gebhart/patrepeval huggingface dataset:
DNA methylation is required to maintain DNA replication timing precision and 3D genome integrity (2020)

Abstract DNA replication timing and three-dimensional (3D) genome organisation occur across large domains associated with distinct epigenome patterns to functionally compartmentalise genome regulation. However, it is still unclear if alternations in the epigenome, in particular cancer-related DNA hypomethylation, can directly result in alterations to cancer higher order genome architecture. Here, we use Hi-C and single cell Repli-Seq, in the colorectal cancer DNMT1 and DNMT3B DNA methyltransferases double knockout model, to determine the impact of DNA hypomethylation on replication timing and 3D genome organisation. First, we find that the hypomethylated cells show a striking loss of replication timing precision with gain of cell-to-cell replication timing heterogeneity and loss of 3D genome compartmentalisation. Second, hypomethylated regions that undergo a large change in replication timing also show loss of allelic replication timing, including at cancer-related genes. Finally, we observe the formation of broad ectopic H3K4me3-H3K9me3 domains across hypomethylated regions where late replication is maintained, that potentially prevent aberrant transcription and loss of genome organisation after DNA demethylation. Together, our results highlight a previously underappreciated role for DNA methylation in maintenance of 3D genome architecture.
Electrospun In2O3/α-Fe2O3 heterostructure nanotubes for highly sensitive gas sensor applications (2013)

In2O3/α-Fe2O3 (IFO) heterostructure nanotubes, with cubic-In2O3 nanocrystals randomly distributed on the surface of α-Fe2O3 nanotube-based backbones, were successfully prepared through a facile single-capillary electrospinning method. The morphologies of the resulting electrospun products were characterized by scanning electron microscopy and transmission electron microscopy. The crystal structures and components were determined by X-ray diffraction and energy-dispersive X-ray spectra, respectively. The results show that the morphology and structure of the products could be tailored by changing the content of indium nitrate in the precursor solutions and the calcination temperatures. Moreover, the IFO-0.1 (In/Fe = 1 : 9, molar ratio) nanotubes based sensor shows a high sensitivity to ethanol with a fast response/recovery time, and the performance is stable at a low operating temperature, which gives a potential application in ethanol gas sensors. A possible gas sensing mechanism based on the role of In2O3 in such a heterostructure is also discussed in detail.
Trials to Trust (2016)

“Trust, but verify” is a thought one might have after reading even a well-conducted scientific study. What is the tipping point when we start believing? How many trials does it take to bring about a change in practice or for a new idea to be accepted as the standard of care? One randomized control trial on its own may not be enough to earn general acceptance and the trust of many. This phenomenon is exemplified in a recent study. A prospective randomized controlled study on the management of Lisfranc injury showed arthrodesis to be better than the traditional practice of internal fixation. Would one change their practice on the basis of the results of this one study? Most likely not—as it is often the case, and as it was in this case, based on a show of hands at a conference. Would it require more than this one study with reproducible results to elicit change? Even after a few more studies showing that arthrodesis is better, not everyone will have adopted the change. How many trials does it take to bring about a change in practice or for a new idea to be accepted as the standard of care? No study is without limitation. A single-surgeon study might limit one aspect of variability, but is deprived of expectations on reproducibility. What works in someone’s hands may or may not work in someone else’s hands. That is why we often hear the adage “in my hands.” Reproducibility in one part of the world leaves open to question the reproducibility in other parts of the world. Therefore, many studies on a subject are needed for the results from trials to become trusted and trusted widely. Our personal training, mentorship from experts, and our own experience apart from the knowledge we gain from scientific trials, all play an important role along with a wide variety of other considerations in terms of individualizing what we do or offer to our patients. In addition, good results after what we do often depends on how good we are at what we do, especially in terms of the technical skill in demanding or challenging situations. One such challenging set of problems in the mid foot is addressed in this issue. We are grateful to Guest Editors, Drs Zide and Brodsky, who put in a lot of time and effort to bring together a great panel of experts to share what works in their hands when managing these difficult sets of problems. Trust or verify or conduct a trial or read these opinions and write to us about your own experience! Vinod K. Panchbhavi, MD, FACS
Finding Out If It Is True: Comparing Mediation and Negotiation Through Research (2002)

