gebhart/patrepeval huggingface dataset:
The role of the NLRP3 inflammasome in pulmonary diseases (2015)

Respiratory diseases and lung injuries are one of the leading causes of death in the world. One critical component of these diseases is exaggerated inflammatory response. The recently discovered inflammasome is believed to play a key role in inflammation. The inflammasome is an oligomer of intracellular proteins that, once activated by an insult or damage signal, produces mature cytokines from the interleukin-1 family that mediate an inflammatory response. Previous research has provided evidence that suggests the role of the inflammasome in the pathogenesis of many chronic respiratory diseases and acute lung injuries, such as transfusion-related acute lung injury, ventilator-induced lung injury, asthma, chronic obstructive pulmonary disease and pulmonary fibrosis. This article summarizes recent research on the inflammasome and reviews proposed molecular models of the role of the inflammasome in several prominent lung diseases and injuries.
Naturally occurring promoter down mutation: nucleotide sequence of the trp promoter/operator/leader region of Shigella dysenteriae 16. (1978)

The promoter/operator/leader region of the trp operon of Shigella dysenteriae 16 has single base pair differences from the corresponding region of Escherichia coli at positions -24 and -13. The difference at -13 was shown to be responsible for the 90% reduction in promoter function characteristic of the trp operon of S. dysenteriae. The base pair difference at position -13 also renders the operator partially constitutive. This allows the organism to maintain relatively high repressed levels of the trp enzymes and increases the relative importance of attenuation as a transcription control mechanism. These findings and the earlier observation that the trpE protein of S. dysenteriae is only slightly active explain the low in vivo expression of the trp operon of this organism. Nutritional studies suggest that operons involved in other amino acid biosynthetic pathways in S. dysenteriae 16 may be similarly partially inactivated.
Effects of IL-12 on the generation of cytotoxic activity in human CD8+ T lymphocytes. (1993)

We have studied the effects of human rIL-12 on the proliferation and generation of cytotoxic activity in human CTL precursors. Purified human blood CD8+ T lymphocytes were stimulated overnight with immobilized alpha-CD3 and cultured 3 to 4 additional days under various conditions. The addition of IL-12 resulted in a marked (10- to 20-fold), dose-dependent, augmentation of cytotoxicity per cell with a smaller (2-fold) increase in cell number. IL-12 augmentation of proliferation and cytotoxicity of CD8+ T cells was not inhibited by a mAb to the p55 subunit of the IL-2 receptor (alpha-Tac) at a concentration sufficient to block the activity of exogenously added IL-2, indicating that the activity of IL-12 did not require IL-2. Addition of IL-12 at the time of alpha-CD3 activation or 1 day later was highly effective at augmenting cytotoxicity, whereas delayed addition of IL-12 (day 2 or 3) resulted in a smaller increase in CTL activity with no increase in cell number. IL-12 at all doses tested synergized with low dose IL-2 in inducing the proliferation and differentiation of CD8+ T cells. The synergistic effect was not blocked by adding neutralizing serum to IFN-gamma. In contrast to this synergistic effect, IL-12 significantly inhibited the proliferation observed in the presence of higher concentrations of IL-2 (4,500 and 13,500 pg/ml). An inhibitory effect of IL-12 was also observed when IL-12 was added to CD8+ T lymphocytes 3 days subsequent to activation with alpha-CD3 and IL-2. This broad set of potent effects of IL-12 on CD8+ T cell responses suggests that IL-12 may play an important immunoregulatory role on CTL development in vivo and may be a useful tool for manipulating this process in vivo for investigational and immunotherapeutic purposes.
A fast and simple method for detecting and quantifying donor-derived cell-free DNA in sera of solid organ transplant recipients as a biomarker for graft function (2015)

Our method represents a universally applicable, simple and cost-effective tool which can potentially be used to detect graft dysfunction in transplant recipients.
Expression of protooncogene c-myb in normal human hematopoietic cells (1989)

