gebhart/patrepeval huggingface dataset:
Programmable probiotics for detection of cancer in urine (2015)

Rapid advances in the forward engineering of genetic circuitry in living cells has positioned synthetic biology as a potential means to solve numerous biomedical problems, including disease diagnosis and therapy. One challenge in exploiting synthetic biology for translational applications is to engineer microbes that are well tolerated by patients and seamlessly integrate with existing clinical methods. We use the safe and widely used probiotic Escherichia coli Nissle 1917 to develop an orally administered diagnostic that can noninvasively indicate the presence of liver metastasis by producing easily detectable signals in urine. Our microbial diagnostic generated a high-contrast urine signal through selective expansion in liver metastases (10(6)-fold enrichment) and high expression of a lacZ reporter maintained by engineering a stable plasmid system. The lacZ reporter cleaves a substrate to produce a small molecule that can be detected in urine. E. coli Nissle 1917 robustly colonized tumor tissue in rodent models of liver metastasis after oral delivery but did not colonize healthy organs or fibrotic liver tissue. We saw no deleterious health effects on the mice for more than 12 months after oral delivery. Our results demonstrate that probiotics can be programmed to safely and selectively deliver synthetic gene circuits to diseased tissue microenvironments in vivo.
Ischemic Stroke Subtypes (1999)

The age-adjusted incidence rate of stroke due to stenosis of the large cervicocephalic vessels is nearly 4 times higher for men than for women. There is no association between preceding transient ischemic attack and stroke mechanism. Diabetes and hypertension are not more common among patients with lacunae. Age- and sex-adjusted incidence rates for ischemic stroke subtypes in this population can be compared with similarly determined rates from other populations.
Affymetrix: genes on chips (1998)

Affymetrix has developed state-of-the-art technology to attach small oligonucleotides onto glass surfaces using methods common to the electronics industry. Such arrays of DNA (gene chips) can be used to screen for mutations in disease genes as well as for changes in viral genomic structure (e.g., HIV-1 and -2). Other companies such as Hyseq have developed similar technologies in parallel and are currently in dispute with Affymetrix over the patent position. Whatever the outcome, the use of DNA attached to glass, quartz or electronic surfaces will be the way forward in mutation detection and gene expression studies.
Human alveolar bone cell adhesion and growth on ion‐implanted titanium (2004)

Surface characteristics play a vital role in determining the biocompatibility of materials used as bone implants. Calcium ion implantation of titanium was previously reported to enhance osseointegration and bone formation in vivo, although the lack of consistent and reproducible effects highlight the need to understand the basic mechanisms involved in the response of target cells to such surfaces. The aim of this study was therefore to measure the precise effects of ion implantation of titanium on bone cells in vitro. Alveolar bone cells were seeded on the surface of polished titanium disks implanted with calcium, potassium, and argon ions. Using radioisotopically tagged bone cells, the results showed that although the calcium ion implanted surface reduced cell adhesion, it nevertheless significantly enhanced cell spreading and subsequent cell growth. In contrast, few differences in bone cell behavior were observed between the potassium- and argon-implanted titanium and the control nonimplanted titanium disks. These findings suggest the possibility that the calcium-implanted surface may significantly affect the biocompatibility of titanium implants by enhancing bone cell growth. Surface modification by ion implantation could thus prove to be a valuable tool for improving the clinical efficacy of titanium for bone repair and regeneration in vivo.
Identification of class I MHC-associated phosphopeptides as targets for cancer immunotherapy (2006)

Alterations in phosphorylation of cellular proteins are a hallmark of malignant transformation. Degradation of these phosphoproteins could generate cancer-specific class I MHC-associated phosphopeptides recognizable by CD8+ T lymphocytes. In a comparative analysis of phosphopeptides presented on the surface of melanoma, ovarian carcinoma, and B lymphoblastoid cells, we find 5 of 36 that are restricted to the solid tumors and common to both cancers. Differential presentation of these peptides can result from differential phosphorylation of the source proteins. Recognition of the peptides on cancer cells by phosphopeptide-specific CD8+ T lymphocytes validates the potential of these phosphopeptides as immunotherapeutic targets.
Robust Identification of Fuzzy Duplicates (2005)

