gebhart/patrepeval huggingface dataset:
Synthesis, characterization, and mechanical properties of PMMA/poly(aromatic/aliphatic siloxane) semi-interpenetrating polymer networks (1996)

Semi-interpenetrating polymer networks (IPNs) composed of poly(methyl methacrylate) (PMMA) and aromatic/aliphatic siloxanes have been made via sequential and simultaneous polymerizations. As the percentage of aliphatic siloxane increases, flexibility and, in general, toughness of the IPNs increases and clarity is reduced. This loss in clarity is due to the mismatch of refractive indices (1.49 form PMMA vs. 1.43 for aliphatic siloxane). PMMA is quite transparent. On the other hand, in making aromatic siloxane/PMMA IPNs clarity is retained as aromatic siloxane is increased due to better matching refractive index (1.49 for PMMA and −1.49 for poly(diphenyl siloxane)). Gel permeation chromatography (GPC) indicates slightly crosslinked IPNs with the THF soluble portions having number-average molecular weight, M¯n, of 105–106. NMRs of IPNs essentially show peaks for the components, PMMA and the siloxane, which make up the respective IPNs. 29Si-NMRs indicate cross-linking and grafting. Mechanical properties show increased toughness of IPNs versus PMMA as percentage of siloxane and crosslinker increases, but with a corresponding loss in tensile strength. © 1996 John Wiley & Sons, Inc.
<title>Pictometry digital video mapping</title> (1995)

Pictometry is a proprietary digital imaging process which computationally maps each pixel of a digital land image to actual geographic coordinates, so that features in a mosaic of land images may be located and or measured.
Phase I clinical study of the recombinant antibody toxin scFv(FRP5)-ETA specific for the ErbB2/HER2 receptor in patients with advanced solid malignomas (2005)

Our results demonstrate that systemic therapy with scFv(FRP5)-ETA can be safely administered up to a maximum tolerated dose of 12.5 microg/kg in patients with ErbB2-expressing tumors, justifying further clinical development.
ClpP: A distinctive family of cylindrical energy‐dependent serine proteases (2007)

Processes maintaining protein homeostasis in the cell are governed by the activities of molecular chaperones that mainly assist in the folding of polypeptide chains and by a large class of proteases that regulate protein levels through degradation. ClpP proteases define a distinctive family of cylindrical, energy-dependent serine proteases that are highly conserved throughout bacteria and eukaryota. They typically interact with ATP-dependent AAA+ chaperones that bind and unfold target substrates and then translocate them into ClpP for degradation. Structural and functional studies have provided a detailed view of the mechanism of function of this class of proteases.
The Human Cytomegalovirus Fc Receptor gp68 Binds the Fc CH2-CH3 Interface of Immunoglobulin G (2008)

Recognition of immunoglobulin G (IgG) by surface receptors for the Fc domain of immunoglobulin G (Fcgamma), FcgammaRs, can trigger both humoral and cellular immune responses. Two human cytomegalovirus (HCMV)-encoded type I transmembrane receptors with Fcgamma-binding properties (vFcgammaRs), gp34 and gp68, have been identified on the surface of HCMV-infected cells and are assumed to confer protection against IgG-mediated immunity. Here we show that Fcgamma recognition by both vFcgammaRs occurs independently of N-linked glycosylation of Fcgamma, in contrast with the properties of host FcgammaRs. To gain further insight into the interaction with Fcgamma, truncation mutants of the vFcgammaR gp68 ectodomain were probed for Fcgamma binding, resulting in localization of the Fcgamma binding site on gp68 to residues 71 to 289, a region including an immunoglobulin-like domain. Gel filtration and biosensor binding experiments revealed that, unlike host FcgammaRs but similar to the herpes simplex virus type 1 (HSV-1) Fc receptor gE-gI, gp68 binds to the C(H)2-C(H)3 interdomain interface of the Fcgamma dimer with a nanomolar affinity and a 2:1 stoichiometry. Unlike gE-gI, which binds Fcgamma at the slightly basic pH of the extracellular milieu but not at the acidic pH of endosomes, the gp68/Fcgamma complex is stable at pH values from 5.6 to pH 8.1. These data indicate that the mechanistic details of Fc binding by HCMV gp68 differ from those of host FcgammaRs and from that of HSV-1 gE-gI, suggesting distinct functional and recognition properties.
Synthetic and cytotoxic studies of alpha-methylene-gamma-butyrolactone bearing pyrimidines. (1993)