Expression of the protooncogene, c-myb, in various subpopulations of normal human hematopoietic cells was characterized. Cells expressing the immature cell surface marker, CD34 (My10), were isolated by immune adherence with the "panning" technique or immunomagnetic microspheres and were shown to be strongly positive for c-myb protein expression in an immunoperoxidase assay. The CD34+ progenitor cell population was further separated into myeloid plus erythroid progenitors (CD34+, CD10-) v B-lymphoid precursors (coexpressing CD34 and CD10) by two-color FACS. Both CD34+ progenitor cell subsets strongly expressed c-myb protein by the immunoperoxidase assay. A flow cytometric assay was then developed which permitted simultaneous detection of a cell-surface antigen (to characterize lineage and stage of maturation) and the nuclear oncoprotein. This assay confirmed that CD34+ cells were strongly positive for c-myb expression and also allowed quantitative comparisons of c-myb expression in selected populations of other normal hematopoietic cells. Most human bone marrow cells appear to express some level of c-myb protein, although the CD34+ progenitor cell population expresses the highest amount.
Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer (2004)

The role of platelets in tumor progression and metastasis has been recognized but the mechanism of their action remains unclear. Five human lung cancer cell lines (A549, CRL 2066, CRL 2062, HTB 183, HTB 177) and a murine Lewis lung carcinoma (LCC) cell line (for an in vivo model of metastasis) were used to investigate how platelet-derived microvesicles (PMV), which are circular fragments shed from the surface membranes of activated platelets, and exosomes released from platelet alpha-granules, could contribute to metastatic spread. We found that PMV transferred the platelet-derived integrin CD41 to most of the lung cancer cell lines tested and stimulated the phosphorylation of mitogen-activated protein kinase p42/44 and serine/threonine kinase as well as the expression of membrane type 1-matrix metalloproteinase (MT1-MMP). PMV chemoattracted 4 of the 5 cell lines, with the highly metastatic A549 cells exhibiting the strongest response. In A549 cells, PMV were shown to stimulate proliferation, upregulate cyclin D2 expression and increase trans-Matrigel chemoinvasion. Furthermore, in these cells, PMV stimulated mRNA expression for angiogenic factors such as MMP-9, vascular endothelial growth factor, interleukin-8 and hepatocyte growth factor, as well as adhesion to fibrinogen and human umbilical vein endothelial cells. Intravenous injection of murine PMV-covered LLC cells into syngeneic mice resulted in significantly more metastatic foci in their lungs and LLC cells in bone marrow than in control animals injected with LCC cells not covered with PMV. Based on these findings, we suggest that PMV play an important role in tumor progression/metastasis and angiogenesis in lung cancer.
Bacterial spores as heat stable vaccine vehicles (2003)

Recently, the first use of bacterial spores as vaccine vehicles was reported, showing that mice orally immunised with Bacillus subtilis spores expressing a tetanus antigen could be protected against lethal challenge with tetanus toxin. Unlike many second generation vaccine systems currently under development, none offer the heat stability of bacterial spores or the flexibility for genetic manipulation. The current use of Bacillus spores as probiotics for both humans and animals may facilitate their eventual licensing as oral vaccines. This review reports the progress that has been made in the establishment of bacterial spores as vaccine vehicles and outlines the potential advantages of the spore vaccine approach.
Hydroxytyrosol Expresses Antifungal Activity In Vitro (2013)

Hydroxytyrosol (HT) is a potent antioxidant found in olive oil and leaves. Using several in vitro approaches, we tested antifungal activity of HT. HT showed broad spectrum of antifungal activity against medically important yeasts and dermatophyte strains with MIC values ranging between 97.6 µgml⁻¹ and 6.25 mgml⁻¹. The antimicrobial activity of HT was also tested using the time-kill methodology. Below the MIC value, HT showed potent damage of cell wall of Candida albicans ATCC 10231 using fluorescent dye-exclusion method. At the subinhibitory concentration, HT also influenced dimorphic transition of Candida indicating that HT is inhibitor of germ-tube formation as one of the most important virulence factor of C. albicans. Furthermore, HT showed disturbances in cell surface hydrophobicity (CSH) of C. albicans. The in vitro results indicate that HT caused a significant cell wall damage and changes in CSH as well as inhibition of germ-tube formation as virulence factor of C. albicans. The study indicates that HT has a considerable in vitro antifungal activity against medically important yeasts.
Hormonal changes affect the bone and bone marrow cells in a rat model (2000)