In this article, we first use existing research evidence to contextualize more clearly the place of civil case mediation in the litigation process. When we understand civil mediation as part of adversarial litigation - rather than as distinct from it - we see the importance of comparing mediation and unassisted negotiation. Next, we discuss research and commentary on the barriers to negotiation and the ways in which mediation might help overcome them. This work provides a more pragmatic and empirically grounded perspective on the potential value of mediation than does "mediation ideology" and suggests a wide range of "hypotheses" to guide future research. Finally, we reexamine briefly the research about preferences for mediation and the modest body of existing studies that do contrast litigant experiences with mediation and unaided negotiation in the context of litigation. This reexamination hints that "it may in fact be true" - that is, participation in mediation may enhance parties' perception of procedural justice. Before we can be confident in the answer to this question, however, research is needed that carefully compares the experiences of parties in mediation with those in unassisted negotiation.
Retrospective Analysis and Forecasted Economic Impact of a Virtual Cardiac Rehabilitation Program in a Third-Party Payer Environment (2021)

<b>Background:</b> Participation in cardiac rehabilitation (CR) is recommended for all patients with coronary artery disease (CAD) following hospitalization for acute coronary syndrome or stenting. Yet, few patients participate due to the inconvenience and high cost of attending a facility-based program, factors which have been magnified during the ongoing COVID pandemic. Based on a retrospective analysis of CR utilization and cost in a third-party payer environment, we forecasted the potential clinical and economic benefits of delivering a home-based, virtual CR program, with the goal of guiding future implementation efforts to expand CR access. <b>Methods:</b> We performed a retrospective cohort study using insurance claims data from a large, third-party payer in the state of Pennsylvania. Primary diagnostic and procedural codes were used to identify patients admitted for CAD between October 1, 2016, and September 30, 2018. Rates of enrollment in facility-based CR, as well as all-cause and cardiovascular hospital readmission and associated costs, were calculated during the 12-months following discharge. <b>Results:</b> Only 37% of the 7,264 identified eligible insured patients enrolled in a facility-based CR program within 12 months, incurring a mean delivery cost of $2,922 per participating patient. The 12-month all-cause readmission rate among these patients was 24%, compared to 31% among patients who did not participate in CR. Furthermore, among those readmitted, CR patients were readmitted less frequently than non-CR patients within this time period. The average per-patient cost from hospital readmissions was $30,814 per annum. Based on these trends, we forecasted that adoption of virtual CR among patients who previously declined CR would result in an annual cost savings between $1 and $9 million in the third-party healthcare system from a combination of increased overall CR enrollment and fewer hospital readmissions among new HBCR participants. <b>Conclusions:</b> Among insured patients eligible for CR in a third-party payer environment, implementation of a home-based virtual CR program is forecasted to yield significant cost savings through a combination of increased CR participation and a consequent reduction in downstream healthcare utilization.
Transcription et réplication des Mononegavirales : une machine moléculaire originale. (2012)