Detecting and eliminating fuzzy duplicates is a critical data cleaning task that is required by many applications. Fuzzy duplicates are multiple seemingly distinct tuples, which represent the same real-world entity. We propose two novel criteria that enable characterization of fuzzy duplicates more accurately than is possible with existing techniques. Using these criteria, we propose a novel framework for the fuzzy duplicate elimination problem. We show that solutions within the new framework result in better accuracy than earlier approaches. We present an efficient algorithm for solving instantiations within the framework. We evaluate it on real datasets to demonstrate the accuracy and scalability of our algorithm.
Antisense oligonucleotides to LRRK2 ameliorate alpha-synuclein pathology and behavioral deficit induced by pre-formed alpha-synuclein fibrils (I1.007) (2016)

Objective: Determine the role of leucine-rich-repeat kinase 2 (LRRK2) in spreading of alpha-synuclein (aSyn) pathology in a mouse model of Parkinson’s disease (PD). Background: LRRK2 mutations are the major cause of familial late-onset PD. However, the interplay between LRRK2 and aSyn in PD pathophysiology is still of debate and undergoing extensive research. To determine whether LRRK2 expression modifies aSyn pathology spreading, we lowered endogenous LRRK2 by antisense oligonucleotide (ASO) in mice injected with pre-formed aSyn fibrils (PFF). Design/Methods: Wildtype mice were injected intracerebroventrically (ICV) with LRRK2 ASOs 2 weeks before intra-striatal inoculation of aSyn PFF. At 8 weeks post ICV injection of LRRK2 ASOs, mice were assessed on the wirehang task for motor coordination and grip strength. LRRK2 mRNA, protein, and phosphorylated aSyn pathology were assessed by RT-QPCR, western blots, and immunohistochemical methods, respectively. Results: Preventive ASO-mediated suppression of endogenous LRRK2 reduced pathological spread of aSyn pathology and protected mice against aSyn pathology-induced wirehang deficit in a-syn PFF inoculation mouse model. Conclusions: LRRK2 may play an important role in aSyn pathology formation and progression. Thus, ASO targeting LRRK2 is of potential therapeutic use for PD and other synucleinopathies.
Expression of Clusterin/Sulfated Glycoprotein‐2 Under Conditions of Heat Stress in Rat Sertoli Cells and a Mouse Sertoli Cell Line (1997)

Clusterin is the major protein produced by rat Sertoli cells and is deposited onto sperm membranes; however, its function is unknown. In order to gain insight into the regulation of clusterin in Sertoli cells, the objective of the present study was to develop a model where the expression of clusterin could be affected in Sertoli cells in vitro. Rat Sertoli cells and mouse Sertoli cells (MSC1) were cultured under heat stress conditions (41 degrees C) for up to 48 hours. The mRNA for clusterin in Sertoli cells was compared to that in human epitheliod cancer cells (A431) to determine if clusterin expression was regulated in a lestis-specific manner. The mRNA for heat shock protein 70 (HSP70) was also examined as it is a known stress-regulated gene. Expression of HSP70 mRNA was increased in all three cell types by 4 hours after the start of heat stress. Clusterin mRNA was increased over that of controls by 4 hours in heat-stressed A431 cells but did not significantly increase in MSC1 or Sertoli cells until 12 hours (P < 0.05). The induction of clusterin mRNA in MSC1 cells continued for at least 48 hours and required the sustained exposure of cells to the 41 degrees C temperature. The increase in the amount of clusterin mRNA was not due to an increase in transcript half-life, as determined by the addition of actinomycin D to the media of control vs. heat-stressed MSC1 cells. From the development of this in vitro model, we have seen that the timing of induction of clusterin by heat stress is Sertoli cell specific and is different than that of HSP70. This response in surviving cells during heat stress may be protective in that clusterin would bind to toxic compounds or solubilize cellular debris released by degenerating cells.
The regulation of plasma relaxin levels during human pregnancy (1994)

