gebhart/patrepeval huggingface dataset:
Thrombospondin-1 type 1 repeat recombinant proteins inhibit tumor growth through transforming growth factor-beta-dependent and -independent mechanisms. (2001)

Thrombospondin-1 (TSP-1) is a potent inhibitor of tumor growth and angiogenesis. The antiangiogenic activity of TSP-1 has been mapped to the procollagen homology region and the type 1 repeats (TSR) using synthetic peptides. To elucidate the molecular mechanisms that are involved in the inhibition of tumor growth by the TSRs, we have expressed recombinant versions of these motifs and have assayed their ability to inhibit the growth of experimental B16F10 melanomas and Lewis lung carcinomas. Recombinant proteins that contain all three TSRs (3TSR) or the second TSR with (TSR2+RFK) or without (TSR2) the transforming growth factor-beta (TGFbeta) activating sequence (RFK) have been expressed in Drosophila S2 cells. In addition, recombinant proteins with mutations in either the RFK sequence (TSR2+QFK) or the WSHWSPW sequence [TSR2 (W/T)] of the second TSR have been prepared. Similar to platelet TSP-1, these proteins are potent inhibitors of endothelial cell migration, and 3TSR of human TSP-1 (3TSR/hTSP-1) and TSR2+RFK activate TGFbeta. An 81% inhibition of B16F10 tumor growth is observed at 2.5 mg (135 nmol)/kg/day of the recombinant 3TSR/hTSP-1. A comparable level of inhibition is observed with 2.5 mg (360 nmol)/kg/day of TSR2+RFK. By contrast, 3TSR of mouse TSP-2 (3TSR/mTSP-2), TSR2+QFK, and TSR2 are significantly less effective. TSR2+RFK and TSR2 reduce tumor vessel density, but TSR2+RFK has a greater effect on B16F10 tumor cell apoptosis and proliferation. Concurrent treatment of B16F10 tumor-bearing mice with TSR2+RFK and either a soluble form of the TGFbeta receptor or an antibody to active TGFbeta reduces the inhibition of B16F10 tumor growth to levels that are comparable with those of TSR2 and TSR2+QFK. By contrast, the presence of the TGFbeta-activating sequence does not increase the level of inhibition of Lewis lung carcinoma experimental tumor growth. These data indicate that the TSRs inhibit tumor growth by inhibition of angiogenesis and regulation of tumor cell growth and apoptosis. The regulation of tumor cell growth and apoptosis is TGFbeta dependent, whereas the inhibition of angiogenesis is not.
Sequence requirements for micro RNA processing and function in human cells (2003)

Most eukaryotes encode a substantial number of small noncoding RNAs termed micro RNAs (miRNAs). Previously, we have demonstrated that miR-30, a 22-nucleotide human miRNA, can be processed from a longer transcript bearing the proposed miR-30 stem-loop precursor and can translationally inhibit an mRNA-bearing artificial target sites. We also demonstrated that the miR-30 precursor stem can be substituted with a heterologous stem, which can be processed to yield novel miRNAs and can block the expression of endogenous mRNAs. Here, we show that a second human miRNA, termed miR-21, can also be effectively expressed when its precursor forms part of a longer mRNA. For both miR-30 and miR-21, mature miRNA production was highly dependent on the integrity of the precursor RNA stem, although the underlying sequence had little effect. In contrast, the sequence of the terminal loop affected miRNA production only moderately. Processing of the initial, miR-30-containing transcript led to the production of not only mature miR-30 but also to the largely nuclear excision of an approximately 65-nucleotide RNA that is likely to represent an important intermediate in miR-30 processing. Consistent with this hypothesis, mutations that affected mature miR-30 production inhibited expression of this miR-30 pre-miRNA to an equivalent degree. Although point mutations could block the ability of both miR-30 and miR-21 to inhibit the translation of mRNAs bearing multiple artificial miRNA target sites, single point mutations only attenuated the miRNA-mediated inhibition of genes bearing single, fully complementary targets. These results suggest that miRNAs, and the closely similar small interfering RNAs, cannot totally discriminate between RNA targets differing by a single nucleotide.
The impact of glycosylation on monoclonal antibody conformation and stability (2011)

