gebhart/patrepeval huggingface dataset:
Gene Expression Pattern Associated with Radiotherapy Sensitivity in Cervical Cancer (2006)

This study shows that such an approach has the potential to differentiate tumor radiosensitivity, although confirmation of such a pattern using other larger independent datasets is necessary before firm conclusions can be drawn.
ADOPTIVE IMMUNOTHERAPY OF METASTATIC B16 MELANOMA WITH ALLOGENEIC IMMUNE CELLS SENSITIZED TO MINOR HISTOCOMPATIBILITY ANTIGENS (1985)

Host mice bearing pulmonary metastases of B16 melanoma were treated by adoptive immunotherapy with allogeneic donor lymphocytes. Rejection of the allogeneic donor cells by the host was delayed by pretreatment immunosuppression of the host with cyclophosphamide and selection of donors that were matched at the major histocompatibility complex (MHC) but disparate for background minor histocompatibility genes. Adoptively transferred normal nonimmune donor cells exhibited no therapeutic activity. However, allogeneic MHC-matched donor cells that were primed in vivo and secondarily sensitized in vitro to host minor histocompatibility antigens expressed on normal lymphocytes were cytotoxic to B16 tumor cells in vitro and mediated a dose-dependent antitumor effect in vivo following i.v. infusion. The therapeutic activity of sensitized allogeneic cells, which presumably reflected recognition of minor histocompatibility antigens expressed both on normal host tissues and on malignant B16 tumor cells, was not associated with any detectable toxicity to these transiently immunosuppressed tumor-bearing hosts.
Pyrosequencing as an Alternative to Single-Strand Conformation Polymorphism Analysis for Detection of N-ras Mutations in Human Melanoma Metastases (2002)

Pyrosequencing is an attractive alternative to SSCP analysis for N-ras mutation detection in malignant melanoma tumor samples because it displays the same sensitivity and accuracy as SSCP analysis and is simple and rapid.
Pak-1 Expression Increases with Progression of Colorectal Carcinomas to Metastasis (2004)

This study demonstrates that Pak-1 expression is increased significantly with malignant progression of human colorectal carcinoma. These data, along with numerous functional studies demonstrating a central role for Pak-1 activity in tumor invasiveness and motility, implicate Pak-1 as an exciting target for therapy of colorectal carcinoma.
An Assessment of Literacy Trends, Past and Present (1996)

Preview this article: An Assessment of Literacy Trends, Past and Present, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/rte/30/3/researchintheteachingofenglish15311-1.gif
Environment‐Sensitive Fluorescent Turn‐On Probes Targeting Hydrophobic Ligand‐Binding Domains for Selective Protein Detection (2013)

Bind and shine: An approach for the selective detection of both enzymes and non-enzymatic proteins using an environment-sensitive fluorescent turn-on probe is described (see scheme). This approach targets the hydrophobic ligand-binding domain of the target protein to trigger the fluorescence turn-on and was shown to be specific for the targeted protein. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Therapeutic advances for blocking heterotopic ossification in fibrodysplasia ossificans progressiva (2018)

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease in which heterotopic bone forms in muscle and soft tissue, leading to joint dysfunction and significant disability. FOP is progressive and many patients are wheelchair-bound by the 3rd decade of life. FOP is caused by an activating mutation in the ACVR1 gene, which encodes the activin A Type 1 receptor. Aberrant signalling through this receptor leads to abnormal activation of the pSMAD 1/5/8 pathway and triggers the formation of bone outside of the skeleton. There is no curative therapy for FOP; however, exciting advances in novel therapies have developed recently. Here, we review the clinical and translational pharmacology of three drugs that are currently in clinical trials (palovarotene, REGN 2477 and rapamycin) as well as other emerging treatment strategies for FOP.
Polyamides as Artificial Regulators of Gene Expression (1997)

Interference with the transcription of specific genes in vivo can be achieved with artificial, low molecular weight pyrrole-imidazole polyamides, as shown by recent studies by Gottesfeld, Dervan et al. This is possible because these ligands are capable of binding with high affinity and specificity to predetermined DNA sequences in the minor groove of double-stranded DNA (see schematic representation on the right; gray: pyrrole, black: imidazole units).
Nanocoatings onto Arteries via Layer-by-Layer Deposition:  Toward the in Vivo Repair of Damaged Blood Vessels (2003)

