Miracle-dz/UniFAR-FTUs huggingface dataset:
Multidrug resistance proteins in primary and metastatic soft-tissue sarcomas: down-regulation of P-glycoprotein during metastatic progression.

BACKGROUND Chemotherapy sensitivity of soft-tissue sarcomas (STS) is limited, which may be due to multidrug resistance (MDR). MDR is associated with expression of P-glycoprotein (P-gp), Multidrug Resistance-associated Protein 1 (MRP1) and Lung Resistance-related Protein (LRP). It is unknown whether in STS metastasis is more resistant than the primary counterpart. MATERIALS AND METHODS In 35 chemonaive STS and their metastases (86% chemonaive), MDR proteins were immunohistochemically assessed. Eleven metastases presented synchronously, 24 metachronously. Expression was scored positive (>5% positive tumour cells) or negative. RESULTS P-gp was positive in 31/34 primaries (91%), versus 22/32 metastases (69%) (p=0.005). This difference was significant for metachronous metastases (p=0.008). MRP1 was positive in 18/32 primaries (56%) and 22/33 metastases (67%). MRP1 was more expressed in synchronous metastases than primaries (p=0.047), but for the overall group this significance disappeared. LRP expression did not differ: 27/34 primaries (80%), versus 28/34 metastases (82%). CONCLUSION P-gp, MRP1, LRP expression in the primary tumours was high. Metastatic progression did not coincide with MDR-protein up-regulation.
Fabrication and field emission property studies of multiwall carbon nanotubes

Well-aligned and randomly grown multiwall nanotubes (MWNTs) fabricated by the radio-field-induced self-bias hot-filament chemical vapour deposition method demonstrate that the growth mechanisms are either ‘tip growth’ or ‘base growth’ depending on the size of the catalyst metal particles involved. The carbon nanotubes (CNTs) can also be successfully grown on iron-like bulk alloys when preceded by hydrogen plasma etching. The high yield of CNT fabricated on oxidized metal alloys is attributed to the high active surface area that ensues from etching. The change in field emission currents of MWNTs with temperature is not sensitive but is detectable within the range 300–20 K. This is interpreted to be due to the high aspect ratio of CNTs.
A new liquid, intravenous immunoglobulin product (IGIV 10%) highly purified by a state‐of‐the‐art process

Background and Objectives The ultimate goal was to generate an industrial‐scale process suitable to produce a high‐yield, safe and stable immunoglobulin G (IgG) preparation for intravenous administration, which is ready to use for customer convenience. This new liquid 10% IgG preparation (IGIV 10%) was compared to Gammagard SD, a licenced lyophilized immunoglobulin in biochemical and preclinical testing.
Hypoxia and stem cell‐based engineering of mesenchymal tissues

Stem cells have the ability for prolonged self‐renewal and differentiation into mature cells of various lineages, which makes them important cell sources for tissue engineering applications. Their remarkable ability to replenish and differentiate in vivo is regulated by both intrinsic and extrinsic cellular mechanisms. The anatomical location where the stem cells reside, known as the “stem cell niche or microenvironment,” provides signals conducive to the maintenance of definitive stem cell properties. Physiological condition including oxygen tension is an important component of the stem cell microenvironment and has been shown to play a role in regulating both embryonic and adult stem cells. This review focuses on oxygen as a signaling molecule and the way it regulates the stem cells' development into mesenchymal tissues in vitro. The physiological relevance of low oxygen tension as an environmental parameter that uniquely benefits stem cells' expansion and maintenance is described along with recent findings on the regulatory effects of oxygen on embryonic stem cells and adult mesenchymal stem cells. The relevance to tissue engineering is discussed in the context of the need to specifically regulate the oxygen content in the cellular microenvironment in order to optimize in vitro tissue development. © 2009 American Institute of Chemical Engineers Biotechnol. Prog. , 2009
Product modeling based integration of robot related engineering activities

