gebhart/patrepeval huggingface dataset:
A preliminary study of the relationship between breast cancer metastasis and loss of heterozygosity by using exome sequencing (2014)

We explored the feasibility of studying loss of heterozygosity (LOH) by using exome sequencing and compared the differences in genetic LOH between primary breast tumors and metastatic lesions. Exome sequencing was conducted to investigate the genetic LOH in the peripheral blood, a primary tumor, and a metastatic lesion from the same patient. LOH was observed in 30 and 48 chromosomal loci of the primary tumor and metastatic lesion, respectively. The incidence of LOH was the highest on chromosome 19, followed by chromosomes 14, 3, and 11 in the metastatic lesion. Among these 'hot' regions, LOH was observed for multiple genes of the CECAM, MMP and ZNF families. Therefore, the use of exome sequencing for studying LOH is feasible. More members of gene families appeared with LOH in 'hot' regions, suggesting that these gene families had synergistic effects in tumorigenesis.
FGF21 Can Be Mimicked In Vitro and In Vivo by a Novel Anti-FGFR1c/β-Klotho Bispecific Protein (2013)

The endocrine hormone FGF21 has attracted considerable interest as a potential therapeutic for treating diabetes and obesity. As an alternative to the native cytokine, we generated bispecific Avimer polypeptides that bind with high affinity and specificity to one of the receptor and coreceptor pairs used by FGF21, FGFR1c and β-Klotho. These Avimers exhibit FGF21-like activity in in vitro assays with potency greater than FGF21. In a study conducted in obese male cynomolgus monkeys, animals treated with an FGFR1c/β-Klotho bispecific Avimer showed improved metabolic parameters and reduced body weight comparable to the effects seen with FGF21. These results not only demonstrate the essential roles of FGFR1c and β-Klotho in mediating the metabolic effects of FGF21, they also describe a first bispecific activator of this unique receptor complex and provide validation for a novel therapeutic approach to target this potentially important pathway for treating diabetes and obesity.
T-cell-receptor-like antibodies – generation, function and applications (2012)

Tumour and virus-infected cells are recognised by CD8+ cytotoxic T cells that, in response, are activated to eliminate these cells. In order to be activated, the clonotypic T-cell receptor (TCR) needs to encounter a specific peptide antigen presented by the membrane surface major histocompatibility complex (MHC) molecule. Cells that have undergone malignant transformation or viral infection present peptides derived from tumour-associated antigens or viral proteins on their MHC class I molecules. Therefore, disease-specific MHC-peptide complexes are desirable targets for immunotherapeutic approaches. One such approach transforms the unique fine specificity but low intrinsic affinity of TCRs to MHC-peptide complexes into high-affinity soluble antibody molecules endowed with a TCR-like specificity towards tumour or viral epitopes. These antibodies, termed TCR-like antibodies, are being developed as a new class of immunotherapeutics that can target tumour and virus-infected cells and mediate their specific killing. In addition to their therapeutic capabilities, TCR-like antibodies are being developed as diagnostic reagents for cancer and infectious diseases, and serve as valuable research tools for studying MHC class I antigen presentation.
Steady-state ALPS for real-valued problems (2009)

The objectives of this paper are to describe a steady-state version of the Age-Layered Population Structure (ALPS) Evolutionary Algorithm (EA) and to compare it against other GAs on real-valued problems. Motivation for this work comes from our previous success in demonstrating that a generational version of ALPS greatly improves search performance on a Genetic Programming problem. In making steady-state ALPS, some modifications were made to the method for calculating age and the method for moving individuals up age layers. To demonstrate that ALPS works well on real-valued problems we compare it against CMA-ES and Differential Evolution (DE) on five challenging, real-valued functions and on one real-world problem. While CMA-ES and DE outperform ALPS on the two unimodal test functions, ALPS is much better on the three multimodal test problems and on the real-world problem. Further examination shows that, unlike the other GAs, ALPS maintains a genotypically diverse population throughout the entire search process. These findings strongly suggest that the ALPS paradigm is better able to avoid premature convergence then the other GAs.
Wat gebeurt er met het waterpeil (2002)

