gebhart/patrepeval huggingface dataset:
Identification of Plasma Biomarkers of TBI Outcome Using Proteomic Approaches in an APOE Mouse Model (2011)

The current lack of diagnostic and prognostic biomarkers for traumatic brain injury (TBI) confounds treatment and management of patients and is of increasing concern as the TBI population grows. We have generated plasma proteomic profiles from mice receiving TBI by controlled cortical impact at either 1.3 mm or 1.8 mm depth, comparing these against those of sham injured-animals to identify plasma biomarkers specific to mild or severe TBI at 24 hours, 1 month, or 3 months post-injury. To identify possible prognostic biomarkers, we used apolipoprotein E (APOE)3 and APOE4 transgenic mice, which demonstrate relatively favorable and unfavorable outcomes respectively, following TBI. Using a quantitative proteomics approach (isobaric tagging for relative and absolute quantitation--iTRAQ) we have identified proteins that are significantly modulated as a function of TBI and also in response to the TBI*APOE genotype interaction, the latter representing potential prognostic biomarkers. These preliminary data clearly demonstrate plasma protein changes that are not only injury dependent but also interaction dependent. Importantly, these results demonstrate the presence of TBI-dependent and interaction-dependent plasma proteins at a 3-month time point, which is a considerable time post-injury in the mouse model, and will potentially be of significance for combat veterans receiving assessment at extended periods post-injury. Furthermore, our identification of clusters of functionally related proteins indicates disturbance of particular biological modules, which potentially increases their value beyond that of solitary biomarkers.
Real-time measurement of in vitro flow by Fourier-domain color Doppler optical coherence tomography (2004)

The possibility of measuring a full Doppler flow depth profile in parallel by use of frequency-domain optical coherence tomography is demonstrated. The method is based on a local phase analysis of the backscattered signal and allows for imaging of bidirectional Doppler flow. The Doppler frequency limit is 5 kHz for the presented measurements and is set by half of the frame rate of the CCD detector array. We measured the flow of 0.3-microm microspheres suspended in distilled water at controlled flow rates and in vitro human blood flow through a 200-microm capillary with a real-time color-encoded Doppler tomogram rate of 2-3/s.
Analysis of mitochondrial morphology and function with novel fixable fluorescent stains. (1996)

Investigation of mitochondrial morphology and function has been hampered because photostable, mitochondrion-specific stains that are retained in fixed, permeabilized cells have not been available. We found that in live cell preparations, the CMXRos and H2-CMXRos dyes were more photostable than rhodamine 123. In addition, fluorescence and morphology of mitochondria stained with the CMXRos and CMXRos-H2 dyes were preserved even after formaldehyde fixation and acetone permeabilization. Using epifluorescence microscopy, we showed that CMXRos and H2-CMXRos dye fluorescence fully co-localized with antibodies to subunit I of cytochrome c oxidase, indicating that the dyes specifically stain mitochondria. Confocal microscopy of these mitochondria yielded colored banding patterns, suggesting that these dyes and the mitochondrial enzyme localize to different suborganellar regions. Therefore, these stains provide powerful tools for detailed analysis of mitochondrial fine structure. We also used poisons that decrease mitochondrial membrane potential and an inhibitor of respiration complex II to show by flow cytometry that the fluorescence intensity of CMXRos and H2-CMXRos dye staining responds to changes in mitochondrial membrane potential and function. Hence, CMXRos has the potential to monitor changes in mitochondrial function. In addition, CMXRos staining was used in conjunction with spectrally distinct fluorescent probes for the cell nucleus and the microtubule network to concomitantly evaluate multiple features of cell morphology.
Preventive Effects of Inhaled Formoterol and Salbutamol on Histamine-lnduced Bronchoconstriction – A Placebo-Controlled Study (1992)

