Miracle-dz/UniFAR-FTUs huggingface dataset:
CD34 selections from myeloma peripheral blood cell autografts contain residual tumour cells due to impurity, not to CD34+ myeloma cells

Malignant cells in haemopoietic autografts can contribute to post‐transplant relapse. Engraftment of myeloma patients with CD34+ peripheral blood progenitors selected from total autografts reduces the number of tumour cells infused by 2.7–4.5 logs. Residual tumour cells detected in CD34+ selected cells may be due to selection impurity or the existence of malignant CD34+ progenitors. In three patients we evaluated the CD34 purity and tumour load of total autografts, CD34+ progenitors selected with immunomagnetic beads and highly purified CD34+ progenitors obtained in two rounds of selection (combining magnetic with flow cytometry activated cell sorting) to determine the cause of residual tumour cells in CD34 selections.
ASPP1 and ASPP2: Common Activators of p53 Family Members

ABSTRACT We recently showed that ASPP1 and ASPP2 stimulate the apoptotic function of p53. We show here that ASPP1 and ASPP2 also induce apoptosis independently of p53. By binding to p63 and p73 in vitro and in vivo, ASPP1 and ASPP2 stimulate the transactivation function of p63 and p73 on the promoters of Bax, PIG3, and PUMA but not mdm2 or p21WAF-1/CIP1. The expression of ASPP1 and ASPP2 also enhances the apoptotic function of p63 and p73 by selectively inducing the expression of endogenous p53 target genes, such as PIG3 and PUMA, but not mdm2 or p21WAF-1/CIP1. Removal of endogenous p63 or p73 with RNA interference demonstrated that (16) the p53-independent apoptotic function of ASPP1 and ASPP2 is mediated mainly by p63 and p73. Hence, ASPP1 and ASPP2 are the first two identified common activators of all p53 family members. All these results suggest that ASPP1 and ASPP2 could suppress tumor growth even in tumors expressing mutant p53.
Vascular endothelial growth factor: Evidence for autocrine signaling in hepatocellular carcinoma cell lines affecting invasion.

BACKGROUND AND AIM Vascular endothelial growth factor (VEGF) is a well-known pivotal regulator of tumor angiogenesis. Apart from endothelial cells, it is also expressed in nonendothelial cells, including tumor cells themselves. Hence the aim of this study was to investigate the autocrine effects of VEGF in hepatocellular carcinoma (HCC) -derived cell lines. MATERIALS AND METHODS Two hepatocellular carcinoma cell lines (Hep3B and HepG2) were screened for expression of VEGF by quantitative real-time polymerase chain reaction (PCR) and its receptors VEGF-R1, VEGF-R2, and neuropilin-1 expression by reverse transcriptase-PCR, respectively. Furthermore, VEGF transcript was silenced by siRNA and the effects on cell migration, viability, and proliferation were determined by the wound healing assay, MTT assay, and propidium iodide staining, respectively. RESULTS Both Hep3B and HepG2 cell lines expressed VEGF and all the three receptors at high levels. VEGF siRNA inhibited VEGF expression significantly in both Hep3B and HepG2 cell lines. Silencing of VEGF showed decreased migration in the Hep3B cell line. In both cell lines tested, there was decreased cell viability but no effect on cellular proliferation. CONCLUSION Our data indicates that autocrine signaling of VEGF through its receptors exists in HCC cell lines, which has important implications for tumor invasion, metastasis, and for designing interventional strategies.
Relationships among Cortical Glutathione Levels, Brain Amyloidosis, and Memory in Healthy Older Adults Investigated In Vivo with 1H-MRS and Pittsburgh Compound-B PET

