gebhart/patrepeval huggingface dataset:
Multi-functional polymeric micelles for chemotherapy-based combined cancer therapy (2021)

Currently, the therapeutic performance of traditional mono-chemotherapy on cancers remains unsatisfactory because of the tumor heterogeneity and multidrug resistance. In light of intricate tumor structures and distinct tumor microenvironments (TMEs), combinational therapeutic strategies with multiple anticancer drugs from different mechanisms can synergistically optimize the outcomes and concomitantly minimize the adverse effects during the therapy process. Extensive research on polymeric micelles (PMs) for biomedical applications has revealed the growing importance of nanomedicines for cancer therapy in the recent decade. Starting from traditional simple delivery systems, PMs have been extended to multi-faceted therapeutic strategies. Here we review and summarize the most recent advances in combinational therapy based on multifunctional PMs including a combination of multiple anticancer drugs, chemo-gene therapy, chemo-phototherapy and chemo-immunotherapy. The design approaches, action mechanisms and therapeutic applications of these nanodrugs are summarized. In addition, we highlight the opportunities and potential challenges associated with this promising field, which will provide new guidelines for advanced combinational cancer chemotherapy.
Transmission line analysis of MCM interconnects (2002)

The transmission line behavior of MCM-D interconnection lines is discussed with particular emphasis on the frequency dependent loss and delay characteristics. A broadband model covering the frequency spectrum from DC to RF is proposed. The applicability of this model is experimentally verified by comparison with measured S-parameters from 45 MHz to 18 GHz on test structures realized with two different MCM-D technologies. The broadband model is integrated in the time-domain network simulator TRANSPLUS. This program was developed for the simulation of the interconnection circuitry between chips, it thus includes models for the output circuits of the chips, the packaging, and the (coupled) interconnection lines. Simulations of different MCM-D interconnections between CMOS and bipolar chips are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Ionization and charge exchange rate coefficients for CTR calculations (1975)

under study: charge-exchange losses during neutral beam injection; the dynamics of plasma build-up during start-up; new approaches to mirror systems such as the ''twin-beam'' mirror. (3) Exploratory studies. Several new studies have been initiated during this period. These include: extension of the mirror neutral-beam injection studies to toroidal geometry and preliminary studies of reversed field configurations. Further details about each of these areas are contained in subsequent sections.
Atrial Fibrillation Spatiotemporal Complexity Is Affected by Pulmonary Vein Isolation (2018)

Introduction Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation. However, it is still unclear how AF complexity observed on body surface is affected by this intervention. This study aims to evaluate whether PVI has an impact on AF complexity as measured through principal component analysis (PCA) of body surface potential maps (BSPMs). Methods BSPMs were acquired with a 252-lead vest in 22 persistent AF patients (20 male, 62 11 years, maximum AF duration: 10 18 months) before and after PVI. The atrial fibrillatory wave signal (96 s) was divided in 0.5-s segments, and AF complexity was assessed by the normalized amplitude norm d and the cosine similarity cos( ) of the multilead error between the input signal at the frame (s) and its PCA projection onto a 3D subspace computed in the previous segment (s -1). AF organization was also quantified by the nondipolar component index (NDI), i.e., the amount of energy non-preserved by the 3D dipolar approximation of cardiac activity in the frame (s). Results A significant reduction in AF complexity was measured by all markers after PVI (d and cos( ): p<0.01; NDI: p<0.0001). Conclusions AF complexity can be reliably measured by the proposed BSPM features and reflect the impact of PVI.
Adaptive nanopores: A bioinspired label-free approach for protein sequencing and identification (2020)