Antibody glycosylation is a common post-translational modification and has a critical role in antibody effector function. The use of glycoengineering to produce antibodies with specific glycoforms may be required to achieve the desired therapeutic efficacy. However, the modified molecule could have unusual behavior during development due to the alteration of its intrinsic properties and stability. In this study, we focused on the differences between glycosylated and deglycosylated antibodies, as aglycosyl antibodies are often chosen when effector function is not desired or unimportant. We selected three human IgG1 antibodies and used PNGase F to remove their oligosaccharide chains. Although there were no detected secondary or tertiary structural changes after deglycosylation, other intrinsic properties of the antibody were altered with the removal of oligosaccharide chains in the Fc region. The apparent molecular hydrodynamic radius increased after deglycosylation based on size-exclusion chromatography analysis. Deglycosylated antibodies exhibited less thermal stability for the CH2 domain and less resistance to GdnHCl induced unfolding. Susceptibility to proteolytic cleavage demonstrated that the deglycosylated version was more susceptible to papain. An accelerated stability study revealed that deglycosylated antibodies had higher aggregation rates. These changes may impact the development of aglycosyl antibody biotherapeutics.
Nanostructured Polymer/Nanophase Ceramic Composites Enhance Osteoblast and Chondrocyte Adhesion (2002)

Osteoblast (bone-forming cell) and chondrocyte (cartilage-synthesizing cell) adhesion on novel nanostructured polylactic/glycolic acid (PLGA) and titania composites were investigated in the present in vitro study. Nanostructured polymers were created by chemically treating micron-structured PLGA with select concentrations of NaOH for various periods of time. Dimensions of ceramics were controlled by utilizing either micron or nanometer grain size titania. Compared with surfaces with conventional or micron surface roughness dimensions, results provided the first evidence of increased osteoblast and chondrocyte adhesion on 100 wt% PLGA films with nanometer polymer surface roughness dimensions. Results also confirmed other literature reports of enhanced osteoblast adhesion on 100 wt% nanometer compared with conventional grain size titania compacts; however, the present study provided the first evidence that decreasing titania grain size into the nanometer range did not influence chondrocyte adhesion. Finally, osteoblast and chondrocyte adhesion increased on 70/30 wt% PLGA/titania composites formulated to possess nanosurface rather than conventional surface feature dimensions. The present study, thus, provided evidence that these nanostructured PLGA/titania composites may possess the ability to simulate surface and/or chemical properties of bone and cartilage, respectively, to allow for exciting alternatives in the design of prostheses with greater efficacy.
CDPD and emerging digital cellular systems (2002)

This paper presents the framework of a wireless data network architecture. Minimizing the coupling between the RF technology and the land based infrastructure using standard network protocols such as IP allows the parallel and independent evolution of the RF data carriage and application technologies. Cellular digital packet data (CDPD) is an overlay on the existing AMPS analogue cellular network. Digital airlink technology is emerging as the vehicle for new cellular and PCS networks. This paper outlines how CDPD conforms to this flexible architecture and facilitates the migration of access methods to include AMPS circuit switched and the emerging CDMA digital technologies. The CDPD architecture is also compared with that of the emerging GSM GPRS model. It is shown how both architectures follow the same general framework. The services offered by these wireless architectures are discussed together with example applications.
Infrared and Raman spectra of the M+Cl3− ion pairs and their chlorine–bromine counterparts isolated in argon matrices (1976)

The argon matrix reactions of alkali chloride salts with Cl2 have been investigated through infrared and Raman spectra. In each infrared experiment, an intense product band was observed between 327 and 375 cm−1 and assigned to the antisymmetric stretching vibration ν3 of the Cl3− anion in the ion pair M+Cl3−. Raman spectra of these reaction mixtures yielded the same ν3 bands and, in addition, new signals between 253 and 276 cm−1 which are assigned to the symmetric stretching vibration ν1 of Cl3− in the M+Cl3− species. The observation of two stretching modes in the Raman spectra indicates that the Cl3− ions are asymmetric in these ion pairs. Bromine counterparts and the mixed chlorine–bromine anions were also formed, and used to verify that the anion in the M+X3− species contains three halogen atoms, with the metal ion beside the anion in an asymmetric ’’T’’ shaped structure.
An adaptive extended Kalman filter using artificial neural networks (2002)