BACKGROUND AND PURPOSE: Oxidative stress has been implicated as an important pathologic mechanism in the development of Alzheimer disease. The purpose of this study was to assess whether glutathione levels, detected noninvasively with proton MR spectroscopy, are associated with brain amyloidosis and memory in a community-dwelling cohort of healthy older adults. MATERIALS AND METHODS: Fifteen cognitively healthy subjects were prospectively enrolled in this study. All subjects underwent 1H-MR spectroscopy of glutathione, a positron-emission tomography scan with an amyloid tracer, and neuropsychological testing by using the Repeatable Battery for the Assessment of Neuropsychological Status. Associations among glutathione levels, brain amyloidosis, and memory were assessed by using multivariate regression models. RESULTS: Lower glutathione levels were associated with greater brain amyloidosis in the temporal (P = .03) and parietal (P = .05) regions, adjusted for apolipoprotein E ε4 carrier status. There were no significant associations between glutathione levels and cognitive scores. CONCLUSIONS: This study found an association between cortical glutathione levels and brain amyloidosis in healthy older adults, suggesting a potential role for 1H-MR spectroscopy measures of glutathione as a noninvasive biomarker of early Alzheimer disease pathogenesis.
Lewy Bodies and the Mechanisms of Neuronal Cell Death in Parkinson's Disease and Dementia with Lewy Bodies

Neuronal loss in specific brain regions and neurons with intracellular inclusions termed Lewy bodies are the pathologic hallmark in both Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Lewy bodies comprise of aggregated intracellular vesicles and proteins and α‐synuclein is reported to be a major protein component. Using human brain tissue from control, PD and DLB and light and confocal immunohistochemistry with antibodies to superoxide dismutase 2 as a marker for mitochondria, α‐synuclein for Lewy bodies and βIII Tubulin for microtubules we have examined the relationship between Lewy bodies and mitochondrial loss. We have shown microtubule regression and mitochondrial and nuclear degradation in neurons with developing Lewy bodies. In PD, multiple Lewy bodies were often observed with α‐synuclein interacting with DNA to cause marked nuclear degradation. In DLB, the mitochondria are drawn into the Lewy body and the mitochondrial integrity is lost. This work suggests that Lewy bodies are cytotoxic. In DLB, we suggest that microtubule regression and mitochondrial loss results in decreased cellular energy and axonal transport that leads to cell death. In PD, α‐synuclein aggregations are associated with intact mitochondria but interacts with and causes nuclear degradation which may be the major cause of cell death.
Coinduction All the Way Up

We revisit coinductive proof principles from a lattice theoretic point of view. By associating to any monotone function a function which we call the companion, we give a new presentation of both Knaster-Tarski’s seminal result, and of the more recent theory of enhancements of the coinductive proof method (up-to techniques). The resulting theory encompasses parameterized coinduction, as recently proposed by Hur et al., and second-order reasoning, i.e., the ability to reason coinductively about the enhancements themselves. It moreover resolves a historical peculiarity about up-to context techniques.Based on these results, we present an open-ended proof system allowing one to perform proofs on-the-fly and to neatly separate inductive and coinductive phases.
Heat Transfer Enhancement using CNT Nanofluids in a Turbulent Flow Heat Exchanger - An Experimental Study

Suspensions of nano-sized particles (<100 nm) in base fluid are termed as Nanofluids, which are believed to be the promising coolant in heat transfer applications due to their enhanced thermal conductivity. In this study, the enhancement in heat transfer of CNT nanaofluids under turbulent flow conditions was investigated experimentally. Carbon nanotube (CNTs) nanofluids of 0.051-0.085 wt%, stabilized by optimum concentrations of gum Arabic were used as hot fluid in a concentric tube turbulent flow heat exchanger. The flow rates of cold fluid (water) was varied from 1.7 - 3 L/min and flow rates of the hot fluid (nanofluid) is varied between 2 - 3.5 L/min. Thermal conductivity, density and viscosity of the nanofluids were also studied as a function of temperature and CNT concentration. Enhancements in the heat transfer were validated with conventional heat transfer correlations for turbulent flow available in the literature. Results showed an enhancement in heat transfer range between 9 - 67% as a function of temperature and CNT concentration. Keywords— Nanofluids, Carbon nanotubes (CNT), gum Arabic, heat transfer enhancement, heat exchanger
Surfactant protein D is a useful biomarker for monitoring acute lung injury in rats

