Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of retinoic acid receptor overexpression in sensitivity to fenretinide and tumorigenicity of human ovarian carcinoma cells

The role of retinoic acid receptor (RAR) expression in sensitivity to N‐(4‐hydroxyphenyl)retinamide (4HPR or fenretinide) as well as on the tumorigenicity of human ovarian carcinoma cells was examined. Two human ovarian cancer cell lines, A2780 and IGROV‐1, with a 10‐fold difference in sensitivity to 4HPR were chosen to study RAR involvement in the response to 4HPR. To determine which RAR was effective, RARα, β and γ were individually overexpressed in A2780 cells, which are the most sensitive to 4HPR. Sensitivity to 4HPR was increased in RARβ‐overexpressing clones, whereas it was slightly decreased in RARα transfectants (which had diminished RARβ expression) and was unchanged in clones transfected with RARγ. IGROV‐1 cells, which are RARβ negative, were transfected with RARβ. Surprisingly, none of the obtained IGROV‐1 RARβ transfectants expressed RARβ protein, in spite of RARβ mRNA transcription. All clones were similar to the parental IGROV‐1 cells in their sensitivity to 4HPR. Treatment with a pharmacologically achievable concentration of 4HPR (1 μM) led to a rapid 2‐fold increase in RARβ mRNA levels in A2780 cells, but it did not induce RARβ expression in IGROV‐1 cells. Analysis of the tumorigenicity of A2780‐transfected clones revealed that overexpression of RARα was associated with a significant reduction in tumor takes (50% and 67%, respectively, vs. 96% for the parent line) and with a reduced growth rate. Oncogenicity was clearly decreased in only 1 of the 2 RARβ‐overexpressing clones (33% takes) and was unchanged in the 2 clones with increased RARγ expression. Our results demonstrate that basal expression and 4HPR inducibility of RARβ play a role in mediating 4HPR response in ovarian cancer cells. The findings of reduced oncogenicity of clones overexpressing RARα and of one clone overexpressing RARβ indicate that RARα and RARβ might have a tumor‐suppressive effect in ovarian tumors. Int. J. Cancer 81:829–834, 1999. © 1999 Wiley‐Liss, Inc.
Explaining farm structural change in the European agriculture: a novel analytical framework

In this paper, we analyse the drivers of farm structural change in the EU-27, applying a novel analytical framework in the field of agricultural economics known as the multiplicative competitive interaction (MCI) model. MCI offers a more parsimonious specification for estimating models of regional farm group shares compared to the often-applied Markov approach. The MCI framework enables farm group-specific equations, which are used to account for drivers specific to certain farm groups. The MCI framework explains farm group shares at the regional level taken from the Farm Structure Survey (FSS) using socio-economic variables from the Farm Accountancy Data Network (FADN) and other databases for the period 1989–2013. We consider eight production specialisations and two size classes at the NUTS 2 regional level. The results indicate that the past farm structure explains approximately 36 per cent of the EU farm structure variation across regions and time, followed by natural conditions (16 per cent), agricultural prices (14 per cent), macroeconomic variables (9 per cent), subsidies (7 per cent), population (6 per cent) and agricultural income (6 per cent). Further, we have run a simulation experiment where we derived elasticities of structural change with respect to time-varying variables. The structural change appears to be the most elastic with respect to income and macroeconomic variables.
Longer delays in tuberculosis diagnosis among women in Vietnam.

SETTING Study conducted in 23 randomly selected districts in four provinces of Vietnam. OBJECTIVE To describe and compare health seeking behaviour between men and women and to measure delays in tuberculosis (TB) diagnosis. DESIGN All patients (n = 1027) aged 15-49 years with new smear-positive pulmonary TB detected in the selected districts during 1996 were interviewed using a structured questionnaire. RESULTS Mean total delay to TB diagnosis was 13.3 weeks (95% confidence interval [CI] 11.5, 15.1) for women and 11.4 weeks (95% CI 10.6, 12.2) for men, including a patient's delay of 7.9 weeks (95% CI 6.5, 9.3) and 7.6 weeks (95% CI 6.9, 8.3) respectively. Doctor's delay was significantly longer among women (5.4 weeks, 95% CI 4.2, 6.6) than among men (3.8 weeks, 95% CI 3.3, 4.3). Women did not start seeking care later than men, nor did they have a different health seeking pattern. Women visited more health care providers than men (1.7 and 1.5 providers, respectively, P = 0.02). CONCLUSION Patient's delay is unacceptably long for both men and women. Women do not receive a diagnosis of TB by doctors or other health care providers as quickly as men once they seek health care. The reasons for this gender difference warrant further investigations.
Protection by remote ischemic preconditioning during coronary artery bypass graft surgery with isoflurane but not propofol – a clinical trial

