gebhart/patrepeval huggingface dataset:
Acne: treatment with minocycline. (1976)

Forty-seven patients with acne, unresponsive to tetracycline and erythromycin, were treated with 100 mg minocycline daily. About one-quarter showed a 50% improvement or better. Five patients became dizzy during the first week of therapy, making it necessary to stop the medication in four instances. Two patients stopped treatment after several months because of esophagitis in one and headaches in another. Vestibular side effects are the most common complication of treatment. Patients should be warned about this side effect and if it occurs should avoid driving or handling machines. In some instances, dizziness may be so severe that the drug will have to be discontinued.
Bioorthogonal chemistry: strategies and recent developments (2013)

The use of covalent chemistry to track biomolecules in their native environment-a focus of bioorthogonal chemistry-has received considerable interest recently among chemical biologists and organic chemists alike. To facilitate wider adoption of bioorthogonal chemistry in biomedical research, a central effort in the last few years has been focused on the optimization of a few known bioorthogonal reactions, particularly with respect to reaction kinetics improvement, novel genetic encoding systems, and fluorogenic reactions for bioimaging. During these optimizations, three strategies have emerged, including the use of ring strain for substrate activation in the cycloaddition reactions, the discovery of new ligands and privileged substrates for accelerated metal-catalysed reactions, and the design of substrates with pre-fluorophore structures for rapid "turn-on" fluorescence after selective bioorthogonal reactions. In addition, new bioorthogonal reactions based on either modified or completely unprecedented reactant pairs have been reported. Finally, increasing attention has been directed toward the development of mutually exclusive bioorthogonal reactions and their applications in multiple labeling of a biomolecule in cell culture. In this feature article, we wish to present the recent progress in bioorthogonal reactions through the selected examples that highlight the above-mentioned strategies. Considering increasing sophistication in bioorthogonal chemistry development, we strive to project several exciting opportunities where bioorthogonal chemistry can make a unique contribution to biology in the near future.
Polyglutamine Diseases: Where does Toxicity Come from? What is Toxicity? Where are We Going? (2010)

Although the genetic basis of polyglutamine diseases has been recognized for 20 years, their molecular basis is still unclear. We have no therapeutic strategies for these intractable neurodegenerative disorders. To adequately treat patients, we must clarify the molecular basis of polyglutamine diseases. Three main issues address their molecular pathogenesis: whether the specific structure of expanded polyglutamine diseases results in cellular toxicity; what type of dysfunction causes them; and how the toxic structure causes dysfunction, that is, the link between structure and dysfunction. For structures, expanded polyglutamine proteins undergo transformation from monomers to oligomers and inclusions. One can hypothesize that one of these structures might cause the polyglutamine disease. Although the expanded polyglutamine protein is toxic, it does not explain the selective vulnerability of specific neurons in each polyglutamine disease. The normal function of each protein, including protein-protein interaction and modification, might also be crucial for pathogenesis. For dysfunction, various molecular mechanisms have been proposed, including dysregulation of transcription, impairment of the ubiquitin-proteasome system, mitochondrial dysfunction, dysregulation of intracellular Ca(2+) homeostasis, impairment of axonal transport and genotoxic stress. These hypotheses might correlate with each other. In addition, the disease pathogenesis of might not be exclusive to one particular structure or dysfunction. To develop a therapeutic strategy for patients with polyglutamine disease, identifying the most toxic structure and the earliest event in the pathogenesis is important. We review the current understanding of the toxic structure and dysfunction by expanded polyglutamine proteins and suggest directions for future studies of polyglutamine diseases.
Combining crossing-based and paper-based interaction paradigms for dragging and dropping between overlapping windows (2004)

Despite novel interaction techniques proposed for virtual desktops, common yet challenging tasks remain to be investigated. Dragging and dropping between overlapping windows is one of them. The fold-and-drop technique presented here offers a natural and efficient way of performing those tasks. We show how this technique successfully builds upon several interaction paradigms previously described, while shedding new light on them.
Bactericidal Treatment of Hatching Eggs V: Efficiency of Repetitive Immersions in Hydrogen Peroxide or Phenol to Eliminate Salmonella from Hatching Eggs (2002)

