gebhart/patrepeval huggingface dataset:
Efflux of Chloroquine from Plasmodium falciparum : Mechanism of Chloroquine Resistance (1987)

Chloroquine-resistant Plasmodium falciparum accumulate significantly less chloroquine than susceptible parasites, and this is thought to be the basis of their resistance. However, the reason for the lower accumulation of chloroquine was unknown. The resistant parasite has now been found to release chloroquine 40 to 50 times more rapidly than the susceptible parasite, although their initial rates of chloroquine accumulation are the same. Verapamil and two other calcium channel blockers, as well as vinblastine and daunomycin, each slowed the release and increased the accumulation of chloroquine by resistant (but not susceptible) Plasmodium falciparum. These results suggest that a higher rate of chloroquine release explains the lower chloroquine accumulation, and thus the resistance observed in resistant Plasmodium falciparum.
Molecular Recognition on Functionalized Self-Assembled Monolayers of Alkanethiols on Gold (1998)

A system for probing molecular recognition events at organic interfaces using fluorescent receptors is described. Receptors formed from the bis(2,6-diaminopyridine) amide of isophthalic acid are incorporated in mixed self-assembled monolayers (SAMs) of alkanethiols on gold and shown to interact with barbituric acid derivatives from solution. Individual parameters that affect the ability of receptors on surfaces to recognize ligands from solution along with varieties of solvents for ligand solutions have been examined.
&#946;-Sheet Breakers for Alzheimers Disease Therapy (2004)

A growing wealth of evidence indicates that the key pathological event in Alzheimers disease is the conversion of the normal soluble amyloid-β peptide into β-sheet-rich oligomeric structures which have a neurotoxic activity and ability to form insoluble amyloid deposits that accumulate in the brain. b-sheet breakers constitute a new class of drugs that are designed to specifically bind amyloid-β peptide and block and / or reverse this abnormal conformational change. In this article we review this approach, describe diverse compounds reported to have this activity and summarize the data supporting the view that b-sheet breakers could be serious candidates to combat this devastating disease.
Cloning, sequence, and photoregulation of al-1, a carotenoid biosynthetic gene of Neurospora crassa. (1990)

Carotenoid biosynthesis is regulated by blue light during growth of Neurospora crassa mycelia. We have cloned the al-1 gene of N. crassa encoding the carotenoid-biosynthetic enzyme phytoene dehydrogenase and present an analysis of its structure and regulation. The gene encodes a 595-residue polypeptide that shows homology to two procaryotic carotenoid dehydrogenases. RNA measurements showed that the level of al-1 mRNA increased over 70-fold in photoinduced mycelia. Transcription run-on studies indicated that the al-1 gene was regulated at the level of initiation of transcription in response to photoinduction. The photoinduced increase of al-1 mRNA levels was not observed in two Neurospora mutants defective in all physiological photoresponses. Analysis of cosmid containing al-1 and of a translocation strain with a breakpoint within al-1 indicated that al-1 transcription proceeds towards the centromere of linkage group I of N. crassa.
Cheek to Chip: Dancing Robots and AI's Future (2008)

Recent generations of humanoid robots increasingly resemble humans in shape and articulatory capacities. This progress has motivated researchers to design dancing robots that can mimic the complexity and style of human choreographic dancing. Such complicated actions are usually programmed manually and ad hoc. However, this approach is both tedious and inflexible. Researchers at the University of Tokyo have developed the learning-from-observation (LFO) training method to overcome this difficulty.1-2 LFO enables a robot to acquire knowledge of what to do and how to do it from observing human demonstrations. Direct mapping from human joint angles to robot joint angles doesn't work well because of the dynamic and kinematic differences between the observed person and the robot (for example, weight, balance, and arm and leg lengths). LFO therefore relies on predesigned task models, which represent only the actions (and features thereof) that are essential to mimicry. Then it adapts these actions to the robot's morphology and dynamics so that it can mimic the movement. This indirect, two-step mapping is crucial for robust imitation and performance.
Scanning electrochemical microscopy. 15. Improvements in imaging via tip-position modulation and lock-in detection (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTScanning electrochemical microscopy. 15. Improvements in imaging via tip-position modulation and lock-in detectionDavid O. Wipf and Allen J. BardCite this: Anal. Chem. 1992, 64, 13, 1362–1367Publication Date (Print):July 1, 1992Publication History Published online1 May 2002Published inissue 1 July 1992https://pubs.acs.org/doi/10.1021/ac00037a011https://doi.org/10.1021/ac00037a011research-articleACS PublicationsRequest reuse permissionsArticle Views364Altmetric-Citations78LEARN 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
Fabrication of DNA Microarrays Using Unmodified Oligonucleotide Probes (2001)

