Miracle-dz/UniFAR-FTUs huggingface dataset:
Nuclear Expression of β-Catenin Promotes RB Stability and Resistance to TNF-Induced Apoptosis in Colon Cancer Cells

Tumor necrosis factor (TNF)-α promotes tumor development under chronic inflammation. Because TNF also activates caspase-8, selective inhibition of TNF-induced extrinsic apoptosis would be required for inflammation-associated tumor growth. In a mouse model of inflammation-associated colon carcinogenesis, we found nuclear expression of β-catenin in tumors of wild-type, but not mutant, mice that were made resistant to TNF-induced apoptosis by a germline mutation blocking caspase cleavage of the retinoblastoma (RB) protein, despite similar frequencies of β-catenin exon-3 mutations in these two genetic backgrounds. TNF-induced apoptosis was also attenuated in human colon cancer cell lines with genetically activated β-catenin. However, we found that HCT116 cells, which contain an activated allele of β-catenin but do not express nuclear β-catenin, were sensitive to TNF-induced apoptosis. In HCT116 cells, TNF stimulated efficient RB cleavage that preceded chromatin condensation. In contrast, TNF did not induce RB cleavage in colon cancer cells expressing nuclear β-catenin and these cells could be sensitized to basal and/or TNF-induced apoptosis by the knockdown of β-catenin or RB. In the apoptosis-resistant colon cancer cells, knockdown of β-catenin led to a reduction in the RB protein without affecting RB mRNA. Furthermore, ectopic expression of the caspase-resistant, but not the wild-type, RB re-established resistance to TNF-induced caspase activation in colon cancer cells without β-catenin. Together, these results suggest that nuclear β-catenin–dependent RB stabilization suppresses TNF-induced apoptosis in caspase-8–positive colon cancer cells. Visual Overview: http://mcr.aacrjournals. org/content/11/3/207/F1.large. jpg. Mol Cancer Res; 11(3); 207–18. ©2012 AACR. Visual Overview
A Time-Resolved Fluorescence Assay to Identify Small-Molecule Inhibitors of HIV-1 Fusion

Fusion of host cell and human immunodeficiency virus type 1 (HIV-1) membranes is mediated by the 2 “heptad-repeat” regions of the viral gp41 protein. The collapse of the C-terminal heptad-repeat regions into the hydrophobic grooves of a coiled-coil formed by the corresponding homotrimeric N-terminal heptad-repeat regions generates a stable 6-helix bundle. This brings viral and cell membranes together for membrane fusion, facilitating viral entry. The authors developed an assay based on soluble peptides derived from the gp41 N-terminal heptad-repeat region (IQN36) as well as from the C-terminal region (C34). Both peptides were labeled with fluorophores, IQN36 with allophycocyanin (APC) and C34 with the lanthanide europium (Eu3+). Formation of the 6-helix bundle brings both fluorophores in close proximity needed for Förster resonance energy transfer (FRET). Compounds that interfere with binding of C34-Eu with IQN36-APC suppress the FRET signal. The assay was validated with various peptides and small molecules, and quenching issues were addressed. Evaluation of a diversified compound collection in a high-throughput screening campaign enabled identification of small molecules with different chemical scaffolds that inhibit this crucial intermediate in the HIV-1 entry process. This study's observations substantiate the expediency of time-resolved FRET-based assays to identify small-molecule inhibitors of protein-protein interactions. (Journal of Biomolecular Screening 2007:865-874)
Decentralized control approach for voltage unbalance compensation in islanded microgrid

Microgrid as an effective complement to large power grid and also as an important achievement of construct smart grid has been widely developed. It is important to enhance the power quality in the island Microgrids (MGs). The voltage and frequency of the microgrid are determined by the Voltage Source Inverters (VSIs); therefore the power quality can be deteriorated under unbalanced and non-linear loads. In this paper, a decentralized control approach for voltage unbalance compensation is proposed, which includes primary and secondary control levels. The primary level comprises distributed generators (DGs) local controllers. The local controllers mainly consist of power droop control loop, voltage and current control loop, and virtual impedance control loop. Also in the secondary control level, the decentralized secondary controller is designed to remove the deviations of voltage unbalance compensation at the Point of Common Coupling (PCC). Each unit is independently controlled and the entire system of controllers is connected by communication network. So the secondary controller to exchange information each other through the network, which sending appropriate control signals to local controller, which avoids the use of a single centralized controller for the secondary level. Comparing to the centralized control system, the proposed method reduces the requirements of communication links bandwidth and be easy to expand. The control system design is discussed in detail. The simulation results show that the PCC voltage unbalance is compensated to the desired value, while active and reactive powers are shared properly.
Reconfiguring diagnostic work in Danish general practice; regulation, triage and the secretaries as diagnostician

