Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic impact of the expression of NCR1 and NCR3 NK cell receptors and PD-L1 on advanced non-small cell lung cancer

ABSTRACT The putative contribution of natural killer (NK) cells to immunosurveillance in non-small cell lung cancer (NSCLC) has been an ongoing conundrum. Here, we used a readily standardizable quantitative real time polymerase chain reaction (qRT-PCR) to measure the expression of NK cell receptors in total peripheral blood mononuclear cells (PBMC) from healthy volunteers (HV), patients with gastrointestinal stromal tumors (GIST), neuroblastoma (NB), melanoma or NSCLC. We quantified NCR1 (which codes for NKp46) and NCR3 (which codes for NKp30), as well as that of three NCR3 splice variants (which give rise to immunostimulatory NKp30A and NKp30B, as well as to immunosuppressive NKp30C). NSCLC patients expressed lower levels of NCR1 than did HV. Remarkably, NCR3 was lower in NSCLC patients than in HV as well as in all other malignancies. Moreover, a discrete proportion of NSCLC patients exhibited a particular low ratio between NKp30B and NKp30C (ΔBC). In the overall cohort, low expression of NCR3 correlated with poor overall and progression-free survival (PFS). When patients were stratified according to the level of PD-L1 expression by NSCLC cells, within the PD-L1high category (>5% positive tumors), the sole parameter that affected prognosis was the expression of NCR1. However, in patients bearing tumors with negative PD-L1 expression on tumor or tumor-infiltrating stromal cells, the ΔBClow patients exhibited a dismal prognosis. Altogether, these results strongly suggest that NK cells mediate immunosurveillance against NSCLC and that measuring NK cell receptor expression by blood cells can yield useful biomarkers for patient stratification.
Classification of biomedical data of thermoacoustic tomography to detect physiological abnormalities in the body tissues

Based on thermal acoustic data from the body tissue in upper arm that has been produced through thermal acoustic tomography method, classification system for the data has been built as a support of decision making about physiological abnormality. The advantages of the system built in this research is able to detect physiological abnormalities in the body tissues without the need for surgery (non-invasive method), such as to detect the existence of tumor or cancer and the damage of kidney or liver. Two classification methods has been evaluated for comparison, which are Backpropagation Neural Network (BP-NN) and Support Vector Machine (SVM). Using SVM that based on boundary optimization and BP-NN that based on error minimization as comparison, it is expected to obtain the most suitable classification method for decision making about physiological abnormalities in body tissues. The experimental results on 60 train data and 40 test data show that the accuracy for classification using Backpropagation Neural Network and Support Vector Machine (SVM) are 70% and 67.5%, respectively. In general, it can be proved that classification using Backpropagation Neural Network takes a longer running time (around 0.9 seconds) than classification using SVM (around 0.05 seconds).
Risk assessment in system FMEA combining fuzzy weighted average with fuzzy decision-making trial and evaluation laboratory

Failure mode and effects analysis (FMEA) is a risk assessment tool that mitigates potential failures in products, processes or systems before they occur. Although many industries use the traditional FMEA technique, it has been criticised for having several setbacks. First, the current FMEA determines the risk priorities of failure modes by using risk priority numbers (RPNs), which require the risk factors, occurrence (O), severity (S) and detection (D), to be evaluated in crisp values. Second, the conventional RPN method has not considered the indirect relations between components of a system and is insufficient for complex systems with many subsystems or components. Therefore, a new risk assessment methodology combining fuzzy weighted average with fuzzy decision-making trial and evaluation laboratory (fuzzy DEMATEL) is proposed in this article to rank the risk of failures in system FMEA. The new method can address some of the inherent limitations of the traditional FMEA. Also, an application to the thin film transistor liquid crystal display (TFT-LCD) product is presented to demonstrate the proposed FMEA. By comparing with the listed approaches, the results show that the proposed method is a suitable and effective method for prioritisation of failures in system FMEA.
Molecular subtyping and characterization of psychrotolerant endospore-forming bacteria in two New York State fluid milk processing systems.

