gebhart/patrepeval huggingface dataset:
Fc Optimization of Therapeutic Antibodies Enhances Their Ability to Kill Tumor Cells In vitro and Controls Tumor Expansion In vivo via Low-Affinity Activating Fcγ Receptors (2007)

Monoclonal antibodies (mAb) are widely used in the treatment of non-Hodgkin's lymphoma and autoimmune diseases. Although the mechanism of action in vivo is not always known, the therapeutic activity of several approved mAbs depends on the binding of the Fcgamma regions to low-affinity Fcgamma receptors (FcgammaR) expressed on effector cells. We did functional genetic screens to identify IgG1 Fc domains with improved binding to the low-affinity activating Fc receptor CD16A (FcgammaRIIIA) and reduced binding to the low-affinity inhibitory Fc receptor, CD32B (FcgammaRIIB). Identification of new amino acid residues important for FcgammaR binding guided the construction of an Fc domain that showed a dramatically enhanced CD16A binding and greater than a 100-fold improvement in antibody-dependent cell-mediated cytotoxicity. In a xenograft murine model of B-cell malignancy, the greatest enhancement of an Fc-optimized anti-human B-cell mAb was accounted for by improved binding to FcgammaRIV, a unique mouse activating FcgammaR that is expressed by monocytes and macrophages but not natural killer (NK) cells, consistent with experimental and clinical data suggesting that mononuclear phagocytes, effector cells expressing both activating and inhibitory FcgammaR, are critical mediators of B-cell depletion in vivo. By using mice transgenic for human CD16A, enhanced survival was observed due to expression of CD16A-158(phe) on monocytes and macrophages as well as on NK cells in these mice. The design of new generations of improved antibodies for immunotherapy should aim at Fc optimization to increase the engagement of activating FcgammaR present on the surface of tumor-infiltrating effector cell populations.
Effect of Levetiracetam on Rapid Motor Learning in Humans (2002)

Levetiracetam interferes with rapid motor learning; this is consistent with a negative influence on long-term potentiation.
Mode-selective noncontact excitation of microcantilevers and microcantilever arrays in air using the ultrasound radiation force (2010)

We demonstrate the use of focused ultrasound waves to excite eigenmodes of microfabricated structures such as atomic force microscopy microcantilevers and coupled microcantilever arrays, among the smallest objects that have been excited in air using ultrasound radiation force. The method is based on the radiation force produced by a double-sideband suppressed carrier ultrasound waveform, centered at 500 kHz. The difference frequency between the sidebands, ranging from 10 to 200 kHz, excited resonances of these structures. Frequency response curves and deflection shapes were consistent with conventional base excitation, demonstrating the feasibility of noncontact excitation for a variety of microscale devices.
Skin Necrosis after a Low-Dose Vasopressin Infusion through a Central Venous Catheter for Treating Septic Shock (2006)

This is a report on a case of severe skin necrosis in a vasodilatory septic shock patient after the infusion of low-dose vasopressin through a central venous catheter. An 84-year-old male was hospitalized for edema on both legs at Asan Medical Center, Seoul, Korea. On hospital day 8, the patient began to complain of dyspnea and he subsequently developed severe septic shock caused by E. coli. After being transferred to the medical intensive care unit, his hypotension, which was refractory to norepinephrine, was controlled by an infusion of low-dose vasopressin (0.02 unit/min) through a central venous catheter into the right subclavian vein. After the infusion of low-dose vasopressin, severe skin necrosis with bullous changes developed, necessitating discontinuation of the low-dose vasopressin infusion. The patient expired from refractory septic shock. Although low-dose vasopressin can control hypotension in septic shock patients, low-dose vasopressin must be used with caution because ischemic complications such as skin necrosis can develop even with administration through a central venous catheter.
Selection of Well Contact Densities for Latchup-Immune Minimal-Area ICs (2010)