Microarrays printed on glass slides are often constructed by covalently linking oligonucleotide probes to a derivatized surface. These procedures typically require relatively expensive amine- or thiol-modified oligonucleotide probes that add considerable expense to larger arrays. We describe a system by which unmodified oligonucleotide probes are bound to either nonderivatized or epoxy-silane-derivatized glass slides. Biotinylated PCR products are heat denatured, hybridized to the arrays, and detected using an enzymatic amplification system. Unmodified probes appear to detach from the slide surface at high pH (> 10.0), suggesting that hydrogen bonding plays a significant role in probe attachment. Regardless of surface preparation, high temperature (up to 65 degrees C) and low ionic strength (deionized water) do not disturb probe attachment; hence, the fabrication method described here is suitable for a wide range of hybridization stringencies and conditions. We illustrate kinetics of room temperature hybridizations for probes attached to nonderivatized slides, and we demonstrate that unmodified probes produce hybridization signals equal to amine-modified, covalently bound probes. Our method provides a cost-effective alternative to conventional attachment strategies that is particularly suitable for genotyping PCR products with nucleic acid microarrays.
Cognitive dysfunction and prefrontal synaptic abnormalities in a mouse model of fragile X syndrome (2011)

Among the hallmark phenotypes reported in individuals with fragile X syndrome (FXS) are deficits in attentional function, inhibitory control, and cognitive flexibility, a set of cognitive skills thought to be associated with the prefrontal cortex (PFC). However, despite substantial clinical research into these core deficits, the PFC has received surprisingly little attention in preclinical research, particularly in animal models of FXS. In this study, we sought to investigate the molecular, cellular, and behavioral consequences of the loss of the fragile X mental retardation protein in the PFC of Fmr1 KO mice, a mouse model of FXS. We identify a robust cognitive impairment in these mice that may be related to the deficits in cognitive flexibility observed in individuals with FXS. In addition, we report that levels of proteins involved in synaptic function, including the NMDA receptor subunits NR1, NR2A, and NR2B; the scaffolding proteins PSD-95 and SAPAP3; and the plasticity-related gene Arc, are decreased in the prefrontal cortex of Fmr1 KO mice and are partly correlated with behavioral performance. Finally, we report that expression of c-Fos, a marker of neuronal activity, is decreased in the PFC of Fmr1 KO mice. Together, these data suggest that Fmr1 KO mice may represent a valuable animal model for the PFC-associated molecular, cellular, and behavioral abnormalities in FXS and that this model may be useful for testing the efficacy of therapeutic strategies aimed at treating the cognitive impairments in FXS.
Log-structured file systems (2003)

A discussion is presented of several techniques for improving I/O performance, including caches, battery-backed-up caches, and cache logging. The authors then examine in particular detail an approach called log-structured file systems, where the file system's only representation on disk is in the form of an append-only log. Log-structured file systems potentially provide order-of-magnitude improvements in write performance. When log-structured file systems are combined with arrays of small disks (which provide high bandwidth) and large main-memory file caches (which satisfy most read accesses), the authors believe it will be possible to achieve 1000-fold improvements in I/O performance over current systems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Wet oxidation of AlAs grown by molecular beam epitaxy (1994)

