gebhart/patrepeval huggingface dataset:
Bispecific Antibodies as Novel Bioconjugates (1998)

Bispecific antibodies are unique macromolecular heterobifunctional cross-linkers with two different binding specificities within a single molecule. As ideal bioconjugates, they can specifically glue any two different molecules together without the need for chemical conjugation. With this unique feature, they have immense potential in biological and immunological fields. Their applications range from immunohistochemistry, immunoassays, radioimmunodiagnosis, radioimmunotherapy, and immunotherapy. Recently, a new second generation of bispecific molecules, bispecific single chain Fv and diabodies, has been produced by DNA recombinant technology. They can be considered as the ultimate magic bullets for in vivo applications. They may theoretically improve tumor or pathogen targeting and minimize side effects, eventually replacing the full-length bispecific antibodies. Emphasizing on developmental methodology and clinical applications of bispecific antibodies, this review gives a bird's-eye view of these unique bioconjugates.
Protein Identification by Peptide Mass Fingerprinting (2002)

Peptide mass fingerprinting is a protein identification technique in which MS is used to measure the masses of proteolytic peptide fragments. The protein then is identified by matching the measured peptide masses to corresponding peptide masses from protein or nucleotide sequence databases. Peptide mass fingerprinting works well for analytical proteomics because it combines a conceptually simple approach with robust, high-throughput instrumentation (typically MALDI-TOF MS). As with other MS-based analytical proteomics techniques, the quality of the protein identifications made depend on the quality of both the MS data, the accuracy of the databases, and the power of the search algorithms and software used. In the remainder of this chapter, we will consider peptide mass fingerprinting in greater detail. We will describe how peptide mass measurements can be used to identify proteins and finally how algorithms and software can automate the identification process.
Catalyst Self-Assembly for Scalable Patterning of Sub 10 nm Ultrahigh Aspect Ratio Nanopores in Silicon (2016)

Nanoporous silicon (NPSi) has received significant attention for its potential to contribute to a large number of applications, but has not yet been extensively implemented because of the inability of current state-of-the-art nanofabrication techniques to achieve sufficiently small pore size, high aspect ratio, and process scalability. In this work we describe the fabrication of NPSi via a modified metal-assisted chemical etching (MACE) process in which silica-shell gold nanoparticle (SiO2-AuNP) monolayers self-assemble from solution onto a silicon substrate. Exposure to the MACE etchant solution results in the rapid consumption of the SiO2 spacer shell, leaving well-spaced arrays of bare AuNPs on the substrate surface. Particles then begin to catalyze the etching of nanopore arrays without interruption, resulting in the formation of highly anisotropic individual pores. The excellent directionality of pore formation is thought to be promoted by the homogeneous interparticle spacing of the gold core nanocatalysts, which allow for even hole injection and subsequent etching along preferred crystallographic orientations. Electron microscopy and image analysis confirm the ability of the developed technique to produce micrometer-scale arrays of sub 10 nm nanopores with narrow size distributions and aspect ratios of over 100:1. By introducing a scalable process for obtaining high aspect ratio pores in a novel size regime, this work opens the door to implementation of NPSi in numerous devices and applications.
Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus (2008)

The mortality of human infection by influenza A/H5N1 virus can exceed 80%. The high mortality and its poor response to the neuraminidase inhibitor oseltamivir have been attributed to uncontrolled virus-induced cytokine storm. We challenged BALB/c mice with 1,000 LD50 of influenza A/Vietnam/1194/04. Survival, body weight, histopathology, inflammatory markers, viral loads, T lymphocyte counts, and neutralizing antibody response were documented in infected mice treated individually or in combination with zanamvir, celecoxib, gemfibrozil, and mesalazine. To imitate the real-life scenario, treatment was initiated at 48 h after viral challenge. There were significant improvements in survival rate (P = 0.02), survival time (P < 0.02), and inflammatory markers (P < 0.01) in the group treated with a triple combination of zanamivir, celecoxib, and mesalazine when compared with zanamivir alone. Zanamivir with or without immunomodulators reduced viral load to a similar extent. Insignificant prolongation of survival was observed when individual agents were used alone. Significantly higher levels of CD4+ and CD8+ T lymphocytes and less pulmonary inflammation were also found in the group receiving triple therapy. Zanamivir alone reduced viral load but not inflammation and mortality. The survival benefits of adding celecoxib and mesalazine to zanamivir could be caused by their synergistic effects in reducing cytokine dysfunction and preventing apoptosis. Combinations of a neuraminidase inhibitor with these immunomodulators should be considered in randomized controlled treatment trials of patients suffering from H5N1 infection.
FIC1 Disease: A Spectrum of Intrahepatic Cholestatic Disorders (2001)

