gebhart/patrepeval huggingface dataset:
Gene-Expression Signatures in Breast Cancer (2009)

This review discusses the results of DNA microarray signatures in breast cancer. These signatures have been useful in the classification of breast cancers, and they have an association with clinical outcomes. Surprisingly, there is little overlap in the types of genes among several useful microarray signatures. The true value of these signatures will become apparent only when prospective trials, now in progress, have been completed.
Directed evolution of Her2/neu-binding IgG1-Fc for improved stability and resistance to aggregation by using yeast surface display (2012)

An Fcab (Fc antigen binding) is a crystallizable fragment of IgG having C-terminal structural loops of CH3 domains engineered for antigen binding. Since introduction of novel binding sites might impair the immunoglobulin fold, repairing strategies are needed for improving the biophysical properties of promising binders without decreasing affinity to the antigen. Here, a directed evolution protocol was developed and applied for stabilization of a Her2/neu-binding Fcab. Distinct loop regions of the parental binder were softly randomized by parsimonious mutagenesis, followed by heat incubation of the yeast displayed protein library and selection for retained antigen binding. Selected Fcabs were expressed solubly in Pichia pastoris and human embryonic kidney 293 cells and characterized. Fcab clones that retained their affinity to Her2/neu but exhibited a significantly increased conformational stability and resistance to aggregation could be evolved. Moreover, we demonstrate that simultaneous selection for binding to the antigen and to structurally specific ligands (FcγRI and an antibody directed against the CH2 domain) yields even more stable Fcabs. To sum up, this study presents a very potent and generally applicable method for improving the fold and stability of antibodies, antibody fragments and alternative binding scaffolds.
Differentiation of thermolysins and serralysins by monoclonal antibodies (1996)

Two monoclonal antibodies (MAbs) to a 36-kDa extracellular metalloprotease (PSCP) from Burkholderia (Pseudomonas) cepacia were found to react with thermolysin, Pseudomonas aeruginosa elastase, alkaline protease (Apr) and LasA, Serratia marcescens protease (SMP), Aeromonas hydrophila protease (AhP), and both the lethal factor (LF) and protective antigen (PA) of Bacillus anthracis on immunoblots. The MAbs were capable of neutralising the proteolytic activity of thermolysin, P. aeruginosa elastase and PSCP but not that of Apr, SMP, and AhP. These results suggest that these MAbs may be able to differentiate between the thermolysin and serralysin family of metalloproteases on the basis of their neutralisation capability and could, therefore, be useful tools in the characterisation of new bacterial proteases.
Investigation of the Self-Organization of Lutein and Lutein Diacetate by Electronic Absorption, Circular Dichroism Spectroscopy, and Atomic Force Microscopy (2001)

Spontaneously forming H- and J-type chiral self-assemblies of lutein and lutein diacetate were studied by means of ultraviolet−visible and circular dichroism spectroscopy (CD). Spectroscopic properties of their thin films has been determined for the first time. Existence of chiral superstructures in both solution and solid phases with opposite and same handedness was demonstrated. The molecular exciton theory and the exciton chirality rule were applied to define both qualitatively and quantitatively the spectral shifts, band shape changes, and the highly intense but quite different excitonic CD activity in the two forms of aggregates. Atomic force microscopy images revealed definite threadlike morphology in lutein diacetate films referring to the formation of a nematic liquid crystal phase which probably exists in the aqueous solution either. On this basis, the vibronically coupled CD bands of lutein diacetate are attributed to an excitonic interaction arised from the twisted nematic layers.
Expression of a Dominant Negative SHP-2 in Transgenic Mice Induces Insulin Resistance (1999)

