gebhart/patrepeval huggingface dataset:
Pharmacokinetics and bactericidal rates of daptomycin and vancomycin in intravenous drug abusers being treated for gram-positive endocarditis and bacteremia (1992)

The pharmacokinetics and bactericidal killing rates (BR) of daptomycin (D) and vancomycin (V) in 12 intravenous drug abusers (6 treated with daptomycin and 6 treated with vancomycin) were evaluated. Pharmacokinetic parameters were determined from multiple serum samples drawn at steady state over a 12-h dosing interval after intravenous infusions of 3 mg of D per kg of body weight and 1,000 mg of V. The BRs were determined from the 1- and 6-h serum samples by using four isolates of Staphylococcus aureus (three methicillin susceptible and one methicillin resistant) obtained from the patients enrolled in the study. Peak serum daptomycin concentrations were lower and volumes of distribution were higher than reported in healthy volunteers. Although not statistically different, D clearance was 22% higher than reported in healthy volunteers. V pharmacokinetics were similar to those reported in previous studies. Daptomycin's BRs, although comparable to those of V in patients' serum, were significantly decreased compared with those found in broth. This may be related to the high degree of protein binding of D (93% versus 50% for V). Conversely, the BRs of V in serum were significantly greater than those in broth. The BRs of D and V in broth were greater when killing curves were performed with test strains in logarithmic versus stationary-phase growth. The ability to kill organisms in stationary phase may be an important factor in determining the performance of an antibiotic in deep-seated infections such as endocarditis.3+
Predominant constitutive CFTR conductance in small airways (2005)

These results indicate that the small airway of the pig is characterized by a constitutively active Cl- conductance that is most likely due to CFTR.
Improved Bone Morphogenetic Protein-2 Retention in an Injectable Collagen Matrix Using Bifunctional Peptides (2013)

To promote healing of many orthopedic injuries, tissue engineering approaches are being developed that combine growth factors such as Bone Morphogenetic Proteins (BMP) with biomaterial carriers. Although these technologies have shown great promise, they still face limitations. We describe a generalized approach to create target-specific modular peptides that bind growth factors to implantable biomaterials. These bifunctional peptide coatings provide a novel way to modulate biology on the surface of an implant. Using phage display techniques, we have identified peptides that bind with high affinity to BMP-2. The peptides that bind to BMP-2 fall into two different sequence clusters. The first cluster of peptide sequences contains the motif W-X-X-F-X-X-L (where X can be any amino acid) and the second cluster contains the motif F-P-L-K-G. We have synthesized bifunctional peptide linkers that contain BMP-2 and collagen-binding domains. Using a rat ectopic bone formation model, we have injected rhBMP-2 into a collagen matrix with or without a bifunctional BMP-2: collagen peptide (BC-1). The presence of BC-1 significantly increased osteogenic cellular activity, the area of bone formed, and bone maturity at the site of injection. Our results suggest that bifunctional peptides that can simultaneously bind to a growth factor and an implantable biomaterial can be used to control the delivery and release of growth factors at the site of implantation.
Transforming Growth Factor β Facilitates β-TrCP-Mediated Degradation of Cdc25A in a Smad3-Dependent Manner (2005)

Ubiquitin-dependent degradation of Cdc25A is a major mechanism for damage-induced S-phase checkpoint. Two ubiquitin ligases, the Skp1-cullin-beta-TrCP (SCFbeta-TrCP) complex and the anaphase-promoting complex (APCCdh1), are involved in Cdc25A degradation. Here we demonstrate that the transforming growth factor beta (TGF-beta)-Smad3 pathway promotes SCF(beta-TrCP)-mediated Cdc25A ubiquitination. Cells treated with TGF-beta, as well as cells transfected with Smad3 or a constitutively active type I TGF-beta receptor, exhibit increased ubiquitination and markedly shortened half-lives of Cdc25A. Furthermore, Cdc25A is stabilized in cells transfected with Smad3 small interfering RNA (siRNA) and cells from Smad3-null mice. TGF-beta-induced ubiquitination is associated with Cdc25A phosphorylation at the beta-TrCP docking site (DS82G motif) and physical association of Cdc25A with Smad3 and beta-TrCP. Cdc25A mutant proteins deficient in DS82G phosphorylation are resistant to TGF-beta-Smad3-induced degradation, whereas a Cdc25A mutant protein defective in APCCdh1 recognition undergoes efficient degradation. Smad3 siRNA inhibits beta-TrCP-Cdc25A interaction and Cdc25A degradation in response to TGF-beta. beta-TrCP2 siRNA also inhibits Smad3-induced Cdc25A degradation. In contrast, Cdh1 siRNA had no effect on Cdc25A down-regulation by Smad3. These data suggest that Smad3 plays a key role in the regulation of Cdc25A ubiquitination by SCFbeta-TrCP and that Cdc25A stabilization observed in various cancers could be associated with defects in the TGF-beta-Smad3 pathway.
Traitement de l’aphtose par la thalidomide et la colchicine (1984)

