gebhart/patrepeval huggingface dataset:
Foundations of Biomedical Ultrasound (2006)

Abstract Biomedical ultrasonics is inherently interdisciplinary, involving mechanics, electrical engineering, physics, biology, and medicine. As such, it can be an extraordinarily difficult subject to cover in one book. Drawn from years of class notes, student interaction and personal experience, Foundations of Biomedical Ultrasound does just that. It covers the fundamental engineering behind ultrasound equipment, properties of acoustic wave motion, the behaviour of waves in various media, non-linear waves and the creation of images. The most comprehensive book on the subject, Foundations of Biomedical Ultrasound is an indispensible reference for any medical professional working with ultrasound imaging, and a comprehensive introduction to the subject for students. The book consists of ten chapters that bridge the spectrum from the fundamental properties of wave propagation through to clinical systems. The first four chapters describe linear and nonlinear propagation, and methods for calculating the field produced by transducers of various designs. A number of problems designed to test the reader's understanding, well-suited for formal class assignments, accompany these chapters. The topics of ultrasound scattering, and transducer design are addressed in chapters 5 and 6. The final four chapters addess methods of imaging and flow measurement. Some 350 drawings, graphs, sketches and colour images have been used. These, together with many tables, have been used to illustrate the various topics covered; a substantial portion of which are appearing for the first time in print.
Injection of anticentromere antibodies in interphase disrupts events required for chromosome movement at mitosis. (1990)

We have used autoantibodies to probe the function of three human centromere proteins in mitosis. These antibodies recognize three human polypeptides in immunoblots: CENP-A (17 kD), CENP-B (80 kD), and CENP-C (140 kD). Purified anticentromere antibodies (ACA-IgG) disrupt mitosis when introduced into tissue culture cells during interphase. We have identified two execution points for antibody inhibition. Antibodies injected into the nucleus greater than or equal to 3 h before mitosis prevent the chromosomes from undergoing normal prometaphase movements in the subsequent mitosis. Antibodies injected in the nucleus during late G2 cause cells to arrest in metaphase. Surprisingly, antibodies introduced subsequent to the beginning of prophase do not block mitosis. These results suggest that the CENP antigens are involved in two essential interphase events that are required for centromere action in mitosis. These may include centromere assembly coordinate with the replication of alpha-satellite DNA at the end of S phase and the structural maturation of the kinetochore that begins at prophase.
An anti-tissue factor monoclonal antibody which inhibits TF.VIIa complex is a potent anticoagulant in plasma. (1991)

Tissue factor (TF) functions as the receptor and cofactor for factor VIIa (VIIa) to form a proteolytically active TF.VIIa complex on cell surfaces. We here demonstrate that most MAbs against human TF were poor inhibitors of TF function in plasma and that they inhibited preformed TF.VIIa complex at a slow rate which was dependent on dissociation of VIIa from the cell surface TF. An exception was defined by one MAb (TF8-5G9) which was an effective immediate anticoagulant in plasma. Binding of TF8-5G9 to TF.VIIa inhibited catalytic function prior to dissociation of the TF.VIIa complex. This analysis thus establishes two distinct mechanisms by which MAbs interfere with TF function. The MAb TF8-5G9 introduces a therapeutic principle for rapid arrest of inappropriate triggering of coagulation by TF as well as the TF.VIIa complex in vivo.
Drugs and genotypes: how pharmacogenetic information could improve smoking cessation treatment (2006)