Abstract Single molecule protein sequencing would tremendously impact in proteomics and human biology and it would promote the development of novel diagnostic and therapeutic approaches. However, its technological realization can only be envisioned, and huge challenges need to be overcome. Major difficulties are inherent to the structure of proteins, which are composed by several different amino-acids. Despite long standing efforts, only few complex techniques, such as Edman degradation, liquid chromatography and mass spectroscopy, make protein sequencing possible. Unfortunately, these techniques present significant limitations in terms of amount of sample required and dynamic range of measurement. It is known that proteins can distinguish closely similar molecules. Moreover, several proteins can work as biological nanopores in order to perform single molecule detection and sequencing. Unfortunately, while DNA sequencing by means of nanopores is demonstrated, very few examples of nanopores able to perform reliable protein-sequencing have been reported so far. Here, we investigate, by means of molecular dynamics simulations, how a re-engineered protein, acting as biological nanopore, can be used to recognize the sequence of a translocating peptide by sensing the “shape” of individual amino-acids. In our simulations we demonstrate that it is possible to discriminate with high fidelity, 9 different amino-acids in a short peptide translocating through the engineered construct. The method, here shown for fluorescence-based sequencing, does not require any labelling of the peptidic analyte. These results can pave the way for a new and highly sensitive method of sequencing.
Dissociation between alveolar transmigration of neutrophils and lung injury in hyperoxia (2006)

The objective of this study was to quantitatively assess changes in cell adhesion molecule (CAM) expression on the pulmonary endothelial surface during hyperoxia and to assess the functional significance of those changes on cellular trafficking and development of oxygen-induced lung injury. Mice were placed in >95% O(2) for 0-72 h, and pulmonary injury and neutrophil (PMN) sequestration were assessed. Specific pulmonary CAM expression was quantified with a dual-radiolabeled MAb technique. To test the role of CAMs in PMN trafficking during hyperoxia, blocking MAbs to murine P-selectin, ICAM-1, or platelet-endothelial cell adhesion molecule-1 (PECAM-1) were injected in wild-type mice. Mice genetically deficient in these CAMs and PMN-depleted mice were also evaluated. PMN sequestration occurred within 8 h of hyperoxia, although alveolar emigration occurred later (between 48 and 72 h), coincident with rapid escalation of the lung injury. Hyperoxia significantly increased pulmonary uptake of radiolabeled antibodies to P-selectin, ICAM-1, and PECAM-1, reflecting an increase in their level on pulmonary endothelium and possibly sequestered blood cells. Although both anti-PECAM-1 and anti-ICAM-1 antibodies suppressed PMN alveolar influx in wild-type mice, only mice genetically deficient in PECAM-1 showed PMN influx suppression. Neither CAM blockade, nor genetic deficiency, nor PMN depletion attenuated lung injury. We conclude that early pulmonary PMN retention during hyperoxia is not temporally associated with an increase in endothelial CAMs; however, subsequent PMN emigration into the alveolar space may be supported by PECAM-1 and ICAM-1. Blocking PMN recruitment did not prevent lung injury, supporting dissociation between PMN infiltration and lung injury during hyperoxia in mice.
Humans Deprived of Normal Binocular Vision Have Binocular Interactions Tuned to Size and Orientation (1979)

A suprathreshold grating presented to one eye elevated the threshold for the discrimination of gratings similar in size and orientation presented to the fellow eye. The magnitude and stimulus specificity of these binocular interactions in human observers with normal bioncular vision were similar to those in observers deprived of normal binocular visual experience; however, the latter showed a failure of binocular summation at threshold or subthreshold contract levels. Whereas strabismus or amblyopia disrupted the normal excitatory interactions between the two eyes, cortical inhibitory binocular connections seem not to have been disrupted.
Photoresponsive Type III Porous Liquids (2022)

Porous materials are the subject of extensive research because of potential applications in areas such as gas adsorption and molecular separations. Until recently, most porous materials were solids, but there is now an emerging class of materials known as porous liquids. The incorporation of intrinsic porosity or cavities in a liquid can result in free-flowing materials that are capable of gas uptakes that are significantly higher than conventional non-porous liquids. A handful of porous liquids have also been investigated for gas separations. Until now, the release of gas from porous liquids has relied on molecular displacement (e.g., by adding small solvent molecules), pressure or temperature swings, or sonication. Here, we explore a new method of gas release which involves photoisomerisable porous liquids comprising a photoresponsive MOF dispersed in an ionic liquid. This results in the selective uptake of CO<sub>2</sub> over CH<sub>4</sub> and allows gas release to be controlled by using UV light.
A Prospective, Randomized Study of Endometrial Telomerase during the Menstrual Cycle (2001)

