gebhart/patrepeval huggingface dataset:
Monoclonal Antibody Radiopharmaceuticals:  Cationization, Pegylation, Radiometal Chelation, Pharmacokinetics, and Tumor Imaging (2003)

The 528 murine monoclonal antibody (MAb) to the human epidermal growth factor receptor (EGFR) was sequentially cationized with hexamethylenediamine and conjugated with diethylenetriaminepentaacetic acid (DTPA) as a potential antibody radiopharmaceutical for imaging EGFR-expressing cancer. The cationized 528 MAb was characterized with isoelectric focusing and electrophoresis, and an immunoradiometric assay, which showed the affinity of the 528 MAb for the human EGFR was retained following cationization. The native or cationized 528 MAb, labeled with (111)In, was injected intravenously in scid mice bearing human U87 flank tumors, which express the EGFR, and tumor imaging was performed with both external detection in live animals and with whole body autoradiography. However, the tumor signal was not increased with the cationized MAb, relative to the native MAb, and this was due to a serum inhibition phenomenon that was confirmed by a pharmacokinetics analysis in control mice. In an attempt to block the serum inhibition, the cationized 528 MAb was pegylated with 2000 Da poly(ethylene glycol), and the cationized/pegylated MAb was conjugated with DTPA and labeled with (111)In. However, a pharmacokinetics analysis showed the pegylation did not reverse the serum inhibition of the cationic charge on the MAb. These studies describe methods for reformulating monoclonal antibodies to develop improved radiopharmaceuticals, but show that radiolabeling a cationized MAb with DTPA produces a serum neutralization of the initial cationization modification.
Oxidative stress and the pathogenesis of Parkinson's disease (1996)

Current concepts of the pathogenesis of Parkinson's disease (PD) center on the formation of reactive oxygen species and the onset of oxidative stress leading to oxidative damage to substantia nigra pars compacta. Extensive postmortem studies have provided evidence to support the involvement of oxidative stress in the pathogenesis of PD; in particular, these include alterations in brain iron content, impaired mitochondrial function, alterations in the antioxidant protective systems (most notably superoxide dismutase [SOD] and reduced glutathione [GSH]), and evidence of oxidative damage to lipids, proteins, and DNA. Iron can induce oxidative stress, and intranigral injections have been shown to induce a model of progressive parkinsonism. A loss of GSH is associated with incidental Lewy body disease and may represent the earliest biochemical marker of nigral cell loss. GSH depletion alone may not result in damage to nigral neurons but may increase susceptibility to subsequent toxic or free radical exposure. The nature of the free radical species responsible for cell death in PD remains unknown, but there is evidence of involvement of hydroxyl radical (OH.), peroxynitrite, and nitric oxide. Indeed, OH. and peroxynitrite formation may be critically dependent on nitric oxide formation. Central to many of the processes involved in oxidative stress and oxidative damage in PD are the actions of monoamine oxidase-B (MAO-B). MAO-B is essential for the activation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to 1-methyl-4-phenylpyridinium ion, for a component of the enzymatic conversion of dopamine to hydrogen peroxide (H2O2), and for the activation of other potential toxins such as isoquinolines and beta-carbolines. Thus, the inhibition of MAO-B by drugs such as selegiline may protect against activation of some toxins and free radicals formed from the MAO-B oxidation of dopamine. In addition, selegiline may act through a mechanism unrelated to MAO-B to increase neurotrophic factor activity and upregulate molecules such as glutathione, SOD, catalase, and BCL-2 protein, which protect against oxidant stress and apoptosis. Consequently, selegiline may be advantageous in the long-term treatment of PD.
Control of leukocyte rolling velocity in TNF-α–induced inflammation by LFA-1 and Mac-1 (2002)

