gebhart/patrepeval huggingface dataset:
Single circulating tumor cell sequencing as an advanced tool in cancer management (2015)

Circulating tumor cells (CTCs) shed by the primary tumor and metastases are considered a real-time 'liquid biopsy', reflecting the disease complexity that evolves during progression, showing in its late stages different genetic, epigenetic and expression features. Consequently, heterogeneity and development of characteristic features upon disease progression are the two main goals that emerging technologies should account for in view of a clinical application. Single-cell analysis, now possible due to technological advances, may help elucidate tumor heterogeneity at the CTC level. This review focuses on the necessary steps for the analysis of CTCs at the single-cell level. A concise overview is given on the alternative methods referring in particular to studies on the mutational status of single CTCs from cancer patients.
A single amino acid substitution in the alpha 3 domain of an H-2 class I molecule abrogates reactivity with CTL. (1987)

We previously described a somatic cell expressing a variant H-2Dd molecule that did not serve as a target for alloreactive anti-Dd CTL. The mutant cell line had been isolated by its failure to express a serological epitope present on the H-2Dd alpha 3 domain. In the present study the alpha 3 domain of the Dd molecule of this somatic cell variant was sequenced and a single nucleotide change resulting in a glutamic acid to lysine substitution at residue 227 was identified. This change was reproduced in the cloned H-2Dd gene by oligonucleotide-directed mutagenesis. Cells transfected with this mutant gene were not killed by anti-H-2Dd CTL. Because previous studies using hybrid H-2 class I molecules had established that the alpha 3 domain does not express allele-specific determinants recognized by CTL, our results raise the possibility that residues in the alpha 3 domain of H-2 class I molecules are critical for CTL recognition and constitute a conserved (or monomorphic) determinant recognized by CTL.
T-cell function in newborn mice and humans (1999)

Neonates mount poor immune responses, and it has been assumed that neonatal T cells differ qualitatively from adult T cells. Here, Becky Adkins discusses this issue in the light of recent data indicating that T cells in neonates are developmentally mature in their capacity to mount protective Th1-type and cytotoxic T lymphocyte responses.
Extreme Acoustic Metamaterial by Coiling Up Space (2012)

We show that by coiling up space using curled perforations, a two-dimensional acoustic metamaterial can be constructed to give a frequency dispersive spectrum of extreme constitutive parameters, including double negativity, a density near zero, and a large refractive index. Such an approach has band foldings at the effective medium regime without using local resonating subwavelength structures, while the principle can be easily generalized to three dimensions. Negative refraction with a double negative prism and tunneling with a density-near-zero metamaterial are numerically demonstrated.
Handbook of therapeutic antibodies : technologies, emerging developments and approved therapeutics (2010)

Section I: Technologies Foreword A Greeting from the Editor PART 0: INTRODUCTION Therapeutic Antibodies - From Past to Future PART I: SELECTING AND SHAPING THE ANTIBODY MOLECULE Selection strategies I: Monoclonal Antibodies Selection strategies II: Antibody Phage Display Selection strategies III: Transgenic Mice Bioinformatic Tools for Antibody Engineering Molecular Engineering I: Humanization Molecular Engineering II: Affinity Maturation Molecular Engineering III: Fc Engineering PART II: THE WAY INTO THE CLINIC Production and Downstream Processing Pharmaceutical Formulation and Clinical Application Immunogenicity of Antibody Therapeutics Regulatory Considerations Intellectual Property Issues Section II: Emerging Developments PART III: BEYOND IGG: MODIFIED ANTIBODIES Immunoscintigraphy and Radioimmunotherapy Bispecific Antibodies Immunotoxins / Targeted RNases PART IV: EMERGING CONCEPTS Automation of Selection and Engineering Emerging Technologies for Antibody Selection Emerging Alternative Production Systems Non-Antibody Scaffolds Emerging Therapeutic Concepts I: ADEPT Emerging Therapeutic Concepts II: Nanotechnology Emerging Therapeutic Concepts III:Cell-bound antibodies Emerging Therapeutic Concepts IV:Anti-idiotypic Antibodies PART V: ONGOING CLINICAL STUDIES: Antibodies in Phase I/II/III: Cancer Therapy Antibodies in Phase I/II/III: Targeting TNF Section III: APPROVED THERAPEUTICS Adalimumab (Humira) Alemtuzumab (Mabcampath) Bevacizumab (Avastin) Cetuximab (Erbitux) Efalizumab (Raptiva) Fanolesomab/Technetium99m (Neutrospec) Gemtuzumab Ozogamicin (Mylotarg) Infliximab (Remicade) Muromonab (Orthoclone) Natalizumab (Tysabri) Omalizumab (Xolair) Palivizumab (Synagis) Rituximab (Rituxan) Trastuzumab (Herceptin) Overview: Abciximab, Arcitumomab, Basiliximab, Capromab, Cotara, Daclizumab, Edrecolomab, Igovomab, Nofetumomab, Satumomab, Sulesomab, Tositumomab and Votumumab Yttrium-90 Ibritumomab Tiuxetan (Zevalin)
Flavopiridol Inhibits P-TEFb and Blocks HIV-1 Replication (2000)