Heavy ion data for custom SRAMs fabricated in a 45-nm CMOS technology demonstrate the effects of N- and P-well contact densities on single-event latchup. Although scaling has improved latchup robustness, process-level immunity has not been achieved, indicating a continued need for latchup mitigation techniques. A simple, algorithmic approach for selecting N- and P-well contact densities is described that ensures latchup immunity while minimizing the area penalty.
Expression of EpCAM is up‐regulated during regeneration of renal epithelia (2008)

The human epithelial cell adhesion molecule (hEpCAM) is involved in epithelial morphogenesis and repair of epithelial tissues. We hypothesized that changes in hEpCAM expression in vivo correlate with regeneration of renal epithelia after ischaemia/reperfusion injury (IRi). Unilateral IRi was performed on kidneys of hEpCAM transgenic mice. Changes in hEpCAM expression were investigated by quantitative RT-PCR in renal cortex and medulla dissected by laser dissection microscopy and expression patterns of hEpCAM in regenerating kidneys were assessed by immunohistochemistry. The mechanism of hEpCAM promoter activation was investigated in vitro, by real-time bioluminescent imaging in HK-2 cells and in primary tubular epithelial cells (PTECs) subjected to hypoxia and reoxygenation. In vivo, the transcription of the human epcam gene significantly increased in the renal cortex during tubular re-epithelialization (p < 0.01). Moreover, the number of tubuli that expressed hEpCAM protein more than doubled in the renal cortex during regeneration. De novo expression of hEpCAM was detected in the S1 segments of proximal tubuli. Under hypoxic conditions in vitro, activity of the hEpCAM promoter was up-regulated two-fold in the HK-2 proximal epithelial cell line. Moreover, both in primary proximal epithelial cells and in HK-2 cells, hEpCAM protein expression was increased after hypoxia and reoxygenation. The significant up-regulation of hEpCAM during post-ischaemic renal regeneration in vivo and during in vitro hypoxia indicates that hEpCAM expression is associated with renal regeneration.
Treatment of severe pertussis: a study of the safety and pharmacology of intravenous pertussis immunoglobulin (1999)

P-IGIV is safe and achieves high pertussis toxin antibody titers in infants. This study provides data for a prospective, controlled trial of P-IGIV.
Outcome measures to be used in clinical trials in systemic lupus erythematosus. (1999)

The optimal outcome measures to be employed in clinical trials of systemic lupus erythematosus (SLE) have yet to be determined. Useful instruments should assess disease outcome in terms of all organ system involvement, as well as measures important to the patient. This article reviews those outcome measures that have been utilized in cohort studies in SLE, as well as their limited use in randomized clinical trials (RCT). Six disease activity measures have been developed: British Isles Lupus Assessment Group Scale (BILAG), European Consensus Lupus Activity Measure (ECLAM), Lupus Activity Index (LAI), National Institutes of Health SLE Index Score (SIS), Systemic Lupus Activity Measure (SLAM), and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). They have been validated in cohort studies as reflecting change in disease activity, and against each other. RCT utilizing SLAM, SLEDAI, BILAG, ECLAM, SIS, SLAM, SLEDAI are ongoing. It is recommended that the disease activity index of choice be selected; but simultaneous computer generation of multiple indices will facilitate comparisons across therapeutic interventions. A damage index has been developed and validated as the Systemic Lupus International Cooperating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index or SDI. In several cohort studies it has been shown sensitive to change over time, and to reflect cumulative disease activity. There is no health status or disability instrument specific to SLE. The Medical Outcomes Survey (SF-20) captures health status/health related quality of life (HRQOL) better than the Health Assessment Questionnaire (HAQ) in patients with SLE, but does not adequately reflect fatigue. The SF-36 does assess fatigue, and correlates closely with the SF-20. These data indicate that any individual measure of clinical response to a therapeutic intervention in SLE may reflect only a portion of what might be termed the "true outcome." Based on this work, the way is now paved to attempt to develop consensus on the important domains to be measured in clinical trials in SLE, the most appropriate instruments to use and the minimal clinically important differences in their results.
Modeling the access market of the two-sided ultra fast broadband platform in New Zealand (2013)

