gebhart/patrepeval huggingface dataset:
Peroxisomes as dynamic organelles: autophagic degradation (2010)

Eukaryotic cells have to regulate peroxisomal metabolism to meet their environmental or developmental requirements. Therefore, the control of peroxisome number, which is mediated not only by proliferation but also by degradation, is an important cellular event. Here we briefly review studies on the autophagic degradation of peroxisomes, a process now termed pexophagy. Recent advances in molecular analyses of both nonselective and selective autophagic pathways have revealed a category of autophagy-related genes (ATG), many of which are shared in different pathways. In this review we introduce the functions of the shared ATG products, along with their interactions with peroxisomal factors. Physiological functions of this process (especially cellular remodeling) in mammalian cells and in a phytopathogenic fungus are also introduced.
One-class Collaborative Filtering with Random Graphs: Annotated Version (2013)

The bane of one-class collaborative filtering is interpreting and modelling the latent signal from the missing class. In this paper we present a novel Bayesian generative model for implicit collaborative filtering. It forms a core component of the Xbox Live architecture, and unlike previous approaches, delineates the odds of a user disliking an item from simply not considering it. The latent signal is treated as an unobserved random graph connecting users with items they might have encountered. We demonstrate how large-scale distributed learning can be achieved through a combination of stochastic gradient descent and mean field variational inference over random graph samples. A fine-grained comparison is done against a state of the art baseline on real world data.
Paraganglioma and Pregnancy: Management of Cesarean Delivery and Subsequent Laparoscopic Adrenalectomy (2014)

Background: Pheochromocytomas and paragangliomas are rare catecholamine-secreting tumors (CSTs) that may lead to severe hypertensive episodes and are associated with high maternal and fetal mortality when undiagnosed or mismanaged. Case: A 28-year-old full-term, normotensive woman with presumed pheochromocytoma underwent a cesarean under epidural anesthesia, which was also used for postoperative pain control, followed by an uncomplicated adrenalectomy under general anesthesia 5 days later. The pathology report revealed a paraganglioma. The patient and her newborn were discharged home in good health 2 days following surgery. Conclusion: We describe the diagnostic workup and perioperative management of a patient with a known CST, as well as the management of her neonate. In addition, we describe potential anesthetic complications in this situation and how these issues were addressed.
Predicting Chlorine Residuals in Unlined Metallic Pipes (2005)

There are numerous factors that can influence the quality of water in distribution systems. These include chemical and biological quality of source water; effectiveness and efficiency of treatment processes, adequacy of treatment facilities, storage facilities and distribution system, the age, type, design, and maintenance of the distribution network, and quality of treated water. Perhaps one of the most serious public health aspects of water quality deterioration in a network is the loss of disinfectant residual which can weaken the barrier against microbial contamination. A factor frequently cited as contributing to the loss of disinfectant residuals is internal corrosion of the pipe wall material. The effect of velocity in contributing to the loss of residual chlorine has been studied in a simulated distribution and has been reported previously. The results of this research has been verified in studies conducted in full scale systems and is reported in this paper.
Systematic Metabolic Engineering of Recombinant Xylose-Utilizing S. cerevisiae: Strategies for Improving Xylose Uptake Rate (2012)

Recent advancements in metabolomics and fluxomics methods and ever-increasing amount of available experimental data necessitate systems-oriented methodologies for efficient and systematic integration of data into consistent large-scale kinetic models capable of giving new insights in cell physiology and providing reliable guidance for metabolic engineering. The development of large scale kinetic models is often hampered by (i) incomplete/no knowledge about rate laws in addition to uncertain or missing information about their kinetic parameters; (ii) difficulties in determining the exact intracellular states due to insufficient experimental information and large degrees of flexibility in the stoichiometry of metabolic networks. ORACLE (Optimization and Risk Analysis of Complex Living Entities), a computational framework that accounts explicitly for mechanistic properties of enzymes and integrates network thermodynamics, physico-chemical constraints in metabolic network and available experimental data can be used to address the aforementioned issues. ORACLE relies on Metabolic Control Analysis (MCA) and Thermodynamic Flux Balance Analysis (TFBA) supported by a range of statistics and systems theory methods, allowing us to uncover all the possible intracellular network states consistent with the available experimental data. This is followed by the computation of control coefficients in the metabolic network to guide the formulation of possible alternatives for metabolic engineering. We demonstrate the application of this methodology in an actual metabolic engineering problem: improving the xylose uptake rate of a glucose-xylose co-utilizing recombinant S. cerevisiae strain through a cycle between experimental lab work and modeling efforts. More specifically, using the given fermentation data we identified network flux and concentration profiles representing possible physiological states of the base strain. Then, we have identified targets that consistently lead to improved flux through xylose transporters (XTR) across these profiles. The targets identified by our kinetic models are experimentally validated demonstrating the predictive capabilities of ORACLE. Time:
The FimH A27V Mutation Is Pathoadaptive for Urovirulence in <i>Escherichia coli</i> B2 Phylogenetic Group Isolates (2003)