Flavopiridol (L86-8275, HMR1275) is a cyclin-dependent kinase (Cdk) inhibitor that is in clinical trials as a cancer treatment because of its antiproliferative properties. We found that the flavonoid potently inhibited transcription by RNA polymerase II in vitro by blocking the transition into productive elongation, a step controlled by P-TEFb. The ability of P-TEFb to phosphorylate the carboxyl-terminal domain of the large subunit of RNA polymerase II was inhibited by flavopiridol with a K(i) of 3 nm. Interestingly, the drug was not competitive with ATP. P-TEFb composed of Cdk9 and cyclin T1 is a required cellular cofactor for the human immunodeficiency virus (HIV-1) transactivator, Tat. Consistent with its ability to inhibit P-TEFb, flavopiridol blocked Tat transactivation of the viral promoter in vitro. Furthermore, flavopiridol blocked HIV-1 replication in both single-round and viral spread assays with an IC(50) of less than 10 nm.
The structure and function of membrane protein photosynthetic reaction center (1990)

The three dimensional structure of the photosynthetic reaction center from Rhodobacter (Rb.) sphaeroides has been determined using x-ray diffraction technique. It has 11 membrane spanning helixes, five each from the L and M subunit and one from the H subunit. There is a pseudo-twofold symmetry between the L and M subunits and their amino acid sequences have some similarity. The pigment components, which are located at the hydrophobic core of the reaction center also have this symmetry. We confirmed that two bacteriochlorophylls have a predicted conformation called a special pair.'' The nonheme iron is liganded with four histidines and one glutamic acid. 13 refs., 2 figs.
The antineoplastic bryostatins affect human basophils and mast cells differently (1995)

Bryostatins, macrocyclic lactones from the marine bryozoan Bugula neritina, are potent antineoplastic agents and multi-potential stimulators of immune cells. We have examined the effects of bryostatins on mediator release from human basophilic leukocytes and human tissue mast cells. Bryostatins 1, 2, and 5 (10 to 3,000 nmol/L) induced histamine secretion from purified and unpurified peripheral blood basophils, whereas they caused no release of peptide-leukotriene C4 from these cells. The rate of histamine release caused by bryostatin 1 was slower than that caused by anti-IgE (t1/2 +/- SEM = 38.2 +/- 4.7 minutes v 8.9 +/- 0.2 minutes; P < .01), whereas the temperature dependence was similar (optimum release at 37 degrees C, approximately 30% less at 30 degrees C, and no release at 22 degrees C or 4 degrees C). The addition of increasing concentrations of extracellular Ca2+ to the medium caused histamine release in the presence of bryostatins. Subeffective concentrations of bryostatins and anti-IgE produced a synergistic effect on histamine release from basophils. Staurosporine, chelerythrine, and calphostin C (0.1 to 10 nmol/L), which are protein kinase C inhibitors, inhibited the histamine secretion activated by bryostatin 1 and tetradecanoylphorbol-acetate (TPA). Preincubation with granulocyte-monocyte colony-stimulating factor (GM-CSF; 1 and 5 nmol/L) and interleukin-3 (IL-3; 10 ng/mL) potentiated the activation of human basophils induced by bryostatin 1. Neither bryostatin 1 nor bryostatin 2 induced the release of histamine from mast cells isolated from human lung or skin tissues. However, brief (10 minutes) preincubation with bryostatin 1 (3 to 300 nmol/L) potently inhibited the histamine secretion induced by anti-IgE from skin or lung mast cells. Bryostatin 1 was a more potent (by approximately 30 times) inhibitor of IgE-mediated histamine release than was TPA. The heterogeneous effects exerted by bryostatins on human basophils and mast cells can be of interest for those designing therapeutic trials using these agents.
EB3 Regulates Microtubule Dynamics at the Cell Cortex and Is Required for Myoblast Elongation and Fusion (2007)