To elucidate the roles of SHP-2, we generated transgenic (Tg) mice expressing a dominant negative mutant lacking protein tyrosine phosphatase domain (DeltaPTP). On examining two lines of Tg mice identified by Southern blot, the transgene product was expressed in skeletal muscle, liver, and adipose tissues, and insulin-induced association of insulin receptor substrate 1 with endogenous SHP-2 was inhibited, confirming that DeltaPTP has a dominant negative property. The intraperitoneal glucose loading test demonstrated an increase in blood glucose levels in Tg mice. Plasma insulin levels in Tg mice after 4 h fasting were 3 times greater with comparable blood glucose levels. To estimate insulin sensitivity by a constant glucose, insulin, and somatostatin infusion, steady state blood glucose levels were higher, suggesting the presence of insulin resistance. Furthermore, we observed the impairment of insulin-stimulated glucose uptake in muscle and adipocytes in the presence of physiological concentrations of insulin. Moreover, tyrosine phosphorylation of insulin receptor substrate-1 and stimulation of phosphatidylinositol 3-kinase and Akt kinase activities by insulin were attenuated in muscle and liver. These results indicate that the inhibition of endogenous SHP-2 function by the overexpression of a dominant negative mutant may lead to impaired insulin sensitivity of glucose metabolism, and thus SHP-2 may function to modulate insulin signaling in target tissues.
On Uniqueness Of Fibrous Materials (2004)

This paper summarizes some remarkable issues in fibrous materials, i.e., any material systems formed by fiber-like constituents such as felt, cloth, paper, muscle and wood. Such interest can go back as far as Galileo who was fascinated by the fact that short fibres can form a long and strong rope via friction between fibers induced by twisting, although a relatively rigorous account for the mechanism has not been available until recently. It is almost exclusively the feature of fibrous materials where pliability, compressibility, high toughness and durability coexist, making the material irreplaceable and indispensable in many engineering applications. The questions regarding fiber packing, flexibility, friction, and fabric formability have inspirited studies not only from fiber scientists, but from science communities at large. Furthermore, the fiber capillary phenomena and the distinct thermal behaviours of the material have provoked many scientific curiosities and endeavours, yielding countless practical applications. Nonetheless, the fibrous materials, arguably the first type of engineering materials, remain perhaps the least understood, not to mention the fact that most biomaterials, plants or body muscles, are formed by fibrous constituents.
Targeting Androgen Receptor Aberrations in Castration-Resistant Prostate Cancer (2016)

Androgen receptor (AR) splice variants (SV) have been implicated in the development of metastatic castration-resistant prostate cancer and resistance to AR targeting therapies, including abiraterone and enzalutamide. Agents targeting AR-SV are urgently needed to test this hypothesis and further improve the outcome of patients suffering from this lethal disease. Clin Cancer Res; 22(17); 4280-2. ©2016 AACRSee related article by Yang et al., p. 4466.
Selective inhibition of telomerase activity during terminal differentiation of immortal cell lines. (1996)

Telomerase, the enzyme that maintains the ends of linear eukaryotic chromosomes, is active in human germ cells and in a majority of tumor tissues and immortalized cell lines. In contrast, most mature somatic cells and tissues contain low or undetectable telomerase activity, implying a stringent negative regulatory control mechanism. We report here that telomerase activity is dramatically inhibited during the terminal differentiation of HL-60 human promyelocytic leukemia cells to monocytic and granulocytic lineages. A loss of telomerase activity was seen in response to three different inducers of differentiation, was independent of differentiation-induced apoptosis, and occurred in the presence of unaltered expression of the RNA component of telomerase. Reduction in telomerase activity was also observed during the differentiation of murine F9 teratocarcinoma and C2C12 myoblast cells. In contrast, induced differentiation of murine p19 embryonal carcinoma and Neuro 2a neuroblastoma cells did not result in a loss of telomerase activity. These results are therefore consistent with the absence of telomerase activity in human somatic cells and the presence of telomerase activity in many somatic murine cells and tissues.
Monoclonal antibodies as carriers for delivering cytotoxic agents. (1991)

Because of their high level of specificity monoclonal antibodies can be used as carriers for delivering cytotoxic agents. However they need to have some other features to be usefully used for this purpose. First of all monoclonal antibodies need to be specific for those membrane antigens which are strongly expressed on target cells but absent from normal cells. Secondly it is important to obtain monoclonal antibodies with as a high affinity as possible, and the biodistribution of the molecule recognized by the monoclonal antibody must be considered with the best attention. Chemical treatment of monoclonal antibodies needs to be performed in such a way that neither the antibody nor the toxic agent will result denaturated. Finally, as an alternative to chemically linked immunoconjugates, bispecific antibodies have successfully been used for delivering cytotoxic agents.
Rapid detection of octamer binding proteins with ‘mini extracts’, prepared from a small number of cells (1989)