Psychrotolerant endospore-forming bacteria Bacillus and Paenibacillus spp. are important spoilage organisms in fluid milk. A recently developed rpoB subtyping method was applied to characterize the diversity and phylogenetic relationships among Bacillus and related sporeformers associated with milk processing systems. Milk samples representing the processing continuum from raw milk to pasteurized products were collected from two fluid milk processing plants, held at 6 degrees C up to the code date that had been established by each processing plant (i.e., either 18 or 21 days), and plated for bacterial enumeration throughout storage. Bacterial colonies selected to represent the visible diversity in colony morphology on enumeration plates were examined further. Among 385 bacterial isolates characterized, 35% were Bacillus spp. , and 65% were Paenibacillus spp. A total of 92 rpoB allelic types were identified among these isolates, indicating considerable diversity among endospore-forming spoilage organisms present in fluid milk systems. Of the 92 allelic types identified, 19 were isolated from samples collected from both processing plants. The same rpoB allelic types were frequently identified in paired raw milk and packaged product samples, indicating that Bacillus and Paenibacillus spp. can enter dairy processing systems through raw milk. Certain subtypes were found exclusively in pasteurized samples, including those that were temporally independent, suggesting the possibility of in-plant sources for these spoilage organisms, including through the persistence of selected subtypes in processing plants. Development of effective control strategies for the diverse array of psychrotolerant endospore-forming organisms that currently limit the shelf lives of high-temperature short-time fluid milk products will require comprehensive, integrated efforts along the entire milk processing continuum.
Automated Stem Curve Measurement Using Terrestrial Laser Scanning

This paper reports on a study of measuring stem curves of standing trees of different species and in different growth stages using terrestrial laser scanning (TLS). Pine and spruce trees are scanned using the multiscan approach in the field, and trees are felled to measure them destructively for the purpose of obtaining reference values. The stem curves are automatically retrieved from laser point clouds, resulting in an accuracy of ~i1 cm. The corresponding manual measurements yield similar accuracy but fewer measurements at the upper parts of tree stems, compared with the automated measurements. The stem volumes based on stem curve data and field measurements and the best Finnish national allometric volume equations (using tree species, height, and diameters at heights of 1.3 and 6 m as predictors) result in similar accuracy. The measurement accuracy of the stem curves and stem volumes is similar for both pine and spruce trees. The results of this paper confirm the feasibility of using TLS to produce stem curve data in an automated, accurate and noninvasive way and indicate that the point cloud provides adequate information to accurately derive stem volumes from standing trees. The stem curves and volumes retrieved from point clouds can be employed in various forest management activities, such as the calibration of national or regional allometric curve functions and the prediction of profits in preharvest inventories.
Contribution of Burkholderia cenocepacia Flagella to Infectivity and Inflammation

ABSTRACT Burkholderia cenocepacia is an opportunistic pathogen that can cause severe lung infections in cystic fibrosis patients. To understand the contribution of B. cenocepacia flagella to infection, a strain mutated in the major flagellin subunit, fliCII, was constructed in B. cenocepacia K56-2 and tested in a murine agar bead model of lung infection. C57/BL6 mice infected with ∼108 wild-type K56-2 bacteria exhibited 40% mortality after 3 days, whereas no mortality was noted in mice infected with the fliCII mutant. Among the mice surviving the infection with either strain, there was no significant difference in the bacterial loads in the lungs and spleen, bacteremia, weight loss, or infiltration of immune effector cells at 3 days postinfection. Similar results were observed at 24 h, prior to expression of the lethality phenotype. KC, a murine interleukin-8 (IL-8) homolog, was elevated in both the bronchoalveolar lavage fluid and serum of mice infected with the wild type compared to the fliCII mutant at 24 h, suggesting that flagella stimulated host cells. To demonstrate that flagella contributed to these responses, the interaction between B. cenocepacia and Toll-like receptor 5 (TLR5) was investigated. Infection of HEK293 cells with heat-killed wild-type K56-2, but not infection with the fliCII mutant, resulted in both NF-κB activation and IL-8 secretion that was dependent upon expression of TLR5. Together, these results demonstrate that B. cenocepacia flagella contribute to virulence in an in vivo infection model, and that induction of host immune responses through interaction with TLR5 may contribute to its overall pathogenic potential.
Factors associated with herbal therapy use by adults in the United States.

