gebhart/patrepeval huggingface dataset:
Improvement of intestinal absorption of biologically active peptides by chemical modification with fatty acids. (1997)

It is well known that the oral bioavailability of peptide and protein drugs is generally poor because they are extensively degraded by proteases in the gastrointestinal tract and impermeable through the intestinal mucosa. Therefore, various approaches have been examined to overcome the delivery problems of these peptides and to improve their absorption via the gastrointestinal tract. Of these approaches, a potentially useful approach to solve these delivery problems may be chemical modification of peptides and proteins to produce prodrugs and analogues. Thus, it is plausible that this chemical approaches may protect peptides against degradation by peptidases and other enzymes present at the mucosal barrier and renders the peptides and proteins more lipophilic, resulting in increased bioavailability. From these standpoints, we synthesized lipophilic derivatives of peptides and proteins such as thyrotropin-releasing hormone (TRH), tetragastrin (TG), calcitonin and insulin by chemical modification with fatty acids. The pharmacological activities of these derivatives were relatively high as compared with the native peptides. A significant increase in the intestinal absorption of these derivatives of peptides was observed in comparison with native peptides. Overall, the effects of acylation on the intestinal absorption of these peptides were more predominant in the large intestine than those in the small intestine. In addition, these derivatives were more stable than the parent peptides in homogenates of the various intestinal mucosae. We also examined the intestinal transport characteristics of TG and its acyl derivatives using Caco-2 cell monolayer system in order to assess the contribution of enzymatic and transport barriers on their intestinal absorption. The degradation clearance of TG on the apical membrane was decreased by chemical modification with fatty acids. In addition, the permeability clearance of TG was improved by the acylation. On the other hand, CLp value of carboxyfluorescein, a paracellular transport marker, was increased by the coadministration with acyl-TGs, suggesting that these derivatives have absorption enhancing actions and may enhance themselves across the Caco-2 cell monolayers. In summary, this chemical modification approaches may be useful to improve the intestinal absorption of peptides and proteins.
Vascular Endothelial Growth Factor as an Immediate-Early Activator of UV-induced Skin Injury (2020)

ABSTRACT The negative health consequences of acute ultraviolet (UV) exposure are evident, with reports of 30,000 emergency room visits annually to treat the effects of sunburn in the United States alone. Acute effects of sunburn include erythema, edema, and severe pain, and chronic overexposure to UV radiation can lead to skin cancer. While the pain associated with the acute effects of sunburn may be relieved by current interventions, existing post-sunburn treatments are not capable of reversing the cumulative and long-term pathological effects of UV exposure, an unmet clinical need. Here we show that activation of the vascular endothelial growth factor (VEGF) pathway is a direct and immediate consequence of acute UV exposure, and activation of VEGF signaling is necessary for the initiating the acute pathological effects of sunburn. In UV-exposed human subjects, VEGF signaling is activated within hours. Topical delivery of VEGF pathway inhibitors, targeted against the ligand VEGF-A (gold nanoparticles conjugated with anti-VEGF antibodies) and small molecule antagonists of VEGF receptor signaling, prevent the development of erythema and edema in UV-exposed mice. Collectively, these findings suggest targeting VEGF signaling may reduce the subsequent inflammation and pathology associated with UV-induced skin damage, which reveals a new post-exposure therapeutic window to potentially inhibit the known detrimental effects of UV on human skin.
Effect of γ34.5 Deletions on Oncolytic Herpes Simplex Virus Activity in Brain Tumors (2012)

