nils-herrmann/clean_scirepeval huggingface dataset:
Importance of integrating nanotechnology with pharmacology and physiology for innovative drug delivery and therapy – an illustration with firsthand examples

Nanotechnology has been applied extensively in drug delivery to improve the therapeutic outcomes of various diseases. Tremendous efforts have been focused on the development of novel nanoparticles and delineation of the physicochemical properties of nanoparticles in relation to their biological fate and functions. However, in the design and evaluation of these nanotechnology-based drug delivery systems, the pharmacology of delivered drugs and the (patho-)physiology of the host have received less attention. In this review, we discuss important pharmacological mechanisms, physiological characteristics, and pathological factors that have been integrated into the design of nanotechnology-enabled drug delivery systems and therapies. Firsthand examples are presented to illustrate the principles and advantages of such integrative design strategies for cancer treatment by exploiting 1) intracellular synergistic interactions of drug-drug and drug-nanomaterial combinations to overcome multidrug-resistant cancer, 2) the blood flow direction of the circulatory system to maximize drug delivery to the tumor neovasculature and cells overexpressing integrin receptors for lung metastases, 3) endogenous lipoproteins to decorate nanocarriers and transport them across the blood-brain barrier for brain metastases, and 4) distinct pathological factors in the tumor microenvironment to develop pH- and oxidative stress-responsive hybrid manganese dioxide nanoparticles for enhanced radiotherapy. Regarding the application in diabetes management, a nanotechnology-enabled closed-loop insulin delivery system was devised to provide dynamic insulin release at a physiologically relevant time scale and glucose levels. These examples, together with other research results, suggest that utilization of the interplay of pharmacology, (patho-)physiology and nanotechnology is a facile approach to develop innovative drug delivery systems and therapies with high efficiency and translational potential.

Field of study: Biology, Chemistry, Medicine
Extraction and Determination of Boron Isotopic Composition in Tourmalines

Tourmaline is an abundant boron-rich alumosilicate mineral with complex chemistry and rich in Fe, Mg, Al, Si elements. In this study, tourmaline samples were decomposed by alkali fusion method, and then the boron was separated and purified using three different procedures. It was found that both Fe3+ and Al3+ ions, rich in tourmaline samples seriously, which affected the accurate determination of boron concentration by Azomethine-H spectrophotometric method and also caused a loss of boron by specific adsorption when large amount of amorphous hydroxide precipitate formed in ion-exchange columns. The addition of small amount of EDTA can eliminate the influence, but brings serious isobaric interference on boron isotopic analysis by TIMS. Finally, a three-column ion-exchange procedure was established including the first mixed resin column, the peristaltic pump coupled boron specific resin column, and the second mixed resin column, which ensures the full recovery of boron (> 99%) from tourmaline samples with complex matrices. The PTIMS-Cs2BO2+-static double-collection method was established by selecting H3-H4 Faraday cups and optimizing parameters in Zoom Optics (Focus Quad: 15; Dispersion Quad: −85) in a Triton TI mass spectrometer. The determined average 11B/10B value of NIST SRM 951 standard boron solution was 4.05044±0.00012 (2σ, n = 8, 1 μg B), which was superior to the dynamic collection method in internal/external precision. A δ11B value of −0.3% for NIST SRM 951 through the same pretreatment procedure was obtained, indicating that there was no isotopic fractionation occurred during the extraction procedure. The comparison of boron isotopic compositions in natural samples by TIMS and MC-ICP-MS after the chemistry procedure indicated that δ11B values determined by the static PTIMS-Cs2BO2+ method were in good agreement with that by MC-ICP-MS.

Field of study: Chemistry
Matching Job Previews to Individual Applicants' Needs

An organizational recruitment simulation was conducted to examine the extent to which applicants' initial impressions of the organization are a function of the extent to which their highly valued needs are addressed and the realism of the portrayal in a job preview. Tailoring the content of job previews to the individual's needs raised applicants' expectations about most work factors in the organization. However, realism in the job preview lowered expectations about the organization as well as anticipated job offer acceptance rates and commitment to the organization.

