gebhart/patrepeval huggingface dataset:
Lessons learned in the development of targeted therapy for malignant gliomas (2007)

The prognosis of patients with glioblastoma, anaplastic astrocytoma, and anaplastic oligodendroglioma remains poor despite standard treatment with radiotherapy and temozolomide. Molecular targeted therapy holds the promise of providing new, more effective treatment options with minimal toxicity. However, the development of targeted therapy for gliomas has been particularly challenging. The oncogenetic process in such tumors is driven by several signaling pathways that are differentially activated or silenced with both parallel and converging complex interactions. Therefore, it has been difficult to identify prevalent targets that act as key promoters of oncogenesis and that can be successfully addressed by novel agents. Several drugs have been tested, including epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (gefitinib and erlotinib), mammalian target of rapamycin (mTOR) inhibitors (temsirolimus and everolimus), and vascular endothelial growth factor receptor (VEGFR), protein kinase C-beta, and other angiogenesis pathways inhibitors (vatalanib, bevacizumab, and enzastaurin). Although preliminary efficacy results of most trials in recurrent disease have fallen short on expectations, substantial advances have been achieved by associated translational research. In this article, we seek to recapitulate the lessons learned in the development of targeted therapy for gliomas, including challenges and pitfalls in the interpretation of preclinical data, specific issues in glioma trial design, insights provided by translational research, changes in paradigms, and future perspectives.
Challenging the Cancer Molecular Stratification Dogma: Intratumoral Heterogeneity Undermines Consensus Molecular Subtypes and Potential Diagnostic Value in Colorectal Cancer (2016)

Gene expression profiles derived from the nonmalignant stromal region can influence assignment of colorectal cancer transcriptional subtypes, questioning the current molecular classification dogma and highlighting the need to consider pathology sampling region and degree of stromal infiltration when employing transcription-based classifiers to underpin clinical decision making in colorectal cancer. Clin Cancer Res; 22(16); 4095-104. ©2016 AACRSee related commentary by Morris and Kopetz, p. 3989.
Recovery and purification of polysaccharides from microbial broth. (1991)

Current industrial practice to recover extracellular microbial polysaccharides from the broth usually requires dilution to permit cell removal followed by precipitation, typically using alcohol. This paper presents a discussion on the solvent precipitation of xanthan and the results of research performed to investigate the behaviour of xanthan solutions during membrane processing using a microporous membrane. Using crossflow microfiltration, flux rates of up to 120 L/m2h were achieved for pure xanthan solutions, with complete rejection of the polysaccharide by the membrane. The thin film model underpredicted flux for xanthan solutions. In fact, flux was independent of xanthan concentration up to 20-25 g/L, and strongly dependent on crossflow velocity. Considerable benefits in terms of purification and reduced solvent requirements can be obtained by the use of an intermediate crossflow microfiltration step during xanthan recovery.
Molecular Characterization of the Drug Resistant Beijing/W-like Strain. (2005)

Please help us populate SUNScholar with the post print version of this article. It can be e-mailed to: scholar@sun.ac.za
Microlipoinjection for the Elevation of Depressed Full‐Thickness Skin Grafts on the Nose (1992)

Microlipoinjection can provide cosmetically useful soft tissue augmentation under depressed full-thickness skin grafts; this augmentation can persist.
A soft decision decoding scheme for wireless COFDM with application to DVB-T (2004)

This paper investigates the soft decision decoding techniques for wireless COFDM systems. A new method to estimate the channel state information (CSI) for the Viterbi decoder is proposed, which overcomes the problem of reliability metric of transmitted signals in wireless as well as mobile channels. The CSI for each subcarrier is calculated as a properly defined squared Euclidean distance. On the basis of which, a soft decision decoding scheme to improve reception performance under multipath fading interference and co-channel interference (CCI) from existing analog broadcasting signals is also proposed. The simulation results show that the scheme can provide a compatible improvement to the terrestrial digital video broadcasting (DVB-T) system. The proposed scheme is also suitable for other wireless COFDM transmission systems.
Multichannel Microchip Electrophoresis Device Fabricated in Polycarbonate with an Integrated Contact Conductivity Sensor Array (2007)