The ICP34.5 protein of herpes simplex virus (HSV) is involved in many aspects of viral pathogenesis; promoting neurovirulence, inhibiting interferon-induced shutoff of protein synthesis, interacting with PCNA and TBK1, inhibiting dendritic cell (DC) maturation, and binding to Beclin 1 to interfere with autophagy. Because of its key role in neuropathogenicity, the γ34.5 gene is deleted in all oncolytic HSVs (oHSVs) currently in clinical trial for treating malignant gliomas. Unfortunately, deletion of γ34.5 attenuates virus replication in cancer cells, especially human glioblastoma stem cells (GSCs). To develop new oHSVs for use in the brain and that replicate in GSCs, we explored the effect of deleting the γ34.5 Beclin 1 binding domain (BBD). To ensure cancer selectivity and safety, we inactivated the ICP6 gene (UL39, large subunit of ribonucleotide reductase), constructing ICP6 mutants with different γ34.5 genotypes: Δ68HR-6, intact γ34.5; Δ68H-6, γ34.5 BBD deleted; and 1716-6, γ34.5 deleted. Multimutated Δ68H-6 exhibited minimal neuropathogenicity in HSV-1-susceptible mice, as opposed to Δ68H and Δ68HR-6. It replicated well in human glioma cell lines and GSCs, effectively killing cells in vitro and prolonging survival of mice bearing orthotopic brain tumors. In contrast, 1716 and 1716-6 barely replicated in GSCs. Infection of glioma cells with Δ68H-6 and 1716-6 induced autophagy and increased phosphorylation of eIF2α, while inhibition of autophagy, by Beclin 1 short hairpin RNA (shRNA) knockdown or pharmacological inhibition, had no effect on virus replication or phosphorylated eIF2α (p-eIF2α) levels. Thus, Δ68H-6 represents a new oHSV vector that is safe and effective against a variety of brain tumor models.
Macrophage Migration Inhibitory Factor Limits Activation-Induced Apoptosis of Platelets via CXCR7-Dependent Akt Signaling (2014)

MIF interaction with CXCR7 modulates platelet survival and thrombotic potential both in vitro and in vivo and thus could regulate thrombosis and inflammation.
Fabrication of three-dimensional periodic microstructures in photoresist SU-8 by phase-controlled holographic lithography (2006)

Three-dimensional (3D) periodic dielectric structures were recorded in a commercial photoresist SU-8 by exposure to intensity patterns created by five interfering coherent femtosecond Ti: sapphire laser pulses. Periodic symmetry of these patterns was controlled by the choice of mutual convergence angles of the beams as well as their phases. The fabricated structures are mechanically and chemically stable, well-connected frameworks of SU-8 regions in air; the smallest dimensions of SU-8 features are in the sub-micrometre range. The structures exhibit a high degree of long-range order across areas as large as 1 mm in cross-section.
Control of Rotational Motion of Fine-Particle Gloud Confined in a weakly-Magnetized Dc Discharge prasma (2001)

A rotation of strongly-coupled fine-particle cloud, levitating above a negatively biased electrode, is observed in a weakly ionized argon dc discharge plasma by applying axial magnetic field in vertical direction' when the magnetic field is applied, fine-particle cloud, constituting multilayers like the Coulomb lattice in vertical direction, start to rotate in azimuthal direction with keeping the interparticle distance almost constant. The rotation direction of fine-particle cloud is controlled by changing radial plasma density profile. In case ofpeaked-type density profile, the rotation direction is paramagnetic of negatively-charged fine particles. conversely, in case of hollow-type density profile, the rotation direction is diamagnetic. A mechanism of the rotation is explained by an effect of ion motion colliding with fine particles in the presence of vertical magnetic field.
Increased processing of SINE B2 non coding RNAs unveils a novel type of transcriptome de-regulation underlying amyloid beta neuro-pathology (2020)

