gebhart/patrepeval huggingface dataset:
SERPINB1 upregulation is associated with in vivo complex formation with neutrophil elastase and cathepsin G in a baboon model of bronchopulmonary dysplasia (2006)

Bronchopulmonary dysplasia (BPD) continues to be a major cause of morbidity in premature infants. An imbalance between neutrophil elastase and its inhibitors has been implicated in BPD. Serine protease inhibitor (SERPIN)B1 is an inhibitor of neutrophil proteases, including neutrophil elastase (NE) and cathepsin G (cat G). Recent studies suggest that SERPINB1 could provide protection in the airways by regulating excess protease activity associated with inflammatory lung disorders. In this study, we determined the distribution and ontogeny of SERPINB1 in the baboon lung and characterized the expression of SERPINB1 in baboon models of BPD. SERPINB1 expression was detected in the conducting airway and glandular epithelial cells in addition to neutrophils, macrophages, and mast cells. SERPINB1 mRNA and protein expression increased with advancing gestational age and in the new BPD model. In contrast, SERPINB1 expression levels were decreased in the old BPD model. Furthermore, SERPINB1 was detected as a high-molecular-mass (HMM) complex in lung tissue and bronchoalveolar lavage fluid samples from the BPD group. Analysis of the HMM complex by coimmunoprecipitation showed that these complexes were formed between SERPINB1 and NE or cat G. High-performance liquid chromatography (HPLC) ion trap mass spectrometry verified the presence of SERPINB1 in HMM complexes. Finally, NE activity level was compared between new and old baboon models of BPD and was found to be significantly lower in new BPD. Thus SERPINB1 upregulation in new BPD may be protective by contributing to the regulation of neutrophil proteases NE and cat G.
PIM-1–specific mAb suppresses human and mouse tumor growth by decreasing PIM-1 levels, reducing Akt phosphorylation, and activating apoptosis (2009)

Provirus integration site for Moloney murine leukemia virus (PIM1) is a proto-oncogene that encodes a serine/threonine kinase with multiple cellular functions. Overexpression of PIM-1 plays a critical role in progression of prostatic and hematopoietic malignancies. Here we describe the generation of a mAb specific for GST-PIM-1, which reacted strongly with most human and mouse cancer tissues and cell lines of prostate, breast, and colon origin but only weakly (if at all) with normal tissues. The mAb binds to PIM-1 in the cytosol and nucleus as well as to PIM-1 on the surface of human and murine cancer cells. Treatment of human and mouse prostate cancer cell lines with the PIM-1-specific mAb resulted in disruption of PIM-1/Hsp90 complexes, decreased PIM-1 and Hsp90 levels, reduced Akt phosphorylation at Ser473, reduced phosphorylation of Bad at Ser112 and Ser136, and increased cleavage of caspase-9, an indicator of activation of the mitochondrial cell death pathway. The mAb induced cancer cell apoptosis and synergistically enhanced antitumor activity when used in combination with cisplatin and epirubicin. In tumor models, the PIM-1-specific mAb substantially inhibited growth of the human prostate cancer cell line DU145 in SCID mice and the mouse prostate cancer cell TRAMP-C1 in C57BL/6 mice. These findings are important because they provide what we believe to be the first in vivo evidence that treatment of prostate cancer may be possible by targeting PIM-1 using an Ab-based therapy.
Internet quarantine: requirements for containing self-propagating code (2004)

It has been clear since 1988 that self-propagating code can quickly spread across a network by exploiting homogeneous security vulnerabilities. However, the last few years have seen a dramatic increase in the frequency and virulence of such "worm" outbreaks. For example, the Code-Red worm epidemics of 2001 infected hundreds of thousands of Internet hosts in a very short period - incurring enormous operational expense to track down, contain, and repair each infected machine. In response to this threat, there is considerable effort focused on developing technical means for detecting and containing worm infections before they can cause such damage. This paper does not propose a particular technology to address this problem, but instead focuses on a more basic question: How well will any such approach contain a worm epidemic on the Internet? We describe the design space of worm containment systems using three key parameters - reaction time, containment strategy and deployment scenario. Using a combination of analytic modeling and simulation, we describe how each of these design factors impacts the dynamics of a worm epidemic and, conversely, the minimum engineering requirements necessary to contain the spread of a given worm. While our analysis cannot provide definitive guidance for engineering defenses against all future threats, we demonstrate the lower bounds that any such system must exceed to be useful today. Unfortunately, our results suggest that there are significant technological and administrative gaps to be bridged before an effective defense can be provided in today's Internet.
A purified population of multipotent cardiovascular progenitors derived from primate pluripotent stem cells engrafts in postmyocardial infarcted nonhuman primates (2010)