Current smoking cessation treatments are not optimal as the long-term abstinence rates are low. Nicotine replacement therapy and bupropion are the only pharmacotherapies widely available to smokers and there is a need to improve current cessation treatments and to develop new drug therapies. Our goal is to use pharmacogenetic information to improve smoking cessation treatments. Candidate genes include those involved in central mechanisms (such as genes encoding the nicotinic acetylcholine receptors, dopamine receptors, dopamine transporters and opioid receptors) and peripheral mechanisms (such as genes encoding the drug-metabolizing enzymes CYP2A6 and CYP2B6). Pharmacogenetics could be used to improve current smoking cessation treatments through two general approaches. The first would be to identify novel drug targets based on genetic variants that are associated with a natural protection against nicotine dependence, decreased smoking behaviour and/or increased smoking cessation. This knowledge could be used to develop drugs that can mimic these advantages, reducing the risk for acquisition, block the rewarding effects of smoking, decreasing the amount smoked and increasing cessation. The second would be to identify smokers with particular genetic variants who are likely to respond better to one treatment (or dose) versus another and to individualize their treatment to maximize long-term abstinence. This review will highlight examples of how pharmacogenetic information from central and peripheral candidate genes could contribute to improving smoking cessation outcomes by these two approaches.
Single-Step Generation of Conditional Knockout Mouse Embryonic Stem Cells (2015)

Induction of double-strand DNA breaks (DSBs) by engineered nucleases, such as CRISPR/Cas9 or transcription activator-like effector nucleases (TALENs), stimulates knockin of exogenous DNA fragments via homologous recombination (HR). However, the knockin efficiencies reported so far have not allowed more complex in vitro genome modifications such as, for instance, simultaneous integration of a DNA fragment at two distinct genomic sites. We developed a reporter system to enrich for cells with engineered nuclease-assisted HR events. Using this system in mouse embryonic stem cells (mESCs), we achieve single-step biallelic and seamless integration of two loxP sites for Cre recombinase-mediated inducible gene knockout, as well as biallelic endogenous gene tagging with high efficiency. Our approach reduces the time and resources required for conditional knockout mESC generation dramatically.
Whole-brain gray matter volume abnormalities in patients with generalized anxiety disorder (2014)

Patients with generalized anxiety disorder (GAD) experience psychological distress because of excessive and uncontrollable anxiety in everyday life. Only a few morphological studies have so far focused on specific brain regions of interest as well as the gray matter volume changes in GAD patients. This study evaluated gray matter volume alterations in whole-brain areas between GAD patients and healthy controls, and sex differences between the specific brain areas with significant volume changes in GAD patients using voxel-based morphometry. Twenty-two patients with GAD (13 men and nine women), who were diagnosed using the DSM-IV-TR, and 22 age-matched healthy controls (13 men and nine women) participated in this study. The high-resolution MRI data were processed using voxel-based morphometry analysis on the basis of diffeomorphic anatomical registration through an exponentiated Lie algebra algorithm in Statistical Parametric Mapping 8. There was no significant difference in the total intracranial volume between GAD patients and controls, but a significant difference was observed between sexes (P<0.05). Patients with GAD showed significant volume reductions in the hippocampus, midbrain, thalamus, insula, and superior temporal gyrus compared with the controls. As for the sex comparison, female patients showed a significant increase in the volume of the dorsolateral prefrontal cortex relative to male patients. Also, the volume of the dorsolateral prefrontal cortex in female patients was correlated positively with the Hamilton Anxiety Rating Scale score (γ=0.68, P=0.04). The specific morphological variations in patient with GAD will be helpful to understand the neural mechanism associated with a symptom of GAD. Furthermore, the findings would be valuable for the diagnostic accuracy of GAD using morphometric MRI analysis.
Chlamydia DNA extraction for use in PCR: Stability and sensitivity in detection (1998)