A 1 μm thick n-type GaAs layer with Si doping density of 1×1017/cm3 and a 1000 Å thick undoped AlAs layer was subsequently grown by molecular beam epitaxy on the n+ GaAs substrate. To perform selective oxidation of the AlAs layer, the wafer was oxidized in N2 bubbled H2O vapor ambient at 370 °C, 400 °C, and 430 °C, each for 3 hours. It is found that the defect-free selective oxidation of AlAs is very critically dependent on oxidation temperature. Both GaAs and AlAs layers were oxidized at the oxidation temperature of 430 °C, and some defects were found by scanning electron microscopy (SEM) on the surface oxidized at 370 °C. Oxidation was, however, stopped at the AlAs/GaAs interface at the oxidation temperature of 400 °C, and no defects were found on the surface. By the slow ramp rate (5 mV/sec) high frequency (100 kHz) C-V measurement, the fixed charge density was estimated to be about 1×1011/cm2 for the metal-oxide-semiconductor (MOS) capacitor fabricated from the oxidized sample at 400 °C.
MicroRNAs Profiling in Murine Models of Acute and Chronic Asthma: A Relationship with mRNAs Targets (2011)

This study highlights that specific miRNAs are likely to be involved in asthma disease and could represent a valuable resource both for biological makers identification and for unveiling mechanisms underlying the pathogenesis of asthma.
Aberrant regulation and function of wild-type p53 in radioresistant melanoma cells. (2000)

Sporadic human tumors and the hereditary cancer predisposition syndrome Li-Fraumeni are frequently associated with mutations in the p53 tumor suppressor gene that compromise its ability to function as a DNA damage checkpoint. A subset of Li-Fraumeni patients with wild-type p53 alleles have mutations in chk2/hcds1, one of the genes signaling the presence of DNA damage to the p53 protein. This suggests that p53 may be kept inactive in human cancer by mutations targeting DNA damage signaling pathways. Melanoma cells are highly radioresistant, yet they express wild-type p53 protein, raising the possibility of defects in the pathways that activate p53 in response to DNA damage. We have described a chk2/hcds1-independent DNA damage signaling pathway that targets Ser-376 within the COOH terminus of p53 for dephosphorylation and leads to increased p53 functional activity. We now report that in several human melanoma cell lines that express wild-type p53, the phosphorylation state of Ser-376 was not regulated by DNA damage. In these cell lines, neither the endogenous wild-type p53 protein nor high levels of ectopic wild-type p53 led to cell cycle arrest or apoptosis. Thus, defective activation of p53 in response to DNA damage may underlie the radioresistance of human melanoma cells.
A Novel Monoclonal Antibody to Fibroblast Growth Factor 2 Effectively Inhibits Growth of Hepatocellular Carcinoma Xenografts (2012)

Expression of fibroblast growth factor 2 (FGF2) is believed to be a contributing factor to the growth of a number of tumor types, including hepatocellular carcinoma (HCC). However, the potential of monoclonal antibodies that neutralize FGF2 for treatment of patients with cancer has not yet been explored in clinical trials. We therefore generated a novel monoclonal antibody (mAb), GAL-F2, specific for FGF2 and characterized its properties in vitro and in vivo. GAL-F2 binds to a different epitope than several previous anti-FGF2 mAbs tested. This novel epitope was defined using chimeric FGF1/FGF2 proteins and alanine scanning mutagenesis and was shown to comprise amino acids in both the amino and carboxy regions of FGF2. GAL-F2 blocked binding of FGF2 to each of its four cellular receptors, strongly inhibited FGF2-induced proliferation and downstream signaling in human umbilical vein endothelial cells, and inhibited proliferation and downstream signaling in two HCC cell lines. Moreover, GAL-F2, administered at 5 mg/kg i.p. twice weekly, potently inhibited growth of xenografts of the SMMC-7721, HEP-G2, and SK-HEP-1 human HCC cell lines in nude mice, and in some models, had a strong additive effect with an anti-VEGF mAb or sorafenib. Treatment with GAL-F2 also blocked angiogenesis and inhibited downstream cellular signaling in xenografts, indicating its antitumor mechanism of action. Our report supports clinical testing of a humanized form of the GAL-F2 mAb for treatment of HCC and potentially other cancers.
Orthogonal GARCH and covariance matrix forecasting: The Nordic stock markets during the Asian financial crisis 1997–1998 (2004)