Cell therapy holds promise for tissue regeneration, including in individuals with advanced heart failure. However, treatment of heart disease with bone marrow cells and skeletal muscle progenitors has had only marginal positive benefits in clinical trials, perhaps because adult stem cells have limited plasticity. The identification, among human pluripotent stem cells, of early cardiovascular cell progenitors required for the development of the first cardiac lineage would shed light on human cardiogenesis and might pave the way for cell therapy for cardiac degenerative diseases. Here, we report the isolation of an early population of cardiovascular progenitors, characterized by expression of OCT4, stage-specific embryonic antigen 1 (SSEA-1), and mesoderm posterior 1 (MESP1), derived from human pluripotent stem cells treated with the cardiogenic morphogen BMP2. This progenitor population was multipotential and able to generate cardiomyocytes as well as smooth muscle and endothelial cells. When transplanted into the infarcted myocardium of immunosuppressed nonhuman primates, an SSEA-1+ progenitor population derived from Rhesus embryonic stem cells differentiated into ventricular myocytes and reconstituted 20% of the scar tissue. Notably, primates transplanted with an unpurified population of cardiac-committed cells, which included SSEA-1- cells, developed teratomas in the scar tissue, whereas those transplanted with purified SSEA-1+ cells did not. We therefore believe that the SSEA-1+ progenitors that we have described here have the potential to be used in cardiac regenerative medicine.
In Activated Mast Cells, IL-1 Up-Regulates the Production of Several Th2-Related Cytokines Including IL-9 (2000)

Mast cells can play detrimental roles in the pathophysiology and mortality observed in anaphylaxis and other Th2-dominated allergic diseases. In contrast, these cells contribute to protective host defense mechanisms against parasitic worm infections. After IgE/Ag activation, mast cells can produce multiple cytokines that may enhance allergic inflammations, while a similar panel of Th2-related cytokines may support immunological strategies against parasites. Here we report that in primary mouse bone marrow-derived mast cells activated by ionomycin or IgE/Ag, the proinflammatory mediator IL-1 (alpha or beta) up-regulated production of IL-3, IL-5, IL-6, and IL-9 as well as TNF, i.e., cytokines implicated in many inflammatory processes including those associated with allergies and helminthic infections. IL-1 did not induce significant cytokine release in the absence of ionomycin or IgE/Ag, suggesting that Ca-dependent signaling was required. IL-1-mediated enhancement of cytokine expression was confirmed at the mRNA level by Northern blot and/or RT-PCR analysis. Our study reveals a role for IL-1 in the up-regulation of multiple mast cell-derived cytokines. Moreover, we identify mast cells as a novel source of IL-9. These results are of particular importance in the light of recent reports that strongly support a central role of IL-9 in allergic lung inflammation and in host defense against worm infections.
Microbial Conversion Products of Leptomycin B (1998)

Leptomycin B (LMB), a secondary metabolite produced by Streptomyces sp. strain ATS 1287, with known antifungal and antitumor effects, inhibits the nucleo-cytoplasmic translocation of the human immunodeficiency virus type 1 regulatory protein Rev and exhibits significant antiproliferative activity. Since LMB itself turned out to be distinctly cytotoxic, a bioconversion screening with a selected set of 29 bacterial and 72 fungal strains was performed in order to obtain metabolites of LMB with reduced antiproliferative effects. Several derivatives of LMB, more polar than the parent compound and produced in yields of > 5%, were detected. Liquid chromatography-mass spectroscopy analysis indicated the type of bioconversion. Fermentations (1-liter scale) of those strains with high rates of transformation were suitable for isolation and characterization of the most prominent metabolites. Thus, bioconversion of LMB with Aspergillus flavus ATCC 9170 and Emericella unguis ATCC 13431 served for isolation of the novel derivatives 26-hydroxy-LMB (30% was the concentration of the metabolite [with respect to LMB] used for bioconversion) and LMB-24-glutaminamide (90%), respectively. Streptomyces rimosus ATCC 28893 converted LMB into 4,11-dihydroxy-LMB (13%) and 2,3-dihydro-LMB (55%). Although the antiproliferative effects of the LMB metabolites could be reduced through microbial conversion, none of these metabolites inhibited the nuclear export of Rev better than LMB itself.
Extracting causal relations on HIV drug resistance from literature (2010)

