gebhart/patrepeval huggingface dataset:
Recent Trends in the Use of Polysaccharides for Improved Delivery of Therapeutic Agents: Pharmacokinetic and Pharmacodynamic Perspectives (2003)

New and innovative methods of delivery of therapeutic agents using polysaccharides have been recently developed, which target site of action, increase the intensity and/or prolong pharmacologic action, and/or reduce toxicity of small molecule drugs, proteins, or enzymes. This review is focused on the role of dextran, pullulan, and mannan polysaccharides in such applications. While dextran and pullulan are glucose polymers with different glucosidic linkages, mannan is composed of mannose units. In terms of pharmacokinetics of the carriers themselves, molecular weight (MW), electric charge, various chemical modifications, and degree of polydispersity and/or branching would mostly determine their fate in vivo. Generally, large MW polysaccharides (MWs > or = 40 kD) have low clearance and relatively long plasma half life, resulting in accumulation in reticuloendothelial or tumor tissues. The tumor accumulation in most cases is a passive targeting due to "enhanced permeation and retention" of macromolecules by tumors. Additionally, drugs such as anticancer agents may be actively targeted to specific cells by polysaccharides to which appropriate ligands are attached. In terms of mode of use, polysaccharides have been utilized in a variety of innovative ways for improvement of drug delivery. Their most important application has been as carriers for preparation of macromolecular prodrugs that are normally inactive and need to release the active drug at the site(s) of interest. Also, they have been used for preparation of macromolecule-protein conjugates, which may retain the activity of the proteins, in order to increase the duration of effect and decrease the immunogenicity of proteins. Several other new applications, such as polysaccharide-anchored liposomal formulations, have also been gained attention recently and are briefly reviewed here. Finally, four recent examples of polysaccharide-based delivery systems involving specific drugs/imaging agents are reviewed in detail in terms of their development, pharmacokinetics, and pharmacodynamics. Collectively, these data suggest that macromolecular polysaccharides are promising agents for improving drug delivery.
Influence of long-term infusions on lidocaine kinetics (1982)

Lidocaine kinetics were examined during continuous infusions in five healthy subjects using stable isotope lidocaine labeled with two deuterium atoms. During phase 1, lidocaine and stable isotope lidocaine (50 mg IV each) were given as a bolus to confirm that the two species were kinetically identical. Phase 2 consisted of a long-term (30 hr) lidocaine infusion designed to produce a steady-state concentration equal to 1.5 microgram/ml. Twenty-four hours into the infusion, stable isotope lidocaine (50 mg) was given as an intravenous bolus and kinetic parameters were calculated. Phase 3 differed from phase 2 in that target steady-state lidocaine concentration was 4 microgram/ml and the stable isotope lidocaine dose was reduced to 40 mg. A gas chromatograph-mass spectrometer was used to determine lidocaine and stable isotope lidocaine serum concentrations. Compared to phase 1, clearance decreased (P less than 0.05) and half-life increased (P less than 0.025) during phases 2 and 3. The volume of distribution at steady-state remained constant during all three phases. Lidocaine cumulated in serum during long-term infusions in all five patients; repeated decreases in infusion rate were necessary to avoid exceeding desired target concentrations in phases 2 and 3.
Expression strategy of a phlebovirus: biogenesis of proteins from the Rift Valley fever virus M segment (1990)