Thalidomide alone (200-300 mg daily) or associated with colchicine (2-3 mg daily) was given orally to 25 patients with aphthosis: 8 patients with recurrent oral aphthae; 4 patients with recurrent mucocutaneous aphthosis, without visceral involvement, and 13 patients with Behçet's disease (Touraine's aphthosis). A major improvement was noted in all groups, with a rapid healing of mucous lesions and a rapid reduction of pain and burning as compared to prior spontaneous regressions. No new outbreaks were noted at a dose of 50-100 mg thalidomide and 1 mg colchicine daily. Under oral administration of the drugs, thrombophlebitis was noted in 1 case (third group) only. In the other patients with Behçet's disease, skin aphthae, ocular symptoms, arthritis, superficial nodular phlebitis quickly disappeared with treatment. The efficiency of the drugs is only temporary, since new lesions usually appeared a few weeks after the end of treatment. Due to the relatively small number of cases studied in each group, no conclusions can be drawn concerning the efficiency of thalidomide alone compared to the association of the two drugs. However, this open trial does support the usefulness of thalidomide, or thalidomide and colchicine, in recurrent mucocutaneous aphthae, aphthosis and Behçet's disease.
Hydroxychloroquine concentration–response relationships in patients with rheumatoid arthritis (2002)

There is a weak, but predictable, relationship between blood DHCQ concentrations and efficacy of treatment with HCQ. In addition, there is an association between gastrointestinal adverse events and elevated blood HCQ concentrations. Further investigation of these relationships is warranted to see if DHCQ may be introduced as a new antirheumatic drug.
Modification of Alternative Splicing by Antisense Oligonucleotides as a Potential Chemotherapy for Cancer and Other Diseases (2001)

It has been estimated that greater than 35% of all human genes undergo alternative splicing. The process of alternative splicing is highly regulated and disruption of a splicing pattern can produce splice variants that have different functions. Certain splice variants that are associated with induction of cell death, regulation of cellular proliferation and differentiation, cell signaling, and angiogenesis are present in a variety of cancers. Several of these cancer-related alternatively spliced genes will be discussed in this review. In addition, alternative splicing is associated with several genetic disorders such as beta-thalassemia, cystic fibrosis, and muscular dystrophy. Control of pre-mRNA splicing patterns with antisense oligonucleotides presents an attractive way to potentially treat and manage a variety of diseases. This review will discuss potential gene targets for antisense oligonucleotide induced modification of alternative splicing patterns. Furthermore, the chemistries and delivery strategies of antisense oligonucleotides will be discussed.
Elementary processes of photochemical reactions (1926)

J. Franck and E. G. Dymond, Trans. Faraday Soc., 1926, 21, 536 DOI: 10.1039/TF9262100536
Intermolecular Binding Sites of Human Immunodeficiency Virus Type 1 Rev Protein Determined by Protein Footprinting (1995)

Human immunodeficiency virus encodes the regulatory protein Rev, which is required for expression of viral structural proteins. It binds to an RNA element (RRE) in the viral transcript and up-regulates the cytoplasmic appearance of unspliced and singly spliced viral mRNA. We have studied the structure of Rev alone and complexed with the RRE and two monoclonal antibodies, using a protein footprinting approach. The method involves radioactive labeling at the C-terminal end of Rev fusion protein followed by limited proteolysis under native conditions, using 10 different proteinases. Rev protein was mainly cleaved within the basic domain and in the C-terminal part. The periodicity of the proteolytic cleavages within the basic domain strongly suggests that it forms an alpha-helical structure with one side facing the solvent. In the presence of RRE, these cleavages became significantly reduced. In addition, strong protection was observed at position 66 outside the basic domain. As a control for the specificity of the footprinting reaction, we confirmed the position of the epitopes for two monoclonal antibodies. This protein footprinting methodology is generally applicable to other proteins for which terminal modifications are acceptable, and provides a useful tool for mapping structure, substrate binding, and conformational changes.
Selective Inhibition of Engineered Receptors via Proximity-Accelerated Alkylation (2003)

A new approach for creating allele-specific inhibitors is demonstrated. In this approach, a receptor and ligand are engineered to contain complementary reactive groups that form a covalent bond via a proximity-accelerated reaction upon formation of the receptor-ligand complex, irreversibly modulating the biological function of the receptor. This approach is demonstrated in the cyclophilin-cyclosporin receptor-ligand system by introducing thiol and acrylamide functional groups in the receptor and ligand, respectively.
Internal-Use Computer Software: The Fixed Asset of the Information Age (1997)