The proposed relation extraction and combination method has a good performance on extracting HIV drug resistance data. It can be used in large-scale relation extraction experiments. The developed methods can also be applied to extract other type of relations such as gene-protein, gene-disease, and disease-mutation.
Structural relations between collagen and mineral in bone as determined by high voltage electron microscopic tomography (1996)

Aspects of the ultrastructural interaction between collagen and mineral crystals in embryonic chick bone have been examined by the novel technique of high voltage electron microscopic tomography to obtain three-dimensional information concerning extracellular calcification in this tissue. Newly mineralizing osteoid along periosteal surfaces of mid-diaphyseal regions from normal chick tibiae was embedded, cut into 0.25 microns thick sections, and documented at 1.0 MV in the Albany AEI-EM7 high voltage electron microscope. The areas of the tissue studied contained electron dense mineral crystals associated with collagen fibrils, some marked by crystals disposed along their cylindrically shaped lengths. Tomographic reconstructions of one site with two mineralizing fibrils were computed from a 5 degrees tilt series of micrographs over a +/- 60 degrees range. Reconstructions showed that the mineral crystals were platelets of irregular shape. Their sizes were variable, measured here up to 80 x 30 x 8 nm in length, width, and thickness, respectively. The longest crystal dimension, corresponding to the c-axis crystallographically, was generally parallel to the collagen fibril long axis. Individual crystals were oriented parallel to one another in each fibril examined. They were also parallel in the neighboring but apparently spatially separate fibrils. Crystals were periodically (approximately 67 nm repeat distance) arranged along the fibrils and their location appeared to correspond to collagen hole and overlap zones defined by geometrical imaging techniques. The crystals appeared to be continuously distributed along a fibril, their size and number increasing in a tapered fashion from a relatively narrow tip containing smaller and infrequent crystals to wider regions having more densely packed and larger crystals. Defined for the first time by direct visual 3D imaging, these data describe the size, shape, location, orientation, and development of early crystals in normal bone collagen. The results suggest that platelet-shaped crystals are arranged in channels or grooves which are formed by collagen hole zones in register and that crystal sizes may exceed the dimensions of hole zones. Such data agree with those from mineral-matrix interaction in normally calcifying avian tendon obtained by similar high voltage tomographic means, but in addition they indicate a possible gradual and continuous deposition of crystals in collagen of bone unlike tendon and imply that individual collagen fibrils in local regions of osteoid are organized such that they all may be aligned in a coherent manner.
Maintenance of Response Readiness in Patients With Parkinson's Disease: Evidence From a Simple Reaction Time Task. (2005)

The authors explored the effect of Parkinson's disease (PD) on the generation and maintenance of response readiness in a simple reaction time task. They compared performance of idiopathic PD patients without dementia, age-matched controls, and younger controls over short (1-, 3-, and 6-s) and long (12- and 18-s) foreperiod intervals. After each trial, the authors probed memory for visual information that also had to be maintained during the trial interval. Patients and controls did not differ overall in their ability to maintain readiness over long delays. However, within the PD group only, errors in maintaining visual information were correlated with difficulty in maintaining readiness, suggesting that systems impaired in PD may facilitate the maintenance of processing in both motor and cognitive domains.
Spontaneous Feline Mammary Carcinoma Is a Model of HER2 Overexpressing Poor Prognosis Human Breast Cancer (2005)