Develops an adaptive state-estimation technique using artificial neural networks, referred to as a neuro-observer. The neuro-observer is an extended Kalman filter structure that has its state-coupling function augmented by an artificial neural network that captures the unmodeled dynamics. The neural network of the neuro-observer trains on-line using an extended Kalman filter training paradigm. Improvement in the system model then provides for a more accurate state estimate in the feedback loop, thus enhancing the control signal so that the system behaves in a closer to optimal fashion.
In silico and in vivo analysis reveal a novel gene in Saccharomyces cerevisiae trehalose metabolism (2003)

These results strongly indicate a central role for Ylr270p in inhibiting trehalase activity, as well as in the regulation of its expression preventing a wasteful futile cycle of synthesis-degradation of trehalose.
A CMOS-MEMS mirror with curled-hinge comb drives (2003)

A micromirror achieves up to ±4.7° angular displacement with 18 Vdc by a comb-drive design that uses vertical angled offset of the comb fingers. Structures are made from a combination of CMOS interconnect layers and a thick underlying silicon layer. Electrical isolation of the silicon fingers is realized with a slight silicon undercut etch, which disconnects sufficiently narrow pieces of silicon under the CMOS microstructures. The 1 mm by 1 mm micromirror is made of an approximately 40 μm-thick single-crystal silicon plate coated with aluminum from the CMOS interconnect stack. The mirror has a peak-to-peak curling of 0.5 μm. Fabrication starts with a conventional CMOS process followed by dry-etch micromachining steps. There is no need for wafer bonding and accurate front-to-backside alignment. Such capability has potential applications in biomedical imaging, optical switches, optical scanners, interferometric systems, and vibratory gyroscopes.
Helicobacter pyloriand Peptic Ulcer Disease (1991)

A GRAM-NEGATIVE, microaerophilic curved bacillus found in gastric-biopsy specimens from patients with histologie gastritis was successfully cultured in Perth, Australia, in 1982 and was soon named Campylobacter pylori 1 (a name later changed to Helicobacterpylori). Little attention had been paid to previous descriptions of spiral organisms in biopsy specimens of human gastric mucosa,2 , 3 but it now appears that at the least the organism is responsible for most cases of gastritis not associated with another known primary cause (e.g., autoimmune gastritis or eosinophilic gastritis) and that it may also be a major factor in the pathogenesis of peptic ulcer disease.The . . .
Protein crystallization: from HTS to kilogram-scale. (2003)

The first experiments on protein crystallization started randomly during the 19th century. This technique has been widely used for the determination of the tertiary structure of proteins since the 1950s, when an understanding of the physics of protein crystallization began to emerge. In the 1980s and 1990s, research focused on the study of protein crystal growth processes in microgravity environments, which were created in space shuttle experiments. High-throughput screening (HTS) systems were developed that later found broader laboratory applications. The combination of HTS with an engineering approach opens new opportunities for the protein crystallization process to become a robust, scalable, reproducible and economically viable industrial unit operation.
Variation of Polyelectrolyte Film Stiffness by Photo-Cross-Linking: A New Way To Control Cell Adhesion (2009)

We report on the preparation of polyelectrolyte films based on biopolymers whose nanomechanical properties can be tuned by photo-cross-linking. Cationic poly(L-lysine) was layer-by-layer assembled with anionic hyaluronan (HA) derivatives modified by photoreactive vinylbenzyl (VB) groups. The study of the multilayer buildup by quartz crystal microbalance with dissipation monitoring showed that the presence of VB groups does not influence significantly the multilayer growth. Then the VB-modified HA incorporated into the films was cross-linked upon UV irradiation. UV spectroscopy measurements showed that the cross-linking rate of the multilayers increases with the amount of VB groups grafted onto HA chains. Force measurements performed by atomic force microscopy with a colloidal probe proved that the rigidity of the cross-linked films increases with the grafting degree of HA chains and consequently the number of cross-links. Cell culture assays performed on non-cross-linked and photo-cross-linked films with myoblast cells demonstrated that cell adhesion and proliferation are considerably improved with increasing film rigidity.
Myelin basic protein gene expression in neurons: developmental and regional changes in protein targeting within neuronal nuclei, cell bodies, and processes (1996)