In previous studies, immersion in hydrogen peroxide and phenol reduced Salmonella-positive eggs without reducing hatchability. This study was carried out to determine if three consecutive dips in a chemical was more effective than a single immersion to eliminate Salmonella from hatching eggs. Eggs were inoculated with a marker strain of Salmonella typhimurium by submerging the egg in a solution containing low numbers (103) or high numbers (105) of the organism. After allowing the eggs to dry, they were immersed for 1, 2, and 3 min in water, a 1.4% solution of hydrogen peroxide, or a 0.39% solution of phenol. With the low inoculation, Salmonella were eliminated from an additional 22%of the eggs when three dips were used as compared to a single dip.
Contributions of Carnitine Acetyltransferases to Intracellular Acetyl Unit Transport in Candida albicans (2010)

Transport of acetyl-CoA between intracellular compartments is mediated by carnitine acetyltransferases (Cats) that reversibly link acetyl units to the carrier molecule carnitine. The genome of the opportunistic pathogenic yeast Candida albicans encodes several (putative) Cats: the peroxisomal and mitochondrial Cat2 isoenzymes encoded by a single gene and the carnitine acetyltransferase homologs Yat1 and Yat2. To determine the contributions of the individual Cats, various carnitine acetyltransferase mutant strains were constructed and subjected to phenotypic and biochemical analyses on different carbon sources. We show that mitochondrial Cat2 is required for the intramitochondrial conversion of acetylcarnitine to acetyl-CoA, which is essential for a functional tricarboxylic acid cycle during growth on oleate, acetate, ethanol, and citrate. Yat1 is cytosolic and contributes to acetyl-CoA transport from the cytosol during growth on ethanol or acetate, but its activity is not required for growth on oleate. Yat2 is also cytosolic, but we were unable to attribute any function to this enzyme. Surprisingly, peroxisomal Cat2 is essential neither for export of acetyl units during growth on oleate nor for the import of acetyl units during growth on acetate or ethanol. Oxidation of fatty acids still takes place in the absence of peroxisomal Cat2, but biomass formation is absent, and the strain displays a growth delay on acetate and ethanol that can be partially rescued by the addition of carnitine. Based on our results, we present a model for the intracellular flow of acetyl units under various growth conditions and the roles of each of the Cats in this process.
Nonthermal Dielectric-Barrier Discharge Plasma-Induced Inactivation Involves Oxidative DNA Damage and Membrane Lipid Peroxidation in Escherichia coli (2011)

Oxidative stress leads to membrane lipid peroxidation, which yields products causing variable degrees of detrimental oxidative modifications in cells. Reactive oxygen species (ROS) are the key regulators in this process and induce lipid peroxidation in Escherichia coli. Application of nonthermal (cold) plasma is increasingly used for inactivation of surface contaminants. Recently, we reported a successful application of nonthermal plasma, using a floating-electrode dielectric-barrier discharge (FE-DBD) technique for rapid inactivation of bacterial contaminants in normal atmospheric air (S. G. Joshi et al., Am. J. Infect. Control 38:293-301, 2010). In the present report, we demonstrate that FE-DBD plasma-mediated inactivation involves membrane lipid peroxidation in E. coli. Dose-dependent ROS, such as singlet oxygen and hydrogen peroxide-like species generated during plasma-induced oxidative stress, were responsible for membrane lipid peroxidation, and ROS scavengers, such as α-tocopherol (vitamin E), were able to significantly inhibit the extent of lipid peroxidation and oxidative DNA damage. These findings indicate that this is a major mechanism involved in FE-DBD plasma-mediated inactivation of bacteria.
Influence of Solid Friction on Polymer Relaxation in Gel Electrophoresis (1993)

Solid friction between a charged polymer and fixed gel points can dramatically affect polymer mobility in gel electrophoresis. The effect is present when a polymer chain is entangled over many gel points along a portion of its length, leading to significantly different behavior than predicted by conventional theory: the mobility of the chain decreases and exhibits a stronger length dependence, which separates long linear charged polymers of different molecular weights.
Fibroblast growth factor receptor 2, gain‐of‐function mutations, and tumourigenesis: investigating a potential link (2005)

