bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel HER2 Aptamer Selectively Delivers Cytotoxic Drug to HER2-positive Breast Cancer Cells in Vitro
Authors: Liu Zhe , Duan Jin-Hong , Song Yong-Mei , Ma Jie , Wang Feng-Dan , Lu Xin , Yang Xian-Da 
Published: July 2012

Abstract

Background
Aptamer-based tumor targeted drug delivery system is a promising approach that may increase the efficacy of chemotherapy and reduce the related toxicity. HER2 protein is an attractive target for tumor-specific drug delivery because of its overexpression in multiple malignancies, including breast, gastric, ovarian, and lung cancers.

Methods
In this paper, we developed a new HER2 aptamer (HB5) by using systematic evolution of ligands by exponential enrichment technology (SELEX) and exploited its role as a targeting ligand for delivering doxorubicin (Dox) to breast cancer cells in vitro.

Results
The selected
aptamer
was an 86-nucleotide DNA molecule that bound to an epitope peptide of HER2 with a K
d of 18.9 nM. The aptamer also bound to the extracellular domain (ECD) of HER2 protein
with a K

d

of 316 nM
, and had minimal cross reactivity to albumin or trypsin. In addition, the aptamer was found to preferentially bind to HER2-positive but not HER2-negative breast cancer cells. An aptamer-doxorubicin complex (Apt-Dox) was formulated by intercalating Dox into the DNA structure of HB5. The Apt-Dox complex could selectively deliver Dox to HER2-positive breast cancer cells while reducing the drug intake by HER2-negative cells in vitro. Moreover, Apt-Dox retained the cytotoxicity of Dox against HER2-positive
breast cancer
cells, but reduced the cytotoxicity to HER2-negative cells.

Conclusions
The results suggest that the selected HER2 aptamer may have application potentials in targeted therapy against HER2-positive
breast cancer cells
.
Acute injury in the peripheral nervous system triggers an alternative macrophage response
Authors: Ydens Elke , Cauwels Anje , Asselbergh Bob , Goethals Sofie , Peeraer Lieve , Lornet Guillaume , Almeida-Souza Leonardo , Van Ginderachter Jo A , Timmerman Vincent , Janssens Sophie 
Published: July 2012

AbstractBackgroundThe activation of the immune system in neurodegeneration has detrimental as well as beneficial effects. Which aspects of this immune response aggravate the neurodegenerative breakdown and which stimulate regeneration remains an open question. To unravel the neuroprotective aspects of the immune system we focused on a model of acute peripheral nerve injury, in which the immune system was shown to be protective.MethodsTo determine the type of immune response triggered after axotomy of the sciatic nerve, a model for Wallerian degeneration in the peripheral nervous system, we evaluated markers representing the two extremes of a type I and type II immune response (classicalvs.alternative) using real-time quantitative polymerase chain reaction (RT-qPCR), western blot, and immunohistochemistry.ResultsOur results showed that acute peripheral nerve injury triggers an anti-inflammatory and immunosuppressive response, rather than a pro-inflammatory response. This was reflected by the complete absence of classical macrophage markers (iNOS, IFNγ, and IL12p40), and the strong up-regulation of tissue repair markers (arginase-1, Ym1, and Trem2). The signal favoring the alternative macrophage environment was induced immediately after nerve damage and appeared to be established within the nerve, well before the infiltration of macrophages. In addition, negative regulators of the innate immune response, as well as the anti-inflammatory cytokine IL-10 were induced. The strict regulation of the immune system dampens the potential tissue damaging effects of an over-activated response.ConclusionsWe here demonstrate that acute peripheral nerve injury triggers an inherent protective environment by inducing the M2 phenotype of macrophages and the expression of arginase-1. We believe that the M2 phenotype, associated with a sterile inflammatory response and tissue repair, might explain their neuroprotective capacity. As such, shifting the neurodegeneration-induced immune responses towards an M2/Th2 response could be an important therapeutic strategy.
Glossopharyngeal neuralgia secondary to vascular compression in a patient with multiple sclerosis: a case report
Authors: Gaitour Emil , Nick Saeed Talebzadeh , Roberts Charles , Gonzalez-Toledo Eduardo , Munjampalli Sai , Minagar Alireza , Vrooman Bruce , Souzdalnitski Dmitri , Zamnifekri Behrouz 
Published: July 2012

