gebhart/patrepeval huggingface dataset:
Recycling MHC class I molecules and endosomal peptide loading (1999)

MHC class I molecules usually present peptides derived from endogenous antigens that are bound in the endoplasmic reticulum. Loading of exogenous antigens on class I molecules, e.g., in cross-priming, sometimes occurs, but the intracellular location where interaction between the antigenic fragment and class I takes place is unclear. Here we show that measles virus F protein can be presented by class I in transporters associated with antigen processing-independent, NH(4)Cl-sensitive manner, suggesting that class I molecules are able to interact and bind antigen in acidic compartments, like class II molecules. Studies on intracellular transport of green fluorescent protein-tagged class I molecules in living cells confirmed that a small fraction of class I molecules indeed enters classical MHC class II compartments (MIICs) and is transported in MIICs back to the plasma membrane. Fractionation studies show that class I complexes in MIICs contain peptides. The pH in MIIC (around 5.0) is such that efficient peptide exchange can occur. We thus present evidence for a pathway for class I loading that is shared with class II molecules.
Signaling in Plant-Microbe Interactions (1997)

Analysis of viral and bacterial pathogenesis has revealed common themes in the ways in which plants and animals respond to pathogenic agents. Pathogenic bacteria use macromolecule delivery systems (types III and IV) to deliver microbial avirulence proteins and transfer DNA-protein complexes directly into plant cells. The molecular events that constitute critical steps of plant-pathogen interactions seem to involve ligand-receptor mechanisms for pathogen recognition and the induction of signal transduction pathways in the plant that lead to defense responses. Unraveling the molecular basis of disease resistance pathways has laid a foundation for the rational design of crop protection strategies.
Acute Myeloid Leukemia (2015)

Many recent biologic insights have shed light on the nosology of acute myeloid leukemia. Although this new knowledge has not yet had a major influence on the treatment of the disease, strategies under investigation may improve outcomes.
Antiproliferative and antitumor effects of azacitidine against the human myelodysplastic syndrome cell line SKM-1. (2012)

Inhibition of DNA methyltransferase by azacitidine contributes to its antiproliferative and antitumor effects against SKM-1 cells and may explain its clinical efficacy in MDS.
A common glycan structure on immunoglobulin G for enhancement of effector functions (2015)

Antibodies have been developed as therapeutic agents for the treatment of cancer, infection, and inflammation. In addition to binding activity toward the target, antibodies also exhibit effector-mediated activities through the interaction of the Fc glycan and the Fc receptors on immune cells. To identify the optimal glycan structures for individual antibodies with desired activity, we have developed an effective method to modify the Fc-glycan structures to a homogeneous glycoform. In this study, it was found that the biantennary N-glycan structure with two terminal alpha-2,6-linked sialic acids is a common and optimized structure for the enhancement of antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and antiinflammatory activities.
Adnexal torsion in a patient with Müllerian agenesis undergoing ovarian stimulation: a case report (2018)

Background: As assisted reproductive technologies become increasingly available to patients, more women with Müllerian agenesis may undergo ovarian stimulation and oocyte retrieval to have genetically-related offspring. The risk of ovarian torsion is increased in patients utilizing assisted reproductive technologies compared to patients who do not undergo these treatments. Case: A 25-year-old G0 with Mayer-Rokitansky-Kuster-Hauser syndrome presented to the emergency room two days after oocyte retrieval with an acute abdomen. During laparoscopy, she was found to have torsion of her left ovary. Summary and Conclusion: As more young women with Müllerian agenesis present for fertility treatment, this anatomically unique patient cohort may be at an especially high risk for ovarian torsion. Physicians should recognize this risk and counsel their patients on this risk when discussing fertility options in patients with Müllerian agenesis.
Challenging the dogma: the hidden layer of non‐protein‐coding RNAs in complex organisms (2003)

