gebhart/patrepeval huggingface dataset:
Efficacy and safety of becaplermin (recombinant human platelet‐derived growth factor‐BB) in patients with nonhealing, lower extremity diabetic ulcers: a combined analysis of four randomized studies (1999)

The results of a combined analysis and separate analyses of four multicenter, randomized, parallel group studies that evaluated the effects of once-daily topical administration of becaplermin gel for the treatment of chronic, full thickness, lower extremity diabetic ulcers are presented. The four studies included a total of 922 patients with nonhealing lower extremity diabetic ulcers of at least 8 weeks' duration. Following initial complete sharp debridement of the ulcer, patients were randomized to receive a standardized regimen of good ulcer care alone, good ulcer care plus placebo gel, or good ulcer care plus becaplermin gel-30 microg/g, or good ulcer care plus becaplermin gel-100 microg/g, with various combinations of regimens used in the four studies. Safety was assessed by monitoring adverse events and by clinical laboratory evaluations. Meta-analytic statistical techniques were used in the combined analysis to establish homogeneity of treatment comparisons across studies. Based on an analysis of patients with baseline ulcer area common to all trials (</= 10 cm2), representing 95% of all patients, becaplermin gel-100 microg/g significantly increased (p = 0.007) the probability of complete healing compared with placebo gel. It was determined that for the median ulcer area of these patients, which was 1.5 cm2, the becaplermin gel-100 microg/g treatment group showed a 39% increase in complete healing compared with that of the placebo gel treatment group (50% vs. 36%, respectively, p = 0.007). Becaplermin gel-100 microg/g significantly decreased (p = 0.01) the time to complete healing compared with placebo gel, with the 35th percentile of time to complete healing being reduced by 30% (14.1 weeks vs. 20. 1 weeks, respectively). In patients with ulcers </= 5 cm2 at baseline (a more homogeneous group), becaplermin gel-100 microg/g also significantly increased the incidence of complete healing with a similar decrease in the time to healing. Adverse events reported during treatment or during a 3-month follow-up period were not unexpected for this patient population and were similar in nature and incidence across all treatment groups. We therefore conclude that treatment with becaplermin gel at a dose of 100 microg/g once daily, in conjunction with good ulcer care, is effective and well tolerated in patients with full thickness lower extremity diabetic ulcers.
A very low operation current InGaAsP/InP total internal reflection optical switch using p/n/p/n current blocking layers (1994)

A very low operation current (20 mA) has been achieved for the first time with an InGaAsP/InP total-internal-reflection optical switch. The optical switch is fabricated on an n/sup +/-InP substrate using p/n/p/n current blocking layers. This switch has a large effective contact area and is a self-aligned structure. This is a promising result for making optical integrated circuits.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Murine macrophage scavenger receptor: in vivo expression and function as receptor for macrophage adhesion in lymphoid and non‐lymphoid organs (1995)

Abstract Macrophage scavenger receptors are trimeric integral membrane glycoproteins which have been implicated in various macrophage functions including uptake of oxidized lipoprotein and the serum‐dependent, divalent cation‐independent adhesion of macrophages to tissue culture‐treated plastic. In this study we have used a recently defined monoclonal antibody (2F8) which recognizes murine macrophage scavenger receptor, to explore its expression in lymphoid and non‐lymphoid organs of the normal adult. Scavenger receptor was detected in the red pulp and marginal zone of normal adult mouse spleen, medulla of the thymus and subcapsular region of lymph nodes. Kupffer cells in the liver, alveolar macrophages in the lung and lamina propria macrophages in the gut all reacted with 2F8 monoclonal antibody. The antigen was not detected on any nonmacrophage cells, with the exception of sinusoidal endothelial cells in the liver. In the spleen, lymph node and liver, scavenger receptor antigen expression was associated specifically with phagocytic cells which had taken up colloidal carbon. To examine macrophage adhesion in a context relevant to the interactions occurring within lymphoid and non‐lymphoid organs, and the contribution of macrophage scavenger receptor to this adhesion, we designed an assay of macrophage adhesion to frozen tissue sections. Adhesion to most tissues was high and uniform in the absence of any chelating agents. The chelation of Ca 2+ and Mg 2+ revealed specific patterns of macrophage adhesion in lymphoid and non‐lymphoid organs which was completely inhibited by 2F8. The ability of this antibody to block the EDTA‐resistant adhesion correlated with tissue expression of the antigen in some tissues. Unlike adhesion to tissue culture‐treated plastic, macrophage scavenger receptor‐dependent adhesion of macrophages to frozen tissue sections did not exhibit an absolute requirement for exogenous fetal bovine serum indicating the presence of an endogenous ligand for scavenger receptor within the tissues. We propose that macrophage scavenger receptor is a candidate homing or retention molecule for macrophage localization within ligand‐rich tissues.
HBT technology and applications, today and tomorrow (1994)

