gebhart/patrepeval huggingface dataset:
Preventing Alzheimer’s Disease (2012)

Despite intensive laboratory and clinical research over three decades, an effective treatment to delay the onset and progression of Alzheimer's disease is not at hand. Recent clinical trial failures suggest that we must treat the disease earlier than in its mild to moderate stages, and major progress in validating presymptomatic biomarkers now makes secondary prevention trials possible. We will learn more about the natural history of the disease and any partial therapeutic responses from detailed analyses of recent trial results. This process will likely position the field for success, but only with much greater investment in all aspects of Alzheimer research and with careful design of future trials.
Image restoration methods for the Large Binocular Telescope(LBT) (2000)

A complete exploitation of the imaging properties of the Large Binocular Telescope (LBT) will require a generalization of the restoration methods which apply to the case of a single image. Several different observations must be combined to obtain a high-resolution representation of a given target. The purpose of this paper is to extend to this problem some of the most used restoration methods, including linear methods such as Tikhonov regularization as well as iterative regularization methods providing positive solution. The proposed methods are implemented and tested on simulated LBT images of diffuse and point-like objects. The results are discussed both from the point of view of the accuracy and from that of the computational efficiency, because LBT images may contain, in principle, up to 108 pixels.
The application of ethopharmacological techniques to behavioural teratology: preliminary investigations. (1986)

Ethopharmacological techniques were used to study the behaviour of the offspring of mice treated with different drugs before and after parturition. The "standard opponent" test was used and the animal's behaviour was recorded on videocassettes. It was found that ethyl alcohol, glutamate, cyproterone acetate, medroxyprogesterone acetate, corticosterone and thiourea changed, while lithium chloride and diazepam had no effect on social, defensive, threatening and aggressive behaviour.
Circulating miRNAs are correlated with tumor progression in prostate cancer (2010)

Circulating miRNAs have recently been indicated as practicable and promising biomarkers for noninvasive diagnosis in various tumor entities. However, cell-free miRNAs have not been found to correlate with clinicopathological variables in epithelial carcinomas. To learn more about the potential clinical relevance of circulating miRNAs in prostate cancer, we screened 667 miRNAs in serum samples from patients with metastatic (n = 7) and localized prostate cancer (n = 14). Various miRNAs were highly abundant in the sera of patients with metastatic disease, and five upregulated miRNAs (miRNA-375, miRNA-9*, miRNA-141, miRNA-200b and miRNA-516a-3p) were selected for further validation. In the first validation study (n = 45), selected miRNAs were analyzed in a prospectively collected serum set taken from different prostate cancer risk groups. Most of the selected miRNAs were significantly correlated with adverse risk factors when different clinicopathological variables were analyzed. Circulating miRNA-375 and miRNA-141 turned out to be the most pronounced markers for high-risk tumors. Their levels also correlated with high Gleason score or lymph-node positive status in a second independent validation study (n = 71). In addition, the expression levels of miRNA-375 and miRNA-141 were monitored in 72 prostate tissue samples (36 tumor vs. 36 benign). Both miRNAs were highly expressed in all samples and significantly upregulated in the tumors compared to normal tissues. Overall, our observations suggest that miRNA-375 and miRNA-141 expression is enhanced in prostate cancer specimens and their release into the blood is further associated with advanced cancer disease.
Lens-free optical tomographic microscope with a large imaging volume on a chip (2011)

We present a lens-free optical tomographic microscope, which enables imaging a large volume of approximately 15 mm(3) on a chip, with a spatial resolution of < 1 μm × < 1 μm × < 3 μm in x, y and z dimensions, respectively. In this lens-free tomography modality, the sample is placed directly on a digital sensor array with, e.g., ≤ 4 mm distance to its active area. A partially coherent light source placed approximately 70 mm away from the sensor is employed to record lens-free in-line holograms of the sample from different viewing angles. At each illumination angle, multiple subpixel shifted holograms are also recorded, which are digitally processed using a pixel superresolution technique to create a single high-resolution hologram of each angular projection of the object. These superresolved holograms are digitally reconstructed for an angular range of ± 50°, which are then back-projected to compute tomograms of the sample. In order to minimize the artifacts due to limited angular range of tilted illumination, a dual-axis tomography scheme is adopted, where the light source is rotated along two orthogonal axes. Tomographic imaging performance is quantified using microbeads of different dimensions, as well as by imaging wild-type Caenorhabditis elegans. Probing a large volume with a decent 3D spatial resolution, this lens-free optical tomography platform on a chip could provide a powerful tool for high-throughput imaging applications in, e.g., cell and developmental biology.
Phase 1 clinical trial of anti-CTLA4 human monoclonal antibody CP-675,206 in patients (pts) with advanced solid malignancies (2004)

