gebhart/patrepeval huggingface dataset:
Factors affecting pharmacokinetics of monoclonal antibodies: Areview article. (2004)

Factors affecting the successful therapy of malignant diseases include the antibody dose used and the schedule of administration, the half-life and fast blood clearance of the antibodies, the presence of circulating antigen, poor tumor penetration of the high/molecular-weight monoclonal antibody (mAb) and the way in which these molecules are catabolized. To circumvent these limitations and achieve higher uptake, increased tumor penetration, faster blood clearance and longer retention in the tumors, there is a need to generate mAbs suitable for diagnosis as well as therapy and to develop novel strategies to increase the efficacy of immunotherapeutic treatments. There is a lack of knowledge about many aspects of the physiological function and metabolism of antibodies. This paper is intended to discuss factors that affect the pharmacokinetics of mAbs in human subjects with the purpose of forming possible strategies to optimize this approach for tumor diagnosis and therapy.
Experimental endocarditis and fosfomycin. (1985)

The effectiveness of fosfomycin in combination with other antibiotics was studied in vitro and in the treatment of left-sided endocarditis in rabbits caused by S. sanguis, S. faecalis, S. aureus or P. aeruginosa. In vitro combinations of fosfomycin plus penicillin, fosfomycin plus cloxacillin, and fosfomycin plus amikacin were synergistic against the strains tested. In vivo synergism was also demonstrated since fosfomycin combinations produced a greater reduction in the number of CFU/g of vegetations than the administration of one antibiotic alone.
Using human factors engineering as the basis for developing medical human-computer systems (2002)

The technology of developing medical human-computer systems (MHCS) is a new research branch in information systems and medical administration. In this paper, an approach based on human factor engineering for developing MHCS is proposed. A prototype system, called Home Health Care Management Information System (HHC-MIS), has been developed, which can be used as a test bed to verify the approach. The approach consists of a overall framework, three basic methods (cooperation, imitation and standardization), an inference model with ten items based on "what-is-what", a modeling method and some optimal solutions in the framework. Finally, the development tool for MHCS and method for system's evaluation are suggested and discussed.
Remineralization of Enamel Subsurface Lesions by Casein Phosphopeptide-stabilized Calcium Phosphate Solutions (1997)

Casein phosphopeptides (CPP) stabilize amorphous calcium phosphate (ACP), localize ACP in dental plaque, and are anticariogenic in animal and in situ human caries model. In this vitro study, CPP-stabilized calcium phosphate solutions were shown to remineralize subsurface lesions in human third-molar enamel. Solutions were used to examine the effect of CPP-calcium phosphate concentration on remineralization. Other solutions were used to examine the effect of increasing pH, which decreased the concentrations of free calcium and phosphate ions and increased the level of CPP-bound ACP. Although most of the remineralizing solutions were supersaturated with respect to the amorphous and crystalline calcium phosphate phases, the solutions were stabilized by the CPP such that spontaneous precipitation of calcium phosphate did not occur. After a ten-day remineralization period, enamel lesions were sectioned, subjected to microradiography, and the mineral content determined by microdensitometry. All solutions deposited mineral into the bodies of the lesions, with the 1.0% CPP-calcium phosphate (pH 7.0) solution replacing 63.9 +/- 20.1% of mineral lost at an averaged rate of 3.9 +/- 0.8 x 10(-8) mol hydroxyapatite/m2/s. The remineralizing capacity was greater for the solutions with the higher levels of CPP-stabilized free calcium and phosphate ions. Remineralization was not significantly correlated with either the CPP-bound ACP of the degrees of saturation for hydroxyapatite, octacalcium phosphate, or ACP. However, remineralization was significantly correlated with the degree of saturation for dicalcium phosphate dihydrate (CaHPO4.2H2O), but his was attributed to the significant correlation of remineralization with the activity gradients from the solution into the lesion of some calcium phosphate ions and ion pairs, in particular the neutral ion pair CaHPO4(0). The CPP, by stabilizing calcium phosphate in solution, maintain high-concentration gradients of calcium and phosphate ions and ion pairs into the subsurface lesion and thus effect high rates of enamel remineralization.
Functional electrical stimulation of abdominal muscles to augment tidal volume in spinal cord injury (2000)