In this paper an integration of product modeling with robot control is discussed. The authors propose a method to enhance applications of geometric and other product and production equipment related information in robot control. Research of the related methodology was motivated by a growing significance of robots in highly flexible manufacturing systems. Difficulties of reproduction of modeled product geometry at its applications resulted a growing importance of online real time communications between a centralized product modeling and several model applications. The reported research concentrates on the creation and application of model data information understandable by robot controls, on communication of model data with robot environments through the Internet, and finally on some related telerobotics issues. It covers one of the actual problem complexes in the integration of engineering modeling with its shop floor level applications. Systems integration, data model, data communication and model processing have been investigated. In the paper an introduction of the robot related activities of engineers and the modeling environment are first given, taking into account the robot control aspect. Following this, key issues regarding robot tasks and their shape model based control are explained. Then an approach to interactive application of Internet-based telerobotics for product model driven control of robots is outlined. Finally, possibilities for an integration of remote robot control applications with product modeling environments are discussed.
TREATMENT OF EXPERIMENTAL TOXOCARA CATI INFECTION IN MICE WITH IVERMECTIN AND MOXIDECTIN

The aim of this study was to investigate the efficacy of two efficient macrocyclic lactone drugs, ivermectin, and moxidectin, on the numbers and distribution of Toxocara cati larvae in experimentally infected mice. Different post-infection periods (48 h and 7 d) and different administration methods (oral and subcutaneous) were compared. Ivermectin and moxidectin were tested (0.2 mg/kg with a single dose) for their larvicidal effects. Each mouse was infected with 1 000embryonated eggs of T. cati. On the 10 d of the infection, the mice in each treatment group and the control group were sacrificed and the presence of T. cati larvae in various organs were determined and compared between groups. Statistically, the treatment regimens in all treatment groups were successful as compared with the controls. The worst results were achieved in the group in which ivermectin was given orally 7 d following egg inoculation. According to the decrease in total larvae recovery, oral administration of moxidectin 48 h following egg inoculation displayed the highest efficacy. The effect of ivermectin administered subcutaneously 7 d following infection was more effective than subcutaneous application of moxidectin after both 48 h and 7 d.
Monitoring of Peptide-Specific and Gamma Interferon-Productive T Cells in Patients with Active and Convalescent Tuberculosis Using an Enzyme-Linked Immunosorbent Spot Assay

ABSTRACT To establish a high-efficiency gamma interferon-specific enzyme-linked immunosorbent spot assay (IFN-γ ELISPOT assay) for detection of tuberculosis (TB), peptides (E6, E7, and C14) and peptide mixtures (E6 plus E7 and E6 plus E7 plus C14) were used to monitor peripheral blood (PBL) samples from patients with pulmonary TB (PTB), as well as control samples. The positive detection rates of the five IFN-γ ELISPOT assays were 78.38%, 74.86%, 55.83%, 90.43%, and 91.51%, respectively, and there were similar detection rates between the two combined peptide mixture IFN-γ ELISPOT assays and the tuberculin skin test (TST) (90.62% versus 95.59%). No significant difference was found between the detection rates of the two combined peptide mixture IFN-γ ELISPOT assays and the T-SPOT.TB assay for 86 patients with PTB (P > 0.05), but the median number of spot-forming cells/106 cells (SFP value) for positive results was higher by the former than by the latter assay (P < 0.05). In contrast, the 29.93% positive detection rate and median SFP value of 482 by the two combined peptide mixture IFN-γ ELISPOT assays were significantly higher than the corresponding values of 14.29% and 152 by T-SPOT.TB assay for the same 147 community donors (P < 0.05). For nine PTB patients tracked, the SFP value of 7 for the two peptide mixture IFN-γ ELISPOT assays began to decrease from the second month after regular treatment. A relatively low, almost normal, SFP level was reached and maintained after the third or fourth month. Two in-house IFN-γ ELISPOT assays and the T-SPOT.TB assay could reduce the false-positive and false-negative detection rates of TST and sputum acid-fast staining. Therefore, these two combined peptide mixture IFN-γ ELISPOT assays have a potential advantage, beyond their greater specificity and sensitivity, for use in screening and detection of active TB infection (TBI) and latent TB infection (LTBI) in China.
Osmotic cell shrinkage activates ezrin/radixin/moesin (ERM) proteins: Activation mechanisms and physiological implications