2505 Background: Cytotoxic T Lymphocyte-associated Antigen 4 (CTLA4) is a T lymphocyte receptor responsible for negative regulation of cellular immune responses. CTLA4 blockade with CP-675,206 may break peripheral immunological tolerance and induce anti-tumor activity. Methods: We studied the safety, pharmacokinetics (PK), immune properties, and clinical activity of CP-675,206 in 39 pts with measurable disease (34) and no evidence of disease (5) (melanoma 34; renal cell 4; colon 1) after a single IV infusion at one of 7 dose levels: 0.01 (3 pts), 0.1 (3), 1.0 (3), 3.0 (8), 6.0 (5), 10.0 (11), and 15 mg/kg (6). Five pts at the lowest dose cohorts were re-enrolled at a higher dose level, for a total of 44 administered doses. Results: Therapy was delivered as planned. CP-675,206 proved safe and overall was well tolerated. Common adverse events included dermatitis (17, 39%), fatigue (17, 39%), pruritus (11, 25%), and diarrhea (11, 25%). DLTs were G3 diarrhea (1 at 6 mg/kg; 3 at 15 mg/kg) and G3 dermatitis (1 at 15mg/kg). The single dose MTD is 10 mg/kg. All observed autoimmunity except vitiligo (asthma, dermatitis, diarrhea, hypophysitis, and hyperthyroidism) was manageable and reversible. Plasma CP-675,206 concentrations were measured by ELISA. Peak concentrations and systemic exposure increase with dose. Concentrations remain >10 μg/mL (target efficacious concentration) for >4 weeks at doses ≥6 mg/kg; t½ is 25.6 days. Immune activation was assessed in a whole blood assay determining secreted IL-2 levels in response to Staphylococcal Enterotoxin A (SEA). CP-675,206 administration increased mean SEA reactivity 1-hr post-dose at all dose levels with a dose-response trend (P < 0.03). There were 2 CRs (18+, 8+ mo), 1 PR, and 6 SDs (3+ to 16 mo) among 34 pts with measurable disease. Conclusions: CTLA4 blockade can be induced with a single injection of CP-675,206. Related autoimmunity is reversible. Observed anti-tumor activity may be associated with breaking peripheral tolerance through this mechanism. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer, Inc. Pfizer, Inc. Pfizer Inc.
Development of a transposon mutagenesis system for Mycobacterium avium subsp. paratuberculosis (1999)

Mycobacterium avium subspecies paratuberculosis, a slow-growing Mycobacterium, is the causative agent of Johne's disease. Although M. paratuberculosis is difficult to manipulate genetically, our laboratory has recently demonstrated the ability to introduce DNA into these bacteria by transformation and phage infection. In the current study we develop the first transposon mutagenesis system for M. paratuberculosis using the conditionally replicating mycobacteriophage phAE94 to introduce the mycobacterial transposon Tn5367. Southern blotting and sequence analysis demonstrated that the transposon insertion sites are distributed relatively randomly throughout the M. paratuberculosis genome. We constructed a comprehensive bank of 5620 insertion mutants using this transposon. The transposition frequency obtained using this delivery system was 1.0×10−6 transposition events per recipient cell. Auxotrophic mutants were observed in this library at a frequency of 0.3%.
A spectrophotometric method for the microdetermination of periodate (1968)