The central dogma of biology holds that genetic information normally flows from DNA to RNA to protein. As a consequence it has been generally assumed that genes generally code for proteins, and that proteins fulfil not only most structural and catalytic but also most regulatory functions, in all cells, from microbes to mammals. However, the latter may not be the case in complex organisms. A number of startling observations about the extent of non-protein-coding RNA (ncRNA) transcription in the higher eukaryotes and the range of genetic and epigenetic phenomena that are RNA-directed suggests that the traditional view of the structure of genetic regulatory systems in animals and plants may be incorrect. ncRNA dominates the genomic output of the higher organisms and has been shown to control chromosome architecture, mRNA turnover and the developmental timing of protein expression, and may also regulate transcription and alternative splicing. This paper re-examines the available evidence and suggests a new framework for considering and understanding the genomic programming of biological complexity, autopoietic development and phenotypic variation.
An efficient procedure for protein extraction from formalin-fixed, paraffin-embedded tissues for reverse phase protein arrays (2012)

With optimized protein extraction methods, FFPE tissues can be a valuable source in generating reproducible and biologically relevant proteomic profiles using RPPA, with specific marker performance varying according to tissue type.
Perspectives and Limitations of Microarray-Based Gene Expression Profiling of Thyroid Tumors (2007)

Microarray technology has become a powerful tool to analyze the gene expression of tens of thousands of genes simultaneously. Microarray-based gene expression profiles are available for malignant thyroid tumors (i.e., follicular thyroid carcinoma, and papillary thyroid carcinoma), and for benign thyroid tumors (such as autonomously functioning thyroid nodules and cold thyroid nodules). In general, the two main foci of microarray investigations are improved understanding of the pathophysiology/molecular etiology of thyroid neoplasia and the detection of genetic markers that could improve the differential diagnosis of thyroid tumors. Their results revealed new features, not known from one-gene studies. Simultaneously, the increasing number of microarray analyses of different thyroid pathologies raises the demand to efficiently compare the data. However, the use of different microarray platforms complicates cross-analysis. In addition, there are other important differences between these studies: 1) some studies use intraindividual comparisons, whereas other studies perform interindividual comparisons; 2) the reference tissue is defined as strictly nonnodular healthy tissue or also contains benign lesions such as goiter, follicular adenoma, and hyperplastic nodules in some studies; and 3) the widely used Affymetrix GeneChip platform comprises several GeneChip generations that are only partially compatible. Moreover, the different studies are characterized by strong differences in data analysis methods, which vary from simple empiric filters to sophisticated statistic algorithms. Therefore, this review summarizes and compares the different published reports in the context of their study design. It also illustrates perspectives and solutions for data set integration and meta-analysis, as well as the possibilities to combine array analysis with other genetic approaches.
Long-term effects of percutaneous laser balloon ablation from the canine coronary sinus. (1992)

Percutaneous transcatheter laser balloon ablation via the coronary sinus produces a lesion that may be anatomically well suited for left-sided accessory pathway ablation. Although coronary sinus narrowing may occur, adverse physiological effects are unlikely due to the development of extensive collateral circulation. Systematic clinical studies of this new approach to catheter ablation appear warranted.
Activation of Wild Type p53 Function by Its Mortalin-binding, Cytoplasmically Localizing Carboxyl Terminus Peptides (2005)

The Hsp70 family member mortalin (mot-2/mthsp70/GRP75) binds to a carboxyl terminus region of the tumor suppressor protein p53. By in vivo co-immunoprecipitation of mot-2 with p53 and its deletion mutants, we earlier mapped the mot-2-binding site of p53 to its carboxyl terminus 312-352 amino acid residues. In the present study we attempted to disrupt mot-2-p53 interactions by overexpression of short p53 carboxyl-terminal peptides. We report that p53 carboxyl-terminal peptides (amino acid residues 312-390, 312-352, 323-390, and 323-352) localize in the cytoplasm, whereas 312-322, 337-390, 337-352, and 352-390 locate mostly in the nucleus. Most interestingly, the cytoplasmically localizing p53 peptides harboring the residues 323-337 activated the endogenous p53 function by displacing it from p53-mortalin complexes and relocating it to the nucleus. Such activation of p53 function was sufficient to cause growth arrest of human osteosarcoma and breast carcinoma cells.
Induction of AIDS Virus-Specific CTL Activity in Fresh, Unstimulated Peripheral Blood Lymphocytes from Rhesus Macaques Vaccinated with a DNA Prime/Modified Vaccinia Virus Ankara Boost Regimen (2000)