Osmotic cell shrinkage elicits multiple cellular events, including rapid cytoskeletal reorganization, activation of Na+/H+ exchanger isoform 1 (NHE1), and, on a longer time scale, programmed cell death. Here, we evaluated the role of ezrin/radixin/moesin (ERM) proteins in these processes. Osmotic shrinkage of Ehrlich Lettre ascites (ELA) cells elicited rapid translocation of ERM proteins to the cell cortex and long microvilli‐like protrusions, and Thr567/564/558 (ezrin/radixin/moesin) phosphorylation of cortical ERM proteins. Shrinkage‐induced ERM protein activation was prevented by PtdIns(4,5)P2 depletion, yet was unaffected by NHE1 inhibition by EIPA, and did not require the presence of NHE1 (as evaluated in AP1 cells +/‐ human NHE1). Constitutively active RhoA increased basal and shrinkage‐induced ERM protein phosphorylation, yet the relative shrinkage‐induced increase was unaffected. Ezrin knockdown by siRNA increased shrinkage‐induced NHE1 activity by about 25%, and appeared to partially prevent the shrinkage‐induced formation/elongation of microvilli‐like protrusions. In contrast, shrinkage‐induced cell death was unaffected by ezrin knockdown. In conclusion, ERM proteins are activated by osmotic shrinkage in a PtdIns(4,5)P2‐dependent, NHE1‐independent manner, and this in turn negatively regulates NHE1 and may contribute to F‐actin rearrangement in the shrunken cells.
Health state utility values in locally advanced and metastatic breast cancer by treatment line: a systematic review

ABSTRACT Introduction: For patients with late-stage (metastatic) breast cancer, the impact of treatment on health-related quality of life is a key factor in decision-making. A systematic review was conducted to identify health state utility values (HSUVs) for late-stage breast cancer, derived using methods preferred by health technology assessment (HTA) agencies, by treatment line. The aim was to generate a list of HSUVs, that could help to justify the values used to populate cost-utility models. Areas covered: Ten electronic databases, international congress websites and online HSUV databases were searched (January 1995–May 2014) for HSUVs for adults with late-stage breast cancer that had been derived from methods favoured by HTA agencies. Publications were included only if they reported studies that originated HSUVs. Expert commentary: Large numbers of HSUVs are available for late-stage breast cancer in the published literature. Contrary to expectations, the HSUVs reported in the literature vary greatly for some health states. As a result, the choice of HSUV can have considerable implications for the outcomes of economic evaluations. Standardization of HSUV methodology is expected to reduce variability; however, further research is recommended for assessing the sensitivity of generic preference-based measures in late-stage (metastatic) breast cancer.
Time tested: re-thinking chronology and sculptural traditions in Preclassic southern Mesoamerica

Abstract Recent reassessment of the sequence at the highland Maya centre of Kaminaljuyu has led to a substantial chronological revision for Preclassic southern Mesoamerica. The new chronology suggests that various centres on the Gulf Coast, in Chiapas and in the Southern Maya Region experienced political disruption or reorganisation at the end of the Middle Preclassic period around 350 BC. It also shifts the initial rise and height of Kaminaljuyu forward 300 years. These shifts dramatically alter our understanding of sculptural developments in the Southern Maya Region, and emphasise the role of inter-regional interaction in the development of Maya civilisation.
Plastic Corticostriatal Circuits for Action Learning

Abstract: Reentrant corticobasal ganglia circuits are important for voluntary action and for action selection. In vivo and ex vivo studies show that these circuits can exhibit a plethora of short‐ and long‐lasting plastic changes. Convergent evidence at the molecular, cellular, and circuit levels indicates that corticostriatal circuits are involved in the acquisition and automatization of novel actions. There is strong evidence that activity in corticostriatal circuits changes during the learning of novel actions, but the plastic changes observed during the early stages of learning a novel action are different than those observed after extensive training. A variety of studies indicate that the neural mechanisms and the corticostriatal subcircuits involved in the initial acquisition of actions and skills differ from those involved in their automatization or in the formation of habits. Dopamine, a critical modulator of short‐ and long‐term plasticity in corticostriatal circuits, is differentially involved in early and late stages of action learning. Changes in dopaminergic transmission have several concomitant effects in corticostriatal function, which may be important for action selection and action learning. These diverse effects may subserve different roles for dopamine in reinforcement and action learning.
Human herpesviruses in the cornea