Functional electrical stimulation (FES) of abdominal muscles as a method of enhancing ventilation was explored in six neurologically intact subjects and five subjects with spinal cord injury (SCI) who had levels of injury between C4 and C7. Pulmonary ventilation was augmented in both groups predominantly due to an increase in tidal volume. The average increase in tidal volume during FES for the neurologically intact group was 350 ml, while in the SCI group it was 220 ml. The FES caused active volume decreases in both the lower thorax and upper abdomen, which together appear to be the mechanism behind the increases seen in tidal volume. Therefore, the proposed method might be useful in future clinical practice. The results indicate that FES of abdominal muscles should be more thoroughly explored as a potential technique of ventilatory support in SCI. The results also point to the necessity for further studies of maintaining the condition of the chest wall in the pulmonary rehabilitation of individuals with tetraplegia.
Crystal structure of the family 7 endoglucanase I (Cel7B) from Humicola insolens at 2.2 Å resolution and identification of the catalytic nucleophile by trapping of the covalent glycosyl-enzyme intermediate (1998)

Cellulose is the major polysaccharide component of the plant cell wall and the most abundant naturally produced macromolecule on Earth. The enzymic degradation of cellulose, by cellulases, is therefore of great environmental and commercial significance. Cellulases are found in 12 of the glycoside hydrolase families classified according to their amino acid sequence similarities. Endoglucanase I (Cel7B), from the soft-rot fungus Humicola insolens, is a family 7 enzyme. The structure of the native form of Cel7B from H. insolens at 2.2 A resolution has been solved by molecular replacement using the known Trichoderma reesei cellobiohydrolase I [Divne, Ståhlberg, Reinikainen, Ruohonen, Pettersson, Knowles, Teeri and Jones (1994) Science 265, 524-528] structure as the search model. Cel7B catalyses hydrolysis of the beta-1,4 glycosidic linkages in cellulose with net retention of anomeric configuration. The catalytic nucleophile at the active site of Cel7B has been identified as Glu-197 by trapping of a 2-deoxy-2-fluorocellotriosyl enzyme intermediate and identification of the labelled peptide in peptic digests by tandem MS. Site-directed mutagenesis of both Glu-197 and the prospective catalytic acid, Glu-202, results in inactive enzyme, confirming the critical role of these groups for catalysis.
Inhibition of Hyperalgesia by Ablation of Lamina I Spinal Neurons Expressing the Substance P Receptor (1997)

Substance P is released in the spinal cord in response to painful stimuli, but its role in nociceptive signaling remains unclear. When a conjugate of substance P and the ribosome-inactivating protein saporin was infused into the spinal cord, it was internalized and cytotoxic to lamina I spinal cord neurons that express the substance P receptor. This treatment left responses to mild noxious stimuli unchanged, but markedly attenuated responses to highly noxious stimuli and mechanical and thermal hyperalgesia. Thus, lamina I spinal cord neurons that express the substance P receptor play a pivotal role in the transmission of highly noxious stimuli and the maintenance of hyperalgesia.
Evidence for CD8+ Cell Increase in Long-Term PUVA-Treated Psoriatic Patients after PUVA Discontinuation (1992)

Long-term PUVA-treated psoriatic patients given maintenance therapy (UVA doses greater than 1,000 J/cm2) have been demonstrated to undergo lymphopenia and a decrease in the total number of circulating CD3+ and CD4+ T cells. The aim of this study was to assess whether the impairment of T cells is detectable also in psoriatic patients after long-lasting PUVA discontinuation. A group of 34 psoriatic patients (25 males, 9 females; mean age 52.7 +/- 12.82 years), who had previously been treated by PUVA therapy (average cumulative dose 1,898.48 +/- 1,207.12 J/cm2), was studied 1 year or more after discontinuation of PUVA therapy. The patients studied failed to show any impairment in CD3+ and CD4+ cells. Nevertheless, a significant increase (p less than 0.05) in circulating CD8+ cells (both in the percentage and the total number) was detectable in PUVA patients as compared to appropriate controls. The significance and implications of this finding are not known and need further investigations.
Structural basis for autorepression of retinoid X receptor by tetramer formation and the AF-2 helix (2000)