Remote ischemic preconditioning (RIPC) of the myocardium by limb ischemia/reperfusion may mitigate cardiac damage, but its interaction with the anesthetic regimen is unknown. We tested whether RIPC is associated with differential effects depending on background anesthesia. Specifically, we hypothesized that RIPC during isoflurane anesthesia attenuates myocardial injury in patients undergoing coronary artery bypass graft (CABG) surgery, and that effects may be different during propofol anesthesia.
J Wave Syndromes: From Cell to Bedside

The J wave is a deflection immediately following the QRS complex of the surface ECG. Several lines of evidence suggest that arrhythmias associated with early repolarization (ER) pattern in the inferior or infero-lateral precordial leads, Brugada syndrome (BrS) as well arrhythmias associated with hypothermia and the acute phase of ST segment elevation myocardial infarction (STEMI), are mechanistically linked to abnormalities in the manifestation of the transient outward current (Ito)-mediated J wave. Although BrS and ER syndrome (ERS) differ with respect to the magnitude and lead location of abnormal J wave manifestation, they can be considered to represent a continuous spectrum of phenotypic expression that we have termed J wave syndromes. We have proposed that ERS be divided into three subtypes: Type 1, displaying an ER pattern predominantly in the lateral precordial leads, which is prevalent among healthy male athletes and is largely benign, only rarely associated with VF; Type 2, displaying an ER pattern predominantly in the inferior or infero-lateral leads, which is associated with a higher level of risk; and Type 3, displaying an ER pattern globally in the inferior, lateral and right precordial leads, which is associated with the highest level of risk for development of malignant arrhythmias and is often associated with electrical storms. BrS has been associated with mutations in 9 different genes, whereas ERS has been associated with mutations in 4 different genes, including KCNJ8, CACNA1C, CACNB2 and CACNA2D1.
Interplay between synaptic endocannabinoid signaling and metaplasticity in neuronal circuit function and dysfunction

Synaptic neuromodulation acts across different functional domains to regulate cognitive processing and behavior. Recent challenges are related to elucidating the molecular and cellular mechanisms through which neuromodulatory pathways act on multiple time scales to signal state‐dependent contingencies at the synaptic level or to stabilise synaptic connections during behavior. Here, we present a framework with the synaptic neuromodulators endocannabinoids (eCBs) as key players in dynamic synaptic changes. Modulation of various molecular components of the eCB pathway yields interconnected functional activation states of eCB signaling (prior, tonic, and persistent), which may contribute to metaplastic control of synaptic and behavioral functions in health and disease. The emerging picture supports aberrant metaplasticity as a contributor to cognitive dysfunction associated with several pathological states in which eCB signaling, or other neuromodulatory pathways, are deregulated.
Elucidating the Essential Role of the A14 Phosphoprotein in Vaccinia Virus Morphogenesis: Construction and Characterization of a Tetracycline-Inducible Recombinant