1. A method is described for measuring the concentration of periodate over the range 0.2-20mum by adding 1,2-di-(p-dimethylaminophenyl)ethane-1,2-diol to a sample solution. Periodate cleaves this compound to from two molecules of p-dimethylaminobenzaldehyde, the extinction of which is then read at 352mmu. 2. The method has been used to follow the course of periodate oxidations of serine methyl ester, ribonuclease A and ribonuclease S-protein. Addition of the reagent stops further periodate reaction by reducing the remaining periodate to iodate. 3. The presence of protein does not interfere with the assay.
Effects of extracorporeal shock wave therapy on wounds of the distal portion of the limbs in horses (2009)

Findings suggested that ESWT may stimulate healing of wounds of the distal portion of the limbs in horses, although the mechanism by which healing was stimulated could not be identified.
A Single Subunit from Avian Myeloblastosis Virus with Both RNA-Directed DNA Polymerase and Ribonuclease H Activity (1973)

Two structurally distinct forms of RNA-directed DNA polymerase from avian myeloblastosis virus were resolved by chromatography on phosphocellulose and purified. In addition to RNA-directed DNA polymerase activity, both enzymes had ribonuclease H (RNase H) activity, which degraded the RNA moiety of RNA.DNA hybrids. As determined by sodium dodecyl sulfate-polyacrylamide disc-gel electrophoresis, one form had two subunits, alpha (alpha) and beta (beta), with molecular weights of 65,000 and 105,000, respectively. The other had a single subunit, alpha, with a molecular weight of 65,000. The sedimentation coefficients of alphabeta and alpha, determined by glycerol gradient centrifugation in 0.35 M KCl, were 7.8 S and 5.2 S, respectively. Both enzymes had similar antigenic determinants and could not be distinguished by a differential response to several different RNA and DNA templates. We suggest that alpha, which contains both RNA-directed DNA polymerase and RNase H activity, is derived by dissociation of alphabeta; the function of the beta subunit is unknown.
Design of microfabricated inductors for microprocessor power delivery (1999)

Microfabricated inductor designs are proposed for converters for microprocessor power delivery. The fabrication process uses anisotropic silicon etching to form V-grooves; granular metal/insulator nanoscale composite magnetic materials; and copper conductors. An application specific calculation procedure results in an inductor design with predicted power density over 200 W/cm/sup 2/ at 95% efficiency for an 8 MHz, 3.6 V to 1.1 V converter.
Broad-band Gaussian noise is most effective in improving motor performance and is most pleasant (2014)

Modern attempts to improve human performance focus on stochastic resonance (SR). SR is a phenomenon in non-linear systems characterized by a response increase of the system induced by a particular level of input noise. Recently, we reported that an optimum level of 0-15 Hz Gaussian noise applied to the human index finger improved static isometric force compensation. A possible explanation was a better sensorimotor integration caused by increase in sensitivity of peripheral receptors and/or of internal SR. The present study in 10 subjects compares SR effects in the performance of the same motor task and on pleasantness, by applying three Gaussian noises chosen on the sensitivity of the fingertip receptors (0-15 Hz mostly for Merkel receptors, 250-300 Hz for Pacini corpuscles and 0-300 Hz for all). We document that only the 0-300 Hz noise induced SR effect during the transitory phase of the task. In contrast, the motor performance was improved during the stationary phase for all three noise frequency bandwidths. This improvement was stronger for 0-300 Hz and 250-300 Hz than for 0-15 Hz noise. Further, we found higher degree of pleasantness for 0-300 Hz and 250-300 Hz noise bandwidths than for 0-15 Hz. Thus, we show that the most appropriate Gaussian noise that could be used in haptic gloves is the 0-300 Hz, as it improved motor performance during both stationary and transitory phases. In addition, this noise had the highest degree of pleasantness and thus reveals that the glabrous skin can also forward pleasant sensations.
Predotar: A tool for rapidly screening proteomes for N ‐terminal targeting sequences (2004)

Probably more than 25% of the proteins encoded by the nuclear genomes of multicellular eukaryotes are targeted to membrane-bound compartments by N-terminal targeting signals. The major signals are those for the endoplasmic reticulum, the mitochondria, and in plants, plastids. The most abundant of these targeted proteins are well-known and well-studied, but a large proportion remain unknown, including most of those involved in regulation of organellar gene expression or regulation of biochemical pathways. The discovery and characterization of these proteins by biochemical means will be long and difficult. An alternative method is to identify candidate organellar proteins via their characteristic N-terminal targeting sequences. We have developed a neural network-based approach (Predotar--Prediction of Organelle Targeting sequences) for identifying genes encoding these proteins amongst eukaryotic genome sequences. The power of this approach for identifying and annotating novel gene families has been illustrated by the discovery of the pentatricopeptide repeat family.
Mechanical regulation of vascular growth and tissue regeneration in vivo (2011)