Abstract

Introduction
Glossopharyngeal neuralgia is an uncommon, painful syndrome, characterized by paroxysms of pain in the sensory distribution of the 9th cranial nerve. Idiopathic glossopharyngeal neuralgia may be due to compression of the glossopharyngeal nerve by adjacent vessels, while secondary glossopharyngeal neuralgia is associated with identifiable lesions affecting the glossopharyngeal nerve at different levels of its neuroanatomic pathway. Glossopharyngeal neuralgia is rare in the general population, but is more common in patients with multiple sclerosis.

Case presentation
A 56-year-old Caucasian woman with multiple sclerosis and migraine presented to our facility with intermittent lancinating pain to the right of her throat, tongue, and the floor of her mouth that had been occurring for the past year. The pain was intense, sharp, and stabbing, which lasted two to six seconds with radiation to the right ear. Initially, the attacks were infrequent, however, they had become more intense and frequent over time. Our patient reported weight loss, headache, painful swallowing, and the inability to maintain sleep due to painful attacks. A neurological examination revealed a right-handed woman with trigger points in the back of the tongue and throat on the right side. She also had dysphagia, hoarseness, and pain in the distribution of the right glossopharyngeal nerve. Mild right hemiparesis, hyperreflexia, dysmetria, and an ataxic gait were present. A magnetic resonance imaging scan of the brain was consistent with multiple sclerosis and magnetic resonance angiography demonstrated a loop of the posterior inferior cerebellar artery compressing the right glossopharyngeal nerve. She responded satisfactorily to carbamazepine. Microvascular decompression and Gamma Knife® radiosurgery were discussed in case of failure of the medical treatment; however, she declined these options.

Conclusions
Glossopharyngeal neuralgia in multiple sclerosis may occur due to vascular compressive lesions and it should not be solely attributed to the underlying demyelinating process. Vascular compression of the glossopharyngeal nerve could independently cause glossopharyngeal neuralgia in patients with multiple sclerosis, and vascular imaging to exclude such a diagnosis is recommended.
The role for scientists in tackling food insecurity and climate change
Authors: Beddington John R , Asaduzzaman Mohammed , Clark Megan E , Bremauntz Adrian Fernández , Guillou Marion D , Jahn Molly M , Lin Erda , Mamo Tekalign , Negra Christine , Nobre Carlos A , Scholes Robert J , Sharma Rita , Van Bo Nguyen , Wakhungu Judi 
Published: July 2012

Abstract
To adapt to climate change and ensure food security, major interventions are required to transform current patterns and practices of food production, distribution and consumption. The scientific community has an essential role to play in informing concurrent, strategic investments to establish climate-resilient agricultural production systems, minimize greenhouse gas emissions, make efficient use of resources, develop low-waste supply chains, ensure adequate nutrition, encourage healthy eating choices and develop a global knowledge system for sustainability. This paper outlines scientific contributions that will be essential to the seven policy recommendations for achieving food security in the context of climate change put forward by the Commission on Sustainable Agriculture and Climate Change. These include improved understanding of agriculture’s vulnerability to climate change, food price dynamics, food waste and consumption patterns and monitoring technologies as well as multidisciplinary investigation of regionally appropriate responses to climate change and food security challenges.
Gene expression profiling and functional analysis of angiogenic markers in murine collagen-induced arthritis
Authors: Raatz Yvonne , Ibrahim Saleh , Feldmann Marc , Paleolog Ewa M 
Published: July 2012

Abstract
Introduction
Dysregulated angiogenesis is implicated in the pathogenesis of rheumatoid arthritis (RA). To provide a more profound understanding of arthritis-associated angiogenesis, we evaluated the expression of angiogenesis-modulating genes at onset, peak and declining phases of collagen-induced arthritis (CIA), a well-established mouse model for RA.