AIMS To determine the sensitivity and specificity of culture, immunohistochemistry (IHC), the polymerase chain reaction (PCR), and in situ hybridisation (ISH) for detecting herpes simplex virus (HSV-1) in the cornea of patients undergoing penetrating keratoplasty. To compare the incidence of HSV-1 in the cornea with that of varicella zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV). METHODS The corneas of 110 patients, 52 with a documented history of herpes keratitis (HSK) and 58 with non-herpetic corneal disease, were investigated using IHC, PCR, ISH, and culture. RESULTS HSV-1 DNA and antigen were detected in 82% and 74% respectively, of corneas of patients with HSK and in 22% and 15% of corneas of patients with no history of HSK. The sensitivity of PCR and IHC was 82% and 74% with a specificity of 78% and 85%, respectively. HSV-1 DNA and antigen were found more frequently and in increased amounts in corneas of patients with a short interval between their last attack of HSK and surgery. There was a good correlation between PCR and IHC in 71%. HSV-1 was isolated by culture in 2%. Latency associated transcripts were not detected using ISH. Evidence of VZV DNA or antigen was found significantly more frequently in the corneas of patients with a history of HSK (p<0.001). No evidence of EBV or CMV was found in any cornea. CONCLUSIONS PCR and IHC are both sensitive for the detection of HSV-1 in the cornea. A combination of PCR and IHC increases the specificity for the diagnosis of HSK to 97%. HSV-1 appears to be slowly removed from the cornea. VZV and HSV-1 may co-infect the cornea.
Technegas - a new ventilation agent for lung scanning

A simple process using technetium-99m generator eluate in a graphite crucible at 2500° C, produces a structured ultra-fine dispersion of labelled carbon. Particle sizes are 5.0 run (0.005μm) and less and adhere to the walls of the alveoli on inhalation. Penetration characteristics are gas-like and the radioactivity per litre of carrier argon allows single breath inhalations of a diagnostic dose.Over 190 patients have been studied including 50 within a formal clinical trial with xenon-133. Results of tomography, dynamic inhalation, and image subtraction using this new agent-'Technegas' - are presented.
MEPE/OF45, a New Dentin/Bone Matrix Protein and Candidate Gene for Dentin Diseases Mapping to Chromosome 4q21

Substantial progress has been made regarding the molecular etiology of the dentin diseases dentinogenesis imperfecta types II and III, and dentin dysplasia type II. Genetic linkage studies have identified the critical loci for these diseases on human chromosome 4q21. Located within an overlapping segment of these disease loci is a dentin/bone gene cluster that includes osteopontin, bone sialoprotein, dentin matrix protein 1, dentin sialophosphoprotein, and a new gene MEPE also known as OF45, renamed osteoregulin. In this paper, we report the location of MEPE/OF45 in relationship to the other members of the dentin/bone gene cluster as well as the genomic organization of the human gene. For the first time, MEPE/OF45 expression was shown in dental tissue, in particular odontoblasts, by reverse-transcription polymerase chain reaction (RT-PCR) amplification and characterization of a partial mouse cDNA. Our data provide the first evidence that MEPE/OF45 is expressed during odontogenesis and should be considered as a candidate gene for dentin structural diseases mapping to human chromosome 4q21.
Inhibitors of Rho kinase (ROCK) signaling revert the malignant phenotype of breast cancer cells in 3D context