Field of study: Psychology
Why scepticism about self‐knowledge is self‐undermining

In Ebbs 1996 and 2001 I explained why I believe that a certain sort of argument that seems to support scepticism about self-knowledge is actually incoherent, or self-undermining. Anthony Brueckner has recently tried to show that even if the central premisses of my explanation are true, the sceptical argument in question is not self-undermining. He has also suggested that even if the sceptical argument is self-undermining, it can still serve as a reductio ad absurdum of the assumption that we have selfknowledge. My goal here is to explain why I think neither of these responses is successful.

Field of study: Philosophy
Noninvasive intracranial compliance and pressure based on dynamic magnetic resonance imaging of blood flow and cerebrospinal fluid flow: review of principles, implementation, and other noninvasive approaches.

Current techniques for intracranial pressure (ICP) measurement are invasive. All require a surgical procedure for placement of a pressure probe in the central nervous system and, as such, are associated with risk and morbidity. These considerations have driven investigators to develop noninvasive techniques for pressure estimation. A recently developed magnetic resonance (MR) imaging-based method to measure intracranial compliance and pressure is described. In this method the small changes in intracranial volume and ICP that occur naturally with each cardiac cycle are considered. The pressure change during the cardiac cycle is derived from the cerebrospinal fluid (CSF) pressure gradient waveform calculated from the CSF velocities. The intracranial volume change is determined by the instantaneous differences between arterial blood inflow, venous blood outflow, and CSF volumetric flow rates into and out of the cranial vault. Elastance (the inverse of compliance) is derived from the ratio of the measured pressure and volume changes. A mean ICP value is then derived based on a linear relationship that exists between intracranial elastance and ICP. The method has been validated in baboons, flow phantoms, and computer simulations. To date studies in humans demonstrate good measurement reproducibility and reliability. Several other noninvasive approaches for ICP measurement, mostly nonimaging based, are also reviewed. Magnetic resonance imaging-based ICP measurement may prove valuable in the diagnosis and serial evaluation of patients with a variety of disorders associated with alterations in ICP.

Field of study: Medicine
Early Ordovician Chaotic Deposits in the Central Volcanic Belt of Northeastern Newfoundland

Boulder-bearing argillite that contains a varied assemblage of both native and exotic sedimentary and volcanic clasts crops out over a large area in southeastern Notre Dame Bay, Newfoundland. It occupies a consistent stratigraphic position throughout this area and is the oldest unit exposed in sequence; it lies beneath Caradocian graptolite-bearing slates. Middle Cambrian trilobites occur in limestone associated with lenticular masses of volcanic rocks that may be allochthonous. The entire unit is thousands of meters thick and is believed to be primarily a sedimentary deposit that has been secondarily remobilized into a chaotic melange. Larger fragments within the argillite consist of graywacke boulders and blocks of lava as much as hundreds of meters long; they float suspended in a matrix of pebbly mudstone. Smaller clasts range from granules of quartz and lithic fragments to cobbles of intrusive and extrusive rocks. The matrix is black, scaly, and pyritiferous with contorted green silty interbeds, commonly all homogenized into a chaotic paste devoid of primary structure. Various lines of evidence suggest polygenetic origin of chaos. Stratigraphic continuity, sedimentary origins of clasts, soft sediment deformation, and brittle rock deformation are all documented as having been important. Structural, stratigraphic, and sedimentological relations are like those in the argille scagliose of the Apennines and suggest similar environments and mechanisms. This chaotic melange records Early Ordovician tectonic movements at the northern extremity of the Appalachian belt. These movements may have heralded the onset of the Taconian Orogeny. Coeval movements in western Ireland were of an almost identical nature.

