gebhart/patrepeval huggingface dataset:
Human antibody recognizing a quaternary epitope in the Puumala virus glycoprotein provides broad protection against orthohantaviruses (2022)

The rodent-borne hantavirus Puumala virus (PUUV) and related agents cause hemorrhagic fever with renal syndrome (HFRS) in humans. Other hantaviruses, including Andes virus (ANDV) and Sin Nombre virus, cause a distinct zoonotic disease, hantavirus cardiopulmonary syndrome (HCPS). Although these infections are severe and have substantial case fatality rates, no FDA-approved hantavirus countermeasures are available. Recent work suggests that monoclonal antibodies may have therapeutic utility. We describe here the isolation of human neutralizing antibodies (nAbs) against tetrameric Gn/Gc glycoprotein spikes from PUUV-experienced donors. We define a dominant class of nAbs recognizing the "capping loop" of Gn that masks the hydrophobic fusion loops in Gc. A subset of nAbs in this class, including ADI-42898, bound Gn/Gc complexes but not Gn alone, strongly suggesting that they recognize a quaternary epitope encompassing both Gn and Gc. ADI-42898 blocked the cell entry of seven HCPS- and HFRS-associated hantaviruses, and single doses of this nAb could protect Syrian hamsters and bank voles challenged with the highly virulent HCPS-causing ANDV and HFRS-causing PUUV, respectively. ADI-42898 is a promising candidate for clinical development as a countermeasure for both HCPS and HFRS, and its mode of Gn/Gc recognition informs the development of broadly protective hantavirus vaccines.
Communicating with the dying (1975)

Telling a patient that the outcome of his illness is not good, or even hopeless, requires sensitivity and the ability to communicate with him in the setting of a hospital which is an unnatural environment divorced from family and friends. It is a task which must be taught and learned by doctors and nurses.
Analysis of Embedded Package Capacitors for High Performance Components (2006)

The ever increasing power requirements of processors and application specific integrated circuits (ASICs) impose stringent requirements on the design of power distribution networks (PDNs). This paper highlights a power analysis methodology and discusses the decoupling requirements of high performance components. The advantages of embedded package capacitors in core and I/O decoupling will be highlighted
Skeletal myogenic differentiation of human urine-derived cells as a potential source for skeletal muscle regeneration (2014)

Stem cells are regarded as possible cell therapy candidates for skeletal muscle regeneration. However, invasive harvesting of those cells can cause potential harvest-site morbidity. The goal of this study was to assess whether human urine-derived stem cells (USCs), obtained through non-invasive procedures, can differentiate into skeletal muscle linage cells (Sk-MCs) and potentially be used for skeletal muscle regeneration. In this study, USCs were harvested from six healthy individuals aged 25-55. Expression profiles of cell-surface markers were assessed by flow cytometry. To optimize the myogenic differentiation medium, we selected two from four different types of myogenic differentiation media to induce the USCs. Differentiated USCs were identified with myogenic markers by gene and protein expression. USCs were implanted into the tibialis anterior muscles of nude mice for 1 month. The results showed that USCs displayed surface markers with positive staining for CD24, CD29, CD44, CD73, CD90, CD105, CD117, CD133, CD146, SSEA-4 and STRO-1, and negative staining for CD14, CD31, CD34 and CD45. After myogenic differentiation, a change in morphology was observed from 'rice-grain'-like cells to spindle-shaped cells. The USCs expressed specific Sk-MC transcripts and protein markers (myf5, myoD, myosin, and desmin) after being induced with different myogenic culture media. Implanted cells expressed Sk-MC markers stably in vivo. Our findings suggest that USCs are able to differentiate into the Sk-MC lineage in vitro and after being implanted in vivo. Thus, they might be a potential source for cell injection therapy in the use of skeletal muscle regeneration. Copyright © 2014 John Wiley & Sons, Ltd.
Towards in vivo imaging of intramolecular fluorescence resonance energy transfer parameters (2009)