This paper briefly reviews the status of GaAs Heterostructure Bipolar Technology (HBT) material, process and device developments. Representative device performance being achieved today is reported. System applications of digital and mixed signal circuits are described. Finally, further development of the HBT technology necessary for commercial applications is discussed.
N‐Myc downstream‐regulated gene 2 (NDRG2) inhibits glioblastoma cell proliferation (2003)

The most severe form of brain glioma, glioblastoma (GBM), is highly malignant and usually resistant to chemotherapy. Therefore, discovery of new targets for gene therapy is important. Using subtraction cloning, we identified the human N-Myc downstream-regulated gene 2 (hNDRG2), located at chromosome 14q11.2, as a gene that is significantly suppressed in GBM tissues. Semiquantitative RT-PCR showed that the hNDRG2 gene transcript is expressed in normal brain tissue and low-grade gliomas but is present at low levels in 15 of 27 (56%) human GBM tissues and all of the 6 human glioblastoma cell lines examined. Furthermore, transfection of human glioblastoma U373 and U138 cells with a cDNA encoding hNDRG2 markedly reduced the cell proliferation. Our findings provide the first evidence to suggest that hNDRG2 may play a role in glioblastoma carcinogenesis.
Exactly the Same but Different: Promiscuity and Diversity in the Molecular Mechanisms of Action of the Aryl Hydrocarbon (Dioxin) Receptor (2011)

The Ah receptor (AhR) is a ligand-dependent transcription factor that mediates a wide range of biological and toxicological effects that result from exposure to a structurally diverse variety of synthetic and naturally occurring chemicals. Although the overall mechanism of action of the AhR has been extensively studied and involves a classical nuclear receptor mechanism of action (i.e., ligand-dependent nuclear localization, protein heterodimerization, binding of liganded receptor as a protein complex to its specific DNA recognition sequence and activation of gene expression), details of the exact molecular events that result in most AhR-dependent biochemical, physiological, and toxicological effects are generally lacking. Ongoing research efforts continue to describe an ever-expanding list of ligand-, species-, and tissue-specific spectrum of AhR-dependent biological and toxicological effects that seemingly add even more complexity to the mechanism. However, at the same time, these studies are also identifying and characterizing new pathways and molecular mechanisms by which the AhR exerts its actions and plays key modulatory roles in both endogenous developmental and physiological pathways and response to exogenous chemicals. Here we provide an overview of the classical and nonclassical mechanisms that can contribute to the differential sensitivity and diversity in responses observed in humans and other species following ligand-dependent activation of the AhR signal transduction pathway.
A survey of the anti-apoptotic Bcl-2 subfamily expression in cancer types provides a platform to predict the efficacy of Bcl-2 antagonists in cancer therapy (2010)

We investigated the mRNA expression levels of all six antiapoptotic Bcl-2 subfamily members in 68 human cancer cell lines using qPCR techniques and measured the ability of known Bcl-2 inhibitors to induce cell death in 36 of the studied tumor cell lines. Our study reveals that Mcl-1 represents the anti-apoptotic Bcl-2 subfamily member with the highest mRNA levels in the lung, prostate, breast, ovarian, renal, and glioma cancer cell lines. In leukemia/lymphoma and melanoma cancer cell lines, Bcl-2 and Bfl-1 had the highest levels of mRNA, respectively. The observed correlation between the cell killing properties of known Bcl-2 inhibitors and the relative mRNA expression levels of anti-apoptotic Bcl-2 proteins provide critical insights into apoptosis-based anticancer strategies that target Bcl-2 proteins. Our data may explain current challenges of selective Bcl-2 inhibitors in the clinic, given that severe expression of Bcl-2 seems to be limited to leukemia cell lines. Furthermore, our data suggest that in most cancer types a strategy targeted to Mcl-1 inhibition, or combination of Bfl-1 and Mcl-1 inhibition for melanoma, may prove to be more successful than therapies targeting only Bcl-2.
Clinical-Scale Cell-Surface-Marker Independent Acoustic Microfluidic Enrichment of Tumor Cells from Blood (2017)