Loss of polarity and quiescence along with increased cellular invasiveness are associated with breast tumor progression. ROCK plays a central role in actin-cytoskeletal rearrangement. We used physiologically relevant 3D cultures of nonmalignant and cancer cells in gels made of laminin-rich extracellular matrix, to investigate ROCK function. Whereas expression levels of ROCK1 and ROCK2 were elevated in cancer cells compared to nonmalignant cells, this was not observed in 2D cultures. Malignant cells showed increased phosphorylation of MLC, corresponding to disorganized F-actin. Inhibition of ROCK signaling restored polarity, decreased disorganization of F-actin, and led to reduction of proliferation. Inhibition of ROCK also decreased EGFR and Integrinβ1 levels, and consequently suppressed activation of Akt, MAPK and FAK as well as GLUT3 and LDHA levels. Again, ROCK inhibition did not inhibit these molecules in 2D. A triple negative breast cancer cell line, which lacks E-cadherin, had high levels of ROCK but was less sensitive to ROCK inhibitors. Exogenous overexpression of E-cadherin, however, rendered these cells strikingly sensitive to ROCK inhibition. Our results add to the growing literature that demonstrate the importance of context and tissue architecture in determining not only regulation of normal and malignant phenotypes but also drug response.
Overt and Mild Subclinical Hypothyroidism Do Not Influence Mean Platelet Volume in Premenopausal Women Having Low Cardiac Risk

Mean platelet volume (MPV) was studied in subclinical hypothyroidism (SH) and the results are conflicting. The aim of this study is to assess how MPV is affected in overt hypothyroidism (OH) and mild SH, the 2 end points of hypothyroidism, in patients having low cardiac risk. Premenopausal women without any cardiac risk, 18 with OH, 30 with mild SH, and 37 euthyroid controls were enrolled. Overt hypothyroidism group had higher low-density lipoprotein cholesterol (LDL-C) and total cholesterol levels than the control group (P < .001 and P < .05, respectively). Increase in MPV was insignificant in OH group when compared with SH and control groups. No correlation was observed between MPV and metabolic and hormonal parameters. Both OH and SH did not influence MPV and high-sensitivity C-reactive protein (hs-CRP) in patients with low cardiovascular risk, but these findings need to be further evaluated in this patient group.
Genetic and host factors for dementia in Down's syndrome.

BACKGROUND The high risk for dementia in adults with Down's syndrome has been attributed to triplication and overexpression of the gene for amyloid precursor protein (APP). But the wide variation in age at onset must be due to other risk factors. AIMS To identify factors which influence age at onset of dementia in Down's syndrome. METHOD Studies of factors which influence formation of beta-amyloid (Abeta) were reviewed, including atypical karyotypes, susceptibility genotypes, gender and oestrogen deficiency, and individual differences in Abeta peptide levels. RESULTS The apolipoprotein E epsilon4 allele, oestrogen deficiency and high levels of Abeta1-42 peptide are associated with earlier onset of dementia, while atypical karyotypes and the apolipoprotein E epsilon2 allele are associated with reduced mortality and reduced risk of dementia. CONCLUSIONS Factors which influence Abeta levels, rather than overexpression of APP, may account for the differences in age at onset of dementia in Down's syndrome.
Development of a simulated earthworm gut for determining bioaccessible arsenic, copper, and zinc from soil

Soil physicochemical characteristics and contamination levels alter the bioavailability of metals to terrestrialinvertebrates. Current laboratory‐derived benchmark concentrations used to estimate risk do not take into account site‐specific conditions, such as contaminant sequestration, and site‐specific risk assessment requires a battery of time‐consuming and costly toxicity tests. The development of an in vitro simulator for earthworm bioaccessibility would significantly shorten analytical time and enable site managers to focus on areas of greatest concern. The simulated earthworm gut (SEG) was developed to measure the bioaccessibility of metals in soil to earthworms by mimicking the gastrointestinal fluid composition of earthworms. Three formulations of the SEG (enzymes, microbial culture, enzymes and microbial culture) were developed and used to digest field soils from a former industrial site with varying physicochemical characteristics and contamination levels. Formulations containing enzymes released between two to 10 times more arsenic, copper, and zinc from contaminated soils compared with control and 0.01 M CaCl2 extractions. Metal concentrations in extracts from SEG formulation with microbial culture alone were not different from values for chemical extractions. The mechanism for greater bioaccessible metal concentrations from enzyme‐treated soils is uncertain, but it is postulated that enzymatic digestion of soil organic matter might release sequestered metal. The relevance of these SEG results will need validation through further comparison and correlation with bioaccumulation tests, alternative chemical extraction tests, and a battery of chronic toxicity tests with invertebrates and plants.