Field of study: Geology
The Influence of Inter-Cooling and Electromagnetic Stirring above Liquidus on the Formation of Primary Al3Zr and Grain Refinement in an Al-0.2%Zr Alloy

The nucleation and grain growth that occur during solidification have been extensively examined, but insight into the influence of an external field on the formation of heterogeneous crystal nuclei above the liquidus remains unclear in the peritectic refinement mechanism. In this work, we studied the effect of cooling rate above the liquidus on the formation of primary Al3Zr and grain refinement in Al-0.2%Zr alloys with inter-cooling annular electromagnetic stirring (IC-AEMS). The results show that the size and distribution of primary Al3Zr are greatly improved, and the morphology transformed from large plate/blocky shapes without IC-AEMS to small blocks with IC-AEMS. Meanwhile, above the liquidus, the addition of an Al-Zr master alloy to pure Al alone did little to enhance the refinement, but after IC-AEMS, the grains were refined dramatically. The refinement result seems to be explained by two hypotheses of pre-nucleation and explosive nucleation.

Field of study: Materials science
Modeling the paleo-seawater radiogenic strontium isotope record: A case study of the Late Jurassic-Early Cretaceous

While uniformitarianism underlies many aspects of the Earth sciences, modeling geochemical cycles throughout Earth history requires critically assessing the reliability and constancy of projecting modern fluxes and their isotope ratios into deep geologic time. In this study, we develop an iterative technique for modeling the radiogenic strontium isotope composition (R87 = 87Sr/86Sr) of seawater (sw) during the Phanerozoic utilizing as a constraint the composite record of McArthur et al. (2012) (McArthur, J. M., Howarth, R. J., & Shields, G. A. (2012). Strontium isotope stratigraphy. In F. M. Gradstein, J. G. Ogg, M. Schmitz, & G. Ogg (Eds.), The Geologic Time Scale 2012 (. The model yields estimates for the Sr isotope composition of the riverine, submarine groundwater discharge, and diagenetic input fluxes. We use the Late Jurassic-Early Cretaceous segment of the marine Sr isotope record as a case study to demonstrate the efficacy of the new method. To begin, 87Sr/86Sr ratios are calculated for a combined riverine and submarine groundwater discharge flux (tw = total weathering) using a prescribed time-variable d dt R 87 , sw determined from the LOWESS FIT 5 of McArthur et al. (2012). The calculated R87,tw values are checked against the range of R87,sw for the time interval of interest, as well as older carbonates available for weathering, to determine the reasonableness of the estimates. From these estimates, different prescribed R87,tw values are tested to identify the best match with target seawater 87Sr/86Sr ratios and the range of d dt R 87 , sw . For model runs focusing on long time intervals (≳ 10 Myr), a single prescribed R87,tw value does not produce a reasonable match to the Sr isotope record. Testing the frequency of variation in R87,tw indicates that during the Early Cretaceous, R87,tw varied at least every 5 Myr, if not more frequently. The minimum frequency at which R87,tw changes likely varied throughout the Phanerozoic, as it depends on the variability of d dt R 87 , sw and residence time of Sr. Model results also demonstrate the significance of estimating variation in the total hydrothermal (high and low temperature) input flux of Sr along with seawater Sr concentrations in the geologic past, which are key for properly estimating R87,tw.

Field of study: Environmental science, Geography
Regulation of phosphatidylcholine and phosphatidylethanolamine synthesis in rat hepatocytes by 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR).

The present study was undertaken to study the role of AMP-activated kinase (AMPK) in the biosynthesis of two major membrane phospholipids, phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Incubation of rat hepatocytes with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), an activator of AMPK, produced dose-dependent inhibition of the incorporation of [(3)H]choline and [(3)H]ethanolamine into PC and PE, respectively. Determination of the cellular uptake of choline and ethanolamine showed that the reduced synthesis of PC and PE did not result from impaired uptake of these two precursors. The decreased synthesis of PC was not mirrored by a reduction in the activities of the enzymes of the CDP-choline pathway. The diminution of PE biosynthesis, however, was paralleled by a depressed activity of CTP:phosphoethanolamine cytidylyltransferase (ET), the pace-setting enzyme of the CDP-ethanolamine pathway. AICAR treatment of hepatocytes stimulated the conversion of choline into betaine, indicating that reduced PC synthesis most probably resulted from a decrease in the availability of choline. In addition, AICAR induced a 50% reduction in the cellular level of diacylglycerols, which may further impair the synthesis of PC and PE. The results thus indicate that AICAR inhibits the biosynthesis of PC and PE and that the effect is exerted at different sites in the two pathways. Increased oxidation of choline to betaine is the main target of AICAR in the PC pathway, whereas inhibition of ET activity is the locus of AICAR action in the PE pathway.