Methods
CIA was induced in DBA/1 mice with type II collagen. Functional capillary density in synovial tissue of knee joints was determined by intravital fluorescence microscopy. To assess the ability of arthritic joint homogenates to induce angiogenesis, an endothelial chemotaxis assay and an in vivo matrigel plug assay were employed. The temporal expression profile of angiogenesis-related genes in arthritic paws was analysed by quantitative real-time RT-PCR using an angiogenesis focused array as well as gene specific PCR. Finally, we investigated the therapeutic effect of a monoclonal antibody specifically blocking the binding of VEGF to neuropilin (NRP)-1.

Results
Although arthritic paw homogenates displayed angiogenic activity in vitro and in vivo, and synovia of arthritic paws appeared highly vascularised on histological examination, the functional capillary density in arthritic knee synovia was significantly decreased, whereas capillary diameter was increased. Of the 84 genes analysed, 41 displayed a differential expression in arthritic paws as compared to control paws. Most significant alterations were seen at the peak of clinical arthritis. Increased mRNA expression could be observed for VEGF receptors (Flt-1, Flk-1, Nrp-1, Nrp-2), as well as for midkine, hepatocyte growth factor, insulin-like growth factor-1 and angiopoietin-1. Signalling through NRP-1 accounted in part for the chemotactic activity for endothelial cells observed in arthritic paw homogenates. Importantly, therapeutic administration of anti-NRP1B antibody significantly reduced disease severity and progression in CIA mice.

Conclusions
Our findings confirm that the arthritic synovium in murine CIA is a site of active angiogenesis, but an altered balance in the expression of angiogenic factors seems to favour the formation of non-functional and dilated capillaries. Furthermore, our results validate NRP-1 as a key player in the pathogenesis of CIA, and support the VEGF/VEGF receptor pathway as a potential therapeutic target in RA.
Robust Portfolio Choice with Learning in the Framework of Regret: Single-Period Case
Authors: Lim Andrew E. B. , Shanthikumar J. George , Vahn Gah-Yi 
Published: July 2012

In this paper, we formulate a single-period portfolio choice problem with parameter uncertainty in the framework of relative regret. Relative regret evaluates a portfolio by comparing its return to a family of benchmarks, where the benchmarks are the wealths of fictitious investors who invest optimally given knowledge of the model parameters, and is a natural objective when there is concern about parameter uncertainty or model ambiguity. The optimal relative regret portfolio is the one that performs well in relation to all the benchmarks over the family of possible parameter values. We analyze this problem using convex duality and show that it is equivalent to a Bayesian problem, where the Lagrange multipliers play the role of the prior distribution, and the learning model involves Bayesian updating of these Lagrange multipliers/prior. This Bayesian problem is unusual in that the prior distribution is endogenously chosen by solving the dual optimization problem for the Lagrange multipliers, and the objective function involves the family of benchmarks from the relative regret problem. These results show that regret is a natural means by which robust decision making and learning can be combined. This paper was accepted by Dimitris Bertsimas, optimization.
When Does It Pay to Delay Supplier Qualification? Theory and Experiments
Authors: Wan Zhixi , Beil Damian R. , Katok Elena 
Published: July 2012

We study a procurement setting in which the buyer seeks a low price but will not allocate the contract to a supplier who has not passed qualification screening. Qualification screening is costly for the buyer, involving product tests, site visits, and interviews. In addition to a qualified incumbent supplier, the buyer has an entrant of unknown qualification. The buyer wishes to run a price-only, open-descending reverse auction between the incumbent and the entrant, and faces a strategic choice about whether to perform qualification screening on the entrant before or after the auction. We analytically study the buyer's optimal strategy, accounting for the fact that under postauction qualification, the incumbent knows he could lose the auction but still win the contract. In our analysis, we derive the incumbent's optimal bidding strategy under postauction qualification and find that he follows a threshold structure in which high-cost incumbents hold back on bidding—or even boycott the auction—to preserve their profit margin, and only lower-cost incumbents bid to win. These results are strikingly different from the usual open-descending auction analysis where all bidders are fully qualified and bidding to win is always a dominant strategy. We test our analytical results in the laboratory, with human subjects. We find that qualitatively our theoretical predictions hold up quite well, although incumbent suppliers bid somewhat more aggressively than the theory predicts, making buyers more inclined to use postauction qualification. This paper was accepted by Martin Lariviere, operations management.
Statistical Comparison of Analysis Results for Lead on Dust Wipe Samples by X-ray Fluorescence Analysis and Flame Atomic Absorption Spectrometry
Authors: Rogers John , Viet Susan , Roda Sandy , Fraser Alexa , Friedman Warren , Zhou Joey , Jacobs David 
Published: July 2012

