gebhart/patrepeval huggingface dataset:
CD19‐Chimeric Antigen Receptor T Cells for Treatment of Chronic Lymphocytic Leukaemia and Acute Lymphoblastic Leukaemia (2015)

Adoptive cell therapy (ACT) for cancer represents a promising new treatment modality. ACT based on the administration of cytotoxic T cells genetically engineered to express a chimeric antigen receptor (CAR) recognizing CD19 expressed by B cell malignancies has been shown to induce complete lasting responses in patients with chronic lymphocytic leukaemia (CLL) and acute lymphoblastic leukaemia (ALL). So far, eleven clinical trials including 99 CLL and ALL patients treated with CAR T cells targeting CD19 have been published, and the results from these trials are promising with impressive clinical responses in heavily pretreated patients. Thus, CAR T cell therapy has induced complete responses in both CLL and ALL, and surprisingly, current results indicate that patients with ALL are more prone to respond than are CLL patients. Importantly, the majority of CAR cell studies have observed severe therapy-associated toxicities, which needs attention. Herein we review current data and discuss key aspects of this powerful approach to treat and potentially cure B cell malignancies.
IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland (2007)

High serum levels of IL-6 correlate with poor outcome in breast cancer patients. However, no data are available on the relationship between IL-6 and mammary stem/progenitor cells, which may fuel the genesis of breast cancer in vivo. Herein, we address this issue in the MCF-7 breast cancer cell line and in primary human mammospheres (MS), multicellular structures enriched in stem/progenitor cells of the mammary gland. MS from node invasive breast carcinoma tissues expressed IL-6 mRNA at higher levels than did MS from matched non-neoplastic mammary glands. In addition, IL-6 mRNA was detected only in basal-like breast carcinoma tissues, an aggressive breast carcinoma variant showing stem cell features. IL-6 treatment triggered Notch-3-dependent upregulation of the Notch ligand Jagged-1 and promotion of MS and MCF-7-derived spheroid growth. Moreover, IL-6 induced Notch-3-dependent upregulation of the carbonic anhydrase IX gene and promoted a hypoxia-resistant/invasive phenotype in MCF-7 cells and MS. Finally, autocrine IL-6 signaling relied upon Notch-3 activity to sustain the aggressive features of MCF-7-derived hypoxia-selected cells. In conclusion, these data support the hypothesis that IL-6 induces malignant features in Notch-3-expressing stem/progenitor cells from human ductal breast carcinoma and normal mammary gland.
Comparative proteomic characterization of articular cartilage tissue from normal donors and patients with osteoarthritis (2007)

Altered protein expression in the disease state is associated with many aspects of the pathogenesis of OA, such as increased proteolysis, lipid metabolism, immune response, and decreased signal transduction. To our knowledge, this is the first time that a large portion of these proteins and their expression patterns were identified in cartilage, thus providing new insights for finding novel pathologic mediators and biomarkers of OA.
Active power filters: A review (2000)

In recent years there has been considerable interest in the development and applications of active filters because of the increasing concern over power quality, at both distribution and consumer levels, and the need to control reactive power and voltage stability at transmission levels. The existing approaches are classified and assessed to provide a framework of references for both researchers in this field and for generators, suppliers and consumers of electrical power who are, or may be, concerned about the problems associated with power quality and are considering installing active filters for their particular sets of problems.
Expression of a glycosylphosphatidylinositol-anchored Trypanosoma brucei transferrin-binding protein complex in insect cells. (1994)