ABSTRACT More than 97% of the mammalian genome is non-protein coding, and repetitive elements account for more than 50% of noncoding space. However, the functional importance of many non-coding RNAs generated by these elements and their connection with pathologic processes remains elusive. We have previously shown that B2 RNAs, a class of non-coding RNAs that belong to the B2 family of SINE repeats, mediate the transcriptional activation of stress response genes (SRGs) upon application of a stimulus. Notably, B2 RNAs bind RNA Polymerase II (RNA Pol II) and suppress SRG transcription during pro-stimulation state. Upon application of a stimulus, B2 RNAs are processed into fragments and degraded, which in turn releases RNA Pol II from suppression and upregulates SRGs. Here, we demonstrate a novel role for B2 RNAs in transcriptome response to amyloid beta toxicity and pathology in the mouse hippocampus. In healthy hippocampi, activation of SRGs is followed by a transient upregulation of pro-apoptotic factors, such as p53 and miRNA-34c, which target SRGs creating a negative feedback loop that facilitates transition to the pro-stimulation state. Using an integrative RNA genomics approach, we show that in mouse hippocampi of an amyloid precursor protein knock-in mouse model and in an in vitro cell culture model of amyloid beta toxicity, this regulatory loop is dysfunctional due to increased levels of B2 RNA processing, constitutively elevated SRG expression and high p53 levels. Evidence indicates that Hsf1, a master regulator of stress response, mediates B2 RNA processing in cells, and is upregulated during amyloid toxicity accelerating the processing of SINE RNAs and SRG hyper-activation. Our study reveals that in mouse, SINE RNAs constitute a novel pathway deregulated in amyloid beta pathology, with potential implications for similar cases in the human brain, such as Alzheimer’s disease (AD). This data attributes a role to SINE RNA processing in a pathological process as well as a new function to Hsf1 that is independent of its transcription factor activity.
Glucocorticoids have opposite effects on ornithine decarboxylase and cell growth in pancreatic acinar AR42J cells. (1993)

This paper reviews the relationships between the effects of glucocorticoids on rat pancreatic acinar AR42J cell polyamine levels and cellular growth and differentiation. Glucocorticoids inhibit the growth of AR42J cells. Glucocorticoids either stimulate or inhibit the formation of polyamines in a variety of cell types. Cells require polyamines for normal growth. Therefore, we tested the hypothesis that polyamines mediate the effects of glucocorticoids on AR42J cells. First, to confirm that AR42J cells required polyamines for growth we examined the effects of inhibiting ornithine decarboxylase (ODC). ODC is the most important and generally rate-limiting enzyme in the synthesis of the polyamines. As expected, the ODC inhibitor difluoromethylornithine (DFMO) inhibited AR42J cell DNA synthesis, and the addition of exogenous putrescine reversed this effect. The levels of growth inhibition by glucocorticoids and DFMO treatment were similar. Second, we examined the effects of glucocorticoids on ODC. Surprisingly, glucocorticoids increased levels of AR42J cell ODC mRNA, ODC activity, and putrescine. Glucocorticoids increased these parameters over a similar time-course as they decreased DNA synthesis. Analog specificity studies indicated that a glucocorticoid receptor mediated both the growth inhibitory and ODC stimulatory effects. Dose-response studies indicated, however, that growth inhibition was more sensitive to dexamethasone (DEX) than were ODC levels. Therefore, polyamines do not account for the effects of glucocorticoids on AR42J cell growth. In these cells, glucocorticoids have opposite and independent effects on ODC and growth.
Eukaryotic Release Factor 3 Is Required for Multiple Turnovers of Peptide Release Catalysis by Eukaryotic Release Factor 1 (2013)

Eukaryotic peptide release factor 3 (eRF3) is a conserved, essential gene in eukaryotes implicated in translation termination. We have systematically measured the contribution of eRF3 to the rates of peptide release with both saturating and limiting levels of eukaryotic release factor 1 (eRF1). Although eRF3 modestly stimulates the absolute rate of peptide release (∼5-fold), it strongly increases the rate of peptide release when eRF1 is limiting (>20-fold). This effect was generalizable across all stop codons and in a variety of contexts. Further investigation revealed that eRF1 remains associated with ribosomal complexes after peptide release and subunit dissociation and that eRF3 promotes the dissociation of eRF1 from these post-termination complexes. These data are consistent with models where eRF3 principally affects binding interactions between eRF1 and the ribosome, either prior to or subsequent to peptide release. A role for eRF3 as an escort for eRF1 into its fully accommodated state is easily reconciled with its close sequence similarity to the translational GTPase EFTu.
MACHINE LEARNING METHODS FOR DETECTING PATTERNS OF MANAGEMENT FRAUD (2012)