A 16-channel microfluidic chip with an integrated contact conductivity sensor array is presented. The microfluidic network consisted of 16 separation channels that were hot-embossed into polycarbonate (PC) using a high-precision micromilled metal master. All channels were 40 microm deep and 60 microm wide with an effective separation length of 40 mm. A gold (Au) sensor array was lithographically patterned onto a PC cover plate and assembled to the fluidic chip via thermal bonding in such a way that a pair of Au microelectrodes (60 microm wide with a 5 microm spacing) was incorporated into each of the 16 channels and served as independent contact conductivity detectors. The spacing between the corresponding fluidic reservoirs for each separation channel was set to 9 mm, which allowed for loading samples and buffers to all 40 reservoirs situated on the microchip in only five pipetting steps using an 8-channel pipettor. A printed circuit board (PCB) with platinum (Pt) wires was used to distribute the electrophoresis high-voltage to all reservoirs situated on the fluidic chip. Another PCB was used for collecting the conductivity signals from the patterned Au microelectrodes. The device performance was evaluated using microchip capillary zone electrophoresis (mu-CZE) of amino acid, peptide, and protein mixtures as well as oligonucleotides that were separated via microchip capillary electrochromatography (mu-CEC). The separations were performed with an electric field (E) of 90 V/cm and were completed in less than 4 min in all cases. The conductivity detection was carried out using a bipolar pulse voltage waveform with a pulse amplitude of +/-0.6 V and a frequency of 6.0 kHz. The conductivity sensor array concentration limit of detection (SNR = 3) was determined to be 7.1 microM for alanine. The separation efficiency was found to be 6.4 x 10(4), 2.0 x 10(3), 4.8 x 10(3), and 3.4 x 10(2) plates for the mu-CEC of the oligonucleotides and mu-CZE of the amino acids, peptides, and proteins, respectively, with an average channel-to-channel migration time reproducibility of 2.8%. The average resolution obtained for mu-CEC of the oligonucleotides and mu-CZE of the amino acids, peptides, and proteins was 4.6, 1.0, 0.9, and 1.0, respectively. To the best of our knowledge, this report is the first to describe a multichannel microchip electrophoresis device with integrated contact conductivity sensor array.
Antistasin, a Leech-derived Inhibitor of Factor Xa (1989)

Antistasin is a 119-amino acid protein isolated from the salivary glands of the Mexican leech Haementeria officinalis. The determination of the primary structure of antistasin revealed that the protein is highly disulfide-bonded with a 2-fold internal homology. Antistasin exhibits a potent anticoagulant activity purportedly due to the selective inhibition of Factor Xa (Tuszinsky, G. P., Gasic, T. B., and Gasic, G. J. (1987) J. Biol. chem. 262, 9718-9723). In the present study a detailed kinetic analysis of the inhibitory interaction between antistasin and Factor Xa was performed. In addition, the specificity of antistasin was examined by testing its ability to inhibit a variety of serine proteinases. Utilizing purified antistasin and a tripetidyl p-nitroanilide substrate, antistasin was shown to act as a reversible inhibitor of Factor Xa which exhibits slow-tight binding kinetics. Antistasin reacts stoichiometrically with Factor Xa with inhibition displaying a mixed, primarily competitive type. The inhibition is partial in the presence of Ca2+ and becomes complete in the absence of Ca2+. The estimated dissociation constant for the enzyme-inhibitor complex is between 0.31 and 0.62 nM. After binding to Factor Xa, antistasin is cleaved at a single site to yield a modified inhibitor. Automated gas-phase sequence analysis of the modified inhibitor indicates the arginine residue at position 34 in antistasin occupies the P1 position of the reactive site. These data indicate that the leech has evolved a highly selective and potent inhibitor of coagulation Factor Xa that shares several mechanistic similarities with other serine proteinase inhibitors.
Topical isoflavonoids reduce experimental cutaneous inflammation in mice (2010)