The preventive effects of inhaled formoterol (a new beta 2-agonist) and salbutamol aerosols on histamine-induced bronchoconstriction were studied in 12 patients with mild or moderate asthma in a placebo-controlled, double-blind study. Three hours after the administration of 12 micrograms formoterol, 200 micrograms salbutamol (doses with equal bronchodilator effects) or placebo via aerosol, histamine challenge was undertaken, using a dosimetric jet nebulizer with controlled tidal breathing. The noncumulative dose of histamine diphosphate aerosol provoking a 15% fall in FEV1 (PD15) was calculated. The PD15 after inhalation of 12 micrograms formoterol was significantly higher than that after 200 micrograms salbutamol (median values 640 and 310 micrograms, respectively; p < 0.01). For both treatments, the PD15 was significantly higher than that after placebo (median 185 micrograms). The results indicate that the preventive effect against histamine-induced bronchoconstriction at 3 h after drug is significantly better with formoterol than with salbutamol when using inhaled doses with an equal acute bronchodilator effect.
Protein structure prediction using hybrid AI methods (2002)

Describes a new approach for predicting protein structures based on artificial intelligence methods and genetic algorithms. We combine nearest neighbor searching algorithms, neural networks, heuristic rules and genetic algorithms to form an integrated system to predict protein structures from their primary amino acid sequences. First, we describe our methods and how they are integrated, and then apply our methods to several protein sequences. The results are very close to the real structures obtained by crystallography. Parallel genetic algorithms are also implemented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells. (2002)

To evaluate the role of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in breast cancer cell survival and therapeutic resistance, we analyzed a panel of six breast cancer cell lines that varied in erbB2 and estrogen receptor status. Akt activity was constitutive in four cell lines and was associated with either PTEN mutations or erbB2 overexpression. Akt promoted breast cancer cell survival because a PI3K inhibitor, LY294002, or transient transfection of a dominant-negative Akt mutant inhibited Akt activity and increased apoptosis. When combined with therapies commonly used in breast cancer treatment, LY294002 potentiated apoptosis caused by doxorubicin, trastuzumab, paclitaxel, or etoposide. Potentiation of apoptosis by LY294002 correlated with induction of Akt by doxorubicin or trastuzumab alone that occurred before the onset of apoptosis. Similar results were observed with tamoxifen. Combining LY294002 with tamoxifen in estrogen receptor-positive cells greatly potentiated apoptosis, which was correlated with tamoxifen-induced Akt phosphorylation that preceded apoptosis. To confirm that the effects of LY294002 on chemotherapy-induced apoptosis were attributable to inhibition of Akt, we transiently transfected breast cancer cells with dominant-negative Akt and observed increased doxorubicin-induced apoptosis. Conversely, stably transfecting cells with constitutively active Akt increased Akt activity and attenuated doxorubicin-induced apoptosis. These studies show that endogenous Akt activity promotes breast cancer cell survival and therapeutic resistance, and that induction of Akt by chemotherapy, trastuzumab, or tamoxifen might be an early compensatory mechanism that could be exploited to increase the efficacy of these therapies.
Transcranial ultrasound in adults and children with movement disorders (2012)

Since the first discovery, that ultrasound can overcome the skull allowing examination of the intracranial blood-flow as well as the first description of substantia nigra (SN) signal alterations via B-mode sonography, a plethora of applications especially in the field of movement disorders have been fostered. Up to now, however, most studies investigated adult individuals, even though numerous of the diseases studied have their onset already during childhood or adolescence. This overview summarizes recent studies of transcranial B-mode sonography (TCS) within the movement disorder field and outlines potential implications for pediatric applications.
Relationship of Porosity and Permeability to Various Parameters Derived from Mercury Injection-Capillary Pressure Curves for Sandstone (1) (1992)

Pore aperture size estimated from mercury injection tests has been used to evaluate seals for traps and to explain the locations of stratigraphic hydrocarbon accumulations. However, mercury injection tests are expensive and therefore not abundant. This paper develops empirical equations for estimating certain pore aperture size parameters from routine core analysis. The relationship of porosity, uncorrected air permeability, and various parameters derived from mercury injection-capillary pressure curves was established using multiple regression on a database of 202 samples of sandstone from 14 formations that range in age from Ordovician to Tertiary. These sandstone formations vary in composition and texture. A series of empirically derived equations also permits the calculation of pore aperture radii corresponding to mercury saturation values that range from 10 to 75% in increments of five. This makes it possible to construct a calculated pore aperture radius distribution curve using porosity and permeability from core analysis.
Protamine Sulfate Provides Enhanced and Reproducible Intravenous Gene Transfer by Cationic Liposome/DNA Complex (1997)

