gebhart/patrepeval huggingface dataset:
Quantitative Proteomics with siRNA Screening Identifies Novel Mechanisms of Trastuzumab Resistance in HER2 Amplified Breast Cancers (2012)

HER2 is a receptor tyrosine kinase that is overexpressed in 20% to 30% of human breast cancers and which affects patient prognosis and survival. Treatment of HER2-positive breast cancer with the monoclonal antibody trastuzumab (Herceptin) has improved patient survival, but the development of trastuzumab resistance is a major medical problem. Many of the known mechanisms of trastuzumab resistance cause changes in protein phosphorylation patterns, and therefore quantitative proteomics was used to examine phosphotyrosine signaling networks in trastuzumab-resistant cells. The model system used in this study was two pairs of trastuzumab-sensitive and -resistant breast cancer cell lines. Using stable isotope labeling, phosphotyrosine immunoprecipitations, and online TiO(2) chromatography utilizing a dual trap configuration, ~1700 proteins were quantified. Comparing quantified proteins between the two cell line pairs showed only a small number of common protein ratio changes, demonstrating heterogeneity in phosphotyrosine signaling networks across different trastuzumab-resistant cancers. Proteins showing significant increases in resistant versus sensitive cells were subjected to a focused siRNA screen to evaluate their functional relevance to trastuzumab resistance. The screen revealed proteins related to the Src kinase pathway, such as CDCP1/Trask, embryonal Fyn substrate, and Paxillin. We also identify several novel proteins that increased trastuzumab sensitivity in resistant cells when targeted by siRNAs, including FAM83A and MAPK1. These proteins may present targets for the development of clinical diagnostics or therapeutic strategies to guide the treatment of HER2+ breast cancer patients who develop trastuzumab resistance.
Elevated rectal temperature produced by all-night bright light is reversed by melatonin infusion in men (1991)

Early morning rectal body temperature is lowest when melatonin levels are highest in humans. Although pharmacological doses of melatonin are hypothermic in humans, the relationship between endogenous melatonin and temperature level has not been investigated. We measured rectal body temperature in nine normal men whose melatonin levels were suppressed by all-night sleep deprivation in bright light and compared values with those seen in sleep in the dark, sleep deprivation in dim light (to control for the stimulatory effect of wakefulness on temperature), and sleep deprivation in bright light with an infusion of exogenous melatonin that replicated endogenous levels. Minimum rectal temperature, calculated from smoothed temperature data from 2300 to 0515 h, was greater in bright-light sleep deprivation, resulting in suppression of melatonin, than in conditions of sleep deprivation in dim light or sleep in the dark. An exogenous melatonin infusion in bright light returned the minimum temperature to that seen in dim-light sleep deprivation. A nonsignificant elevation in mean and minimum temperature was noted in all conditions of sleep deprivation relative to sleep. We conclude that melatonin secretion contributes to the lowering of core body temperature seen in the early morning in humans.
Cell-mediated immunity in aged mice: an underlying lesion in IL 2 synthesis. (1982)

It is well established that immune potential declines with age and that aged animals are unable to mount vigorous cell-mediated immune responses. Production of the lymphokine, Interleukin 2 (IL 2) in response to the T cell mitogen concanavalin A or allogeneic stimulation is also diminished in aged individuals. This lesion in IL 2 synthesis in aged mice underlies their deficiency in cell-mediated responses. Mixed lymphocyte responses, cell-mediated lympholysis, and antigen-induced T cell proliferation are all markedly enhanced by supplementation with this lymphokine.
Learning Monocular Depth by Distilling Cross-domain Stereo Networks (2018)

Monocular depth estimation aims at estimating a pixelwise depth map for a single image, which has wide applications in scene understanding and autonomous driving. Existing supervised and unsupervised methods face great challenges. Supervised methods require large amounts of depth measurement data, which are generally difficult to obtain, while unsupervised methods are usually limited in estimation accuracy. Synthetic data generated by graphics engines provide a possible solution for collecting large amounts of depth data. However, the large domain gaps between synthetic and realistic data make directly training with them challenging. In this paper, we propose to use the stereo matching network as a proxy to learn depth from synthetic data and use predicted stereo disparity maps for supervising the monocular depth estimation network. Cross-domain synthetic data could be fully utilized in this novel framework. Different strategies are proposed to ensure learned depth perception capability well transferred across different domains. Our extensive experiments show state-of-the-art results of monocular depth estimation on KITTI dataset.
Co-planar stereotaxic atlas of the human brain : 3-dimensional proportional system : an approach to cerebral imaging (1988)