ABSTRACT Purpose: The purpose of this study is to investigate the serial changes in the SP-D concentrations of serum and bronchoalveolar lavage fluid (BALF) in a bleomycin-induced lung injury rat model and compare them with the levels of conventional biochemical markers. Materials and Methods: Male Wister rats were anesthetized and intratracheally administered bleomycin (1.0 mg/kg). We evaluated the histological changes and SP-D expression of their lung tissues. We also measured the concentrations of SP-D, albumin, and lactate dehydrogenase (LDH) and the numbers of various types of cells in BALF, and the serum levels of SP-D and conventional markers, including LDH, high mobility group box 1, monocyte chemoattractant protein-1, and C-reactive protein. Results: The BALF SP-D level increased and peaked on day 3, and then gradually decreased. These variations were significantly correlated with the changes in the BALF albumin level and granulocyte cell count. The serum SP-D level increased from day 5, peaked on day 10, and then gradually decreased until day 28. The changes in the serum SP-D level accurately reflected the extent of the histological changes caused by the lung injury. On the other hand, the serum levels of conventional biomarkers were only elevated for a few days or did not change during the study period. Conclusions: The SP-D level is the most useful marker of the severity of lung injuries. These results suggest that the measurement of SP-D levels is an additional tool for monitoring acute lung injuries in rats.
Graft-versus-Host Disease Is Independent of Innate Signaling Pathways Triggered by Pathogens in Host Hematopoietic Cells

Graft-versus-host disease (GVHD) is initiated by APCs that prime alloreactive donor T cells. In antipathogen responses, Ag-bearing APCs receive signals through pattern-recognition receptors, including TLRs, which induce the expression of costimulatory molecules and production of inflammatory cytokines, which in turn mold the adaptive T cell response. However, in allogeneic hematopoietic stem cell transplantation (alloSCT), there is no specific pathogen, alloantigen is ubiquitous, and signals that induce APC maturation are undefined. To investigate APC activation in GVHD, we used recipient mice with hematopoietic cells genetically deficient in pathways critical for APC maturation in models in which host APCs are absolutely required. Strikingly, CD8-mediated and CD4-mediated GVHD were similar whether host APCs were wild-type or deficient in MyD88, TRIF, or MyD88 and TRIF, which excludes essential roles for TLRs and IL-1β, the key product of inflammasome activation. Th1 differentiation was if anything augmented when APCs were MyD88/TRIF−/−, and T cell production of IFN-γ did not require host IL-12. GVHD was also intact when APCs lacked the type I IFNR, which amplifies APC activation pathways that induce type I IFNs. Thus in GVHD, alloreactive T cells can be activated when pathways critical for antipathogen T cell responses are impaired.
Construction of human corneal endothelial cDNA library and identification of novel active genes.

PURPOSE To describe genes expressed in human corneal endothelial cells and identify novel genes. METHODS Sixteen human donor corneas that had no history of corneal disease, infection, or intraocular surgery were used within 7 days of death. Total RNA was extracted from corneal endothelial cells with attached Descemet membranes. A 3'-directed cDNA library was constructed from mRNA by using a pUC19-based primer. These sequences were compared with each other to determine their frequency and were searched against GenBank for identification. To identify novel specific and abundant transcript genes in corneal endothelial cells, the novel genes were compared with an expressed sequence tag database, the expected sequence extended, and 5' rapid amplification of cDNA ends-polymerase chain reaction cloning performed. RESULTS The human corneal endothelial cDNA library showed that the most abundant transcript was prostaglandin D2 synthase. The remaining transcript genes that were present in abundance consisted of lactate dehydrogenase-A, gene signature (GS) 3582, which is a novel gene without a known function, and matrix Gla protein. The full-length sequence of GS3582 showed similarity to genes obtained in ovary and TESTIS. CONCLUSIONS A human corneal endothelial cDNA library was constructed. An expression profile of corneal endothelium provides probes to monitor physiologic and pathologic conditions of this tissue in terms of gene expression.
System on chip battery state estimator: E-bike case study

This paper discusses the hardware implementation and experimental validation of a model-based battery state estimator. The model parameters are identified online using the moving window least squares method. The estimator is implemented in a field programmable gate array device as a hardware block, which interacts with the embedded processor to form a system on a chip battery management system (BMS). As a case study, the BMS is applied to the battery pack of an e-bike. Road tests show that the implemented estimator may provide very good performance in terms of maximum and rms estimation errors. This work also proposes a new methodology to assess the performance of a battery state estimator.
Empirical Risk Minimization under Fairness Constraints