In this study, we used a rat model to investigate the effects of gonad hormones and replacement therapy on bone structure and the immune system. In the first phase of the study, 3- and 11-month-old F344 rats underwent ovariectomy (OVX) or were sham operated. Three months later, severe osteopenia was histologically observed in OVX rats of both age groups. The changes in the bone marrow structure of OVX rats included deterioration of cancellous bone that was associated with a remarkable increase of adipocyte cells. Furthermore, differential analyses for the expression of cell surface antigens by lymph-myeloid cells was studied using flow cytometry (FACS). The number of myeloid cells expressing ED-9(+) or CD-44(+) was similar in both age groups, and unaffected by OVX. However, an augmentation of T-lymphoid cells expressing CD4(+), CD5(+), or both, were observed with age, as well as after OVX. In the second phase of the study, 11-month-old rats were divided into five experimental groups: sham-operated, OVX, and OVX treated with sustained-release pellets of 17beta-estradiol (OVX-E), progesterone (OVX-P), or both (OVX-E/P). Hormone replacement therapy maintained low physiological levels, and rats were tested 12 weeks after treatment initiation. Administration of 17beta-E, with or without the addition of progesterone, prevented the rise of T lymphoid cells observed in OVX rats, whereas progesterone alone had no effect. In agreement with findings from the first phase, neither OVX nor replacement therapy affected the myeloid cells expression of ED-9 or CD-44. In summary, the cellular changes in the bone marrow of OVX rats were associated with an increase in adipocytes that was correlated with bone atrophy. An augmentation of T-lymphopoiesis was noted with increase in age or after OVX. This increase was reversed to baseline levels by 17beta-E treatment.
Effects of Alkaline Reagent on the Rheological Properties of Wheat Flour and Noodle Property (1996)

The effects of sodium carbonate (Na), potassuim carbonate (K) and their mixtures (Na/K=0.7-2.0) on pasting properties by amylograph and mixing properties by farinograph of wheat flour (9.45% protein), and of alkali mixtures (0.16%) on noodle property were examined. The concentrations of alkali used were 0.08%, 0.10% and 0.16% based on flour weight (14% mb). The salt (1.7%) and alkali decreased the initial pasting temperature but increased the amylograph peak viscosity. The peak viscosity increased with the increase of alkali concentration, but the mixing ratio at a fixed concentration had no effect on peak viscosity. The farinograph absorption decreased by salt, but the effect of salt diminished in the presence of alkali. The salt and alkali increased the farinograph stability, of which the former was more pronounced. The effect of alkali alone and mixtures in the presence of salt on amylograph and farinograph were essentially the same regardless the concentrations and mixing ratios. The yellowness and breaking force of dry noodle prepared with salt and alkali was higher than that prepared with salt only. The weight and volume gain of the optimum cooked noodle remained essentially constant, but the shear force and compression force were increased by the alkali.
High-Solids Enzymatic Saccharification Screening Method for Lignocellulosic Biomass (Poster) (2009)

The purpose of this study was to test the effectiveness of a telephone intervention to reduce fatigue and the resulting symptom distress of mothers in Iceland who reported having a behaviourally difficult infant of 2-3 months of age. A sample of 78 mothers who reached distress criteria of depressive symptoms and parental stress was selected and randomly allocated in a controlled experimental study. In a brief intervention both maternal distress and infant difficulty were discussed. Results indicate a significant (P < 0.001) intervention effect on fatigue and its side-effects. It is concluded that intervention by telephone can be effective with fatigued mothers caring for a difficult infant.
RESEARCH PROGRESS IN NATURAL ANTIOXIDANT DIHYDROMYRICETIN (2007)

Dihydromyricetin,i.e.ampelopsin belongs to a kind of flavonoids,which shows very high biological activities.It can be used as an antioxidant and food preservative in food industry.The compound has also much high effectiveness such as eliminating free radicales,inflammation,relieving a cough,reducing fattiness in blood and protecting liver.These properties have attracted the interesting of many food chemists,medicinal scientists and biologists.In the present article,we give a review on the chemical properties,the methods of determination,extraction,and purification of dihydromyricetin.
Antibody conjugation and formulation (2019)

