gebhart/patrepeval huggingface dataset:
Simultaneous primary and contralateral revision total knee arthroplasty. (1999)

Seven patients underwent primary and contralateral revision total knee arthroplasty (TKA) under one anesthetic in a sequential fashion. The average patient age was 67.6+/-6.9 years. Average blood loss was 764+/-568 cc, average operative time was 269+/-107 minutes, and average length of hospital stay was 9.6+/-3.4 days. One patient with a history of hypertension, diabetes, and coronary heart disease died from pulmonary embolism 7 days after surgery. Deep infection with enterococcus developed in the revised knee of another patient 3 months after surgery. For the six surviving patients, knee pain and function were improved by surgery. However, in this small series of patients, two major complications occurred. These results indicate that if this procedure is considered at all, it should be reserved for only healthy patients with relatively uncomplicated knee reconstructions.
Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet (2013)

Within the myelodysplastic syndrome (MDS) work package of the European LeukemiaNet, an Expert Panel was selected according to the framework elements of the National Institutes of Health Consensus Development Program. A systematic review of the literature was performed that included indexed original papers, indexed reviews and educational papers, and abstracts of conference proceedings. Guidelines were developed on the basis of a list of patient- and therapy-oriented questions, and recommendations were formulated and ranked according to the supporting level of evidence. MDSs should be classified according to the 2008 World Health Organization criteria. An accurate risk assessment requires the evaluation of not only disease-related factors but also of those related to extrahematologic comorbidity. The assessment of individual risk enables the identification of fit patients with a poor prognosis who are candidates for up-front intensive treatments, primarily allogeneic stem cell transplantation. A high proportion of MDS patients are not eligible for potentially curative treatment because of advanced age and/or clinically relevant comorbidities and poor performance status. In these patients, the therapeutic intervention is aimed at preventing cytopenia-related morbidity and preserving quality of life. A number of new agents are being developed for which the available evidence is not sufficient to recommend routine use. The inclusion of patients into prospective clinical trials is strongly recommended.
Small Molecule Inhibitors of MDM2-p53 and MDMX-p53 Interactions as New Cancer Therapeutics (2013)

Inactivation of the function of tumor suppressor p53 is common in human cancers. In approximately half of human cancers, the tumor suppressor function of p53 is inactivated by deletion or mutation of TP53, the gene encoding p53 protein. In the remaining 50% of human cancers, p53 tumor suppressor function can be effectively inhibited by oncoprotein MDM2 or its homolog MDMX. Since inhibition of p53 by MDM2 or MDMX protein is mediated by their direct interaction with p53, small-molecule inhibitors designed to block the MDM2-p53 or MDMX-p53 protein-protein interaction (MDM2 or MDMX inhibitors) can activate p53 in tumor cells retaining wild-type p53. In the last few years, several classes of potent, selective, and efficacious small molecule MDM2 inhibitors have been designed and developed, and six such compounds are being evaluated in clinical trials as new anticancer drugs. Additionally, non-peptide, small-molecule MDMX inhibitors have been reported. We review herein the design and development of potent small-molecule MDM2 and MDMX inhibitors.
Slow Feature Analysis: Unsupervised Learning of Invariances (2002)

Invariant features of temporally varying signals are useful for analysis and classification. Slow feature analysis (SFA) is a new method for learning invariant or slowly varying features from a vectorial input signal. It is based on a nonlinear expansion of the input signal and application of principal component analysis to this expanded signal and its time derivative. It is guaranteed to find the optimal solution within a family of functions directly and can learn to extract a large number of decorrelated features, which are ordered by their degree of invariance. SFA can be applied hierarchically to process high-dimensional input signals and extract complex features. SFA is applied first to complex cell tuning properties based on simple cell output, including disparity and motion. Then more complicated input-output functions are learned by repeated application of SFA. Finally, a hierarchical network of SFA modules is presented as a simple model of the visual system. The same unstructured network can learn translation, size, rotation, contrast, or, to a lesser degree, illumination invariance for one-dimensional objects, depending on only the training stimulus. Surprisingly, only a few training objects suffice to achieve good generalization to new objects. The generated representation is suitable for object recognition. Performance degrades if the network is trained to learn multiple invariances simultaneously.
Structural Requirements for a Specificity Switch and for Maintenance of Affinity Using Mutational Analysis of a Phage-Displayed Anti-Arsonate Antibody of Fab Heavy Chain First Complementarity-Determining Region (1998)