During muscle differentiation, myoblasts elongate and fuse into syncytial myotubes [1]. An early event during this process is the remodeling of the microtubule cytoskeleton, involving disassembly of the centrosome and, crucially, the alignment of microtubules into a parallel array along the long axis of the cell [2-5]. To further our understanding on how microtubules support myogenic differentiation, we analyzed the role of EB1-related microtubule-plus-end-binding proteins. We demonstrate that EB3 [6] is specifically upregulated upon myogenic differentiation and that knockdown of EB3, but not that of EB1, prevents myoblast elongation and fusion into myotubes. EB3-depleted cells show disorganized microtubules and fail to stabilize polarized membrane protrusions. Using live-cell imaging, we show that EB3 is necessary for the regulation of microtubule dynamics and microtubule capture at the cell cortex. Expression of EB1/EB3 chimeras on an EB3-depletion background revealed that myoblast fusion depends on two specific amino acids in the calponin-like domain of EB3, whereas the interaction sites with Clip-170 and CLASPs are dispensable. Our results suggest that EB3-mediated microtubule regulation at the cell cortex is a crucial step during myogenic differentiation and might be a general mechanism in polarized cell elongation.
Induction of immune responsiveness in a genetically low‐responsive tumor‐host combination by chemical modification of the immunogen (1976)

Trinitrophenylated Moloney virus-induced YAC cells induced a higher cytotoxic antibody response and better protection against small tumor cell doses in syngeneic, low-responsive strain A mice than nonmodified YAC cells that had been inactivated by irradiation or mitomycin C treatment. The results indicated that genetically determined low responsiveness to a virally induced antigen can be overcome, at least to some extent, by coupling the immunizing cells to a strong immunogenic hapten.
Detection of Loss of Heterozygosityat Microsatellite Loci in Esophageal Squamous-Cell Carcinoma (1999)

Microsatellite alterations at 3 genetic loci (chromosomes 2p, 3p and 17p) were analyzed in 25 tumors (20 primary tumors and 5 metastatic lymph nodes) from 20 patients after surgical treatment for esophageal cancer. DNA samples from tumors were compared with control DNA from lymphocytes obtained from the peripheral blood of the individual patients. Microsatellite alterations [microsatellite instability (MSI) and loss of heterozygosity (LOH)] were detected in 15% of 20 primary tumors with marker D2S123 (chromosome 2p), 55% with marker D3S1067 (chromosome 3p) and 50% with marker TP53 (chromosome 17p). The 3-year disease-free survival rate of the 10 patients who had tumors without alterations or with an alteration at only 1 of 3 microsatellite loci was 75% and it was better than that of the 10 patients who had tumors with alterations at 2 or 3 microsatellite loci (48%, p = 0.049). This finding suggests that esophageal cancer with alterations at multiple microsatellite loci might have strong malignant potential. However, MSI was only detected in one of 20 patients, which suggests that MSI might not play an important role in the development of this cancer. Three of 5 metastatic lymph nodes showed no LOH even though primary tumors of these patients exhibited LOH with 1 or 2 markers, and 1 metastatic lymph node had LOH that was detected with D3S1067 even though the primary tumor of this patient had no LOH with all markers. Thus, clonal heterogeneity might exist in esophageal squamous-cell carcinomas.
Inability of Single Carrier Tunneling Barriers to Give Subthermal Subthreshold Swings in MOSFETs (2010)

A simple potential mapping is used to show that tunneling through a single barrier, as in Schottky-barrier tunneling or source-to-drain tunneling in MOSFETs, cannot give rise to subthreshold swings below the thermionic limit (60 mV/decade at room temperature). While cognizant of the difficulty of proving a negative, it is thus highly unlikely that Schottky-barrier tunneling alone can result in reported instances of subthreshold swings that are less than 60 mV/decade.
The Ndc80p Complex from Saccharomyces cerevisiae Contains Conserved Centromere Components and Has a Function in Chromosome Segregation (2001)