ABSTRACT Health care systems as well as bodies of medical knowledge are dynamic and change as the result of political and social transformations. In recent decades, health care systems have been subjected to a whole assemblage of regulatory practices. The local changes undertaken in Denmark that are being explored here are indicative of a long-term shift that has occurred in many welfare states intended to make public services in the Global North more efficient and transparent. Departing in prolonged field work in Danish general practice and the anthropological literature on audit culture, this paper suggests that the introduction of regulatory practices has enhanced the need for triage as a key organising principle. The term triage literally means separating out and refers to the process of sorting and placing patients in time and space. The paper suggests that an increasing introduction of triage feeds into a reconfiguration of diagnostic work, where the clinical setting is gradually becoming more intertwined with the governing domains of policy, and the work of the secretary is gradually becoming more intertwined with that of the doctor. Finally, the paper argues that an increasing regulation of general practice poses an ethically charged challenge to existing welfare politics of responsibility between the state and the public, as it makes it increasingly difficult to negotiate access to care.
Attractor-based person identification

This paper presents a facial identification system which is based on attractors of a set of two dimensional affine transformation of subparts of facial images. In this approach, the attractor models of the known images are calculated and stored in the database. Then, for each known image, its attractor model is iterated from the input image. If the input image and the known image belong to the same person, the iteration of the attractor model produces an image that is similar to the input image. Otherwise, the iteration process changes the content of the input image significantly. Experimental results are reported and discussed.
Characterization of Two Methanopterin Biosynthesis Mutants of Methylobacterium extorquens AM1 by Use of a Tetrahydromethanopterin Bioassay

ABSTRACT An enzymatic assay was developed to measure tetrahydromethanopterin (H4MPT) levels in wild-type and mutant cells of Methylobacterium extorquens AM1. H4MPT was detectable in wild-type cells but not in strains with a mutation of either the orf4 or the dmrA gene, suggesting a role for these two genes in H4MPT biosynthesis. The protein encoded by orf4 catalyzed the reaction of ribofuranosylaminobenzene 5′-phosphate synthase, the first committed step of H4MPT biosynthesis. These results provide the first biochemical evidence for H4MPT biosynthesis genes in bacteria.
Psychometric Properties of Functional Balance Assessment in Children With Cerebral Palsy

Background. Children with cerebral palsy often suffer from a lack of balance compared with typically developing children. Because balance capacity is relevant to functional activities, reliable and valid functional balance measures are crucial for the pediatric clinical setting. Objective. This study examined the reliability and validity of 3 functional balance measures. Methods. Thirty children aged 60 to 142 months with Gross Motor Function Classification System (GMFCS) levels of I to IV were recruited. For test-retest reliability, the same physical therapist administered the Functional Reach Test (FRT), Berg Balance Scale (BBS), and Timed Up and Go (TUG) twice. For interrater reliability, the testing processes were video recorded and later scored by another therapist. For convergent validity, children with cerebral palsy received the Gross Motor Function Measures (GMFM), walking speed, and 10-second sit-to-stand test within 1 week and the results evaluated. Results. The 3 functional balance measures had excellent test-retest reliability (intraclass correlation coefficient [ICC] >0.95) and interrater reliability (ICC = 0.98-1.00). With regard to convergent validity, the BBS and the TUG were highly correlated with GMFM total score, walking speed, and the 10-second sit-to-stand test. The discriminate validity indicates that the FRT can distinguish children with cerebral palsy with different GMFCS levels, whereas the BBS total score and TUG failed to distinguish between children with cerebral palsy with GMFCS levels of I and II. Conclusion. The 3 functional balance measures are simple, valid, and reliable for examining children with cerebral palsy and are thus suitable for clinical practice.
Efficacy of Integrated Pest Management in Reducing Cockroach Allergen Concentrations in Urban Public Housing