How should an entity account for the costs of computer software med internally? Don't look for any financial accounting standards on the topic-- they aren't there. That situation is on the verge of change, however. The American Institute of CPAs accounting standards executive committee has issued an exposure draft of a Statement of Position, Accounting for the Costs of Computer Software Developed or Obtained for Internal Use. The ED applies to all entities except governmental. Accounting practices for internal-use software are diverse as a remit of a lack of authoritative guidance and escalating costs totaling billions of dollars annually. Some entities expense all costs as incurred, some capitalize most costs and some capitalize the costs of purchased internal-use software but expense costs of internally developed internal-use software. None of these entities is necessarily violating any standards. History In 1994, the staff of the Securities and Exchange Commission asked the Financial Accounting Standards Board emerging issues task force (EITF) to develop financial reporting guidance for internal-use software. The EITF, FASB and AcSEC concluded that AcSEC should handle the project because it was able to provide the necessary due process, including exposure for public comment, that such a broad project warrants. Relationship to existing standards The ED basically follows a fixed asset accounting model with what may become an exception for some entities: The ED does not allow entities to capitalize indirect costs such as overhead. The draft recognizes that certain costs incurred for software developed internally are research and development costs and that such costs must be expensed as incurred in actor. dance with FASB Statement no. 2, Accounting for Research and Development Costs. Similarly, certain costs incurred for fixed assets constructed internally might be R&D costs. Like FASB Statement no. 86, Accounting for the Costs of Computer Software to Be Sold, Leased, or Otherwise Marketed, the ED strives to help entities determine when a project is in an R&D phase. However, the SOP would require capitalization of non-R&D costs at an earlier stage of the software development cycle than Statement no. 86 does. Software as an asset AcSEC concluded that certain non-R&D costs of internal-use software should be recorded as assets. Entities use software often for the same purposes they use other long-lived assets: to reduce costs, operate more efficiently, improve internal controls, service customers better and gain competitive advantages. In fact, some would argue that as society moves farther away from the industrial age and into the information age, computer software is a more important asset to many entities than a fixed asset. However, reporting internal-use software costs as assets would have its price. For example, an entity would have to devote resources to tracking and monitoring capitalizable costs. …
Nanoplatelet Size to Control the Alignment and Thermal Conductivity in Copper–Graphite Composites (2014)

A controlled alignment of graphite nanoplatelets in a composite matrix will allow developing materials with tailored thermal properties. Achieving a high degree of alignment in a reproducible way, however, remains challenging. Here we demonstrate the alignment of graphite nanoplatelets in copper composites produced via high-energy ball milling and spark plasma sintering. The orientation of the nanoplatelets in the copper matrix is verified by polarized Raman scattering and electron microscopy showing an increasing order with increasing platelet size. The thermal conductivity k along the alignment direction is up to five times higher than perpendicular to it. The composite with the highest degree of alignment has a thermal diffusivity (100 mm(2) s(-1)) comparable to copper (105 mm(2) s(-1)) but is 20% lighter. By modeling the thermal properties of the composites within the effective medium approximation we show that (i) the Kapitza resistance is not a limiting factor for improving the thermal conductivity of a copper-graphite system and (ii) copper-graphite-nanoplatelet composites may be expected to achieve a higher thermal conductivity than copper upon further refinement.
Multiple Antigen-Specific Processing Pathways for Activating Naive CD8+ T Cells In Vivo (2001)

Current knowledge of the processing of viral Ags into MHC class I-associated ligands is based almost completely on in vitro studies using nonprofessional APCs (pAPCs). This is two steps removed from real immune responses to pathogens and vaccines, in which pAPCs activate naive CD8(+) T cells in vivo. Rational vaccine design requires answers to numerous questions surrounding the function of pAPCs in vivo, including their abilities to process and present peptides derived from endogenous and exogenous viral Ags. In the present study, we characterize the in vivo dependence of Ag presentation on the expression of TAP by testing the immunogenicity of model Ags synthesized by recombinant vaccinia viruses in TAP1(-/-) mice. We show that the efficiency of TAP-independent presentation in vitro correlates with TAP-independent activation of naive T cells in vivo and provide the first in vivo evidence for proteolytic processing of antigenic peptides in the secretory pathway. There was, however, a clear exception to this correlation; although the presentation of the minimal SIINFEKL determinant from chicken egg OVA in vitro was strictly TAP dependent, it was presented in a TAP-independent manner in vivo. In vivo presentation of the same peptide from a fusion protein retained its TAP dependence. These results show that determinant-specific processing pathways exist in vivo for the generation of antiviral T cell responses. We present additional findings that point to cross-priming as the likely mechanism for these protein-specific differences.
Enhanced apoptosis with combination C225/radiation treatment serves as the impetus for clinical investigation in head and neck cancers. (2000)

This preclinical work serves as important support for the ongoing clinical investigation of C225 and radiotherapy for patients with head and neck carcinomas. The initial results of these clinical studies have been promising.
Quality of service analysis and control for wireless sensor networks (2005)