In risk management, modelling large numbers of assets and their variances and covariances in a unified framework is often important. In such multivariate frameworks, it is difficult to incorporate GARCH models and thus a new member of the ARCH-family, Orthogonal GARCH, has been suggested as a remedy to inherent estimation problems in multivariate ARCH modelling. Orthogonal GARCH creates positive definite covariance matrices of any size but builds on assumptions that partly break down during stress scenarios. This article therefore assesses the stress performance of the model by looking at four Nordic stock indices and covariance matrix forecasts during the highly volatile years of 1997 and 1998. Overall, Orthogonal GARCH is found to perform significantly better than traditional historical variance and moving average methods. Out-of-sample evaluation measures include symmetric loss functions (RMSE), asymmetric loss functions, operational methods suggested by the Basle Committee on Banking Supervision, as well as a forecast evaluation methodology based on pricing of simulated 'rainbow options'.
IFN-γ Shapes Immune Invasion of the Central Nervous System Via Regulation of Chemokines (2000)

Dynamic interplay between cytokines and chemokines directs trafficking of leukocyte subpopulations to tissues in autoimmune inflammation. We have examined the role of IFN-gamma in directing chemokine production and leukocyte infiltration to the CNS in experimental autoimmune encephalomyelitis (EAE). BALB/c and C57BL/6 mice are resistant to induction of EAE by immunization with myelin basic protein. However, IFN-gamma-deficient (BALB/c) and IFN-gammaR-deficient (C57BL/6) mice developed rapidly progressing lethal disease. Widespread demyelination and disseminated leukocytic infiltration of spinal cord were seen, unlike the focal perivascular infiltrates in SJL/J mice. Gr-1+ neutrophils predominated in CNS, and CD4+ T cells with an activated (CD69+, CD25+) phenotype and eosinophils were also present. RANTES and macrophage chemoattractant protein-1, normally up-regulated in EAE, were undetectable in IFN-gamma- and IFN-gammaR-deficient mice. Macrophage inflammatory protein-2 and T cell activation gene-3, both neutrophil-attracting chemokines, were strongly up-regulated. There was no induction of the Th2 cytokines, IL-4, IL-10, or IL-13. RNase protection assays and RT-PCR showed the prevalence of IL-2, IL-3, and IL-15, but no increase in IL-12p40 mRNA levels in IFN-gamma- or IFN-gammaR-deficient mice with EAE. Lymph node cells from IFN-gamma-deficient mice proliferated in response to myelin basic protein, whereas BALB/c lymph node cells did not. These findings show a regulatory role for IFN-gamma in EAE, acting on T cell proliferation and directing chemokine production, with profound implications for the onset and progression of disease.
Study on lignin coverage of masson pine fiber (2010)

In order to obtain the adhesion force of fiber in a paper sheet easily, the relationships between internal bonding strength (IBS) and surface lignin content of masson pine CTMP treated with peracetic acid (PAA) have been investigated with XPS technique, and the surface morphology of fibers was also imaged by AFM. The results showed that the extent of lignin covered on the fiber surface was two times as high as that of whole pulp lignin, and the IBS was inversely proportional to surface lignin. The relationship between IBS and lignin coverage was formulated based on the experimental data. The mutual adhesion forces, cellulose-to-cellulose and lignin-to-lignin, were calculated using these equations, and the results were 28.69 mN/m and 2.487mN/m, respectively.
Apparatus for Measuring the Dynamic Solids-Settling Rates in Drilling Fluids (2006)