We previously showed that a single mutation at heavy (H) position 35 of Abs specific for p-azophenylarsonate (Ars) resulted in acquisition of binding to the structurally related hapten p-azophenylsulfonate (Sulf). To explore the sequence and structural diversity of the H chain first complementarity-determining region (HCDR1) in modulating affinity and specificity, positions 30-36 in Ab 36-65 were randomly mutated and expressed as Fab in a bacteriophage display vector. Ab 36-65 is germline encoded, lacking somatic mutations. Following affinity selection on Sulf resins, 55 mutant Fab were isolated, revealing seven unique HCDR1 sequences containing different amino acids at position H:35. All Fab bound Sulf, but not Ars. Site-directed mutagenesis in a variety of HCDR1 sequence contexts indicates that H:35 is critical for hapten specificity, independent of the sequence of the remainder of HCDR1. At H:35, Asn is required for Ars specificity, consistent with the x-ray crystal structure of the somatically mutated anti-Ars Ab 36-71, while Sulf binding occurs with at least seven different H:35 residues. All Sulf-binding clones selected following phage display contained H:Gly33, observed previously for Ars-binding Abs that use the same germline V(H) sequence. Site-directed mutagenesis at H:33 indicates that Gly plays an essential structural role in HCDR1 for both Sulf- and Ars-specific Abs.
Diagnostic Potential of Monoclonal Antibodies Specific to the Unique O-Antigen of Multidrug-Resistant Epidemic Escherichia coli Clone ST131-O25b:H4 (2014)

The Escherichia coli lineage sequence type 131 (ST131)-O25b:H4 is a globally spread multidrug-resistant clone responsible for a great proportion of extraintestinal infections. Driven by the significant medical needs associated with this successful pathogenic lineage, we generated murine monoclonal antibodies (MAbs) against its lipopolysaccharide (LPS) O25b antigen in order to develop quick diagnostic tests. Murine monoclonal antibodies were generated by immunizing mice with whole killed nonencapsulated ST131-O25b E. coli cells and screening hybridoma supernatants for binding to purified LPS molecules obtained from an E. coli ST131-O25b clinical isolate. The MAbs selected for further study bound to the surface of live E. coli O25b strains irrespective of the capsular type expressed, while they did not bind to bacteria or purified LPS from other serotypes, including the related classical O25 antigen (O25a). Using these specific MAbs, we developed a latex bead-based agglutination assay that has greater specificity and is quicker and simpler than the currently available typing methods. The high specificities of these MAbs can be explained by the novel structure of the O25b repeating unit elucidated in this article. Based on comparative analysis by nuclear magnetic resonance (NMR) and mass spectrometry, the N-acetyl-fucose in the O25a O-antigen had been replaced by O-acetyl-rhamnose in the O25b repeating unit. The genetic determinants responsible for this structural variation were identified by aligning the corresponding genetic loci and were confirmed by trans-complementation of a rough mutant by the subserotype-specific fragments of the rfb operons.
Quantification of Granulocyte Elastase Inhibitors in Human Mixed Saliva and in Pure Parotid Secretion (1983)