ABSTRACT We have previously reported the construction and characterization of vindH1, an inducible recombinant in which expression of the vaccinia virus H1 phosphatase is regulated experimentally by IPTG (isopropyl-β-d-thiogalactopyranoside) (35). In the absence of H1 expression, the transcriptional competence and infectivity of nascent virions are severely compromised. We have sought to identify H1 substrates by characterizing proteins that are hyperphosphorylated in H1-deficient virions. Here, we demonstrate that the A14 protein, a component of the virion membrane, is indeed an H1 phosphatase substrate in vivo and in vitro. A14 is hyperphosphorylated on serine residues in the absence of H1 expression. To enable a genetic analysis of A14's function during the viral life cycle, we have adopted the regulatory components of the tetracycline (TET) operon and created new reagents for the construction of TET-inducible vaccinia virus recombinants. In the context of a virus expressing the TET repressor (tetR), insertion of the TET operator between the transcriptional and translational start sites of a late viral gene enables its expression to be tightly regulated by TET. We constructed a TET-inducible recombinant for the A14 gene, vindA14. In the absence of TET, vindA14 fails to form plaques and the 24-h yield of infectious progeny is reduced by 3 orders of magnitude. The infection arrests early during viral morphogenesis, with the accumulation of large numbers of vesicles and the appearance of “empty” crescents that appear to adhere only loosely to virosomes. This phenotype corresponds closely to that observed for an IPTG-inducible A14 recombinant whose construction and characterization were reported while our work was ongoing (47). The consistency in the phenotypes seen for the IPTG- and TET-inducible recombinants confirms the efficacy of the TET-inducible system and reinforces the value of having a second, independent system available for generating inducible recombinants.
An approach to inter-provider quality of service negotiation in NGN

This paper presents an overview of the authors' recent research work regarding end-to-end quality of service provisioning in next generation networks. Service level agreement is considered as a basis for service negotiation and management. We discuss the main features of the two basic service negotiation models, namely the bilateral model and the third party model. We argue that the third party model is more suitable for the next generation network environment. Starting from a functional model of the third party entity, an efficient algorithm for per-domain class selection has been presented and evaluated by simulation. Simulation tool has been developed in a form of an object-oriented application for management of service level agreements. Simulation results have verified the benefits of our approach in the sense of fairness, flexibility, adaptability and reduction of the implementation complexity.
Ewing sarcomas with p53 mutation or p16/p14ARF homozygous deletion: a highly lethal subset associated with poor chemoresponse.

PURPOSE EWS-FLI1 fusion type, p53 mutation, and homozygous deletion of p16/p14ARF have each been shown to be prognostically significant in Ewing sarcoma (ES). We provide the first combined prognostic analysis of these three molecular parameters in ES. PATIENTS AND METHODS We studied 60 patients with ES (stage: localized in 54, metastatic in six). All cases were confirmed to contain the EWS-FLI1 (29 type 1, 12 type 2, 14 other types) or EWS-ERG fusions (five cases). Homozygous deletion of p16/p14ARF, and p53 mutations were determined by fluorescent in situ hybridization and Affymetrix (Santa Clara, CA) p53 GeneChip microarray hybridization, respectively. RESULTS Eight cases (13.3%) contained point mutations of p53, and eight cases (13.3%) showed p16/p14ARF deletion, including one case with both alterations. Among 32 cases with data on histologic chemoresponse, all 10 with alterations in p53 or p16/p14ARF showed a poor chemoresponse (P = .03). Variables predicting poorer overall survival included p53 mutation alone (P < .001), either p53 or p16/p14ARF alteration (P < .001), and stage (P < .01). In multivariate analysis, alterations of p53 and/or p16/p14ARF as a single variable, was the most adverse prognostic factor (P < .001), followed by stage (P = .04). In a multivariate analysis with alterations of p53 and p16/p14ARF as separate variables, both were significant (P < .001 and P = .03, respectively). Six cases with p16/p14ARF deletion were also studied for co-deletion of the contiguous methylthioadenosine phosphorylase gene, and this was detected in four cases. CONCLUSION Alterations in p53 or p16/p14ARF are found in a fourth of ES cases and define a subset with highly aggressive behavior and poor chemoresponse.
Bioenergetics of the Archaea