Viruses with a non-segmented negative-sense RNA genome, or Mononegavirales, are important pathogens for plants, animals and humans with major socio-economic and health impacts. Among them are well-known human pathogens such as measles, mumps and respiratory syncytial virus. Moreover, animal reservoirs appear much larger than previously thought, hence broadening the risk of emergence of life-threatening zoonotic viruses such as Rabies, Ebola, Marburg, Nipah or Hendra related viruses. These viruses have peculiar transcription and replication machinery that make them unique in the living world. Indeed, their genomic RNA, when naked, is non-infectious because it can be neither transcribed nor translated, and the L RNA-dependent RNA-polymerase is at best able to initiate the synthesis of an RNA copy of a few of tens of nucleotides in length. To serve as a template, the genomic RNA must be encapsidated in a helicoidal homopolymer made of a regular and continuous array of docked N protomers in which the ribose-phosphate backbone is fully embedded. This complex, or nucleocapsid, is recognized by the L polymerase thanks to its cofactor, the P protein, to sequentially transcribe the five genes into five processed mRNAs for the simplest viruses. Subsequently, a switch occurs and the polymerase replicates a full copy of antigenomic RNA that is concurrently encapsidated. This new template is then used for the production of new infectious genomic nucleocapsids. This review summarizes current structural, dynamic and functional data of this peculiar molecular machinery and provides a unified model of how it can function. It illuminates the overall common strategies and the subtle variations in the different viruses, along with the key role of the dual ordered/disordered structure of the protein components in the dynamics of the viral polymerase machinery.
Chemical modification of urokinase with human serum albumin fragments. (1989)

A therapeutically) important fibrinolytic enzyme, urokinase, has been modified with fragmented human serum albumin (mol wt., 1000-7000) by reaction with glutaraldehyde as a coupling agent. The chemically modified enzyme was separated by gel filtration with Sephadex G-150 into products which underwent conjugation with albumin fragments to various extents. The major modification product, with a molecular weight of about 70, 000, and retaining 40 % of the original urokinase activity, was significantly more resistant to inactivation by protease inhibitors in rat plasma than the unmodified enzyme. It also showed an in vivo half-life ten times longer than the native one during circulation in blood. The rabbit antiserum raised against the modified urokinase reacted not only with the antigen but also with both the unmodified enzyme and the human serum albumin. The modified enzyme did not elicit specific antibodies in an immunized rabbit, and the enzyme that had been modified excessively with albumin fragments lost the antigenicity of urokinase. These results indicate that the chemical modification with albumin fragments is useful for improvement of in vitro and in vivo stabilities of chemotherapeutic enzymes.
Effect of anticoagulants and glucose on refractometric estimation of protein in canine and rabbit plasma. (1978)

The effect of ethylenediaminetetraacetate (EDTA) compounds on the refractometric estimation of plasma protein concentration was attributed largely to osmotic fluid shifts, as reflected in changes in hematocrit, and to addition of total solids to the plasma. With H4EDTA, these two mechanisms were additive and caused increased plasma protein readings of significant magnitude even at recommended (1--2 mg/ml) anticoagulant concentrations. For the potassium and sodium salts, the two mechanisms were partly compensatory, which ameliorated the effect at 1--2 mg/ml concentration. At higher concentrations, such as might occur if a blood collecting tube were incompletely filled, all of the EDTA compounds caused technically significant over-estimation of plasma protein. When dextrose (d-glucose) was added in-vitro to canine blood, in amounts analogous to clinical hyperglycemia, the effect upon plasma protein estimation was minimal.
Metal-polymer composite films based on polyacrylonitrile and silver nanoparticles. Preparation and properties (2010)

The structures consisting of silver nanoparticles and polyacrylonitrile (PAN) are synthesized by the photopolymerization method yielding a homogeneous dispersion and a small size spread of nanoinclusions in PAN matrices, which is observed in images of transmission electron microscopy. The optical properties of the nanocomposites are studied to depend upon conditions of their obtaining. The minimum in the transmission spectra in a wavelength region of 430 nm, which is attributed to the surface plasmon resonance of silver nanoparticles, is found. The absorption peaks in the infrared range are observed at ∼820 and ∼1110 cm−1 for the silver nitrate (AgNO3) and the photoinitiator, respectively.
Optimization of out of memory killer for embedded Linux environments (2011)

When a swapless Linux system runs out of memory, the system reclaims memory by invoking Out of Memory (OOM) Killer. The OOM killer terminates arbitrary processes. The running time of selecting victim processes is proportional to the number of processes in the system. In this paper, we propose a novel selection scheme which runs in O(1) time. The experimental results showed that the proposed selection scheme outperformed the existing one in terms of the running time.
Ubiquitin-interacting Motifs Inhibit Aggregation of PolyQ-expanded Huntingtin (2007)

