gebhart/patrepeval huggingface dataset:
A haemagglutinin (HA1)-specific FAb neutralizes influenza A virus by inhibiting fusion activity (2001)

H9-D3-4R2 (referred to as H9), a murine monoclonal HA1-specific IgG3, recognizes an epitope within antigenic site Cb of influenza virus A/PR/8/34 (H1N1). At 50% neutralization, inhibition of virus-mediated fusion was responsible for the majority of neutralization but, at higher antibody concentrations, the attachment of virus to target cells was also inhibited and may have contributed to neutralization. H9 FAb was also neutralizing, although the concentration needed was two orders of magnitude greater than for the IgG. Functional affinity of the IgG and affinity of the FAb were almost identical, and it is not clear why the neutralization efficiency of the FAb was so low. Unlike its IgG, H9 FAb had no detectable effect on virus attachment but inhibited virus fusion activity. It thus appears that monovalent binding by this antibody is sufficient to inhibit fusion activity and that this was directly responsible for neutralization of infectivity.
Dependence of distortion-product otoacoustic emissions on primary levels in normal and impaired ears. I. Effects of decreasing L2 below L1 (1995)

The 2f1-f2 distortion-product otoacoustic emission (DPOAE) is evoked by two primary tones of frequencies f1 < f2, and levels L1 and L2. Previous reports indicate that decreasing L2 below L1 = L2 can; (1) increase DPOAE amplitude in normal ears, and (2) increase the degree to which DPOAE amplitudes are reduced by cochlear trauma. Although both of these factors could be advantageous for clinical applications of DPOAEs, neither has been explored in detail. In the present study, 2f1-f2 DPOAE-amplitude frequency functions were collected from normal and impaired ears of rabbits and humans, with L1 = L2, and with L2 < L1, at each of three values of L1. In rabbits, controlled tonal or noise overexposures were used to produce permanent reductions of DPOAE amplitudes. Comparison of pre- and postexposure DPOAE-amplitude frequency functions demonstrated that the frequency-specific reductions of DPOAEs were enhanced by decreasing L2 below L1. In humans, DPOAE-amplitude frequency functions obtained with the various L1 and L2 combinations were collected from 16 normal ears to provide preliminary normative data for each stimulus-level condition. The L1-L2 that produced the maximum DPOAE amplitude in normal ears was systematically dependent on L1. Thus at most frequencies, decreasing L2 below L1 = L2 substantially reduced mean DPOAE amplitude when L1 > or = 75 dB SPL, but increased mean DPOAE amplitudes at L1 = 65 dB SPL. However, the increase of mean DPOAE amplitude obtained by decreasing L2 below L1 = 65 dB SPL was small, being less than 3.5 dB at most frequencies. More importantly, at L1 = 65 dB SPL, L2 could be decreased considerably below L1 = L2 without reducing mean DPOAE amplitude relative to that at L1 = L2. Inspection of DPOAE-amplitude frequency functions obtained from subjects with mild or moderate sensorineural hearing losses indicated that, in frequency regions of hearing impairment, decreasing L2 below L1 can enhance the degree of reduction of DPOAEs below the corresponding normative amplitudes, without reducing the normative amplitude. It is concluded that decreasing L2 below L1 = L2 has the potential to enhance the performance of DPOAEs in clinical applications.
Human cytomegalovirus: taking the strain (2015)

In celebrating the 60th anniversary of the first isolation of human cytomegalovirus (HCMV), we reflect on the merits and limitations of the viral strains currently being used to develop urgently needed treatments. HCMV research has been dependent for decades on the high-passage strains AD169 and Towne, heavily exploiting their capacity to replicate efficiently in fibroblasts. However, the genetic integrity of these strains is so severely compromised that great caution needs to be exercised when considering their past and future use. It is now evident that wild-type HCMV strains are not readily propagated in vitro. HCMV mutants are rapidly selected during isolation in fibroblasts, reproducibly affecting gene RL13, the UL128 locus (which includes genes UL128, UL130 and UL131A) and often the U(L)/b' region. As a result, the virus becomes less cell associated, altered in tropism and less pathogenic. This problem is not restricted to high-passage strains, as even low-passage strains can harbour biologically significant mutations. Cloning and manipulation of the HCMV genome as a bacterial artificial chromosome (BAC) offers a means of working with stable, genetically defined strains. To this end, the low-passage strain Merlin genome was cloned as a BAC and sequentially repaired to match the viral sequence in the original clinical sample from which Merlin was derived. Restoration of UL128L to wild type was detrimental to growth in fibroblasts, whereas restoration of RL13 impaired growth in all cell types tested. Stable propagation of phenotypically wild-type virus could be achieved only by placing both regions under conditional expression. In addition to the development of these tools, the Merlin transcriptome and proteome have been characterized in unparalleled detail. Although Merlin may be representative of the clinical agent, high-throughput whole-genome deep sequencing studies have highlighted the remarkable high level of interstrain variation present in circulating virus. There is a need to develop systems capable of addressing the significance of this diversity, free from the confounding effects of genetic changes associated with in vitro adaptation. The generation of a set of BAC clones, each containing the genome of a different HCMV strain repaired to match the sequence in the clinical sample, would provide a pathway to address the biological and clinical effects of natural variation in wild-type HCMV.
Performance analysis of a dispersion compensator using arrayed-waveguide gratings (2000)