SUMMARY In the late 1970s, on the basis of rRNA phylogeny, Archaea (archaebacteria) was identified as a distinct domain of life besides Bacteria (eubacteria) and Eucarya. Though forming a separate domain, archaea display an enormous diversity of lifestyles and metabolic capabilities. Many archaeal species are adapted to extreme environments with respect to salinity, temperatures around the boiling point of water, and/or extremely alkaline or acidic pH. This has posed the challenge of studying the molecular and mechanistic bases on which these organisms can cope with such adverse conditions. This review considers our cumulative knowledge on archaeal mechanisms of primary energy conservation, in relationship to those of bacteria and eucarya. Although the universal principle of chemiosmotic energy conservation also holds for Archaea, distinct features have been discovered with respect to novel ion-transducing, membrane-residing protein complexes and the use of novel cofactors in bioenergetics of methanogenesis. From aerobically respiring archaea, unusual electron-transporting supercomplexes could be isolated and functionally resolved, and a proposal on the organization of archaeal electron transport chains has been presented. The unique functions of archaeal rhodopsins as sensory systems and as proton or chloride pumps have been elucidated on the basis of recent structural information on the atomic scale. Whereas components of methanogenesis and of phototrophic energy transduction in halobacteria appear to be unique to archaea, respiratory complexes and the ATP synthase exhibit some chimeric features with respect to their evolutionary origin. Nevertheless, archaeal ATP synthases are to be considered distinct members of this family of secondary energy transducers. A major challenge to future investigations is the development of archaeal genetic transformation systems, in order to gain access to the regulation of bioenergetic systems and to overproducers of archaeal membrane proteins as a prerequisite for their crystallization.
Immunopathogenic mechanisms in psoriasis

Psoriasis is a common autoimmune skin disease characterized by T cell‐mediated hyperproliferation of keratinocytes. The disease has a strong but complex genetic background with a concordance of approximately 60% in monozygotic twins, and recent linkage and high resolution association studies indicate that HLA‐Cw*0602 is itself a major susceptibility allele for psoriasis. Patients carrying this allele have been shown to have different clinical features and earlier age of disease onset, and patients homozygous for this allele have about 2·5 times higher disease risk than heterozygotes. Published data indicate that CD8+ T cells may play a major effector role in psoriasis. Epidermal infiltration of predominantly oligoclonal CD8+ T cells, and probably also of CD4+ T cells in the dermis, is a striking feature of chronic psoriasis lesions, indicating that these cells are responding to specific antigens. We argue that CD4+ T cells are essential for initiating and maintaining the pathogenic process of psoriasis but that cross‐primed CD8+ T cells are the main effector cells responding to antigens in the HLA‐Cw*0602 binding pocket of keratinocytes. It is further proposed that CD8+ T cells are involved in the control of the Th1 polarization, which is observed in psoriasis lesions, through a complex interplay between CD4+, CD8+ T cells and cross‐presenting dendritic cells. It is also suggested that spontaneous remissions or fluctuations in disease activity may be determined by a balance within the lesions between effector and suppressor CD4+ and CD8+ T cells.
Origin of multidrug resistance in cells with and without multidrug resistance genes: Chromosome reassortments catalyzed by aneuploidy

Cancer cells and aneuploid cell lines can acquire resistance against multiple unrelated chemotherapeutic drugs that are over 3,000-fold those of normal levels and display spontaneous resistances up to 20-fold of normal levels. Two different mechanisms were proposed for this phenotype: (i) classical mutation of drug metabolizing genes or (ii) chromosome reassortments, catalyzed by cancer- and cell line-specific aneuploidy, which generate, via new gene dosage combinations, a plethora of cancer phenotypes, including drug resistance. To distinguish between these mechanisms, we have asked whether three mouse cell lines can become drug resistant, from which two or three genes have been deleted, and on which multidrug resistance is thought to depend: Mdr1a, Mdr1b, and Mrp1. Because all three lines could acquire multidrug resistance and were aneuploid, whereas diploid mouse cells could not, we conclude that aneuploid cells become drug resistant via specific chromosome assortments, independent of putative resistance genes. We have asked further whether aneuploid drug-resistant Chinese hamster cells revert spontaneously to drug sensitivity in the absence of cytotoxic drugs at the high rates that are typical of chromosome reassortments catalyzed by aneuploidy or at the very low or zero rates (i.e., deletion) of gene mutation. We found that four drug-resistant hamster cell lines reverted to drug sensitivity at rates of about 2–3% per generation, whereas two closely related lines remained resistant under our conditions. Thus, the karyotypic instability generated by aneuploidy emerges as the common source of the various levels of drug resistance of cancer cells: minor spontaneous resistances reflect accidental chromosome assortments, the high selected resistances reflect complex specific assortments, and multidrug resistance reflects new combinations of unselected genes located on the same chromosomes as selected genes.
Avian thermoregulation in the heat: efficient evaporative cooling allows for extreme heat tolerance in four southern hemisphere columbids