A total of ten pyrimidine alpha-methylene-gamma-butyrolactones were synthesized as potential antitumor agents on the basis of their possible action as Michael acceptors for DNA/RNA and cellular enzymes. The synthesis of these heterocycles involved a convenient Reformatsky-type reaction of pyrimidinyl ketones with ethyl alpha-(bromomethyl)acrylate. The preliminary in vitro cytotoxic assay indicated that these synthetic compounds were essentially active against the growth of KB, Hep-2, HeLa and Colo-205 cells. Among them, 5'-biphenyl-5'-(uracil-1-ylmethyl)-2'-oxo-3'-methylenetetrahydr ofuran (5f) demonstrated to be the most potent antileukemic agent.
Phenolic glycolipids of Mycobacterium bovis: new structures and synthesis of a corresponding seroreactive neoglycoprotein (1989)

The glycolipid that characterizes the majority of isolates of Mycobacterium bovis and that has come to be known as M. bovis-identifying lipid is the phenolic glycolipid mycoside B described in the literature by others. However, when mycoside B obtained from M. bovis BCG, field isolates, and infected tissues was examined in detail, it was shown to be different from that described in the literature in some important respects. In particular, the glycosyl substituent is 2-O-methyl-alpha-L-rhamnopyranose rather than 2-O-methyl-beta-D-rhamnopyranose. With this information, a seroreactive neoglycoprotein (neoantigen) containing the 2-O-methyl-alpha-L-rhamnopyranosyl substituent suitable for the serodiagnosis of bovine tuberculosis was synthesized. M. bovis also contains other minor seroreactive phenolic glycolipids, one of which is a deacylated form of mycoside B and another of which contains an alpha-L-rhamnopyranosyl unit rather than 2-O-methyl-alpha-L-rhamnopyranose.
Dynamic frequency and voltage control for a multiple clock domain microarchitecture (2003)

We describe the design, analysis, and performance of an on-line algorithm to dynamically control the frequency/voltage of a Multiple Clock Domain (MCD) microarchitecture. The MCD microarchitecture allows the frequency/voltage of microprocessor regions to be adjusted independently and dynamically, allowing energy savings when the frequency of some regions can be reduced without significantly impacting performance. Our algorithm achieves on average a 19.0% reduction in Energy Per Instruction (EPI), a 3.2% increase in Cycles Per Instruction (CPI), a 16.7% improvement in Energy-Delay Product, and a Power Savings to Performance Degradation ratio of 4.6. Traditional frequency/voltage scaling techniques which apply reductions globally to a fully synchronous processor achieve a Power Savings to Performance Degradation ratio of only 2-3. Our Energy-Delay Product improvement is 85.5% of what has been achieved using an off-line algorithm. These results were achieved using a broad range of applications from the MediaBench, Olden, and Spec2000 benchmark suites using an algorithm we show to require minimal hardware resources.
Interleukin-1 and tumor necrosis factor-alpha as radio- and chemoprotectors of bone marrow. (1993)

Administration of interleukin 1 (IL-1) or tumor necrosis factor-alpha (TNF alpha) protects bone marrow precursor cells (BMPC) from ionizing radiation and antineoplastic drugs. The time of injection is critical: the best protective results being obtained when cytokines are given around 24h prior to the induced injury. Multiple daily cytokine injections that precede irradiation or drug administration are more effective than single ones although single doses are quite effective at increasing survival in mice. Protection is positively correlated with both rapid granulocyte recovery and BMPC survival. Mechanisms involved in BMPC radioprotection include: (1) push to the S/G2 + M or arrest in the G0 phases of the cell cycle by IL-1 or TNF alpha, respectively, and (2) induction of mitochondrial manganous superoxide dismutase synthesis. For BMPC chemoprotection, proposed mechanisms are: (1) increase of aldehyde dehydrogenase synthesis, and (2) modulation of multiple-drug resistant gene expression. Stimulation of glutathione synthesis in BMPC could be operating in both radio- and chemoprotection. These findings point to the relevance of IL-1 or TNF alpha in cancer therapy as a means of reducing BMPC sensitivity to cytoreductive drugs or irradiation (including radioimmunotherapy) as well as in in vitro tumor cell purging with drugs in autologous BMT. Prior administration of these cytokines should be also considered for people in imminent danger of exposure to radiation.
Incidence of haematological malignancies by ethnic group in England, 2001–7 (2013)