We have developed a dispersion compensator that uses arrayed-waveguide gratings (AWGs) and a spatial filter. The compensator using AWGs with 380 waveguides in each array and the diffraction order of 53, can compensate a total second-order dispersion of 260 ps/nm with an eye-closure penalty of 1 dB for a 40-Gb/s nonreturn-to-zero (NRZ) signal. It is shown that the required spatial resolution of the spatial phase filter for compensation is 2.55 /spl mu/m for silica AWGs of usual design. The acceptable fluctuation in the refractive index of the waveguides in the AWGs is as large as 5/spl times/10/sup -5/.
Meta-analysis: Antithrombotic Therapy to Prevent Stroke in Patients Who Have Nonvalvular Atrial Fibrillation (2007)

Adjusted-dose warfarin and antiplatelet agents reduce stroke by approximately 60% and by approximately 20%, respectively, in patients who have atrial fibrillation. Warfarin is substantially more efficacious (by approximately 40%) than antiplatelet therapy. Absolute increases in major extracranial hemorrhage associated with antithrombotic therapy in participants from the trials included in this meta-analysis were less than the absolute reductions in stroke. Judicious use of antithrombotic therapy importantly reduces stroke for most patients who have atrial fibrillation.
166. Synthetic antimalarials. Part XVI. 4-Dialkylaminoalkylaminoquinazolines. Variation of substituents in the 6- and 7-positions (1947)

N. B. Chapman, G. M. Gibson and F. G. Mann, J. Chem. Soc., 1947, 890 DOI: 10.1039/JR9470000890
Manganese‐enhanced magnetic resonance imaging (MEMRI) (2004)

Manganese ion (Mn2+) is an essential metal that participates as a cofactor in a number of critical biological functions, such as electron transport, detoxification of free radicals and synthesis of neurotransmitters. Mn2+ can enter excitable cells using some of the same transport systems as Ca2+ and it can bind to a number of intracellular sites because it has high affinity for Ca2+ and Mg2+ binding sites on proteins and nucleic acids. Paramagnetic forms of manganese ions are potent MRI relaxation agents. Indeed, Mn2+ was the first contrast agent proposed for use in MRI. Recently, there has been renewed interest in combining the strong MRI relaxation effects of Mn2+ with its unique biology, in order to further expand the already broad assortment of useful information that can be measured by MRI. Such an approach has been continuously developed in the past several years to provide unique tissue contrast, to assess tissue viability, to act as a surrogate marker of calcium influx into cells and to trace neuronal connections. This special issue of NMR in Biomedicine on manganese-enhanced MRI (MEMRI) is aimed at providing the readers of this journal with an extensive review of some of the most prominent applications of MEMRI in biological systems. Written by several of the leaders in the field, the reviews and original research articles featured in this special issue are likely to offer an exciting and inspiring view of the broad range of applications of MEMRI.
Selective Targeting of Malignant Cells with Cytotoxin-Folate Conjugates (1994)