Collectively, these studies indicate the value of utilizing MAbs for identifying and characterizing functionally significant ZP determinants. MAbs recognizing sequential epitopes will help in the elucidation of the amino acid sequence of the epitopes, which will subsequently help in design of synthetic immunocontraceptive vaccines.
Crystal structure prediction of organic pigments: quinacridone as an example (2007)

The structures of the alpha, beta and gamma polymorphs of quinacridone (Pigment Violet 19) were predicted using Polymorph Predictor software in combination with X-ray powder diffraction patterns of limited quality. After generation and energy minimization of the possible structures, their powder patterns were compared with the experimental ones. On this basis, candidate structures for the polymorphs were chosen from the list of all structures. Rietveld refinement was used to validate the choice of structures. The predicted structure of the gamma polymorph is in accordance with the experimental structure published previously. Three possible structures for the beta polymorph are proposed on the basis of X-ray powder patterns comparison. It is shown that the alpha structure in the Cambridge Structural Database is likely to be in error, and a new alpha structure is proposed. The present work demonstrates a method to obtain crystal structures of industrially important pigments when only a low-quality X-ray powder diffraction pattern is available.
Inhibition of cell growth by lovastatin is independent of ras function. (1991)

We have investigated the inhibition of cell growth by lovastatin (previously known as mevinolin), an antagonist of hydroxymethylglutaryl coenzyme A reductase which blocks the processing and membrane localization of ras proteins via inhibition of polyisoprenylation. A series of NIH 3T3 cells transformed by oncogenes with activities that are dependent or independent of isoprenylated ras were studied, including cells transformed by myristylated ras protein that is isoprenylation independent. Treatment with lovastatin at concentrations ranging from 5 to 15 microM for up to 96 h resulted in a time- and dose-dependent inhibition of cell growth in all lines tested. The inhibition ranged from 25 to 50% when cells were treated with 5 microM lovastatin for 48 h, to 72-90% for cells treated with 15 microM lovastatin for 96 h. Cells transformed by c-ras, v-ras, v-src, v-raf, and the myristylated ras genes displayed similar sensitivities; the parental NIH 3T3 line was the most resistant of the lines tested. Metabolic labeling of control and lovastatin-treated cells with [35S]methionine or tritiated lipids revealed that 15 microM lovastatin blocked the processing of both endogenous ras and v-ras proteins yet had no effect on the lipidation of myristylated ras proteins. Addition of 300 microM mevalonic acid overcame the inhibition induced by 15 microM lovastatin. Thus the inhibition of cell growth in vitro by lovastatin did not show specificity for cells the transformation of which is dependent upon isoprenylated ras protein. It is therefore likely that the inhibition of other pathways affected by lovastatin, such as cholesterol biosynthesis or the processing of other cellular proteins, are responsible for the growth inhibition by lovastatin.
Tachykinins and Their Receptors: Contributions to Physiological Control and the Mechanisms of Disease (2014)

The tachykinins, exemplified by substance P, are one of the most intensively studied neuropeptide families. They comprise a series of structurally related peptides that derive from alternate processing of three Tac genes and are expressed throughout the nervous and immune systems. Tachykinins interact with three neurokinin G protein-coupled receptors. The signaling, trafficking, and regulation of neurokinin receptors have also been topics of intense study. Tachykinins participate in important physiological processes in the nervous, immune, gastrointestinal, respiratory, urogenital, and dermal systems, including inflammation, nociception, smooth muscle contractility, epithelial secretion, and proliferation. They contribute to multiple diseases processes, including acute and chronic inflammation and pain, fibrosis, affective and addictive disorders, functional disorders of the intestine and urinary bladder, infection, and cancer. Neurokinin receptor antagonists are selective, potent, and show efficacy in models of disease. In clinical trials there is a singular success: neurokinin 1 receptor antagonists to treat nausea and vomiting. New information about the involvement of tachykinins in infection, fibrosis, and pruritus justifies further trials. A deeper understanding of disease mechanisms is required for the development of more predictive experimental models, and for the design and interpretation of clinical trials. Knowledge of neurokinin receptor structure, and the development of targeting strategies to disrupt disease-relevant subcellular signaling of neurokinin receptors, may refine the next generation of neurokinin receptor antagonists.
A mouse model of severe von Willebrand disease: Defects in hemostasis and thrombosis (1998)