The antioxidant and anti-proliferative biological effects of isoflavonoids are relevant properties to counteract the characteristics of many cutaneous diseases. This study uses ultraviolet (UV)B irradiation to induce inflammation in the mouse skin, as a model for some symptoms of cutaneous inflammatory and hyperproliferative diseases such as psoriasis in humans, with the objective of testing two topically applied isoflavonoid compounds for therapeutic properties. UVB exposure resulted in the overexpression of the cytokines, tumour necrosis factor (TNF)-α, interleukin (IL)-6 and the adhesion molecule P-cadherin. Infiltration into the dermal compartment of mast cell populations was also induced. These factors are also overexpressed in psoriatic skin. The effect of topical applications of two isoflavonoids, equol and a synthetic analogue NV-38, was tested. Both isoflavonoids dose dependently inhibited the UVB induction of cutaneous TNF-α mRNA and protein, a cytokine critical for the initiation of psoriatic inflammation. Expression of IL-6 mRNA and protein was also decreased, and the number of infiltrating mast cells into the dermis was reduced by both isoflavonoids. Furthermore, the upregulated mRNA and protein levels of P-cadherin, a marker characteristic of cutaneous hyperproliferation, were also normalized by both isoflavonoids. These results suggest that this class of compounds has the potential for useful, innocuous anti-inflammatory therapy from topical application in human cutaneous diseases.
Isolation of the oncogene and epidermal growth factor-induced transin gene: complex control in rat fibroblasts. (1986)

Various oncogenes or epidermal growth factor (EGF) induce transcription of a 1.9-kilobase RNA (transin RNA) in rat fibroblasts. The induction by EGF can be blocked by cycloheximide. Thus the response of the transin gene to EGF appears to require de novo protein synthesis. Transin RNA induction is specific to EGF, as neither insulin, platelet-derived growth factor, fibroblast growth factor, nor transforming growth factor beta could elicit the same response. However, transforming growth factor beta could block the EGF induction of transin RNA. Whereas the calcium ionophore A23187 and the tumor promoter TPA, either alone or administered together, did not increase transin RNA levels, TPA could synergise with a serum factor to effect such an increase. Dibutyryl cyclic AMP also induced transin RNA. Treatment of cells with the microfilament-disrupting agent cytochalasin B, but not the microtubule-disrupting agent colcemid, resulted in an increase in transin RNA levels, suggesting a role for the cytoskeleton in control of transin gene expression. The transin RNA does not contain repeated sequences and appears to be encoded by a single-copy gene. The protein sequence encoded by the last four exons of the transin gene shows some homology to two regions of the heme-binding protein hemopexin.
Partial biochemical characterization of cell surface hydrophobicity and hydrophilicity of Candida albicans (1990)

Hydrophobic yeast cells of Candida albicans are more virulent than hydrophilic yeast cells in mice. Results of experiments performed in vitro suggest that surface hydrophobicity contributes to virulence in multiple ways. Before definitive studies in vivo concerning the contribution of fungal surface hydrophobicity to pathogenesis can be performed, biochemical, physiological, and immunochemical characterization of the macromolecules responsible for surface hydrophobicity must be accomplished. This report describes our initial progress toward this goal. When hydrophobic and hydrophilic yeast cells of C. albicans were exposed to various enzymes, only proteases caused any change in surface hydrophobicity. Hydrophobic cell surfaces were sensitive to trypsin, chymotrypsin, pronase E, and pepsin. This indicates that surface hydrophobicity is due to protein. Papain, however, had no significant effect. The hydrophobicity of hydrophilic cells was altered only by papain. The proteins responsible for surface hydrophobicity could be removed by exposure to lyticase, a beta 1-3 glucanase, for 30 to 60 min. When 60-min lyticase digests of hydrophobic and hydrophilic cell walls were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with a 12.5% resolving gel, each protein population contained a single unique protein that was not evident in the other protein population. However, when the cell wall surface proteins of hydrophobic and hydrophilic cells were first labeled with 125I and then removed by lyticase and analyzed by SDS-PAGE, at least four low-molecular-mass (less than 65 kilodaltons) proteins associated with hydrophobic cells were either absent or much less abundant in the hydrophilic cell digests. This result was seen for both C. albicans strains that we tested. When late-exponential-phase hydrophilic cells were treated with tunicamycin, high levels of surface hydrophobicity were obtained by stationary phase. These results indicate that the surface hydrophobicity of C. albicans reflects changes in external surface protein exposure and that protein mannosylation may influence exposure of hydrophobic surface proteins.
Review: Cyclophosphamide in multiple sclerosis: scientific rationale, history and novel treatment paradigms (2009)