Previous work has shown that proteins can be nondestructively delivered into the cytoplasm of folate receptor-bearing cells if the proteins are conjugated to folic acid prior to addition to cells. In view of other reports suggesting the membrane receptor for folic acid is vastly overexpressed on tumor cells, we decided to explore whether malignant cells might be selectively targeted in a co-culture with nontransformed cells using ligated folate as the targeting agent. Exploiting the cytotoxicity of the ribosome-inactivating toxin, momordin, to assay successful intracellular protein delivery, we demonstrate that HeLa and KB cells (two malignant human cell lines) can be selectively and quantitatively killed in co-cultures with WI38 and Hs67 cells (two normal human cell types). Not only are the normal cells not damaged by treatment of the co-cultures with momordin-folate, but their rates of proliferation actually accelerate, presumably due to increased availability of nutrients otherwise consumed by the transformed cells. Analysis of folate receptor number before and after momordin-folate treatment indicates that receptor density may be a good predictor of toxin-folate sensitivity. Taken together, the data suggest that conjugates of folic acid with cytotoxic proteins warrant further examination as possible tumor-specific chemotherapeutic agents.
POLYMYXIN P, NEW ANTIBIOTICS OF POLYMYXIN GROUP (1969)

In our screening studies of peptide antibiotics produced by soil bacteria, a new antibiotic complex, polymyxin P was isolated from a culture of strain T-39, obtained from soil collected at Suma-ku, Kobe City, Japan.
[Peroral long-term treatment of psoriasis using fumaric acid derivatives]. (1987)

Oral treatment of psoriasis on an outpatient basis, using a preparation containing fumaric acid derivatives, was evaluated as initial monotherapy (3 months) and as long-term basic therapy (12-14 months) in 13 and 11 patients, respectively. The course of the disease was analysed in each individual case. After completion of both parts of the trial, half of the patients that had only responded poorly to conventional antipsoriatic therapy showed a significant improvement which occurred after several weeks of treatment. In 4 patients the medication had to be stopped because of abdominal pain. No severe side effects, particularly of a renal, hepatic or haematological nature, could be established. Studies in mice and rats disclosed only a low acute toxicity of the fumaric acid derivatives used. In additional analyses, hypotheses were dealt with concerning the mechanism of action of fumaric acid in psoriasis. To establish fumaric acid derivatives in the treatment of psoriasis, studies on chronic toxicity and pharmacokinetics will have to be conducted. Further clinical trials should evaluate a single fumaric acid derivative instead of mixtures.
Prevention of UVB-induced skin inflammation, genotoxicity, and photocarcinogenesis in mice by WHI-P131, a dual-function inhibitor of Janus kinase 3 and EGF receptor kinase (2011)

The current study examined the chemopreventive potential of the dual-function JAK3/EGFR tyrosine kinase inhibitor WHI-P131 (CAS 202475-60-3) in photocarcinogenesis of non-melanoma skin cancer (NMSC). Prophylactic WHI-P131 exhibited significant anti-inflammatory activity in the SKH-1 mouse model of sunburn and afforded significant protection against the inflammatory skin damage that results from UVB exposure. UVB exposure (400 mJ/cm2) increased the mutation rate of the transgene target in UVB-exposed skin of BigBlue mice by a factor of 3.7 from 8.6 x 10(-5) to 31.7 x 10(-5) but this genotoxicity was almost completely prevented by topically administered prophylactic WHI-Pl31 (1.5 mg/cm2). Chronic and repetitive exposure of vehicle-treated SKH-1 mice to 35 mJ/cm2 UVB, three times per week for 20 weeks resulted in appearance of a spectrum of lesions from actinic keratoses and squamous cell carcinoma (SCC) in situ to invasive SCC. Both the number and size of the skin lesions progressively increased over time. Notably, topical administration of WHI-P131 (1.0 mg/cm2) over the UVB target skin area on the dorsal surface 15 min before each UVB exposure significantly suppressed the photocarcinogenesis as documented by a 4-week delay in the onset of visible skin lesions, decreased total lesion volume per mouse (1.9 +/- 0.5 mm3 vs. 2.5 +/- 0.5 mm3/lesion at 20 weeks), and decreased number (1.6 +/- 0.4/mouse vs. 4.2 +/- 1.6/mouse at 20 weeks, P < 0.05) as well as smaller size of lesions and consequently a smaller total lesion volume ("skin cancer burden") (10.6 +/- 4.3 mm3 vs. 3.2 +/- 0.9 mm3 at 20 weeks, P < 0.05). These experimental findings provide unprecedented evidence that WHI-P131 may be useful as a chemopreventive agent against NMSC.
δ‐Ca2/calmodulin‐dependent protein kinase II expression pattern in adult mouse heart and cardiogenic differentiation of embryonic stem cells (2000)