Expansion of polyglutamine (polyQ) tracts within proteins underlies a number of neurodegenerative diseases, such as Huntington disease, Kennedy disease, and spinocerebellar ataxias. The resulting mutant proteins are unstable, forming insoluble aggregates that are associated with components of the ubiquitin system, including ubiquitin, ubiquitin-like proteins, and proteins that bind to ubiquitin. Given the presence of these ubiquitin-binding proteins in the insoluble aggregates, we examined whether heterologous expression of short motifs that bind ubiquitin, termed ubiquitin-interacting motifs (UIMs), altered the aggregation of polyQ-expanded huntingtin (Htt), the protein product of the Huntington disease gene. We found that a subset of UIMs associated with mutant Htt. The ability to interact with ubiquitin was necessary, but not sufficient, for interaction with mutant Htt. Furthermore, we found that expression of single, isolated UIMs inhibited aggregation of mutant Htt. These data suggest that isolated UIMs might serve as potential inhibitors of polyQ-aggregation in vivo.
Extracting Local Binary Patterns with MIPA4k vision processor (2010)

In this paper we show how the MIPA4k vision processor can be used to extract and process local image features called Local Binary Patterns (LBPs). Using these low level image features more advanced higher level processing can be performed. LBP histograms can be extracted with wide field of potential applications. Also, directional thresholding results, which are part of LBP extraction process, can be used for higher level processing such as face localization. The MIPA4k vision processor consists of an array of 64 × 64 mixed-mode processing units with on-chip image capture sensors.
A Syndrome with Congenital Neutropenia and Mutations inG6PC3 (2008)

Defective function of glucose-6-phosphatase, catalytic subunit 3, underlies a severe congenital neutropenia syndrome associated with cardiac and urogenital malformations.
Evaluation of the economic impact of the CCP assay in localized prostate cancer. (2015)

e16037 Background: Stratification of localized prostate cancer based on disease aggressiveness remains challenging, resulting in overtreatment of low−risk patients and under treatment of high−risk patients. A biopsy−based, cell cycle progression (CCP) gene expression assay can aid physicians in predicting prostate cancer aggressiveness, leading to more appropriate patient management. This study quantifies the economic impact of the CCP assay on a US commercial health plan. Methods: A fact−based economic model was developed for a hypothetical cohort of prostate cancer patients with localized disease. Patients were followed in the model for 10 years with management and progression assumptions based on published clinical data and interviews with board−certified physicians. Total cost of care was calculated for a reference scenario (current clinical practice) and a test scenario where patient management was altered based on CCP test results. Cost inputs were set for each unit of care that a patient might undergo (diagnostic/surgical/radiotherapy procedures and pharmacological therapy); costs were assigned based on published costs of care. Total cost of care was compared between the two scenarios to determine overall system economic impact. Results: The CCP test reduced costs by $2,850/patient tested over 10 years after accounting for test cost. For a health plan with 10 million members, this would translate to over $16 million in savings with two−thirds of those savings achieved in the first year after testing. The majority of savings came from increased use of active surveillance in AUA low− and intermediate−risk patients. No single model input, when changed within a range of values, caused the model to show that the test was no longer cost saving. Costs of the test scenario were never greater than the reference scenario, resulting in cost savings over the 10 years modeled. Conclusions: Use of the CCP test in a US commercial health plan has the potential to result in cost savings to payers. Savings are due to increased use of active surveillance in low− and intermediate−risk patients with less aggressive disease, but also from reduced progression rates in high−risk patients with more aggressive disease who transition to multi−modality therapy.
Cytostasis induced in L1210 murine leukaemia cells by the S-adenosyl-l-methionine decarboxylase inhibitor 5′-([(Z)-4-amino-2-butenyl]methylamino)-5′-deoxyadenosine may be due to hypusine depletion (1992)