The observed role of CTL in the containment of AIDS virus replication suggests that an effective HIV vaccine will be required to generate strong CTL responses. Because epitope-based vaccines offer several potential advantages for inducing strong, multispecific CTL responses, we tested the ability of an epitope-based DNA prime/modified vaccinia virus Ankara (MVA) boost vaccine to induce CTL responses against a single SIVgag CTL epitope. As assessed using both 51Cr release assays and tetramer staining of in vitro stimulated PBMC, DNA vaccinations administered to the skin with the gene gun induced and progressively increased p11C, C-->M (CTPYDINQM)-specific CD8+ T lymphocyte responses in six of six Mamu-A*01+ rhesus macaques. Tetramer staining of fresh, unstimulated PBMC from two of the DNA-vaccinated animals indicated that as much as 0.4% of all CD3+/CD8alpha+ T lymphocytes were specific for the SIVgag CTL epitope. Administration of MVA expressing the SIVgag CTL epitope further boosted these responses, such that 0.8-20.0% of CD3+/CD8alpha+ T lymphocytes in fresh, unstimulated PBMC were now Ag specific. Enzyme-linked immunospot assays confirmed this high frequency of Ag-specific cells, and intracellular IFN-gamma staining demonstrated that the majority of these cells produced IFN-gamma after peptide stimulation. Moreover, direct ex vivo SIV-specific cytotoxic activity could be detected in PBMC from five of the six DNA/MVA-vaccinated animals, indicating that this epitope-based DNA prime/MVA boost regimen represents a potent method for inducing high levels of functionally active, Ag-specific CD8+ T lymphocytes in non-human primates.
Two-photon pumped cavity lasing in novel dye doped bulk matrix rods (1995)

Trans-4-[p-(N-ethyl-N-hydroxyethylamino)styryl]-N-methylpyridi that possesses a much greater two-photon absorption cross section and much stronger upconversion fluorescence emission than common organic dyes (such as rhodamine), when excited with near infrared laser radiation. Utilizing ASPT doped bulk polymer rods, two-photon pumped frequency upconverted cavity lasing has been accomplished using a Q-switched Nd:YAG laser as the pump source. The wavelength and pulse duration were ∼600 nm and 3–6 ns, respectively, for the cavity lasing; whereas the corresponding values for pump pulses were 1.06 μm and ∼10 ns, respectively. For a 7 mm long sample rod with a dopant concentration d0=8×10−3 M/L, the conversion efficiency from the absorbed pump energy to the cavity lasing output was ∼3.5% at a pump energy level of 1.3 mJ. The lasing lifetime, in terms of pulse numbers, was more than 4×104 pulses at 2 Hz repetition rate and room temperature.
A systematic analysis of the effect of target RNA structure on RNA interference (2007)

RNAi efficiency is influenced by local RNA structure of the target sequence. We studied this structure-based resistance in detail by targeting a perfect RNA hairpin and subsequently destabilized its tight structure by mutation, thereby gradually exposing the target sequence. Although the tightest RNA hairpins were completely resistant to RNAi, we observed an inverse correlation between the overall target hairpin stability and RNAi efficiency within a specific thermodynamic stability (DeltaG) range. Increased RNAi efficiency was shown to be caused by improved binding of the siRNA to the destabilized target RNA hairpins. The mutational effects vary for different target regions. We find an accessible target 3' end to be most important for RNAi-mediated inhibition. However, these 3' end effects cannot be reproduced in siRNA-target RNA-binding studies in vitro, indicating the important role of RISC components in the in vivo RNAi reaction. The results provide a more detailed insight into the impact of target RNA structure on RNAi and we discuss several possible implications. With respect to lentiviral-mediated delivery of shRNA expression cassettes, we present a DeltaG window to destabilize the shRNA insert for vector improvement, while avoiding RNAi-mediated self-targeting during lentiviral vector production.
Heat shock protein-70 induction mediates luteal regression in the rat. (1995)