δ-isoforms of the Ca2+/calmodulin-dependent protein kinase type II (CaMKII) are considered to substantially influence cardiac functions. However, no data exist on the expression of these isoforms in the mouse heart. We analyzed the transcript pattern of non-neuronally expressed δ-isoforms in heart and skeletal muscle of adult mice by RT-PCR. For members of the δ-CaMKII subclass with both variable domains (subclass II), weak transcriptional expression of isoforms δ2 and δ 3 was found in the heart. In skeletal muscle no δ3-specific transcript was detectable. In cardiac tissue, stronger signals result from amplifications of δ9 and from members of the subclass I lacking the second variable domain. Western blotting was performed using a subclass II-specific antibody. In murine cardiac and skeletal muscle tissue a δ-CaMKII protein pattern was obtained similar to that described for rat. To gain insight into the expression of δ-CaMKII during the earliest steps of cardiogenic differentiation, we analyzed the transcript pattern of murine embryonic stem cell-derived cardiomyocytes in various differentiation stages. Reproducible RT-PCR signals could be obtained for δ6 and δ10, both belonging to the δ-CaMKII subclass I. Transcripts for δ6 were ubiquitously expressed, whereas transcripts for δ10 were detectable in increasing amounts after 7–10 days of the onset of cardiogenic differentiation. Our results point to a differentiation-dependent expression of the two δ-CaMKII subclasses, and also to differences in the expression of individual members of subclass I during the early stages of cardiogenic differentiation. J. Cell. Biochem. 79:293–300, 2000. © 2000 Wiley-Liss, Inc.
Protective Immunity to Cytomegalovirus (CMV) Retinitis in AIDS Is Associated with CMV‐Specific T Cells That Express Interferon‐γ and Interleukin‐2 and Have a CD8+Cell Early Maturational Phenotype (2006)

To determine potential correlates of immune recovery from AIDS-related cytomegalovirus retinitis (CMVR), multiparameter flow cytometry was used to characterize CMV-specific T cells from subjects with CMVR. Individuals with active retinitis were compared with those who had been clinically immunorestored by antiretroviral therapy and had > or =2 years of ophthalmologic follow-up without anti-CMV therapy or retinitis reactivation or progression. In comparison with patients with active retinitis, immunorestored patients had higher circulating CD4(+) and CD8(+) T cells expressing interleukin-2 and interferon- gamma in response to combined CMV pp65 and IE1 peptide pool stimulation. CD4(+) T cell responses were predominantly to pp65, whereas CD8(+) T cell responses were predominantly to IE. Immunorestored patients, compared with patients with active retinitis, had increased levels of circulating CMV-specific CD8(+) T cells with "early" (CD27(+)CD28(+)CD45RA(+), CD27(+)CD28(+)CD45RA(-)) and "intermediate" (CD27(-)CD28(+)CD45RA(-)) phenotypes. Recovery from AIDS-related CMVR after the initiation of antiretroviral therapy may be mediated by CMV-specific CD4(+) and CD8(+) T cells capable of promoting antigen-specific CD8(+) T cell proliferation.
Low frequency of the common Norwegian and Finnish LDL‐receptor mutations in Swedish patients with familial hypercholesterolaemia (1998)

The mutation pattern in Swedish FH patients differs considerably from that in Finland and Norway. The two new mutations discovered will probably cause serious functional disturbances in the LDL-receptor function. Thus far, no predominant mutation was seen in Swedish FH-patients.
A secreted form of the human interleukin 2 receptor encoded by an "anchor minus" cDNA. (1986)

The DNA sequence encoding all of the putative intracytoplasmic domain and most of the trans-membrane domain of the human IL 2 receptor was deleted from a full length receptor cDNA. After expression in mouse L cells, the resultant "anchor minus" cDNA was found to direct the synthesis of a secreted rather than membrane-associated form of the IL 2 receptor. The secreted receptor protein (44,000 to 46,000 Mr) retained the capacity to bind both IL 2 and the monoclonal anti-Tac antibody, as evidenced by retention on IL 2 and anti-Tac affinity columns, inhibition of [3H]-anti-Tac binding to HUT 102B2 cells, and partial inhibition of IL 2-induced CTLL proliferation. Removal of these domains from the IL 2 receptor did not alter the posttranslational processing or rate of export of the truncated receptor protein. These data confirm the proposed membrane orientation of the IL 2 receptor (NH2 terminus out, COOH terminus in) and underscore the anchoring function of this carboxy terminal receptor segment. The availability of such anchor minus receptor cDNA constructs may facilitate purification of large quantities of receptor protein for further analysis of receptor structure, valency, and localization of the IL 2 binding site(s).
A Sparsity-Aware Approach for NBI Estimation in MIMO-OFDM (2011)