Enumeration of circulating tumor cells (CTCs) predicts overall survival and treatment response in metastatic cancer, but as many commercialized assays isolate CTCs positive for epithelial cell markers alone, CTCs with little or no epithelial cell adhesion molecule (EpCAM) expression stay undetected. Therefore, CTC enrichment and isolation by label-free methods based on biophysical rather than biochemical properties could provide a more representative spectrum of CTCs. Here, we report on a clinical-scale automated acoustic microfluidic platform processing 5 mL of erythrocyte-depleted paraformaldehyde (PFA)-fixed blood (diluted 1:2) at a flow rate of 75 μL/min, recovering 43/50 (86 ± 2.3%) breast cancer cell line cells (MCF7), with 0.11% cancer cell purity and 162-fold enrichment in close to 2 h based on intrinsic biophysical cell properties. Adjustments of the voltage settings aimed at higher cancer cell purity in the central outlet provided 0.72% cancer cell purity and 1445-fold enrichment that resulted in 62 ± 8.7% cancer cell recovery. Similar rates of cancer-cell recovery, cancer-cell purity, and fold-enrichment were seen with both prostate cancer (DU145, PC3) and breast cancer (MCF7) cell line cells. We identified eosinophil granulocytes as the predominant white blood cell (WBC) contaminant (85%) in the enriched cancer-cell fraction. Processing of viable cancer cells in erythrocyte-depleted blood provided slightly reduced results as to fixed cells (77% cancer cells in the enriched cancer cell fraction, with 0.2% WBC contamination). We demonstrate feasibility of enriching either PFA-fixed or viable cancer cells with a clinical-scale acoustic microfluidic platform that can be adjusted to meet requirements for either high cancer-cell recovery or higher purity and can process 5 mL blood samples in close to 2 h.
α-CD/Crown-Appended Diazophenol for Selective Sensing of Amines (2006)

[reaction: see text] Azophenol dyes having the permethylated cyclodextrin and/or crown moieties have been synthesized. Compound 1 provides critical information on discriminating 1-3 degrees amines with unique color changes. Addition of 1 degrees and 2 degrees amines to 1 shifts the absorbance maximum of 1 from 380 to approximately 580 and approximately 530 nm, respectively, but no change is observed with 3 degrees amines. The high selectivity of 1 is mainly due to H-bonding between the ammonium H atoms of the amine and oxygen atoms of the crown-6.
Scanners and Data Acquisition (2004)

This chapter includes the following topics: Basic Principles of Scanners Basic Principles of Imagers Calibration and PMT Gain Characteristics of Different Noise Sources
Architectures of incorporating MPEG-4 AVC into three-dimensional wavelet video coding (2004)

3D wavelet video coding provides an elegant fulldimensional solution for scalable video coding. However, due to the Motion-Compensated Temporal Filtering (MCTF) with open-loop structure and no good rate distortion optimization trade-off between the texture coding and overhead coding of the corresponding mode and motion vectors within narrow bandwidth, its performance is unsatisfactory at low bit-rates. On the other hand, video data below a certain spatial, temporal or SNR resolution are not required in most applications of scalable video coding. The introduction of a base layer in three-dimensional scalable video coding scheme can provide a lot of advantages such as close-loop temporal prediction, in-loop filter and rate-distortion optimization without any constraint occurred in pure 3D wavelet codec and also compatibility with existing video compression standards. This paper presents the architectures about how to efficiently incorporate base layer codec MPEG-4 AVC into 3D wavelet video coding.
Detection and characterization of high affinity plasma membrane receptors for human interleukin 1. (1985)