Local Fibre Companies (LFCs) and the government of New Zealand (NZ) are jointly implementing a nation-wide fibre-optics network, a project known as the Ultra-Fast Broadband (UFB) initiative, expected to cover 75% of households by 2019. New opportunities are expected to open up because the UFB network by regulation forbids LFCs to directly provide retail services. Consumers will need to purchase fibre services from Retail Service Providers (RSPs). The UFB represents a scenario of a two-sided platform, with consumers and RSPs on each side. Using two-sided platform theory and normative economics this paper presents the results of an agent-based model of platform access dynamics. The UFB platform currently subsidizes fibre lines for consumers. As the industry debates whether subsidization should continue, the results indicate that subsidy can be reduced when a large number of users on either side appear in the market. This case study presents us with a timely unique opportunity to analyze the issues involved as the market evolves and stabilizes.
Inversion of enzyme enantioselectivity mediated by the solvent (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInversion of enzyme enantioselectivity mediated by the solventShinichirou Tawaki and Alexander M. KlibanovCite this: J. Am. Chem. Soc. 1992, 114, 5, 1882–1884Publication Date (Print):February 1, 1992Publication History Published online1 May 2002Published inissue 1 February 1992https://pubs.acs.org/doi/10.1021/ja00031a054https://doi.org/10.1021/ja00031a054research-articleACS PublicationsRequest reuse permissionsArticle Views371Altmetric-Citations180LEARN 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
Incidence and case fatality rates of stroke subtypes in a multiethnic population: the South London Stroke Register (2002)

Although the black population is at increased risk of stroke and most subtypes of stroke, this is not translated into significant differences in survival. Hence black/white differences in mortality are mainly driven by incidence of stroke. There are striking demographic inequalities in the risk of stroke in this multiethnic inner city population that need to be tackled through interagency working. Although the reasons for the increased risk in the black population are unclear, demographic factors such as socioeconomic status do seem to play a significant independent part.
Anti-Angiogenesis Therapy in the Vx2 Rabbit Cancer Model with a Lipase-cleavable Sn 2 Taxane Phospholipid Prodrug using αvβ3-Targeted Theranostic Nanoparticles (2014)

In nanomedicine, the hydrophobic nature of paclitaxel has favored its incorporation into many nanoparticle formulations for anti-cancer chemotherapy. At lower doses taxanes are reported to elicit anti-angiogenic responses. In the present study, the facile synthesis, development and characterization of a new lipase-labile docetaxel prodrug is reported and shown to be an effective anti-angiogenic agent in vitro and in vivo. The Sn 2 phosphatidylcholine prodrug was stably incorporated into the lipid membrane of α(v)β₃-integrin targeted perfluorocarbon (PFC) nanoparticles (α(v)β₃-Dxtl-PD NP) and did not appreciably release during dissolution against PBS buffer or plasma over three days. Overnight exposure of α(v)β₃-Dxtl-PD NP to plasma spiked with phospholipase enzyme failed to liberate the taxane from the membrane until the nanoparticle integrity was compromised with alcohol. The bioactivity and efficacy of α(v)β₃-Dxtl-PD NP in endothelial cell culture was as effective as Taxol(®) or free docetaxel in methanol at equimolar doses over 96 hours. The anti-angiogenesis effectiveness of α(v)β₃-Dxtl-PD NP was demonstrated in the Vx2 rabbit model using MR imaging of angiogenesis with the same α(v)β₃-PFC nanoparticle platform. Nontargeted Dxtl-PD NP had a similar MR anti-angiogenesis response as the integrin-targeted agent, but microscopically measured decreases in tumor cell proliferation and increased apoptosis were detected only for the targeted drug. Equivalent dosages of Abraxane(®) given over the same treatment schedule had no effect on angiogenesis when compared to control rabbits receiving saline only. These data demonstrate that α(v)β₃-Dxtl-PD NP can reduce MR detectable angiogenesis and slow tumor progression in the Vx2 model, whereas equivalent systemic treatment with free taxane had no benefit.
Use of Bone-Graft Substitutes in Distal Radius Fractures (1999)