Companion animal spontaneous tumors are suitable models for human cancer, primarily because both animal population and the tumors are genetically heterogeneous. Feline mammary carcinoma (FMC) is a highly aggressive, mainly hormone receptor-negative cancer, which has been proposed as a model for poor prognosis human breast cancer. We have identified and studied the feline orthologue of the HER2 gene, which is both an important prognostic marker and therapeutic target in human cancer. Feline HER2 (f-HER2) gene kinase domain is 92% similar to the human HER2 kinase. F-HER2-specific mRNA was found 3- to 18-fold increased in 3 of 3 FMC cell lines, in 1 of 4 mammary adenomas and 6 of 11 FMC samples using quantitative reverse transcription-PCR. Western blot showed that an anti-human HER2 antibody recognized a protein comigrating with the human p185HER2 in FMC cell lines. The same antibodies strongly stained 13 of 36 FMC archival samples. These data show that feline HER2 overexpression qualifies FMC as homologous to the subset of HER2 overexpressing, poor prognosis human breast carcinomas and as a suitable model to test innovative approaches to therapy of aggressive tumors.
Membership Inference Attacks Against Machine Learning Models (2017)

We quantitatively investigate how machine learning models leak information about the individual data records on which they were trained. We focus on the basic membership inference attack: given a data record and black-box access to a model, determine if the record was in the model's training dataset. To perform membership inference against a target model, we make adversarial use of machine learning and train our own inference model to recognize differences in the target model's predictions on the inputs that it trained on versus the inputs that it did not train on. We empirically evaluate our inference techniques on classification models trained by commercial "machine learning as a service" providers such as Google and Amazon. Using realistic datasets and classification tasks, including a hospital discharge dataset whose membership is sensitive from the privacy perspective, we show that these models can be vulnerable to membership inference attacks. We then investigate the factors that influence this leakage and evaluate mitigation strategies.
Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer (2009)

MicroRNA (miRNA) opens up a new field for molecular diagnosis of cancer. However, the role of circulating miRNAs in plasma/serum in cancer diagnosis is not clear. The aim of this study was to investigate whether plasma miRNAs can be used as biomarkers for the early detection of colorectal carcinoma (CRC). We measured the levels of 12 miRNAs (miR-134, -146a, -17-3p, -181d, -191, -221, -222, -223, -25, -29a, -320a and -92a) in plasma samples from patients with advanced colorectal neoplasia (carcinomas and advanced adenomas) and healthy controls using real-time RT-PCR. We found that plasma miR-29a and miR-92a have significant diagnostic value for advanced neoplasia. MiR-29a yielded an AUC (the areas under the ROC curve) of 0.844 and miR-92a yielded an AUC of 0.838 in discriminating CRC from controls. More importantly, these 2 miRNAs also could discriminate advanced adenomas from controls and yielded an AUC of 0.769 for miR-29a and 0.749 for miR-92a. Combined ROC analyses using these 2 miRNAs revealed an elevated AUC of 0.883 with 83.0% sensitivity and 84.7% specificity in discriminating CRC, and AUC of 0.773 with 73.0% sensitivity and 79.7% specificity in discriminating advanced adenomas. Collectively, these data suggest that plasma miR-29a and miR-92a have strong potential as novel noninvasive biomarkers for early detection of CRC.
Pharmacodynamic characterization of chemopreventive triterpenoids as exceptionally potent inducers of Nrf2-regulated genes (2007)

Synthetic triterpenoids have been developed, which are potent inducers of cytoprotective enzymes and inhibitors of inflammation, greatly improving on the weak activity of naturally occurring triterpenoids. An imidazolide triterpenoid derivative, 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im or TP235), has been previously shown to potently protect against hepatic tumorigenesis, acting in part by inducing cytoprotective genes through Keap1-Nrf2-antioxidant response element (ARE) signaling. In these studies, the pharmacodynamic activity of CDDO-Im is characterized in two distinct lines of ARE reporter mice and by measuring increases in Nqo1 transcript levels as a marker of cytoprotective gene induction. Oral administration of CDDO-Im induces ARE-regulated cytoprotective genes in many tissues in the mouse, including liver, lung, kidney, intestines, brain, heart, thymus, and salivary gland. CDDO-Im induces Nqo1 RNA transcripts in some organs at doses as low as 0.3 mumol/kg body weight (orally). A structure activity evaluation of 15 additional triterpenoids (a) confirmed the importance of Michael acceptor groups on both the A and C rings, (b) showed the requirement for a nitrile group at C-2 of the A ring, and (c) indicated that substituents at C-17 dramatically affected pharmacodynamic action in vivo. In addition to CDDO-Im, other triterpenoids, particularly the methyl ester CDDO-Me (TP155) and the dinitrile TP225, are extremely potent inducers of cytoprotective genes in mouse liver, lung, small intestine mucosa, and cerebral cortex. This pharmacodynamic characterization highlights the chemopreventive promise of several synthetic triterpenoids in multiple target organs.
Chemical applications of scanning tunneling microscopy (1986)