Interleukin 1 (IL-1) is a polypeptide hormone that acts as a central mediator of inflammation. Since IL-1 action is presumably mediated by specific cell surface receptor(s), we have characterized the binding of this hormone to cells. Purified human IL-1 was labeled to high specific activity with 125I, using Bolton-Hunter reagent. The labeled protein binds specifically to LBRM-33-1A5 (a murine T lymphoma line previously shown to produce IL-2 in response to phytohemagglutinin and IL-1) with an affinity of approximately 0.2-2 X 10(10)/M and, at saturation, to approximately 500 receptors per cell, on intact cells at 8 degrees C in the presence of sodium azide. The affinity of unmodified IL-1 for the murine plasma membrane receptor is 0.9-2 X 10(10)/M, as measured by the inhibition of 125I-IL-1 binding. The murine receptor specificity has been confirmed by demonstrating that, among a series of 12 polypeptide hormones, only IL-1 inhibits 125I-IL-1 binding to LBRM-33-1A5 cells. Treatment of surface-bound 125I-IL-1 with bivalent water-soluble crosslinkers identified a membrane polypeptide of Mr 79,500 to which IL-1 is crosslinked. A variety of cell types have been surveyed for the capacity to bind 125I-IL-1 specifically. The presence of specific binding correlates with the capacity of the cells tested to respond to IL-1. Our results indicate that the biological effects of the polypeptide hormone IL-1 are mediated by high affinity plasma membrane receptors. The identification of these receptors should provide valuable insight into the apparently diverse biological activities of IL-1.
An MDP-Based Vertical Handoff Decision Algorithm for Heterogeneous Wireless Networks (2008)

The architecture for the Beyond 3rd Generation (B3G) or 4th Generation (4G) wireless networks aims at integrating various heterogeneous wireless access networks. One of the major design issues is the support of vertical handoff. Vertical handoff occurs when a mobile terminal switches from one network to another (e.g., from wireless local area network to code-division multiple-access 1x radio transmission technology). The objective of this paper is to determine the conditions under which vertical handoff should be performed. The problem is formulated as a Markov decision process with the objective of maximizing the total expected reward per connection. The network resources that are utilized by the connection are captured by a link reward function. A signaling cost is used to model the signaling and processing load incurred on the network when vertical handoff is performed. The value iteration algorithm is used to compute a stationary deterministic policy. For performance evaluation, voice and data applications are considered. The numerical results show that our proposed scheme performs better than other vertical handoff decision algorithms, namely, simple additive weighting, the technique for order preference by similarity to ideal solution, and Grey relational analysis.
Interdependence of Hemagglutinin Glycosylation and Neuraminidase as Regulators of Influenza Virus Growth: a Study by Reverse Genetics (2000)

The hemagglutinin (HA) of fowl plague virus A/FPV/Rostock/34 (H7N1) carries two N-linked oligosaccharides attached to Asn123 and Asn149 in close vicinity to the receptor-binding pocket. In previous studies in which HA mutants lacking either one (mutants G1 and G2) or both (mutant G1,2) glycosylation sites had been expressed from a simian virus 40 vector, we showed that these glycans regulate receptor binding affinity (M. Ohuchi, R. Ohuchi, A. Feldmann, and H. D. Klenk, J. Virol. 71:8377-8384, 1997). We have now investigated the effect of these mutations on virus growth using recombinant viruses generated by an RNA polymerase I-based reverse genetics system. Two reassortants of influenza virus strain A/WSN/33 were used as helper viruses to obtain two series of HA mutant viruses differing only in the neuraminidase (NA). Studies using N1 NA viruses revealed that loss of the oligosaccharide from Asn149 (mutant G2) or loss of both oligosaccharides (mutant G1,2) has a pronounced effect on virus growth in MDCK cells. Growth of virus lacking both oligosaccharides from infected cells was retarded, and virus yields in the medium were decreased about 20-fold. Likewise, there was a reduction in plaque size that was distinct with G1,2 and less pronounced with G2. These effects could be attributed to a highly impaired release of mutant progeny viruses from host cells. In contrast, with recombinant viruses containing N2 NA, these restrictions were much less apparent. N1 recombinants showed lower neuraminidase activity than N2 recombinants, indicating that N2 NA is able to partly overrule the high-affinity binding of mutant HA to the receptor. These results demonstrate that N-glycans flanking the receptor-binding site of the HA molecule are potent regulators of influenza virus growth, with the glycan at Asn149 being dominant and that at Asn123 being less effective. In addition, we show here that HA and NA activities need to be highly balanced in order to allow productive influenza virus infection.
RNA modulation, repair and remodeling by splice switching oligonucleotides. (2004)