Een gesprek met Joop Verheul, bedrijfsleider van Zegveld, over de toekomst van het veenweidegebied, is vooral een gesprek over het waterpeil.
Fluosol DA-20 in the treatment of severe anemia (1990)

We evaluated the safety and efficacy of Fluosol DA-20% (FDA) as a blood substitute in the treatment of severe anemia. Thirty-six patients received either FDA (n = 21) or crystalloid/hydroxyethyl starch (CHS) (n = 15) as part of a randomized, controlled trial. Ten patients received FDA as part of a humanitarian protocol. All were Jehovah's Witnesses who refused transfusion, had bled recently, and had average Hgb levels of 4.3 g/dl. After pulmonary artery catheter insertion, each patient was infused with CHS to attain a pulmonary artery wedge pressure (WP) of 10 to 18 mm Hg. FDA was given as a one-time dose of 30 ml/kg. Data were collected at baseline, 12, 24, and 48 h. None of the patients with negative reactions to a 0.5-ml test dose of FDA had adverse reactions to the subsequent infusion. The plasma or dissolved component of oxygen content was significantly higher in the FDA group at 12 h (FDA group 1.58 +/- 0.47 ml/dl, control group 1.01 +/- 0.31 ml/dl, p less than .02, t-test). Nineteen patients died: 12 (37.5%) FDA, seven (46.6%) control. The difference was not significant. We conclude the following: a) FDA can be given safely to severely anemic patients in doses of 30 ml/kg; b) FDA significantly increased the dissolved component of oxygen content after 12 h but the effect did not persist; c) severely anemic patients can survive without transfusion although mortality is high. In this study, inability of FDA to sustain increased oxygen content was due in part to the rapid elimination of FDA and also to the limited amount given.(ABSTRACT TRUNCATED AT 250 WORDS)
Microfabricated device coupled with an electrospray ionization quadrupole time-of-flight mass spectrometer: protein identifications based on enhanced-resolution mass spectrometry and tandem mass spectrometry data (1998)

We describe the coupling of a microfabricated fluidic device to an electrospray ionization (ESI) quadrupole time-of-flight mass spectrometer (QqTOFMS) for the identification of protein samples. The microfabricated devices consisted of three reservoirs connected via channels to a main capillary, which in turn was linked via a microspray interface to the QqTOFMS. Here we present preliminary results obtained using this system. Standardized solutions of myoglobin tryptic digest were analyzed indicating a limit of detection at the low to sub fmol/microL. The combination of the microfabricated device for rapid sample delivery and the rapid acquisition capability, enhanced resolution and mass accuracy of the QqTOF offers unique possibilities for the rapid identification of proteins by database searching. This platform can generate MS data suitable for protein database searching by the peptide-mass fingerprinting approach and MS/MS data suitable for protein database searching. Here the results of the two database-searching approaches are compared and the possibilities of combining the two approaches for rapid identification of protein are discussed. Also, we present a comparison of the results obtained using the three-position microfabricated device coupled to the ESI-QqTOFMS and to an ESI-ion trap MS. Finally the combination of C-terminal 18O labeling of peptides and the microfabricated system for automated combined peptide-mass fingerprinting and sequence-tag database searching is discussed.
A possible role for humoral immunity in the pathogenesis of Parkinson's disease (2005)