The middle (M) RNA segment of Rift Valley fever virus (RVFV) encodes four proteins: the major viral glycoproteins G2 and G1, a 14-kilodalton (kDa) protein, and a 78-kDa protein. These proteins are derived from a single large open reading frame (ORF) present in the virus-complementary M-segment mRNA. We used recombinant vaccinia viruses in which sequences representing the M-segment ORF were engineered as a surrogate system to study phlebovirus protein expression. To investigate the translational initiation codon requirements for synthesis of these proteins, we constructed a series of vaccinia virus recombinants containing specific sequence changes which eliminated select ATG codons found in the region of the ORF preceding the mature glycoprotein-coding sequences (the preglycoprotein region). Examination of phleboviral proteins synthesized in cells infected with these vaccinia virus recombinants clearly showed that the first ATG of the ORF was required for the production of the 78-kDa protein, while synthesis of the 14-kDa protein was absolutely dependent on the second in-phase ATG codon. Efficient biosynthesis of glycoprotein G2 was shown to depend on one or more ATG codons within the preglycoprotein region, but not the first one of the ORF. Synthesis of about one-half of the total glycoprotein G1 was affected by the amino acid changes that eliminated ATG codons, while production of the remainder appeared to be independent of all ATG codons in the preglycoprotein region. These data indicated that the means for glycoprotein G1 biosynthesis was distinct from those of the other three M-segment gene products. The results presented herein suggest that a surprisingly complex expression strategy is employed by the RVFV M segment. Although the full nature of the mechanisms involved in the biogenesis of the four RVFV M-segment proteins remains unclear, it does involve the use of at least two (ATG codons 1 and 2), and likely more, distinct translation start sites within the same ORF to produce its complete complement of gene products.
LA PROFESIONALIZACION DEL TRABAJO SOCIAL SURGIO EN MEXICO HACE 50 ANOS (1994)

EL LIBRO EL TRABAJO SOCIAL EN MEXICO, DESARROLLO Y PERSPECTIVAS, DE LA MAESTRA AIDA VALERO CHAVEZ, COORDINADORA DE INVESTIGACION EN LA ESCUELA NACIONAL DE TRABAJO SOCIAL (ENTS) FUE PRESENTADO EN LA CASA UNIVERSITARIA DEL LIBRO. EL LIBRO, EDITADO POR LA ENTS, EXPONE LAS DIVERSSAS ETAPAS QUE HAN CARACTERIZADO A ESTA DISCIPLINA, ASI COMO LAS TENDENCIAS ACTUALES Y FUTURAS.
Kinetic study of enzymatic urea hydrolysis in the pH range 4-9 (2003)

The enzymatic hydrolysis of urea by jack bean urease was investigated at 25degreesC over the pH range 4-9. Reaction rate data were found to be well described by a modified Michaelis-Menten equation with a pH-dependent rate coefficient and a product inhibition term. The influence of pH on activity was interpreted in terms of perturbation of the enzyme distribution among three differently protonated forms. Kinetic analysis yielded a Michaelis constant of 3.21 mmol l(-1) and indicated that the inhibition mechanism was of the fully non-competitive type, with K-P = 12.2 mmol l(-1). The estimated activation energy was 35.3 kJ mol(-1). The resulting kinetic expression was tested by comparing model predictions with the experimental behaviour observed in unbuffered media and over a long-teen period.
Monoclonal anti‐dipeptide antibodies cross‐react with detyrosinated and glutamylated forms of tubulins (1995)

Two monoclonal antibodies, GLU-1 and A1.6, raised against gamma-L-glutamyl-L-glutamic acid dipeptide (Glu-Glu) and Ca(2+)-dependent ATPase from Paramecium, respectively, recognized the dipeptide Glu-Glu sequence. Whereas the antibodies immunofluorescently stained very few, if any, cytoskeletal fibers in cultured mammalian cells, almost all interphase as well as mitotic spindle microtubules became visible after treatment of cells with carboxypeptidase A. Immunoblot analysis demonstrated intense cross-reaction of the antibodies to the alpha-tubulin subunit. alpha-Tubulin isotypes produced as fusion proteins in bacteria were labeled by both the antibodies only when the proteins did not contain a tyrosine residue at the C terminus, indicating that GLU-1 and A1.6 specifically recognize the detyrosinated form of alpha-tubulin. When microtubule protein purified from brain was probed, not only alpha-but also, to a lesser extent, beta-tubulin were revealed by the dipeptide antibodies. A synthetic tripeptide YED containing one glutamyl group linked to the second residue of the peptide via the gamma position was also recognized by the antibodies. Since this peptide sequence corresponds to the amino acid sequence of polyglutamyated class III beta isotype at amino acid position 437 to 439, it is suggested that GLU-1 and A1.6 are able to recognize the glutamylated form of beta-tubulin. These results indicate that the C-terminal Glu-Glu sequence displays strong antigenicity, and the antibodies recognize the sequence present in the C terminus of the detyrosinated form of alpha-tubulin and the glutamyl side chain of beta-tubulin. Particularly strong immunoreaction was detected with ciliary and flagellar microtubules; thus, stable axonemal microtubules appear to be rich in post-translationally modified tubulin subunits.
Nasal-Associated Lymphoid Tissue Is a Mucosal Inductive Site for Virus-Specific Humoral and Cellular Immune Responses (2002)