For patients with relapsing-remitting multiple sclerosis (RRMS), there are currently six approved medications that have been shown to alter the natural course of the disease. The approved medications include three beta interferon formulations, glatiramer acetate, natalizumab and mitoxantrone. Treating aggressive forms of RRMS and progressive disease forms of MS still presents a great challenge to neurologists. Intense immunosuppression has long been thought to be the only feasible therapeutic option. In patients with progressive forms of MS, lymphoid tissues have been detected in the central nervous system (CNS) that may play a critical role in perpetuating local inflammation. Agents that are currently approved for patients with MS have no or very limited bioavailability in the brain and spinal cord. In contrast, cyclophosphamide (CYC), an alkylating agent, penetrates the blood-brain barrier and CNS parenchyma well. However, while CYC has been used in clinical trials and off-label in clinical practice in patients with MS for over three decades, data on its efficacy in very heterogeneous groups of study patients have been conflicting. New myeloablative treatment paradigms with CYC may provide a therapeutic option in patients that do not respond to other agents. In this article we review the scientific rationale that led to the initial clinical trials with CYC. We will also outline the safety, tolerability and efficacy of CYC and provide neurologists with guidelines for its use in patients with MS and other inflammatory disorders of the CNS, including neuromyelitis optica (NMO). Finally, an outlook into relatively novel treatment approaches is provided.
Impact of oxygen on the work functions of Mo in vacuum and on ZrO2 (2005)

The electronic properties of molybdenum surfaces and interfaces with monoclinic zirconia (Mo∕m-ZrO2) of different stoichiometries are investigated through first-principles calculations. We show that oxygen adsorption on the Mo(110) surface strongly increases the Mo vacuum work function, and that a similar trend is observed for the Mo(110) work function on zirconia upon oxygenation of the stoichiometric Mo∕m-ZrO2 interface, albeit to a smaller extent. As expected, Mo∕m-ZrO2 interface reduction/oxidation decreases/increases the Mo effective work function. However, interface overoxidation leading to the formation of a thin MoOx layer between Mo and m-ZrO2 (Mo∕MoOx∕m-ZrO2) causes a work-function decrease with respect to the stoichiometric Mo∕m-ZrO2 interface value. This result is especially surprising because calculations indicate that subsurface oxidation of Mo slabs increases the Mo vacuum work function. Moreover, the calculated vacuum work function of rutile MoO2(110) slab is ∼6.0eV, considerably larger than that of Mo(110) (∼4.9eV). The physical origin of this effect is explained in terms of a partial cancellation interface dipoles.
A Snowman‐like Array of Colloidal Dimers for Antireflecting Surfaces (2004)

Fabrication of motheye‐like colloidal surface patterns as an antireflection coating is presented. Using layer‐by‐layer assembly and a novel colloid‐on‐colloid stamping strategy, snowman‐like patterns consisting of different‐sized colloids were fabricated (see Figure). The pattern spacing and height can be easily tailored by varying the salt concentration and the number of colloidal layers attached, respectively.
Microtubule flux in mitosis is independent of chromosomes, centrosomes, and antiparallel microtubules. (1994)

We investigated the mechanism of poleward microtubule flux in the mitotic spindle by generating spindle subassemblies in Xenopus egg extracts in vitro and assaying their ability to flux by photoactivation of fluorescence and low-light multichannel fluorescence video-microscopy. We find that monopolar intermediates of in vitro spindle assembly (half-spindles) exhibit normal poleward flux, as do astral microtubule arrays induced by the addition of dimethyl sulfoxide to egg extracts in the absence of both chromosomes and conventional centrosomes. Immunodepletion of the kinesin-related microtubule motor protein Eg5, a candidate flux motor, suggests that Eg5 is not required for flux. These results suggest that poleward flux is a basic element of microtubule behavior exhibited by even simple self-organized microtubule arrays and presumably underlies the most elementary levels of spindle morphogenesis.
Staking Out the Graphics Display Pipeline (1984)