Fluorescence resonance energy transfer (FRET) is a nonradiative energy transfer process based on dipole-dipole interaction between donor and acceptor fluorophores that are spatially separated by a distance of a few nanometers. FRET has proved to be of immense value in the study of cellular function and the underlying cause of disease due to, for example, protein misfolding (of consequence in Alzheimer's disease). The standard parameterization in intramolecular FRET is the lifetime and yield, which can be related to the donor-acceptor (DA) distance. FRET imaging has thus far been limited to in vitro or near-surface microscopy because of the deleterious effects of substantial scatter. We show that it is possible to extract the microscopic FRET parameters in a highly scattering environment by incorporating the FRET kinetics of an ensemble of DA molecules connected by a flexible or rigid linker into an optical diffusion tomography (ODT) framework. We demonstrate the efficacy of our approach for extracting the microscopic DA distance through simulations and an experiment using a phantom with scattering properties similar to tissue. Our method will allow the in vivo imaging of FRET parameters in deep tissue, and hence provide a new vehicle for the fundamental study of disease.
Internet Technologies Demonstration Session II (1999)

This session will highlight recent technical innovations in user interface technologies for the Internet. The Internet poses many unique challenges for the user interface designer. It also enables functional capabilities that may be applied in a variety of domains. Attendees will have an opportunity to have first-hand experience with developmental technologies that offer a sampling of the latest ideas. Developers participating in the session will interact with small groups of attendees and provide a brief demonstration and discussion. Through this session, the intent is to raise HFES attendee's awareness of the direction of technological innovation for the Internet and to provide a context for the exchange of insights and ideas among all those concerned with interface design and product design in general, for the Internet.
Epidermal growth factor receptor-dependent stimulation of amphiregulin expression in androgen-stimulated human prostate cancer cells. (1994)

Amphiregulin is a heparin-binding epidermal growth factor (EGF)-related peptide that binds to the EGF receptor (EGF-R) with high affinity. In this study, we report a role for amphiregulin in androgen-stimulated regulation of prostate cancer cell growth. Androgen is known to enhance EGF-R expression in the androgen-sensitive LNCaP human prostate carcinoma cell line, and it has been suggested that androgenic stimuli may regulate proliferation, in part, through autocrine mechanisms involving the EGF-R. In this study, we demonstrate that LNCaP cells express amphiregulin mRNA and peptide and that this expression is elevated by androgenic stimulation. We also show that ligand-dependent EGF-R stimulation induces amphiregulin expression and that androgenic effects on amphiregulin synthesis are mediated through this EGF-R pathway. Parallel studies using the estrogen-responsive breast carcinoma cell line, MCF-7, suggest that regulation of amphiregulin by estrogen may also be mediated via an EGF-R pathway. In addition, heparin treatment of LNCaP cells inhibits androgen-stimulated cell growth further suggesting that amphiregulin can mediate androgen-stimulated LNCaP proliferation. Together, these results implicate an androgen-regulated autocrine loop composed of amphiregulin and its receptor in prostate cancer cell growth and suggest that the mechanism of steroid hormone regulation of amphiregulin synthesis may occur through androgen upregulation of the EGF-R and subsequent receptor-dependent pathways.
Increasing persistence through scattering environments by using circularly polarized light (2015)

We present simulation results that show circularly polarized light persists through scattering environments better than linearly polarized light. Specifically, we show persistence is enhanced through many scattering events in an environment with a size parameter representative of advection fog at infrared wavelengths. Utilizing polarization tracking Monte Carlo simulations we show a larger persistence benefit for circular polarization versus linear polarization for both forward and backscattered photons. We show the evolution of the incident polarization states after various scattering events which highlight the mechanism leading to circular polarization’s superior persistence.
Data-mining-assisted resonance labeling in ring-based DWDM transceivers (2020)

An algorithm using hierarchical clustering is proposed to label resonances in ring-based DWDM transceivers. By identifying missing resonances and split-peaks due to reflection, the algorithm enables binning of individual ring resonances by passive optical tests.
Tuning Methods for Uncooled Low-Cost Tunable Lasers in WDM-PON (2011)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text M. Roppelt, F. Pohl, K. Grobe, M. Eiselt, and J. Elbers, "Tuning Methods for Uncooled Low-Cost Tunable Lasers in WDM-PON," in Optical Fiber Communication Conference/National Fiber Optic Engineers Conference 2011, OSA Technical Digest (CD) (Optica Publishing Group, 2011), paper NTuB1. Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Early prediction of anti-epidermal growth factor receptor (EGFR) therapy with 18[F]FDG-PET: A preclinical and clinical correlation (2007)

