gebhart/patrepeval huggingface dataset:
Virus Entry as a Target for Anti-HIV Intervention (2003)

The replicative cycle of the human immunodeficiency virus (HIV) can be interrupted at several stages. Until recently only the viral reverse transcriptase and protease were the only enzymes targeted by antiretroviral agents. However, the first HIV entry inhibitor (T-20, Enfuvirtide, Fuseon) to be used in humans has been approved by the Food and Drug Administration (FDA). The HIV entry process is considered as an attractive target for chemotherapeutic intervention, as blocking HIV entry into its target cell leads to suppression of viral infectivity, replication and the cytotoxicity induced by virus-cell contacts. HIV-1 entry into target cells is a multistep process: virus attachment is initiated by the binding of trimeric envelope glycoprotein gp120 complexes on the virions to glycosylated T-cell surface receptor (CD4) and HIV GPCR coreceptors (CCR5 or CXCR4) leading to envelope glycoprotein gp41-dependent fusion-pore formation and membrane fusion. A number of compounds are being developed to specifically target each of these steps leading to virus entry and some compounds have reached early clinical development. Conversely, agents such as the CCR5 antagonist Tak-779 and the CXCR4 antagonist AMD3100 are not longer being thought as relevant anti-HIV agents but have given way to new analogues with improved properties. This review summarizes the current state of HIV entry inhibitors, their mechanisms of action and their therapeutic value against HIV infection and AIDS.
Quantitative kinetics of [124I]FIAU in cat and man. (2001)

The PET marker substrate FIAU does not penetrate the intact BBB significantly and, hence, is not the marker substrate of choice for the noninvasive localization of HSV-1-tk gene expression in the central nervous system under conditions in which the BBB is likely to be intact. However, substantial levels of [(124)I]FIAU-derived radioactivity may occur within areas of BBB disruption (e.g., glioblastoma), which is an essential prerequisite for imaging clinically relevant levels of HSV-1-tk gene expression in brain tumors after gene therapy by FIAU PET. For this purpose, washout of nonspecific radioactivity should be allowed for several days.
Structure-Based Drug Design of RN486, a Potent and Selective Bruton’s Tyrosine Kinase (BTK) Inhibitor, for the Treatment of Rheumatoid Arthritis (2014)

Structure-based drug design was used to guide the optimization of a series of selective BTK inhibitors as potential treatments for Rheumatoid arthritis. Highlights include the introduction of a benzyl alcohol group and a fluorine substitution, each of which resulted in over 10-fold increase in activity. Concurrent optimization of drug-like properties led to compound 1 (RN486) ( J. Pharmacol. Exp. Ther. 2012 , 341 , 90 ), which was selected for advanced preclinical characterization based on its favorable properties.
Inheritance of Trans Chromosomal Methylation patterns from Arabidopsis F1 hybrids (2014)

Hybridization in plants leads to transinteractions between the parental genomes and epigenomes that can result in changes to both 24 nt siRNA and cytosine methylation ((m)C) levels in the hybrid. In Arabidopsis the principle processes altering the hybrid methylome are Trans Chromosomal Methylation (TCM) and Trans Chromosomal deMethylation (TCdM) in which the (m)C pattern of a genomic segment attains the same (m)C pattern of the corresponding segment on the other parental chromosome. We examined two loci that undergo TCM/TCdM in the Arabidopsis C24/Landsberg erecta (Ler) F1 hybrids, which show patterns of inheritance dependent on the properties of the particular donor and recipient chromosomal segments. At At1g64790 the TCM- and TCdM-derived (m)C patterns are maintained in the F2 generation but are transmitted in outcrosses or backcrosses only by the C24 genomic segment. At a region between and adjacent to At3g43340 and At3g43350, the originally unmethylated Ler genomic segment receives the C24 (m)C pattern in the F1, which is then maintained in backcross plants independent of the presence of the parental C24 segment. In backcrosses to an unmethylated Ler allele, the newly methylated F1 Ler segment may act as a TCM source in a process comparable to paramutation in maize. TCM-derived (m)C patterns are associated with reduced expression of both At3g43340 and At3g43350 in F1 and F2 plants, providing support for such events influencing the transcriptome. The inheritance of the F1 (m)C patterns and the segregation of other genetic and epigenetic determinants may contribute to the reduced hybrid vigor in the F2 and subsequent generations.
Obesity and Vascular Risk Factors at Midlife and the Risk of Dementia and Alzheimer Disease (2005)