Correlations between FimH mutations and virulence were established by studying a collection of human commensal and extraintestinal pathogenic Escherichia coli natural isolates. Pathoadaptive (A27V and, to a lesser extent, A119V) and "commensal-adaptive" (A202V) mutations were evidenced in B2 phylogenetic group strains. fimH phylogenetic analysis indicates that these pathoadaptive mutations occurred several times.
Preparation and X-ray crystallographic analysis of the Ca<sup>2+</sup>-discharged photoprotein obelin (2004)

Ca(2+)-regulated photoproteins belong to the EF-hand Ca(2+)-binding protein family. The addition of calcium ions initiates bright blue bioluminescence of the photoproteins, a result of the oxidative breakdown of coelenterazine peroxide to coelenteramide. Crystals of the Ca(2+)-discharged W92F mutant of obelin from Obelia longissima have been grown, representing the first crystallization of a photoprotein after the Ca(2+)-triggered bioluminescence. A green fluorescence observed from the crystals clearly demonstrates that coelenteramide, the bioluminescence product of coelenterazine peroxide, is bound within the protein. The diffraction pattern exhibits tetragonal Laue symmetry. Systematic absences indicate that the space group is either P4(3)2(1)2 or P4(1)2(1)2. The unit-cell parameters are a = b = 53.4, c = 144.0 A. The crystals diffract to 1.9 A resolution.
CD3<sup>+</sup> and CD8<sup>+</sup> tumor-infiltrating lymphocyte (TIL) densities to prognostically stratify DNA mismatch repair-deficient (dMMR) colon cancer patients (pts): NCCTG N0147 (Alliance). (2018)

3598 Background: Colorectal cancers (CRC) with dMMR typically have abundant TILs indicating an enhanced host immune response. However, the prognostic impact of TILs identified by CD3+ and CD8+ T cells has not been adequately studied in dMMR tumors. While dMMR is considered a predictive biomarker for anti-PD-1 therapy in advanced CRC, ~60% of dMMR pts do not respond, which may be relevant in dMMR stage III where adjuvant PD-L1 blockade is being studied. We report the first evaluation of CD3+/CD8+ TILs with prognosis in dMMR tumors from a clinical trial cohort. Methods: CD3+ and CD8+ TILs at the invasive margin (IM) and central tumor (CT) were analyzed in 561 stage III colon cancers (dMMR n = 278; randomly selected pMMR n = 283) from a phase 3 trial of FOLFOX-based adjuvant therapy (N = 3270 [dMMR 376, pMMR 2894]). Median follow up was 6.3 y. Immunostaining was quantified by image analysis (0-100 scale). Associations with overall survival (OS) were evaluated by multivariable Cox regression. Results: Densities of CD3+ and CD8+ TILs were higher in dMMR vs pMMR tumors (P < .001), and were heterogeneous between pts in each MMR group. CD3+ IM was the strongest prognostic marker; the other markers (CD3+ CT, CD8+ IM, CD8+ CT), alone or combined, did not add further value. Among dMMR tumors, using an optimized cutpoint, 58% had low CD3+ IM, and these pts had significantly shorter OS v dMMR tumors with high CD3+ IM, independent of covariates. See Table for full results. OS of dMMR tumors with low CD3+ IM was comparable to the overall pMMR cohort (n = 2611; P = .8). Pts with high CD3+ IM pMMR tumors had an OS similar to TIL-unselected dMMR tumors (n = 376; P = .3). Conclusions: CD3+ IM TILs can prognostically stratify pts with dMMR stage III colon cancer for OS. These findings of heterogeneity within dMMR may have implications for immunotherapy responsiveness in dMMR tumors. CD3+ IM (cutpoint) n (%) HRadj Padj 5y OS rate dMMR Per 10-unit decrease 1.1 .015 High (≥ 49) 111 (42) Ref .026 84% Low (≤ 48) 167 (58) 2.1 70% pMMR Per 10-unit decrease 1.2 .009 High (≥ 21) 177 (63) Ref .073 83% Low (≤ 20) 106 (37) 1.7 73% Adjustments included T, N, grade, BRAF/KRAS, tumor side, age, smoking
DNA-Assembled Plasmonic Waveguides for Nanoscale Light Propagation to a Fluorescent Nanodiamond (2018)