The deposition of polysaccharide-based self-assembled nanocoatings onto damaged arteries is described as a means not only to protect a damaged artery against thrombogenesis, but also to control the healing processes by incorporating biologically active components within the multilayer. As shown by confocal microscopy, the polysaccharide multilayer was retained on the artery in physiological condition and prevented platelet adhesion. Diffusion of the polysaccharides within the artery was also observed and may be used to efficiently target the vascular wall. The NO-precursor l-arginine was used a drug model and incorporated within the self-assembled layers.
Preclinical Efficacy and Safety Comparison of CD3 Bispecific and ADC Modalities Targeting BCMA for the Treatment of Multiple Myeloma (2019)

The restricted expression pattern of B-cell maturation antigen (BCMA) makes it an ideal tumor-associated antigen (TAA) for the treatment of myeloma. BCMA has been targeted by both CD3 bispecific antibody and antibody-drug conjugate (ADC) modalities, but a true comparison of modalities has yet to be performed. Here we utilized a single BCMA antibody to develop and characterize both a CD3 bispecific and 2 ADC formats (cleavable and noncleavable) and compared activity both <i>in vitro</i> and <i>in vivo</i> with the aim of generating an optimal therapeutic. Antibody affinity, but not epitope was influential in drug activity and hence a high-affinity BCMA antibody was selected. Both the bispecific and ADCs were potent <i>in vitro</i> and <i>in vivo</i>, causing dose-dependent cell killing of myeloma cell lines and tumor regression in orthotopic myeloma xenograft models. Primary patient cells were effectively lysed by both CD3 bispecific and ADCs, with the bispecific demonstrating improved potency, maximal cell killing, and consistency across patients. Safety was evaluated in cynomolgus monkey toxicity studies and both modalities were active based on on-target elimination of B lineage cells. Distinct nonclinical toxicity profiles were seen for the bispecific and ADC modalities. When taken together, results from this comparison of BCMA CD3 bispecific and ADC modalities suggest better efficacy and an improved toxicity profile might be achieved with the bispecific modality. This led to the advancement of a bispecific candidate into phase I clinical trials.
Nucleic acid hybridization for measurement of effects of antiviral compounds on human cytomegalovirus DNA replication (1983)

A nucleic acid hybridization technique has been developed to study the effect of different antiviral compounds on the replication of human cytomegalovirus in vitro. One laboratory strain of human cytomegalovirus, Ad. 169, and six clinical isolates were studied. Doses needed for 50% inhibition of viral DNA replication were calculated for foscarnet, acyclovir, and arabinosyladenine. The mean 50% inhibition dose values obtained were 179 microM for foscarnet, 82 microM for acyclovir, and 44 microM for arabinosyladenine. This method yields values that agree with earlier reports, and it offers great advantages over usual methods to date for studying inhibition of viral DNA replication.
Rheumatoid arthritis treated with tenidap and piroxicam clinical associations with cytokine modulation by tenidap (1995)

Tenidap was differentiated from piroxicam by lower levels of acute-phase proteins, ESR, and IL-6 after tenidap treatment. These treatment differences were significantly correlated with clinical parameters.
DNA Adducts of cis-Diamminedichloroplatinum(II) and Its Trans Isomer Inhibit RNA Polymerase II Differentially in Vivo (1995)