Obesity at midlife is associated with an increased risk of dementia and AD later in life. Clustering of vascular risk factors increases the risk in an additive manner. The role of weight reduction for the prevention of dementia needs to be further investigated.
Getting to Know Ovarian Cancer Ascites: Opportunities for Targeted Therapy-Based Translational Research (2013)

More than one third of ovarian cancer patients present with ascites at diagnosis, and almost all have ascites at recurrence. The presence of ascites correlates with the peritoneal spread of ovarian cancer and is associated with poor disease prognosis. Malignant ascites acts as a reservoir of a complex mixture of soluble factors and cellular components which provide a pro-inflammatory and tumor-promoting microenvironment for the tumor cells. Subpopulations of these tumor cells exhibit cancer stem-like phenotypes, possess enhanced resistance to therapies and the capacity for distal metastatic spread and recurrent disease. Thus, ascites-derived malignant cells and the ascites microenvironment represent a major source of morbidity and mortality for ovarian cancer patients. This review focuses on recent advances in our understanding of the molecular, cellular, and functional characteristics of the cellular populations within ascites and discusses their contributions to ovarian cancer metastasis, chemoresistance, and recurrence. We highlight in particular recent translational findings which have used primary ascites-derived tumor cells as a tool to understand the pathogenesis of the disease, yielding new insights and targets for therapeutic manipulation.
Secure and robust error correction for physical unclonable functions (2010)

Physical unclonable functions (PUFs) offer a promising mechanism that can be used in many security, protection, and digital rights management applications. One key issue is the stability of PUF responses that is often addressed by error correction codes. The authors propose a new syndrome coding scheme that limits the amount of leaked information by the PUF error-correcting codes.
Characteristics of hypertension in young adults with autosomal dominant polycystic kidney disease compared with the general U.S. population (2004)

These data indicate that renal ultrasound screening of young hypertensive individuals (aged 20 to 34 years) should be considered when searching for causes of secondary hypertension. Identifying affected ADPKD individuals early in their disease will permit aggressive blood pressure treatment and early inhibition of the renin-angiotensin-aldosterone system, which has been shown to reverse left ventricular hypertrophy, an important cardiovascular risk factor. In the present era of renal replacement therapy, cardiovascular complications are the main cause of death in patients with ADPKD.
MONOCYTE-DERIVED DENDRITIC CELL PRECURSORS FACILITATE TOLERANCE TO HEART ALLOGRAFTS AFTER TOTAL LYMPHOID IRRADIATION1 (1998)

The intravenous injection of donor dendritic cell precursors derived from blood monocytes facilitates long-term acceptance of heart allografts.
A Combinatorial G Protein-coupled Receptor Reconstitution System on Budded Baculovirus (2003)

To investigate the coupling selectivity of G proteins and G protein-coupled receptors (GPCRs), we developed a reconstitution system made up of GPCR and heterotrimeric G proteins on extracellular baculovirus particles (budded virus (BV)). BV released from Sf9 cells infected with a recombinant baculovirus coding for human leukotriene B4 receptor (BLT1) cDNA exhibited a high level of BLT1 expression (27.3 pmol/mg of protein) and specific [3H]leukotriene B4 binding activity (Kd = 3.67 nm). The apparent low affinity of the expressed BLT1 is thought to be due to relative non-availability of the Galphai isoform, which couples to BLT1, in BV. Co-infection of heterotrimeric G protein recombinant viruses led to co-expression of BLT1 and G protein subunits on BV. A guanosine-5'-(beta,gamma-imido)triphosphate-sensitive, high affinity ligand binding was observed in the BLT1 BV co-expressing Galphai1beta1gamma2 (Kd = 0.17 nm). A relatively large amount of high affinity receptor protein was recovered in the co-expressing BV fraction (6.81 pmol/mg of protein). A combination of BLT1 and Galphai1 without Gbeta1gamma2 did not exhibit high affinity ligand binding on BV, indicating the low background environment for the GPCR-G protein coupling in this BV reconstitution system. To test other G proteins for coupling, various Galpha subunits were combinatorially expressed in BV with BLT1 and Gbeta1gamma2. The BLT1 BV co-expressing GalphaoAbeta1gamma2 exhibited a comparably high affinity ligand binding as well as ligand-stimulated guanosine 5'-3-O-(thio)triphosphate binding to Galphai1beta1gamma2. Co-expression of other Galpha isoforms such as Galphas, Galpha11, Galpha14, Galpha16, Galpha12, or Galpha13 did not exhibit any significant effects on ligand binding affinity in this system. These results reveal that BLT1 and coupled trimeric G proteins were functionally reconstituted on BV and that Galphao as well as Galphai couples to BLT1. This expression system should prove highly useful for pharmacological characterization, biosensor chip applications, and also drug discovery directed at highly important targets of the membrane receptor proteins.
Identification of "B" receptor for natriuretic peptide in human kidney. (1992)