Plasmonic waveguides consisting of metal nanoparticle chains can localize and guide light well below the diffraction limit, but high propagation losses due to lithography-limited large interparticle spacing have impeded practical applications. Here, we demonstrate that DNA-origami-based self-assembly of monocrystalline gold nanoparticles allows the interparticle spacing to be decreased to ∼2 nm, thus reducing propagation losses to 0.8 dB per 50 nm at a deep subwavelength confinement of 62 nm (∼λ/10). We characterize the individual waveguides with nanometer-scale resolution by electron energy-loss spectroscopy. Light propagation toward a fluorescent nanodiamond is directly visualized by cathodoluminescence imaging spectroscopy on a single-device level, thereby realizing nanoscale light manipulation and energy conversion. Simulations suggest that longitudinal plasmon modes arising from the narrow gaps are responsible for the efficient waveguiding. With this scalable DNA origami approach, micrometer-long propagation lengths could be achieved, enabling applications in information technology, sensing, and quantum optics.
ChemInform Abstract: SOLVENT AND COUNTERION EFFECTS ON THE STEREOCHEMISTRY AND THE COMPETITION BETWEEN ELECTRON‐TRANSFER AND SN2 MECHANISMS IN THE REACTIONS OF (TRIMETHYLSTANNYL)ALKALIS WITH BROMIDES (1985)

Abstract Für die Produktverteilung bei den Reaktionen der Trimethylstannyl‐alkalimetalle (I) mit den Alkylbromiden (II) ist die Konkurrenz zwischen zwei verschiedenen Reaktionsmechanismen maßgebend: der direkten SNZ‐Substitution und dem Elektronentransfer (ET) von (I) zu (II) (der zu freien Radikalen als Zwischenstufe führt).
P2‐101: EVALUATION OF THE PRESYNAPTIC PROTEIN SNAP‐25 AS A NOVEL CEREBROSPINAL FLUID MARKER FOR SYNAPTIC PATHOLOGY IN ALZHEIMER'S DISEASE (2014)

Synaptic pathology seems to be occurring early in Alzheimer's disease (AD) development and cognitive alterations in patients with AD are suggested to be associated with synaptic loss. The cerebrospinal fluid (CSF) biomarkers reflecting synaptic pathology might therefore be valuable for earlier diagnosis, assessment of progression of disease and evaluation of treatment. Synaptosomal-associated protein 25 (SNAP-25) is a component of the SNARE protein complex, that is involved in the regulation of the synaptic neurotransmitter release. We have developed a novel affinity mass spectrometry approach allowing reproducibly measurements of the low abundant proteolytic fragments of SNAP-25 in CSF samples from individual subjects. By applying this novel affinity mass spectrometry strategy on three separate cohorts of patients the SNAP-25 as a novel CSF biomarker for AD was assessed for the first time. The CSF SNAP-25 proteoforms were immunoprecipitated, digested with trypsin and stable isotope labeled peptides were added. Quantification of SNAP-25 was performed by high resolution selected ion monitoring (HR-SIM-MS) on a Quadrupole-Orbitrap Mass Spectrometer (Q Exactive). The first clinical set of CSF samples were from patients with prodromal AD (N=7), AD (N=9) and controls (N=9) (German cohort). The second clinical material consisted of CSF samples from non-demented controls (N=6) and patients with AD (N=10) (Swedish cohort I). The third clinical material consisted of CSF samples from healthy controls (N=16) and patients with AD (N=17) (Swedish cohort II). Levels of CSF SNAP-25 were found to be increased in early as well as later stages of AD in three independent case-control cohorts. Almost all of the measured tryptic peptides of SNAP-25 could differentiate AD from controls with an area under the curve of 0.800 to 1.000 depending on cohorts studied. We have developed a sensitive method to analyze SNAP-25 levels in individual CSF samples that to our knowledge never have been done before. Levels of CSF SNAP-25 were found to be increase in early as well as later stages of AD in three independent case-control cohorts suggesting SNAP-25 to be a valuable marker.
The Design of an Adaptable Distributed System (1986)