The predominant inhibitors of granulocyte elastase in plasma (alpha 1-proteinase inhibitor and alpha 2-macroglobulin) together with antileukoproteinase were quantified in parotid secretion and mixed saliva. Antileukoproteinase was the only inhibitor found in parotid saliva and was present in a concentration about 30 times the serum level, suggesting a local production. In mixed saliva, antileukoproteinase accounted for more than 70% of the molar concentration of the granulocyte elastase inhibitors studied. alpha 1-Proteinase inhibitor was measurable in about 1/3 of the specimens of mixed saliva. In parotid secretion, antileukoproteinase was present only as a free, active inhibitor. In mixed saliva about 15% of antileukoproteinase was in complex with granulocyte elastase, while the remaining amount of 85% was inhibitorily active. This suggests that antileukoproteinase has a biological function in a local defence mechanism directed towards the effects of granulocyte elastase in the oral cavity and salivary glands.
7-Oxabicyclo[2.2.1]heptane-2,3-dicarboximides with anticonvulsant activity (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT7-Oxabicyclo[2.2.1]heptane-2,3-dicarboximides with anticonvulsant activityEarl R. Bockstahler, Lawrence C. Weaver, and Donald L. WrightCite this: J. Med. Chem. 1968, 11, 3, 603–606Publication Date (Print):May 1, 1968Publication History Published online1 May 2002Published inissue 1 May 1968https://pubs.acs.org/doi/10.1021/jm00309a045https://doi.org/10.1021/jm00309a045research-articleACS PublicationsRequest reuse permissionsArticle Views73Altmetric-Citations8LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Differences in Response Among Inbred Mouse Strains to Infection with Small Doses of Mycobacterium bovis BCG (1981)

Intravenous infection of six inbred mouse strains with small doses of dispersed cells of Mycobacterium bovis BCG (15.5 x 10(3) or 15.5 x 10(4) colony-forming units) separated them into resistant (C3H/HeCr, A/J, and DBA/2) and sensitive (B10.A, C57BL/6, and BALB/c) strains as assessed by the magnitude of bacterial multiplication in the spleens at 28 days. The two groups were more sharply separated after infection with the lower dose of BCG (15.5 x 10(3) colony-forming units), which allowed for true multiplication of the bacteria in the spleens of permissive hosts, expressed as the ratio of the number of BCG recovered from the spleens to the number of BCG injected. This coefficient of increase was less than 1 in resistant strains, whereas it was higher than 2.5 in sensitive strains. Significant splenomegaly developed only in mice of the sensitive strains infected with BCG when compared with uninfected controls. There was no correlation between the magnitude of the delayed-type hypersensitivity (DTH) to BCG and susceptibility to infection: DTH was absent in both the sensitive and the resistant strains when the smaller dose of BCG was used for infection. Moreover, significant DTH was detected in animals of the most sensitive (BALB/c) as well as of the most resistant (C3H/HeCr) strain when the higher dose of BCG (15.5 x 10(4)) was used for immunization. These results document significant genetic differences in the ability of inbred mice to inhibit bacterial multiplication after infection with small dispersed doses of BCG. Resistance to BCG multiplication, in this model, does not appear to be related to the establishment of DTH.
Patient Satisfaction with Psoriasis Therapies: An Update and Introduction to Biologic Therapy (2004)

Biologic agents offer new hope for patients with psoriasis that their chronic condition can be controlled in a manner that improves their quality of life and may lead to high levels of satisfaction with their treatment.
The Use of β-Agonists and the Risk of Death and near Death from Asthma (1992)

An increased risk of death or near death from asthma was associated with the regular use of inhaled beta 2-agonist bronchodilators, especially fenoterol. Regardless of whether beta-agonists are directly responsible for these adverse effects or are simply a marker for more severe asthma, heavy use of these agents should alert clinicians that it is necessary to reevaluate the patient's condition.
Large scale purification and immunolocalization of bovine uroplakins I, II, and III. Molecular markers of urothelial differentiation. (1990)

The differentiation of mammalian urothelium culminates in the formation of asymmetrical unit membrane (AUM). Using gradient centrifugation and detergent wash, we purified milligram quantities of AUMs which, interestingly, contained three major proteins (15, 27, and 47 kDa) that appeared to be identical to the three immunoaffinity purified, putatively AUM-associated proteins that we described earlier (Yu, J., Manabe, M., Wu, X.-R., Xu, C., Surya, B., and Sun, T.-T. (1990) J. Cell Biol., 111, 1207-1216). Peptide mapping and immunoblotting established that these three proteins were distinct molecules. Using monospecific antibodies to these three proteins, we showed that they were all restricted to the superficial urothelial cells and were AUM-associated. The 27- and 15-kDa proteins were detected exclusively on the luminal side of mature, apical AUMs. In contrast, epitopes of the 47-kDa protein were detected on both sides of apical AUMs suggesting a transmembranous configuration. These results (i) provide the strongest evidence thus far that AUM contains three major proteins (the 27-kDa uroplakin I, 15-kDa uroplakin II, and 47-kDa uroplakin III) which form an extremely insoluble complex, (ii) suggest that uroplakin II, like uroplakin I (Yu, J., Manabe, M., Wu, X.-R., Xu, C., Surya, B., and Sun, T.-T. (1990) J. Cell. Biol. 111, 1207-1216), translocates from one side of the membrane to another during AUM maturation, (iii) indicate that uroplakin III may play a different structural role than uroplakins I and II in AUM formation, and (iv) establish the three uroplakins as markers for an advanced stage of urothelial differentiation.
Production of Polyhydroxybutyrate by Polycistronic Expression of Bacterial Genes in Tobacco Plastid (2004)