The 9-cis-retinoic acid receptors (RXRalpha, RXRbeta, and RXRgamma) are nuclear receptors that play key roles in multiple hormone-signaling pathways. Biochemical data indicate that, in the absence of ligand, RXR can exist as an inactive tetramer and that its dissociation, induced by ligand, is important for receptor activation. In this article we report the inactivated tetramer structures of the RXRalpha ligand-binding domain (LBD), either in the absence of or in the presence of a nonactivating ligand. These structures reveal that the RXR LBD tetramer forms a compact, disc-shaped complex, consisting of two symmetric dimers that are packed along helices 3 and 11. In each monomer, the AF-2 helix protrudes away from the core domain and spans into the coactivator binding site in the adjacent monomer of the symmetric dimer. In this configuration, the AF-2 helix physically excludes the binding of coactivators and suggests an autorepression mechanism that is mediated by the AF-2 helix within the tetramer. The RXR-tetramer interface is assembled from amino acids that are conserved across several closely related receptors, including the HNF4s and COUP transcription factors, and may therefore provide a model for understanding structure and regulation of this subfamily of nuclear receptors.
Zero-crossing rates of functions of Gaussian processes (1991)

Formulas for the expected zero-crossing rates of random processes that are monotone transformations of Gaussian processes can be obtained by using two different techniques. The first technique involves derivation of the expected zero-crossing rate for discrete-time processes and extends the result of the continuous-time case by using an appropriate limiting argument. The second is a direct method that makes successive use of R. Price's (1958) theorem, the chain rule for derivatives, and S.O. Rice's (1954) formula for the expected zero-crossing rate of a Gaussian process. A constant, which depends on the variance of the transformed process and a second-moment of its derivative, is derived. Multiplying Rice's original expression by this constant yields the zero-crossing formula for the transformed process. The two methods can be used for the general level-crossing problem of random processes that are monotone functions of a Gaussian process.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Yeast mutants deficient in protein glycosylation. (1983)

The synthesis of asparagine-linked oligosaccharides involves the formation of a lipid-linked precursor oligosaccharide that has the composition Glc3Man9GlcNAc2. We have used a [3H]mannose suicide selection to obtain mutants in yeast that are blocked in the synthesis of this precursor oligosaccharide. The alg1 mutant accumulated lipid-linked GlcNAc2, alg2 mutants accumulated Man1-2GlcNAc2, alg3 mutants accumulated Man5GlcNAc2, alg4 mutants accumulated Man1-8GlcNAc2, and alg5 and alg6 mutants accumulated Man9GlcNAc2. Some of these mutants appeared to transfer oligosaccharides other than Glc3Man9GlcNAc2 from the lipid carrier to invertase. These aberrant protein-linked oligosaccharides were processed by the addition of outer chain residues in the alg3, alg5, and alg6 mutants. There was virtually no outer chain addition in the alg2 and alg4 mutants. alg4 was the only mutant that failed to secrete invertase.
Nestin expression in hair follicle sheath progenitor cells (2003)