There is a need to design large database systems that are not rigid in their choice of algorithms and are responsive to faults/failures and performance degradation. To attack this challenge, we fonnalize and experiment with design principles that allow the implementation of an adaptable distributed system. By adaptable, we imply that systems can be reconfigured at run-time based on perfonnance and continuity of operations requirements and load conditions. Our research focus is on algorithms for concurrency control, resiliency to site failures, network partitioning, and failure of communication systems. The strategies for dynamic reconfiguration of the software algorithms and determining their impact are being studied both theoretically and via experiments on a prototype system called RAID being developed at Purdue. We describe a layered design for a dislributed operating system with dislributed protocols that can be modified -or even completely changed -while the system is running. This capability will be a help in tuning the system to improve its perfonnance and reliability. In addition, the increased flexibility of this design makes it suitable for diverse applications. and capable of incorporating new distributed systems technology as it becomes available, unlike existing systems.
&lt;title&gt;Ultra-low voltage organic light-emitting diodes based on PiN structures&lt;/title&gt; (2002)

We demonstrate an efficient organic electroluminescent devices with p-i-n structure. Anamorphous starburst, 4,4',4'-tris(3-methylphenylphenylamino)triphenylamine doped with a strong organic acceptor, tetrafluoro-tetracyano- quinodimethane serves as the p-type hole transport layer, and 4,7-diphenyl-1, 10-phenanthroline doped with Li as the n-type electron transport layer. A breakthrough is achieved in the performances of device based on pure 8-tris- hydroxyquinoline as an emitter: 100cd/m<SUP>2</SUP> at 2.52V, 1,000cd/m<SUP>2</SUP> at 2.9V and the maximum luminance and efficiency reach 66,000cd/m<SUP>2</SUP> and 5.25 cd/A, respectively. The efficiency can be kept above 3cd/A in a very large luminance region from 100 to 55,000cd/m<SUP>2</SUP>.
Biomarker Analyses in Patients With Advanced Solid Tumors Treated With the LAT1 Inhibitor JPH203 (2020)

BCAAs and BMI are useful predictors of the efficacy of JPH203, which shows promising activity against BTC.
Variations in "adequate" own-voice level used by speakers and preferred by listeners when communicating across a distance (2007)

This paper describes a follow-up study to two pilot experiments on hearing-aid users’ ability to control the level of their own voice. In particular, the role of the so-called intervener in the experiments was examined. The intervener’s task is to supervise the speakers into speaking at the adequate level for the occasion. The study reveals that there are indeed differences among interveners, but that in broad terms the variation among interveners is similar in magnitude to the individual intervener’s test-retest consistency. Also the test-retest consistency of the speakers was examined, and was found to be similar to the aforementioned intervener-variations. The between-speaker variation is about twice as large, though. This suggests that it is highly necessary to include several speakers in experiments on own-voice level control, whereas relying on a single intervener is only mildly problematic.
Introduction to commentary by Laurent Mottron and responses (2021)

Commentaries and review articles are a regular feature of Autism Research and we invite our readers to suggest topics that they would like to cover in one of these formats. Submission of a commentary or review article must be approved before submission. For the commentary that follows, Professor Laurent Mottron has tackled a controversial issue related to how best to most efficiently pursue Autism Research in the future. We suspected that there may be a diverse set of opinions of his proposal and we solicited some short responses from several autism researchers. We received thoughtful responses from John N. Constantino, MD, Michael V. Lombardo, PhD, and Christopher Gillberg, MD, PhD. A response to the response was then provided by Professor Mottron. I believe that this is a thought-provoking series of essays which hopefully will lead to further discussions on this topic. If others would like to respond to this commentary, we would welcome additional letters to the editor submitted as usual through the ScholarOne Autism Research website.
Inhibition of <i>Pseudomonas aeruginosa</i> and <i>Mycobacterium tuberculosis</i> disulfide bond forming enzymes (2018)