The effects of cis-diamminedichloroplatinum(II) (cis-DDP) and trans-DDP adducts on mammalian transcription in vivo have been investigated. A plasmid containing the beta-galactosidase (beta-gal) reporter gene was modified with either of the two platinum compounds and transfected into human or hamster cell lines. A 2-3 fold higher level of transcription was observed in both cell lines from plasmids containing trans-DDP adducts as compared to plasmids modified by cis-DDP. This difference in transcriptional activity was not decreased in human and rodent nucleotide excision repair deficient cell lines, indicating that more efficient excision repair of the trans-DDP adducts was not the cause of its lower ability to block transcription in this assay. For this conclusion to be valid, it is assumed that trans-DDP adducts are repaired primarily by the nucleotide excision repair pathway, as is the case with the adducts of cis-DDP. The possibility that trans-DDP adducts are preferentially bypassed by RNA polymerase was examined by monitoring the elongation of beta-gal mRNA on damaged templates in vivo. Nascent beta-gal mRNA transcripts were recovered from excision repair deficient xeroderma pigmentosum A cells transfected with platinated plasmids, and the extent of RNA synthesis was measured by using ribonuclease protection. Fourfold more trans-DDP than cis-DDP adducts were required to inhibit transcription elongation by 63%. RNA polymerase II bypassed cis- and trans-DDP DNA adducts with efficiencies of 0-16% and 60-70%, respectively. These data provide insight into the differential toxicity of the two platinum isomers.
Photodynamic inactivation of retrovirus by benzoporphyrin derivative: a feline leukemia virus model (1992)

The ability of a photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA), and either broad-spectrum (400-1200 nm) or narrow-band (600-700 nm) red light to kill feline leukemia virus (FeLV) and FeLV-infected cat T cells (cell line 3201) was investigated in culture medium containing fetal calf serum and in blood from infected cats. A molecular clone of FeLV, 61E, is minimally pathogenic and productively infects 3201 cells while causing no change in rate of cell division, viability, or size. Active virus (either free or within infected cells) was quantified by using a limiting dilution assay that involved cocultivation of test samples with naive 3201 cells, after which either the polymerase chain reaction or a reverse transcriptase assay was used to detect the presence of virus. It was shown that 61E-infected T cells in culture were slightly more sensitive to photodynamic killing than were uninfected cells. Infected cells and free virus were eliminated from whole blood taken from infected cats by using 4 micrograms per mL of BPD-MA and 40 J per cm2 of red light. These results correlate well with previous results with BPD-MA and vesicular stomatitis virus in whole human blood and suggest that this photosensitizer is a promising agent for the elimination of retroviruses that are either free or located within infected cells in blood.
Investigating Bacterial N-Linked Glycosylation:  Synthesis and Glycosyl Acceptor Activity of the Undecaprenyl Pyrophosphate-Linked Bacillosamine (2005)

The chemical synthesis and biological activity of undecaprenyl pyrophosphate bacillosamine (Und-PP-Bac), an obligatory intermediate in the asparagine-linked glycosylation pathway of Campylobacter jejuni, are reported. The key transformation involves the coupling of bacillosamine phosphate and undecaprenyl phosphate. The synthetic Und-PP-Bac can be used to investigate the activity of the enzyme PglA, which catalyzes the first glycosyl transfer in substrate biosynthesis for N-linked protein glycosylation in the pathogenic gram-negative bacterium. The availability of this synthetic substrate makes it possible to access polyprenyl-linked oligosaccharides, such as the GalNAc-alpha-1,3-bacillosamine-alpha-1-PP-Und intermediate, that will enable exploration of the remaining enzymes in the prokaryotic glycosylation pathway. Study of the bacterial glycosylation system will provide insight into the corresponding eukaryotic process, which is currently poorly understood.
A case study of the reproducibility of transcriptional reporter cell-based RNAi screens in Drosophila (2007)

Off-target effects have been demonstrated to be a major source of false-positives in RNA interference (RNAi) high-throughput screens. In this study, we re-assess the previously published transcriptional reporter-based whole-genome RNAi screens for the Wingless and Hedgehog signaling pathways using second generation double-stranded RNA libraries. Furthermore, we investigate other factors that may influence the outcome of such screens, including cell-type specificity, robustness of reporters, and assay normalization, which determine the efficacy of RNAi-knockdown of target genes.
Cloning, Expression, and Sequence Conservation of Pathogenesis-Related Gene Transcripts of Potato (1989)