Activating germline mutations in the fibroblast growth factor receptor (FGFR) gene family have been identified in several dominantly inherited skeletal disorders; in the case of FGFR3, the same somatically arising mutations have also been isolated from a variety of tumour tissues. Whilst the role of FGFR2 mutations in congenital syndromes has been well documented, their relationship with cancer has not been clearly defined. Based on evidence that gain-of-function mutations in FGFR2 drive positive selection in adult spermatogonia, the present study investigated, by denaturing high-performance liquid chromatography (DHPLC), DNA sequencing, and restriction digestion, the prevalence of FGFR2 mutations in 58 tumour cell lines of various types, and 29 testicular germ cell tumour samples. Although sequence variations and allelic imbalance were identified in FGFR2, none of the previously documented dominant mutations was detected in any of the tumour types examined. This suggests that gain-of-function FGFR2 mutations are not commonly encountered in tumourigenesis and specifically excludes a major contribution in testicular tumours.
Influence of epitope polarity and adjuvants on the immunogenicity and efficacy of a synthetic peptide vaccine against Semliki Forest virus (1993)

The antibody response to a previously defined B-cell epitope of Semliki Forest virus (SFV) was investigated in male BALB/c (H-2d) mice. The B-cell epitope, located at amino acid positions 240 to 255 of the E2 protein, was linked to an H-2d-restricted T-helper cell epitope of SFV located at positions 137 to 151 of the E2 protein. Colinearly synthesized peptides, of either T-B or B-T polarity, mixed with different adjuvants (the nonionic block copolymer L 180.5, a water-oil-water [W/O/W] emulsion of L 180.5, Montanide, and Q VAC) were used for immunization. Generally, after one booster immunization, high serum antibody titers were measured against either peptide. With Q VAC and W/O/W L 180.5 as adjuvants, the titers of SFV-reactive (nonneutralizing) antibodies were consistently much higher after immunization with the T-B peptide than with the B-T peptide, which was reflected in a higher vaccine efficacy. With these two adjuvants, the survival ratio in T-B peptide-immunized mice was 82%, compared with 8% in B-T peptide-immunized mice. Intermediate results were obtained with the adjuvant Montanide. L 180.5 alone was ineffective in this study. All immunoglobulin G (IgG) isotypes were induced with either adjuvant, but Q VAC was clearly the most effective in inducing IgG2a and IgG2b isotypes with the T-B peptide as the antigen. Subsequently, monoclonal antibodies (MAbs) of IgM, IgG1, IgG2a, IgG2b, and IgG3 subclasses were prepared against the B-cell epitope. These nonneutralizing but SFV-reactive MAbs protected 40 to 80% of mice against a lethal challenge with SFV. Control mice all died. The availability of those antipeptide MAbs allowed competition binding assays with a previously characterized panel of E2-specific MAbs. Binding of enzyme-labeled antipeptide MAbs was very effectively inhibited by two strongly SFV-neutralizing mutually competitive MAbs, suggesting that the linear B-cell epitope (amino acids 240 to 255) is associated with a major neutralization site of SFV.
Decorin Binds to a Narrow Region of the Epidermal Growth Factor (EGF) Receptor, Partially Overlapping but Distinct from the EGF-binding Epitope (2002)

Decorin, a small leucine-rich proteoglycan, is a key regulator of tumor growth by acting as an antagonist of the epidermal growth factor receptor (EGFR) tyrosine kinase. To search for cell surface receptors interacting with decorin, we generated a decorin/alkaline phosphatase chimeric protein and used it to screen a cDNA library by expression cloning. We identified two strongly reactive clones that encoded either the full-length EGFR or its ectodomain. A physiologically relevant interaction between decorin and EGFR was confirmed in the yeast two-hybrid system and further validated by experiments using EGF/EGFR interaction and transient cell transfection assays. Using a panel of deletion mutants, decorin binding was mapped to a narrow region of the EGFR within its ligand-binding L2 domain. Moreover, the central leucine-rich repeat 6 of decorin was required for interaction with the EGFR. Site-directed mutagenesis of the EGFR L2 domain showed that a cluster of residues, His(394)-Ile(402), was essential for both decorin and EGF binding. In contrast, K465, previously shown to be cross-linked to epidermal growth factor (EGF), was required for EGF but not for decorin binding. Thus, decorin binds to a discrete region of the EGFR, partially overlapping with but distinct from the EGF-binding domain. These findings could lead to the generation of protein mimetics capable of suppressing EGFR function.
N,N-dimethylformamide-induced alteration of cell culture characteristics and loss of tumorigenicity in cultured human colon carcinoma cells. (1979)