This paper investigates wireless sensor network spatial resolution as a measurement of quality of service (QoS). We seek to control the network in such a way that sensors participate equally in the network while conserving energy and maintaining the desired spatial resolution. This work provides an analytic solution of a sensor network QoS control strategy demonstrated recently through simulation. General conclusions about the selection of parameters to control network performance, specifically the mean and variance of the QoS are presented. We show that there is a tradeoff between the static and dynamic QoS performance, as well as energy usage and conclude by presenting the several potential applications that are enabled by ability to control both the mean and variance of network QoS.
Active immunity against the CD4 receptor by using an antibody antigenized with residues 41-55 of the first extracellular domain. (1993)

Using the process of "antibody antigenization," we engineered two antibody molecules carrying in the third complementarity-determining region of the heavy chain variable domain a 7-mer or a 15-mer peptide epitope of the first extracellular domain (D1) of human CD4 receptor--namely, Ser-Phe-Leu-Thr-Lys-Gly-Pro-Ser (SFLTKGPS; positions 42 through 49) and Gly-Ser-Phe-Leu-Thr-Lys-Gly-Pro-Ser-Lys-Leu-Asn-Asp-Arg-Ala (GSFLTKGPSKLNDRA; positions 41 through 55). These amino acid sequences are contained in the consensus binding site for the human immunodeficiency virus (HIV) on CD4 receptor. Both antigenized antibodies (AgAbs) bound recombinant gp120 and were recognized by a prototype monoclonal antibody to CD4 whose binding site is within amino acid residues 41-55. AgAbs were then used as immunogens in rabbits and mice to elicit a humoral response against CD4. Only the AgAb carrying the sequence 41GSFLTKGPSKLN-DRA55 induced a response against CD4. The induced antibodies showed specificity for the amino acid sequence of CD4 engineered in the AgAb molecule, were able to inhibit the formation of syncytia between human CD4+ T cells MOLT-3 and 8E5 (T cells that are constitutively infected with HIV), and stained human CD4+ CEM T cells. Four murine monoclonal antibodies were used to analyze the relationship between syncytia inhibition and CD4 binding at the single antibody level, and indicated that recognition of native CD4 is not an absolute requirement for inhibition of syncytia. This study demonstrates that antigenized antibodies can be used as immunogens to elicit site-specific and biologically active immunity to CD4. The importance of this approach as a general way to induce anti-receptor immunity and as a possible new measure to immunointervention in HIV infection is discussed.
On the acoustic radiation pressure on spheres (1934)

Abstract Although frequent reference is made to acoustic radiation pressure in treatises and memoirs on sound, there appears to be no systematic theoretical development of the subject enabling actual pressures on obstacles of simple geometrical form to be calculated. In the audible range of acoustic frequencies, it is possible to devise, in a number of ways, means of measuring pressure amplitudes in sound waves as first order effects. At supersonic frequencies, however, these methods are no longer serviceable. When the dimensions of resonators of diaphragms become comparable with the wave-length, the physical effects which enable the pressure amplitude to be measured involve intractable diffraction problems, while the extremely high frequencies and small amplitudes involved make the employment of stroboscopic methods of observation extremely difficult. It has been shown, however, that at supersonic frequencies the acoustic radiation pressures on spheres and discs become sufficiently large to be measured easily, at any rate, in liquids. The mean pressure is generally assumed to be proportional to the energy density in the neighbourhood of the obstacle, and on this basis relative measurements can be made, for instance, in the radiation field of a supersonic oscillator. Such formulæ may be obtained without restriction as to wave-length, for spheres in plane progressive and stationary radiation fields, and the magnitude of the pressure is found to be of entirely different orders of magnitude in the two cases.
Mechanical culture conditions effect gene expression: gravity-induced changes on the space shuttle (2000)

Three-dimensional suspension culture is a gravity-limited phenomenon. The balancing forces necessary to keep the aggregates in suspension increase directly with aggregate size. This leads to a self-propagating cycle of cell damage by balancing forces. Cell culture in microgravity avoids this trade-off. We determined which genes mediate three-dimensional culture of cell and tissue aggregates in the low-shear stress, low-turbulent environment of actual microgravity. Primary cultures of human renal cortical cells were flown on the space shuttle. Cells grown in microgravity and ground-based controls were grown for 6 days and fixed. RNA was extracted, and automated gene array analysis of the expression of 10, 000 genes was performed. A select group of genes were regulated in microgravity. These 1,632 genes were independent of known shear stress response element-dependent genes and heat shock proteins. Specific transcription factors underwent large changes in microgravity including the Wilms' tumor zinc finger protein, and the vitamin D receptor. A specific group of genes, under the control of defined transcription factors, mediate three-dimensional suspension culture under microgravity conditions.