The expression site-associated gene ESAG 6 was previously implicated in transferrin binding in the protozoan parasite Trypanosoma brucei. ESAG 6 and the closely related ESAG 7 of T. brucei strain AnTat1.3 have now been expressed in insect cells using the baculovirus expression system. Expression of ESAG 6 alone in insect cells gives rise to a glycosylated protein of approximately 52 kDa, which is cell surface-associated through a glycosylphosphatidylinositol anchor at its C terminus. The ESAG 7 product of about 42 kDa is also glycosylated, but lacks the glycosylphosphatidylinositol modification, and is located intracellularly. No transferrin-binding activity is observed when either ESAG is expressed independently. However, their expression results in a cell surface complex of ESAG 6 and 7 products that specifically binds transferrin. This shows that both ESAG 6 and 7 products are necessary and sufficient for binding to transferrin.
Oligomerization Partially Explains the Lowering of Aβ42 in Alzheimer’s Disease Cerebrospinal Fluid (2009)

Combining denaturing and non-denaturing quantifications of Abeta42 into an oligomer ratio enables the assessment of Abeta oligomers in biological samples. The increased Abeta42 oligomer ratio for AD and MCI indicates the presence of oligomers in CSF and that the lowering of natively measured Abeta42 is caused by oligomerization.
Molecular Genetics and Epidemiology of Prostate Carcinoma (1999)

I. Introduction A. Prostate carcinoma epidemiology: mortality rates, incidence, and prevalence B. Familial clustering of prostate carcinoma C. Scope of the review II. Somatic Genetic Alterations in Prostate Carcinoma A. Alterations in DNA methylation B. The androgen signaling cascade C. Vitamin D and prostate carcinoma D. Oncogenes E. TSGs F. Metastasis suppressor genes (MSGs) G. Telomerase activity III. Etiology of Familial Clustering of Prostate Carcinoma IV. Human Papillomavirus and Prostate Carcinoma V. Morphological Diversity of Prostate Carcinoma VI. Concluding Remarks
Interaction between CXCR4 and CCL20 Pathways Regulates Tumor Growth (2009)

The chemokine receptor CXCR4 and its ligand CXCL12 is overexpressed in the majority of tumors and is critically involved in the development and metastasis of these tumors. CXCR4 is expressed in malignant tumor cells whereas its ligand SDF-1 (CXCL12) is expressed mainly by cancer associated fibroblasts (CAF). Similarly to CXCR4, the chemokine CCL20 is overexpressed in variety of tumors; however its role and regulation in tumors is not fully clear. Here, we show that the chemokine receptor CXCR4 stimulates the production of the chemokine CCL20 and that CCL20 stimulates the proliferation and adhesion to collagen of various tumor cells. Furthermore, overexpression of CCL20 in tumor cells promotes growth and adhesion in vitro and increased tumor growth and invasiveness in vivo. Moreover, neutralizing antibodies to CCL20 inhibit the in vivo growth of tumors that either overexpress CXCR4 or CCL20 or naturally express CCL20. These results reveal a role for CCL20 in CXCR4-dependent and -independent tumor growth and suggest a therapeutic potential for CCL20 and CCR6 antagonists in the treatment of CXCR4- and CCL20-dependent malignancies.
Challenges and Opportunities in the Chinese Herbal Drug Industry (2007)

Tremendous achievements have been made in Western medicine in the past that provide fast relief of symptoms at the disease sites, particularly under critical conditions. However, some are either ineffective or produce undesirable adverse effects, or are too costly in some complex diseases, especially chronic diseases. On the other hand, traditional medicines strive to focus on the balance of the body in a holistic manner. Traditional medicines are increasing popular in the Western world, as reflected in the name changes from “alternative medicines” to “complementary medicines” or even “integrative medicines.” Traditional Chinese medicines (TCM) have been used in China for more than 2000 yr and have always followed the philosophy and principle of restoration, i.e., the yin and yang (balance of the body). As an important part of the pharmaceutical sector, the Chinese herbal drug industry has made rapid progress over the past decades. This chapter provides a review of its current status, including challenges and opportunities, specifically with regard to modernization and globalization of TCM.
Generation of Functional Radial Glial Cells by Embryonic and Adult Forebrain Neural Stem Cells (2003)