In this paper, we present a novel approach based on compressive sensing theory to estimate and mitigate asynchronous narrow-band interference (NBI) in orthogonal frequency division multiplexing systems with multiple transmit and/or multiple receive antennas. We consider the practical scenarios where one or multiple asynchronous NBI signals experience fast fading and/or frequency-selective fading channels. Furthermore, we propose a novel technique for estimating the desired signal's channel in the presence of unknown NBI. Our approach does not require any prior information about the NBI. Simulation results demonstrate the effectiveness of our proposed techniques in mitigating NBI and approaching the interference-free performance limit over practical ranges of NBI power levels, spectral widths, and mobility levels.
CONTROLLING SYNCHRONIZATION IN A NEURON-LEVEL POPULATION MODEL (2007)

We have studied coupled neural populations in an effort to understand basic mechanisms that maintain their normal synchronization level despite changes in the inter-population coupling levels. Towards this goal, we have incorporated coupling and internal feedback structures in a neuron-level population model from the literature. We study two forms of internal feedback--regulation of excitation, and compensation of excessive excitation with inhibition. We show that normal feedback actions quickly regulate/compensate an abnormally high coupling between the neural populations, whereas a pathology in these feedback actions can lead to abnormal synchronization and "seizure"-like high amplitude oscillations. We then develop an external control paradigm, termed feedback decoupling, as a robust synchronization control strategy. The external feedback decoupling controller acts to achieve the operational objective of maintaining normal-level synchronous behavior irrespective of the pathology in the internal feedback mechanisms. Results from such an analysis have an interesting physical interpretation and specific implications for the treatment of diseases such as epilepsy. The proposed remedy is consistent with a variety of recent observations in the human and animal epileptic brain, and with theories from nonlinear systems, adaptive systems, optimization, and neurophysiology.
Customizing conception: a survey of preimplantation genetic diagnosis and the resulting social, ethical, and legal dilemmas. (2002)

One in six American couples experience difficulties conceiving a child. With fertility rates at an all time low, the business of treating infertility is booming. However, due to the United States prohibition on government funding for embryonic research, the $4 billion industry of assisted reproductive technologies (ART) has been incompletely monitored and largely removed from oversight. Additionally, due to the fervent abortion debate, in vitro fertilization (IVF) was introduced in the United States without a research phase and procedures have been forced to evolve in the private sector. Thus, the checks and balances on medical innovation that are generally imposed by the federal government for consumer protection are lacking. Decisions about when to go from the laboratory to the clinic are often left solely to the discretion of private physicians. Preimplantation genetic diagnosis (PGD) is just one of many such treatments offered by these clinics. This iBrief examines how, why, and to whom the reproductive procedure of PGD is offered. In addition, it evaluates the prospective effects to society that arise when PGD is used for sex selection and for nontherapeutic or enhancement purposes. Finally, it explores whether and how to regulate PGD in the United States by investigating approaches to policy making that have been adopted by the United Kingdom.
Several rAAV Vectors Efficiently Cross the Blood–brain Barrier and Transduce Neurons and Astrocytes in the Neonatal Mouse Central Nervous System (2011)

Noninvasive systemic gene delivery to the central nervous system (CNS) has largely been impeded by the blood-brain barrier (BBB). Recent studies documented widespread CNS gene transfer after intravascular delivery of recombinant adeno-associated virus 9 (rAAV9). To investigate alternative and possibly more potent rAAV vectors for systemic gene delivery across the BBB, we systematically evaluated the CNS gene transfer properties of nine different rAAVEGFP vectors after intravascular infusion in neonatal mice. Several rAAVs efficiently transduce neurons, motor neurons, astrocytes, and Purkinje cells; among them, rAAVrh.10 is at least as efficient as rAAV9 in many of the regions examined. Importantly, intravenously delivered rAAVs did not cause abnormal microgliosis in the CNS. The rAAVs that achieve stable widespread gene transfer in the CNS are exceptionally useful platforms for the development of therapeutic approaches for neurological disorders affecting large regions of the CNS as well as convenient biological tools for neuroscience research.
Low-Dose Streptokinase Therapy for Subclavian Vein Thrombosis (1984)

We have described the use of low-dose local infusion of streptokinase to treat subclavian vein thrombosis in a 30-year-old woman. Streptokinase was infused at 5,000 units per hour for three days, resulting in complete resolution of the thrombus.