Abstract
The traditional method of determining dust lead loading (mass per unit area) on surfaces is to send dust wipe samples to a laboratory for analysis, and typically it takes one or more days to obtain results. Field-portable techniques taking 10 to 15 min for dust wipe lead analysis have been developed but need to be further evaluated. Dust wipe samples (n = 878) collected from a nationally representative sample of child care centers were tested by means of x-ray fluorescence (XRF) analysis with two XRF analyzer instrument models and subsequently analyzed for lead using flame atomic absorption spectrometry (FAAS). Samples were collected from floors and interior window sills and included blank and spiked quality control samples. Weighted linear regression was used to model the relationship between XRF and FAAS measurements. The correlations between FAAS and XRF measurements exceeded 0.80 (p &lt; 0.0001). The highly significant statistical correlation suggests that the XRF method could be used to quantify dust lead loadings to determine compliance with dust lead hazard standards as defined by the U.S. Environmental Protection Agency. Small, but significant, differences in regression parameters were found between floor or sill and quality control sample types. The use of 95 % prediction intervals could allow for rapid screening of clearance samples in the field if method standards were developed. Additional work is needed in order for researchers to understand differences among XRF instruments and the conditions under which the use of XRF testing in the field could reduce the time or cost required in order to complete clearance testing.
Laboratory method for determining the air content of fresh concrete
Authors: McIntosh J. D. , Preston A. G. 
Published: July 2012

Summary: A method for determining the amount of air entrained in fresh concrete, based on the variation of air volume with pressure, is described and illustrated. It is intended for laboratory use, and from the point of view of convenience in making the test is particularly suitable for this purpose. One form of apparatus can be readily assembled from standard chemical equipment and other common materials. The reproducibility and accuracy of results appear to be good.
Continuous reinforcement in concrete pavement
Authors: Cashell Harry D. , Benham Sanford W. 
Published: July 2012

Summary: Concrete pavements, unless constructed with closely spaced transverse joints, generally crack transversely at frequent intervals. These cracks tend to open appreciably with time unless the pavement is reinforced. For some years there has been a continued interest on the part of highway engineers regarding the practicability of concrete pavements constructed without transverse joints and reinforced longitudinally with continuous bonded steel in sufficient amount to hold all cracks closed. In the autumn of 1938 a considerable number of continuously reinforced sections, ranging from 20 to 1,310 ft in length, were constructed near Stilesville, Indiana, on US 40 as a co-operative research project to study the effects of varying amounts of longitudinal steel in sections of various lengths. The behaviour of the sections during the first ten years of service life shows conclusively that continuous reinforcement can be depended upon to prevent the opening of transverse cracks in concrete pavements. In the long, heavily reinforced sections many fine cracks have developed in the central region. These cracks have not opened and have ravelled only slightly with traffic and exposure, a condition that has required no maintenance and may be considered superficial. The sections have remained strong, durable structural units. The presence of even the heaviest longitudinal bar reinforcement has apparently not affected adversely the condition of the concrete in the pavement. The concrete appears to be sound throughout, there has been no spalling, and there is a complete absence of longitudinal cracking above the bars. Infact, the manner in which the steel has held closed all cracks, especially those in the more heavily reinforced sections, is believed to have been conducive to distributed interfacial pressure at the cracks which should tend to minimize damage to the concrete from concentrations of presswe such as sometimes develop at cracks in plain concrete pavements. Pumping has developed at many of the transverse joints, but, wth two exceptions, has not been observed at any of the vast number of transverse cracks. This indicates that a concrete pavement without transverse joints and containing adequate longitudinal reinforcement is not nearly so susceptible to pumping as pavements of other designs. In spite of the many transverse cracks that have developed in the long sections, the riding quality of the pavement has remained excellent and the pavement itself has been protected from damaging impact forces such as tend to develop where the surface alinement is not maintained.
The use of unstressed wires in pre-tensioned concrete members
Authors: Lazarides T. O. 
Published: July 2012