Peyer's patches are known as mucosal inductive sites for humoral and cellular immune responses in the gastrointestinal tract. In contrast, functionally equivalent structures in the respiratory tract remain elusive. It has been suggested that nasal-associated lymphoid tissue (NALT) might serve as a mucosal inductive site in the upper respiratory tract. However, typical signs of mucosal inductive sites like development of germinal center reactions after Ag stimulation and isotype switching of naive B cells to IgA production have not been directly demonstrated. Moreover, it is not known whether CTL can be generated in NALT. To address these issues, NALT was structurally and functionally analyzed using a model of intranasal infection of C3H mice with reovirus. FACS and histological analyses revealed development of germinal centers in NALT in parallel with generation and expansion of IgA(+) and IgG2a(+) B cells after intranasal reovirus infection. Reovirus-specific IgA was produced in both the upper respiratory and the gastrointestinal tract, whereas production of reovirus-specific IgG2a was restricted to NALT, submandibular, and mesenteric lymph nodes. Moreover, virus-specific CTL were detected in NALT. Limiting dilution analysis showed a 5- to 6-fold higher precursor CTL frequency in NALT compared with a cervical lymph node. Together these data provide direct evidence that NALT is a mucosal inductive site for humoral and cellular immune responses in the upper respiratory tract.
Permeation of antigen protein-conjugated nanoparticles and live bacteria through microneedle-treated mouse skin (2011)

Transcutaneous immunization on a microneedle-treated skin area with antigens carried by nanoparticles can potentially induce a strong immune response, and the risk of bacterial infection associated with microneedle treatment is no greater than that with a hypodermic injection.
3-D Pore-Scale Modelling of Sandstones and Flow Simulations in the Pore Networks (1997)

Summary A new method for generating realistic homogenous and heterogeneous 3-D pore-scale sandstone models is presented. The essence of our method is to build sandstone models which are analogs of actual sandstones by numerically modelling the results of the main sandstone-forming geological processes - sandgrain sedimentation, compaction, and diagenesis. The input data for the modelling are obtained from image analyses of thin section images of the actual sandstone. The spatial continuity of the sandstone model in the X, Y, and Z directions is determined using a scale-independent invasion percolation based algorithm. The resulting spatial continuity function, which is an ellipsoid, may be used as a heterogeneity descriptor for the sandstone model. Heterogeneity analyses show that compaction reduces the spatial continuity in the horizontal direction more rapidly than in the vertical one. The architecture and geometry of the network representation of the pore space are determined by applying various 3-D image analysis algorithms directly on the fully characterised sandstone model. A 3-D pore network which was generated from thin section data from a strongly water wet Bentheimer sandstone is used as input to a two-phase network flow simulator. Simulated transport properties for the sandstone model are in good agreement with those determined experimentally.
Direct manipulation of free-form deformations (1992)

Fme-form defommtion (FFD) is a powerful modeting tool, but contmtling the shape of an object under complex deformations is often ~cult.
New Colorimetric Cytotoxicity Assay for Anticancer-Drug Screening (1990)