The development of bone-graft substitutes potentially provides the benefits of bone grafting without the risks of autograft harvest. During the past few years, the US Food and Drug Administration has approved several different types of products. These vary considerably in composition, structural strength, osteoinductive and osteoconductive potential, and mechanisms and rates at which they are resorbed or remodeled. The products now approved for orthopaedic applications in the United States include those based on naturally occurring materials (e.g., demineralized human bone matrix, bovine collagen mineral composites, and processed coralline hydroxyapatite) as well as synthetic materials (e.g., calcium sulfate pellets, bioactive glass, and calcium phosphate cement). Materials in development include variations on available products and a new generation of biologically active materials employing growth factors. Rigorous comparison of the products is difficult, as there are no universally accepted preclinical assays and comparable clinical studies. Despite the limitations of the data now available, controlled studies and anecdotal reports suggest that use of bone-graft substitutes may result in improved treatment outcomes for patients with fractures of the distal radius.
“Probe, Sample, and Instrument (PSI)”: The Hat-Trick for Fluorescence Live Cell Imaging (2018)

Cell Imaging Platforms (CIPs) are research infrastructures offering support to a number of scientific projects including the choice of adapted fluorescent probes for live cell imaging. What to detect in what type of sample and for how long is a major issue with fluorescent probes and, for this, the “hat-trick” “Probe–Sample–Instrument” (PSI) has to be considered. We propose here to deal with key points usually discussed in CIPs including the properties of fluorescent organic probes, the modality of cell labeling, and the best equipment to obtain appropriate spectral, spatial, and temporal resolution. New strategies in organic synthesis and click chemistry for accessing probes with enhanced photophysical characteristics and targeting abilities will also be addressed. Finally, methods for image processing will be described to optimize exploitation of fluorescence signals.
Facile Preparation of 3-Substituted Benzisothiazoles fromo-Mercaptoacylphenones (2010)

A synthesis of 3-substituted benzisothiazoles starting from readily available o-mercaptoacylphenones is presented. The key cyclization step features a mild S-nitrosation and its succeeding intramolecular aza-Wittig reaction leading to the construction of the title compounds.
Determination of absolute two-photon excitation cross sections by in situ second-order autocorrelation (1995)

It is shown that one can obtain absolute two-photon fluorescence excitation (TPE) cross sections without prior knowledge of the temporal profile of the excitation pulse. It is sufficient to record the fluorescence generated by two spatially superimposed but temporally shifted halves of the excitation beam as a function of their relative delay. Measurements employed a Michelson interferometer with a mode-locked Ti:sapphire laser as the excitation source. The TPE cross section for fluorescein [(46 ± 10) × 10−58 m4 s/photon] obtained at 782 nm with this technique agrees with single-mode cw excitation data. We find no indication of a deviation from the power-squared dependence of TPE.
Is the proximal tubular cell a proinflammatory cell? (2000)

In the past few decades, accumulating evidence has been generated on the central role of the proximal tubular cell in renal injury and dysfunction, such as can be found in some patients with glomerular proteinuria and in chronic renal rejection or following ischaemic insult. Following initial injury or stimulation of the proximal tubular cells, various cascades of mediator systems can be activated leading, for example, to enhanced local production of complement, chemokines, cytokines and matrix components. The locally produced mediators subsequently can lead to amplification of injury either directly or indirectly by enhancement of influx of proinflammatory cells such as macrophages, polymorphonuclear leukocytes and T cells. The concerted production of cytokines and chemokines may tip the balance to a more proinflammatory pathway leading to irreversible interstitial injury of the kidney and loss of renal function.
Pharmacokinetics of glucosamine in man. (1993)