Field of study: Biology, Computer science
Effects of atmospheric pollution on lichen biodiversity (LB) in a Mediterranean region (Liguria, northwest Italy).

The effects of air pollution on lichen biodiversity (LB) were monitored in Liguria (northwest Italy). A systematic sampling strategy was adopted in order to avoid the influence of spatial autocorrelation on the results. An eight LB class scale permitted to point out the levels of naturality/alteration in the region. The comparison of these results with the ones obtained by mean of physico-chemical methodologies shows a good accordance. The results of this study suggest the possibility of designing an integrated monitoring network, in which biological monitoring will allow to estimate the level of alteration in remote areas, which account for most of this region and which are currently not covered by measurements with automatic systems.

Field of study: Environmental science
Delayed and current stimulus control in successive discriminations.

In a successive discrimination in which successively alternating red and green hues signaled component variable-interval schedules, sensitivity of the ratio of responses in the two components to variation in the component reinforcer ratio decreased systematically during the course of the component. This decrease in stimulus control or discrimination over the course of the component was shown to be the result of delayed control of responding during the component by the stimulus transition between components. When the red-green stimulus transition was altered by interpolating a white stimulus at the end of each 60-s component, discrimination at the beginning of the component (measured by the power-function exponent for sensitivity to reinforcement) was reduced. Conditions with the white stimulus inserted in other quarters of the component indicated that the current discriminative stimulus exerts control over responding throughout the component, whereas during about the first half of the component, response differentials are influenced by the transition between discriminative stimuli.

Field of study: Biology, Psychology
Surviving the Future: Mexican Health Policies and Deceitfulness of Universal Coverage in the State of Puebla, México

Two years ago, the Governor of the Mexican State of Puebla declared that his State was fully covered by health services, which is not true. According to the World Health Organization (WHO) and the Mexican Constitution, health is one of the most important human rights for every citizen. However, according to our statistics, many indigenous communities of that State are still waiting for those services, even though the budget designated for that purpose has been incremented ten times in the last seven years. Since I have been working for years in the highlands of the northern part of the State, I will prove that medical services are not covering the total population, which means that the future survival of these people is rather grim.

Field of study: Political science
Polydrug use in adolescent drinkers with and without DSM-IV alcohol abuse and dependence.

Alcohol and other substance use disorders are highly comorbid, but little is known about patterns of polydrug use in adolescents with different levels of alcohol involvement. This research examined patterns and correlates of polydrug use in 176 adolescent drinkers with DSM-IV alcohol dependence (n = 61), alcohol abuse (n = 57), and no alcohol diagnosis (n = 58). Alcohol and other Substance Use Disorders were assessed using a modified version of the Structured Clinical Interview for the DSM. Lifetime histories of alcohol use and other drug use were assessed using a structured interview. Subjects also completed a questionnaire measure of the frequency of use of specific alcohol-drug combinations. The total number of illicit drugs ever used was greater in the alcohol dependence (mean = 3.8, SD = 2.1) and abuse groups (mean = 3.0, SD = 2.1), compared with the no-alcohol diagnosis group (mean = 1.9, SD = 1.3). Consistent with previous findings, there was a consistent pattern in the age of onset of psychoactive substance use: alcohol, followed by marijuana, followed by other drugs. The recent use of alcohol and other drugs in combination was reported by a greater percentage of subjects in the alcohol dependence (69%) and abuse groups (72%), compared with drinkers without an alcohol diagnosis (45%). The most common alcohol-drug combination was alcohol with marijuana (58% of the total sample), followed by alcohol-hallucinogens (16%). The frequency and extent of polydrug use was associated with being older and having higher levels of behavioral undercontrol and negative emotionality. Adolescent polydrug use, particularly the use of alcohol and other drugs in combination, is an important area for research, treatment, and prevention.