Three distinct receptor types for natriuretic peptides (NP) have been identified in human tissue. "A" and "B" receptors initiate biological actions, whereas the "C" receptor has a clearance function. It has been proposed that the natural ligand for the B receptor is c-type natriuretic peptide (CNP), rather than atrial natriuretic peptide (ANP), and that the B receptor is only found in the central nervous system (CNS) and is responsible for all NP-mediated effects in the CNS. Contrary to this hypothesis, we have identified, by means of the polymerase chain reaction (PCR), the B receptor in human kidney tissue. To detect A and C receptors, the PCR reaction was performed with primers which yielded predicted 600 and 378 base pair (bp) products, respectively. For the B receptor, 3 different primer sets were used, resulting in the expected 785, 453 and 228 bp fragments. Restriction mapping of the latter two products with Rsa I yielded the expected fragment numbers and sizes, indicating the PCR products were from B receptor mRNA. These results indicate that the human kidney has B as well as A and C receptors. Thus CNP may have a renal as well as a CNS site of action.
Nutrition: A Critical Component of Wound Healing (1990)

Nutrients are essential to wound healing and patients in critical care are often at risk for lack of sufficient nutrients that may result in impaired healing. Understanding the role of the various nutrients in healing provides the basis for assessment and therapy. Use of a practical and consistent nutritional assessment technique is an important part of care for critically ill patients with wounds. The health care team must provide care based on current knowledge of the effects of nutrition on wound healing and work collaboratively in doing nutritional assessment and providing nutritional support to optimize wound healing outcomes.
Single-cell label-free photoacoustic flowoxigraphy in vivo (2013)

Label-free functional imaging of single red blood cells (RBCs) in vivo holds the key to uncovering the fundamental mechanism of oxygen metabolism in cells. To this end, we developed single-RBC photoacoustic flowoxigraphy (FOG), which can image oxygen delivery from single flowing RBCs in vivo with millisecond-scale temporal resolution and micrometer-scale spatial resolution. Using intrinsic optical absorption contrast from oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR), FOG allows label-free imaging. Multiple single-RBC functional parameters, including total hemoglobin concentration (C(Hb)), oxygen saturation (sO2), sO2 gradient (VsO2), flow speed (v(f)), and oxygen release rate (rO2), have been quantified simultaneously in real time. Working in reflection instead of transmission mode, the system allows minimally invasive imaging at more anatomical sites. We showed the capability to measure relationships among sO2, VsO2, v(f), and rO2 in a living mouse brain. We also demonstrated that single-RBC oxygen delivery was modulated by changing either the inhalation gas or blood glucose. Furthermore, we showed that the coupling between neural activity and oxygen delivery could be imaged at the single-RBC level in the brain. The single-RBC functional imaging capability of FOG enables numerous biomedical studies and clinical applications.
Treatment of refractory rheumatoid arthritis with a monoclonal antibody to intercellular adhesion molecule 1 (1994)

Anti-ICAM-1 MAb therapy was well tolerated, resulted in a transient alteration in T lymphocyte recirculation, and effected clinical improvement in some RA patients.
Cardiomyocytes can be generated from marrow stromal cells in vitro (1999)

