gebhart/patrepeval huggingface dataset:
In vitro differentiation of embryonic stem cells: Immunophenotypic analysis of cultured embryoid bodies (1997)

The process of in vitro embryonic stem cell differentiation and embryoid body development was monitored using a panel of antibodies against surface markers traditionally associated with embryonic tissue (Forssman, SSEA-1) and hematopoietic progenitor cells (Fall-3, HSA, Sca-1, Thy-1.2, ER-MP12, CD45, AA4.1, and c-kit). All markers with the exception of CD45 and AA4.1 were initially detected in cultures of undifferentiated ES cells. During the first 11 days of differentiation, distinct and reproducible patterns of surface expression were observed for each marker. Using the kinetic display of surface markers as a gauge of differentiation, perturbations in embryoid body development were detected in cultures supplemented with interleukin-11, a gp130-activating cytokine thought to affect embryonic stem cell differentiation. In the absence of exogenous cytokines, microbead immunoselected day 7 c-kit, ER-MP12, and CD45-positive embryoid body cells were enriched for hematopoietic progenitors as detected by methylcellulose colony assays, while no significant enrichment of hematopoietic progenitors was observed with Sca-1, Thy-1.2, Fall-3, and Forssman-immunoselected cells. These results indicate that the process of early embryoid body development is associated with a programmed sequence of cell surface marker display, concomitant with the development of phenotypically definable embryonic cell lineages.
Internet Telephony: Call Processing Protocols (2000)

From the Publisher:
The key source for the principal Internet telephony services and standards. 

The Internet now handles extensive video, teleconferencing, fax, and voice communications, in addition to basic data transfer. But overlapping standards for mixed media transmissions can confuse even the most sophisticated engineers. Experienced telecom leader Uyless Black brings together all the tools and protocols for call processing in this single authoritative source. 

Internet Telephony begins with an overview of basic telephony call processing, focussing on the differences between traditional circuit switching and the more contemporary packet-based networks. A special section discusses telephony routing over IP. Along the way, Black explores the major standards and protocols in detail. Highlights include: 

H.323: the ITU standard for transmitting mixed media signals via LANS and WANs
SIP: the IETF's Session Initiation Protocol used for IP teleconferencing
Megaco Protocol: a combined IETF/ITU standard for multimedia conferencing
MGCP: a call processing protocol, published as an informational RFC


For engineers, managers, or users, Internet Telephony is the one book to cover all the technologies.
Nanonails:  A Simple Geometrical Approach to Electrically Tunable Superlyophobic Surfaces (2007)

In this work, dynamically tunable, superlyophobic surfaces capable of undergoing a transition from profound superlyophobic behavior to almost complete wetting have been demonstrated for the first time. In the initial state, with no voltage applied, these surfaces exhibit contact angles as high as 150 degrees for a wide variety of liquids with surface tensions ranging from 21.8 mN/m (ethanol) to 72.0 mN/m (water). Upon application of an electrical voltage, a transition from the superlyophobic state to wetting is observed. We have examined experimentally and theoretically the nature of these transitions. The reported results provide novel methods of manipulating liquids on the microscale.
Noncompetitive Inhibition of N‐Methyl‐D‐Aspartate by Conantokin‐G: Evidence for an Allosteric Interaction at Polyamine Sites (1992)