The intermediate filament protein, nestin, marks progenitor cells of the CNS. Such CNS stem cells are selectively labeled by placing GFP under the control of the nestin regulatory sequences. During early anagen or growth phase of the hair follicle, nestin-expressing cells, marked by GFP fluorescence in nestin-GFP transgenic mice, appear in the permanent upper hair follicle immediately below the sebaceous glands in the follicle bulge. This is where stem cells for the hair follicle outer-root sheath are thought to be located. The relatively small, oval-shaped, nestin-expressing cells in the bulge area surround the hair shaft and are interconnected by short dendrites. The precise locations of the nestin-expressing cells in the hair follicle vary with the hair cycle. During telogen or resting phase and in early anagen, the GFP-positive cells are mainly in the bulge area. However, in mid- and late anagen, the GFP-expressing cells are located in the upper outer-root sheath as well as in the bulge area but not in the hair matrix bulb. These observations show that the nestin-expressing cells form the outer-root sheath. Results of the immunohistochemical staining showed that nestin, GFP, keratin 5/8, and keratin 15 colocalize in the hair follicle bulge cells, outer-root sheath cells, and basal cells of the sebaceous glands. These data indicate that nestin-expressing cells, marked by GFP, in the hair follicle bulge are indeed progenitors of the follicle outer-root sheath. The expression of the unique protein, nestin, in both neural stem cells and hair follicle stem cells suggests their possible relation.
k-Wave: MATLAB toolbox for the simulation and reconstruction of photoacoustic wave fields (2010)

A new, freely available third party MATLAB toolbox for the simulation and reconstruction of photoacoustic wave fields is described. The toolbox, named k-Wave, is designed to make realistic photoacoustic modeling simple and fast. The forward simulations are based on a k-space pseudo-spectral time domain solution to coupled first-order acoustic equations for homogeneous or heterogeneous media in one, two, and three dimensions. The simulation functions can additionally be used as a flexible time reversal image reconstruction algorithm for an arbitrarily shaped measurement surface. A one-step image reconstruction algorithm for a planar detector geometry based on the fast Fourier transform (FFT) is also included. The architecture and use of the toolbox are described, and several novel modeling examples are given. First, the use of data interpolation is shown to considerably improve time reversal reconstructions when the measurement surface has only a sparse array of detector points. Second, by comparison with one-step, FFT-based reconstruction, time reversal is shown to be sufficiently general that it can also be used for finite-sized planar measurement surfaces. Last, the optimization of computational speed is demonstrated through parallel execution using a graphics processing unit.
Signal Transduction by DR3, a Death Domain-Containing Receptor Related to TNFR-1 and CD95 (1996)

Tumor necrosis factor receptor-1 (TNFR-1) and CD95 (also called Fas or APO-1) are cytokine receptors that engage the apoptosis pathway through a region of intracellular homology, designated the "death domain." Another death domain-containing member of the TNFR family, death receptor 3 (DR3), was identified and was shown to induce both apoptosis and activation of nuclear factor kappaB. Expression of DR3 appears to be restricted to tissues enriched in lymphocytes. DR3 signal transduction is mediated by a complex of intracellular signaling molecules including TRADD, TRAF2, FADD, and FLICE. Thus, DR3 likely plays a role in regulating lymphocyte homeostasis.
A human brain glycoprotein related to the mouse cell adhesion molecule L1. (1988)

We have employed monoclonal antibody 5G3, an antibody used to label human tumor cells of neural origin (Mujoo, K., Spiro, R.C., and Reisfeld, R. A. (1986) J. Biol. Chem. 261, 10299-10305), to isolate and characterize a large glycoprotein from normal adult human brain. This protein was compared to mouse L1 (Rathjen, F. G., and Schachner, M. (1984) EMBO J. 3, 1-10), a neural cell surface glycoprotein implicated predominantly in neurite-neurite interactions. On the basis of the following results the 5G3 antigen is considered to be the human homologue of mouse L1. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis, both proteins share similar molecular masses of their carbohydrate-depleted or undepleted components. In tryptic fingerprint analyses of the iodinated L1 and 5G3 components, 65% of the resolved peptides comigrated. Comparison of NH2-terminal amino acid sequences revealed a high degree of homology between human 5G3 and mouse L1, with 11 of 15 residues being identical. Furthermore, polyclonal antibodies to human 5G3 antigen were found to be cross-reactive with mouse L1 antigen and vice versa. All components of 5G3 and L1 antigens show considerable charge heterogeneity with partial overlapping of regions in isoelectric focusing followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. These findings provide a basis for studying the role of the human L1 homologue in human diseases.
Pulmonary rehabilitation programs in Canada: national survey. (1999)