We have isolated a cardiomyogenic cell line (CMG) from murine bone marrow stromal cells. Stromal cells were immortalized, treated with 5-azacytidine, and spontaneously beating cells were repeatedly screened. The cells showed a fibroblast-like morphology, but the morphology changed after 5-azacytidine treatment in approximately 30% of the cells; they connected with adjoining cells after one week, formed myotube-like structures, began spontaneously beating after two weeks, and beat synchronously after three weeks. They expressed atrial natriuretic peptide and brain natriuretic peptide and were stained with anti-myosin, anti-desmin, and anti-actinin antibodies. Electron microscopy revealed a cardiomyocyte-like ultrastructure, including typical sarcomeres, a centrally positioned nucleus, and atrial granules. These cells had several types of action potentials, such as sinus node-like and ventricular cell-like action potentials. All cells had a long action potential duration or plateau, a relatively shallow resting membrane potential, and a pacemaker-like late diastolic slow depolarization. Analysis of the isoform of contractile protein genes, such as myosin heavy chain, myosin light chain, and alpha-actin, indicated that their muscle phenotype was similar to that of fetal ventricular cardiomyocytes. These cells expressed Nkx2.5/Csx, GATA4, TEF-1, and MEF-2C mRNA before 5-azacytidine treatment and expressed MEF-2A and MEF-2D after treatment. This new cell line provides a powerful model for the study of cardiomyocyte differentiation.
Gag-Specific CD8+ T Lymphocytes Recognize Infected Cells before AIDS-Virus Integration and Viral Protein Expression (2007)

CD8(+) T cells are a key focus of vaccine development efforts for HIV. However, there is no clear consensus as to which of the nine HIV proteins should be used for vaccination. The early proteins Tat, Rev, and Nef may be better CD8(+) T cell targets than the late-expressed structural proteins Gag, Pol, and Env. In this study, we show that Gag-specific CD8(+) T cells recognize infected CD4(+) T lymphocytes as early as 2 h postinfection, before proviral DNA integration, viral protein synthesis, and Nef-mediated MHC class I down-regulation. Additionally, the number of Gag epitopes recognized by CD8(+) T cells was significantly associated with lower viremia (p = 0.0017) in SIV-infected rhesus macaques. These results suggest that HIV vaccines should focus CD8(+) T cell responses on Gag.
Extending OLAP querying to external object databases (2000)

On-Line Analytical Processing (OLAP) systems based on a multidimensional view of data have found widespread use in business applications and are being used increasingly in non-standard applications. These systems provide good performance and ease-of-use. However, the complex structures and relationships inherent in data in non-standard applications are not accommodated well by OLAP systems. In contrast, object database systems are built to handle such complexity, but do not support OLAP-type querying well.
Synthesis, Characterization, and Thermal Properties of Nanoscale Lead-Free Solders on Multisegmented Metal Nanowires (2009)

Nanoscale lead-free solders (“nanosolders”) have been synthesized directly onto multisegmented metal nanowires using an electrodeposition method in nanoporous templates. The nanosolders fabricated include tin (Sn), tin/silver (Sn/Ag), and indium (In), and the diameter of the nanosolder nanowires ranges from 30 nm to 200 nm and the length from 1 to 10 μm. The microstructures of the lead-free nanosolders on nanowires have been characterized using optical microscopy and electron microscopy including a field-emission scanning electron microscope (FESEM) and a transmission electron microscope (TEM), along with energy-dispersive X-ray spectroscopy (EDS). Thermal properties of lead-free nanosolders on nanowires were characterized using a temperature-programmable furnace tube under a controlled atmosphere. It was found that nitrogen plays an important role in the nanosolder reflow process. The effect of base layer, barrier layer, and wetting layer on nanosolder reflow was studied, and an optimal nanowire nanosolder system with effective barrier and wetting layers was obtained. A liquid phase-based solder reflow process was developed, in which the nanosolder nanowires were assembled in a liquid medium and solder joints were formed between nanowires.
Nab-paclitaxel and carboplatin with or without trastuzumab (trast) as part of neoadjuvant chemotherapy (NCT) in patients (pts) with stage II-III breast cancer (BC) (2008)