The pharmacokinetics of glucosamine sulfate (CAS 29031-19-4) was investigated in 6 healthy male volunteers (2 per administration route) using 14C uniformly labelled glucosamine sulfate and administering it in single dose by intravenous (i.v.), intramuscular (i.m.) or oral route. The results show that after i.v. administration the radioactivity due to glucosamine appears in plasma and is rapidly eliminated, with an initial t1/2 of 0.28 h. 1-2 h after administration the radioactivity due to glucosamine disappears almost completely and is replaced by a radioactivity originating from plasma proteins, in which glucosamine or its metabolites are incorporated. This radioactivity reaches a peak after 8-10 h and then declines with a t1/2 of 70 h. About 28% of the administered radioactivity is recovered in the urine of the 120 h following the administration and less than 1% is recovered in the feces. After i.m. administration similar pharmacokinetic patterns are observed. After oral administration a proportion close to 90% of glucosamine sulfate is absorbed. Free glucosamine is not detectable in plasma. The radioactivity incorporated in the plasma proteins follows pharmacokinetic patterns which are similar to those after i.v. or i.m. administration, but its concentration in plasma is about 5 times smaller than that after parenteral administration. The AUC after oral administration is 26% of that after i.v., or i.m. administration. The smaller plasma levels of radioactivity after oral administration are probably due to a first pass effect in the liver which metabolizes a notable proportion of glucosamine into smaller molecules and ultimately to CO2, water and urea.(ABSTRACT TRUNCATED AT 250 WORDS)
TGF-β drives epithelial-mesenchymal transition through δEF1-mediated downregulation of ESRP (2011)

Epithelial-mesenchymal transition (EMT) is a crucial event in wound healing, tissue repair and cancer progression in adult tissues. We have recently shown that transforming growth factor (TGF)-β-induced EMT involves isoform switching of fibroblast growth factor receptors by alternative splicing. We performed a microarray-based analysis at single exon level to elucidate changes in splicing variants generated during TGF-β-induced EMT, and found that TGF-β induces broad alteration of splicing patterns by downregulating epithelial splicing regulatory proteins (ESRPs). This was achieved by TGF-β-mediated upregulation of δEF1 family proteins, δEF1 and SIP1. δEF1 and SIP1 each remarkably repressed ESRP2 transcription through binding to the ESRP2 promoter in NMuMG cells. Silencing of both δEF1 and SIP1, but not either alone, abolished the TGF-β-induced ESRP repression. The expression profiles of ESRPs were inversely related to those of δEF1 and SIP in human breast cancer cell lines and primary tumor specimens. Further, overexpression of ESRPs in TGF-β-treated cells resulted in restoration of the epithelial splicing profiles as well as attenuation of certain phenotypes of EMT. Therefore, δEF1 family proteins repress the expression of ESRPs to regulate alternative splicing during TGF-β-induced EMT and the progression of breast cancers.
Detection of Toxin-Producing Cyanobacteria by Use of Paramagnetic Beads for Cell Concentration and DNA Purification (1998)

Early detection of water blooms caused by potential toxin-producing cyanobacteria is important in environmental monitoring. We present a new nucleic acid-based method for detection of cyanobacteria in water that utilizes the same paramagnetic solid phase (beads) for both bacterial cell concentration and subsequent DNA purification. In the cell concentration step, the beads were attracted to a magnet after cell adsorption (in an alcohol- and salt-containing solution), and the supernatant was removed. For DNA purification, a buffer containing guanidine thiocyanate and Sarkosyl lysed the concentrated cells. The addition of alcohol precipitated the released DNA onto the same solid phase as was used for the cell concentration. Finally, to remove PCR inhibitors, the DNA was washed twice in alcohol while bound to the beads. All of the bead-DNA complex was used in the subsequent PCR amplification. The detection limit, as measured by 16S rDNA PCR amplification, was 50 cells in a 0.5-ml water sample, which is considerably lower than the limit (500 cells/ml) of toxic cyanobacteria tolerated in drinking water (New South Wales Blue-Green Algae Task Force, 1992). Testing of water from natural habitats showed a detection limit in the same range as that for the defined samples. The detection limits and the simplicity of the method (paramagnetic beads can be handled in automated systems) suggest that our method is suitable for routine environmental monitoring.