acted as outliers, the residuals (2hPG minus predicted 2hPG) of the investigated models were far from being normally distributed. After including FPG and BMI in the regression models, the residuals were reasonably normally distributed. After controlling for age, FPG and BMI using linear regression, a significant gender coefficient was found for 2hPG (men < women). This gender difference disappeared after further adjusting for height. Height showed a negative relationship with 2hPG within each sex despite adjustment for age, FPG and BMI (men: β = − 0.03, P = 0.009; women: β = − 0.03, P = 0.056). The sex difference in 2hPG also completely disappeared after alternatively controlling for fat-free mass (kg) instead of height (Table 1). A significant inverse association of FFM(kg) with 2hPG was found in men after adjustment (age, FPG, BMI) ( β = − 0.06, P < 0.001), while there was no significant relationship in women ( β = − 0.03, P = 0.195). In conclusion, the smaller height of women could explain higher 2hPG after glucose challenge, suggesting that the glucose load of the OGTT should be varied according to body size. Our analyses indicate that fat-free mass (kg), which is substantially higher in men than in women, is an alternative explanation for the gender difference in 2hPG. FFM(kg) is an
Current advances in modern wound healing

Under normal circumstances, wounds are expected to heal within a reasonable period of time through a series of a regulated cascade of events. However, when the cascade becomes interrupted, wounds fail to heal in a timely manner, resulting in chronic non-healing wounds (ulcers). Over the years, a variety of measures have been attempted in the treatment of non-healing wounds, including a range of different dressing products, drugs and devices. However, not all wounds respond to the above modalities of treatment and, consequently, non-healing, refractory wounds continue to be a significant burden in the hospital as well as the community.
Electron paramagnetic resonance study of the stereochemistry of nitrosylhemoglobin.

Paramagnetic resonance spectra of single crystals of nitrosylhemoglobin (HbNO) have been obtained at − 195°C. There are four nonequivalent paramagnetic atoms which form two sets; the members of each set are related by the [010] dyad axis. The principal values of the g tensor are: gxx = 2.0820, gyy = 2.0254, and gzz = 1.9909; the isotropic g value is 2.039. The principal values of the hyperfine A tensors are: Tξξ = 77 MHz, Tηη = 54 MHz, and Tξξ = 18 MHz; the isotropic coupling constant has a value of 50 MHz. The calculated principal values for the dipolar T′ tensors are: tξξ′ = 27 MHz, tηη′ = 5 MHz, and tξξ′ = −32 MHz. The principal axes of the g tensor do not coincide with these of the T tensor; the results were interpreted to give a bent Fe–N–O angle of 110°. The N–O axes of the ligands of one set lie in the ab plane; those of the others are inclined at an angle of about 80° to the ab plane. The electrostatic interaction of the oxygen atom with the imidazolium group of the distal histidine and the nonpol.
EGFR gene status predicts response and survival benefit in a preclinical gastric cancer trial treating patient‑derived xenografts with cetuximab.

Cetuximab has been evaluated as a first-line treatment with conflicting results. The aim of the present study was to investigate the relationship between epidermal growth factor receptor (EGFR) status, and response and survival benefit following cetuximab treatment in gastric cancer (GC). Using 20 patient-derived GC xenograft (PDX) models, the mice (10 mice/model) were randomly assigned into two groups. The control group and treatment group were treated with PBS and cetuximab, respectively. The drug response was evaluated by monitoring tumor growth. Survival benefit was evaluated by comparing the survival curves corresponding to the time for the tumors to reach 600 mm3. Our results revealed that the PDX models treated with cetuximab had better survival than that noted for the non-treated group (P<0.05). The EGFR status was measured by FISH, qPCR, RNAish and immunohistochemistry, respectively. Four cases in the treated group were identified as responsive to cetuximab. EGFR mRNA and protein overexpression were associated with the response to cetuximab (P<0.05). EGFR amplification, mRNA and protein overexpression were associated with prolonged survival in the cetuximab-treated PDX models. Moreover, in the PDX models with EGFR amplification, mRNA or protein overexpression, cetuximab treatment was associated with a better survival compared with that noted in the untreated group in the PDX models (P<0.05), while the survival was not statistically different in the other cases (P>0.05). In conclusion, cetuximab provided survival benefit in the trial. The level of EGFR amplification and overexpression significantly predicted response and survival benefit, particularly the mRNA and protein expression level. A combination of mRNA and protein expression may predict efficacy of cetuximab more efficiently.
Effects of Valenced Media Frames of Cancer Diagnoses and Therapies: Quantifying the Transformation and Establishing of Evaluative Schemas

Journalists portray health issues within different frames, which may shape news recipients’ evaluations, attitudes, and behaviors. As the research on framing continues to face theoretical challenges and methodological concerns, this study examines the transformation and establishing of evaluative schemas, which are steps in the process toward attitudinal change. The study measures recipients’ evaluations of actual television clips dealing with cancer diagnoses and cancer therapies. Two valenced (positive vs. negative) media frames were tested in a 3-week online panel (n = 298) using a pretest–posttest design with a German sample. The results offer limited support for the hypothesis that media frames transform participants’ schemas, but do not support the hypothesis that new schemas are established in response to media frames. The study also investigates interactions between framing and participants’ issue involvement, as well as between framing and topic-specific interest and media use.
Shared Aperture Technology Development