The factors that determine the circulating levels of relaxin during pregnancy have been investigated by comparing the plasma levels of relaxin throughout pregnancy in women who became pregnant spontaneously (singleton, n = 240) or following superovulation (singleton and multifetal pregnancies (two to ten conceptuses), n = 83). Some of the women with multifetal pregnancies underwent selective fetal reduction to twin pregnancies. Relaxin levels were higher at 7-34 weeks of gestation in singleton pregnancies achieved following superovulation when compared with levels in spontaneously conceived singleton pregnancies (p < 0.05-0.001). In samples obtained between 10 and 12 weeks of gestation (before fetal reduction for the multifetal pregnancies), plasma relaxin levels correlated with fetal number (r = 0.526, P = 0.0001). Reduction in fetal number to a twin pregnancy did not alter relaxin levels. These data suggest that the circulating levels of relaxin throughout pregnancy are determined during the cycle of conception by gonadotrophin stimulation, and within the first 10 weeks of pregnancy by the luteotrophic stimulus from the conceptus. Furthermore, once corpus luteum synthesis of relaxin is established, then reduction in the luteotrophic stimulus does not appear to affect it.
Design of controlled drug delivery system with optimal release characteristics (2006)

The biodegradable controlled-release system with large array of micro chambers is a new controlled drug delivery system. The structure of the system is designed using the MEMS technology, combining the drug release condition and the biodegradable characteristic of the polymer. This type of drug delivery system has some unique advantages in controlled long-term drug delivery, such as more drug loading than the matrices release systems, easier control the release rate, and so on. It is necessary to optimum the structure for the long-term drug delivery. This paper founds the simulated modeling which can simulate the erosion and the drug delivery from this controlled-release system. Further more the thickness of the chamber's wall is taken as the design variable. An optimized modeling for the drug delivery from the biodegradable controlled-release system is developed. This model can optimize the structure of the controlled release system for the desired release characteristics. The results indicate that this method can be used to design the drug delivery system based on the biodegradable polymer.
A Proposed Model of Boundary Lubrication by Synovial Fluid: Structuring of Boundary Water (1979)

On the basis of data obtained from in-vitro friction tests using both cartilage and widely differing artificial surfaces, a general model for boundary lubrication of joint cartilage by synovial fluid is presented. It postulates that one portion of the synovial lubricating glycoprotein (LGP) is adsorbed to the surface. Reduction in surface shear is accomplished by formation of hydration shells about the polar portions of the adsorbed LGP creating a thin layer of viscous structured water at the surface. Mutual electrostatic repulsion between charged polysaccharide moieties aids in separation of the adsorbed surface layers. The hydration shell also serves as a check valve to control the movement of water out of and into the cartilage matrix during motion.
Genetic and Functional Diversification of Small RNA Pathways in Plants (2004)

Multicellular eukaryotes produce small RNA molecules (approximately 21-24 nucleotides) of two general types, microRNA (miRNA) and short interfering RNA (siRNA). They collectively function as sequence-specific guides to silence or regulate genes, transposons, and viruses and to modify chromatin and genome structure. Formation or activity of small RNAs requires factors belonging to gene families that encode DICER (or DICER-LIKE [DCL]) and ARGONAUTE proteins and, in the case of some siRNAs, RNA-dependent RNA polymerase (RDR) proteins. Unlike many animals, plants encode multiple DCL and RDR proteins. Using a series of insertion mutants of Arabidopsis thaliana, unique functions for three DCL proteins in miRNA (DCL1), endogenous siRNA (DCL3), and viral siRNA (DCL2) biogenesis were identified. One RDR protein (RDR2) was required for all endogenous siRNAs analyzed. The loss of endogenous siRNA in dcl3 and rdr2 mutants was associated with loss of heterochromatic marks and increased transcript accumulation at some loci. Defects in siRNA-generation activity in response to turnip crinkle virus in dcl2 mutant plants correlated with increased virus susceptibility. We conclude that proliferation and diversification of DCL and RDR genes during evolution of plants contributed to specialization of small RNA-directed pathways for development, chromatin structure, and defense.
Stenting of Symptomatic M1 Stenosis of Middle Cerebral Artery (2004)