We have purified a complex from Saccharomyces cerevisiae containing the spindle components Ndc80p, Nuf2p, Spc25p, and Spc24p. Temperature-sensitive mutants in NDC80, SPC25, and SPC24 show defects in chromosome segregation. In spc24-1 cells, green fluorescence protein (GFP)-labeled centromeres fail to split during spindle elongation, and in addition some centromeres may detach from the spindle. Chromatin immunoprecipitation assays show an association of all four components of the complex with the yeast centromere. Homologues of Ndc80p, Nuf2p, and Spc24p were found in Schizosaccharomyces pombe and GFP tagging showed they were located at the centromere. A human homologue of Nuf2p was identified in the expressed sequence tag database. Immunofluorescent staining with anti-human Nuf2p and with anti-HEC, the human homologue of Ndc80p, showed that both proteins are at the centromeres of mitotic HeLa cells. Thus the Ndc80p complex contains centromere-associated components conserved between yeasts and vertebrates.
Separation, Identification, and Characterization of Microorganisms by Capillary Electrophoresis (2003)

The use of capillary electrophoresis (CE) for the analysis, identification, and characterization of microorganisms has been gaining in popularity. The advantages of CE, such as small sample requirements, minimal sample preparation, rapid and simultaneous analysis, ease of quantitation and identification, and viability assessment, make it an attractive technique for the analysis of microbial analytes. As this instrumental method has evolved, higher peak efficiencies have been achieved by optimizing CE conditions, such as pH, ionic strength, and polymer additive concentration. Experimental improvements have allowed better quantitation and more accurate results. Many practical applications of this technique have been investigated. Viability and identification of microbes can be accomplished in a single analysis. This is useful for evaluation of microbial analytes in consumer products. Diagnosis of microbe-based diseases is now possible, in some cases, without the need for culture methods. Microbe-molecule, virus-antibody, or bacteria-antibiotic interactions can be monitored using CE, allowing for the screening of possible drug candidates. Fermentation can be monitored using this system. This instrumental approach can be adapted to many different applications, including assessing the viability of sperm cells. Progress has been made in the development of microelectrophoresis instrumentation. These advances will eventually allow the development of small, dedicated devices for the rapid, repetitive analyses of specific microbial samples. Although these methods may never fully replace traditional approaches, they are proving to be a valuable addition to the collection of techniques used to analyze, quantitate, and characterize microbes. This review outlines the recent developments in this rapidly growing field.
Detection of Giardia lamblia,Entamoeba histolytica/Entamoeba dispar, andCryptosporidium parvum Antigens in Human Fecal Specimens Using the Triage Parasite Panel Enzyme Immunoassay (2000)

The Triage parasite panel (BIOSITE Diagnostics, San Diego, Calif.) is a new qualitative enzyme immunoassay (EIA) panel for the detection of Giardia lamblia , Entamoeba histolytica / E. dispar , and Cryptosporidium parvum in fresh or fresh, frozen, unfixed human fecal specimens. By using specific antibodies, antigens specific for these organisms are captured and immobilized on a membrane. Panel performance was evaluated with known positive and negative stool specimens (a total of 444 specimens) that were tested by the standard ova and parasite (O&amp;P) examination as the “gold standard,” including staining with both trichrome and modified acid-fast stains. Specimens with discrepant results between the reference and Triage methods were retested by a different method, either EIA or immunofluorescence. A number of samples with discrepant results with the Triage device were confirmed to be true positives. After resolution of discrepant results, the number of positive specimens and the sensitivity and specificity results were as follows: for G. lamblia , 170, 95.9%, and 97.4%, respectively; for E. histolytica / E. dispar , 99, 96.0%, and 99.1%, respectively; and for C. parvum , 60, 98.3%, and 99.7%, respectively. There was no cross-reactivity with other parasites found in stool specimens, including eight different protozoa (128 challenges) and three different helminths (83 challenges). The ability to perform the complete O&amp;P examination should remain an option for those patients with negative parasite panel results but who are still symptomatic.
Pharmacokinetics and Posterior Segment Biodistribution of ESBA105, an Anti–TNF-α Single-Chain Antibody, upon Topical Administration to the Rabbit Eye (2009)