T he demand for increasingly sophisticated sensor and communications systems aboard military platforms has grown while space and weight constraints have become more stringent. These opposing factors have created a strong desire to reduce the number of associated antenna systems by combining the functions of several systems into a single antenna. Shared aperture antennas are a new class of phased array antennas that combine the functionality of several antennas into one aperture using wideband multiple beam technology. Applications for shared apertures include radar, communications, and electronic warfare. This article describes an experimental shared aperture antenna under development at the Applied Physics Laboratory. The antenna incorporates key shared aperture technologies, including wideband dual-polarized tapered notch radiating elements and dual-channel monolithic microwave integrated circuit receive modules.
Echographic evaluation with image analysis of irritant reactions induced by nonanoic acid and hydrochloric acid

Skin reactions to 40% nonanoic acid in propanol (NON) and to 4% hydrochloric acid were evaluated by image analysis of 20 MHz B scan recordings (Dermascan C, Cortex Technology). 18 women, aged 18 to 45, were patch tested with 24‐h application time, and clinical and instrumental evaluations were performed at the beginning of the experiment, and 24 and 48 h after patch testing. To check possible regional variations in reactivity to NON and HC1, both substances were applied 2 × on the same forearm. As control tests, saline solution, propanol and sodium lauryl sulfate (SLS) 3% were applied. Echographic images were processed by a program enabling numerical representation of picture data, based on attribution of fictional values to the echoes' amplitudes, selection of amplitude bands of interest, binary transformation of the image, and calculation of the extension of areas reflecting within the same amplitude range. Sonographic recordings were evaluated by an amplitude interval marking hyporeflecting parts of the dermis (corresponding to edema and inflammatory infiltration), and by a band highlighting the entrance echo (epidermis). Our evaluations showed that extension of the hypoechogenic area of the dermis increases according to intensity of inflammatory reaction for all irritant substances. A clear decrease in reflectivity of the epidermis echo at 24 h was visible at SLS patch test test sites, whereas at patch test sites performed with NON and HCl, there was a trend towards an increase in values of hyperreflecting pixels. No significant variations between data recorded at proximal compared to distal skin sites were observed for NON and HCl. In conclusion, the echographic technique provides a method for quantification of the dermal inflammatory reaction, and also for description of skin reactions induced by irritant substances, according to their specific epidermal effects.
Collision avoidance among multiple mobile robots based on rules and communication

An autonomous and decentralized robot system, ACTRESS, is being developed as an intelligent robot system which is composed of multiple robotic agents. The basic concept and strategy for path planning in a dynamically changing environment with multiple autonomous mobile robots are introduced. Collision avoidance with dynamic path planning according to the complexity of the situations is also discussed. A method for collision avoidance based on rules and negotiation by communication is presented. Finally, this method is applied to a developed prototype system consisting of two mobile robots, and the result of experiments operating on real robots is given. <<ETX>>
Involvement of metabotropic glutamate receptor 5 in the inhibition of methamphetamine‐associated contextual memory after prolonged extinction training

Addiction is thought to be a memory process between perception and environmental cues and addicted patients often relapse when they come into contact with the drug‐related context once again. Here, we used a conditioned place preference protocol to seek a more effective extinction methodology of methamphetamine (METH) memory and delineate its underlying mechanism. Conditioning METH for 3 days in mice markedly increased the time spent in the METH‐paired compartment. Then the mice were conditioned with saline for 6 days, from day 6 to day 11, a procedure termed extinction training. However, METH memory returned after a priming injection of METH. We prolonged extinction duration from 6 to 10 days and found that this extensive extinction (EE) training prevented priming effect. At the molecular level, we discovered that prolonged extinction training reversed the METH‐conditioned place preference‐induced increase in surface expression of GluA2 and alpha‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA)/NMDA ratio in the basolateral amygdala. In addition, we found that extinction with metabotropic glutamate receptor 5 (mGluR5) activation had similar results to EE: reduced relapse after extinction, decreased synaptic AMPA receptors AMPARs and the AMPA/NMDA ratio. On the contrary, EE with mGluR5 inhibition suppressed the results of EE. These data indicate that EE training‐elicited inhibition of METH‐primed reinstatement is mediated by the mGluR5.
Cutting Edge: Emergence of CD127high Functionally Competent Memory T Cells Is Compromised by High Viral Loads and Inadequate T Cell Help1

In this report we have inspected whether difficulties in controlling viral infections negatively impacts the generation of CD127high memory T cells. Using both MHC class I and II tetramers we reveal that CD127low T cells are not necessarily rapidly deleted but can persist in a pseudoeffector state in which they display the hallmarks of activated effector cells but are functionally inferior. CD127high cells can, however, emerge if the infection is contained. We also show that in the absence of CD4 T cell help significant populations of CD127high CD8 T cells fail to emerge. Analyses of cytokine-producing activities by both mouse and human CD8 T cells further document that the extended maintenance of T cells in a CD127low state has functional consequences which manifest as an impairment of IL-2 production.
Microbiology of airway disease in patients with cystic fibrosis