Previously it was shown that beta(2)-integrins are necessary for slow leukocyte rolling in inflamed venules. In this study, mice that are deficient for either one of the beta(2)-integrins, alpha(L)beta(2) (LFA-1) or alpha(M)beta(2) (Mac-1), were used to determine which of the beta(2)-integrins are responsible for slowing rolling leukocytes. The cremaster muscles of these mice were treated with tumor necrosis factor-alpha and prepared for intravital microscopy. The average rolling velocities in venules were elevated in LFA-1(-/-) mice (11.0 +/- 0.7 microm/s) and Mac-1(-/-) mice (10.1 +/- 1.1 microm/s) compared to wild-type mice (4.8 +/- 0.3 microm/s; P <.05), but were lower than in CD18(-/-) mice (28.5 +/- 2.1 microm/s). When both LFA-1 and Mac-1 were absent or blocked, rolling velocity became dependent on shear rate and approached that of CD18(-/-) mice. In addition, leukocyte adhesion efficiency was decreased in LFA-1(-/-) mice to near CD18(-/-) levels, but decreased only slightly in Mac-1(-/-) mice. Thus, both LFA-1 and Mac-1 contribute to slowing down rolling leukocytes, although LFA-1 is more important than Mac-1 in efficiently inducing firm adhesion.
A 3-Gb/s optical detector in standard CMOS for 850-nm optical communication (2005)

This paper presents a monolithic optical detector, consisting of an integrated photodiode and a preamplifier in a standard 0.18-/spl mu/m CMOS technology. A data rate of 3 Gb/s at BER <10/sup -11/ was achieved for /spl lambda/=850 nm with 25-/spl mu/W peak-peak optical power. This data rate is more than four times than that of current state-of-the-art optical detectors in standard CMOS reported so far. High-speed operation is achieved without reducing circuit responsivity by using an inherently robust analog equalizer that compensates (in gain and phase) for the photodiode roll-off over more than three decades. The presented solution is applicable to various photodiode structures, wavelengths, and CMOS generations.
Transvision : A Hand-held Augmented Reality System for Collaborative Design (1996)

This paper presents the shared augmented reality system called TransVision. TransVision augments real table-top with the computer graphics objects. Two or more participants hold a palmtop size see-through display and look at the world through the display. They can share the same virtual environment in the real world environment. Since users are not isolated from the real world, natural mutual communications such as body gestures can effectively be used during collaboration. This paper describes the architecture of the TransVision system and reports some early experiences. 1 Introduction In traditional design studios, when a group of engineers is designing a new automobile, they would build a clay model of the automobile and examine it. During this process, discussions among engineers are often supported by gazing (e.g., looking at some part of the model and saying something) and hand gestures (e.g., one engineer pointing at a part of the model and saying &amp;quot;the design of this part has t...
Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine* (2009)

The 2007 update continues to emphasize early use of age-specific therapies to attain time-sensitive goals, specifically recommending 1) first hour fluid resuscitation and inotrope therapy directed to goals of threshold heart rates, normal blood pressure, and capillary refill <or=2 secs, and 2) subsequent intensive care unit hemodynamic support directed to goals of central venous oxygen saturation >70% and cardiac index 3.3-6.0 L/min/m.
In vitro up-regulation of E-selectin and induction of interleukin-6 in endothelial cells by autoantibodies in Wegener's granulomatosis and microscopic polyangiitis. (1999)

Our data suggest that the activation of endothelial cells in patients with WG and MPA can be induced by circulating autoantibodies. Both ANCA and AECA can be responsible for this effect.
PTEN-Mediated Resistance to Epidermal Growth Factor Receptor Kinase Inhibitors (2007)

Molecularly targeted therapies are transforming the treatment of cancer. Elucidating the dynamic signaling networks that underlie sensitivity and resistance to these inhibitors is critical for successful clinical application. There is considerable evidence to suggest that constitutively activating mutations in kinases that regulate cellular growth may result in tumor cell "addiction" and favorable response to targeted inhibition. However, there is emerging evidence to suggest that clinical response may also be determined by other changes in the molecular circuitry of cancer cells, such as loss of key tumor-suppressor proteins. Here, we will discuss resistance to epidermal growth factor receptor tyrosine kinase inhibitors in glioblastoma patients that is mediated by loss of the PTEN tumor-suppressor protein.
Stability of sperm characteristics in men with disturbances in sperm quality (1989)