Radial glial cells (RGCs), a transient cell population present only in the developing CNS, function both as precursor cells and as scaffolds to support neuron migration. Their cellular origin, however, is not understood. In the present study, we tested the hypothesis that functional RGCs can be generated by multipotent neural stem cells. Embryonic forebrain neural stem cells were studied in vitro to identify putative signals that promote the generation and differentiation of functional RGCs, determined by their ability to support neuronal migration. Epidermal growth factor receptor signaling was sufficient to regulate both the generation and differentiation of morphologically, antigenically, and functionally defined RGCs. In contrast, fibroblast growth factor-2 promoted the generation of RGCs but was unable to support their differentiation. Although RGCs are not normally present in the adult brain, epidermal growth factor stimulated adult forebrain neural stem cells to generate RGCs in vitro and functional RGCs within the adult forebrain subependyma in vivo. Surprisingly, epidermal growth factor receptor signaling also promoted adult forebrain ependymal cells to dedifferentiate and adopt a radial morphology in vivo. These results suggest that neural stem cells can give rise to RGCs and that RGC-guided neuronal migration can be recapitulated in the adult CNS.
Regression Shrinkage and Selection Via the Lasso (1996)

SUMMARY We propose a new method for estimation in linear models. The ‘lasso’ minimizes the residual sum of squares subject to the sum of the absolute value of the coefficients being less than a constant. Because of the nature of this constraint it tends to produce some coefficients that are exactly 0 and hence gives interpretable models. Our simulation studies suggest that the lasso enjoys some of the favourable properties of both subset selection and ridge regression. It produces interpretable models like subset selection and exhibits the stability of ridge regression. There is also an interesting relationship with recent work in adaptive function estimation by Donoho and Johnstone. The lasso idea is quite general and can be applied in a variety of statistical models: extensions to generalized regression models and tree-based models are briefly described.
Development outreach 7 (1) : a better investment climate for everyone (2005)

Development outreach has asked the leaders of the WDR 2005 team, Warrick P. Smith and Mary C. Hallward-Driemeier to put together the special report featured in this issue in order to provide comments by world renowned specialists on issues raised in the WDR 2005 and expand discussions beyond its parameters. This report opens with an editorial by Warrick P. smith and Mary C. Hallward-Driemeie on the theme of the WDR 2005. Ricardo Hausmann, Lant Pritchett and Dani Rodrik, presents, Initiating a Growth Boom. William Kalema, examines the role of Public-Private Sector Dialog in Uganda's Reform Process. Raj M. Desai and Sanjay Pradhan, offer their views on, Governing the Investment Climate. Daniel Kaufmann, focus on, Click Refresh Button : investment climate reconsidered. Erica Field, talks about, Entitled to Work : informal enterprise in urban Peru. Frances Lund and Caroline Skinner, focus on a South Africa example, Local Government Innovations for the Informal Economy : creating a positive investment climate. Qimiao Fan, Alberto Criscuolo and Iva Ilieva-Hamel, present, Whither SME Policies? Ahmed Galal, discusses Potential Winners & Losers from Business Formalization. Finally, Stefano Scarpetta, discusses, Getting the Best Out of Creative Destruction : productivity growth and job creation
Prior Subspace Analysis for Drum Transcription (2003)

This paper introduces the technique of Prior Subspace Analysis (PSA) as an alternative to Independent Subspace Analysis (ISA) in cases where prior knowledge about the sources to be separated is available. The use of prior knowledge overcomes some of the problems associated with ISA, in particular the problem of estimating the amount of information required for separation. This results in improved robustness for drum transcription purposes. Prior knowledge is incorporated by use of a set of prior frequency subspaces that characterise features of the sources to be extracted. The effectiveness and robustness of PSA is demonstrated by its use in a simple drum transcription algorithm.
High-throughput DNA methylation profiling using universal bead arrays (2006)