A novel lipid/polycation/DNA (LPD) formulation has been developed for in vivo gene transfer. It involves the condensation of plasmid DNA with protamine sulfate, a cationic polypeptide, followed by the addition of DOTAP cationic liposomes. Compared with DOTAP/DNA complex, LPD offers greater protection of plasmid DNA against enzymatic digestion and gives consistently higher gene expression in mice via tail vein injection. The in vivo efficiency of LPD was dependent upon charge ratio and was also affected by the lipid used. Increasing the amount of DNA delivered induced an increase in gene expression. The optimal dose was approximately 50 μg per mouse, at which concentration approximately 10 ng luciferase protein per mg extracted tissue protein could be detected in the lung. Gene expression in the lung was detected as early as 1 h after injection, peaked at 6 h, and declined thereafter. Using LacZ as a reporter gene, it was shown that endothelial cells were the primary locus of transgene expression in both lung and spleen. No sign of inflammation in these organs was noticed. Since protamine sulfate has been proven to be non-toxic and only weakly immunogenic in humans, this novel vector may be useful for the clinical use of gene therapy.
[A comparison of the hormonal and etholotropic activity of luliberin and its analogs]. (1990)

The paper is devoted to comparative analysis of the activity of peptides (LH-RH analogs) with relation to their action on ovulation as well as on the learning capabilities and their effect on immobilization stress in rats. The acceleration of learning processes and elimination of immobilization stress were shown to be caused by LH-RH and its analogs, regulating actively ovulation under experimental conditions. The comparative evaluation of their action has shown that LH-RH analogs-antagonists produce a more marked effect on the process of learning and elimination of stress consequences than its analogs-agonists.
Space-time-frequency trellis coding for frequency-selective fading channels (2003)

A novel space-time-frequency (STF) trellis coding scheme is developed for multi-antenna OFDM transmissions over frequency-selective Rayleigh fading channels. Incorporating subcarrier grouping and choosing appropriate system parameters, we first convert our system into a set of group STF (GSTF) systems. This enables simplification of STF block coding within each GSTF system. We derive design criteria for STF trellis coding, and exploit existing ST trellis coding techniques to construct STF trellis codes. The resulting codes are shown capable of achieving maximum diversity gains, while affording low-complexity decoding. The performance merits of our design is confirmed by corroborating simulations, and compared with existing alternatives.
ASC, a Novel 22-kDa Protein, Aggregates during Apoptosis of Human Promyelocytic Leukemia HL-60 Cells (1999)

The cytoskeletal and/or nuclear matrix molecules responsible for morphological changes associated with apoptosis were identified using monoclonal antibodies (mAbs). We developed mAbs against Triton X-100-insoluble components of HL-60 cells pretreated with all-trans retinoic acid. In particular, one mAb recognized a 22-kDa protein that exhibited intriguing behavior by forming an aggregate and appearing as a speck during apoptosis induced by retinoic acid and other anti-tumor drugs. Cloning and sequencing of its cDNA revealed that this protein comprises 195 amino acids and that its C-terminal half has a caspase recruitment domain (CARD) motif, characteristic of numerous proteins involved in apoptotic signaling. We referred to this protein as ASC (apoptosis-associated speck-like protein containing a CARD). The ASC gene was mapped on chromosome 16p11.2-12. The antisense oligonucleotides of ASC were found to reduce the expression of ASC, and consequently, etoposide-mediated apoptosis of HL-60 cells was suppressed. Our results indicate that ASC is a novel member of the CARD-containing adaptor protein family.
Development of β-Lapachone Prodrugs for Therapy Against Human Cancer Cells with Elevated NAD(P)H:Quinone Oxidoreductase 1 Levels (2005)