Transgenic techniques are used to enhance and improve crop production, and their application to the production of chemical resources in plants has been under investigation. To achieve this latter goal, multiple-gene transformation is required to improve or change plant metabolic pathways; when accomplished by plant nuclear transformation, however, this procedure is costly and time consuming. We succeeded in the metabolic engineering of the tobacco plant by introducing multiple genes within a bacteria-like operon into a plastid genome. A tobacco plastid was transformed with a polycistron consisting of the spectinomycin resistance gene and three bacterial genes for the biosynthesis of the biodegradable polyester, poly[(R)-3-hydroxybutyrate] (PHB), after modification of their ribosome binding sites. DNA and RNA analysis confirmed the insertion of the introduced genes into the plastid genome and their polycistronic expression. As the result, the transplastomic tobacco accumulated PHB in its leaves. The introduced genes and the PHB productivity were maternally inherited, avoiding genetic spread by pollen diffusion, and were maintained stably in the seed progeny. Despite the low PHB productivity, this report demonstrates the feasibility of transplastomic technology for metabolic engineering. This "phyto-fermentation" system can be applied to plant production of various chemical commodities and pharmaceuticals.
Differential Activation of Innate Immune Responses by Adenovirus and Adeno-Associated Virus Vectors (2002)

Adenovirus vectors induce acute inflammation of infected tissues due to activation of the innate immune system and expression of numerous chemokines and cytokines in transduced target cells. In contrast, adeno-associated virus (AAV) vectors are not associated with significant inflammation experimentally or clinically. We tested the ability of AAV vectors to induce the expression of chemokines in vitro and to activate the innate immune system in vivo. In human HeLa cells and murine renal epithelium-derived cells (REC cells) the adenovirus vector AdlacZ induced the expression of multiple inflammatory chemokines including RANTES, interferon-inducible protein 10 (IP-10), interleukin-8 (IL-8), MIP-1beta, and MIP-2 in a dose-dependent manner. The use of AAVlacZ did not induce the expression of these chemokines above baseline levels despite 40-fold-greater titers than AdlacZ and greater amounts of intracellular AAVlacZ genomes according to Southern and slot blot analysis. This finding confirmed that the lack of AAVlacZ induction of chemokine was not due to reduced transduction. In DBA/2 mice, the intravenous administration of 2.5 x 10(11) particles of AAVlacZ resulted in the rapid induction of liver tumor necrosis factor alpha (TNF-alpha), RANTES, IP-10, MIP-1beta, MCP-1, and MIP-2 mRNAs. However, 6 h following injection, chemokine mRNA levels returned to baseline. As expected, administration of 10-fold less AdlacZ caused an induction of liver TNF-alpha and chemokine mRNAs that persisted for more than 24 h posttransduction. Whereas intravenous administration of 2.5 x 10(11) particles of AAVlacZ triggered a transient infiltration of neutrophils and CD11b(+) cells into liver, this response stood in contrast to widespread inflammation and toxicity induced by AdlacZ. Kupffer cell depletion abolished AAVlacZ but not AdlacZ-induced chemokine expression and neutrophil infiltration. In summary, these results show that AAV vectors activate the innate immune system to a lesser extent than do adenovirus vectors and offer a possible explanation for the reduced inflammatory properties of AAV compared to adenovirus vectors.
Lactoferrin Derived Peptides: Mechanisms of Action and their Perspectives as Antimicrobial and Antitumoral Agents (2009)