Induction of heat shock protein 70 (HSP-70) is associated with inhibition of hormone-sensitive steroidogenesis and interruption of cholesterol translocation to or into the mitochondria. A number of pharmacological and physiological inhibitors of luteal cell function stimulate HSP-70 synthesis via activation of the heat shock transcription factor (HSF). In the present study we address the following questions: 1) is HSP-70 synthesis increased during prostaglandin F2 alpha (PGF2 alpha)-induced luteolysis or natural luteal regression? 2) Does blocking HSP-70 synthesis reverse the inhibition of hormone-sensitive steroidogenesis induced by heat stress and PGF2 alpha? Gel-retardation assays demonstrated HSF activation within 7.5 min after PGF2 alpha (400 micrograms) administered in vivo. Western blotting revealed HSP-70 synthesis by 1 h with higher levels seen at 2 h. The stress response was similarly activated during natural regression of the corpus luteum in rats. Gel retardation assays demonstrated maximal HSF activation 10 days after ovulation. Western blotting showed that HSP-70 levels increased dramatically on this same day and were sustained for several days after the initiation of luteal regression. Inhibition of HSP-70 synthesis was investigated in isolated luteal cells using a cholesteryl-conjugated phosphorothioate antisense oligodeoxynucleotide. The control was an oligodeoxynucleotide with the same base composition, but with scrambled base sequence. Incubation with 3 microM antisense oligodeoxynucleotide for 2 h before a 42 C heat shock prevented synthesis of HSP-70 while up to 4.5 microM control oligodeoxynucleotide had no effect on HSP-70 synthesis in response to heat shock. Preincubation with antisense oligodeoxynucleotide partially reversed heat stress-induced inhibition of LH-stimulated steroidogenesis. More importantly, preincubation with antisense oligodeoxynucleotide also significantly reversed inhibition of cAMP-stimulated steroidogenesis induced by PGF2 alpha. Treatment with control oligodeoxynucleotide did not reverse heat shock or PGF2 alpha inhibition of hormone-dependent steroidogenesis. The findings that the synthesis of HSP-70 coincides with the loss of luteal function and that blocking its synthesis reverses inhibition of hormone-dependent steroidogenesis strongly suggest a role for HSPs as physiological mediators of luteal regression.
Vaccination with synthetic analog peptides derived from WT1 oncoprotein induces T-cell responses in patients with complete remission from acute myeloid leukemia (2010)

A pilot study was undertaken to assess the safety, activity, and immunogenicity of a polyvalent Wilms tumor gene 1 (WT1) peptide vaccine in patients with acute myeloid leukemia in complete remission but with molecular evidence of WT1 transcript. Patients received 6 vaccinations with 4 WT1 peptides (200 microg each) plus immune adjuvants over 12 weeks. Immune responses were evaluated by delayed-type hypersensitivity, CD4+ T-cell proliferation, CD3+ T-cell interferon-gamma release, and WT1 peptide tetramer staining. Of the 9 evaluable patients, 7 completed 6 vaccinations and WT1-specific T-cell responses were noted in 7 of 8 patients. Three patients who were HLA-A0201-positive showed significant increase in interferon-gamma-secreting cells and frequency of WT1 tetramer-positive CD8+ T cells. Three patients developed a delayed hypersensitivity reaction after vaccination. Definite related toxicities were minimal. With a mean follow-up of 30 plus or minus 8 months after diagnosis, median disease-free survival has not been reached. These preliminary data suggest that this polyvalent WT1 peptide vaccine can be administered safely to patients with a resulting immune response. Further studies are needed to establish the role of vaccination as viable postremission therapy for acute myeloid leukemia.
The 1A4 molecule (CD27) is involved in T cell activation (1991)

We developed a new mAb, anti-1A4, which recognizes an epitope on the CD27 molecule distinct from those recognized by several known anti-CD27 mAb. Although it has been suggested that the CD27 molecule is a T cell activation Ag, there was little direct evidence that the structure was involved in the T cell activation process. In this study, we showed that anti-1A4 inhibited anti-CD2, anti-CD3, mitogens, or soluble Ag-induced T cell proliferation as well as PWM-driven B cell IgG synthesis. Interestingly, anti-1A4 inhibited IL-2 secretion without affecting IL-2R expression. In addition, pretreatment of T cells with anti-1A4 inhibited the normally sustained intracellular calcium mobilization seen after triggering of T cells via the CD2 or CD3 pathways. Thus, binding of anti-1A4 to the CD27 molecule appears to induce a negative effect on T cell activation. This may be due to either a direct signal to T cells or the blocking of an interaction between T cells and accessory cells or both. These findings support the notion that the CD27 molecule plays an integral role in the process of T cell activation.
Antibiotics Enhance Prevention and Eradication Efficacy of Cathodic-Voltage-Controlled Electrical Stimulation against Titanium-Associated Methicillin-Resistant Staphylococcus aureus and Pseudomonas aeruginosa Biofilms (2019)