Stenting appears to be an effective and feasible therapy for symptomatic M1 stenoses, but also appears to have the higher periprocedural complications, which need strict procedural and periprocedural management to reduce the mortality and morbidity. The LMA classification seems to be helpful to work out the individual therapy and predict the results of stenting. A further study is needed to confirm the benefits of stenting of MCA stenosis.
Physics and Device Applications of Optical Microcavities (1992)

Optical microcavities are resonators that have at least one dimension on the order of a single optical wavelength. These structures enable one to control the optical emission properties of materials placed inside them. They can, for example, modify the spatial distribution of radiation power, change the spectral width of the emitted light, and enhance or suppress the spontaneous emission rate. In addition to being attractive for studying the fundamental physics of the interaction between materials and vacuum field fluctuations, optical microcavities hold technological promise for constructing novel kinds of light-emitting devices. One of their most dramatic potential features is thresholdless lasing. In this way and others, controlled spontaneous emission is expected to play a key role in a new generation of optical devices.
Containment and growth of neuroblastoma cells on chemically patterned substrates (1993)

Patterned substrates offer the promise of controlled positioning and directional guidance of growing neurites. Therefore, they could be useful for constructing small neuronal networks with defined geometry in vitro. We have fabricated chemically patterned substrates using self-assembled monolayer films with a lithographic mask technique and demonstrated the feasibility for geometrically patterning neuroblastoma cells in culture. N-octadecyltrichlorosilane (OTS) was chemically bonded to glass and fused silica substrates, rendering the surface hydrophobic and non-adhesive to cells. Using surface analysis techniques, we have confirmed that OTS films were true monolayers and can be photocleaved from the surface by deep UV irradiation. An adhesive pattern of n-(2-aminoethyl-3-aminopropyl)trimethoxysilane was formed on a selectively irradiated OTS surface via a deep UV lithographic procedure. The chemically patterned surface was then seeded with SK-N-SH human neuroblastoma cells, and cellular attachment and growth were monitored by optical microscopy. The use of 2-dimensional substrates supported the containment and growth of neuroblastoma cells within the pattern for at least 15 days in culture. These chemical patterns may also be useful in controlled arrangements of hearts cells or muscle cells on prosthetic implant devices.
Discovery of Potent, Selective, Orally Bioavailable Stearoyl-CoA Desaturase 1 Inhibitors (2007)

Stearoyl-CoA desaturase 1 (SCD1) catalyzes the committed step in the biosynthesis of monounsaturated fatty acids from saturated, long-chain fatty acids. Studies with SCD1 knockout mice have established that these animals are lean and protected from leptin deficiency-induced and diet-induced obesity, with greater whole body insulin sensitivity than wild-type animals. In this work, we have discovered a series of potent, selective, orally bioavailable SCD1 inhibitors based on a known pyridazine carboxamide template. The representative lead inhibitor 28c also demonstrates excellent cellular activity in blocking the conversion of saturated long-chain fatty acid-CoAs (LCFA-CoAs) to monounsaturated LCFA-CoAs in HepG2 cells.
Stabilization of the Activated αMβ2Integrin by a Small Molecule Inhibits Leukocyte Migration and Recruitment (2006)

Integrins are potential targets for the development of antiinflammatory agents. Here we develop a novel high-throughput assay by allowing a chemical library to compete with phage display peptide binding and identify a novel small-molecule ligand to the leukocyte-specific alpha(M)beta(2) integrin. The identified thioxothiazolidine-containing compound, IMB-10, had an unexpected activity in that it stabilized binding of alpha(M)beta(2) to its endogenous ligands proMMP-9 and fibrinogen. Single amino acid substitutions in the activity-regulating C-terminal helix and the underlying region in the ligand-binding I domain of the integrin suppressed the effect of IMB-10. A computational model indicated that IMB-10 occupies a distinct cavity present only in the activated form of the integrin I domain. IMB-10 inhibited alpha(M)beta(2)-dependent migration in vitro and inflammation-induced neutrophil emigration in vivo. Stabilization of integrin-mediated adhesion by a small molecule is a novel means to inhibit cell migration and may have a utility in treatment of inflammatory diseases involving leukocyte recruitment.
J Antimicrob Chemother 1994; 33: 350–351 (1994)