Summary Sixty‐one men referred to our laboratory for semen analysis, and subsequently judged to exhibit some form of sperm pathology, were asked to return for a second analysis, not less than 2 months after the first, in order to assess the stability of the pathological changes observed. In almost half of the cases, the referring physician had, on his own initiative, started hormone or antibiotic treatment. The sperm parameters studied included sperm count, sperm motility judged by laser‐Doppler spectroscopy, and sperm morphology and viability. The motility characteristics included percentage motile, their average velocity, and percentage swimming in a progressive manner, and their progressive velocity. In untreated subjects, there was no significant difference between the first and second analysis in any of the sperm parameters measured. This was also true for both oligozoospermic individuals (&lt;20 × 10 6 sperm/ml) and the group with higher sperm concentrations. All parameters were highly correlated on the two occasions. The average coefficients of variation of the paired observations were highest for sperm count (approximately 25%) and lowest for sperm velocities and the proportion of abnormal and viable cells in the ejaculate (1–9%). No major differences in the extent of variation could be detected between the low and high sperm density groups. In general, the unsystematic antibiotic and hormone regimens (clomiphene or androgen) used by the referring physicians had no discernable effect on any aspect of sperm quality, indicating the need for more controlled and standardized programmes of treatment.
What can randomized controlled trials tell us about nutrition and cancer prevention? (1999)

Randomized controlled trials are regarded as the most definitive of study designs. The randomized controlled trials that have tested nutritional factors for cancer prevention are reviewed. Trials that have tested the effects of nutrients given as high-dose supplements have been largely disappointing, typically showing either no or harmful effects. Possible benefits of vitamin E for prostate cancer prevention and selenium for prostate, colorectal, and lung cancer prevention have emerged only as secondary endpoints in trials conducted for other purposes; confirmatory new trials for these nutrients are now underway or are planned. The limitations of both past and current randomized controlled trials for studying diet-cancer relationships are discussed. The disappointing findings that have emerged from short-term studies of high-dose supplements cannot be interpreted as direct tests of the diet-cancer relationship because high-dose supplements cannot fully simulate the effects of whole foods on cancer risk. As we await findings from current and future trials, we should not forget that the ample evidence from observational epidemiologic research--suggesting that diets rich in fruits and vegetables can reduce the risk of many of the most common cancers--can provide a sound basis for nutritional recommendations aimed at reducing cancer risk.
Multi-Agent Meeting Scheduling: Preliminary Experimental Results (1996)

We view meeting scheduling as a distributed task where each agent knows its user&amp;apos;s preferences and calendar availability in order to act on behalf of its user. Although we may have some intuitions about how some parameters could affect the meeting scheduling efficiency and meeting quality, we run several experiments in order to explore the tradeoffs between different parameters. Our experiments show how the calendar and preference privacy affect the efficiency and the meeting joint quality under different experimental scenarios. The results show how the meeting scheduling performance is more stable and constant when agents try to keep their calendar and preference information private. We believe that these parameters play a key role in the distributed meeting scheduling task, specially if we are interested in building distributed systems with truly autonomous and independent agents where there is not a fixed control agent. Introduction In our daily life, meeting scheduling is a natura...
Adaptations of the in vitro MN assay for the genotoxicity assessment of nanomaterials (2010)

The issue of appropriate testing strategies has been raised for the genotoxicity assessment of nanomaterials. Recently, efforts have been made to evaluate the adequacy of Organisation for Economic Co-operation and Development-standardised tests to assess the genotoxicity of nanomaterials. The aim of this review was to examine whether the current guideline for the in vitro micronucleus (MN) assay is applicable for testing nanomaterials. From a Pubmed literature search, 21 available studies were identified for analysis. We reviewed all protocols used for testing nanomaterials with the in vitro MN assay. All studies were categorised based on the particle type and size. Different aspects of the protocols were evaluated such as the exposure (duration and doses), the cytochalasin-B treatment, serum levels and cytotoxicity assessment. Sixteen of the 21 studies demonstrated increased frequencies of MN. Some recommendations regarding the protocol were formulated to maximise sensitivity and avoid false negatives. Determination of the cellular dose was advised for a better interpretation of MN frequency results. The level of serum can modulate the cellular response, therefore the serum percentage used should enable cell growth and proliferation and a maximal sensitivity of the assay. Furthermore, different types of cytochalasin-B treatment were used, co-treatment, post-treatment and delayed co-treatment. In order to avoid decreased cellular uptake as a consequence of actin inhibition, post-treatment or delayed co-treatment is suggested. Exposure during mitosis should be recommended to allow contact with the chromatin or mitotic apparatus for nanomaterials that are unable to cross the nuclear membrane. With these adaptations, the in vitro MN assay can be recommended for genotoxicity testing of nanomaterials.
X-ray videodensitometric methods for blood flow and velocity measurement: A critical review of literature (2000)