We evaluated multiple procedures for extracting chlamydial DNA from specimens for detection in PCR tests. Commercial kits and an in-house method were tested for their sensitivity and utility. Quantifiable chlamydial elementary bodies (EB) were used for spiking buffy coats from EDTA-collected blood. EBs of Chlamydia pneumoniae at 2,500 and 25 EB/ml were used as specimens for DNA extraction using seven different procedures. These included either columns (3 procedures), centrifugation (1), glass (1), or patented extraction matrices (2), coupled with either alcohol precipitation (6) or heat-detergent treatment (1). Five procedures required 10-40 minutes manipulation; two required 2-5 hours. PCR results for DNA extracts using chlamydial 16S genus primers were generally more intensely positive with denser bands on electrophoresis gels for the higher concentrations of EB (up to 4+ for stained product on gels) than was PCR with lower EB concentrations (up to 2+). Further, the incidence of procedures with positive results was: 5 of 7 for chlamydial genus primers with 5 EB vs. 6 of 7 with 500 EB. Maximal sensitivity for one of the extractions was in the range of 2.5-5.0 EB/ml of test specimen with 4 of 5 replicates being positive with EB controls or extracts. Extracts were stable up to 2+ weeks at 4 degrees C and were effective in multiplexing with fluorescent-tagged primers. Taking into consideration the time factor and sensitivities, the two procedures with extraction matrices are favored for routine laboratory use.
Speech recognition with deep recurrent neural networks (2013)

Recurrent neural networks (RNNs) are a powerful model for sequential data. End-to-end training methods such as Connectionist Temporal Classification make it possible to train RNNs for sequence labelling problems where the input-output alignment is unknown. The combination of these methods with the Long Short-term Memory RNN architecture has proved particularly fruitful, delivering state-of-the-art results in cursive handwriting recognition. However RNN performance in speech recognition has so far been disappointing, with better results returned by deep feedforward networks. This paper investigates deep recurrent neural networks, which combine the multiple levels of representation that have proved so effective in deep networks with the flexible use of long range context that empowers RNNs. When trained end-to-end with suitable regularisation, we find that deep Long Short-term Memory RNNs achieve a test set error of 17.7% on the TIMIT phoneme recognition benchmark, which to our knowledge is the best recorded score.
<title>Use Of Fresnel Lenses In Optical Systems: Some Advantages And Limitations</title> (1979)

The use of Fresnel lenses is expanding rapidly and they are now found in highly sophisticated optical systems. Their use has helped to solve many difficult optical problems but has also introduced some new design considerations. This paper will explain some of the advantages as well as some of the limitations of Fresnel lenses. &quot;Special&quot; optical design problems related to Fresnels will be discussed briefly. A description of tooling and part manufacturing methods and their related tolerances will be covered. Examples of existing Fresnel and &quot;hybrid&quot; systems will be given. On-going improvements and future developments that will make the use of Fresnels even more widespread will be described.
CRISPR/Cas9 mediated targeted mutagenesis of the fast growing cyanobacterium Synechococcus elongatus UTEX 2973 (2016)

High expression levels of the Cas9 protein in Synechococcus 2973 appear to be toxic and result in cell death. However, introduction of a CRISPR/Cas9 genome editing system on a plasmid backbone that leads to transient cas9 expression allowed for efficient markerless genome editing in a wild type genetic background.
α1,3 Fucosyltransferase VII plays a role in colorectal carcinoma metastases by promoting the carbohydration of glycoprotein CD24 (2010)

Changes in the expression levels of alpha1,3 FucT-VII and carbohydrate product SLe X have been reported in certain types of malignant transformations. However, the specific role of FucT-VII in human colorectal carcinoma is still not clear. We evaluated the expression of FucT-VII in tumor specimens from 30 colorectal carcinoma patients by RT-PCR and immunohistochemistry. The alteration of metastatic potential of LOVO cells before and after alpha1,3 FucT-VII gene transfection was also assayed. The expression change of glycoprotein CD24 and carbohydrate antigen SLe X after stable transfection of LOVO was also examined in vitro. Higher mRNA and protein expression of FucT-VII were observed in colorectal tumors compared with adjacent normal ones. The cell chemotactic migration and invasion were enhanced after alpha1,3 FucT-VII transfection in LOVO cells. There was a positive correlation between alpha1,3 FucT-VII mRNA expression and lymph node status (p=0.009) and AJCC stage (p=0.007), similar correlation was also observed at protein level (p=0.042 and 0.022, respectively). Overexpression of alpha1,3 FucT-VII promoted the expression of CD24 and SLe X in LOVO cells. Our findings suggest that alpha1,3 FucT-VII might play a role in colorectal carcinoma metastases by promoting the carbohydration of glycoprotein CD24.
Probiotics and inflammatory bowel diseases (2000)