Individuals with cystic fibrosis have abbreviated life spans primarily due to chronic airway infection. A limited number of types of organisms are responsible for these infections, with Staphylococcus aureus and Pseudomonas aeruginosa being of primary importance. In the pre-antibiotic era, greater than 90% of deaths due to infection were caused by S. aureus and death usually occurred in the first 2 years of life. With the advent of effective antistaphylococcal therapy, life spans increased and P. aeruginosa became the pathogen of primary importance. P. aeruginosa isolates recovered from patients with cystic fibrosis have a unique phenotypic characteristic referred to as "mucoid. " The mucoid phenotype is due to the production of a mucoid exopolysaccharide. A mucoid exopolysaccharide is believed to play a central role in the establishment of chronic pseudomonal lung infection in these patients. A third organism, Pseudomonas cepacia, has recently been detected in the airways of older patients with cystic fibrosis and is associated with increased mortality. The virulence of P. cepacia is not understood, but the organism is extremely refractory to antimicrobial therapy. Other bacteria, including Haemophilus influenzae and members of the family Enterobacteriaceae, appear to play a secondary role in airway infection. Aspergillus fumigatus is the most important fungal agent causing allergic bronchopulmonary disease. The role of viruses has only recently been examined. At least in some patients with cystic fibrosis, respiratory syncytial virus may be important in predisposing to subsequent bacterial infections.
Liver‐enriched transcription factors and hepatocyte differentiation

Liver‐specific gene expression in adult hepatocytes relies on four families of evolutionary conserved transcription factors that are liver‐enriched but not restricted to this tissue. These factors function in unique combinations, often synergisti‐cally, to stimulate cell‐specific transcription. Each family is composed of several members displaying similar, if not identical, DNA recognition properties and sharing structural homology in their DNA binding domains. The homo‐ and heterodimerization between members of a particular transcription factor family adds an additional level of complexity in gene regulation. The consequences of inactivating differ‐ent family members in the mouse by homologous recombination, together with recent studies of their regulation, suggest a model for liver differentiation involving a regulatory network rather than a completely hierarchical genetic circuitry. These studies also indicate that individual regulators appear to serve multiple developmental functions. Their possible role in the progression through different stages of hepatic cell commitment and differentiation is discussed. —Cereghini, S. Liver‐enriched transcription factors and hepatocyte differentiation. FASEB J. 10,267‐282 (1996)
Active Power Factor Correction (PFC) Circuit With Resistor-Free Zero-Current Detection

An active power-factor correction (PFC) circuit is presented that employs a newly proposed resistor-free zero-current detection (ZCD). While the conventional ZCD requires either a sensing resistor or auxiliary transformer, the proposed ZCD requires only one OFF-chip capacitor. The active PFC circuit with the proposed resistor-free ZCD has been implemented in a 0.35-μm BCDMOS process and the power factor is improved up to 9% from the one employing the conventional ZCD. The proposed resistor-free ZCD scheme can be applied to any type of switch-mode dc-dc power converter.
Angiotensin receptors in the eyes of arterial hypertensive rats

Purpose: The aim of the present study was to determine whether the eye tissues of arterial hypertensive rats evince expression of angiotensin receptors (AT1 and AT2) as well as the novel Mas receptor, whose endogenous ligand is vasorelaxing Angiotensin (1–7) [Ang (1–7)].
Optical fiber twist sensor with two orthogonally oriented mechanically induced long-period grating sections

We propose and demonstrate, for the first time, an optical fiber twist sensor consisting of two mechanically induced long-period grating sections, whose birefringent axes are mutually orthogonal. The twist sensor, whose temperature stability is supposedly high and sensitivity is tunable by pressure, is based on the change in the loss peak separation due to the twist-induced polarization rotation.
Effects of post‐hepatectomized rat sera on cultured cells

These experiments suggest that serum obtained subsequent to partial hepatectomy of rats is capable of stimulating the growth of and enhancing the final population and cell viability achieved in antibiotic‐free suspension cultures of L929 cells. Preliminary enzymatic inhibition of post‐hepatectomy serum suggests that one of the humoral factors involved may be RNA.
TraceAnalyzer: a system for processing performance traces

The performance of a program often varies significantly over the course of the program's run. Thus, to understand the performance of a program it is valuable to look not just at end‐to‐end metrics (e.g. total number of cache misses) but also the time‐varying performance of the program. Unfortunately, analyzing time‐varying performance is both cumbersome and difficult. This paper makes three contributions, all geared toward helping others in working with traces. First, it describes a system, the TraceAnalyzer, designed specifically for working with performance traces; a performance trace captures the time‐varying performance of a program run. Second, it describes lessons that we have learned from many years of working with these traces. Finally, it uses a case study to demonstrate how we have used the TraceAnalyzer to understand a performance anomaly. Copyright © 2010 John Wiley & Sons, Ltd.