The efficacy of residential interventions to reduce cockroach allergens in public housing developments was evaluated over months of follow-up. Repeated measurements were collected from 39 apartments, with longitudinal analyses used to evaluate changes over time. Bla g 1 kitchen concentrations were reduced 71% and bed concentrations 53% (86% and 70% for Bla g 2, respectively) by 6 months post-intervention, after which concentrations began to increase. Apartments with higher concentrations were usually in poorer condition and benefited most from pest management efforts. Intensive interventions can significantly reduce the allergen burden in public housing apartments, but intervention efforts must be sustained.
Spatiotemporal dynamics of HSV genome nuclear entry and compaction state transitions using bioorthogonal chemistry and super-resolution microscopy

We investigated the spatiotemporal dynamics of HSV genome transport during the initiation of infection using viruses containing bioorthogonal traceable precursors incorporated into their genomes (HSVEdC). In vitro assays revealed a structural alteration in the capsid induced upon HSVEdC binding to solid supports that allowed coupling to external capture agents and demonstrated that the vast majority of individual virions contained bioorthogonally-tagged genomes. Using HSVEdC in vivo we reveal novel aspects of the kinetics, localisation, mechanistic entry requirements and morphological transitions of infecting genomes. Uncoating and nuclear import was observed within 30 min, with genomes in a defined compaction state (ca. 3-fold volume increase from capsids). Free cytosolic uncoated genomes were infrequent (7–10% of the total uncoated genomes), likely a consequence of subpopulations of cells receiving high particle numbers. Uncoated nuclear genomes underwent temporal transitions in condensation state and while ICP4 efficiently associated with condensed foci of initial infecting genomes, this relationship switched away from residual longer lived condensed foci to increasingly decondensed genomes as infection progressed. Inhibition of transcription had no effect on nuclear entry but in the absence of transcription, genomes persisted as tightly condensed foci. Ongoing transcription, in the absence of protein synthesis, revealed a distinct spatial clustering of genomes, which we have termed genome congregation, not seen with non-transcribing genomes. Genomes expanded to more decondensed forms in the absence of DNA replication indicating additional transitional steps. During full progression of infection, genomes decondensed further, with a diffuse low intensity signal dissipated within replication compartments, but frequently with tight foci remaining peripherally, representing unreplicated genomes or condensed parental strands of replicated DNA. Uncoating and nuclear entry was independent of proteasome function and resistant to inhibitors of nuclear export. Together with additional data our results reveal new insight into the spatiotemporal dynamics of HSV genome uncoating, transport and organisation.
State-Space Modeling of Proton Exchange Membrane Fuel Cell

In this paper, a nonlinear state-space model of the 500-W proton exchange membrane (PEM) fuel cell is developed. The open-circuit output voltage of the PEM fuel cell, mass balance, and thermodynamic energy balance inside the PEM fuel cell, voltage losses in the PEM fuel cell, along with the formation of a double layer charge in the PEM fuel cell system are modeled. The model is simulated in MATLAB/Simulink, and the transient response of the PEM fuel cell model over short and long time periods is analyzed. Also, the behavior of the model under the resistive load is studied, and the results are shown.
Testosterone and dihydrotestosterone, but not estradiol, enhance survival of new hippocampal neurons in adult male rats