Abstract Barite Sag is a reoccurring problem with many oil-based drilling fluids. Attempts to correlate sag tendencies to various rheological properties commonly used to benchmark drilling fluids have had limited success in prevention and anticipation of sag problems in the field. Herein is presented a new testing apparatus for dynamic and static settling rate (sag) measurements, which has been proven to provide a better understanding of the sag phenomena as well as provide a better means to characterize fluid performance. This apparatus greatly expands the precision of sag measurements over previous techniques and allows testing conditions similar to those experienced downhole. Good correlation has been found between settling rate measurements and performance of drilling fluids in the field.
Probing the role of packing specificity in protein design (1997)

By using a protein-design algorithm that quantitatively considers side-chain packing, the effect of specific steric constraints on protein design was assessed in the core of the streptococcal protein G beta1 domain. The strength of packing constraints used in the design was varied, resulting in core sequences that reflected differing amounts of packing specificity. The structural flexibility and stability of several of the designed proteins were experimentally determined and showed a trend from well-ordered to highly mobile structures as the degree of packing specificity in the design decreased. This trend both demonstrates that the inclusion of specific packing interactions is necessary for the design of native-like proteins and defines a useful range of packing specificity for the design algorithm. In addition, an analysis of the modeled protein structures suggested that penalizing for exposed hydrophobic surface area can improve design performance.
'Spiders in the Centre of Their Webs': The NSW Police and Bushranging in the 1860s (2006)

This article looks at police interaction with more than 300 men convicted of bushranging offences in the 1860s. Many bushrangers were the offspring of convicts, mostly young Roman Catholic rural labourers. Armed robbery was their definitive crime, but in a minority of cases they wounded, assaulted, attempted murder or murdered their victims. Bushranging was not necessarily flamboyant or daring. Very few held up whole towns or robbed wealthy landowners, staying to yarn, eat, drink and dance. Many hold-ups were expeditious affairs aimed at acquiring money and goods with minimal risk. Though the most infamous men sometimes flaunted their identity, most minor criminals wore disguises. Many committed armed robberies in or near their home districts and were not involved in wild pursuits through the bush. Most had short careers and were apprehended soon after their first hold-up.
Cyclin B1 is useful to predict occult cervical lymph node metastases in tongue carcinoma. (2006)

Cyclin B1 plays an important role in regulating the G2-M transition of the cell cycle. In this study, we evaluated the immunohistochemical expression of cyclin B1 in a series of 40 oral tongue squamous cell carcinomas and analyzed the findings in relation to both clinicopathological variables and the Ki-67 labeling index. In normal squamous epithelium, cyclin B1 was localized in the nucleus and was expressed only in several cells of the basal and parabasal layers. By contrast, in dysplastic epithelium, cyclin B1 was localized in the cytoplasm and nuclei, and the numbers of cyclin B1 positive cells increased compared with normal epithelium. In tumor tissues, cyclin B1 expression was observed mainly in the cytoplasm, and the cyclin B1 labeling index ranged from 2 to 21%, with a mean of 11%. Cyclin B1 overexpression was positively correlated with occult cervical lymph node metastases and the number of mitotic cells. In addition, there was a positive relationship between labeling indices of cyclin B1 and Ki-67. These findings indicate that cyclin B1 could be a useful prognostic marker of occult cervical lymph node metastases in tongue carcinoma.
ChemInform Abstract: Practical Computational Approaches to Molecular Properties (1998)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Central receptors mediating the cardiovascular actions of melanocyte stimulating hormones (2006)

Both MSH peptides exert their hypertensinogenic effects through central sites of action, which probably reflect the activation of sympathetic outflow. The actions of intracerebroventricular alpha-MSH appear to be mediated via Mc4r, whereas those of gamma-MSH are independent of its receptor Mc3r, but reflect the activation of a sodium channel in the central nervous system. These results help to reconcile the hypertensive action of gamma-MSH injections with the hypertension observed in states of gamma-MSH deficiency.