Periprosthetic joint infection (PJI) develops clinically, even with antibiotic treatment, and methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) and <i>Pseudomonas aeruginosa</i> are predominant causes of these infections. Due to biofilm formation, antibiotic treatment for patients with PJI can perpetuate resistance, further complicating the use of noninvasive treatments. This study evaluated cathodic-voltage-controlled electrical stimulation (CVCES) of titanium, in combination with a clinically relevant antibiotic, to synergistically prevent MRSA and <i>P. aeruginosa</i> PJIs by inhibiting bacterial adherence or as a treatment for eradicating established biofilms. CVCES of -1.0 V, -1.5 V, or -1.8 V (versus Ag/AgCl), with or without vancomycin for MRSA or gentamicin for <i>P. aeruginosa</i>, was applied to sterile titanium incubated with cultures to evaluate prevention of attachment or eradication of preestablished biofilms. Treatments were 24 h long and included open-circuit potential controls, antibiotic alone, CVCES, and CVCES plus antibiotic. Biofilm-associated and planktonic CFU were enumerated. In general, CVCES at -1.8 V alone or with antibiotic completely eradicated biofilm-associated CFU for both strains, and these parameters were also highly effective against planktonic bacteria, resulting in a >6-log reduction in MRSA and no detectable planktonic <i>P. aeruginosa</i> All CFU were reduced ∼3 to 5 logs from controls for prevention CVCES plus antibiotics at -1.0 V and -1.5 V against MRSA. Remarkably, there were no detectable <i>P. aeruginosa</i> CFU following prevention CVCES at -1.0 V or -1.5 V with gentamicin. Our results suggest that CVCES in combination with antibiotics may be an effective approach for prevention and treatment of PJI.<b>IMPORTANCE</b> Periprosthetic joint infections (PJIs) develop clinically in the presence of antibiotic therapies and are responsible for increased patient morbidity and rising health care costs. Many of these infections involve bacterial biofilm formation on orthopedic hardware, and it has been well established that these biofilms are refractory to most antibiotic treatments. Recent studies have focused on novel methods to prevent and eradicate infection. Cathodic-voltage-controlled electrical stimulation (CVCES) has previously been shown to be effective as a method for prevention and eradication of Gram-positive and Gram-negative infections. The present study revealed that the utility of CVCES for prevention and eradication of methicillin-resistant <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i> is enhanced in the presence of clinically relevant antibiotics. The synergistic effects of CVCES and antibiotics are effective in a magnitude-dependent manner. The results of this study indicate a promising alternative method to current PJI mitigation techniques.
Optical lattice laser (2006)

Atoms with narrow-linewidth transition trapped within the Lamb-Dick regime of optical lattice are proposed be used as laser gain medium to build a laser. The gain medium atoms can be the alkaline-earth species, Magnesium, Calcium, and Strontium, including Ytterbium. These atoms possess promising super-narrow optical clock transitions, but here, this clock transition is proposed to be used as the lasing transition of the output laser. This optical lattice laser with expected super-narrow linewidth is an active optical clock with high accuracy and stability.
Biomaterial Films of Bombyx Mori Silk Fibroin with Poly(ethylene oxide) (2004)

Phase separation into controllable patterned microstructures was observed for Bombyx mori silkworm silk and poly(ethylene oxide) (PEO) (900000 g/mol) blends cast from solution. The evolution of the microstructures with increasing PEO volume fraction is strikingly similar to the progression of phases and microstructures observed with surfactants. The chemically patterned materials obtained provide engineerable biomaterial surfaces with predictable microscale features which can be used to create topographically patterned or chemically functionalized biomaterials. Solution blending was used to incorporate water-soluble PEO into silk to enhance elasticity and hydrophilicity. The sizes of the globule fibroin phase ranged from 2.1 +/- 0.5 to 18.2 +/- 2.1 microm depending on the ratio of silk/PEO. Optical microscopy and SEM analysis confirmed the micro-phase separation between PEO and silk. Surface properties were determined by XPS and contact angle. Methanol can be used to control the conformational transition of silk fibroin to the insoluble beta-sheet state. Subsequentially, the PEO can be easily extracted from the films with water to generate silk matrixes with definable porosity and enhanced surface roughness. These blend films formed from two biocompatible polymers provide potential new biomaterials for tissue engineering scaffolds.