14064 Background: Predictive biomarkers for response to anti-EGFR therapy are of significant clinical importance. We hypothesized that early changes in 18[F]FDG tumor uptake predict response to anti-EGFR therapy. We investigated this in a mice model and correlated these findings with human patients undergoing anti-EGFR therapy. Methods: Mice bearing two head and neck squamous cell cancer (HnNSCC) xenografts (Hep2, Cal27) received vehicle or erlotinib for 3 weeks. 18[F]FDG uptake were imaged with small animal micro- PET at baseline and after 1 week of therapy, and reported in SUVmax. For clinical correlation, human patients with HnNSCC receiving erlotinib were identified from an ongoing clinical trial. 18[F]FDG-PET images were obtained at baseline and after 2 weeks of erlotinib monotherapy. Tumor specimens were obtained by fine-needle aspiration biopsy at the same time as PET. A panel of pharmacodynamic markers (including Ki-67 and pMAPK) were assessed . Results: Hep2 was resistant to erlotinib therapy (Tumor/Control [T/C]: 0.8) while Cal27 was sensitive (T/C: 0.2). SUVmax in the resistant Hep2 xenografts was not significantly different from the control (86% ± 70% of control) while SUVmax in the treated sensitive Cal27 xenografts showed a significant decrease than control (-2% ± 7%). Ki-67 in the treated Hep2 was not significantly different from control while that in Cal27 was &lt;50% of control. For clinical correlation, ki-67 score was higher after 2 weeks in the patient resistant to erlotinib monotherapy by 18[F]FDG-PET (SUVmax increased by 14%, ± 11%) and was lower in the patient who was 18[F]FDG-PET sensitive (SUVmax decreased by 56%, ± 13%). pMAPK decreased in all cases and had a poor correlation with efficacy. Conclusions: Early dynamic changes in 18[F]FDG tumor uptake is predictive of response to anti-EGFR therapy and correlates with changes in ki-67 expression, both in a preclinical and a clinical scenario. No significant financial relationships to disclose.
αβ and γδ T cell subsets in chronic renal failure in children on dialysis treatment (2002)

The T cell depletion in chronic renal failure (CRF) patients primarily results from uremic-related toxicities, rather than from CAPD or HD-related incompatibilities. We showed a significant decrease of gammadelta T cells in CRF patients on HD, that may be partly responsible for impaired T-dependent responsiveness in that group. The intradialytic changes of gammadelta Tcells may result from a different degree of biocompatibility during the application of various dialysis membranes.
Task-level robot learning: juggling a tennis ball more accurately (2003)

Results are presented from a preliminary investigation of task-level learning, an approach to learning from practice. The authors programmed a robot to juggle a single ball in three dimensions by batting it upwards with a large paddle. The robot uses a real-time binary vision system to track the ball and measure its performance. Task-level learning consists of building a model of performance errors at the task level during practice, and using that model to refine task-level commands. A polynomial surface was fitted to the errors in the path which the ball took after each hit, and this task model is used to refine how the ball is hit. This application of task-level learning dramatically increased the number of consecutive hits the robot could execute before the ball was hit out of range of the paddle.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Multiscale Topology Optimization for Additively Manufactured Objects (2018)

The precise control of mass and energy deposition associated with additive manufacturing (AM) processes enables the topological specification and realization of how space can be filled by material in multiple scales. Consequently, AM can be pursued in a manner that is optimized such that fabricated objects can best realize performance specifications. In the present work, we propose a computational multiscale method that utilizes the unique meso-scale structuring capabilities of implicit slicers for AM, in conjunction with existing topology optimization (TO) tools for the macro-scale, in order to generate structurally optimized components. The use of this method is demonstrated on two example objects including a load bearing bracket and a hand tool. This paper also includes discussion concerning the applications of this methodology, its current limitations, a recasting of the AM digital thread, and the future work required to enable its widespread use.
Practical Measurement Issues (2010)