Treatment of potato tuber disks with arachidonic acid elicits the accumulation of several mRNAs. cDNA clones corresponding to two of these mRNAs were isolated and characterized. Nucleotide sequence analysis reveals that both clones (pSTH-2 and pSTH-21) contain an open-reading frame coding for a 155-amino acid polypeptide. The polypeptides encoded by the two clones differ by only six amino acids and show a high degree of similarity with PR protein sequences from pea (approximately 42%) and parsley (approximately 37%). mRNAs corresponding to the two potato cDNA clones also accumulate in Solanum chacoense and in tomato following elicitor treatment. Maximum accumulation of the mRNAs corresponding to the two cDNA clones is reached 24 hr after elicitor treatment of the tuber disks. pSTH-2-related mRNAs also accumulate in tubers after wounding or treatment with eicosapentaenoic acid and are detected in potato and tomato leaves treated with a Phytophthora infestans mycelium homogenate. The presence of these conserved genes in species from three plant families and the similarity of their induction pattern suggest an important function during the plant defense response.
A new viscosupplement based on partially hydrophobic hyaluronic acid: A comparative study (2011)

A novel partially hydrophobized derivative of hyaluronic acid (HYADD® 4), containing a low number of C16 side-chains per polysaccharide backbone, provides injectable hydrogels stabilized by side-chain hydrophobic interactions. The rheological properties of Hymovis®, a physical hydrogel based on the hyaluronic acid derivative HYADD® 4, were evaluated using as reference a solution of the parent natural polysaccharide, hyaluronic acid. The rheological measurements were performed both in flow and oscillation regimes at the physiological frequency values of the knee, typically spanning the range from 0.5 Hz (walking frequency) to 3 Hz (running frequency). Moreover, the viscoelastic features of Hymovis® were compared with the market-available viscosupplementation products in view of its use in joint diseases.The different behavior of the investigated materials in crossover frequency measurements and in structure recovery experiments can be explained on the basis of the structural and dynamic properties of the polymeric systems.
Mechanistic Studies of Antibody-Mediated Clearance of Tau Aggregates Using an ex vivo Brain Slice Model (2011)

Recent studies have shown that immunotherapy clears amyloid beta (Aβ) plaques and reduces Aβ levels in mouse models of Alzheimer's disease (AD), as well as in AD patients. Tangle pathology is also relevant for the neurodegeneration in AD, and our studies have shown that active immunization with an AD related phospho-tau peptide reduces aggregated tau within the brain and slows the progression of tauopathy-induced behavioral impairments. Thus, clearance of neurofibrillary tangles and/or their precursors may reduce synaptic and neuronal loss associated with AD and other tauopathies. So far the mechanisms involved in antibody-mediated clearance of tau pathology are yet to be elucidated. In this study we have used a mouse brain slice model to examine the uptake and localization of FITC labeled anti-tau antibodies. Confocal microscopy analysis showed that the FITC labeled anti-tau antibody co-stained with phosphorylated tau, had a perinuclear appearance and co-localized with markers of the endosomal/lysosomal pathway. Additionally, tau and FITC-IgG were found together in an enriched lysosome fraction. In summary, antibody-mediated clearance of intracellular tau aggregates appears to occur via the lysosomal pathway.
Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer’s-like pathology (2016)

The proliferation and activation of microglial cells is a hallmark of several neurodegenerative conditions. This mechanism is regulated by the activation of the colony-stimulating factor 1 receptor (CSF1R), thus providing a target that may prevent the progression of conditions such as Alzheimer's disease. However, the study of microglial proliferation in Alzheimer's disease and validation of the efficacy of CSF1R-inhibiting strategies have not yet been reported. In this study we found increased proliferation of microglial cells in human Alzheimer's disease, in line with an increased upregulation of the CSF1R-dependent pro-mitogenic cascade, correlating with disease severity. Using a transgenic model of Alzheimer's-like pathology (APPswe, PSEN1dE9; APP/PS1 mice) we define a CSF1R-dependent progressive increase in microglial proliferation, in the proximity of amyloid-β plaques. Prolonged inhibition of CSF1R in APP/PS1 mice by an orally available tyrosine kinase inhibitor (GW2580) resulted in the blockade of microglial proliferation and the shifting of the microglial inflammatory profile to an anti-inflammatory phenotype. Pharmacological targeting of CSF1R in APP/PS1 mice resulted in an improved performance in memory and behavioural tasks and a prevention of synaptic degeneration, although these changes were not correlated with a change in the number of amyloid-β plaques. Our results provide the first proof of the efficacy of CSF1R inhibition in models of Alzheimer's disease, and validate the application of a therapeutic strategy aimed at modifying CSF1R activation as a promising approach to tackle microglial activation and the progression of Alzheimer's disease.
Confidence-scoring post-processing for off-line handwritten-character recognition verification (2004)