FIC1 disease collectively refers to a group of autosomal-recessive familial liver disorders characterized by intrahepatic cholestasis due to mutations in the ATP8B1 gene (initially named FIC1). Classically, FIC1 disease comprises two different disorders: progressive familial intrahepatic cholestasis type 1 (PFIC1) and benign recurrent intrahepatic cholestasis (BRIC). However, we now view these two disorders as two ends of a continuum. Current therapeutic strategies for FIC1 disease, both medical and surgical, may relieve symptoms, but are presently insufficiently evaluated. ATP8B1 encodes a protein belonging to a recently defined subfamily of P-type ATPases. The biochemical and cellular functions of its product, FIC1, and the mechanisms by which its absence or dysfunction leads to cholestasis are currently elusive. Further studies to elucidate FIC1's function will be essential to unravel the pathogenesis of FIC1 disease. Such studies will also have a general impact on our understanding of the molecular mechanisms of bile formation and may therefore improve clinical management of both hereditary and acquired forms of cholestasis.
Electrical impedence tomography and heterogeneity of pulmonary perfusion and ventilation in porcine acute lung injury (2009)

EIT can be used to assess the heterogeneity of regional pulmonary ventilation and perfusion and V/Q matching during endotoxinaemic ALI, identifying pivotal pathophysiological changes.
Characterization of a new megakaryocytic cell line: the Dami cell (1988)

A new human megakaryocytic cell line (Dami) has been established from the blood of a patient with megakaryoblastic leukemia. The Dami cells grow primarily in suspension with a doubling time of 24 to 30 hours. By light and electron microscopy, the Dami cells range in size from 12 to 120 micron in diameter and have lobulated nuclei characteristic of megakaryocytes. At least 89% of the cells react with monoclonal antibodies against platelet glycoproteins (GP) Ib and IIB/IIIa, and glycophorin. The cells do not react with antibodies against lymphoid, monocyte, granulocyte, or macrophage antigens. Thirteen percent of the cells become polyploid, spontaneously achieving greater than 4N DNA ploidy levels. In response to phorbol myristate acetate (PMA), the proportion of cells with ploidy levels greater than 4N increased threefold and could be separated into discrete ploidy groups. PMA also increased the expression of GPIb, the GPIIb/GPIIIa complex,l and von Willebrand factor. Cytogenetic analysis revealed a human male hyperdiploid karyotype with a modal chromosome number of 54 to 64 and several consistent clonal chromosomal abnormalities. These included a partial deletion of chromosome 5 and a translocation involving chromosome 3. In contrast to other megakaryocytic cell lines in which only a small portion of the cells express the megakaryocytic phenotype, nearly all of the Dami cells express platelet glycoproteins. Thus, the Dami cells provide a superior model in which to study human megakaryocyte biochemistry and differentiation.
X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management (2012)

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. The disease is caused by mutations in the ABCD1 gene that encodes the peroxisomal membrane protein ALDP which is involved in the transmembrane transport of very long-chain fatty acids (VLCFA; ≥ C22). A defect in ALDP results in elevated levels of VLCFA in plasma and tissues. The clinical spectrum in males with X-ALD ranges from isolated adrenocortical insufficiency and slowly progressive myelopathy to devastating cerebral demyelination. The majority of heterozygous females will develop symptoms by the age of 60 years. In individual patients the disease course remains unpredictable. This review focuses on the diagnosis and management of patients with X-ALD and provides a guideline for clinicians that encounter patients with this highly complex disorder.
Stochastic transport in disordered systems (1983)