The purpose of this study was to characterize telomerase activity during the menstrual cycle, focusing on the luteal phase. A total of 84 endometrial biopsy samples were obtained from 72 participants. Daily urinary LH testing (OvuQuick, Quidel) was used to establish the day of the LH rise, and participants were randomized to return during the secretory phase. Twelve women returned on the identical day during the luteal phase of a subsequent cycle to allow intercycle comparisons of telomerase activity. Telomerase activity was evaluated using a modified TRAP-eze (Intergen) detection protocol. At the time of each endometrial biopsy, serum estrogen and progesterone were measured. Proliferative phase endometrium showed high telomerase activity. At the onset of the luteal phase telomerase activity was high, but it decreased during the early luteal phase, disappeared by the midluteal phase (6 d after LH surge detected), and then rose to moderate levels in the late luteal phase beginning on luteal d 10. Serum progesterone levels were inversely related to telomerase activity. In conclusion, endometrial telomerase activity is dynamic: high during the proliferative phase but inhibited during the midsecretory phase of the menstrual cycle. The timing of expression coincides with the rise and fall of progesterone levels and the time period of maximal uterine receptivity for embryo implantation. This supports a relationship between sex steroid levels and telomerase regulation.
Diverse immunoglobulin gene usage and convergent epitope targeting in neutralizing antibody responses to SARS-CoV-2 (2021)

It is unclear whether individuals with enormous diversity in B cell receptor repertoires are consistently able to mount effective antibody responses against SARS-CoV-2. We analyzed antibody responses in a cohort of 55 convalescent patients and isolated 54 potent neutralizing monoclonal antibodies (mAbs). While most of the mAbs target the angiotensin-converting enzyme 2 (ACE2) binding surface on the receptor binding domain (RBD) of SARS-CoV-2 spike protein, mAb 47D1 binds only to one side of the receptor binding surface on the RBD. Neutralization by 47D1 is achieved independent of interfering RBD-ACE2 binding. A crystal structure of the mAb-RBD complex shows that the IF motif at the tip of 47D1 CDR H2 interacts with a hydrophobic pocket in the RBD. Diverse immunoglobulin gene usage and convergent epitope targeting characterize neutralizing antibody responses to SARS-CoV-2, suggesting that vaccines that effectively present the receptor binding site on the RBD will likely elicit neutralizing antibody responses in a large fraction of the population.
Low complexity digital perturbation back-propagation (2011)

A novel back-propagation algorithm is proposed based on perturbation analysis to compensate the intra-channel nonlinearity. It reduces 85% back-propagation stages in an experiment of dual polarization QPSK transmission over 1500 km dispersion uncompensated link.
Dynamic Coupled Fault Diagnosis With Propagation and Observation Delays (2013)

In this paper, we propose a delay dynamic coupled fault diagnosis (DDCFD) model to deal with the problem of coupled fault diagnosis with fault propagation/transmission delays and observation delays with imperfect test outcomes. The problem is to determine the most likely set of faults and their time evolution that best explains the observed test outcomes over time. It is formulated as a combinatorial optimization problem, which is known to be NP-hard. Since the faults are coupled, the problem does not have a decomposable structure as, for example, in dynamic multiple fault diagnosis, where the coupled faults and delays are not taken into account. Consequently, we propose a partial-sampling method based on annealed maximum a posteriori (MAP) algorithm, a method that combines Markov chain Monte Carlo and simulated annealing, to deal with the coupled-state problem. By reducing the number of samples and by avoiding redundant computations, the computation time of our method is substantially smaller than the regular annealed MAP method with no noticeable impact on diagnostic accuracy. Besides the partial-sampling method, we also propose an algorithm based on block coordinate ascent and the Viterbi algorithm (BCV) to solve the DDCFD problem. It can be considered as an extension of the method used to solve the dynamic coupled fault diagnosis (DCFD) problem. The model and algorithms presented in this paper are tested on a number of simulated systems. The results show that the BCV algorithm has better accuracy but results in large computation time. It is only feasible for problems with small delays. The partial-sampling algorithm has a smaller computation time with an acceptable diagnostic accuracy. It can be used on systems with large delays and complex topological structure.
H3K36 methylation promotes longevity by enhancing transcriptional fidelity (2015)