This first comprehensive national survey of PR programs in Canada shows that there are similarities in the format, content and staffing of PR programs. Programs are only able to service a small percentage of patients with chronic respiratory conditions.
Nuclear import and export pathways (1999)

Macromolecules enter or leave the nucleus by using nuclear localization signals (NLS), or nuclear export signals (NES), respectively. Different types of NLS and NES are recognized directly or indirectly via adapters, by transport receptors. All transport receptors identified thus far are members of the same family and share an ability to shuttle between the nucleus and the cytoplasm, and to interact with the small GTPase Ran and with nucleoporins at the nuclear pore complex (NPC). The GTPase Ran regulates the interaction of transport receptors with either cargoes, or adapters, or nucleoporins and is crucial in providing directionality to nuclear import and export. Surprisingly, GTP hydrolysis by Ran is not required for translocation of some receptor/cargo complexes through the NPC. One of the challenges for the future will be to establish the mechanisms of translocation through the NPC of different transport receptors together with their cargoes. J. Cell. Biochem. Suppls. 32/33:76-83, 1999.
Inflammatory status and insulin resistance (2002)

Recent studies on diseases which involve insulin insensitivity (e.g. obesity, type 2 diabetes and atherosclerosis) also show increased cytokine production and markers of inflammation. Evidence at present favours chronic inflammation as a trigger for chronic insulin insensitivity, rather than the reverse situation.
High‐Affinity Anti‐Ganglioside IgG Antibodies Raised in Complex Ganglioside Knockout Mice (2000)

Gangliosides, sialic acid-bearing glycosphingolipids, are highly enriched in the vertebrate nervous system. Anti-ganglioside antibodies are associated with various human neuropathies, although the pathogenicity of these antibodies remains unproven. Testing the pathogenic role of anti-ganglioside antibodies will be facilitated by developing high-affinity IgG-class complement-fixing monoclonal anti-bodies against major brain gangliosides, a goal that has been difficult to achieve. In this study, mice lacking complex gangliosides were used as immune-naive hosts to raise anti-ganglioside antibodies. Wild-type mice and knockout mice with a disrupted gene for GM2/GD2 synthase (UDP-N-acetyl-D-galactosamine : GM3/GD3 N-acetyl-D-glactosaminyltransferase) were immunized with GD1a conjugated to keyhole limpet hemocyanin. The knockout mice produced a vigorous anti-GD1a IgG response, whereas wildtype littermates failed to do so. Fusion of spleen cells from an immunized knockout mouse with myeloma cells yielded numerous IgG anti-GD1a antibody-producing colonies. Ganglioside binding studies revealed two specificity classes; one colony representing each class was cloned and characterized. High-affinity monoclonal antibody was produced by each hybridoma : an IgG1 that bound nearly exclusively to GD1a and an IgG2b that bound GD1a, GT1b, and GT1aalpha. Both antibodies readily readily detected gangliosides via ELISA, TLC immune overlay, immunohistochemistry, and immunocytochemistry. In contrast to prior reports using anti-GD1a and anti-GT1b IgM class monoclonal antibodies, the new antibodies bound avidly to granule neurons in brain tissue sections and cell cultures. Mice lacking complex gangliosides are improved hosts for raising high-affinity, high-titer anti-ganglioside IgG antibodies for probing for the distribution and physiology of gangliosides and the pathophysiology of anti-ganglioside antibodies.
Crowdsourced Fabrication (2016)

In recent years, extensive research in the HCI literature has explored interactive techniques for digital fabrication. However, little attention in this body of work has examined how to involve and guide human workers in fabricating larger-scale structures. We propose a novel model of crowdsourced fabrication, in which a large number of workers and volunteers are guided through the process of building a pre-designed structure. The process is facilitated by an intelligent construction space capable of guiding individual workers and coordinating the overall build process. More specifically, we explore the use of smartwatches, indoor location sensing, and instrumented construction materials to provide real-time guidance to workers, coordinated by a foreman engine that manages the overall build process. We report on a three day deployment of our system to construct a 12-tall bamboo pavilion with assistance from more than one hundred volunteer workers, and reflect on observations and feedback collected during the exhibit.