In this chapter, we will consider a variety of practical issues related to MTF measurement, including the cascade property of MTF multiplication, the quality of the auxiliary optics such as collimators and relay lenses, the issue of source coherence, and the finite size of the source for a PSF or LSF test. We will also look at the instrumental-MTF contribution of the detector or the sensor array that receives the image-irradiance data. We will investigate ways to increase the signal-to-noise ratio, making use of redundancy in the source and image planes. We will conclude with some comments about repeatability and accuracy of MTF measurements and the use of computers for data acquisition and processing. At the end of the chapter we will consider four different instrument approaches that are representative of commercial MTF equipment, and identify the design tradeoffs that were made.
Anti-drug Antibodies in Normal Subjects Receiving a Single Dose of Intravenous Infliximab and Their Pharmacokinetic Effects (2017)

Introduction: Pharmacokinetic (PK) studies of infliximab (IFX) are generally performed in patients receiving chronic IFX therapy for autoimmune diseases, including IBD. In these patients, antidrug antibodies (ADAs) to IFX increase IFX clearance, resulting in diminished serum levels and decreased drug efficacy. This study investigates the development of ADAs in normal subjects receiving a single dose of intravenous IFX, and details the PK effects of these ADAs. Methods: Data was obtained from a published single-blind, parallel group, single-dose study of 159 normal subjects randomized to receive 5 mg/kg of intravenous SB2 (IFX biosimilar), EU-sourced Remicade (EU-IFX) or US-sourced Remicade (US-IFX), (Shin D, et al. BioDrugs (2015) 29:381-388). Serum IFX levels were measured at 1, 2, 3, 6, 12, 24, 48, 72 hours and 5, 7, 14, 21, 28, 42, 56, and 70 days after administration. ADAs were measured pre-dose and at 29 and 71 days. Results from the first 10 subjects randomized to each treatment arm were utilized for this study. A two-compartment model was developed for PK analysis, resulting in the following parameters: K1 and K2 (distribution and elimination rate constants), and AUC C0-Clast = area under the serum vs time curve to the last measured data point. Formulas for calculated parameters included: T ½ elim (elimination half time) =0.693/K2 AUC C0-C∞ (AUC to infinity) = AUC C0-Clast+Clast/K2 IFX CL=Dose/ AUC C0-C∞ Comparison for parameters of interest (IFX Cl, T ½ elim, serum IFX 8 and serum IFX at 10 weeks) in subjects with and without ADAs were performed using unpaired T tests. A linear regression model was developed to explore the relationship of serum IFX levels and IFX clearance. Results: At 10 weeks, 11 subjects (37%) developed ADA. IFX Cl was increased in subjects with ADA compared to without ADA (12.89 +/- 2.69 ml/hr vs 9.90 +/-1.74 ml/hr, p < 0.0005). Shorter T ½ elim occurred in subjects with ADA, (282.4 +/-56.4 vs 343.3+/-61.9 hours, p < 0.01). Markedly decreased serum IFX levels at 8 and 10 weeks were seen in subjects with ADAs (Table 1). Serum IFX measured at 8 weeks correlated closely with IFX Cl (R2= 0.5494, p< 0.0001) (Figure 1).FigureTable: Table. Pharmacokinetic Parameters in Normal Subjects with and without Development of Anti-Drug Antibodies (ADA) Following a Single Dose of Intravenous Infliximab (IFX)Conclusion: ADAs occur commonly in normal subjects after a single intravenous dose of IFX. The development of IFX ADAs result in faster IFX clearance and lower serum IFX levels. These data favor early intervention to prevent ADAs and maximize efficacy of biologic therapy.
Supplementary Tables 1 - 3 from PD-1 Expression on Peripheral Blood Cells Increases with Stage in Renal Cell Carcinoma Patients and Is Rapidly Reduced after Surgical Tumor Resection (2023)

&lt;p&gt;PDF file - 79K, Supplemental Table S1. Donor Characteristics. Supplemental Table S2. Antibody staining panel. Supplemental Table S3. Specific immune parameters analyzed.&lt;/p&gt;
Gene Therapy for Hemophilia A (1997)