In an era where ultra-high antibody concentrations, high viscosities, low volumes, auto-injectors and long storage requirements are already complex problems with the current unconjugated monoclonal antibodies on the market, the formulation demands for antibody-drug conjugates (ADCs) are significant. Antibodies have historically been administered at relatively low concentrations through intravenous (IV) infusion due to their large size and the inability to formulate for oral delivery. Due to the high demands associated with IV infusion and the development of novel antibody targets and unique antibody conjugates, more accessible routes of administration such as intramuscular and subcutaneous are being explored. This review will summarize various site-specific and non-site-specific antibody conjugation techniques in the context of ADCs and the demands of formulation for high concentration clinical implementation.
On certifying mobile code for secure applications (2002)

Summary form only given. The security issues in mobile code arise from the fact that someone else's program is running on your machine often without your knowledge and approval, often without controls on its privileges, and often without knowledge for how trustworthy that program is. Several different approaches have emerged for providing some assurance against malicious behavior. Javasoft implemented a "sandbox" for constraining the privileges of applets executing within a browser. Microsoft has implemented a trust-based approach called Authenticode which comes in the form of a certificate attached to any mobile piece of software. The approach espoused by this author is to combine the best of both solutions. The proposed solution involves distributing certificates with mobile code that verify not only the authenticity of the organization or individual that produced the code, but also the secure behavior of that code. Certification would be based on a process that involves testing the program for security-related defects (such as buffer overflow flaws) and verifying that the program is free from malicious code. The former activity can benefit from software reliability engineering (SRE), while the latter cannot. While SRE can be useful for producing reliable, if not correct, code, it does not address malicious intentions of either developers or hackers. To this end, software produced from an SRE process or otherwise must be certified as being free from security-related defects and malicious behavior.
Overexpression of membrane-type matrix metalloproteinase-1 gene induces mammary gland abnormalities and adenocarcinoma in transgenic mice. (2001)

To investigate the role of membrane-type matrix metalloproteinase-1 (MT1-MMP) in mammary gland development and tumorigenesis, transgenic mice overexpressing MT1-MMP in mammary gland under the control of the mouse mammary tumor virus long terminal repeat-promoter were generated. The mouse mammary tumor virus/MT1-MMP transgenic mice displayed abnormalities in 82% of female mammary glands. The abnormalities were verified as lymphocytic infiltration, fibrosis, hyperplasia, alveolar structure disruption, dysplasia, and adenocarcinoma. Northern and reverse transcription-PCR analyses demonstrated that MT1-MMP mRNA was overexpressed in mammary glands exhibiting abnormalities. Western blot analysis and immunohistochemical studies have revealed that the protein expression level was also increased in these glands. In addition, the beta-casein gene as a functional epithelial cell marker was poorly expressed in the mammary glands of transgenic mice exhibiting abnormalities. Gelatin zymography showed significantly increased MMP-2 activation in these mammary glands. These results showed that overexpression of MT1-MMP induced remodeling of the extracellular matrix and tumor formation in the mammary glands of transgenic mice. Therefore, we suggest that overexpression of MT1-MMP may play a key role in development and tumorigenesis in mammary glands.
Posttranslational Protein Translocation Across the Membrane of the Endoplasmic Reticulum (1999)

Posttranslational protein translocation across the membrane of the endoplasmic reticulum is mediated by the Sec complex. This complex includes a transmembrane channel formed by multiple copies of the Sec61 protein. Translocation of a polypeptide begins when the signal sequence binds at a specific site within the channel. Binding results in the insertion of the substrate into the channel, possibly as a loop with a small segment exposed to the lumen. While bound, the signal sequence is in contact with both protein components of the channel and the lipid of the membrane. Subsequent movement of the polypeptide through the channel occurs when BiP molecules interact transiently with a luminal domain of the Sec complex, hydrolyze ATP, and bind to the substrate. Bound BiP promotes translocation by preventing the substrate from diffusing backwards through the channel, and thus acts as a molecular ratchet.
An efficient method for creation and functional analysis of libraries of hybrid type I polyketide synthases (2004)