Journal Article Rapid detection of octamer binding proteins with ‘mini extracts’, prepared from a small number of cells Get access Edgar Schreiber, Edgar Schreiber Institut für Molekularbiologie II der Universität ZürichHōnggerberg, CH-8093 Zürich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Patrick Matthias, Patrick Matthias Institut für Molekularbiologie II der Universität ZürichHōnggerberg, CH-8093 Zürich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael M. Müller, Michael M. Müller Institut für Molekularbiologie II der Universität ZürichHōnggerberg, CH-8093 Zürich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Walter Schaffner Walter Schaffner Institut für Molekularbiologie II der Universität ZürichHōnggerberg, CH-8093 Zürich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 17, Issue 15, 11 August 1989, Page 6419, https://doi.org/10.1093/nar/17.15.6419 Published: 11 August 1989 Article history Received: 05 July 1989 Published: 11 August 1989
Zirconium‐Mediated Intramolecular Coupling of Terminal Alkynes and Their Subsequent Carbonylation: Novel Synthesis of Seven‐ and Eight‐Membered Heterocycles (1997)

Abstract The development of a new method for the intramolecular coupling of terminal alkynes and for the synthesis of seven‐ and eight‐membered benzoheterocycles is reported. The key steps involve the generation of zirconocene‐alkyne complexes from 2‐bromoalkenes and the subsequent intramolecular carbometalation of olefins or acetylides. The 8‐unsubstituted zirconabicyclopentenes were carbonylated to afford unexpected products and allow access to polyfunctionalized molecules from simple starting materials.
Constitutive gain‐of‐function mutants in a nucleotide binding site–leucine rich repeat protein encoded at the Rx locus of potato (2002)

Rx in potato encodes a protein with a nucleotide binding site (NBS) and leucine-rich repeats (LRR) that confers resistance against Potato virus X. The NBS and LRR domains in Rx are present in many disease resistance proteins in plants and in regulators of apoptosis in animals. To investigate structure-function relationships of NBS-LRR proteins we exploited the potential of Rx to mediate a cell death response. With wild-type Rx cell death is elicited only in the presence of the viral coat protein. However, following random mutagenesis of Rx, we identified mutants in which cell death is activated in the absence of viral coat protein. Out of 2500 Rx clones tested there were seven constitutive gain-of-function mutants carrying eight independent mutations. The mutations encoded changes in the LRR or in conserved RNBS-D and MHD motifs of the NBS. Based on these findings we propose that there are inhibitory domains in the NBS and LRR. The constitutive gain-of-function phenotypes would be due to deletion or modification of these inhibitory domains. However activation of Rx is not simply release of negative regulation by the LRR and adjacent sequence because deleted forms of Rx that lack constitutive gain of function mutations are not active unless the protein is overexpressed.
Reduction of Doxorubicin Cardiotoxicity by Prolonged Continuous Intravenous Infusion (1982)

Doxorubicin (Adriamycin) was administered by continuous infusion to reduce peak plasma levels and thus lessen cardiac toxicity. Cardiotoxicity was monitored by noninvasive methods, and endomyocardial biopsy specimens were studied by electronmicroscopy. Cardiotoxicity was compared in 21 patients receiving doxorubicin intravenously over 48 or 96 hours and in 30 control patients treated by standard intravenous injection. Both groups were studied prospectively and were well matched by risk factors for doxorubicin cardiotoxicity. The median cumulative dose for those receiving continuous infusion was 600 mg/m2 body surface area (range, 360 to 1500 mg/m2) compared with 465 mg/m2 (range 290 to 680 mg/m2) in the control group (p = 0.002). Fourteen of the 30 patients in the control group showed severe morphologic changes in the biopsy specimens, precluding further doxorubicin administration, as compared with two of 21 patients receiving the drug by continuous infusion (p less than 0.02). The mean pathologic score for the infusion group, 0.9, was lower than the mean for the control group, 1.6 (p = 0.004). Antitumor activity was not compromised. Decreasing peak plasma levels of doxorubicin by continuous infusion reduces cardiotoxicity.
Overexpression of PrPc, combined with MGr1‐Ag/37LRP, is predictive of poor prognosis in gastric cancer (2014)