The pathogenesis of idiopathic Parkinson's disease is unknown, but nigral degeneration and depigmentation are associated with microglial inflammation and anti-inflammatory medications appear to protect against the disease. The possibility that humoral immunity may play a role in initiating or regulating the inflammation has been suggested by experimental studies triggering dopamine cell death using a variety of transfer strategies and the observation of CD8+ T lymphocytes and complement in the nigra in Parkinson's disease. We analysed the association between degeneration and humoral immune markers in brain tissue of patients with idiopathic (n = 13) or genetic (n = 2 with alpha-synuclein and n = 1 with parkin mutations) Parkinson's disease and controls without neurological disease (n = 12) to determine the humoral immune involvement in Parkinson's disease. Formalin-fixed tissue samples from the substantia nigra and primary visual cortex for comparison were stained for alpha-synuclein, major histocompatibility complex II (HLA), immunoglobulin M (IgM), immunoglobulin G (IgG), IgG subclasses 1-4 and IgG receptors FcgammaR I-III. Antigen retrieval and both single immunoperoxidase and double immunofluorescence procedures were employed to determine the cell types involved and their pattern and semiquantitative densities. Significant dopamine neuron loss occurred in all patients with Parkinson's disease, negatively correlating with disease duration (r = -0.76, P = 0.002). Although all patients had increased inflammatory HLA immunopositive microglia, the degree of inflammation was similar throughout the disease (r = 0.08, P = 0.82). All patients with Parkinson's disease had IgG binding on dopamine neurons but not IgM binding. Lewy bodies were strongly immunolabelled with IgG. A mean 30 +/- 12% of dopamine nigral neurons were immunoreactive for IgG in Parkinson's disease with the proportion of IgG immunopositive neurons negatively correlating with the degree of cell loss in the substantia nigra (r = -0.67, P < 0.0001) and positively correlating with the number of HLA immunopositive microglia (r = 0.51, P = 0.01). Most neuronal IgG was the IgG1 subclass with some IgG3 and less IgG2 also found in the damaged substantia nigra. The high affinity activating IgG receptor, FcgammaRI, was expressed on nearby activated microglia. The low affinity activating IgG receptor, FcgammaRIII was expressed on cells morphologically resembling lymphocytes, whereas immunoreactivity for the inhibitory IgG receptor FcgammaRII was absent in all cases. This pattern of humoral immune reactivity is consistent with an immune activation of microglia leading to the targeting of dopamine nigral neurons for destruction in both idiopathic and genetic cases of Parkinson's disease.
Three-dimensional finite-element analyses for radio-frequency hepatic tumor ablation (2002)

Radio-frequency (RF) hepatic ablation, offers an alternative method for the treatment of hepatic malignancies. We employed finite-element method (FEM) analysis to determine tissue temperature distribution during RF hepatic ablation. We constructed three-dimensional (3-D) thermal-electrical FEM models consisting of a four-tine RF probe, hepatic tissue, and a large blood vessel (10-mm diameter) located at different locations. We simulated our FEM analyses under temperature-controlled (90 degrees C) 8-min ablation. We also present a preliminary result from a simplified two-dimensional (2-D) FEM model that includes a bifurcated blood vessel. Lesion shapes created by the four-tine RF probe were mushroom-like, and were limited by the blood vessel. When the distance of the blood vessel was 5 mm from the nearest distal electrode 1) in the 3-D model, the maximum tissue temperature (hot spot) appeared next to electrodes A. The location of the hot spot was adjacent to another electrode 2) on the opposite side when the blood vessel was 1 mm from electrode A. The temperature distribution in the 2-D model was highly nonuniform due to the presence of the bifurcated blood vessel. Underdosed areas might be present next to the blood vessel from which the tumor can regenerate.
Segmentation of sputum color image for lung cancer diagnosis (2002)

The paper presents a method for automatic segmentation of sputum cells color images, to develop an efficient algorithm for lung cancer diagnosis based on a Hopfield neural network. We formulate the segmentation problem as a minimization of an energy function constructed with two terms, the cost-term as a sum of squared errors, and the second term a temporary noise added to the network as an excitation to escape certain local minima with the result of being closer to the global minimum. To increase the accuracy in segmenting the regions of interest, a preclassification technique is used to extract the sputum cell regions within the color image and remove those of the debris cells. The proposed technique has yielded correct segmentation of complex scene of sputum prepared by ordinary manual staining method in most of the tested images selected from our database containing thousands of sputum color images.
STAT proteins as novel targets for cancer drug discovery (2004)