Conantokins T and G are polypeptide toxins present in snails of the genus Conus. These substances were recently reported to act as N-methyl-D-aspartate (NMDA) antagonists. In the present study, we examined the possible mechanisms producing this antagonism. Conantokin-G inhibited spermine- and spermidine-stimulated [3H]MK-801 binding to extensively washed rat forebrain membranes in a noncompetitive manner with IC50 values of approximately 507 and approximately 946 nM, respectively. In contrast, glutamate-enhanced [3H]MK-801 binding was unaffected by conantokin-G concentrations of less than or equal to 20 microM. At concentrations greater than or equal to 5 microM, conantokin-G effected a modest, noncompetitive inhibition of glycine-stimulated [3H]MK-801 binding and also produced a small enhancement of basal [3H]MK-801 binding. Conantokin-G reduced (IC50 approximately 1.08 microM) the NMDA-stimulated accumulation of cyclic GMP in cerebellar granule cell cultures to basal values, but did not affect kainate-mediated increases in cyclic GMP. These findings indicate that conantokin-G acts as a noncompetitive NMDA antagonist through an allosteric inhibition of polyamine responses. The neurochemical profile of this polypeptide is distinct from previously described noncompetitive NMDA antagonists.
A Complex of Soluble MD-2 and Lipopolysaccharide Serves as an Activating Ligand for Toll-like Receptor 4 (2004)

MD-2, a glycoprotein that is essential for the innate response to lipopolysaccharide (LPS), binds to both LPS and the extracellular domain of Toll-like receptor 4 (TLR4). Following synthesis, MD-2 is either secreted directly into the medium as a soluble, active protein, or binds directly to TLR4 in the endoplasmic reticulum before migrating to the cell surface. Here we investigate the function of the secreted form of MD-2. We show that secreted MD-2 irreversibly loses activity over a 24-h period at physiological temperature. LPS, but not lipid A, prevents this loss in activity by forming a stable complex with MD-2, in a CD14-dependent process. Once formed, the stable MD-2.LPS complex activates TLR4 in the absence of CD14 or free LPS indicating that the activating ligand of TLR4 is the MD-2.LPS complex. Finally we show that the MD-2.LPS complex, but not LPS alone, induces epithelial cells, which express TLR4 but not MD-2, to secrete interleukin-6 and interleukin-8. We propose that the soluble MD-2.LPS complex plays a crucial role in the LPS response by activating epithelial and other TLR4(+)/MD-2(-) cells in the inflammatory microenvironment.
Overexpression of CuZn-Superoxide Dismutase Reduces Hippocampal Injury After Global Ischemia in Transgenic Mice (1997)

CuZn-SOD plays a protective role in the pathogenesis of selective hippocampal injury after brief ischemia, whether the insult is relatively mild or intense. Furthermore, CuZn-SOD may reduce both necrotic and DNA fragmented neuronal death after global ischemia.
Laser range scanning for cortical surface characterization during neurosurgery (2003)

In this work, preliminary quantitative results are presented that characterize the cortical surface during neurosurgery using a laser range scanner. Intra-operative cortical surface data is collected from patients undergoing cortical resection procedures and is registered to patient-specific pre-operative data. After the skull bone-flap has been removed and the dura retracted, a laser range scanner (LRS) is used to capture range data of the brain's surface. An RGB bitmap is also captured at the time of scanning, which permits texturing of the range data. The textured range data is then registered to textured surfaces of the brain generated from pre-operative images. Registration is provided by a rigid-body transform that is based on iterative-closest point transforms and mutual information. Preliminary results using the LRS during surgery demonstrate a good visual alignment between intra-operative and pre-operative data. The registration algorithm is able to register surfaces using both sulcal and vessel patterns. Target registration errors on the order of 2mm have been achieved using the registration algorithm in a clinical setting. Results from the analysis of laser range scan data suggest that the unique feature-rich cortical surface may provide a robust method for intra-operative registration and deformation measurement. Using laser range scan data as a non-contact method of acquiring spatially relevant data in a clinical setting is a novel application of this technology. Furthermore, the work presented demonstrates a viable framework for current IGS systems to computationally account for brain shift.
Template Synthesis of Stimuli-Responsive Nanoporous Polymer-Based Spheres via Sequential Assembly (2006)