ABSTRACT Birds show phylogenetic variation in the relative importance of respiratory versus cutaneous evaporation, but the consequences for heat tolerance and evaporative cooling capacity remain unclear. We measured evaporative water loss (EWL), resting metabolic rate (RMR) and body temperature (Tb) in four arid-zone columbids from southern Africa [Namaqua dove (Oena capensis, ∼37 g), laughing dove (Spilopelia senegalensis, ∼89 g) and Cape turtle dove (Streptopelia capicola, ∼148 g)] and Australia [crested pigeon (Ocyphaps lophotes), ∼186 g] at air temperatures (Ta) of up to 62°C. There was no clear relationship between body mass and maximum Ta tolerated during acute heat exposure. Maximum Tb at very high Ta was 43.1±1.0, 43.7±0.8, 44.7±0.3 and 44.3±0.8°C in Namaqua doves, laughing doves, Cape turtle doves and crested pigeons, respectively. In all four species, RMR increased significantly at Ta above thermoneutrality, but the increases were relatively modest with RMR at Ta=56°C being 32, 60, 99 and 11% higher, respectively, than at Ta=35°C. At the highest Ta values reached, evaporative heat loss was equivalent to 466, 227, 230 and 275% of metabolic heat production. The maximum ratio of evaporative heat loss to metabolic production observed in Namaqua doves, 4.66, exceeds by a substantial margin previous values reported for birds. Our results support the notion that cutaneous evaporation provides a highly efficient mechanism of heat dissipation and an enhanced ability to tolerate extremely high Ta. Summary: Arid-zone pigeons and doves dissipate heat primarily through cutaneous evaporative pathways, which has minimal metabolic costs, is highly efficient and allows for the defense of a relatively low body temperature under extreme heat conditions.
Domestication of Lambda Phage Genes into a Putative Third Type of Replicative Helicase Matchmaker

Abstract At the onset of the initiation of chromosome replication, bacterial replicative helicases are recruited and loaded on the DnaA-oriC nucleoprotein platform, assisted by proteins like DnaC/DnaI or DciA. Two orders of bacteria appear, however, to lack either of these factors, raising the question of the essentiality of these factors in bacteria. Through a phylogenomic approach, we identified a pair of genes that could have substituted for dciA. The two domesticated genes are specific of the dnaC/dnaI- and dciA-lacking organisms and apparently domesticated from lambdoid phage genes. They derive from λO and λP and were renamed dopC and dopE, respectively. DopE is expected to bring the replicative helicase to the bacterial origin of replication, while DopC might assist DopE in this function. The confirmation of the implication of DopCE in the handling of the replicative helicase at the onset of replication in these organisms would generalize to all bacteria and therefore to all living organisms the need for specific factors dedicated to this function.
Driving fatigue prediction with pre-event electroencephalography (EEG) via a recurrent fuzzy neural network

We propose an electroencephalography (EEG) prediction system based on a recurrent fuzzy neural network (RFNN) architecture to assess drivers' fatigue degrees during a virtual-reality (VR) dynamic driving environment. Prediction of fatigue degrees is a crucial and arduous biomedical issue for driving safety, which has attracted growing attention of the research community in the recent past. Meanwhile, combined with the benefits of measuring EEG signals facilitates, many EEG-based brain-computer interfaces (BCIs) have been developed for use in real-time mental assessment. In the literature, EEG signals are severely blended with stochastic noise; therefore, the performance of BCIs is constrained by low resolution in recognition tasks. For this rationale, independent component analysis (ICA) is usually used to find a source mapping from original data that has been blended with unrelated artificial noise. However, the mechanism of ICA cannot be used in real-time BCI design. To overcome this bottleneck, the proposed system in this paper utilizes a recurrent self-evolving fuzzy neural work (RSEFNN) to increase memory capability for adaptive noise cancellation when assessing drivers' mental states during a car driving task. The experimental results without the use of ICA procedure indicate that the proposed RSEFNN model remains superior performance compared with the state-of-the-arts models.