The pathogenesis of inflammatory bowel diseases remains elusive. However, the resident luminal bacteria seem to be an important factor in their development and chronicity. There is evidence to suggest that inflammatory bowel diseases may represent an aggressive immunological response to the resident luminal flora, rather than an alteration in the normal flora. In prior research, probiotic bacteria were effective in managing certain acute diarrheal diseases, and investigators reported that certain Lactobacilli strains seem to have protective immunomodulating and bowel flora manipulating properties. We report the results of recent studies with probiotics in animal models, in which promising effects for the treatment of chronic inflammatory bowel disease, pouchitis, and ulcerative colitis were observed. Future research may clarify a precise role for probiotic bacteria in managing chronic inflammatory bowel diseases.
Downregulation of runt‐related transcription factor 3 associated with poor prognosis of adenoid cystic and mucoepidermoid carcinomas of the salivary gland (2010)

Runt-related transcription factor 3 (RUNX3) is a transcription factor of the transforming growth factor (TGF)-β superfamily and acts as a tumor suppressor gene, which is silenced by hypermethylation of the promoter region in various cancers. In this study, we examined the expression and methylation status of RUNX3 in the salivary gland cancers pleomorphic adenoma (PA), adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC). The cytoplasmic expression rates of RUNX3 in PA, ACC and MEC were 65% (13/20), 22.2% (8/36) and 20.6% (7/34), respectively. Low expression or deletion of RUNX3 in ACC and MEC was significantly associated with tumor progression and poor prognosis. Using microdissected cDNA, we found that RUNX3 mRNA expression was lower in ACC and MEC than in PA and noncancerous salivary glands; furthermore, hypermethylation of RUNX3 was detected more frequently in PA (2/8, 25%), ACC (6/8, 75%) and MEC (7/8, 87.5%) than in noncancerous salivary glands (0/8, 0%). Our results suggest that low expression or deletion of RUNX3 in salivary gland tumors might play a pivotal role in tumorigenesis and tumor progression and poor prognosis in the case of salivary gland ACC and MEC. Recovery of the tumor suppressive function of RUNX3 might inhibit tumorigenesis and cancer progression in the human salivary gland.
Time-dependent behavior of interstitial fluid pressure in solid tumors: implications for drug delivery. (1995)

Elevated interstitial fluid pressure (IFP) may constitute a significant physiological barrier to drug delivery in solid tumors. Strategies for overcoming this barrier have not been developed to date. To identify and characterize various mechanisms regulating IFP and to develop strategies for overcoming the IFP barrier, we modeled the tumor as a poroelastic solid. We used this model to simulate the effect of changes in microvascular pressure and tumor blood flow (TBF) on IFP. To test model predictions, the effects of changes in arterial pressure and TBF on IFP were measured using a tissue-isolated tumor preparation. IFP in the center of an isolated tumor was predicted to follow variation of the arterial pressure with a time delay of the order of magnitude of 10 s, and this delay was found to be 11 +/- 6 s experimentally. Following a cessation of TBF, the time constant of the drop in IFP was predicted to be of the order of 1000 s and was found to be 1500 +/- 900 s experimentally. The former time scale is characteristic of transcapillary fluid exchange, and the latter of percolation of fluid through the interstitial matrix. Relying on the good agreement between theoretical predictions and experimental data, we estimated the effect of blood pressure modulation on macromolecular uptake in solid tumors. Our results show that no appreciable increase of macromolecular uptake should occur either by an acute or by a chronic increase of blood pressure. On the other hand, higher uptake would result from periodic modulation of blood pressure. Therefore, the effectiveness of a vasoconstrictor such as angiotensin II to increase macromolecular delivery should be significantly enhanced by periodic rather than bolus or continuous administration of the vasoactive agent.
Cell biology of autoimmune diseases (1998)