New vascular network formation is a critical step in the wound healing process and a primary limiting factor in functional tissue regeneration. Like many tissues, neovascular networks have been shown in vitro to be highly sensitive to mechanical conditions; however, the effects of matrix deformations on neovascular network formation and remodeling in engineered tissue regeneration in vivo have not been evaluated. We quantified the effects of early and delayed functional loading on neovascular growth in a rat model of large bone defect regeneration using compliant fixation plates that were unlocked to allow transfer of ambulatory loads to the defect either at the time of implantation (early), or after 4 wk of stiff fixation (delayed). Neovascular growth and bone regeneration were quantitatively evaluated 3 wk after the onset of loading by contrast-enhanced microcomputed tomography and histology. The initial vascular response to bone injury featured robust angiogenesis and collateral vessel formation, increasing parameters such as vascular volume and connectivity while decreasing degree of anisotropy. Application of early mechanical loading significantly inhibited vascular invasion into the defect by 66% and reduced bone formation by 75% in comparison to stiff plate controls. In contrast, delaying the onset of loading by 4 wk significantly enhanced bone formation by 20% and stimulated vascular remodeling by increasing the number of large vessels and decreasing the number of small vessels. Together, these data demonstrate the mechanosensitivity of neovascular networks and highlight the capacity of biomechanical stimulation to modulate postnatal vascular growth and remodeling.
Nanotechnology for Alzheimer’s disease detection and treatment (2011)

In this paper, we present the role of nanotechnology in the development and improvement of techniques for early diagnosis and effective treatment of Alzheimer's disease (AD). Since AD pathology is almost irreversible and present-day medications for AD only lower its associated symptoms, application of disease-modifying treatments could be successful only if AD early diagnosis is possible. The nanodiagnostic methods reported and compared in this paper include both of in vitro and in vivo nature. Of the in vitro approaches, the DNA-nanoparticle conjugates (bio-barcode assay), nanoparticle surface plasmon resonance, scanning tunneling microscopy, and two-photon Rayleigh spectroscopy are presented here. Of the in vivo methods, MRI and optical imaging techniques are discussed here. The nanotreatment methods for AD are numerous. They are categorized in this report under neuroprotective methods from toxicity of amyloid- peptide (A) oligomers, oxidative stress of free radicals and nanocarriers for targeted drug delivery. The important agents for neuroprotection include nanogels, fullerene, nano-ceria, dendrimers, gold nanoparticles, and diamondoid derivatives. The major nanocarriers presented here include cholinesterase inhibitors nanocarriers, acetylcholine nanocarrier, metal chelator nanocarriers, (Iron chelators and copper chelators), curcuminoids nanocarrier, anti-oxidant nanocarriers, and gene nanocarriers. Considering that the AD is a multi-factorial disease with several pathogenetic mechanisms and pathways, a multifunctional nanotechnology approach will be needed to target its main molecular culprits. These molecular targets must include, but not limited to, A oligomers, reactive oxygen species (ROS), excessive metal ions, tau phosphorylating kinases and cell cycle proteins.
Designing better phages (2001)

We propose a method to engineer the genome of bacteriophages to increase their effectiveness as antibacterial agents. Specifically, we exploit the redundancy of the triplet code to design genomes that avoid restriction sites while producing the same proteins as wild-type phages. We give an efficient algorithm to minimize the number of restriction sites against sets of cutter sequences, and demonstrate that that phage genomes can be significantly protected against surprisingly large sets of enzymes with no loss of function. Finally, we develop a model to explain why evolution has failed to eliminate many possible restriction sites despite selective pressure, thus motivating the need for genome-level sequence engineering.
Interspecies Dose Extrapolation for Inhaled Dimethyl Sulfate: A PBPK Model-Based Analysis using Nasal Cavity N7-Methylguanine Adducts (2004)