The myelin basic protein (MBP) gene is part of the golli-mbp gene complex. In mouse, the golli-mbp gene produces two families of mRNAs from different transcription start sites that generate either MBPs or golli proteins (which contain MBP sequences in addition to unique peptide sequences). In situ hybridization and immunocytochemical analyses indicate that golli products are expressed in selected neuronal populations in postnatal mouse brain, in addition to oligodendrocytes, as shown earlier. The principal subcellular location of golli proteins in neurons was in axonal and dendritic processes. In a small subset of neurons, golli proteins were located in nuclei. With development and neuronal maturation, golli-mbp expression decreased and/or there was a striking shift in subcellular localization from nuclei and cell soma to the cell processes in specific neuronal populations. Golli protein was localize in neurites of migrating cerebellar granule cells, but it shifted to a nuclear localization when the cells took up residence in the internal granule cell layer. In some regions, (e.g., olfactory bulb and cerebellum) golli proteins were expressed over the entire postnatal period examined (birth to 75 d). The unique patterns of developmental expression within individual populations of neurons, and the unusual shift in subcellular localization of golli proteins with neuronal migration and maturation, suggest a complex regulation of this gene at both the transcriptional and posttranslational levels. The data also suggest that the cellular function(s) of the golli proteins is very different from the structurally related MBPs.
Human Leukocyte Interferon to Control Thrombocytosis in Chronic Myelogenous Leukemia (1983)

Nine patients with refractory chronic myelogenous leukemia and severe symptomatic thrombocytosis (greater than or equal to 1 X 10(6) platelets/mm3) were given partially purified human leukocyte interferon-alpha. A significant decline in platelet counts, from a mean (+/- SE) of 1.71 +/- 0.53 X 10(6)/mm3 to a mean of 0.52 +/- 0.24 X 10(6)/mm3 (p less than 0.01), resulted in all patients. Maintenance of low platelet counts was achieved in two patients for more than 143 and 300 days, respectively. Treatment with human leukocyte interferon-alpha was stopped in the remaining patients because of increases in the leukocyte count, toxicity, or both. Our preliminary observations suggest that human leukocyte interferon-alpha may significantly alleviate progressive thrombocytosis in advanced chronic myelogenous leukemia. Further studies of human leukocyte interferon-alpha and chemotherapeutic agents are indicated.
Cytotoxic effects induced by a combination of cyclopamine and gefitinib, the selective hedgehog and epidermal growth factor receptor signaling inhibitors, in prostate cancer cells (2005)

Although the blockade of the hedgehog cascade by using cyclopamine has been reported to inhibit the growth of some cancer cell types, few studies on the mechanism by which this drug alone or in combination with other cytotoxic agents induces its cytotoxic effect have been reported. In our study, we evaluate, for the first time, the antiproliferative and cytotoxic effects induced by a combination of selective SMO inhibitor, cyclopamine and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib on metastatic prostate cancer (PC) cells. The results revealed that cyclopamine, alone or at a lower concentration in combination with gefitinib, inhibited the growth of sonic hedgehog- (SHH), epidermal growth factor- (EGF) and serum-stimulated androgen-sensitive LNCaP-C33 and LNCaP-LN3 and androgen-independent LNCaP-C81, DU145 and PC3 cells. The antiproliferative effect of cyclopamine and gefitinib, alone or in combination, was mediated via a blockade of the PC3 cells in the G1 phase of the cell cycle. Importantly, the combined cyclopamine and gefitinib also caused a higher rate of apoptotic death of PC cells compared to single agents. The cytotoxic effect induced by these drugs in PC3 cells appears to be mediated at least, in part, via the mitochondrial pathway through the depolarization of the mitochondrial membrane and the release of cytochrome c and reactive oxygen species into the cytosol. This was also accompanied by the activation of caspase cascades, PARP cleavage and DNA fragmentation. Additionally, the combined cyclopamine and gefitinib were more effective at suppressing the invasiveness of PC3 cells through matrigel in vitro as the drugs alone. These findings indicate that the simultaneous blockade of SHH-GLI-1 and EGF-EGFR signaling, which results in the growth arrest and massive rate of apoptotic cell death, represents a promising strategy for a more effective treatment of metastatic PC forms.
Aging and proinflammatory cytokines (2001)