OBJECTIVE To examine the patterns of herbal therapy use among adults in the United States and to describe factors associated with herb use. DESIGN We examined the use of natural herbs from the 2002 National Health Interview Survey (NHIS). We analyzed factors associated with herb use and reasons for herb use with logistic regression. RESULTS Factors associated with herb use include the following: age (45-64 years old), being uninsured, being female, having a higher education, living in the West, using prescription medications or over-the-counter (OTC) medications, and self-identified as "non-Hispanic other. " Factors associated with no herb use include being non-Hispanic black and living in the South or Midwest. Seventy-two percent of those who used herbs used prescription medications, and 84% of those who used herbs also used an OTC medication in the prior 12 months. Among adults who used herbs, the most commonly mentioned were echinacea (41%), ginseng (25%), gingko (22%), and garlic (20%). The most frequent conditions for herb use were head or chest cold (30%), musculoskeletal conditions (16%), and stomach or intestinal illness (11%). Among those who used herbs in the prior year, factors associated with using herbs because conventional medical treatments were too expensive included being uninsured, having poor health, and being 25-44 years old. CONCLUSIONS Nearly 1 in 5 people in the US population report using an herb for treatment of health conditions and/or health promotion. More than half did not disclose this information to a conventional medical professional.
Divergent Response to LPS and Bacteria in CD14-Deficient Murine Macrophages1

Gram-negative bacteria and the LPS constituent of their outer membranes stimulate the release of inflammatory mediators believed to be responsible for the clinical manifestations of septic shock. The GPI-linked membrane protein, CD14, initiates the signaling cascade responsible for the induction of this inflammatory response by LPS. In this paper, we report the generation and characterization of CD14-null mice in which the entire coding region of CD14 was deleted. As expected, LPS failed to elicit TNF-α and IL-6 production in macrophages taken from these animals, and this loss in responsiveness is associated with impaired activation of both the NF-κB and the c-Jun N-terminal mitogen-activated protein kinase pathways. The binding and uptake of heat-killed Escherichia coli, measured by FACS analysis, did not differ between CD14-null and wild-type macrophages. However, in contrast to the findings with LPS, whole E. coli stimulated similar levels of TNF-α release from CD14-null and wild-type macrophages at a dose of 10 bioparticles per cell. This effect was dose dependent, and at lower bacterial concentrations CD14-deficient macrophages produced significantly less TNF-α than wild type. Approximately half of this CD14-independent response appeared to be mediated by CD11b/CD18, as demonstrated by receptor blockade using neutrophil inhibitory factor. An inhibitor of phagocytosis, cytochalasin B, abrogated the induction of TNF-α in CD14-deficient macrophages by E. coli. These data indicate that CD14 is essential for macrophage responses to free LPS, whereas other receptors, including CD11b/CD18, can compensate for the loss of CD14 in response to whole bacteria.
A proteomic view of the facultatively chemolithoautotrophic lifestyle of Ralstonia eutropha H16

Ralstonia eutropha H16 is an H2‐oxidizing, facultative chemolithoautotroph. Using 2‐DE in conjunction with peptide mass spectrometry we have cataloged the soluble proteins of this bacterium during growth on different substrates: (i) H2 and CO2, (ii) succinate and (iii) glycerol. The first and second conditions represent purely lithoautotrophic and purely organoheterotrophic nutrition, respectively. The third growth regime permits formation of the H2‐oxidizing and CO2‐fixing systems concomitant to utilization of an organic substrate, thus enabling mixotrophic growth. The latter type of nutrition is probably the relevant one with respect to the situation faced by the organism in its natural habitats, i.e. soil and mud. Aside from the hydrogenase and Calvin‐cycle enzymes, the protein inventories of the H2‐CO2‐ and succinate‐grown cells did not reveal major qualitative differences. The protein complement of the glycerol‐grown cells resembled that of the lithoautotrophic cells. Phosphoenolpyruvate (PEP) carboxykinase was present under all three growth conditions, whereas PEP carboxylase was not detectable, supporting earlier findings that PEP carboxykinase is alone responsible for the anaplerotic production of oxaloacetate from PEP. The elevated levels of oxidative stress proteins in the glycerol‐grown cells point to a significant challenge by ROS under these conditions. The results reported here are in agreement with earlier physiological and enzymological studies indicating that R. eutropha H16 has a heterotrophic core metabolism onto which the functions of lithoautotrophy have been grafted.
Simultaneous intravenous and intramiddle-ear dosing to determine cefditoren influx and efflux clearances in middle ear fluid in freely moving chinchillas.