The effects of inhibition of the capacity to form spermidine and spermine on cell growth were investigated using murine leukaemia L1210 cells and 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine (MDL 73811, AbeAdo), an enzyme-activated irreversible inhibitor of S-adenosyl-L-methionine decarboxylase. Putrescine levels were increased 80-fold, and spermidine and spermine levels were greatly reduced after a 3-day exposure to a maximally inhibitory dose of 10 microM-AbeAdo. Addition of AbeAdo to the culture medium inhibited the growth of L1210 cells measured 3 days later in a dose-dependent manner, but, even at a dose of 10 microM, which was maximally effective, exposure to AbeAdo was not immediately cytostatic. However, the growth rate of L1210 cells chronically exposed to 10 microM-AbeAdo declined steadily until day 12, when the cells stopped growing. L1210 cells exposed to AbeAdo for 12 days could not be rescued from cytostasis by removal of the drug from the culture, but could be rescued by exposure to exogenous spermidine or spermine, indicating that the growth-inhibitory effects of AbeAdo were a result of spermidine and/or spermine depletion. It is suggested that elevated intracellular putrescine in AbeAdo-treated cells sustained limited growth in the absence of physiological levels of spermidine and spermine until certain critical and specific physiological role(s) fulfilled by spermidine (and/or spermine) became deficient resulting in cytostasis. N-(3-Aminopropyl)-1,4-diamino-cis-but-2-ene, a spermidine analogue that is a substrate for deoxyhypusine synthase, was able to mimic the effects of spermidine in reversing AbeAdo-induced cytostasis. Spermidine analogues such as 5,5-dimethylspermidine, which are not substrates for deoxyhypusine synthase, were not active in this way. These results provide evidence that the formation of hypusine in the protein-synthesis initiation factor eIF-5A may be a critical role of spermidine essential for cell growth.
Distribution of selected bacterial species on intraoral surfaces (2003)

Proportions of bacterial species differed markedly on different intraoral surfaces. The microbiota of saliva was most similar to that of the dorsal and lateral surfaces of the tongue. The microbiotas of the soft tissues resembled each other more than the microbiotas that colonized the teeth both above and below the gingival margin.
Thrombosis and atherosclerosis (1997)

The initial step in atherosclerosis is the rapid targeting of monocytes to the sites of inflammation and endothelial injury. Serum levels of intercellular adhesion molecule-1 were found to be increased in ischaemic heart disease patients and polymorphisms in the E-selectin gene were associated with accelerated atherosclerosis in young (age < 40 years) patients, further suggesting a role of inflammation in atherosclerosis. Cholesterol loading in macrophages was found to induce interleukin-8 expression, suggesting an association between foam cell formation and beta 2-integrin-dependent adhesion of leukocytes. Enhanced endothelium-platelet interaction induced by hypercholesterolaemia is mediated by von Willebrand factor, whereas platelet adhesion to subendothelial matrix is mediated by fibulin-fibrinogen complexes. Activated platelets mediate the homing of leukocytes by interaction with the subendothelial matrix under shear stresses that do not allow neutrophil adhesion. They may also contribute to the oxidative modification of LDL, provide a source of lipids for foam cell generation and contribute to smooth muscle cell proliferation. Oxidized LDL induces tissue factor in macrophages that also provide sites for fibrin polymerization and decreases the anticoagulant activity of endothelium by interfering with thrombomodulin expression and inactivating tissue factor pathway inhibitor. Intravascular fibrinolysis induced by tissue-type plasminogen activator or urokinase may contribute to the initiation of atherosclerosis by inducing P-selectin and platelet activating factor as well as to plaque rupture, either directly or indirectly, by activating metalloproteinases. Plasminogen activator inhibitor-1 inhibits smooth muscle cell migration and, in the presence of vitronectin, promotes the clearance of thrombin by LDL receptor-related protein at sites of endothelial injury.