On topical administration, ESBA105 is efficiently absorbed and distributed to all compartments of the eye, whereby systemic drug exposure is very low. Based on its unique intraocular biodistribution and pharmacokinetics and the absolute intraocular levels reached, topical ESBA105 appears highly attractive for treatment of various ophthalmological disorders.
Tissue Engineered Bone Formation with Polymer/Ceramic Composites by Press-and-Baking Method (2005)

This DOI is not currently attached to any metadata records. DOIs can’t actually ever be deleted (they’re persistent), but sometimes our members create DOIs in error. We do have a process to approximate deletion which we follow only in rare cases where the DOI has been genuinely created in error, and most crucially, if the DOI has never been published anywhere online or in print and never otherwise distributed to or communicated with anyone (authors, readers, reviewers, etc.
Pharmacokinetic and pharmacodynamic interaction of vildagliptin and voglibose in Japanese patients with Type 2 diabetes (2013)

Plasma vildagliptin levels were decreased when voglibose was co-administered, although DPP- 4 inhibition remained unchanged. Co-administration led to significantly better pharmacodynamic response compared with each treatment alone, including higher active GLP-1 and lower glucose levels. The results indicate that this coadministration may be beneficial in the clinical situation. Vildagliptin and voglibose treatments, alone or when co-administered, were well tolerated in Japanese patients with Type 2 diabetes.
Cosuspensions of Microcrystals and Engineered Microparticles for Uniform and Efficient Delivery of Respiratory Therapeutics from Pressurized Metered Dose Inhalers (2012)

Engineered porous phospholipid microparticles with aerodynamic diameters in the respirable range of 1-2 μm were cosuspended in 1,1,1,2-tetrafluoroethane, a propellant, with microcrystals of glycopyrrolate, formoterol fumarate dihydrate, or Mometasone furoate-three drugs with different solubilities in the propellant, and different physical, chemical, and pharmacological attributes. The drug microcrystals were added individually, in pairs, or all three together to prepare different cosuspensions, contained in a pressurized metered dose inhaler (pMDI). The drug microcrystals irreversibly associated with the porous particles, and the resultant cosuspensions possessed greatly improved suspension stability compared with suspensions of drug microcrystals alone. In general, all cosuspensions showed efficient dose delivery of the drugs, with fine particle fractions of more than 60% for a wide range of doses, including those as low as 300 ng per inhaler actuation. In the cosuspension pMDIs, comparable fine particle fractions were delivered for all tested drugs, whether or not they were emitted from an inhaler containing one, two, or three drugs. We demonstrate that the cosuspension approach solves at least three long-standing problems in the clinical development of pMDI-based products: (1) dose and drug dependent delivery efficiency, (2) inability to formulate dose strengths below 1 μg to fully explore drug efficacy and safety, and (3) combination suspensions delivering a different fine particle fraction than individual drug suspensions.
Ferric Carboxymaltose-Mediated Attenuation of Doxorubicin-Induced Cardiotoxicity in an Iron Deficiency Rat Model (2014)

Since anthracycline-induced cardiotoxicity (AIC), a complication of anthracycline-based chemotherapies, is thought to involve iron, concerns exist about using iron for anaemia treatment in anthracycline-receiving cancer patients. This study evaluated how intravenous ferric carboxymaltose (FCM) modulates the influence of iron deficiency anaemia (IDA) and doxorubicin (3-5 mg per kg body weight [BW]) on oxidative/nitrosative stress, inflammation, and cardiorenal function in spontaneously hypertensive stroke-prone (SHR-SP) rats. FCM was given as repeated small or single total dose (15 mg iron per kg BW), either concurrent with or three days after doxorubicin. IDA (after dietary iron restriction) induced cardiac and renal oxidative stress (markers included malondialdehyde, catalase, Cu,Zn-superoxide dismutase, and glutathione peroxidase), nitrosative stress (inducible nitric oxide synthase and nitrotyrosine), inflammation (tumour necrosis factor-alpha and interleukin-6), and functional/morphological abnormalities (left ventricle end-diastolic and end-systolic diameter, fractional shortening, density of cardiomyocytes and capillaries, caveolin-1 expression, creatinine clearance, and urine neutrophil gelatinase-associated lipocalin) that were aggravated by doxorubicin. Notably, iron treatment with FCM did not exacerbate but attenuated the cardiorenal effects of IDA and doxorubicin independent of the iron dosing regimen. The results of this model suggest that intravenous FCM can be used concomitantly with an anthracycline-based chemotherapy without increasing signs of AIC.