This study was conducted to determine cefditoren (CDTR) transport kinetics between plasma and middle ear fluid (MEF) by characterizing influx (CLin) and efflux (CLout) clearances expressed in terms of unbound concentrations and their ratio. Simultaneous intravenous bolus and intramiddle-ear dose were administered to two groups of chinchillas: normal control and infected. In vivo microdialysis was employed to determine protein-unbound CDTR levels in MEF. Compartmental and noncompartmental analysis was performed. Parameters determined in both groups were compared to assess the effect of infection and inflammation on CDTR distribution kinetics. CLin and CLout estimates obtained by compartmental and noncompartmental analysis agreed well. The calculated CLin/CLout ratio was 0.76 +/- 0.23 and 0.56 +/- 0.25 in normal (n = 9) and infected (n = 6) animals, respectively. The 95% confidence interval of this ratio in both groups does not include unity. Statistical tests showed no difference (p > 0.05) in CLin, CLout, and their ratio between the two groups. In conclusion, middle ear infection and inflammation does not affect CDTR distribution. The CLin/CLout ratio determined in chinchillas compares well with values estimated from data in pediatric patients. An active efflux mechanism in middle ear mucosa may be involved in CDTR distribution in MEF.
Interleukin‐1‐induced activation of a protein kinase co‐precipitating with the type I interleukin‐1 receptor in T cells

We have investigated the possibility of a protein kinase participating in the signal transduction mechanisms of the interleukin‐1 (IL‐1) type I receptor (IL‐1RI). Our data show that a protein kinase was co‐precipitated with the IL‐1 RI from the two murine T helper cell lines D10N and EL‐4. The kinase activity was detected in an in vitro kinase assay performed with the immuno beads in the presence of exogenous substrates. IL‐1 treatment of the cells resulted in a rapid activation of this protein kinase in a concentration‐dependent manner. Both forms of IL‐1, IL‐1α and IL‐1β, induced this kinase activity, whereas the IL‐1 receptor antagonist (IL‐1ra) was inactive. In excess IL‐1ra competitively antagonized IL‐1 stimulation. In the in vitro kinase assay the exogenous substrates myelin basic protein and histone H1 were phosphorylated, whereas casein or heat‐shock protein HSP27 were not accepted, reflecting a certain selectivity of this protein kinase. The IL‐1RI co‐precipitable protein kinase showed a serine/threonine specificity and was inhibited by staurosporine, but not by inhibitors specific for protein tyrosine kinases or protein kinase C. These results show that a serine/threonine protein kinase directly interacts with the IL‐1RI at the plasma membrane level of T helper cells forming a novel type of IL‐1 inducible signaling complex. This protein kinase may resemble the link coupling the plasma membrane IL‐1 receptor to cytosolic downstream elements in the IL‐1 signaling pathway.
In Vivo Demonstration that Human Parathyroid Hormone 1–38 Inhibits the Expression of Osteoprotegerin in Bone with the Kinetics of an Immediate Early Gene