We develop a theory of stochastic transport in disordered media, starting from a linear master equation with random transition rates. A Green function formalism is employed to reduce the basic equation to a form suitable for the construction of a class of effective medium approximations (EMAs). The lowest order EMA, developed in detail here, corresponds to recent approximations proposed by Odagaki and Lax [Phys. Rev. B 24, 5284 (1981], Summerfield [Solid State Commun. 39, 401 (1981)], and Webman [Phys. Rev. Lett. 47, 1496 (1981)]. It yields an effective transition rate Wm which can be identified as the memory kernel of a generalized master equation, and used to define an associated continuous-time random walk on a uniform lattice. The long-time behavior of the mean-squared displacement arising from an initially localized state can be found from Wm, as can diffusion constants in any case where the long-time behavior of the system is diffusive. Detailed calculations are presented for seven lattice systems in one, two, and three dimensions, and for a variety of probability density functions f(w) for the transitions rates. For percolation-type densities, i.e., those with only a fraction p&amp;lt;1 of the bonds transmitting, the EMA predicts three distinct kinds of behavior: localization, ‘‘fractal’’ transport with slower than linear growth of the mean-squared displacement, and diffusion in the cases p&amp;lt;pc, p=pc, p≳pc, respectively, where pc is the bond percolation threshold of the lattice. Depending on the form of f(w) near w=0, critical exponents may take values independent of f(w) (‘‘universality’’) or heavily dependent on f(w) (‘‘nonuniversality’’).
[Relationship between analgesic activity and opiate receptor binding affinity of 5 derivatives of 3-aza-bicyclo(3,3,1)nonanes]. (1984)

By means of mouse hot plate test, writhing test and rat tail-flick test; highpressure liquid chromatography and receptorbinding assay, the results are as follows: 1) 5 derivatives of 3-azabicyclo [3,3,1] nonanes showed potent analgesic acticities. 2) Their partition coefficients were>3. 3) 5 derivatives possessed higher binding affinities for opiate receptors in mice brain. 4) There was a good correlation between the analgesic activities and the potencies to inhibit the binding of μ-receptor specific [3H] ligands to opiate receptors for 5 derivatives. However, the analgesic activities of 5 derivatives did not correlate with their partition coefficients. From the abovementioned results, it is concluded that the analgesic actibities of 5 derivatives to opiate receptors and their analgesia is mainly related to μ receptor. In addition, sodium response ratio, GTP response ratio and GTP+NaCl response ratio suggest that P7542, P 7542, P 7522 and P7534 are opioid agonists, but P 7521 and P7520 may be mixed agonist-antagonists.
Fiber-based polarization-sensitive Fourier domain optical coherence tomography using B-scan-oriented polarization modulation method (2006)

Fiber-based high-speed polarization-sensitive Fourier domain optical coherence tomography (PS-FD-OCT) is developed at 840 nm wavelength using polarization modulation method. The incident state of polarization is modulated along B-scan. The spectrometer has a polarizing beamsplitter and two line-CCD cameras operated at a line rate of 27.7 kHz. From the 0th and 1st orders of the spatial frequencies along the B-scanning, a depth-resolved Jones matrix can be derived. Since continuous polarization modulation along B-scan causes fringe washout, equivalent discrete polarization modulation is applied to biological measurements. For the demonstration, an in vitro chicken breast muscle, an in vivo finger pad, and an in vivo caries lesion of a human tooth are measured. Three dimensional phase retardation images show the potentials for applying the system to biological and medical studies.
Efficacy of Sacral Neuromodulation on Urological Diseases: A Multicentric Research Project (2012)

This multicenter research project confirmed the midterm safety and effectiveness of sacral neuromodulation in the treatment of refractory overactive bladder syndrome and urinary retention, showing high cure rates and low complication rates.
Influence of ApoE Content on Receptor Binding of Large, Buoyant LDL in Subjects With Different LDL Subclass Phenotypes (1998)