Discovery of financial fraud has profound social consequences. Loss of stockholder value, bankruptcy, and loss of confidence in the professional audit firms have resulted from failure to detect financial fraud. Previous studies that have attempted to discover fraud patterns from publicly available information have achieved only moderate levels of success. This study explores the capabilities of recently developed statistical learning and data mining methods in an attempt to advance fraud discovery performance to levels that have potential for proactive discovery or mitigation of financial fraud. The partially adaptive methods we test have achieved success in a number of complex problem domains and are easily interpretable. Ensemble methods, which combine predictions from multiple models via boosting, bagging, or related approaches, have emerged as among the most powerful data mining and machine learning methods. Our study includes random forests, stochastic gradient boosting, and rule ensembles. The results for ensemble models show marked improvement over past efforts, with accuracy approaching levels of practical potential. In particular, rule ensembles do so while maintaining a degree of interpretability absent in the other ensemble methods.
Known Cellular and Receptor Interactions of Animal and Human Coronaviruses: A Review (2022)

This article aims to review all currently known interactions between animal and human coronaviruses and their cellular receptors. Over the past 20 years, three novel coronaviruses have emerged that have caused severe disease in humans, including SARS-CoV-2 (severe acute respiratory syndrome virus 2); therefore, a deeper understanding of coronavirus host-cell interactions is essential. Receptor-binding is the first stage in coronavirus entry prior to replication and can be altered by minor changes within the spike protein-the coronavirus surface glycoprotein responsible for the recognition of cell-surface receptors. The recognition of receptors by coronaviruses is also a major determinant in infection, tropism, and pathogenesis and acts as a key target for host-immune surveillance and other potential intervention strategies. We aim to highlight the need for a continued in-depth understanding of this subject area following on from the SARS-CoV-2 pandemic, with the possibility for more zoonotic transmission events. We also acknowledge the need for more targeted research towards glycan-coronavirus interactions as zoonotic spillover events from animals to humans, following an alteration in glycan-binding capability, have been well-documented for other viruses such as Influenza A.
A population‐based longitudinal study on the implications of demographics on future blood supply (2016)

Changes in demography and medical practice impact the delicate balance between available blood supply and potential future transfusion needs. In times of pronounced demographic changes, regular monitoring of the blood demand and age structure of blood recipients and donors is required to allow strategic planning to prevent blood shortages or overproduction.
ANALYSIS OF REST-ACTIVITY RHYTHMS AND RISK OF INCIDENT MILD COGNITIVE IMPAIRMENT AND DEMENTIA IN OLDER WOMEN (2019)

Abstract In older adults, desynchronized circadian rhythms have been associated with medical illness, including Alzheimer Disease. Activity, which can be easily measured using actigraphy over consecutive 24-hour periods, is a valid marker of entrained sleep phase and correlates with entrained endogenous circadian phase. We compare results of both parametric and non-parametric analyses to test the association of rest-activity patterns with incident MCI and dementia in 2132 older women who had 2 or more 24-hrs periods of actigraphy data collected at baseline. Follow-up neuropsychological testing approximately 5 years later is used to classify women as normal, MCI, or dementia. Logistic regression models are adjusted for age, clinic site, race, education, body mass index, functional status, comorbidities, medication use, and health habits. Results suggest the importance of overall amplitude and rhythmicity, as well as timing of activity patterns over the 24-hour day as risk factors for incident MCI/dementia.
Bulk Semiconductor Quasi-Optical Concept for Guided Waves for Advanced Millimeter Wave Devices (1971)

Recent suggestions have been made for the design of bulk semiconductor millimeter wave devices, and in particular, a new type of phase shifter. In order for these designs to perform in a satisfactory manner it was found necessary to demonstrate that that electromagnetic propagation would occur largely in the interior of a semiconductor dielectric waveguide with relatively low loss. In this report an analysis is made of electromagnetic waves guided in an infinite slab of material with the properties of high resistivity silicon. Calculations and preliminary experiments are demonstrated at frequencies near 16.0 GHz. It is concluded that propagation in the semiconductor medium offers the possibility of low loss circuitry and satisfies the requisites for device design.
Recommendations in a marketplace (2019)