We address the problem of algorithmic fairness: ensuring that sensitive variables do not unfairly influence the outcome of a classifier. We present an approach based on empirical risk minimization, which incorporates a fairness constraint into the learning problem. It encourages the conditional risk of the learned classifier to be approximately constant with respect to the sensitive variable. We derive both risk and fairness bounds that support the statistical consistency of our approach. We specify our approach to kernel methods and observe that the fairness requirement implies an orthogonality constraint which can be easily added to these methods. We further observe that for linear models the constraint translates into a simple data preprocessing step. Experiments indicate that the method is empirically effective and performs favorably against state-of-the-art approaches.
A stochastic model to investigate the effects of control strategies on calves exposed to Ostertagia ostertagi

SUMMARY Predicting the effectiveness of parasite control strategies requires accounting for the responses of individual hosts and the epidemiology of parasite supra- and infra-populations. The first objective was to develop a stochastic model that predicted the parasitological interactions within a group of first season grazing calves challenged by Ostertagia ostertagi, by considering phenotypic variation amongst the calves and variation in parasite infra-population. Model behaviour was assessed using variations in parasite supra-population and calf stocking rate. The model showed the initial pasture infection level to have little impact on parasitological output traits, such as worm burdens and FEC, or overall performance of calves, whereas increasing stocking rate had a disproportionately large effect on both parasitological and performance traits. Model predictions were compared with published data taken from experiments on common control strategies, such as reducing stocking rates, the ‘dose and move’ strategy and strategic treatment with anthelmintic at specific times. Model predictions showed in most cases reasonable agreement with observations, supporting model robustness. The stochastic model developed is flexible, with the potential to predict the consequences of other nematode control strategies, such as targeted selective treatments on groups of grazing calves.
Reinforcement-Learning-Based Robust Controller Design for Continuous-Time Uncertain Nonlinear Systems Subject to Input Constraints

The design of stabilizing controller for uncertain nonlinear systems with control constraints is a challenging problem. The constrained-input coupled with the inability to identify accurately the uncertainties motivates the design of stabilizing controller based on reinforcement-learning (RL) methods. In this paper, a novel RL-based robust adaptive control algorithm is developed for a class of continuous-time uncertain nonlinear systems subject to input constraints. The robust control problem is converted to the constrained optimal control problem with appropriately selecting value functions for the nominal system. Distinct from typical action-critic dual networks employed in RL, only one critic neural network (NN) is constructed to derive the approximate optimal control. Meanwhile, unlike initial stabilizing control often indispensable in RL, there is no special requirement imposed on the initial control. By utilizing Lyapunov's direct method, the closed-loop optimal control system and the estimated weights of the critic NN are proved to be uniformly ultimately bounded. In addition, the derived approximate optimal control is verified to guarantee the uncertain nonlinear system to be stable in the sense of uniform ultimate boundedness. Two simulation examples are provided to illustrate the effectiveness and applicability of the present approach.
Protective effect of crocetin on bovine spermatozoa against oxidative stress during in vitro fertilization

Oxidative stress is one of the major factors that contribute to poor semen quality and low rates of in vitro fertilization. Crocetin, a main constituent of saffron (Crocus sativus L.) possesses potent antioxidant activity, by scavenging reactive oxygen species (ROS) and/or enhancing the activity of intracellular antioxidant enzymes. The aim of this study was to investigate, for the first time, the effect of crocetin on the quality characteristics of bull spermatozoa and fertilization rate. For this reason, frozen/thawed bovine spermatozoa were incubated with crocetin (1, 2.5, and 5 μm), for 120 or 240 min, in the presence of a negative control, and evaluated in terms of motility, viability, acrosomal status, DNA fragmentation index, intracellular ROS, and lipid peroxidation. In order to evaluate the impact of crocetin on cleavage and blastocyst rate, the compound was added in the IVF medium at the previously identified optimal concentration (2.5 μm). The results indicate that incubation of spermatozoa with 2.5 μm of crocetin resulted in a statistically significant lower production of superoxide anion and hydrogen peroxide, lower lipid peroxidation, and in better maintenance of motility parameters, viability, and acrosomal integrity, with a very small number of cells with DNA fragmentation, compared to the other groups (p < 0.05). The presence of crocetin (2.5 μm) in the fertilization medium also resulted in a significant increase in acrosome‐reacted spermatozoa and blastocyst production, compared to the control group (p < 0.01). These data indicate that crocetin (2.5 μm) positively affects bovine sperm quality characteristics during a 240‐min incubation and improves its fertilizing ability, directly and/or indirectly, by regulating ROS concentration and lipid peroxidation.
Endothelial γ-Glutamyltransferase Contributes to the Vasorelaxant Effect of S-Nitrosoglutathione in Rat Aorta