In bacteria, disulfide bonds confer stability on many proteins exported to the cell envelope or beyond, including bacterial virulence factors. Thus, proteins involved in disulfide bond formation represent good targets for the development of inhibitors that can act as antibiotics or anti-virulence agents, resulting in the simultaneous inactivation of several types of virulence factors. Here, we present evidence that the disulfide bond forming enzymes, DsbB and VKOR, are required for Pseudomonas aeruginosa pathogenicity and Mycobacterium tuberculosis survival respectively. We also report the results of a HTS of 216,767 compounds tested against P. aeruginosa DsbB1 and M. tuberculosis VKOR using Escherichia coli cells. Since both P. aeruginosa DsbB1 and M. tuberculosis VKOR complement an E. coli dsbB knockout, we screened simultaneously for inhibitors of each complemented E. coli strain expressing a disulfide-bond sensitive β-galactosidase reported previously. The properties of several inhibitors obtained from these screens suggest they are a starting point for chemical modifications with potential for future antibacterial development.
The COX-2/PGE2 pathway suppresses apical elimination of RasV12-transformed cells from epithelia (2020)

At the initial stage of carcinogenesis, when RasV12-transformed cells are surrounded by normal epithelial cells, RasV12 cells are apically extruded from epithelia through cell competition with the surrounding normal cells. In this study, we demonstrate that expression of cyclooxygenase (COX)-2 is upregulated in normal cells surrounding RasV12-transformed cells. Addition of COX inhibitor or COX-2-knockout promotes apical extrusion of RasV12 cells. Furthermore, production of Prostaglandin (PG) E<sub>2</sub>, a downstream prostanoid of COX-2, is elevated in normal cells surrounding RasV12 cells, and addition of PGE<sub>2</sub> suppresses apical extrusion of RasV12 cells. In a cell competition mouse model, expression of COX-2 is elevated in pancreatic epithelia harbouring RasV12-exressing cells, and the COX inhibitor ibuprofen promotes apical extrusion of RasV12 cells. Moreover, caerulein-induced chronic inflammation substantially suppresses apical elimination of RasV12 cells. These results indicate that intrinsically or extrinsically mediated inflammation can promote tumour initiation by diminishing cell competition between normal and transformed cells.
Development and external validation of nomograms predicting distant metastases and overall survival after neoadjuvant chemotherapy and surgery for patients with nonmetastatic osteosarcoma: A multi‐institutional study (2015)

The nomograms were externally validated and verified to be useful for the prediction of MFS and OAS and for the assessment of the postoperative prognosis. They can be used for counseling patients and for establishing appropriate surveillance strategies after surgery.
Role of SEREX-defined immunogenic wild-type cellular molecules in the development of tumor-specific immunity (2001)

Recognition of altered self-antigens in tumor cells by lymphocytes forms the basis for antitumor immune responses. The effector cells in most experimental tumor systems are CD8(+) T cells that recognize MHC class I binding peptides derived from molecules with altered expression in tumor cells. Although the need for CD4(+) helper T cells in regulating CD8(+) T cells has been documented, their target epitopes and functional impact in antitumor responses remain unclear. We examined whether broadly expressed wild-type molecules in murine tumor cells eliciting humoral immunity contributed to the generation of CD8(+) T cells and protective antitumor immune responses to unrelated tumor-specific antigens [mutated ERK2 (mERK2) and c-erbB2/HER/neu (HER2)]. The immunogenic wild-type molecules, presumably dependent on recognition by CD4(+) helper T cells, were defined by serological analysis of recombinant cDNA expression libraries (SEREX) using tumor-derived lambda phage libraries screened with IgG antibodies of hosts bearing transplanted 3-methylchoranthrene-induced tumors. Coimmunization of mice with plasmids encoding SEREX-defined murine wild-type molecules and mERK2 or HER2 led to a profound increase in CD8(+) T cells specific for mERK2 or HER2 peptides. This heightened response depended on CD4(+) T cells and copresentation of SEREX-defined molecules and CD8(+) T cell epitopes. In tumor protection assays, immunization with SEREX-defined wild-type molecules and mERK2 resulted in an inhibition of pulmonary metastasis, which was not achieved by immunization with mERK2 alone.