We have developed a rapid, sensitive, and inexpensive method for measuring the cellular protein content of adherent and suspension cultures in 96-well microtiter plates. The method is suitable for ordinary laboratory purposes and for very large-scale applications, such as the National Cancer Institute's disease-oriented in vitro anticancer-drug discovery screen, which requires the use of several million culture wells per year. Cultures fixed with trichloroacetic acid were stained for 30 minutes with 0.4% (wt/vol) sulforhodamine B (SRB) dissolved in 1% acetic acid. Unbound dye was removed by four washes with 1% acetic acid, and protein-bound dye was extracted with 10 mM unbuffered Tris base [tris (hydroxymethyl)aminomethane] for determination of optical density in a computer-interfaced, 96-well microtiter plate reader. The SRB assay results were linear with the number of cells and with values for cellular protein measured by both the Lowry and Bradford assays at densities ranging from sparse subconfluence to multilayered supraconfluence. The signal-to-noise ratio at 564 nm was approximately 1.5 with 1,000 cells per well. The sensitivity of the SRB assay compared favorably with sensitivities of several fluorescence assays and was superior to those of both the Lowry and Bradford assays and to those of 20 other visible dyes. The SRB assay provides a colorimetric end point that is nondestructive, indefinitely stable, and visible to the naked eye. It provides a sensitive measure of drug-induced cytotoxicity, is useful in quantitating clonogenicity, and is well suited to high-volume, automated drug screening. SRB fluoresces strongly with laser excitation at 488 nm and can be measured quantitatively at the single-cell level by static fluorescence cytometry.
Development of lattice-matched 1.7 eV GalnAsP solar cells grown on GaAs by MOVPE (2016)

To advance the state-of-the-art in III-V multijunction solar cells towards high concentration efficiencies approaching 50%, development of a high-quality ~1.7 eV second junction solar cell is of key interest for integration in five or more junction devices. Quaternary GalnAsP solar cells grown lattice-matched on GaAs allows bandgap tunability in the range from 1.42 to 1.92 eV and offers an attractive Al-free alternative to conventional AlGaAs solar cells. In this work, we investigate the role of growth temperature towards understanding the optimal growth window for realizing high-quality GalnAsP alloys. We demonstrate bandgap tunability from 1.6 to 1.8 eV in GalnAsP alloys for compositions close to the miscibility gap, while still maintaining lattice-matched condition to GaAs. We perform an in-depth investigation to understand the impact of varying base thickness and doping concentration on the carrier collection and performance of these 1.7 eV GalnAsP solar cells. The photo-response of these cells is found to be very sensitive to p-type zinc dopant incorporation in the base layer. We demonstrate prototype 1.7 eV GalnAsP solar cell designs that leverage enhanced depletion width as an effective method to overcome this issue and boost long-wavelength carrier collection. Short-circuit current density (J <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">SC</sub> ) measured in field-aided devices were as high as 17.25 m A/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . The best GalnAsP solar cell in this study achieved an efficiency of 17.2% with a J <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">SC</sub> of 17 m A/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> and a fill-factor of 86.4%. The corresponding open-circuit voltage (V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">OC</sub> ) 1.7 eV measured on this cell represents the highest V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">oc</sub> reported for a 1.7 eV GalnAsP solar cell. These initial cell results are encouraging and highlight the potential of Al-free GalnAsP solar cells for integration in the next generation of III-V multijunction solar cells.
A 1.6-GByte/s DRAM with flexible mapping redundancy technique and additional refresh scheme (1999)

We implemented 72-Mb direct Rambus DRAM with new memory architecture suitable for multibank. There are two novel schemes: flexible mapping redundancy (FMR) technique and additional refresh scheme. This paper shows that multibank reduces redundancy area efficiency. But with the FMR technique, this 16-bank DRAM realizes the same area efficiency as a single-bank DRAM. In other words, FMR reduces chip area by 13%. This paper also describes that additional refresh scheme reduces data retention power to 1/4. Its area efficiency is about four times better than that of the conventional redundancy approach.
Molecular Control of Acid Phosphatase Secretion into the Rhizosphere of Proteoid Roots from Phosphorus-Stressed White Lupin (2001)