Journal Article J Antimicrob Chemother 1994; 33: 350–351 Get access ELIZABETH M. O'SHAUGHNESSY, ELIZABETH M. O'SHAUGHNESSY Department of Medical Microbiology, St Bartholomew's Hospital Medical CollegeWest Smithfield, London EC1A 7BE, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar SATYA S. DAS SATYA S. DAS Department of Medical Microbiology, St Bartholomew's Hospital Medical CollegeWest Smithfield, London EC1A 7BE, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Antimicrobial Chemotherapy, Volume 33, Issue 2, February 1994, Pages 350–351, https://doi.org/10.1093/jac/33.2.350 Published: 01 February 1994
Canine lung transplantation after more than twenty-four hours of normothermic preservation. (1997)

This study shows that the lungs were well preserved for more than 24 hours of preservation when the normothermic multiorgan block preparation was used. The transplanted left lung was able to support the anesthetized dog after the opposite pulmonary artery was occluded.
Constructing, conducting and interpreting animal social network analysis (2015)

1. Animal social networks are descriptions of social structure which, aside from their intrinsic interest for understanding sociality, can have significant bearing across many fields of biology. 2. Network analysis provides a flexible toolbox for testing a broad range of hypotheses, and for describing the social system of species or populations in a quantitative and comparable manner. However, it requires careful consideration of underlying assumptions, in particular differentiating real from observed networks and controlling for inherent biases that are common in social data. 3. We provide a practical guide for using this framework to analyse animal social systems and test hypotheses. First, we discuss key considerations when defining nodes and edges, and when designing methods for collecting data. We discuss different approaches for inferring social networks from these data and displaying them. We then provide an overview of methods for quantifying properties of nodes and networks, as well as for testing hypotheses concerning network structure and network processes. Finally, we provide information about assessing the power and accuracy of an observed network. 4. Alongside this manuscript, we provide appendices containing background information on common programming routines and worked examples of how to perform network analysis using the r programming language. 5. We conclude by discussing some of the major current challenges in social network analysis and interesting future directions. In particular, we highlight the under-exploited potential of experimental manipulations on social networks to address research questions.
Tuning between the metallic antiferromagnetic and ferromagnetic phases ofLa1−xSrxMnO3nearx=0.5by digital synthesis (2009)

We investigated cation-ordered ${\text{La}}_{1\ensuremath{-}x}{\text{Sr}}_{x}{\text{MnO}}_{3}$ about the half-doping level $x\ensuremath{\sim}0.5$ in superlattices of alternating, single-unit-cell layers of ${\text{LaMnO}}_{3}$ and ${\text{SrMnO}}_{3}$. The effect of La/Sr cation order was addressed by comparing the structural, magnetic and transport properties of these superlattices with random-alloy films of equivalent composition. The samples were synthesized by ozone-assisted molecular-beam epitaxy onto ${\text{SrTiO}}_{3}$ substrates. The superlattices could be tuned between ferromagnetic and antiferromagnetic metallic states by inserting extra single-unit-cell layers of ${\text{LaMnO}}_{3}$ and ${\text{SrMnO}}_{3}$, respectively. For $x&lt;0.5$, a ferromagnetic, metallic phase was observed. For $x=0.50$ and 0.55, $A$-type antiferromagnetic order was confirmed by neutron diffraction, with a N\'eel temperature of 300 K, significantly higher than bulk values. The enhanced N\'eel temperature was attributed to lattice strain rather than cation order.
Phase I trial and pharmacokinetic study of all-trans-retinoic acid administered on an intermittent schedule in combination with interferon-alpha2a in pediatric patients with refractory cancer. (1997)

An intermittent schedule of ATRA administration appears to circumvent the low plasma drug exposure that is a result of the sustained upregulation of metabolism when this drug is administered on a chronic daily schedule. Based on the results of this trial, a phase II trial of ATRA/IFN-alpha2a in neuroblastoma and Wilms' tumor using this schedule is in progress.