Signal transducer and activator of transcription (STAT) proteins are latent cytoplasmic transcription factors that were discovered in the context of cytokine and growth factor signalling. Normal STAT signalling is tightly controlled with finite kinetics, which is in keeping with standard cellular responses. However, persistent STAT activation has also been observed and is frequently associated with malignant transformation. Constitutive activation of STAT proteins, notably of Stat3 and Stat5, is detected in many human tumour cells and cells transformed by oncoproteins that activate tyrosine kinase signalling pathways. It is well-established that constitutively active Stat3 is one of the molecular abnormalities that has a causal role in oncogenesis. Aberrant Stat3 promotes uncontrolled growth and survival through dysregulation of gene expression, including cyclin D1, c-Myc, Bcl-xL, Mcl-1 and survivin genes, and thereby contributes to oncogenesis. Moreover, recent studies reveal that persistently active Stat3 induces tumour angiogenesis by upregulation of vascular endothelial growth factor induction, and modulates immune functions in favour of tumour immune evasion. Overall, studies have validated Stat3 as a novel target for cancer therapy, and hence provided the rationale for developing small-molecule Stat3 inhibitors. This review will discuss current evidence for the critical role of aberrant STAT signalling in malignant transformation, and examine the validity as well as the therapeutic potential of Stat3 as a cancer target. An update on the efforts to develop novel Stat3 inhibitors for therapeutic application will also be provided.
Writing Skills in Practice: A Practical Guide for Health Professionals (2001)

Introduction. Section 1: Writing for Clinical Practice. 1. The purpose of written material. 2. How to record information. 3. The legal framework. 4. Record keeping 5. Reports/letters 6. Information leaflets for clients Section 2: Writing for Teaching and Learning. 7. Writing as an aid to learning. 8. Preparing materials for teaching. 9. Note-taking 10. Essays 11. Assessment. 12. Dissertations 13. Research projects. Section 3: Writing for Publication. 14. Developing an idea. 15.Managing your time effectively. 16. Determining your style. 17. Getting the best out of your personal computer. 18. Presenting your work. 19. Protecting your rights. 20. Journal articles 21. Books 22. Articles for the media. References. Index.
Spatial resolution of the primary beta-amyloidogenic process induced in postischemic hippocampus. (1994)

Proteolytic modifications of amyloid precursor protein (APP) play key roles in the development of Alzheimer's disease. However, each specific in vivo process has not yet been fully resolved in spatial terms because the orthodox approach employing electrophoretic analysis requires homogenization of samples and thus provides limited information on the localization of the process. To acquire such spatial information for the primary process involved in beta-amyloidogenesis, we have designed and developed a novel antibody exclusively specific to APP fragments possessing the exact amino terminus of the major beta-amyloid (A beta) peptide. Use of this antibody revealed that cleavage of APP at the amino terminal position of the A beta sequence is a normal steady-state process in gerbil hippocampus. Furthermore, nonfatal transient (10 min) forebrain ischemia followed by reperfusion enhanced the initial beta-amyloidogenic reaction mainly in pyramidal cells of CA1 sector and of dentate gyrus prior to and along with delayed neuronal degeneration. The APP fragments accumulated in cell bodies and dendrites of the neurons. These results suggest that beta-amyloidogenesis may involve a process that is also activated in postischemic brain and that ischemia-like conditions may contribute to pathogenic A beta accumulation.
Detectable BRAF mutation in serum DNA samples from patients with papillary thyroid carcinomas (2009)

BACKGROUND.: An activating point mutation of the BRAF oncogene results in a V600E amino acid missense mutation found in a majority of papillary thyroid carcinomas (PTC). METHODS.: In this study, 28 matched tumor and serum samples obtained from patients with both benign and malignant thyroid disorders were analyzed for BRAF mutation using a gap-ligase chain reaction technique. RESULTS.: The BRAF mutation was absent in tumor DNA samples obtained from patients with benign adenomas, follicular neoplasms or carcinoma, and thyroid lymphoma. In contrast, 5 of 14 PTC tumors were positive for the BRAF mutation. Moreover, 3 of 14 patients with PTC were positive for BRAF mutation in serum and tumor. Of these 3 patients, 2 had lymph node metastasis and 2 had PTC in background of the Hashimoto's thyroiditis. CONCLUSIONS.: The detection of free circulating mutant BRAF in patients with PTC is possible and future studies are warranted to determine its clinical significance.
Molecular Bases of Odor Discrimination: Reconstitution of Olfactory Receptors that Recognize Overlapping Sets of Odorants (2001)