Targeting splicing by antisense oligonucleotides allows RNA modifications that are not possible with RNA interference or other antisense techniques that destine the RNA for destruction. By changing the ratio of naturally occurring splice variants the expression of mRNA is modulated. By preventing the use of an aberrant splice site created by a mutation and enforcing re-selection of correct splice sites the RNA is repaired. Antisense induced skipping of the exon that carries a nonsense mutation remodels the mRNA and restores the reading frame of the defective protein. All of the above approaches have clinical applications. Modulation of splice variants is particularly important since close to 60% of all genes code for alternatively spliced pre-mRNA.
Safety and Antioxidant Activity of a Pomegranate Ellagitannin-Enriched Polyphenol Dietary Supplement in Overweight Individuals with Increased Waist Size (2007)

The consumption of pomegranate juice (PJ), a rich source of antioxidant polyphenols, has grown tremendously due to its reported health benefits. Pomegranate extracts, which incorporate the major antioxidants found in pomegranates, namely, ellagitannins, have been developed as botanical dietary supplements to provide an alternative convenient form for consuming the bioactive polyphenols found in PJ. Despite the commercial availability of pomegranate extract dietary supplements, there have been no studies evaluating their safety in human subjects. A pomegranate ellagitannin-enriched polyphenol extract (POMx) was prepared for dietary supplement use and evaluated in two pilot clinical studies. Study 1 was designed for safety assessment in 64 overweight individuals with increased waist size. The subjects consumed either one or two POMx capsules per day providing 710 mg (435 mg of gallic acid equivalents, GAEs) or 1420 mg (870 mg of GAEs) of extracts, respectively, and placebo (0 mg of GAEs). Safety laboratory determinations, including complete blood count (CBC), chemistry, and urinalysis, were made at each of three visits. Study 2 was designed for antioxidant activity assessment in 22 overweight subjects by administration of two POMx capsules per day providing 1000 mg (610 mg of GAEs) of extract versus baseline measurements. Measurement of antioxidant activity as evidenced by thiobarbituric acid reactive substances (TBARS) in plasma were measured before and after POMx supplementation. There was evidence of antioxidant activity through a significant reduction in TBARS linked with cardiovascular disease risk. There were no serious adverse events in any subject studied at either site. These studies demonstrate the safety of a pomegranate ellagitannin-enriched polyphenol dietary supplement in humans and provide evidence of antioxidant activity in humans.
The loading rate determines tumor targeting properties of methotrexate albumin conjugates in rats (1997)

Albumin dominates the plasma proteins in man. Following our observation that albumin turnover in rodent tumors is markedly increased, we will present evidence that albumin can be employed as an efficient carrier for targeting cytostatic agents like methotrexate (MTX) into tumors. The considerable discrepancy in the molecular weight of MTX (454 Da) and albumin (about 67,000 Da) tempted researchers to load multiple drug molecules on one carrier molecule. It was supposed that the optimal therapeutic efficacy of MTX protein conjugates could be achieved by increasing the number of the molecules of MTX attached to the carrier. In this paper we will show that only loading rates of close to 1 mol of the cytostatic drug MTX/mol of albumin offer optimal conditions for targeting MTX-albumin conjugates into rodent tumors. Conjugates bearing 5, 7, 10 and 20 molecules of MTX on average showed considerable alterations in the HPLC profiles of the conjugates compared to albumin. Conjugates carrying 5-20 mol MTX, tagged with a residualizing radiolabel, were efficiently trapped by the liver before reaching the tumor. The tumor uptake rates of these conjugates declined dramatically with an increasing molecular load of the cytotoxic drug linked to albumin. Competition experiments with maleylated bovine serum albumin and fucoidan revealed that scavenger receptors present on the cells of the liver monocyte macrophage system were involved in this process. For further preclinical and clinical studies, we chose MTX-albumin conjugates, derivatized at a molar ratio of 1:1. These conjugates enjoy the same favorable tumor targeting properties like albumin, e.g. high tumor uptake rates, low liver uptake rates and a very long biological half-life.