Blood flow rate and velocity are important parameters for the study of vascular systems, and for the diagnosis, monitoring and evaluation of treatment of cerebro- and cardiovascular disease. For rapid imaging of cerebral and cardiac blood vessels, digital x-ray subtraction angiography has numerous advantages over other modalities. Roentgen-videodensitometric techniques measure blood flow and velocity from changes of contrast material density in x-ray angiograms. Many roentgen-videodensitometric flow measurement methods can also be applied to CT, MR and rotational angiography images. Hence, roentgen-videodensitometric blood flow and velocity measurement from digital x-ray angiograms represents an important research topic. This work contains a critical review and bibliography surveying current and old developments in the field. We present an extensive survey of English-language publications on the subject and a classification of published algorithms. We also present descriptions and critical reviews of these algorithms. The algorithms are reviewed with requirements imposed by neuro- and cardiovascular clinical environments in mind.
Metal-directed assembly of chiral bis-Zn(ii) Schiff base structures (2012)

Tetra-Schiff bases derived from (chiral) bis-salphen ligand scaffolds furnish, upon metalation with appropriate metal reagents, their multinuclear structures with associated Zn(OAc)(2) or Zn(OH)(2) fragments. The tendency of retaining these salts was investigated using four different (chiral) bis-salphen scaffolds. The presence of the additional Zn ions was supported by NMR studies, mass determinations and X-ray crystallography showing in two cases the possible mode of coordination within these multinuclear structures. In one case, dimerization of the Zn(3) complex leads to a unique hexanuclear Zn(6) complex being a mixture of diastereoisomeric complexes as revealed by NMR spectroscopy.
Population‐Based Exposure‐Efficacy Modeling of Ustekinumab in Patients With Moderate to Severe Plaque Psoriasis (2009)

Ustekinumab, a human immunoglobulin G1 kappa (IgG1k) monoclonal antibody that binds with high affinity to human interleukin-12 and interleukin-23, has demonstrated efficacy in patients with psoriasis. The objective of this study was to perform exposure-response modeling to increase the understanding of reduction in disease severity following treatment with ustekinumab in patients with moderate to severe psoriasis who participate in two phase III studies (PHOENIX 1 and PHOENIX 2). Patients were randomly assigned to receive ustekinumab 45 mg or 90 mg (n = 1312; 11,624 Psoriasis Area and Severity Index [PASI] scores) or placebo (n = 665; 3278 PASI scores). Disease severity was assessed using PASI scores. A population mechanism-based exposure-response model of ustekinumab using NONMEM was developed using serum ustekinumab concentrations and PASI scores. The pharmacodynamic response effect was the reduction in PASI score. The placebo effect, although minor, was also integrated into the model. None of the covariate factors evaluated (eg, demographics, baseline disease characteristics, comorbidities) significantly contributed to the between-subject variability in the pharmacodynamic parameters. The developed exposure-response model can serve as a basis to support future alternative dosing regimens for ustekinumab in patients with moderate to severe plaque psoriasis. A robust exposure-response relationship has been confirmed for ustekinumab in psoriasis.
Design and Locomotion Control of a Biomimetic Underwater Vehicle With Fin Propulsion (2011)