The development of a scanning tunneling microscope at the California Institute of Technology is well under way. Electron tunneling has been demonstrated, and preliminary surface images of gold films have been obtained. Additional instrumental development is required to achieve the atomic resolution which is required for the study of chemical processes on surfaces. A theoretical model is also being developed for the study of tunneling of electrons from the probe to surfaces with molecular species adsorbed, and with atomic and molecular species intervening between the probe and the surface. These experimental tools and theoretical models, which are being developed concurrently, will be applied to the study of chemical systems and processes on surfaces. Some of the first molecular species for study will include benzene and pyridine on metal surfaces, and porphyrins and phthalocyanines on pyrolytic graphite. The applications that can be imagined for STM in surface chemistry are very broad, and the choice of additional systems for study will be based on the results of these initial experiments.
Adhesion and permeability of polyimide–clay nanocomposite films for protective coatings (2003)

Abstract A polyimide (PI)–clay nanocomposite was prepared from a solution of poly(amic acid), a precursor of 2,2‐bis[4‐(3,4‐dicarboxyphenoxy)phenyl]propane dianhydride and p ‐phenylenediamine, and dodecylamine–montmorillonite. Fourier transform infrared spectroscopy, thermogravimetric analysis, X‐ray diffraction, and atomic absorption spectroscopy were used to verify the incorporation of the modifying agents into the clay structure and the intercalation of the modified clay into the PI matrix. Both PI and PI–clay films were subsequently prepared by solution casting. The gas permeability, resistivity, and adhesion properties were determined. In the case of gas permeability, only a 3 wt % addition of clay reduced oxygen permeability to less than half that of unfilled PI. Furthermore, this hybrid showed an improvement in electrical resistivity because of the prevention of electrical tree growth by clay particles. More importantly, adhesion between the films and silicon increased with increasing clay content. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 2875–2881, 2003
Deep learning microscopy (2017)

We demonstrate that a deep neural network can significantly improve optical microscopy, enhancing its spatial resolution over a large field of view and depth of field. After its training, the only input to this network is an image acquired using a regular optical microscope, without any changes to its design. We blindly tested this deep learning approach using various tissue samples that are imaged with low-resolution and wide-field systems, where the network rapidly outputs an image with better resolution, matching the performance of higher numerical aperture lenses and also significantly surpassing their limited field of view and depth of field. These results are significant for various fields that use microscopy tools, including, e.g., life sciences, where optical microscopy is considered as one of the most widely used and deployed techniques. Beyond such applications, the presented approach might be applicable to other imaging modalities, also spanning different parts of the electromagnetic spectrum, and can be used to design computational imagers that get better as they continue to image specimens and establish new transformations among different modes of imaging.
Ultrafast and High Sensitive UV/IR Photodetector Based on a Single SnO 2 Nanowire (2014)

Tin oxide, SnO2 has potential applications in many research areas. Using a chemical vapor deposition CVD method, high-quality single crystalline SnO2 nanowire (NW) was synthesized on a large scale. Individual SnO2 nanowire based ultraviolet photodetector was fabricated by simply transferring individual nanowire to Pt interdigital electrodes. The photodetector exhibited excellent photoconductive performance in terms of high sensitivity to the ultraviolet 375 nm and infrared 750 nm UV illuminations, fast response and recovery time. It also has perfect stability and reliability, revealing n-type semiconducting behaviour of the tin oxide ultraviolet and infrared photodetecors as an excellent material not only for fabricating highly sensitive photodetecors but also valuable additives that provide new functionality in photodetecors, which will enable the development of high-performance photodetecors.