Autoimmune diseases such as insulin-dependent diabetes mellitus, rheumatoid arthritis, and multiple sclerosis are common in the western world and are often devastating diseases which pose serious health problems. The key feature of such diseases is the development and persistence of inflammatory processes in the apparent absence of pathogens, leading to chronic breakdown of selected tissues. To date, no comprehensive explanation can be given for the onset or persistence of autoimmunity. As a rule, the chronic activation of helper T lymphocytes reactive against self proteins appears to be crucial for fueling the destructive autoimmune process, but why this occurs remains to be established. In this review, we present an overview on the rules that govern activation of T lymphocytes and on the factors that control it. The contribution of both genetic and environmental factors are discussed, clarifying that most autoimmune disease are of multifactorial origin. Special emphasis is given to the contribution of infectious events and the role of stress proteins in the process. In attempts to dissect the mechanisms involved in autoimmunity and to develop ways of blocking disease, experimental animal models are widely employed. We describe the various experimental models that exist for the study of multiple sclerosis, diabetes, and other autoimmune diseases and on the experience that has been gained in such models with experimental therapies to block the activation of self-reactive T lymphocytes. The lessons that can be drawn from these studies provide hope that continued efforts will lead to the successful development of antigen-specific strategies which block the development of autoimmunity also in humans.
Unique features of the apoptotic endonuclease DFF40/CAD relative to micrococcal nuclease as a structural probe for chromatinThis paper is one of a selection of papers published in this Special Issue, entitled 27th International West Coast Chromatin and Chromosome Conference, and has undergone the Journal's usual peer review process. (2006)

The gold standard for studies of nucleosomal chromatin structure for the past 30 years has been the enzyme micrococcal nuclease (MNase). During the course of our studies on the elucidation of the mechanism of action of the apoptotic nuclease DNA fragmentation factor-40 / caspase-activated deoxyribonuclease (DFF40/CAD) on naked DNA and chromatin substrates, it became clear that this enzyme is superior in certain respects to MNase for studying several aspects of chromatin structure. Here we review our published results supporting this statement. Relative to MNase, we have found that DFF40/CAD has the following properties: (i) it does not cut within nucleosomes to generate subnucleosomal DNA fragments; (ii) it is more specific for the linker regions between nucleosomes; (iii) it lacks exonuclease activity; (iv) it is specific for double-stranded DNA and makes exclusively double-stranded breaks; and (v) it attacks histone-H1-containing chromatin more efficiently. Taken together, these facts explain why DFF40/CAD generates sharper oligonucleosomal DNA ladders compared with those generated by MNase. We therefore recommend the following uses for DFF40/CAD for chromatin research: nucleosome isolation, chromatin-remodeling assays, repeat length measurements, and nucleosome-positioning assays along specific sequences. Other uses include footprinting assays of transcription factor positions, shearing chromatin for immunopreciptitation experiments (ChIP), and shearing DNA for recombinant DNA library preparation or for shotgun cloning for sequencing.
The amino acid sequence of residues 1-104 of CTL-1, a bovine H1 histone. (1981)

The amino acid sequence of the first 104 residues of calf thymus H1 histone subfraction (CTL-1), one of the H1 histones from bovine thymus, was determined by use of peptides derived from chymotryptic and staphylococcus protease digestion. The first 35 residues differ from the corresponding regions of a rabbit thymus H1 (RTL-3) and trout H1 by 30 and 39%, respectively, while in the region between residues 36 and 104 CTL-1 differs from the rabbit histone by only 4% and from the trout histone by only 16%. Although the differences between CTL-1 and sea urchin H1 are much greater, it is still evident that the sequence between residue 36 and residue 104 has been conserved much more than that between residues 1 and 35.