Summary: In the serial fabrication of pre-tensioned concrete members the odd lengths of wire left over are often considered as waste. At the very slight cost of straightening them, these odd lengths of wire could be put to very efficient use. Used as a tensile reinforcement, unstressed wires make it possible to reduce or prevent the formation of cracks and so to increase the ultimate safety factor or to reduce the section or the prestress of a member designed for a given load and span. Used as a shear reinforcement in I-shaped members, unstressed wires are very efficacious in preventing failure by differential shear and so make possible the use of a thinner web; quite short lengths of wire may be used in this fashion.
The deformation of concrete
Authors: Freyssinet E. 
Published: July 2012

Summary: Attention is drawn to our lack of knowledge of the laws of the deformation of concrete, and examples are given of slabs prestressed in two directions which have carried loads four or five times greater than those predicted by classical computation, without cracks being formed. To explain these and similar cases, the author develops his theory of the constitution of concrete; that it is a complex “solid-liquid” to which the laws of thermodynamics may be applied. This enables general laws to be formulated which explain known experimental results and allow new ones to be predicted. In this way shrinkage, creep, and—in general terms—everything concerning the elastic, plastic, instantaneous and time-dependent deformation of concrete is explained, as well as the well known autogenous healing property of cracked concrete. The paper ends with a discussion of the deformation of concrete in shear.
The compaction of concrete slabs by surface vibration: first series of experiments
Authors: Kirkham R. H. H. , Whiffin A. C. 
Published: July 2012

Summary: An experimental vibrator, operating on the top surface, has been used to compact freshly placed concrete (mix 1:2½:5; water-cement ratio 0·60) of low to very low workability. A study has been made of the effects on the compaction of slabs 18 in. thick of varying the frequency of vibration within the range 1,500-6,000 v.p.m., the acceleration within the range up to 12g, the amplitude within the range 0·004 to 0·064 in., and forward speeds of travel within the range 1-8ft per min. The density of the concrete was measured after test, while measurements were made during the experiments of the vibration occurring at various depths in the concrete. A small variation in the workability of the concrete was found to have a considerable efIect on the surcharge required and the depth of compaction achieved. Consequently the effect of the method of compaction has only been studied so far for concrete of one workability, only those tests where the compacting factor was within a narrow range around 0·80 being considered. When the vibrator operated at constant acceleration and constant number of vibrations per foot of travel, increase of amplitude of the beam increased the depth of compaction. At constant acceleration and amplitude of the beam, slower speeds of travel gave increased depth of compaction. When both the amplitude of the beam and number of vibrations per foot run were constant, the depth of compaction was unaffected by change of acceleration. The total work done on a particle at a given depth was found to be related to the density attained at that depth. A connexion has been found between equivalent depth of compaction and the product of the amplitude of the beam and the number of vibrations per foot run. The depth of compaction increases with this factor but attains a limiting value, probably dependent on the concrete mix and the characteristics of the vibrator. It seems desirable, with vibrators designed to operate at constant acceleration, to operate them with a large amplitude and low frequency.
Tests on concrete beams reinforced with 12 gauge wires of an ultimate strength of 120 tons per sq.in.
Authors: Hajnal-Kónyi K. 
Published: July 2012

Summary: Two beams of 8 × 18 in. cross-section, 12 ft long, reinforced with twenty-eight 12 gauge wires of an ultimate strength of 120 tons per sq.in. were rested to failure on a span of 11 ft. The concrete cube strength was 3,990 and 5,400 lb per sq.in. respectively. In both cases failure occurred by fracture of the reinforcement although the wires were not prestressed. Strain measurements taken at various stages of loading show a linear distribution. The actual steel stress at failure was much higher than the stress obtained from the stress-strain diagram of the steel on the basis of the average strain measured at 97 per cent of the maximum load.