Significant progress has been made on the development of gene therapy for the treatment of hemophilia A, a common bleeding disorder caused by subnormal levels of blood coagulation factor VIII (FVIII). Recent advances in gene transfer technology have enabled the expression of therapeutic to physiological levels of human FVIII in normal animals as well as hemophiliac mice and dogs. However, the in vivo persistence of FVIII expression was variable, ranging from one day to over five months. Despite recent advances in the development of hemophilia A gene transfer vectors, each still faces limitations to its clinical utility. Current research is focused on improving gene transfer vehicles and delivery methods to enable sustained clotting factor expression, treatment readministration, and circumvention of the host immune response to the treatment.
Curcumin in the treatment of osteoarthritis: the proof-of-concept. (2010)

peer reviewed
Targeted systematic evolution of an RNA platform neutralizing DNMT1 function and controlling DNA methylation (2020)

Abstract DNA methylation is a fundamental epigenetic modification regulating gene expression. Aberrant DNA methylation is the most common molecular lesion in cancer cells. However, medical intervention has been limited to the use of toxic, unspecific demethylating drugs. Aptamers are novel high affinity targeting ligand molecules. By conjugating the inherent DNMT1 inhibiting capabilities of RNA to an aptamer platform, we generated a first-of-its kind aptamer approach that can target and neutralize DNMT1 function – the aptaDiR. Molecular modelling of RNA-DNMT1 complexes coupled with biochemical and cellular assays enabled the identification and characterization of aptaDiR. This novel RNA bio-drug blocks DNA methylation and impairs cancer cell viability. Collectively, we present an innovative RNA-based approach to modulate DNMT1 activity in cancer or diseases characterized by aberrant DNA methylation and suggest the first alternative strategy to overcome the limitations of currently approved hypomethylating protocols, which will greatly improve clinical intervention on DNA methylation.
Toward URLLC with Proactive HARQ Adaptation (2022)

In this work, we propose a dynamic decision maker algorithm to improve the proactive HARQ protocol for beyond 5G networks. Based on Lyapunov stochastic optimization, our adaptation control framework dynamically selects the number of proactive retransmissions for intermittent URLLC traffic scenarios under time-varying channel conditions without requiring any prior knowledge associated with this stochastic process. It then better exploits the trade-off between Radio Access Network (RAN) latency, reliability and resource efficiency, which is still limited in its realization on current HARQ designs. We then evaluate the performance of several HARQ strategies and show that our proposal further improves latency over the reactive regime without affecting the resource efficiency such as fixed proactive retransmission while maintaining target reliability.
Sentiment analysis (2003)

This paper illustrates a sentiment analysis approach to extract sentiments associated with polarities of positive or negative for specific subjects from a document, instead of classifying the whole document into positive or negative.The essential issues in sentiment analysis are to identify how sentiments are expressed in texts and whether the expressions indicate positive (favorable) or negative (unfavorable) opinions toward the subject. In order to improve the accuracy of the sentiment analysis, it is important to properly identify the semantic relationships between the sentiment expressions and the subject. By applying semantic analysis with a syntactic parser and sentiment lexicon, our prototype system achieved high precision (75-95%, depending on the data) in finding sentiments within Web pages and news articles.
Exploiting the mevalonate pathway to distinguish statin-sensitive multiple myeloma (2010)

Statin inhibitors, used to control hypercholesterolemia, trigger apoptosis of hematologic tumor cells and therefore have immediate potential as anticancer agents. Evaluations of statins in acute myelogenous leukemia and multiple myeloma have shown that statin efficacy is mixed, with only a subset of tumor cells being highly responsive. Our goal was to distinguish molecular features of statin-sensitive and -insensitive myeloma cells and gain insight into potential predictive markers. We show that dysregulation of the mevalonate pathway is a key determinant of sensitivity to statin-induced apoptosis in multiple myeloma. In sensitive cells, the classic feedback response to statin exposure is lost. This results in deficient up-regulation of 2 isoforms of hydroxymethylglutaryl coenzyme A reductase: the rate-limiting enzyme of the mevalonate pathway and hydroxymethylglutaryl coenzyme A synthase 1. To ascertain the clinical utility of these findings, we demonstrate that a subset of primary myeloma cells is sensitive to statins and that monitoring dysregulation of the mevalonate pathway may distinguish these cancers. We also show statins are highly effective and well tolerated in an orthotopic model of myeloma using cells harboring this dysregulation. This determinant of sensitivity further provides molecular rationale for the significant therapeutic index of statins on these tumor cells.