von Willebrand factor (vWf) deficiency causes severe von Willebrand disease in humans. We generated a mouse model for this disease by using gene targeting. vWf-deficient mice appeared normal at birth; they were viable and fertile. Neither vWf nor vWf propolypeptide (von Willebrand antigen II) were detectable in plasma, platelets, or endothelial cells of the homozygous mutant mice. The mutant mice exhibited defects in hemostasis with a highly prolonged bleeding time and spontaneous bleeding events in approximately 10% of neonates. As in the human disease, the factor VIII level in these mice was reduced strongly as a result of the lack of protection provided by vWf. Defective thrombosis in mutant mice was also evident in an in vivo model of vascular injury. In this model, the exteriorized mesentery was superfused with ferric chloride and the accumulation of fluorescently labeled platelets was observed by intravital microscopy. We conclude that these mice very closely mimic severe human von Willebrand disease and will be very useful for investigating the role of vWf in normal physiology and in disease models.
Activating Mutations ofc-Kitat Codon 816 Confer Drug Resistance in Human Leukemia Cells (2001)

An improved understanding of how leukemia cells grow and become resistant to treatment remains critical for developing more effective therapies. We have identified activating mutations of c-kit at codon 816 (Asp(816) ) from a revertant of the cytokine-dependent acute myeloid leukemia (AML) cell line, MO7e (D816H), and de novo childhood AML (D816N). Following transduction of the mutant c-kit cDNAs, MO7e cells acquire a growth advantage and resistance to apoptosis in response to chemotherapeutic drugs and ionizing radiation, in addition to cytokine-independent survival. Although stimulation of mutant c-kit-bearing MO7e cells with stem cell factor (SCF), a ligand for c-Kit, does not have a significant effect on cell proliferation, SCF further inhibits apoptosis induced by cytotoxic agents. These results suggest a potentially important role of Asp(816) mutations of c-kit in both malignant cell proliferation and resistance to therapy.
Proton nuclear magnetic resonance study on the dynamics of the conformation of the hinge segment of human G1 immunoglobulin (1985)

A proton nuclear magnetic resonance (NMR) study is reported for the dynamics of the conformation of the hinge segment of human G1 immunoglobulin. The hinge fragment (Thr223-His-Thr-Cys-Pro-Pro-Cys-Pro-Ala-Pro-Glu-Leu234)2 was obtained by tryptic digestion of F(ab')2, a peptic fragment of IgG1. Comparisons of the NMR results obtained for the hinge fragment with those for the intact IgG1 and its fragments led us to conclude that a significant change in conformation of the segment preceding the disulfide-linked Cys-Pro-Pro-Cys core is induced when the Fab portion is cleaved off and the presence or absence of the Fc portion affects very little, if any, of the conformation of this part of the hinge. On the basis of the present NMR results along with those which we have obtained previously using the intact IgG1 and its fragments, it was concluded that the conformation of the segment preceding the Cys-Pro-Pro-Cys core of the intact IgG1 can be maintained only when it is flanked by the Fab portion and the Cys-Pro-Pro-Cys core. An X-ray crystallographic study [Marquart, M., Deisenhofer, J., Huber, R., & Palm, W. (1980) J. Mol. Biol. 141, 369-392] showed that segment Cys-220-Thr-225 forms a one-turn helix with little inherent stability. Upon loss of Fab or Fc, residual segments of the hinge would become too short to form the helix.(ABSTRACT TRUNCATED AT 250 WORDS)
SEMICONDUCTOR WAFER BONDING (1998)