We apply confidence-scoring techniques to verify the output of an off-line handwritten-character recognizer. We evaluate a variety of scoring functions, including likelihood ratios and estimated posterior probabilities of correctness, in a post-processing mode, to generate confidence scores. Using the post-processor in conjunction with a neural-net-based recognizer, on mixed-case letters, receiver-operating-characteristic (ROC) curves reveal that our post-processor is able to reject correctly 90% of recognizer errors while only falsely rejecting 18.6% of correctly-recognized letters. For isolated-digit recognition, we achieve a correct rejection rate of 95% while keeping false rejection down to 8.7%.
Vasopressor therapy for hypotension due to epidural anesthesia for cesarean section (1988)

Maternal hemodynamic changes and neonatal acid-base status were assessed in 127 healthy patients undergoing elective cesarean section under epidural anesthesia. An impedance cardiograph was used to measure stroke volume (SV), ejection fraction (EF) and end-diastolic volume (EDV). In addition, neonatal umbilical venous and arterial PO2, PCO2, pH, base excess, lactate, pyruvate, excess lactate, and L/P ratio were measured at birth. Patients were divided into three groups. Group 1 (n = 53) required no vasopressor (normotensive controls). In Group 2 (n = 37), mean blood pressure (BP) decreased from 90 mmHg (13.3 kPa). In Group 3 (n = 37), BP decreased from 83 mmHg to 62 mmHg (11.1 to 8.2 kPa), and phenylephrine was administered in 100 micrograms increments to maintain systolic BP greater than 100 mmHg (13.3 kPa). In Groups 2 and 3 the SV and EDV decreased 43% and 33% respectively when hypotension developed. Both vasopressors restored BP, SV and EDV to near baseline values. Neonatal Apgar scores and acid-base profiles were not significantly different among the three groups of neonates, nor were they different between the two hypotensive groups. It is concluded that: 1) transient maternal hypotension does not affect neonatal acid-base status; 2) both ephedrine and phenylephrine increase cardiac preload; and 3) an alpha agent like phenylephrine does not cause fetal acidosis when used for treating maternal hypotension.
Soluble HLA-G1 inhibits angiogenesis through an apoptotic pathway and by direct binding to CD160 receptor expressed by endothelial cells (2006)

HLA-G is a major histocompatibility complex class Ib molecule whose constitutive tissue distribution is restricted mainly to trophoblast cells at the maternal-fetal interface during pregnancy. In this study, we demonstrated the ability of the soluble HLA-G1 (sHLA-G1) isoform to inhibit fibroblast growth factor-2 (FGF2)-induced capillary-like tubule formation. Using a rabbit corneal neovascularization model, we further showed that sHLA-G1 inhibits FGF2-induced angiogenesis in vivo. We also demonstrated that sHLA-G1 induces endothelial cell apoptosis through binding to BY55/CD160, a glycosylphosphatidylinositolanchored receptor expressed by endothelial cells. Furthermore, we showed that the specific CL1-R2 anti-CD160 monoclonal antibody mimics sHLA-G1-mediated inhibition of endothelial cell tube formation and induction of apoptosis. Thus, the engagement of CD160 in endothelial cells may be essential for the inhibition of angiogenesis. sHLA-G1/CD160-mediated antiangiogenic property may participate in the vascular remodeling of maternal spiral arteries during pregnancy, and, given that we found that CD160 is strongly expressed in the vasculature of a murine tumor, it offers an attractive therapeutic target for preventing pathologic neovascularization.
Gut Microbiota in Human Adults with Type 2 Diabetes Differs from Non-Diabetic Adults (2010)

The results of this study indicate that type 2 diabetes in humans is associated with compositional changes in intestinal microbiota. The level of glucose tolerance should be considered when linking microbiota with metabolic diseases such as obesity and developing strategies to control metabolic diseases by modifying the gut microbiota.