We investigated the influence of apolipoprotein (apo) E-containing particles on LDL receptor binding of large, buoyant LDL subfractions (LDL I) from subjects with predominantly large (phenotype A) and small (phenotype B) LDL particles. Direct binding by human fibroblast LDL receptors was tested at 4 degrees C before and after removal of apoE-containing particles by immunoaffinity chromatography. The binding affinity of total LDL I in phenotype B was greater than that in phenotype A (Kd of 1.83+/-0.3 and 3.43+/-0.9 nmol/L, respectively, P<.05). LDL I from phenotype B subjects had a higher apoE to apoB molar ratio than did that from phenotype A (0.16+/-0.04 versus 0.06+/-0.02, P<.05). Nondenaturing gradient gel electrophoresis of apoE-containing LDL I isolated by immunoaffinity chromatography revealed a substantially larger peak particle diameter than in apoE-free LDL I, and comparison of LDL I composition before and after immunoaffinity chromatography suggested an increase in triglyceride content of apoE-containing particles. After removal of these particles, there was a greater than twofold reduction in LDL receptor affinity of phenotype B LDL (Kd of 1.83+/-0.3 to 3.76+/-0.6, P<.01), whereas in phenotype A no change was observed (Kd of 3.43+/-0.9 to 3.57+/-0.4, respectively). The receptor affinity of apoE-free LDL I from phenotype A and B subjects did not differ. These findings confirm that large, buoyant LDL particles from phenotype B subjects have a higher LDL receptor affinity than does LDL I from phenotype A subjects and suggest that this difference is due to an increased content of large, triglyceride-enriched, apoE-containing lipoproteins. It is possible that the accumulation of these particles reflects abnormalities in the metabolism of remnant lipoproteins that contribute to atherosclerosis risk in phenotype B subjects.
A Primer-dependent Polymerase Function of Pseudomonas aeruginosa ATP-dependent DNA Ligase (LigD) (2004)

Pseudomonas aeruginosa encodes two putative DNA ligases: a classical NAD(+)-dependent DNA ligase (LigA) plus an ATP-dependent DNA ligase (LigD). LigD exemplifies a family of bacterial proteins that consist of a ligase domain fused to flanking domains that resemble nucleases and/or polymerases. Here we purify LigD and show that it possesses an intrinsic polymerase function resident within an autonomous C-terminal polymerase domain, LigD-(533-840), that flanks an autonomous DNA ligase domain, LigD-(188-527). Native LigD and the polymerase domain are both monomeric proteins. The polymerase activity is manifest in three ways: (i) non-templated nucleotide addition to a blunt-ended duplex DNA primer; (ii) non-templated addition to a single-stranded DNA primer; and (iii) templated extension of a 5'-tailed duplex DNA primer-template. The divalent cation cofactor requirement for non-templated and templated polymerase activity is satisfied by manganese or cobalt. rNTPs are preferred over dNTPs as substrates for non-templated blunt-end addition, which typically entails the incorporation of only 1 or 2 nucleotides at the primer terminus. Templated dNMP addition to a 5'-tailed substrate is efficient with respect to dNTP utilization; the primer is elongated to the end of the template strand and is then further extended with a non-templated nucleotide. The polymerase activity is abolished by alanine substitution for two aspartates (Asp-669 and Asp-671) within the putative metal-binding site. We speculate that polymerase activity is relevant to LigD function in nonhomologous end-joining.
Biocompatibility of Solid-Dosage Forms of Anti-Human Immunodeficiency Virus Type 1 Microbicides with the Human Cervicovaginal Mucosa Modeled Ex Vivo (2006)

Topical anti-human immunodeficiency virus (HIV) microbicides are being sought to reduce the spread of HIV type 1 (HIV-1) during sexual intercourse. The success of this strategy depends upon the selection of formulations compatible with the natural vaginal mucosal barrier. This study applied ex vivo-modeled human cervicovaginal epithelium to evaluate experimental solid-dosage forms of the anti-HIV-1 microbicide cellulose acetate 1,2-benzenedicarboxylate (CAP) and over-the-counter (OTC) vaginal products for their impact on inflammatory mediators regarded as potential HIV-1-enhancing risk factors. We assessed product-induced imbalances between interleukin-1alpha (IL-1alpha) and IL-1beta and the natural IL-1 receptor antagonist (IL-1RA) and changes in levels of IL-6, tumor necrosis factor alpha, IL-8, gamma interferon inducible protein 10 (IP-10), and macrophage inflammatory protein 3alpha (MIP-3alpha), known to recruit and activate monocytes, dendritic cells, and T cells to the inflamed mucosa. CAP film and gel formulation, similarly to the hydroxyethylcellulose universal vaginal placebo gel and the OTC K-Y moisturizing gel, were nontoxic and caused no significant changes in any inflammatory biomarker. In contrast, OTC vaginal cleansing and contraceptive films containing octoxynol-9 or nonoxynol-9 (N-9) demonstrated similar levels of toxicity but distinct immunoinflammatory profiles. IL-1alpha, IL-1beta, IL-8, and IP-10 were increased after treatment with both OTC vaginal cleansing and contraceptive films; however, MIP-3alpha was significantly elevated by the N-9-based film only (P < 0.01). Although both films increased extracellular IL-1RA, the cleansing film only significantly elevated the IL-1RA/IL-1 ratio (P < 0.001). The N-9-based film decreased intracellular IL-1RA (P < 0.05), which has anti-inflammatory intracrine functions. This study identifies immunoinflammatory biomarkers that can discriminate between formulations better than toxicity assays and should be clinically validated in relevance to the risk of HIV-1 acquisition.
Angiotensin II stimulates migration of retinal microvascular pericytes: involvement of TGF-β and PDGF-BB (2002)