beta-Lapachone, an o-naphthoquinone, induces a novel caspase- and p53-independent apoptotic pathway dependent on NAD(P)H:quinone oxidoreductase 1 (NQO1). NQO1 reduces beta-lapachone to an unstable hydroquinone that rapidly undergoes a two-step oxidation back to the parent compound, perpetuating a futile redox cycle. A deficiency or inhibition of NQO1 rendered cells resistant to beta-lapachone. Thus, beta-lapachone has great potential for the treatment of specific cancers with elevated NQO1 levels (e.g., breast, non-small cell lung, pancreatic, colon, and prostate cancers). We report the development of mono(arylimino) derivatives of beta-lapachone as potential prodrugs. These derivatives are relatively nontoxic and not substrates for NQO1 when initially diluted in water. In solution, however, they undergo hydrolytic conversion to beta-lapachone at rates dependent on the electron-withdrawing strength of their substituent groups and pH of the diluent. NQO1 enzyme assays, UV-visible spectrophotometry, high-performance liquid chromatography-electrospray ionization-mass spectrometry, and nuclear magnetic resonance analyses confirmed and monitored conversion of each derivative to beta-lapachone. Once converted, beta-lapachone derivatives caused NQO1-dependent, mu-calpain-mediated cell death in human cancer cells identical to that caused by beta-lapachone. Interestingly, coadministration of N-acetyl-l-cysteine, prevented derivative-induced cytotoxicity but did not affect beta-lapachone lethality. Nuclear magnetic resonance analyses indicated that prevention of beta-lapachone derivative cytotoxicity was the result of direct modification of these derivatives by N-acetyl-l-cysteine, preventing their conversion to beta-lapachone. The use of beta-lapachone mono(arylimino) prodrug derivatives, or more specifically a derivative converted in a tumor-specific manner (i.e., in the acidic local environment of the tumor tissue), should reduce normal tissue toxicity while eliciting tumor-selective cell killing by NQO1 bioactivation.
Peptide Based Interleukin-1.BETA. Converting Enzyme(ICE) Inhibitors: Synthesis, Structure Activity Relationships and Crystallographic Study of the ICE-inhibitor Complex. (1999)

Based on the X-ray structure of the complex of Ac-Tyr-Val-Ala-Asp-H (L-709049) and interleukin-1 beta converting enzyme (ICE), we synthesized compounds which were derived from 2-NapCO-Val-Pro-Asp-CH2OPh (1) to obtain a potent inhibitor in the cell assay. Among these compounds, (3S)-N-methanesulfonyl-3-[[1-[N-(2-naphthoyl)-L-valyl]-L-prolyl]amino]- 4-oxobutanamide (27c) showed high potency not only in the enzyme assay but also cell assay with IC50 values of 38 nM and 0.23 microM, respectively. Compound 27c, with a c log P value of 1.76, had a more hydrophilic character compared with 1. Compound 27c also dose dependently inhibited LPS-primed ATP-induced IL-1 beta release in mice. The crystal structure of the complex of compound 27c and ICE revealed that compound 27c had further interactions with ICE in the naphthoyl group at the P4 position and in the methyl group of the methanesulfonamidecarbonyl group at the P1 position, compared with L-709049. To our knowledge, compound 27c is the first example that shows a strong inhibitory activity without the carboxyl group at the P1 position.
New Generation Taxoids and Hybrids of Microtuble-Stabilizing Anticancer Agents (2001)

Structure-activity relationship (SAR) studies on taxoids derived from 14-OH-baccatin III led to the discovery of a highly potent anticancer agent IDN5109. IDN5109 exhibits much superior activity against a variety of drug-resistant cancers as compared to paclitaxel and docetaxel, and is orally active with excellent bioavailability. Human clinical trials began on the basis of highly promising preclinical study results. A series of other "Second Generation Taxoids" that possess 2-3 orders of magnitude higher potencies against drug-resistant human cancer cell lines as compared to paclitaxel have been developed as well. On the basis of SAR results, conformational analyses, and molecular modeling, a common pharmacophore for paclitaxel, epothilones, eleutherobin, and discodermolide, all of which stabilize microtubules, has been proposed. Based on this common pharmacophore, various hybrids that would become significant lead compounds for the next generation de novo microtubule-stabilizing anticancer agents have been synthesized and their activities assayed. Photoaffinity labeling of microtubules and P-glycoprotein using photoreactive radiolabeled taxoids has disclosed the drug binding domain of tubulin as well as Pgp. Together with the information for microtubule-bound conformation of fluorine-labeled paclitaxel/taxoid obtained by solid state 19F NMR studies, the bioactive conformation of paclitaxel and taxoids appears to emerge, which is extremely important for the design and development of the next generation anticancer agents targeting microtubules.
A continuous intracerebral gene delivery system for in vivo liposome-mediated gene therapy. (1996)