Field of study: Medicine
Anti-fibrotic Effects via Regulation of Transcription Factor Sp1 on Hepatic Stellate Cells

Hepatic stellate cells (HSCs), the central cells in hepatic fibrosis, are characterized by sustaining activation, a process that consists in increased proliferation and over-expression of fibrotic genes. Transcription factor Sp1 mediates the expression of a variety of fibrotic genes expression and thereby play an important role in fibrosis. In addition, previous reports have indicated that Sp1 binding activity is greatly increased in activated HSCs. Thus, our aim was to investigate the anti-proliferative and anti-fibrotic effects of the oligonuceotide decoy of the transcription factor Sp1, ODN, a potent inhibitor of Sp1-activated transcription.  We optimized Lipofectamin 2000 (LF2000):ODN DNA ratio for the transfection of hepatic stellate cells HSC-T6. Then we measure the effect of transfected ODN on HSC-T6 cells′ proliferation and fibrotic gene expression, and study the mechanism involved.  At a DNA concentration of 1 µM and a ratio ODN DNA:LF2000 of 1:3, HSC-T6 cells have the maximal transfection efficiency with the lowest toxicity. Transfected ODN effectively blocks Sp1 binding to the promoter regions of cell cycle regulatory proteins cyclin D1, p27KIP1 and fibrotic genes, including transforming growth factor (TGF)-β1, Platelet-derived growth factor (PDGF)-BB, α-SMA, α1 (I) collagen and tissue inhibitor of metalloproteinases-1 (TIMP-1). ODN inhibits HSC-T6 proliferation and fibrotic genes expression in vitro.  Sp1 is a key transcription factor that mediates proliferation and fibrotic gene synthesis of HSC-T6, inhibition of Sp1 with decoy ODN may be an effective approach to prevent the progression of hepatic fibrosis.

Field of study: Biology, Chemistry
Very high energy γ rays from close active galactic nuclei Mkn 421, Mkn 501, and NGC 1275

The results of observations of two types of metagalactic sources, BLLacs Mkn 421 (z = 0.031) and Mkn 501 (z = 0.034) and the Seyfert galaxy NGC 1275 (z = 0.017) are reported. These observations have been carried out with the SHALON mirror telescope (Lebedev Institute of Physics, Russian Academy of Sciences). The γ-ray fluxes (with energies E > 0.8 TeV) from Mkn 421 and Mkn 501, averaged over the entire observation period, were estimated to be (0.63 ± 0.14) × 10−12 and (0.86 ± 0.13) × 10−12 cm−2 s−1, respectively. The flux from the source NGC 1275 was (0.78 ± 0.13) × 10−12 cm−2 s−1. The energy spectra of γ rays and images of the sources are reported.

Field of study: Physics
Defect evolution in a product line environment

One mechanism used for monitoring the development of the Space Shuttle flight control software, in order to minimize any risks to the missions, is the independent verification and validation (IV&V) process. Using data provided by both the Shuttle software developer and the IV&V contractor, in this paper we describe the overall IV&V process as used on the Space Shuttle program and provide an analysis of the use of metrics to document and control this process over multiple releases of this software. Our findings reaffirm the value of IV&V, show the impact of IV&V on multiple releases of a large complex software system, and indicate that some of the traditional measures of defect detection and repair are not applicable in a multiple-release environment such as this one.

Field of study: Computer science, Engineering
Study of High Chromium Cast Iron Roller

The production process for high-chromium cast iron roller was introduced.By choosing chemical composition of Cr20 material reasonably and developing casting process and heat treatment process via combining solidification characteristics of high-chromium cast iron,the targets which are the roller hardness 53 HRC in the cast state and 61 HRC after heat treatment can be achieved,making sure the roller non-destructive testing qualified as well,and the casting quality achieve the advanced level of domestic equivalent products.

Field of study: Materials science