▪ Abstract When mirror-polished, flat, and clean wafers of almost any material are brought into contact at room temperature, they are locally attracted to each other by van der Waals forces and adhere or bond. This phenomenon is referred to as wafer bonding. The most prominent applications of wafer bonding are silicon-on-insulator (SOI) devices, silicon-based sensors and actuators, as well as optical devices. The basics of wafer-bonding technology are described, including microcleanroom approaches, prevention of interface bubbles, bonding of III-V compounds, low-temperature bonding, ultra-high vacuum bonding, thinning methods such as smart-cut procedures, and twist wafer bonding for compliant substrates. Wafer bonding allows a new degree of freedom in design and fabrication of material combinations that previously would have been excluded because these material combinations cannot be realized by the conventional approach of epitaxial growth.
CCL19 induces rapid dendritic extension of murine dendritic cells (2002)

Dendritic cells (DCs) possess numerous dendrites that may be of great advantage to interaction with T cells. However, it has been poorly understood how the dendritic morphology of a DC is controlled. In the present study, using a murine spleen-derived DC line, we analyzed effects of CCR7 ligands, CCL19 and CCL21, on dendritic morphology. Mature DCs, but not immature DCs, showed vigorous migration to either CCL19 or CCL21. CCL19 also rapidly (within 30 minutes) induced marked extension of dendrites of mature DCs that was maintained at least for 24 hours. On the other hand, CCL21 failed to induce rapid dendritic extension, even though a modest dendritic extension of mature DCs, compared to that by CCL19, was induced 8 or 24 hours after treatment with CCL21. In addition, pretreatment with a high concentration of CCL21 significantly inhibited the rapid dendritic extension induced by CCL19. Thus, it is suggested that CCL19 and CCL21 exert agonistic and antagonistic influences on the initiation of dendritic extension of mature DCs. The CCL19-induced morphologic changes were completely blocked by Clostridium difficile toxin B that inhibits Rho guanosine triphosphatase proteins such as Rho, Rac, and Cdc42, but not by Y-27632, a specific inhibitor for Rho-associated kinase. These findings suggest that Rac or Cdc42 (or both), but not Rho, are involved in the CCL19-induced dendritic extension of mature DCs.
Evaluation of a new antacid, almagate. (1984)

Almagate (Al2Mg6(OH)14(CO3)2 X 4 H2O, Almax), a crystalline hydrated aluminium-magnesium hydroxycarbonate, was compared with a number of other known antacids in a battery of tests designed to demonstrate the properties of an ideal antacid. In dynamic tests for measurement of velocity of neutralization, total acid consuming capacity and duration of activity, almagate like other crystalline aluminium magnesium hydroxide derivatives such as hydrotalcite and magaldrate was rapidly acting, neutralized a high proportion of its theoretical acid consumption and maintained gastric pH between 3 and 5 for a prolonged period of time. It was more active than these two substances in respect of rapidity of action and did not lose antacid activity as the pH was raised. Like these compounds it had considerable advantages over the amorphous gels and co-gels of aluminium and magnesium hydroxides or hydroxycarbonates in respect of both rapidity of action and acid consuming capacity. It inhibited the activity of pepsin and was shown to adsorb bile acids and had a low sodium content.
A New Dataset and Method for Automatically Grading ESOL Texts (2011)

We demonstrate how supervised discriminative machine learning techniques can be used to automate the assessment of ‘English as a Second or Other Language ’ (ESOL) examination scripts. In particular, we use rank preference learning to explicitly model the grade relationships between scripts. A number of different features are extracted and ablation tests are used to investigate their contribution to overall performance. A comparison between regression and rank preference models further supports our method. Experimental results on the first publically available dataset show that our system can achieve levels of performance close to the upper bound for the task, as defined by the agreement between human examiners on the same corpus. Finally, using a set of ‘outlier ’ texts, we test the validity of our model and identify cases where the model’s scores diverge from that of a human examiner. 1
Randomized Comparison of Surveillance Intervals after Colonoscopic Removal of Newly Diagnosed Adenomatous Polyps (1993)

Colonoscopy performed three years after colonoscopic removal of adenomatous polyps detects important colonic lesions as effectively as follow-up colonoscopy after both one and three years. An interval of at least three years is recommended before follow-up colonoscopy after both one and three years. An interval of at least three years is recommended before follow-up examination after colonoscopic removal of newly diagnosed adenomatous polyps. Adoption of this recommendation nationally should reduce the cost of post-polypectomy surveillance and screening.
Treating Cancer by Targeting a Weakness (2005)