Human colon carcinoma cell lines established in this laboratory were treated in vitro with N,N-dimethylformamide. This polar solvent caused morphological changes in the cells as well as alterations in their growth properties. Untreated cells had cloning efficiencies of up to 77% in soft agar; treatment with N,N-dimethylformamide resulted in a complete loss of clonogenicity in semisolid medium. Growth in the presence of the polar solvent also effected a marked reduction in the tumorigenicity of the cells. Ten of ten nude mice that received a s.c. inoculum of 1 X 10(6) untreated cells developed tumors histologically similar to colonic adenocarcinomas in 10 to 14 days, whereas nine of ten nude mice inoculated with 1 X 10(6) treated cells have shown no sign of tumor 3 to 6 months postinjection. Removal of the polar solvent from the culture medium was accompanied by the reappearance of tumorigenicity and the original cell culture characteristics. Therefore, it appears that N,N-dimethylformamide can reversibly effect the reversion of cultured human colon carcinoma cells to less malignant cell types.
Self-tuning histograms (1999)

In this paper, we introduce self-tuning histograms. Although similar in structure to traditional histograms, these histograms infer data distributions not by examining the data or a sample thereof, but by using feedback from the query execution engine about the actual selectivity of range selection operators to progressively refine the histogram. Since the cost of building and maintaining self-tuning histograms is independent of the data size, self-tuning histograms provide a remarkably inexpensive way to construct histograms for large data sets with little up-front costs. Self-tuning histograms are particularly attractive as an alternative to multi-dimensional traditional histograms that capture dependencies between attributes but are prohibitively expensive to build and maintain. In this paper, we describe the techniques for initializing and refining self-tuning histograms. Our experimental results show that self-tuning histograms provide a low-cost alternative to traditional multi-dimensional histograms with little loss of accuracy for data distributions with low to moderate skew.
Robust speech interface based on audio and video information fusion for humanoid HRP-2 (2005)

For cooperative work of robots and humans in the real world, a communicative function based on speech is indispensable for robots. To realize such a function in a noisy real environment, it is essential that robots be able to extract target speech spoken by humans from a mixture of sounds by their own resources. We have developed a method of detecting and extracting speech events based on the fusion of audio and video information. In this method, audio information (sound localization using a microphone array) and video information (human tracking using a camera) are fused by a Bayesian network to enable the detection of speech events. The information of detected speech events is then utilized in sound separation using adaptive beam forming. In this paper, some basic investigations for applying the above system to the humanoid robot HRP-2 are reported. Input devices, namely a microphone array and a camera, were mounted on the head of HRP-2, and acoustic characteristics for sound localization/separation performance were investigated. Also, the human tracking system was improved so that it can be used in a dynamic situation. Finally, overall performance of the system was tested via off-line experiments.
Wyner-Ziv Coding with Temporal and Spatial Correlations for Motion Video (2006)

Distributed video coding (DVC), now has become one of the fastest evolving coding techniques in the current signal processing world. It has its remarkable low complex yet powerful encoder which is essential for some applications in the consumer market. In this paper we propose a novel Wyner-Ziv architecture that splits a frame in to two sub frames and leave one as a key sub frame while encoding the other as a WZ sub frame. The split key sub frame is encoded using a conventional coding scheme as in the other DVC techniques. At the decoder end the sub key frame is used to exploit the spatial and temporal correlations using an intra prediction technique and temporal motion search in order to generate the side information for the corresponding WZ sub frame. Simulation results show that over 1 dB PSNR gain can be obtained with the proposed algorithm over the results of the algorithm presented in the literature at the same bit rate
Sensing with microstructured optical fibres (2001)