Antimicrobial peptides, AMPs, exert their function acting mainly at the membrane level. In the wide AMPs panorama a particular position is occupied by lactoferrin derived peptides. They also possess antiviral, antifungal and antitumor activities and their parent molecules are available in several mammalian fluids and in dairy industries waste.
Trends and challenges in broadband wireless access (2002)

This paper gives an overview of broadband wireless access systems, discusses the current trends, and highlights the major technical challenges for future systems. The study covers local multipoint distribution service (LMDS) networks that operate at millimeter wave radio frequencies above 20 GHz, as well as broadband wireless access at microwave frequencies below 11 GHz. We outline the current standardization work in this field by the ETSI in Europe and the IEEE 802.16 Group in the US. We point out that one of the major problems is the intercell interference which limits the frequency reuse factor and the cell capacity. We address the issue of increasing cell capacity using adaptive modulation, code-division multiple access (CDMA), and adaptive antennas. We also discuss the basic transmission technologies for lower frequency bands (below 11 GHz) where a significant amount of multipath propagation must be compensated.
Bovine serum albumin nanoparticles modified with multilayers and aptamers for pH-responsive and targeted anti-cancer drug delivery (2012)

The widely used bovine serum albumin (BSA) nanoparticles (NPs) were modified with poly(allylamine hydrochloride) (PAH)/sodium poly(4-styrene sulfonate) (PSS) multilayers and aptamers to improve their suspension stability and targeting ability. For this to occur, a PAH-g-poly(ethylene glycol) (PAH-g-PEG–COOH) layer was further adsorbed onto the (PAH/PSS)2 multilayer-coated BSA NPs and used to covalently bond the aptamer AS1411, which is known to specifically bind the over-expressed nucleolin on cancer cell membranes. The PEGylated multilayer-coated BSA NPs showed good suspension stability in diverse media, in particular in a serum containing medium. By a mechanism of spontaneous deposition, doxorubicin (DOX) was effectively loaded into the pre-formed BSA NPs with both good encapsulation efficiency (98.6%) and loading percentage (9%). The loaded drug showed a pH-dependent release behaviour, i.e. faster at pH 5.5 than at pH 7.4. The multilayer coating did not significantly influence either both drug loading or release. In vitro cell culture demonstrated that the as-prepared BSA NPs could be specifically delivered to liver cancer cells, leading to higher cellular uptake and cytotoxicity.
Allelism Found between Two Common Bean Genes, Hilum Ring Color (D) and Partly Colored Seedcoat Pattern (Z), formerly Assumed to Be Independent (1999)

Inheritance of two phenotypes, the virgarcus pattern of partly colored seedcoats and the margo d seedcoat pattern, were studied in common bean ( Phaseolus vulgaris L.) materials that segregated jointly for genes controlling the two phenotypes to test the hypothesis of allelism of two genes, D and Z . The F 2 progeny from the cross j margo BC 3 5-593 × t z virgarcus BC 3 5-593 produced an unexpected phenotypic class, margo d , suggesting possible allelism of D and Z . The F 2 also produced another unexpected phenotypic class, white seedcoat, for which the genetic hypothesis t j z was made. The F 2 from the cross t j marginata BC 3 5-593 × t z virgarcus BC 3 5-593 provided supporting evidence for the new genotype, t j z , for a white seedcoat. Analysis of the F 2 and F 3 progenies of 80 random F 2 plants from the cross t z virgarcus BC 3 5-593 × d j (margo d ) BC 3 5-593 provided support for the hypothesis that the D and Z loci are allelic. Production of two different phenotypes (white vs. white with two tiny pale gray dots, one each at the raphe and micropyle) for t J / j z in two different genetic and cytoplasmic backgrounds is discussed. The F 2 from the crosses d j (margo d ) BC 2 5-593 × j v margo BC 2 5-593 and d j (margo d ) BC 3 5-593 × j margo BC 3 5-593 segregated for d (vs. D ) phenotypes, which were found not to be independent of a randomly amplified polymorphic DNA (RAPD) marker (AM10 560 ) associated (1.4 cM) with the Z locus. Because the Z gene symbol has priority, we propose to retain Z for the locus.