Epigenetic mechanisms, including histone post-translational modifications, control longevity in diverse organisms. Relatedly, loss of proper transcriptional regulation on a global scale is an emerging phenomenon of shortened life span, but the specific mechanisms linking these observations remain to be uncovered. Here, we describe a life span screen in Saccharomyces cerevisiae that is designed to identify amino acid residues of histones that regulate yeast replicative aging. Our results reveal that lack of sustained histone H3K36 methylation is commensurate with increased cryptic transcription in a subset of genes in old cells and with shorter life span. In contrast, deletion of the K36me2/3 demethylase Rph1 increases H3K36me3 within these genes, suppresses cryptic transcript initiation, and extends life span. We show that this aging phenomenon is conserved, as cryptic transcription also increases in old worms. We propose that epigenetic misregulation in aging cells leads to loss of transcriptional precision that is detrimental to life span, and, importantly, this acceleration in aging can be reversed by restoring transcriptional fidelity.
Influence of water and enzyme SpnF on the dynamics and energetics of the ambimodal [6+4]/[4+2] cycloaddition (2018)

SpnF is the first monofunctional Diels-Alder/[6+4]-ase that catalyzes a reaction leading to both Diels-Alder and [6+4] adducts through a single transition state. The environment-perturbed transition-state sampling method has been developed to calculate free energies, kinetic isotope effects, and quasi-classical reaction trajectories of enzyme-catalyzed reactions and the uncatalyzed reaction in water. Energetics calculated in this way reproduce the experiment and show that the normal Diels-Alder transition state is stabilized by H bonds with water molecules, while the ambimodal transition state is favored in the enzyme SpnF by both intramolecular hydrogen bonding and hydrophobic binding. Molecular dynamics simulations show that trajectories passing through the ambimodal transition state bifurcate to the [6+4] adduct and the Diels-Alder adduct with a ratio of 1:1 in the gas phase, 1:1.6 in water, and 1:11 in the enzyme. This example shows how an enzyme acts on a vibrational time scale to steer post-transition state trajectories toward the Diels-Alder adduct.
Effects of Probiotic Supplementation on the Gut Microbiota and Antibiotic Resistome Development in Preterm Infants (2018)

<b>Objectives:</b> In 2014 probiotic supplementation (<i>Lactobacillus acidophilus</i> and <i>Bifidobacterium longum</i> subspecies <i>infantis;</i> Infloran<sup>Ⓡ</sup>) was introduced as standard of care to prevent necrotizing enterocolitis (NEC) in extremely preterm infants in Norway. We aimed to evaluate the influence of probiotics and antibiotic therapy on the developing gut microbiota and antibiotic resistome in extremely preterm infants, and to compare with very preterm infants and term infants not given probiotics. <b>Study design:</b> A prospective, observational multicenter study in six tertiary-care neonatal units. We enrolled 76 infants; 31 probiotic-supplemented extremely preterm infants <28 weeks gestation, 35 very preterm infants 28-31 weeks gestation not given probiotics and 10 healthy full-term control infants. Taxonomic composition and collection of antibiotic resistance genes (resistome) in fecal samples, collected at 7 and 28 days and 4 months age, were analyzed using shotgun-metagenome sequencing. <b>Results:</b> Median (IQR) birth weight was 835 (680-945) g and 1,290 (1,150-1,445) g in preterm infants exposed and not exposed to probiotics, respectively. Two extremely preterm infants receiving probiotic developed NEC requiring surgery. At 7 days of age we found higher median relative abundance of <i>Bifidobacterium</i> in probiotic supplemented infants (64.7%) compared to non-supplemented preterm infants (0.0%) and term control infants (43.9%). <i>Lactobacillus</i> was only detected in small amounts in all groups, but the relative abundance increased up to 4 months. Extremely preterm infants receiving probiotics had also much higher antibiotic exposure, still overall microbial diversity and resistome was not different than in more mature infants at 4 weeks and 4 months. <b>Conclusion:</b> Probiotic supplementation may induce colonization resistance and alleviate harmful effects of antibiotics on the gut microbiota and antibiotic resistome. <b>Clinical Trial Registration:</b> Clinicaltrials.gov: NCT02197468. https://clinicaltrials.gov/ct2/show/NCT02197468.
Effect of Surfactant on Unilamellar Polymeric Vesicles:  Altered Membrane Properties and Stability in the Limit of Weak Surfactant Partitioning (2002)