We have developed a high-throughput method for analyzing the methylation status of hundreds of preselected genes simultaneously and have applied it to the discovery of methylation signatures that distinguish normal from cancer tissue samples. Through an adaptation of the GoldenGate genotyping assay implemented on a BeadArray platform, the methylation state of 1536 specific CpG sites in 371 genes (one to nine CpG sites per gene) was measured in a single reaction by multiplexed genotyping of 200 ng of bisulfite-treated genomic DNA. The assay was used to obtain a quantitative measure of the methylation level at each CpG site. After validating the assay in cell lines and normal tissues, we analyzed a panel of lung cancer biopsy samples (N = 22) and identified a panel of methylation markers that distinguished lung adenocarcinomas from normal lung tissues with high specificity. These markers were validated in a second sample set (N = 24). These results demonstrate the effectiveness of the method for reliably profiling many CpG sites in parallel for the discovery of informative methylation markers. The technology should prove useful for DNA methylation analyses in large populations, with potential application to the classification and diagnosis of a broad range of cancers and other diseases.
Astrovirus as a possible cause of congenital tremor type AII in piglets? (2014)

The results do not support previous studies identifying porcine circovirus type 2 as the cause of congenital tremor. The demonstration of astrovirus in the brain of piglets suffering from congenital tremor is interesting. However, astrovirus was demonstrated in both healthy and diseased individuals and therefore, further studies are warranted to determine the possible involvement of astrovirus in the pathogenesis of congenital tremor in pigs.
Rescue of Rabies Virus from Cloned cDNA and Identification of the Pathogenicity-Related Gene: Glycoprotein Gene Is Associated with Virulence for Adult Mice (2001)

In order to identify the viral gene related to the pathogenicity of rabies virus, we tried to establish a reverse genetics system of the attenuated RC-HL strain, which causes nonlethal infection in adult mice after intracerebral inoculation. A full-length genome plasmid encoding the complete antigenomic cDNA of the RC-HL strain and helper plasmids containing cDNAs of the complete open reading frame of the N, P, and L genes, respectively, were constructed. After transfection of these plasmids into BHK-21 cells infected with the T7 RNA polymerase-expressing vaccinia virus, infectious rabies virus with almost the same biological properties as those of the wild-type RC-HL strain was rescued. Using this reverse genetics system of the RC-HL strain, we generated a chimeric virus with the open reading frame of the glycoprotein gene from the parent Nishigahara strain, which kills adult mice after intracerebral inoculation, in the background of the RC-HL genome. Since the chimeric virus killed adult mice following intracerebral inoculation, it became evident that the open reading frame of the glycoprotein gene is related to the pathogenicity of the Nishigahara strain for adult mice.
Annexin V-Affinity assay: A review on an apoptosis detection system based on phosphatidylserine exposure (1998)

Apoptosis is a programmed, physiological mode of cell death that plays an important role in tissue homeostasis. Understanding of the basic mechanisms that underlie apoptosis will point to potentially new targets of therapeutic treatment of diseases that show an imbalance between cell proliferation and cell loss. In order to conduct such research, techniques and tools to reliably identify and enumerate death by apoptosis are essential. This review focuses on a novel technique to detect apoptosis by targeting for the loss of phospholipid asymmetry of the plasma membrane. It was recently shown that loss of plasma membrane asymmetry is an early event in apoptosis, independent of the cell type, resulting in the exposure of phosphatidylserine (PS) residues at the outer plasma membrane leaflet. Annexin V was shown to interact strongly and specifically with PS and can be used to detect apoptosis by targeting for the loss of plasma membrane asymmetry. Labeled annexin V can be applied both in flow cytometry and in light microscopy in both vital and fixed material by using appropriate protocols. The annexin V method is an extension to the current available methods. This review describes the basic mechanisms underlying the loss of membrane asymmetry during apoptosis and discusses the novel annexin V-binding assay.
Sequence and structure comparison suggest that methionine aminopeptidase, prolidase, aminopeptidase P, and creatinase share a common fold. (1994)