Prion protein (PrPc) has been previously reported to be involved in gastric cancer (GC) development and progression. However, the association between expression of PrPc and GC prognosis is yet poorly characterized. In the present study, the expressions of PrPc and MGr1-Ag/37LRP, a protein interacting with PrPc, were detected using the tissue microarray technique and immunohistochemical method to compare clinicopathological parameters of 238 GC patients. We found that the expressions of PrPc and MGr1-Ag/37LRP were upregulated in GC lesions compared with their expressions in adjacent noncancerous tissues (p<0.01). High expression of PrPc was detected in 37.39% (89/238) of GC patients and positively correlated with the expression of MGr1-Ag/37LRP (r=0.532, p<0.001). PrPc expression was associated with a number of clinicopathological parameters including depth of invasion and lymph node metastasis of the tumor (p<0.001). High expression of PrPc brought a poorer prognosis than low PrPc expression. Moreover, GC patients with high level of PrPc and high level of MGr1-Ag/37LRP had the poorest prognosis. Multivariate survival analysis suggested that, along with other parameters, combined expression of PrPc and MGr1-Ag/37LRP was independent prognostic factors for GC patients. These data indicates that overexpression of PrPc, combined with MGr1-Ag/37LRP, is predictive of poor prognosis in GC and thereby could be used to guide the clinical decision.
Synthesis of novel N-phosphonoalkyl dipeptide inhibitors of human collagenase (1994)

The synthesis of a series of N-phosphonalkyl dipeptides 6 is described. Syntheses were devised that allowed the preparation of single diastereoisomers and the assignment of stereochemistry. The compounds were evaluated in vitro for their ability to inhibit the degradation of radiolabeled collagen by purified human lung fibroblast collagenase. Several of the compounds were potent collagenase inhibitors and were at least 10-fold more potent than their corresponding N-carboxyalkyl analogues. Activity was lost when the phosphonic acid group P(O)(OH)2 was replaced by the phosphinic acid groups P(O)(H)(OH) and P(O)(Me)(OH). At the P1 position, (R)- or (S)-alkyl groups, especially ethyl and methyl (e.g., 12a,b, 52a,b, and 53a,b), or an (R)-phenethyl moiety (55a) conferred high potency (IC50 values in the range 0.23-0.47 microM). (S)-Stereochemistry was preferred for the P1' isobutyl side chain. Structure-activity relationships were also investigated at the P2' site, and interestingly, compounds with basic side chains, such as the guanidine 57a, were equipotent with more lipophilic compounds, such as 52a. As with other series of collagenase inhibitors, potency was enhanced by introducing bicyclic aromatic P2' substituents. The most potent phosphonic acid of the series was the bicyclic aromatic P2' tryptophan analogue 59a (IC50 0.05 microM).
The Nephrotic Syndrome (1998)

The nephrotic syndrome is defined by a urinary protein level exceeding 3.5 g per 1.73 m2 of body-surface area per day. At the turn of the century, clinicians distinguished a nephritic syndrome of inflammatory origin and a nephrotic syndrome of presumed degenerative origin. Today these concepts are outmoded, but the term “nephrotic syndrome” is clinically useful and has persisted, because heavy proteinuria, irrespective of its origin, is associated with a spectrum of clinically important sequelae, particularly sodium retention, hyperlipoproteinemia, and thromboembolic and infectious complications. The definition given above is arbitrary, however, and special significance should not be given to the . . .
Crystallographic Identification of a Noncompetitive Inhibitor Binding Site on the Hepatitis C Virus NS5B RNA Polymerase Enzyme (2003)

The virus-encoded nonstructural protein 5B (NS5B) of hepatitis C virus (HCV) is an RNA-dependent RNA polymerase and is absolutely required for replication of the virus. NS5B exhibits significant differences from cellular polymerases and therefore has become an attractive target for anti-HCV therapy. Using a high-throughput screen, we discovered a novel NS5B inhibitor that binds to the enzyme noncompetitively with respect to nucleotide substrates. Here we report the crystal structure of NS5B complexed with this small molecule inhibitor. Unexpectedly, the inhibitor is bound within a narrow cleft on the protein's surface in the "thumb" domain, about 30 A from the enzyme's catalytic center. The interaction between this inhibitor and NS5B occurs without dramatic changes to the structure of the protein, and sequence analysis suggests that the binding site is conserved across known HCV genotypes. Possible mechanisms of inhibition include perturbation of protein dynamics, interference with RNA binding, and disruption of enzyme oligomerization.
Absorption of Antisense Oligonucleotides in Rat Intestine: Effect of Chemistry and Length (2000)