567 Background: Pathologic complete response (pCR) and minimal residual cancer burden (RCB) after NCT may predict improved survival (Symmans et al. J Clin Oncol 25:4414–22, 2007). Hence, improved NCT regimens and molecular markers that predict both response and/or resistance are needed. Methods: Pts with stages II-III HER2 - BC were prospectively randomized to receive 6 cycles of docetaxel 75 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2 with filgrastim support (TAC, arm A) versus a novel regimen of A 60 mg/m2 and C 600 mg/m2 given every 2 weeks x 4, followed by 3 weekly doses of carboplatin (AUC 2) and nab-paclitaxel 100 mg/m2 given every 4 weeks x 3 cycles ( arm B). Pts with HER2 + BC received NCT similar to arm B but with the addition of 12 weekly doses of tras given with carboplatin and nab-paclitaxel (arm C). Core biopsies were performed prior to and mid-NCT, and samples were procured at surgery. When feasible, specimens from each time point were preserved fresh frozen, in RNA-later, as well as formalin-fixed in paraffin, and in ethanol. Results: Of 52 pts accrued, 40 pts (median age: 50 years; range, 31–69) with stages II (n:18) and III BC (n: 22, including 9 with inflammatory BC) have completed NCT, and 39 pts undergone surgery (1 pt refused). Fifty-eight percent of BC were ER-positive and 25% were HER2+. Eighty percent of pts on Arm A received all planned NCT cycles, while 100% and 90% of pts received all cycles on arms B and C. Grade 3 reversible neuropathies were seen in arm B (n: 2, 13%)n and C (n:1, 10%). Grade 3/4 neutropenia or neutropenic fever were more prevalent on Arm A (67 % and 20%) versus arm B (33% and 0%). pCR and minimal RCB as response to PCT were observed as follows: arm A (n:15):7% and 23%; Arm B (n: 14): 7% and 23 %; Arm C (n:10): 40% and 0 %. Microarray analysis and immunohistochemical analysis of HER2, EGFR, IGFR, and p-Stat3, p-AKT, p-Src, Survivin, P21, P27, Ki67 are ongoing. Conclusions: The addition of carboplatin and nab-paclitaxel with or without trastuzumab is feasible and active as NCT. The results of planned comparative interim analysis (set to occur after 17 pts each will have completed NCT) and correlative studies will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration NCI
Corneal subepithelial infiltrates following excimer laser photorefractive keratectomy (1995)

Corneal subepithelial opacification associated with pain, photophobia, and injection has been reported in the first to third day following photorefractive keratectomy (PRK). Regardless of treatment, the resolution has generally left the patient with permanent corneal scarring and a one to two line reduction in visual acuity. We surveyed 50 PRK surgeons and received responses from 17 on 30 cases of this complication, which occurs in approximately one in 300 cases. The etiology is unknown. Cases were first reported when nonsteroidal anti-inflammatory drugs, with or without occlusive contact lens, were substituted for conventional bandage occlusion in the postoperative protocol for PRK.
Bacterial Nanomachines: The Flagellum and Type III Injectisome (2010)

The bacterial flagellum and the virulence-associated injectisome are complex, structurally related nanomachines that bacteria use for locomotion or the translocation of virulence factors into eukaryotic host cells. The assembly of both structures and the transfer of extracellular proteins is mediated by a unique, multicomponent transport apparatus, the type III secretion system. Here, we discuss the significant progress that has been made in recent years in the visualization and functional characterization of many components of the type III secretion system, the structure of the bacterial flagellum, and the injectisome complex.
Digital techniques for computer voice response: Implementations and applications (1976)

Digital techniques for implementing voice response systems are discussed. In particular, attention is focused on practical methods for computer voice response that are likely to be important in the near future. The general method of concatenating isolated words and phrases to form a message is discussed, along with the various possibilities for digital representations of speech signals. The techniques used to implement an all-digital voice response system with multiline capability are presented. A wide variety of experimental applications of this particular system are also included.
A Behavioral Dynamic Nonlinear Model for Time-Interleaved ADC Based on Volterra Series (2019)

The non-ideal circuit implementations cause a significant degradation in the performance of the time-interleaved analog-to-digital converter (TIADC) system. In this paper, a behavioral model for the TIADC based on Volterra series is proposed to model the dynamic nonlinearities in TIADC. The time-domain and frequency-domain expressions of the behavioral model based on hybrid Volterra series are derived first. Then, the discrete-time equivalent model is proposed by transforming the hybrid TIADC system to a discrete time one based on discrete-time Volterra series only. The derivations give a theoretical foundation to use discrete-time Volterra series to model the mixed-domain TIADC system, which makes it possible to make full use of the related existing derivations, conclusions, and methodologies on discrete-time Volterra series. We also summarize some common special cases of Volterra series to provide practical guidelines for ADC and TIADC practitioners. We present the main features of these models and their relationship with the Volterra series. The simulation and experimental results show the effectiveness of the proposed model.