The optical and geometrical properties of microstructured optical fibres present new alternatives for a range of sensing applications. We present the design criteria for achieving significant overlap between the light guided in the fibre and the air holes and hence for producing efficient evanescent field devices. In addition, the novel dispersive properties combined with the tight mode confinement possible in holey fibres make ultra-broadband single-mode sources and new source wavelengths a possibility. Microstructuring technology can be readily extended to form multiple-core fibres, which have applications in bend/deformation sensing. Finally, fibre-based atom waveguides could ultimately be used for rotational or gravitational sensing.
Automated Cough Assessment on a Mobile Platform (2014)

The development of an Automated System for Asthma Monitoring (ADAM) is described. This consists of a consumer electronics mobile platform running a custom application. The application acquires an audio signal from an external user-worn microphone connected to the device analog-to-digital converter (microphone input). This signal is processed to determine the presence or absence of cough sounds. Symptom tallies and raw audio waveforms are recorded and made easily accessible for later review by a healthcare provider. The symptom detection algorithm is based upon standard speech recognition and machine learning paradigms and consists of an audio feature extraction step followed by a Hidden Markov Model based Viterbi decoder that has been trained on a large database of audio examples from a variety of subjects. Multiple Hidden Markov Model topologies and orders are studied. Performance of the recognizer is presented in terms of the sensitivity and the rate of false alarm as determined in a cross-validation test.
Activation of progelatinase B (MMP-9) by gelatinase A (MMP-2). (1995)

The M(r) 72,000 (MMP-2; gelatinase A) and M(r) 92,000 (MMP-9; gelatinase B) gelatinases are two members of the family of matrix metalloproteinases (MMPs). These proteinases are thought to play a critical role in tumor cell invasion and are frequently coexpressed in human cancers. Gelatinases are secreted in a latent inactive form, and their conversion to the active species can be accomplished by other proteolytic enzymes, including other MMPs. We report herein that organomercurial or plasma membrane-activated M(r) 72,000 gelatinase A activates progelatinase B to an M(r) 82,000 active form in a process inhibited by tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. Progelatinase B activation was accomplished by the two active species of gelatinase A, the M(r) 62,000 and M(r) 45,000 forms, generated after plasma membrane or organomercurial activation of TIMP-2-free progelatinase A. The M(r) 45,000 species of gelatinase A lacks both the NH2-terminal profragment and the COOH-terminal domain known to play a role in plasma membrane activation and the regulation of TIMP-2 inhibition. These results suggest a novel mechanism of activation of progelatinase B mediated by gelatinase A species that may be localized in the surface of tumor cells and enhance matrix degradation during cancer metastasis.
Purification and Cloning of Hepatocyte Growth Factor Activator Inhibitor Type 2, a Kunitz-type Serine Protease Inhibitor (1997)

Hepatocyte growth factor (HGF) activator is a serine protease responsible for proteolytic activation of HGF in response to tissue injury and thus plays an important role in the regulation of biological functions of HGF in regenerating tissue. We previously purified an inhibitor of HGF activator (HGF activator inhibitor type 1, HAI-1) from the conditioned medium of a human stomach carcinoma cell line MKN45 and cloned its cDNA. HAI-1 is a novel member of the Kunitz family of serine protease inhibitors. In the present study, we purified a second type of HGF activator inhibitor (HAI-2) from the conditioned medium of MKN45 cells and molecularly cloned its cDNA. The cDNA sequence revealed that HAI-2 is derived from a precursor protein of 252 amino acids and contains two Kunitz domains, indicating that HAI-2 is also a member of the Kunitz family of serine protease inhibitors. The primary translation product of HAI-2 has a hydrophobic sequence in the COOH-terminal region, suggesting that, like HAI-1, HAI-2 is produced in a membrane-associated form and secreted in a proteolytically truncated form. Because HAI-2 and HAI-1 are potent inhibitors specific for HGF activator, they may be involved in regulation of proteolytic activation of HGF in injured tissues.
Unleashing the Power of Proteomics to Develop Blood-Based Cancer Markers (2012)

The realization of the potential of proteomics to yield blood biomarkers will benefit from a collaborative approach and a substantial investment in resources.