We studied the promigratory effect of angiotensin II (ANG II) on cultured bovine retinal microvascular pericytes. ANG II stimulated migration of pericytes by 86% at 10(-8) M, but this effect was lost at 10(-4) M. Migratory responses were inhibited by the ANG II type 1 (AT(1)) receptor antagonist losartan but not by PD-123319, an AT(2) antagonist. Addition of PD-123319 to the 10(-4) M ANG II dose restored migratory responses. The promigratory effect of ANG II (10(-7) M) was reduced by 59% in absence of gradient. Although ANG II augmented the latent matrix metalloproteinase-2 (MMP-2) activity of the pericyte by 35%, it also doubled tissue inhibitors of MMPs. ANG II-induced migration was not altered by a broad-spectrum MMP inhibitor (GM6001); it was inhibited by ~50% by antibodies against transforming growth factor (TGF)-beta(1/2/3) and was abolished by antibodies against platelet-derived growth factor (PDGF)-BB. We conclude that ANG II induces chemotactic responses on retinal microvascular pericytes acting through the AT(1) receptor. This effect is opposed by the AT(2) receptor. ANG II-induced chemotaxis is mediated by PDGF-BB and involves TGF-beta, but it is independent of MMP activity. It is also independent of vascular endothelial growth factor (VEGF) because VEGF did not stimulate pericyte migration. ANG II can contribute to the regulation of retinal neovascularization by stimulating pericyte migration.
The Complete Nucleotide Sequence of Swine Vesicular Disease Virus (1989)

SUMMARY The complete nucleotide sequence of the genome of the enterovirus swine vesicular disease virus (SVDV; H/3 76) isolated from a healthy pig has been determined using molecular cloning and DNA sequencing techniques. The RNA genome was 7400 nucleotides long, excluding the poly(A) tract, and appeared to encode a single polyprotein of 2185 amino acids. The predicted amino acid sequence of the polyprotein showed close homology (around 90%) to that of the previously sequenced coxsackie-viruses B1, B3 and B4, and also showed homology (around 60%) to that of poliovirus. This homology allows us to predict the possible cleavage sites of the polyprotein and to identify other features of structural and functional significance, which seem to be important to the biological integrity of the virus. A detailed analysis of homology between SVDV and coxsackieviruses shows that non-structural proteins are highly conserved whereas the structural proteins are less well conserved. The 5′ and 3′ non-coding regions are also conserved, although there are several divergent nucleotide stretches. These stretches may differentiate SVDV from coxsackieviruses.
Androgenetic alopecia and prostate cancer: findings from an Australian case-control study. (2002)

The purpose of this study was to examine the relationship between androgenetic alopecia (AA) and prostate cancer with particular emphasis on early age at diagnosis and higher grade tumors. We conducted an age-stratified, population-based case-control study in Australia of men who were diagnosed before 70 years of age during 1994-1997 with histopathology-confirmed adenocarcinoma of the prostate, excluding well-differentiated tumors. Controls were selected from the electoral rolls, and the frequency was matched on age. After excluding subjects with missing values, the analysis was based on 1446 cases and 1390 controls of whom direct observations were made of their pattern of AA during face-to-face interviews. Our data suggest an association between prostate cancer and vertex baldness; compared with men who had no balding, the adjusted odds ratio (OR) was 1.54 (1.19-2.00). No associations were found between prostate cancer and frontal baldness or when frontal baldness was present concurrently with vertex baldness. The ORs were 0.98 (0.79-1.23) and 1.14 (0.90-1.45), respectively. The highest ORs were for high-grade disease in men 60-69 years of age: 1.80 (1.02-3.16) for frontal baldness; 2.91 (1.59-5.32) for vertex baldness; and 1.95 (1.10-3.45) for frontal and vertex baldness. This association between the pattern of AA and prostate cancer points to shared androgen pathways that are worthy of additional investigation.