Dimethyl sulfate (DMS) is a volatile sulfuric acid ester used principally as a methylating agent in a wide variety of industrial applications. DMS reacts with organic macromolecules by a SN2 mechanism. The weight of experimental evidence suggests that DMS possesses genotoxic and carcinogenic potential. Inhalation studies have shown that repeated exposure to DMS leads to tumors in the nasal cavity and lower respiratory tract in both rats and mice. Here we present a quantitative assessment for cross-species dose extrapolation for inhaled DMS using a physiologically based pharmacokinetic (PBPK) model. The model is designed to simulate N7-methylguanine (N7 mG) DNA adduct levels in the nasal mucosa following DMS exposure in rats and humans. This model was parameterized and predictions were tested by comparison against experimentally measured N7 mG DNA adduct levels in rat nasal mucosa following inhalation exposure to DMS. The model-based interspecies dose comparison, using N7 mG adduct levels in the nasal respiratory tissue as the appropriate dose metrics, predicts a dose rate seven times higher in rats compared to humans.
Modelling free-carrier absorption in solar cells (1997)

Free-carrier absorption can be a significant parasitic optical absorption process in solar cells. Although estimates of its influence have been made in the past, it has not previously been incorporated into a numerical semiconductor device simulator and studied in conjunction with other effects. A finite element model of free-carrier absorption is presented that incorporates the dependency of the absorption coefficient on the carrier concentration profile, including the change in carrier density that occurs across a single finite element. This model has been implemented in the semiconductor modelling program PC1D for Windows, and used to simulate the effects of free-carrier absorption on several types of silicon solar cells. It was found to have only a very small effect on cell efficiency, but can significantly affect the long-wavelength spectral response, which has implications for device characterization. Empirical equations for the behaviour of free-carrier absorption in a variety of materials are presented. © 1997 John Wiley & Sons, Ltd.
Assessment of Bet v 1-Specific CD4+ T Cell Responses in Allergic and Nonallergic Individuals Using MHC Class II Peptide Tetramers (2008)

In this study, we used HLA-DRB1*0101, DRB1*0401, and DRB1*1501 peptide tetramers combined with cytokine surface capture assays to characterize CD4(+) T cell responses against the immunodominant T cell epitope (peptide 141-155) from the major birch pollen allergen Bet v 1, in both healthy and allergic individuals. We could detect Bet v 1-specific T cells in the PBMC of 20 birch pollen allergic patients, but also in 9 of 9 healthy individuals tested. Analysis at a single-cell level revealed that allergen-specific CD4(+) T cells from healthy individuals secrete IFN-gamma and IL-10 in response to the allergen, whereas cells from allergic patients are bona fide Th2 cells (producing mostly IL-5, some IL-10, but no IFN-gamma), as corroborated by patterns of cytokines produced by T cell clones. A fraction of Bet v 1-specific cells isolated from healthy, but not allergic, individuals also expresses CTLA-4, glucocorticoid-induced TNF receptor, and Foxp 3, indicating that they represent regulatory T cells. In this model of seasonal exposure to allergen, we also demonstrate the tremendous dynamics of T cell responses in both allergic and nonallergic individuals during the peak pollen season, with an expansion of Bet v 1-specific precursors from 10(-6) to 10(-3) among circulating CD4(+) T lymphocytes. Allergy vaccines should be designed to recapitulate such naturally protective Th1/regulatory T cell responses observed in healthy individuals.
Algorithms for optimal scheduling and management of hidden Markov model sensors (2002)

The author considers a hidden Markov model (HMM) where a single Markov chain is observed by a number of noisy sensors. Due to computational or communication constraints, at each time instant, one can select only one of the noisy sensors. The sensor scheduling problem involves designing algorithms for choosing dynamically at each time instant which sensor to select to provide the next measurement. Each measurement has an associated measurement cost. The problem is to select an optimal measurement scheduling policy to minimize a cost function of estimation errors and measurement costs. The optimal measurement policy is solved via stochastic dynamic programming. Sensor management issues and suboptimal scheduling algorithms are also presented. A numerical example that deals with the aircraft identification problem is presented.