The vertebrate olfactory system discriminates a wide variety of odorants by relaying coded information from olfactory sensory neurons in the olfactory epithelium to olfactory cortical areas of the brain. Recent studies have shown that the first step in odor discrimination is mediated by approximately 1000 distinct olfactory receptors, which comprise the largest family of G-protein-coupled receptors. In the present study, we used Ca(2+) imaging and single-cell reverse transcription-PCR techniques to identify mouse olfactory neurons responding to an odorant and subsequently to clone a receptor gene from the responsive cell. The functionally cloned receptors were expressed in heterologous systems, demonstrating that structurally related olfactory receptors recognized overlapping sets of odorants with distinct affinities and specificities. Our results provide direct evidence for the existence of a receptor code in which the identities of different odorants are specified by distinct combinations of odorant receptors that possess unique molecular receptive ranges. We further demonstrate that the receptor code for an odorant changes with odorant concentration. Finally, we show that odorant receptors in human embryonic kidney 293 cells couple to stimulatory G-proteins such as Galphaolf, resulting in odorant-dependent increases in cAMP. Odor discrimination is thus determined by differences in the receptive ranges of the odorant receptors that together encode specific odorant molecules.
Ground-State Singlet L3Fe-(μ-N)-FeL3 and L3Fe(NR) Complexes Featuring Pseudotetrahedral Fe(II) Centers (2005)

Pseudotetrahedral iron(II) coordination complexes that contain bridged nitride and terminal imide linkages, and exhibit singlet ground-state electronic configurations, are described. Sodium amalgam reduction of the ferromagnetically coupled dimer, {[PhBP(3)]Fe(mu-1,3-N(3))}(2) (2) ([PhBP(3)] = [PhB(CH(2)PPh(2))(3)](-)), yields the diamagnetic bridging nitride species [{[PhBP(3)]Fe}(2)(mu-N)][Na(THF)(5)] (3). The Fe-N-Fe linkage featured in the anion of 3 exhibits an unusually bent angle of approximately 135 degrees , and the short Fe-N bond distances (Fe-N(av) approximately equal to 1.70 A) suggest substantial Fe-N multiple bond character. The diamagnetic imide complex {[PhBP(3)]Fe(II)(triple bond)N(1-Ad)}{(n)()Bu(4)N} (4) has been prepared by sodium amalgam reduction of its low-spin iron(III) precursor, [PhBP(3)]Fe(III)(triple bond)N(1-Ad) (5). Complexes 4 and 5 have been structurally characterized, and their respective electronic structures are discussed in the context of a supporting DFT calculation. Diamagnetic 4 provides a bona fide example of a pseudotetrahedral iron(II) center in a low-spin ground-state configuration. Comparative optical data strongly suggest that dinuclear 3 is best described as containing two high-spin iron(II) centers that are strongly antiferromagnetically coupled to give rise to a singlet ground-state at room temperature.
A three-dimensional DRAM using floating body cell in FDSOI devices (2012)

This paper describes the capacitorless 1-transistor (1T) DRAMs exploits the floating body (FB) effect of Fully depleted (FD) SOI devices, where the transistor body is used as a charge storage node. A novel three-tier, 3D, 1T embedded DRAM is presented that can be vertically integrated with the microprocessor achieving low cost, high density on-chip main memory. A 394Kbits test chip is designed and fabricated in a 0.15um fully depleted SOI CMOS process. The measured retention time under holding conditions is higher than 10ms. In the continuous read mode, every read should be followed by a refresh. The test chip is designed to work with an access time of 50ns and operates at 10MHz.
Cytotoxic activity of Propionibacterium acnes and other skin organisms (1985)

Culture supernatants from four species of skin micro-organisms were tested against VERO (monkey kidney cells) and skin fibroblasts for cytotoxic activity. Cytotoxic activity was produced by the three species of Propionibacterium tested (P. acnes, P. avidum and P. granulosum), and this activity was highest when cultures were grown in the presence of glucose. In contrast, Staphylococcus epidermidis was devoid of cytotoxic activity whether grown in the presence of glucose or not. The agent responsible for the cytotoxic activity was heat stable, of low molecular weight and removable from supernatants by ether extraction. These properties, coupled with the finding that the levels of cytotoxicity are directly proportional to the concentrations of propionate measured in samples, suggests that propionate is the agent responsible for the cytotoxicity of the culture supernatants. Pure propionate and the salts of other carboxylic acids (CI to C5) were tested at the same concentrations and showed different degrees of cytotoxicity depending on their chain length. Propionate may have an important role in the aetiology of the disease acne vulgaris.