Surfactant incorporation into bilayer vesicle membranes made of diblock copolymers was examined for the case of weak affinity between the membrane [poly(ethyl ethylene)-co-poly(ethylene oxide)] and the surfactant [Pluronic L31]. For copolymer vesicles formed in the absence of surfactant and subsequently exposed to surfactant solutions, a micropipet aspiration technique was employed to monitor surfactant incorporation kinetics and to characterize surfactant-induced changes in the membranes. Though the surfactant incorporation was weak and reversible, it reduced the area expansion modulus by almost a factor of 2, while dramatically increasing the vesicles' susceptibility to lysis. Additionally, water permeability was increased by a factor of 2. The surfactant incorporation rates were proportional to the free surfactant concentration, and other features of the membrane response to surfactant exposure were consistent with transport-limited surfactant attack of the membranes. The most plausible mechanism for surfactant interaction with the membrane is that the surfactant resides at the interface between the hydrophobic membrane core and the poly(ethylene oxide) corona, reducing the interfacial tension of the lamella and allowing the membrane to thin slightly, also increasing its area per unit mass. Observations suggest slow surfactant penetration of the hydrophobic core such that this particular surfactant acts on both inner and outer leaflets.
Fibrous hamartoma of infancy: an experience of a single institute (2011)

Purpose: Fibrous hamartoma (FH) of infancy is a distinctive fibrous growth that most frequently occurs at birth and during the postnatal period. It is important for clinicians and pathologists to recognize this entity to avoid an aggressive approach. Methods: We herein describe the clinicopathologic features of 9 FHs diagnosed at a single institution between 1997 and 2010. Results: There were 7 boys and 2 girls, and the mean age of presentation was 14.7 months. The common locations were the lower back and gluteal region (n = 3) and scrotum (n = 2). They were solitary lesions, and measured 1.0 to 7.0 cm in maximum diameter (mean, 4.9 cm). The excised masses tended to be poorly circumscribed, and consisted of an intimate mixture of firm, gray-white tissue with fat. Histologically, these lesions were composed of 3 components forming a vague, irregular, organoid pattern: well-defined intersecting trabeculae of fibrocollagenous tissue; loosely textured areas of small, rounded, primitive mesenchymal cells; and mature fat. Over a median follow-up of 72 months, no patient showed recurrence. Conclusion: FH should be distinguished from other forms of fibromatosis and malignant tumors because it is benign and usually cured by local excision.
Poly-vectoral reverse navigation (2001)

A shared node is a packet of information accessible from more than one context. A few techniques exist for displaying and navigating shared nodes, but they are either not optimal for web environments, or are lacking in richness and ease-of-use. Poly-vectoral reverse navigation (PVRN) is a technique we developed to provide information within a context about other contexts that share a node. From within a shared node, PVRN provides ready navigation to other contexts that share the node. The technique was successfully used in a commercial web site.
Tumoricidal activity of human dendritic cells (2013)

Dendritic cells (DCs) are a family of professional antigen-presenting cells (APCs) that are able to initiate innate and adaptive immune responses against pathogens and tumor cells. The DC family is heterogeneous and is classically divided into two main subsets, each with its unique phenotypic and functional characteristics: myeloid DCs (mDCs) and plasmacytoid DCs (pDCs). Recent results have provided intriguing evidence that both DC subsets can also function as direct cytotoxic effector cells; in particular, against cancer cells. In this review, we delve into this understudied function of human DCs and discuss why these so-called killer DCs might become important tools in future cancer immunotherapies.