The aetiology of most haematological malignancies is largely unknown. Studies of migrant populations can provide insights into the relative importance of genetic and environmental risk factors for these diseases. This study compares incidence rates in British Indians, Pakistanis, Bangladeshis, Black Africans, Black Caribbeans, Chinese and Whites in England from 2001 to 2007. We analysed 134,302 haematological cancer registrations with ethnicity obtained by linkage to the Hospital Episodes Statistics database. Mid-year population estimates from 2001 to 2007 were used. Incidence rate ratios adjusted for age, sex and income were calculated, comparing the six ethnic groups to Whites and to each other. Whites had the highest rates for most subtypes. However, Blacks experienced more than double the incidence of plasma cell and mature T-cell neoplasms compared to other ethnic groups. There were also significant differences in incidence between Indians, Pakistanis and Bangladeshis for Hodgkin lymphoma and mature B-cell neoplasms and between Black African and Black Caribbeans for mature B-cell and other lymphoid neoplasms (all P < 0.001). Our results show that the risk of haematological cancers varies greatly by ethnic group, including within those groups that have traditionally been grouped together (South Asians and Blacks) with many of these differences not explicable by known risk factors.
Resting and activated subsets of mouse multipotent hematopoietic stem cells. (1990)

The fluorescent vital dye rhodamine 123 (Rh-123), which preferentially accumulates in mitochondrial membranes, can be used as a probe to indicate mitochondrial and hence cellular activity. In this study, mouse bone marrow hematopoietic stem cells were subdivided into Rh-123lo, Rh-123med, and Rh-123hi populations. The Rh-123lo (resting) population was significantly enriched in cells with a higher proliferative potential compared to the Rh-123hi (activated) population. The resting population exhibited a 20-fold greater ability to differentiate into splenic colony-forming units (CFU-S) relative to the activated population, whereas the activated population contained about 4-fold more day 13 CFU-S on primary transfer relative to the resting population. The two populations produced morphologically distinct splenic colonies; however, the frequency and morphology of in vitro colonies were very similar. Only the resting population provided sufficient stem cells to transfer long-term hematopoietic repopulation to secondary recipient animals after lethal irradiation. On a single cell level, the resting and activated populations exhibited an equivalent ability to differentiate into lymphoid and myeloid progeny. These observations provide further insight into the heterogeneous nature of CFU-S and directly demonstrate that multipotent hematopoietic stem cells are heterogeneous with regard to their clonogenic capacities.
A Validated Tumorgraft Model Reveals Activity of Dovitinib Against Renal Cell Carcinoma (2012)

Most anticancer drugs entering clinical trials fail to achieve approval from the U.S. Food and Drug Administration. Drug development is hampered by the lack of preclinical models with therapeutic predictive value. Herein, we report the development and validation of a tumorgraft model of renal cell carcinoma (RCC) and its application to the evaluation of an experimental drug. Tumor samples from 94 patients were implanted in the kidneys of mice without additives or disaggregation. Tumors from 35 of these patients formed tumorgrafts, and 16 stable lines were established. Samples from metastatic sites engrafted at higher frequency than those from primary tumors, and stable engraftment of primary tumors in mice correlated with decreased patient survival. Tumorgrafts retained the histology, gene expression, DNA copy number alterations, and more than 90% of the protein-coding gene mutations of the corresponding tumors. As determined by the induction of hypercalcemia in tumorgraft-bearing mice, tumorgrafts retained the ability to induce paraneoplastic syndromes. In studies simulating drug exposures in patients, RCC tumorgraft growth was inhibited by sunitinib and sirolimus (the active metabolite of temsirolimus in humans), but not by erlotinib, which was used as a control. Dovitinib, a drug in clinical development, showed greater activity than sunitinib and sirolimus. The routine incorporation of models recapitulating the molecular genetics and drug sensitivities of human tumors into preclinical programs has the potential to improve oncology drug development.
Selective inhibition of the epidermal growth factor and HER2/neu receptors by tyrphostins (1993)