As a novel biologically inspired underwater vehicle, a robotic manta ray (RoMan-II) has been developed for potential marine applications. Manta ray can perform diversified locomotion patterns in water by manipulating two wide tins. These motion patterns have been implemented on the developed fish robot, including swimming by flapping fins, turning by modulating phase relations of fins, and online transition of different motion patterns. The movements are achieved by using a model of artificial central pattern generators (CPGs) constructed with coupled nonlinear oscillators. This paper focuses on the analytical formulation of coupling terms in the CPG model and the implementation issues of the CPG-based control on the fish robot. The control method demonstrated on the manta ray robot is expected to be a frame- work that can tackle locomotion control problems in other types of multifin-actuated fish robots or more general robots with rhythmic movement patterns.
PREPARATION, MODIFICATION, AND APPLICATIONS OF CHITIN NANOWHISKERS: A REVIEW (2012)

This paper provides an overview of the most up-to-date information available relating to chitin nanowhiskers. This paper presents aspects about chitin nanowhiskers, including methods of extraction and preparation, chemical modification and applications. Chitin nanowhiskers can be obtained by hydrochloric acid hydrolysis, TEMPO-mediated oxidation, partial deacetylation with NaOH by fibril surface cationization, ultrasonication, electrospinning, aqueous counter collision treatment, a simple grinding treatment and gelation with 1-allyl-3- methylimidazolium bromide. An introduction into the methods used to prepare chitin nanowhiskers is given. The chitin nanowhiskers applications are used mainly as reinforcing polymer nanocomposites, but also to prepare scaffolds, hydrogels and wound dressings, as adsorbents in industry, water purification, for protein immobilization, transformation of bacteria by exogenous genes, stabilization of oil-in-water emulsion and nematic gels, formation of CaCO 3 /chitin-whisker hybrids and as carbon precursors.
The use of β-galactosidase as a marker gene to define the regulatory sequences of the herpes simplex virus type 1 glycoprotein C gene in recombinant herpesviruses (1988)

The expression of Herpes Simplex Virus 1 (HSV-1) glycoprotein C (gC), a well defined herpesvirus late gene, was studied by linking the promoter-regulatory region of this gene to the coding sequences for the bacterial enzyme, beta-galactosidase (beta-gal). A chimeric gene, containing the beta-gal gene under the control of gC sequences from -1350 to +30 relative to the mRNA start site, was inserted by homologous recombination into the thymidine kinase (TK) locus of the HSV-1 genome. Selection of the TK- recombinant virus by plaque assay was facilitated by addition of a beta-gal indicator to the agarose overlay. Recombinant virus containing the gC promoter-beta-gal chimeric gene faithfully expressed beta-gal as a viral late gene, as shown by the absence of beta-gal expression when viral DNA replication was inhibited with phosphonoacetic acid. In contrast, the inhibition of viral DNA replication had no effect on the expression of beta-gal when the beta-gal gene was under the control of the early HSV-1 TK promoter in a separate recombinant virus. Analysis of recombinant viruses containing 5' to 3' deletions in the gC regulatory region revealed no apparent difference in beta-gal expression as deletions extended from -1350 to -109 base-pairs (bp) before the RNA start site, demonstrating that sequences between -109 and +30 are sufficient for regulated gC expression in the viral genome. Analysis of the mRNA made by these recombinant viruses confirmed the results of the beta-gal assays, and demonstrated that the transcriptional start sites of the gC promoter-beta-gal chimeric genes were the same as the start site of the gC gene.
Application of the System for Total Environmental Management (STEM) to dysmineralization, dental erosion and tooth wear (2008)

he underlying concept of STEM is that the oralenvironment has physical, ionic and microbialelements which can be measured, manipu-lated, and then monitored over time, in order toreduce the risk for oral disease (Table 1). While appli-cable to dental caries and other oral diseases, thisbrief article focuses on the STEM approach for hardtissue problems other than dental caries, namely dys-mineralization, dental erosion and tooth wear, andillustrates the management of four clinical cases.STEM includes the following components: astructured interview; structured clinical assess-ment; systematic personalized advice regardinghome care; targeted regeneration; hard tissuerepair; and recall and monitoring. The logicalsequence is as follows:1.
Respecting the Evidence: The Achievement Crisis Remains Real. (1996)

Wherein Stedman answers Berliner and Biddle's reply to his review of "The Manufactured Crisis"