Past research suggested that androgens may play a role in the regulation of adult neurogenesis within the dentate gyrus. We tested this hypothesis by manipulating androgen levels in male rats. Castrated or sham castrated male rats were injected with 5‐Bromo‐2′deoxyuridine (BrdU). BrdU‐labeled cells in the dentate gryus were visualized and phenotyped (neural or glial) using immunohistochemistry. Castrated males showed a significant decrease in 30‐day cell survival within the dentate gyrus but there was no significant change in cell proliferation relative to control males, indicating that androgens positively affect cell survival, but not cell proliferation. To examine the role of testosterone on hippocampal cell survival, males were injected with testosterone s.c. for 30 days starting the day after BrdU injection. Higher doses (0.5 and 1.0 mg/kg) but not a lower dose (0.25 mg/kg) of testosterone resulted in a significant increase in neurogenesis relative to controls. We next tested the role of testosterone's two major metabolites, dihydrotestosterone (DHT), and estradiol, upon neurogenesis. Thirty days of injections of DHT (0.25 and 0.50 mg/kg) but not estradiol (0.010 and 0.020 mg/kg) resulted in a significant increase in hippocampal neurogenesis. These results suggest that testosterone enhances hippocampal neurogenesis via increased cell survival in the dentate gyrus through an androgen‐dependent mechanism. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007.
Repeatability and Reproducibility of Retinal Neuronal and Axonal Measures on Spectral-Domain Optical Coherence Tomography in Patients with Cognitive Impairment

Background With increasing interest in determining if measurement of retinal neuronal structure with spectral-domain optical coherence tomography (SD-OCT) is useful in accessing neurodegenerative process in cognitive decline and development of dementia, it is important to evaluate whether the SD-OCT measurements are repeatable and reproducible in these patients. Methods This is a retrospective cohort study. Patients with Alzheimer’s disease (AD) or mild cognitive impairment (MCI) with no change in global clinical dementia rating (CDR) score at 1-year follow-up were eligible to be included. Ganglion cell-inner plexiform layer (GC-IPL) and retinal nerve fiber layer (RNFL) parameters were measured with SD-OCT at baseline, 6-month, and 1-year follow-up visits. At baseline, SD-OCT scans were repeated to access intra-visit repeatability of the SD-OCT measurement. SD-OCT measurement over three visits was used to access inter-visit reproducibility. We calculated intraclass correlation coefficients (ICC) and coefficients of variation (CoVs). Results We included 32 patients with stable AD and 29 patients with stable MCI in the final analysis. For GC-IPL measures, the average intra-visit ICC was 0.969 (range: 0.948–0.985), and CoV was 1.81% (range: 1.14–2.40); while the average inter-visit ICC was 0.968 (0.941–0.985), and CoV was 1.91% (range: 1.24–2.32). The average ICC and CoV of intra-visit RNFL measured were 0.965 (range: 0.937–0.986) and 2.32% (range: 1.34–2.90%), respectively. The average ICC and CoV of inter-visit RNFL measures were 0.927 (range: 0.845–0.961) and 3.83% (range: 2.71–5.25%), respectively. Conclusion Both GC-IPL and RNFL measurements had good intra-visit repeatability and inter-visit reproducibility over 1 year in elderly patients with no decline in cognitive function, suggesting that SD-OCT is a reliable tool to assess neurodegenerative process over time.
Articular chondrocytes express connexin 43 hemichannels and P2 receptors – a putative mechanoreceptor complex involving the primary cilium?

Mechanical loading is essential for the health and homeostasis of articular cartilage, although the fundamental mechanotransduction pathways are unclear. Previous studies have demonstrated that cyclic compression up‐regulates proteoglycan synthesis via an intracellular Ca2+ signalling pathway, mediated by the release of ATP. However, the mechanism(s) of ATP release has not been elucidated. The present study examines expression of the putative mechanosensitive ATP‐release channel, connexin 43 and whether it is expressed on the chondrocyte primary cilium, which acts as a mechanosensor in a variety of other cell types. In addition the study characterized the expression of a range of purine receptors through which ATP may activate downstream signalling events controlling cell function. Bovine articular chondrocytes were isolated by sequential enzyme digestion and seeded in agarose constructs. To verify the presence of functional hemichannels, Lucifer yellow (LY) uptake into viable cells was quantified following treatment with a hemichannel agonist (EGTA) and antagonist (flufenamic acid). LY uptake was observed in 45% of chondrocytes, increasing to 83% following EGTA treatment (P < 0.001). Treatment with the hemichannel blocker, flufenamic acid, significantly decreased LY uptake to less than 5% with and without EGTA. Immunofluorescence and confocal microscopy confirmed the presence of primary cilia and the expression of connexin 43. Approximately 50% of bovine chondrocyte primary cilia were decorated with connexin 43. Human chondrocytes in situ within cartilage explants also expressed connexin 43 hemichannels. However, expression was confined to the upper 200 µm of the tissue closest to the articular surface. Immunofluorescence revealed the expression of a range of P2X and P2Y receptor subtypes within human articular cartilage. In conclusion, the expression of functional hemichannels by articular chondrocytes may represent the mechanism through which mechanical loading activates ATP release as part of a purinergic mechanotransduction pathway. Furthermore, the expression of connexin 43 on the chondrocyte primary cilium suggests the possible involvement of the cilium in this pathway.
Macro-modeling of analog blocks for SystemC-AMS simulation: A chemical sensor case-study