Nanoporous polymer-based spheres were synthesized via sequential assembly of macromolecules (e.g., polyelectrolytes (PEs), peptides, and proteins) in mesoporous silica (MS) particles, followed by removal of the MS templates. The sequential infiltration of PEs in the mesopores for the model system poly(acrylic acid) (PAA) and poly(allylamine hydrochloride) (PAH) was demonstrated by various methods, including nitrogen sorption, thermogravimetric analysis, Fourier transform infrared, and confocal laser scanning microscopy (CLSM). The influence of parameters such as layer cross-linking, solution pH, ionic strength, and MS pore size on the synthesis of the PAA/PAH nanoporous polymer spheres (NPS) was investigated. Cross-linking between PAA and PAH was found to add structural integrity to the NPS, while the solution pH and ionic strength govern the conformation of the PEs in solution and the subsequent ability of the PEs to infiltrate the mesopores and thereby form intact NPS. Transmission and scanning electron microscopy data show that the PAA/PAH NPS have pores ranging from about 5−50 nm, which was further confirmed by CLSM of protein-loaded NPS. The PAA/PAH NPS exhibited a high capacity for enzyme loading (ca. 470 mg mL-1 for lysozyme), with stimuli-responsive reversible loading and release of the protein triggered by changes in solution pH. The general applicability of the reported approach is demonstrated by the preparation of NPS containing peptides, proteins, and low molecular weight molecules. MS fibers were also used as templates to generate PAA/PAH nanoporous fibers, showing that this process is applicable to templates with different morphologies. These nanoporous materials are envisaged to find application in biosensing, enzyme catalysis, and controlled drug delivery.
Synergistic Effect of the γ-Secretase Inhibitor PF-03084014 and Docetaxel in Breast Cancer Models (2013)

Notch signaling mediates breast cancer cell survival and chemoresistance. In this report, we aimed to evaluate the antitumor efficacy of PF-03084014 in combination with docetaxel in triple-negative breast cancer models. The mechanism of action was investigated. PF-03084014 significantly enhanced the antitumor activity of docetaxel in multiple xenograft models including HCC1599, MDA-MB-231Luc, and AA1077. Docetaxel activated the Notch pathway by increasing the cleaved Notch1 intracellular domain and suppressing the endogenous Notch inhibitor NUMB. PF-03084014 used in combination with docetaxel reversed these effects and demonstrated early-stage synergistic apoptosis. Docetaxel elicited chemoresistance by elevating cytokine release and expression of survivin and induced an endothelial mesenchymal transition (EMT) phenotype by increasing the expressions of Snail, Slug, and N-cadherin. When reimplanted, the docetaxel-residual cells not only became much more tumorigenic, as evidenced by a higher fraction of tumor-initiating cells (TICs), but also showed higher metastatic potential compared with nontreated cells, leading to significantly shortened survival. In contrast, PF-03084014 was able to suppress expression of survivin and MCL1, reduce ABCB1 and ABCC2, upregulate BIM, reverse the EMT phenotype, and diminish the TICs. Additionally, the changes to the ALDH(+) and CD133(+)/CD44(+) subpopulations following therapy corresponded with the TIC self-renewal assay outcome. In summary, PF-03084014 demonstrated synergistic effects with docetaxel through multiple mechanisms. This work provides a strong preclinical rationale for the clinical utility of PF-03084014 to improve taxane therapy.
The Impact of Weight Gain on Motivation, Compliance, and Metabolic Control in Patients with Type 2 Diabetes Mellitus (2009)

Patients with type 2 diabetes, approximately 85% of whom are overweight or obese, often have an increased incidence of cardiovascular disease (CVD) risk factors such as hypertension and dyslipidemia. Both type 2 diabetes and obesity are independent risk factors for CVD. Unfortunately, many therapies aimed at maintaining and improving glucose control are associated with weight gain. Among the older antidiabetes agents, most, including the insulin secretagogues and sensitizers, can lead to weight gain, except for metformin, which is weight-neutral. Among the newer agents, the dipeptidyl peptidase-4 inhibitors generally are weight-neutral in addition to lowering glucose, while the glucagon-like peptide-1 receptor agonists lead to weight reduction. Patients with type 2 diabetes are at an increased risk for both diabetes- and CV-related outcomes, and weight reduction is an important component of diabetes management. Weight gain in patients with type 2 diabetes can contribute to patient frustration and may negatively impact their compliance to therapeutic regimens. The selection of antidiabetes agents that not only improve glucose control but reduce or have a neutral effect on weight with beneficial effects on lipids are ideal options for managing patients with type 2 diabetes.
Near-infrared Raman spectroscopy of single optically trapped biological cells (2002)