Most targeted therapies for cancer are designed to bind a specific protein expressed by cancer cells. Two recent studies indicate that a new approach may work: attacking a tumor at its weak spot.
Chronic blockade of cannabinoid CB2receptors induces anxiolytic‐like actions associated with alterations in GABAAreceptors (2011)

The opposing behavioural and molecular changes observed after chronic treatment with AM630 or JWH133 support the key role of CB(2) receptors in the regulation of anxiety. Indeed, the efficacy of AM630 in reducing the anxiety of the spontaneously anxious DBA/2 strain of mice strengthens the potential of the CB(2) receptor as a new target in the treatment of anxiety-related disorders.
Bioinspired Reversible Interlocker Using Regularly Arrayed High Aspect‐Ratio Polymer Fibers (2011)

A reversible interlocker that is inspired by the wing locking device of beetles is presented. It exploits the van der Waals force-assisted binding between high-aspect-ratio polymer fibers. The two-layered interlocker is highly flexible and displays an extremely high shear locking force and easy normal lift-off.
Inhibition of E2F Abrogates the Development of Cardiac Myocyte Hypertrophy (2003)

Growth of the post-natal mammalian heart occurs primarily by cardiac myocyte hypertrophy. Previously, we and others have shown that a partial re-activation of the cell cycle machinery occurs in myocytes undergoing hypertrophy such that cells progress through the G1/S transition. In this study, we have examined the regulation of the E2F family of transcription factors that are crucial for the G1/S phase transition during normal cardiac development and the development of myocyte hypertrophy in the rat. Thus, mRNA and protein levels of E2F-1, 3, and 4 and DP-1 and DP-2 were down-regulated during development to undetectable levels in adult myocytes. Interestingly, E2F-5 protein levels were substantially up-regulated during development. In contrast, an induction of E2F-1, 3, and 4 and the DP-1 protein was observed during the development of myocyte hypertrophy in neonatal myocytes treated with serum or phenylephrine, whereas the protein levels of E2F-5 were decreased with serum stimulation. E2F activity, as measured by a cyclin E promoter luciferase assay and E2F-DNA binding activity, increased significantly during the development of hypertrophy with serum and phenylephrine compared with non-stimulated cells. Inhibiting E2F activity with a specific peptide that blocks E2F-DP heterodimerization prevented the induction of hypertrophic markers (atrial natriuretic factor and brain natriuretic peptide) in response to serum and phenylephrine, reduced the increase in myocyte size, and inhibited protein synthesis in stimulated cells. Thus, we have shown that the inhibition of E2F function prevents the development of hypertrophy. Targeting E2F function might be a useful approach for treating diseases that cause pathophysiological hypertrophic growth.
Cutting Edge: NKT Cell Development Is Selectively Impaired in Fyn- Deficient Mice (1999)

Most NK1.1+ T (NKT) cells express a biased TCRalphabeta repertoire that is positively selected by the monomorphic MHC class I-like molecule CD1d. The development of CD1d-dependent NKT cells is thymus dependent but, in contrast to conventional T cells, requires positive selection by cells of hemopoietic origin. Here, we show that the Src protein tyrosine kinase Fyn is required for development of CD1d-dependent NKT cells but not for the development of conventional T cells. In contrast, another Src kinase, Lck, is required for the development of both NKT and T cells. Impaired NKT cell development in Fyn-deficient mice cannot be rescued by transgenic expression of CD8, which is believed to increase the avidity of CD1d recognition by NKT cells. Taken together, our data reveal a selective and nonredundant role for Fyn in NKT cell development.
The goubau multi element monopole antenna - revisited (2007)

Several top loaded monopole antennas leading to the Goubau multi element configuration are investigated. Their input impedance, bandwidth, and radiation pattern characteristics obtained using full-wave simulators, are discussed in detail.
Nutritional implications of the use of frusemide in older people (2006)

Furosemide is a common inclusion in medication regimens of older people but it has specific nutritional implications. Some of the effects of furosemide on nutritional health are summarised. (non- author abstract)