Bacterial type I polyketide synthases (PKSs) generate a structurally diverse group of natural products with a wide range of biological activities. Hybrid type I PKSs in which domains of one multifunctional polypeptide are replaced with components from heterologous systems have generated significant interest over the past decade. Almost invariably only one or several specific hybrids are made at a time and tested for functionality. This approach is slow, dependent upon a fortuitous choice of specific fusions points, and often leads to inactive or minimally active hybrid systems. We describe herein a method for generating and screening a library of hybrid pikAI complementation plasmids (encoding the loading domain and the first two extension domains of pikromycin PKS) able to restore pikromycin in a BB138 Streptomyces venezuelae pikAI-deletion mutant. In the first step the plasmid sequence encoding the loading domain AT(0)-ACP(0) was replaced by a counter selectable marker, sacB. DNA family shuffling was then used to generate a diverse library of chimeric AT(0)-ACP(0) fragments, which were used to replace sacB by lambda-Red-mediated in vivo recombination in an Escherichia coli host. This method resulted in the rapid and efficient generation of a large number of hybrid pikAI complementation plasmids, which were used to transform S.venezuelae BB138. A bioassay of over 4000 of these transformants successfully revealed three different PikAI hybrids which were able to lead to pikromycin production. The study suggests that most of the hybrids are not detectably functional, and underscores the need to generate and screen large and diverse libraries in which different fusion points are tried. The methodologies applied in this study address this need and can be used for directed evolution of any component of the PikPKS, and potentially other type I PKS systems.
Approaches for Functional Characterization of Diatom Silicic Acid Transporters (2005)

A major component of the diatom cell wall is silica, derived from silicon taken up from the environment. Due to limiting environmental concentrations of silicon, and a substantial requirement during cell wall synthesis, diatoms must transport silicon into the cell against a steep concentration gradient. This is accomplished through the silicic acid transporters (SITs). The SITs were first identified in the marine pennate diatom Cylindrotheca fusiformis. Five distinct SITs were found and have been classified as a novel family of transporters. This review covers our current understanding of silicon transport in diatoms with a focus on the SITs. Approaches for in-depth functional characterization of the SITs are discussed, including (1) isolating SITs from evolutionarily distant diatom species to identify conserved amino acids that may be important for function, (2) developing expression systems to assay the function of selected SITs, and (3) determining the cellular location and membrane topology of the C. fusiformis SITs to further clarify their roles in diatom silicon metabolism. Because of the specificity of interaction between the SITs and silicon, and the ability of the SITs to transport silicic acid across lipid bilayers, the SITs may have applications in nanotechnology.
Supervised and unsupervised methods in employing discourse relations for improving opinion polarity classification (2009)

This work investigates design choices in modeling a discourse scheme for improving opinion polarity classification. For this, two diverse global inference paradigms are used: a supervised collective classification framework and an unsupervised optimization framework. Both approaches perform substantially better than baseline approaches, establishing the efficacy of the methods and the underlying discourse scheme. We also present quantitative and qualitative analyses showing how the improvements are achieved.
Molecular and cellular signatures of human vaccine adjuvants (2008)

Oil-in-water emulsions are potent human adjuvants used for effective pandemic influenza vaccines; however, their mechanism of action is still unknown. By combining microarray and immunofluorescence analysis, we monitored the effects of the adjuvants MF59 oil-in-water emulsion, CpG, and alum in the mouse muscle. MF59 induced a time-dependent change in the expression of 891 genes, whereas CpG and alum regulated 387 and 312 genes, respectively. All adjuvants modulated a common set of 168 genes and promoted antigen-presenting cell recruitment. MF59 was the stronger inducer of cytokines, cytokine receptors, adhesion molecules involved in leukocyte migration, and antigen-presentation genes. In addition, MF59 triggered a more rapid influx of CD11b+ blood cells compared with other adjuvants. The early biomarkers selected by microarray, JunB and Ptx3, were used to identify skeletal muscle as a direct target of MF59. We propose that oil-in-water emulsions are the most efficient human vaccine adjuvants, because they induce an early and strong immunocompetent environment at the injection site by targeting muscle cells.