Aging is associated with increased inflammatory activity reflected by increased circulating levels of TNF-alpha, IL-6, cytokine antagonists and acute phase proteins in vivo. Epidemiologic studies suggest that chronic low-grade inflammation in aging promotes an atherogenic profile and is related to age-associated disorders (eg, Alzheimer disease, atherosclerosis, type 2 diabetes, etc.) and enhanced mortality risk. Accordingly, a dysregulated production of inflammatory cytokines has an important role in the process of aging. Studies of age-related differences in the production of proinflammatory cytokines in response to acute stimulations in vitro have yielded inconsistent results. However, in vivo infectious models show delayed termination of inflammatory activity and a prolonged fever response in elderly humans, suggesting that the acute phase response is altered in aging. However, a causal relation between the acute phase response and the increased mortality because of bacterial infections in older patients remains to be demonstrated.
Chromium Fluoride Attenuated Phase-Shifting Mask for Argon Fluoride Excimer Laser Lithography (1996)

Chromium fluoride (CrF) film was chosen as the phase shifter for attenuated phase-shifting masks because of its high transmittance at 193 nm. The refractive index n and absorption coefficient k was derived by using the reflectance-transmittance (RT) method. Using argon fluoride (ArF) excimer laser exposure equipment and a chemically amplified positive resist, fine hole patterns were resolved. Depth of focus (DOFs) with 0.24 µm were extended to 30%. The resolution limit was 0.20 µm, while it was 0.22 µm with a conventional mask.
Processing of asparagine-linked oligosaccharides in insect cells. N-Acetylglucosaminyltransferase I and II activities in cultured lepidopteran cells (1993)

The levels of beta 1,2-N-acetylglucosaminyltransferase (GlcNAc-T) I and II activities in cultured cells from Bombyx mori (Bm-N), Mamestra brassicae (IZD-Mb-0503) and Spodoptera frugiperda (Sf-9 and Sf-21) were investigated. Apart from initial experiments with Man alpha-3(Man alpha 1-6)-Man beta 1-O(CH2)8COOH3 and 3H-labelled UDP-GlcNAc as substrates, GlcNAc-T I activity was measured with a non-radioactive HPLC method using pyridylaminated Man3-GlcNAc2 and Man5GlcNAc2 as acceptor oligosaccharides. It was shown by reversed-phase HPLC, exoglycosidase digestion and methylation analysis that the product obtained with Man3GlcNAc2 contained a terminal GlcNAc residue linked beta 1,2 to the alpha 1,3 arm of the acceptor. Compared to the enzyme from the human hepatoma cell line HepG2, insect cell GlcNAc-T I exhibited a much higher preference for the Man5 substrate. The GlcNAc-T I from Mb-0503 cells had apparent Km and Vmax values for pyridylaminated Man3- and Man5GlcNAc2 of 2.15 and 0.21 mM, and of 3.4 and 11.4 nmol/h/mg of cell protein, respectively. When Man5GlcNAc2 was used as the acceptor substrate, the levels of GlcNAc-T I activity in the four insect cell lines ranged between 7.5 and 14.7 nmol/h/mg of cell protein, and thus were comparable to that of HepG2 cells. Evidence is presented for the dependence of lepidopteran fucosyltransferase on the presence of terminal N-acetylglucosamine.(ABSTRACT TRUNCATED AT 250 WORDS)
Application-controlled file caching policies (1994)

We consider how to improve the performance of file caching by allowing user-level control over file cache replacement decisions. We use two-level cache management: the kernel allocates physical pages to individual applications (allocation), and each application is responsible for deciding how to use its physical pages (replacement). Previous work on two-level memory management has focused on replacement, largely ignoring allocation. The main contribution of this paper is our solution to the allocation problem. Our solution allows processes to manage their own cache blocks, while at the same time maintains the dynamic allocation of cache blocks among processes. Our solution makes sure that good user-level policies can improve the file cache hit ratios of the entire system over the existing replacement approach. We evaluate our scheme by trace-based simulation, demonstrating that it leads to significant improvements in hit ratios for a variety of applications. 1 Introduction File caching...