Using a minipump combined with stereotaxic techniques allows continuous delivery of therapeutic genetic materials into the brain. We investigated the therapeutic efficacy of liposome-mediated HSVtk gene transfer of experimental brain F98 glioma followed by treatment with ganciclovir. A single injection of DNA-liposome complexes showed a therapeutically significant decrease in the tumor volume. Continuous intracerebral delivery of DNA-liposome complexes using an osmotic minipump led to complete tumor regression in 36.4% of the treated animals. The safety and toxicity of this gene delivery system were also assessed. No organ pathology was observed in the experimental animals. The continuous gene delivery system could be a useful means of achieving higher doses with less toxicity and without the need for frequent injections.
Genomic DNA differences between pathogenic and nonpathogenic Entamoeba histolytica. (1989)

cDNA libraries were constructed from pathogenic (HM-1:IMSS) and nonpathogenic (SAW 1734) isolates of Entamoeba histolytica. A cDNA clone (cEH-P1) specific for pathogenic amoebae was identified by screening with a pool of sera from patients with invasive amoebiasis that had been absorbed with nonpathogenic amoebae. This clone was used for the identification of a homologous clone (cEH-NP1) in the cDNA from nonpathogenic amoebae. Sequence analysis and comparison of the predicted amino acid sequences for both clones disclosed 12% evolutionary divergence in structure. Hybridization of both cDNA probes to genomic DNA from four pathogenic and five nonpathogenic E. histolytica isolates revealed two distinct Southern blot patterns, one characteristic for pathogenic amoebae and the other for nonpathogenic amoebae. Further, the complex pattern of restriction fragments hybridizing to an actin cDNA probe was also different between pathogenic and nonpathogenic isolates but was conserved within each group of amoebae. The results indicate that pathogenic isolates of E. histolytica are genetically distinct from nonpathogenic isolates.
<title>Conceptual monolithic pad grid array connector for transducer interconnects</title> (1992)

In this paper we describe and demonstrate a unique termination scheme whereby an array of coaxial wires is efficiently fabricated into a monolithic substrate resulting in a two-dimensional array structure forming a pad grid array connector. This structure has significant implications for high density cable interconnect applications in ultrasound transducer systems, circuit board and hybrid interconnect structures. A connector concept is proposed in which the interconnect is used as an in-line connector for a user-friendly transducer probe interconnect system. Future applications of the connector are described including use as an integrated substrate onto which both one and two-dimensional arrays can be fabricated or connected. Results including electrical testing are shown for a 12.7 mm (0.5') diameter, 100 position, 0.6 mm (.25') center-to-center rectilinear pad array connector utilizing 40 gauge 50 (Omega) coaxial wires.
Crystallographic refinement of interleukin 1 beta at 2.0 A resolution. (1989)

The structure of human recombinant interleukin 1 beta (IL-1 beta) has been refined by a restrained least-squares method to a crystallographic R factor of 17.2% to 2.0 A resolution. One-hundred sixty-eight solvent molecules have been located, and isotropic temperature factors for each atom have been refined. The overall structure is composed of 12 beta-strands that can best be described as forming the four triangular faces of a tetrahedron with hydrogen bonding resembling normal antiparallel beta-sheets only at the vertices. The interior of this tetrahedron is filled by hydrophobic side chains. Analysis of sequence alignments with IL-1 beta from other mammalian species shows the interior to be very well conserved with the exterior residues markedly less so. There does not appear to be a clustering of invariant amino acid side chains on the surface of the molecule, suggesting an area of interaction with the IL-1 receptor. Comparison of the IL-1 beta structure with IL-1 alpha sequences indicates that IL-1 alpha probably has a similar overall folding as IL-1 beta but binds to the receptor in a different fashion. The three-dimensional structure of the IL-1 beta is analyzed in light of what has been suggested by previously published work on mutants and fragments of the molecule.