The HER2 (neu/erb-B2) proto-oncogene codes for a transmembrane receptor with tyrosine kinase activity and with high homology to the EGF receptor (HER1). The high incidence of HER2 overexpression in breast and ovary carcinomas prompted us to synthesize protein tyrosine kinase inhibitors (tyrphostins) which selectively inhibit the HER2 kinase activity. Two groups of tyrphostins were developed: one highly selective in inhibiting HER1 as opposed to HER2, the other highly selective in inhibiting HER2. Both the HER1 and the HER2 selective blockers were competitive with ATP binding. This suggests that even though the kinase domains of the respective receptors show an 80% degree of homology it is possible to design small molecules capable of discriminating between them. These results also show that the two kinases differ in their ATP binding sites. Mitogenic signaling induced by EGF in NIH3T3 cells overexpressing either HER1 or HER1-2 (possessing the HER2 kinase domain) was blocked identically by the agents that discriminate between the two in vitro. This paradox was further explored and elucidated. We propose that high intracellular ATP levels prevent inhibitor binding to the receptor. The antiproliferative action of the two distinct selective tyrphostins observed may result from the inhibition of a downstream element, presumably a tyrosine kinase, which mediates mitogenic signaling.
5'-Methyl-DNA-A New Oligonucleotide Analog: Synthesis and Biochemical Properties (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT5'-Methyl-DNA-A New Oligonucleotide Analog: Synthesis and Biochemical PropertiesAshis K. Saha, Cheryl Waychunas, Thomas J. Caulfield, Donald A. Upson, Cheryl Hobbs, and Anne M. YawmanCite this: J. Org. Chem. 1995, 60, 4, 788–789Publication Date (Print):February 1, 1995Publication History Published online1 May 2002Published inissue 1 February 1995https://pubs.acs.org/doi/10.1021/jo00109a003https://doi.org/10.1021/jo00109a003research-articleACS PublicationsRequest reuse permissionsArticle Views252Altmetric-Citations31LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Real-time observation of a single DNA digestion by lambda exonuclease under a fluorescence microscope field (2001)

A fluorescence microscopy technique has been developed to visualize the behavior of individual DNA and protein molecules. Real-time direct observation of a single DNA molecule can be used to investigate the dynamics of DNA-protein interactions, such as the DNA digestion reaction by lambda exonuclease. In conventional methods it is impossible to analyze the dynamics of an individual lambda exonuclease molecule on a DNA because they can only observe the average behavior of a number of exonuclease molecules. Observation of a single molecule, on the other hand, can reveal processivity and binding rate of an individual exonuclease molecule. To evaluate the dynamics of lambda exonuclease, a stained lambda DNA molecule with one biotinylated terminal was fixed on an avidin-coated coverslip and straightened using a d.c. electric field. Microscopic observation of digestion of a straightened DNA molecule by lambda exonuclease revealed that the DNA digestion rate was approximately 1000 bases/s and also demonstrated high processivity.
Is the Cannabinoid CB1 Receptor a 2-Arachidonoylglycerol Receptor? Structural Requirements for Triggering a Ca2+ Transient in NG108-15 Cells (1997)