Osteoprotegerin (OPG) is a potent inhibitor of osteoclast formation and function. To elucidate how OPG is regulated in bone, we examined (1) the expression and localization of OPG protein in bone tissue, (2) the effect of human parathyroid hormone 1–38 (hPTH 1–38) on OPG messenger RNA (mRNA) levels in rat femur metaphyseal and diaphyseal bone, and (3) the effect of hPTH(1–38) on expression of OPG mRNA in cultured osteoblast‐like cells derived from the metaphysis and diaphysis, and in ROS 17/2.8 osteosarcoma cells. Because PTH has been shown to stimulate osteoblast activity via the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signal transduction pathway we also investigated whether PTH action on OPG in vivo is dependent on activation of cAMP/PKA pathway. Immunohistochemistry was used to evaluate OPG protein expression and Northern blot hybridization was used to analyze OPG mRNA expression both in vivo and in vitro. Immunohistochemistry of OPG protein expression in the rat distal femur metaphysis revealed that it was localized predominantly in preosteoblasts, osteoblasts, lining cells, and the osteoid layer, with occasional immunoreactivity in osteocytes and cells of the bone marrow. Subcutaneous (sc) administration of a single injection of hPTH(1–38) at 80 μg/kg induced a rapid and transient decrease in OPG mRNA expression in both metaphyseal and diaphyseal bone. The decrease in OPG message was evident by 1 h and mRNA levels returned to baseline after 3 h. PTH analog PTH(1–31), which stimulates intracellular cAMP accumulation, inhibited OPG expression, whereas PTH analogs (3–34 and 7–34) that do not stimulate cAMP production had no effect on expression. In contrast to PTH, prostaglandin E2 (PGE2) had no effect on OPG mRNA expression in vivo in the metaphyseal bone cells, under conditions in which PGE2 does promote expression of the c‐fos gene. The in vivo effects of hPTH(1–38) on OPG mRNA were confirmed in isolated primary osteoblast cultures derived from either metaphyseal or diaphyseal bone as well as in ROS 17/2.8 osteosarcoma cells. We propose that the rapid and transient decrease in OPG expression may initiate a cascade of events resulting in the differentiation of osteoclast progenitor. Such a spatially and temporally programmed effect of PTH might contribute to bone turnover. (J Bone Miner Res 2000;15:863–871)
Negative Regulation of PYK2/Related Adhesion Focal Tyrosine Kinase Signal Transduction by Hematopoietic Tyrosine Phosphatase SHPTP1*

Related adhesion focal tyrosine kinase (RAFTK) (also known as PYK2) is a cytoplasmic tyrosine kinase related to the focal adhesion kinase (FAK) p125FAK. RAFTK is rapidly phosphorylated on tyrosine residues in response to various stimuli, such as tumor necrosis factor-α, changes in osmolarity, elevation in intracellular calcium concentration, lysophosphatidic acid, and bradykinin. Overexpression of RAFTK induces activation of c-Jun amino-terminal kinase (also known as stress-activated protein kinase), mitogen-activated protein kinase (MAPK), and p38 MAPK. The present studies demonstrate that RAFTK binds constitutively to the protein tyrosine phosphatase SHPTP1. In contrast to PTP1B, overexpression of wild-type SHPTP1 blocks tyrosine phosphorylation of RAFTK. The results further demonstrate that RAFTK is a direct substrate of SHPTP1 in vitro. Moreover, treatment of PC12 cells with bradykinin is associated with inhibition in tyrosine phosphorylation of RAFTK in the presence of SHPTP1. Furthermore, in contrast to the phosphatase-dead SHPTP1 C453S mutant, overexpression of wild-type SHPTP1 blocks interaction of RAFTK with the SH2-domain of c-Src and inhibits RAFTK-mediated MAPK activation. Significantly, cotransfection of RAFTK with SHPTP1 did not inhibit RAFTK-mediated c-Jun amino-terminal kinase activation. Taken together, these findings suggest that SHPTP1 plays a negative role in PYK2/RAFTK signaling by dephosphorylating RAFTK.
Detritivorous crustaceans become herbivores on jasmonate-deficient plants

The jasmonate signal pathway is known to control defenses against herbivores, such as leaf eaters (folivores). Does the reach of the pathway extend to defense against other types of animal? Among the arthropods attracted to seed baits placed below flowering Arabidopsis thaliana plants are 2 largely nocturnal isopod crustaceans generally considered as detritivores: Porcellio scaber and Armadillidium vulgare. Parallel laboratory experiments identified the isopods as being capable of predation on intact plants. Isopod feeding was strongly facilitated in jasmonate-deficient Arabidopsis and rice plants. The feeding activity of isopods revealed potentially detritivore-sensitive, jasmonate-protected Achilles' heels in these architecturally different plants (petioles and inflorescence stems in Arabidopsis, and lower stem and mesocotyl in rice). The work addresses the question of what stops 2 detritivores from attacking living plants and provides evidence that it is, in part, the jasmonate signal pathway. Furthermore, senescent leaves from an Arabidopsis jasmonate mutant were consumed more rapidly than senescent wild-type leaves, suggesting that past activity of the jasmonate signal pathway in leaves may slow carbon recycling through detritivory.