Amino acid sequence comparison suggests that the structure of Escherichia coli methionine aminopeptidase (EC 3.4.11.18) and the C-terminal domain of Pseudomonas putida creatinase (EC 3.5.3.3) are related. A detailed comparison of the three-dimensional folds of the two enzymes confirms this homology: with an approximately 260-residue chain segment, 218 C alpha atoms of the structures superimpose within 2.5 A; only 41 of these overlapping positions (i.e., 19%) feature identical amino acids in the two protein chains. Notwithstanding this striking correspondence in structure, methionine aminopeptidase binds and is stimulated by Co2+, while creatinase is not a metal-dependent enzyme. Searches of protein data banks using sequence and structure-based profiles reveal other enzymes, including aminopeptidase P (EC 3.4.11.9), prolidase (EC 3.4.13.9), and agropine synthase, that likely share the same "pita-bread" fold common to creatinase and methionine aminopeptidase.
Mechanism of electrospray mass spectrometry. Electrospray as an electrolysis cell (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMechanism of electrospray mass spectrometry. Electrospray as an electrolysis cellArthur T. Blades, Michael G. Ikonomou, and Paul. KebarleCite this: Anal. Chem. 1991, 63, 19, 2109–2114Publication Date (Print):October 1, 1991Publication History Published online1 May 2002Published inissue 1 October 1991https://pubs.acs.org/doi/10.1021/ac00019a009https://doi.org/10.1021/ac00019a009research-articleACS PublicationsRequest reuse permissionsArticle Views2108Altmetric-Citations302LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
The modular phosphorylation and activation of p70s6k (1997)

The activation of p70s6k is accompanied by a complex series of phosphorylation events. In this review we propose a model of activation which divides p70s6k into four functional modules that cooperate in leading to full enzyme activity. In the light of the model, we suggest how candidate effectors of p70s6k activation might function by directing the phosphorylation of specific sites.
The Florey Lecture, 1990 How is the cell division cycle regulated? (1991)

It is argued in this lecture that in most eukaryotic cells onset of mitosis is coupled to attainment of a critical cell mass and to completion of the previous S-phase. In fission yeast these controls operate through a regulatory gene network that activates the p34cdc2 protein kinase at mitosis. This is brought about by dephosphorylation of a tyrosine residue located in the ATP binding site of the kinase. The p34cdc2 protein kinase is also important for regulating the onset of mitosis in vertebrate cells suggesting that there is a universal control regulating mitosis in all eukaryotic cells.
Reprogramming Tumor-Associated Dendritic Cells In Vivo Using miRNA Mimetics Triggers Protective Immunity against Ovarian Cancer (2012)

Modulating the activity of miRNAs provides opportunities for novel cancer interventions. However, low bioavailability and poor cellular uptake are major challenges for delivering miRNA mimetics specifically to tumor cells. Here, we took advantage of the spontaneous enhanced endocytic activity of ovarian cancer-associated dendritic cells (DC) to selectively supplement the immunostimulatory miRNA miR-155. In vivo processing of nanoparticles carrying oligonucleotide duplexes mimicking the bulged structure of endogenous pre-miRNA (but not siRNA-like oligonucleotides) dramatically augmented miR-155 activity without saturating the RNA-induced silencing complex. Endogenous processing of synthetic miR-155 favored Ago2 and, to a lesser extent, Ago4 loading, resulting in genome-wide transcriptional changes that included silencing of multiple immunosuppressive mediators. Correspondingly, tumor-infiltrating DCs were transformed from immunosuppressive to highly immunostimulatory cells capable of triggering potent antitumor responses that abrogated the progression of established ovarian cancers. Our results show both the feasibility and therapeutic potential of supplementing/replenishing miRNAs in vivo using nonviral approaches to boost protective immunity against lethal tumors. Thus, we provide a platform, an optimized design, and a mechanistic rationale for the clinical testing of nonviral miRNA mimetics.