The effects of delta9-tetrahydrocannabinol and 2-arachidonoylglycerol on the intracellular free Ca2+ concentration ([Ca2+]i) in NG108-15 cells were examined in detail. We found that delta9-tetrahydrocannabinol induces a rapid, modest increase in [Ca2+]i. The response was detectable with 3 nM delta9-tetrahydrocannabinol. We also found that very low concentrations of 2-arachidonoylglycerol elicit a rapid, more prominent increase in [Ca2+]i. Such a response was observed not only in NG108-15 cells but also in N18TG2 cells. The response induced by 2-arachidonoylglycerol in either NG108-15 cells or N18TG2 cells was abolished by pretreatment of the cells with a cannabinoid CB1 receptor specific antagonist, SR141716A, suggesting that 2-arachidonoylglycerol interacts with the CB1 receptor to induce the response. The results of an experiment involving a phospholipase C inhibitor suggested that phospholipase C is involved in the rapid increase in [Ca2+]i induced by 2-arachidonoylglycerol. We also found that 1(3)-arachidonoylglycerol exhibits similar activity to that of 2-arachidonoylglycerol, although its activity at low concentrations was somewhat weak compared with that of 2-arachidonoylglycerol. We further confirmed that several structural analogues of 2-arachidonoylglycerol were less active compared with 2-arachidonoylglycerol. These results suggest that the structure of 2-arachidonoylglycerol is strictly recognized by the CB1 receptor, which raises the possibility that the CB1 receptor is originally a 2-arachidonoylglycerol receptor.
Blockage of the urokinase receptor on the cell surface: Construction and characterization of a hybrid protein consisting of the N‐terminal fragment of human urokinase and human albumin (1994)

Receptor-bound urokinase is likely to be a crucial determinant in both tumor invasion and angiogenesis. We report here that a yeast-derived genetic conjugate between human serum albumin and the 1-135 N-terminal residues of urokinase (u-PA) competitively inhibits the binding of exogenous and endogenous u-PA to its cell-anchored receptor (u-PAR). This hybrid molecule (ATF-HSA) also inhibits in vitro pro-urokinase-dependent plasminogen activation in the presence of u-PAR bearing cells. These effects are probably responsible for the observed in vitro inhibition of tumor cell invasion in a reconstituted basement membrane extract (Matrigel).
β-Lactones as Specific Inhibitors of ClpP Attenuate the Production of Extracellular Virulence Factors of Staphylococcus aureus (2008)

To approach the daunting problem of multidrug resistant bacterial pathogens, a multidisciplinary chemical proteomic strategy was applied and functionalized beta-lactones were identified as potent, cell permeable inhibitors for specific and selective targeting of the key virulence regulator complex ClpP in S. aureus and methicillin resistant S. aureus (MRSA) strains. ClpP represents the central protease complex responsible for the activation of numerous virulence factors including many with devastating effects for human health such as hemolysins, proteases, lipases, and DNases. Although the crucial role of this enzyme was validated by genetic knockouts, no inhibitor has been reported to date. In fact, our most potent inhibitor was able to completely abolish hemolytic and proteolytic activities and showed a dramatic decrease in the activities of virulence associated lipases and DNases. These effects were also observed in a multiresistant strain emphasizing the potential value of such compounds. Targeting this virulence factor may therefore likely represent an attractive strategy for neutralizing the harmful effects of bacterial pathogens and help the host immune response to eliminate the disarmed bacteria. Since ClpP is not essential for viability and highly conserved in many pathogens, our strategy could represent a global approach for the treatment of infectious diseases without the pressing problem of antibiotic pressure and resistance development.
Isotropic Lifshitz Behavior in Block Copolymer-Homopolymer Blends (1995)

A series of mixtures composed of a symmetric $A\ensuremath{-}B$ diblock copolymer and a symmetric blend of $A$ and $B$ homopolymers was investigated by small-angle neutron scattering. Mean-field theory predicts that a line of lamellar-disorder transitions with wave-vector instability ${q}^{*}&gt;0$ will meet a line of critical points with ${q}^{*}=0$ in the three-component mixture at an isotropic Lifshitz point. Mean-field Lifshitz behavior ($\ensuremath{\gamma}=1$ and $\ensuremath{\nu}=\frac{1}{4}$) was observed in the disordered state at the anticipated composition to within 1 K of the phase transition.
c-erbB-2 Oncoprotein and Epidermal Growth Factor Receptor in Cervical Lesions (1997)

Epidermal growth factor receptor (EGF-R) and the oncogene product of c-erbB-2 have been shown to be expressed in human tumors and in some cases relate to clinical outcome. This study investigates the correlation between the presence of these receptor proteins and various histological grades of cervical tissues. Immunocytochemical analysis of benign, premalignant and malignant cervical tissues showed a highly significant correlation between the expression of the two proteins and the histological grade of the lesions. Moreover, the overall frequency of coexpression of these proteins was similar. This study suggests that these proteins may be involved in cellular proliferation and have a significant role in the progression of cervical cancer.