SystemC-AMS allows the simulation of complex heterogeneous systems, including software and hardware, in particular Analogue and Mixed-Signal (AMS) or radio-frequency (RF) blocks. These blocks require specific Models of Computation (MoC) to model the analog behavior. This paper presents techniques for the generation of analog macro-models that can be simulated using these MoCs. Both static and dynamic analog behavior are considered. While modeling the static behavior is straightforward, the modeling of the dynamic case requires a linearization of the block behavior. The approach proposed in this work consists of exploiting the frequency response of the focused component in order to obtain a fitted transfer function in the bandwidth of operation of the target block. The Laplace transfer function obtained is next modified in order to be described using the syntax and the primitive libraries offered by the current SystemC-AMS release. This resulting model is de facto a SystemC-AMS module that uses the Synchronous multi-rate Data Flow (SDF) MoC supported by the 0.15RC5 release of SystemC-AMS. We will illustrate these techniques for the case of a chemical sensor that uses a Surface Acoustic Wave (SAW) and a Phase-Locked-Loop (PLL) microelectronics interface.
Qualification and application of a liquid chromatography-quadrupole time-of-flight mass spectrometric method for the determination of trastuzumab in rat plasma.

An liquid chromatography-quadrupole time-of-flight (QqTOF) mass spectrometric method was developed for the determination of humanized or human monoclonal antibodies in rat plasma at the early drug discovery stage. Trastuzumab was used as a model monoclonal antibody. The method consisted of immunoprecipitation followed by tryptic digestion for sample preparation and LC-TOF-MS/MS analysis of specific signature peptides in the positive ion mode using electrospray ionization for analysis. A stable isotope-labeled signature peptide was also used as internal standard. A quadratic regression (weighted 1/concentration(2) ), with an equation y = ax(2) + bx + c, was used to fit calibration curves over the concentration range of 0.500-100 µg/mL for trastuzumab. Samples from a pharmacokinetic study in rat were analyzed by this qualified LC-TOF-MS/MS method and concentrations were compared with those generated by enzyme linked immunosorbent assays method. The LC-TOF-MS/MS method was accurate and precise, with quantitative results comparable with those of ELISA. The qualification run met the acceptance criteria of ±25% accuracy and precision values for quality control samples. Within-run accuracy ranged from 1.53 to 9.20% with precision values ≤10.29%. This LC-TOF-MS/MS method approach could be used as a complementary method for humanized or human monoclonal antibodies at the early drug discovery stage.
Systematic comparative study of computational methods for T‐cell receptor sequencing data analysis

Abstract High‐throughput sequencing technologies have exposed the possibilities for the in‐depth evaluation of T‐cell receptor (TCR) repertoires. These studies are highly relevant to gain insights into human adaptive immunity and to decipher the composition and diversity of antigen receptors in physiological and disease conditions. The major objective of TCR sequencing data analysis is the identification of V, D and J gene segments, complementarity‐determining region 3 (CDR3) sequence extraction and clonality analysis. With the advancement in sequencing technologies, new TCR analysis approaches and programs have been developed. However, there is still a deficit of systematic comparative studies to assist in the selection of an optimal analysis approach. Here, we present a detailed comparison of 10 state‐of‐the‐art TCR analysis tools on samples with different complexities by taking into account many aspects such as clonotype detection [unique V(D)J combination], CDR3 identification or accuracy in error correction. We used our in silico and experimental data sets with known clonalities enabling the identification of potential tool biases. We also established a new strategy, named clonal plane, which allows quantifying and comparing the clonality of multiple samples. Our results provide new insights into the effect of method selection on analysis results, and it will assist users in the selection of an appropriate analysis method.