Pipelined architecture dramatically off-loads the host computer. Here's a quick look at how eight companies are applyingthis technology to graphics display.
Molecular cloning and functional characterization of a novel member of the C-C chemokine family (1995)

Chemokines play an important role in immune and inflammatory responses by inducing migration and adhesion of leukocytes. We have isolated a novel chemokine cDNA, designated CCF18, from a cDNA library of an IL-3-dependent murine pro-B cell line, Ba/F3. The cDNA encodes a protein structurally related to the C-C chemokine members. Among this family, C10 shows the highest homology to CCF18, and MIP-1 alpha also has a significant homology but to a lesser extent. CCF18 produced from COS cells induced chemotaxis and Ca2+ flux in CD4+ T cell clones. Moreover, prior administration of MIP-1 alpha desensitized the cells to CCF18. The CCF18 gene (Scya10) was mapped to a middle region of murine chromosome 11, where other genes for several C-C chemokine members are localized. These results clearly indicate that CCF18 is a new member of the C-C chemokine family. Since a high level of CCF18 mRNA is constitutively expressed in macrophage and myeloid cell lines, CCF18 may play a role in inflammatory processes.
High-Capacity Adenoviral Vector-Mediated Reduction of Huntingtin Aggregate Load In Vitro and In Vivo (2007)

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat in exon 1 of the huntingtin (htt) gene. Emergence and progression of HD depend on continuous expression of mutant Huntingtin protein (Htt). Therefore, blocking expression of mutant Htt might be a promising therapeutic strategy. We generated a high-capacity adenoviral (HC-Ad) vector expressing a short hairpin RNA (shRNA) targeted to exon 1 of the htt gene. In vitro, this vector efficiently inhibited Htt expression in neuronal and nonneuronal cell lines. In addition, the number of Htt-immunoreactive (IR) aggregates, a hallmark of HD pathology, was significantly reduced after gene transfer with this vector. Importantly, the attenuation of aggregate formation by shRNA was observed in vivo after stereotaxic injection into the striatum of mouse models of HD. The vector was tested in two models: the R6/2 transgenic mouse model and a mouse model based on the local injection of an adenoviral vector expressing a truncated version of mutant Htt. In both models an efficient reduction in mutant Htt aggregate load measured by decreased Htt-IR aggregate formation was observed. Our results support the further development of shRNA for HD therapy.
The design and long-term use of a personal electronic notebook (1996)

This article describes the design and use of a personal electronic notebook. The findings provide a useful data point for those interested in the issue of how to design highly customizable systems for managing personal information. After a description of the notebook's interface and the usag6 practices that have co-evolved with the interface, I discuss some of the features which have made the notebook useful over the long term, and trends in the evolution of its design.
PDA-based mobile robot system with remote monitoring for home environment (2009)

This paper proposes a home automation system using a PDA(Personal Digital Assistants)-based intelligent robot system architecture which consists of three layers; a user layer, a manager layer, and an action layer. In the user layer, users manage and control the robot, and get visual information via the remote monitoring system. In the case of showing maps with the status of the robot, synchronization is very important. In the manager layer, there are three parts; a server part, a home appliances part, and a storage part. The server part manages all the status information of the house, the home appliances part controls all appliances, and the storage system stores all the status information of the house. In the action layer, the main robot system uses a PDA instead of a computer. As a PDA has limited performance, simple algorithms are required. It has an intelligent functional engine for SLAM(Simultaneous Localization And Mapping) and vision processing. We have developed the PDA-based mobile robot system for home automation based on this architecture in order to verify its efficiency.
Direct analog rank filtering (1995)

An analog method is developed for selecting a rank order element directly from a set of samples. Simple nonlinear equations are presented for the order statistic and the weighted order statistic and these equations are implemented with analog MOS circuits. The circuit contains no sorting subsystem and no clock signal. The length of wiring in the circuit is proportional only linearly to the number of input samples.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>