An in situ single-pass perfusion model was used to assess the effect of chemical modification and length on permeability and absorption of various oligonucleotides in rat intestine. Phosphorothioate oligodeoxynucleotides (PS-ODN) were compared with oligoribonucleotides with 2'-methoxyethyl (MOE) or 2'-O-methyl (OMe) modifications. A 25-mer PS-OMe-modified oligonucleotide showed relatively poor permeability in this model, as did unmodified 20-mer PS-ODN (permeability coefficient [P(eff)] = 2-8 X 10(-6)cm/sec). Modifying some or all of the oligonucleotides with 2'-MOE groups on deoxyribose and 5'-methylation of the cytosines substantially increased intestinal permeability of oligonucleotides. Both partially and fully modified PS-MOE oligonucleotides showed a (2-4)-fold increase in permeability as compared with unmodified PS-ODN. The presence of a phosphodiester backbone in MOE-modified compounds led to further increases in intestinal permeability. PS-MOE composed of 6, 8, 10, 12, 14, 16, 18, 20, and 22 nucleotides were also examined. It was found that the permeability of these oligonucleotides increased linearly with decreasing length.
High-Fidelity Readout in Circuit Quantum Electrodynamics Using the Jaynes-Cummings Nonlinearity (2010)

We demonstrate a qubit readout scheme that exploits the Jaynes-Cummings nonlinearity of a superconducting cavity coupled to transmon qubits. We find that, in the strongly driven dispersive regime of this system, there is the unexpected onset of a high-transmission "bright" state at a critical power which depends sensitively on the initial qubit state. A simple and robust measurement protocol exploiting this effect achieves a single-shot fidelity of 87% using a conventional sample design and experimental setup, and at least 61% fidelity to joint correlations of three qubits.
A Texas Trilogy: Seven Years in East Jesus (2004)

Everything is bigger in Texas. The chili is hotter, the beer is colder, and the stars are brighter. In fact, as a travel ad campaign informed us a few years back. Texas is really like 'a whole other country'. President George W. Bush not only proudly hails from Texas, his 'western Whitehouse' is located in Crawford, Texas, just a stone's throw from Waco, once the home of the Branch Davidians cult. As 'Dubya' clears brush and consolidates power all eyes, national and international, are often on Texas. Yes, things do seem to be bigger there. [ILLUSTRATION OMITTED] Seven Years in Jesus, a recent video by filmmaker and university professor Mary Slaughter, casts an outsider's gaze on Waco, Texas. A transplanted Californian, Slaughter spent seven years in Waco while teaching at Baylor University, and her subtle but critical eye has resulted in a piece that attempts to delve beneath the easy stereotypes that TV news soundbytes often relay of Texans. However, what is ultimately revealed does not comfort the viewer. Behind shirtsleeve patriotism and howdy ma'am vernacular Slaughter reveals an uncomfortable and sometimes frightening relationship between religion, violence, and intolerance. Seven Years in is structured as a trilogy with each of the three sections delineated by a title. Beginning in an impressionistic space, each succeeding section becomes more visually and philosophically concrete as the filmmaker moves through space, place, and ideology in an attempt to 'understand' this 'foreign country' she has landed in. Slaughter uses the elements of air, earth, water, and fire as organizing devices within and between the three sections. Section one, Where Grackles Swarm is an impressionistic rendering of the Texas landscape. As flocks of black birds swoop and converge, a parade of Texas icons marches across the screen. Manipulated shots of rodeo events, cowgirls, and midway rides depict an unsettling celebration in the making. A cryptic chorus of sound accompanies these series of visions while a swirling and undulating hot air balloon figure slowly inflates under the night sky. As in a waking dream, the viewer is initiated into a nocturnal world where once familiar things induce apprehension in the viewer, offering a premonition of the unsettling events to come. The title East Jesus appears signaling the start of section 2 of the trilogy as the night visions give way to daylight. is a local nickname for Waco and a Christian-themed message seems to meet inhabitants at every turn in the form of billboards, church signs, and media communications. The earth/air dichotomy is more concretely developed here as earth bound humans struggle to be worthy of a heaven bound Christ figure depicted as an enormous hot air balloon. …