White lupin (Lupinus albus) grown under P deficiency displays a suite of highly coordinated adaptive responses. Included among these is secretion of copious amounts of acid phosphatase (APase). Although numerous reports document that plants secrete APases in response to P deficiency, little is known of the biochemical and molecular events involved in this process. Here we characterize the secreted APase protein, cDNA, and gene from white lupin. The secreted APase enzyme is a glycoprotein with broad substrate specificity. It is synthesized as a preprotein with a deduced M(r) of 52,000 containing a 31-amino acid presequence. Analysis of the presequence predicts that the protein is targeted to outside the cell. The processed protein has a predicted M(r) of 49,000 but migrates as a protein with M(r) of 70,000 on sodium dodecyl sulfate gels. This is likely due to glycosylation. Enhanced expression is fairly specific to proteoid roots of P-stressed plants and involves enhanced synthesis of both enzyme protein and mRNA. Secreted APase appears to be encoded by a single gene containing seven exons interrupted by six introns. The 5'-upstream putative promoter of the white lupin-secreted APase contains a 50-base pair region having 72% identity to an Arabidopsis APase promoter that is responsive to P deficiency. The white lupin-secreted APase promoter and targeting sequence may be useful tools for genetically engineering important proteins from plant roots.
Relative Efficiencies of the Fitch-Margoliash, Maximum-Parsimony, Maximum-Likelihood, Minimum-Evolution, and Neighbor-joining Methods of Phylogenetic Tree Construction in Obtaining the Correct Tree (1989)

The relative efficiencies of several tree-making methods for obtaining the correct phylogenetic tree were studied by using computer simulation. The methods examined were the Fitch-Margoliash (FM), maximum-parsimony (MP), maximumlikelihood (ML), minimum-evolution (ME), and neighbor-joining (NJ) methods. We simulated the evolutionary changes of six DNA sequences each with a length of either 300 or 600 nucleotides.
Colossal dielectric and electromechanical responses in self-assembled polymeric nanocomposites (2005)

An electroactive polymer nanocomposite, in which high dielectric constant copper phthalocyanine oligomer (o-CuPc) nanoparticles are incorporated into the block polyurethane (PU) matrix by the combination of “top down” and “bottom up” approaches, was realized. Such an approach enables the nanocomposite to exhibit colossal dielectric and electromechanical responses with very low volume fraction of the high dielectric constant o-CuPc nanofillers (∼3.5%) in the composite. In contrast, a simple blend of o-CuPc and PU composite with much higher o-CuPc content (∼16% of o-CuPc) shows much lower dielectric and electromechanical responses.
Modulation-level-selectable optical modulator with a hybrid configuration of silica PLCs and LiNbO<inf>3</inf> phase modulators (2010)

We devised and fabricated a modulation-level-selectable (from 4, 8, and 16 levels) optical modulator. A novel lattice configuration enables dynamic modulation-level switching simply by using tunable optical couplers as well as mitigating the modulation losses. Operations at 20-Gbaud were successful.
GM2-KLH conjugate vaccine: increased immunogenicity in melanoma patients after administration with immunological adjuvant QS-21. (1995)

The cell surface gangliosides GM2, GD2, and GD3 are often overexpressed in malignant melanoma. We have shown previously that immunization of melanoma patients with GM2 and Bacillus Calmette-Guérin induced an IgM antibody response in most patients and that patients with high titer GM2 antibodies showed increased survival. As is commonly seen with carbohydrate antigens (which are T independent), the IgM response was short lived, and an IgG response was rarely observed. To increase immunogenicity, we conjugated GM2 covalently with keyhole limpet hemocyanin (KLH). GM2-KLH vaccine was given to melanoma patients alone or with one of the three adjuvants: Bacillus Calmette-Guérin, DETOX, or QS-21. The most effective vaccine was GM2-KLH with QS-21. It induced a much higher titer, a longer-lasting IgM GM2 antibody response, and a consistent IgG response (isotype IgG1 and IgG3). It also induced the highest titer anti-KLH response. The results suggest that the conjugate GM2-KLH plus QS-21 vaccine elicited significant T-cell help. Because there was no serious toxicity, this vaccine approach is attractive for augmenting the immunogenicity of other gangliosides, such as GD2 and GD3, and to determine the effects of ganglioside antibodies on the course of melanoma. In addition, the finding that QS-21 significantly increased the immunogenicity of GM2-KLH suggests that it may do the same for other conjugate vaccines, many of which are currently used without adjuvant.