In recent years, two sided marketplaces have emerged as viable business models in many real world applications (e.g. Uber, AirBnb), wherein the platforms have customers not only on the demand side (e.g. users), but also on the supply side (e.g. drivers, hosts). Such multi-sided marketplace involves interaction between multiple stakeholders among which there are different individuals with assorted needs. While traditional recommender systems focused specifically towards increasing consumer satisfaction by providing relevant content to consumers, two-sided marketplaces face an interesting problem of optimizing their models for supplier preferences, and visibility. In this tutorial, we consider a number of research problems which need to be address when developing a recommendation framework powering a multi-stakeholder marketplace, and provides audience with a profound introduction to this upcoming area and presents directions of further research. Tutorial material available at: https://rishabhmehrotra.github.io/recs-in-marketplace/
Open-Loop Distributed Beamforming Using Wireless Frequency Synchronization (2020)

We present an open-loop microwave distributed beamforming system using a self-mixing circuit for wireless frequency synchronization between two transmitting nodes in relative motion. Distributed beamforming on arrays of wireless nodes requires accurate coordination of the electrical states of each node to ensure that transmitted signals arrive at the desired destination with sufficient phase alignment for high signal gain. Of the necessary coordination parameters, synchronizing the frequencies of the internal oscillators is among the most crucial to ensure distributed coherence. In this work, we demonstrate distributed beamforming between separate microwave wireless transmitters using wireless frequency synchronization in a hierarchical coordination topology that is directly scalable to larger array sizes. The primary node transmits a spectrally sparse two-tone waveform that is received by a self-mixing circuit at the secondary node. A 10-MHz frequency reference of the primary node is modulated onto the tone separation of the waveform; upon self-mixing, the demodulated 10-MHz frequency reference is passed to a phase-locked loop to discipline the oscillator of the secondary node. We demonstrate beamforming at a 1.5-GHz carrier frequency between the two nodes, performed while moving the primary node, demonstrating the ability to maintain greater than 90% ideal distributed beamforming gain.
BWCCA 2013: Keynotes (2013)

These keynote speeches discuss the following: Secure Data Processing: Perspectives and Challenges; Optimization Problems for Efficient Exploitation of High-performance Computing Systems.
Who should fix this bug? (2006)

Open source development projects typically support an open bug repository to which both developers and users can report bugs. The reports that appear in this repository must be triaged to determine if the report is one which requires attention and if it is, which developer will be assigned the responsibility of resolving the report. Large open source developments are burdened by the rate at which new bug reports appear in the bug repository. In this paper, we present a semi-automated approach intended to ease one part of this process, the assignment of reports to a developer. Our approach applies a machine learning algorithm to the open bug repository to learn the kinds of reports each developer resolves. When a new report arrives, the classifier produced by the machine learning technique suggests a small number of developers suitable to resolve the report. With this approach, we have reached precision levels of 57% and 64% on the Eclipse and Firefox development projects respectively. We have also applied our approach to the gcc open source development with less positive results. We describe the conditions under which the approach is applicable and also report on the lessons we learned about applying machine learning to repositories used in open source development.
Optimizing the Outcome of Core Decompression (2001)

This communication presents the author's perspective on recent advances in the study of osteonecrosis, explores the controversies that have arisen in the literature relating to treatment alternatives, and suggests an approach to the use of core decompression in the early stages of osteonecrosis that can prove useful to the practicing orthopaedist. Currently available diagnostic measures can identify osteonecrosis at very early stages of femoral head involvement. Quantitation of femoral head involvement on magnetic resonance imaging can differentiate lesions by the volume of head involvement and the location of the involvement relative to the weight-bearing articular surface. Although it is not yet known whether lesion size determines the effectiveness of treatment with core decompression in disease that is not yet radiographically apparent, bigger lesions are likely to respond differently then small lesions. The author applies this rationale to stage I and early stage II disease, for which core decompression is the preferred treatment. Core decompression without supplementary steps does not appear adequate for larger stage II lesions or more advanced disease. A technique that is safe and predictable should provide proper placement of the core tract, biopsy of the lesional area (desirable), and is chosen for the appropriate patient. All willing patients should be encouraged to enter into randomized prospective treatment protocols.