S-nitrosoglutathione (GSNO) involved in storage and transport of nitric oxide (•NO) plays an important role in vascular homeostasis. Breakdown of GSNO can be catalyzed by γ-glutamyltransferase (GGT). We investigated whether vascular GGT influences the vasorelaxant effect of GSNO in isolated rat aorta. Histochemical localization of GGT and measurement of its activity were performed by using chromogenic substrates in sections and in aorta homogenates, respectively. The role of GGT in GSNO metabolism was evaluated by measuring GSNO consumption rate (absorbance decay at 334 nm), •NO release was visualized and quantified with the fluorescent probe 4,5-diaminofluorescein diacetate. The vasorelaxant effect of GSNO was assayed using isolated rat aortic rings (in the presence or absence of endothelium). The role of GGT was assessed by stimulating enzyme activity with cosubstrate glycylglycine, as well as using two independent inhibitors, competitive serine borate complex and non-competitive acivicin. Specific GGT activity was histochemically localized in the endothelium. Consumption of GSNO and release of free •NO decreased and increased in presence of serine borate complex and glycylglycine, respectively. In vasorelaxation experiments with endothelium-intact aorta, the half maximal effective concentration of GSNO (EC50 = 3.2±0.5.10−7 M) increased in the presence of the two distinct GGT inhibitors, serine borate complex (1.6±0.2.10−6 M) and acivicin (8.3±0.6.10−7 M), while it decreased with glycylglycine (4.7±0.9.10−8 M). In endothelium-denuded aorta, EC50 for GSNO alone increased to 2.3±0.3. 10−6 M, with no change in the presence of serine borate complex. These data demonstrate the important role of endothelial GGT activity in mediating the vasorelaxant effect of GSNO in rat aorta under physiological conditions. Because therapeutic treatments based on GSNO are presently under development, this endothelium-dependent mechanism involved in the vascular effects of GSNO should be taken into account in a pharmacological perspective.
Quantifying the Resistance to Airflow during Iron Ore Sintering

Sintering tests, involving airflow measurements before and after bed ignition, were carried out on three optimized iron ore blends-containing only hematite (HAEM), hematite with pisolite (PISO), and hematite with pisolite and hematite-goethite (PIMM)-to assess the resistance of the flame front and associated regions. Results showed that post-ignition airflow rates for the three blends were comparable for the same pre-ignition airflow rate, indicating that reactive ores i.e. pisolite and hematite-goethite ores, did not have an adverse effect on flame front resistance. For the PIMM blend, increasing the level of fines (minus 0.15 mm fraction) also did not have any effect on the flame front resistance. Reducing the coke level in all the three blends and increasing basicity decreased the value of the resistance. The resistance was shown to be a strong function of green bed airflow velocity and semi-empirical equations, with single variables, were derived to characterize the ‘sinterability’ of iron ore mixes.
An Improved Optimization Model of Internet Charging Scheme in Multi Service Networks

This article will analyze new improved charging scheme with base price, quality premium and QoS networks involved. Sain and Herpers [5] already attempted to obtain revenue maximization by creating charging scheme of internet. The plan is attempted to solve multi service networks scheme as an optimization model to obtain revenue maximization using our improved model based on Byun and Chatterjee [2] and Sain and Herpers [5]. The results show that improved model can be solved optimally using optimization tool LINGO to achieve better revenue maximization. Better results are obtained in all cases rather than in [5]. The advantage of our new model is that ISP also can set up their base price and quality premium based on ISP preferences. For some cases for getting revenue maximization, we do not offer one service and just utilize some of the services.