We report on the development and testing of a compact laser tweezers Raman spectroscopy (LTRS) system. The system combines optical trapping and near-infrared Raman spectroscopy for manipulation and identification of single biological cells in solution. A low-power diode laser at 785 nm was used for both trapping and excitation for Raman spectroscopy of the suspended microscopic particles. The design of the LTRS system provides high sensitivity and permits real-time spectroscopic measurements of the biological sample. The system was calibrated by use of polystyrene microbeads and tested on living blood cells and on both living and dead yeast cells. As expected, different images and Raman spectra were observed for the different cells. The LTRS system may provide a valuable tool for the study of fundamental cellular processes and the diagnosis of cellular disorders.
Bioavailability of dexmedetomidine after extravascular doses in healthy subjects (2003)

Dexmedetomidine is well absorbed systemically through the oral mucosa, and therefore buccal dosing may provide an effective, noninvasive route to administer the drug.
Prospective, Randomized, Double-Blind Trial Investigating the Effect of Doxycycline on Matrix Metalloproteinase Expression Within Atherosclerotic Carotid Plaques (2002)

Doxycycline penetrated atherosclerotic plaques with acceptable tissue levels. This resulted in a reduction in MMP-1 concentration because of decreased expression.
Expression of CXCR4 in Eosinophils: Functional Analyses and Cytokine-Mediated Regulation (2000)

We examined the expression of transcripts of a panel of chemokine receptors in human eosinophils and found intense constitutive expression of CXCR4 mRNA. Although surface CXCR4 protein was hardly detectable in the peripheral blood or freshly isolated eosinophils, surface expression of CXCR4 became gradually apparent during incubation at 37 degrees C. In contrast, the level of CCR3 expression was virtually unchanged during the incubation. Stromal cell-derived factor-1alpha (SDF-1alpha), the natural ligand of CXCR4, elicited an apparent Ca2+ influx in these cells and induced a strong migratory response comparable to that by eotaxin. The surface expression of CXCR4 in eosinophils was up-regulated by IFN-gamma, TNF-alpha, and TGF-beta while it was down-regulated by IL-4 and eosinophil-directed hemopoietins such as IL-5. The CXCR4 expression did not always parallel the apoptotic changes in cytokine-treated eosinophils. In contrast to IL-4 and IFN-gamma, IL-5 potently reduced the level of CXCR4 mRNA. It seems unlikely that CXCR4 is fundamentally involved in the pathogenesis of allergic disorders by inducing the migration of eosinophils toward inflammatory sites, because a Th2-dominant state down-regulates eosinophil CXCR4 expression. However, CXCR4 may affect the size of the mobilizable pool by holding eosinophils at noninflamed tissues. Th2-dominant state may favor the liberation of eosinophils by down-regulating CXCR4 expression. The interplay between CXCR4 and SDF-1alpha in eosinophils potentially plays an important role in the accumulation of these cells at the allergic inflammatory sites.
Power considerations in the design of the Alpha 21264 microprocessor (1998)

Power dissipation is rapidly becoming a limiting factor in high performance microprocessor design due to ever increasing device counts and clock rates. The 21264 is a third generation Alpha microprocessor implementation, containing 15.2 million transistors and operating at 600 MHz. This paper describes some of the techniques the Alpha design team utilized to help manage power dissipation. In addition, the electrical design of the power, ground, and clock networks is presented.
Identification of CRG-2. An interferon-inducible mRNA predicted to encode a murine monokine. (1990)

In order to identify novel proteins produced by activated macrophages, a cDNA library was made from cultures of the mouse macrophage-like cell line RAW 264.7 that had been treated with conditioned medium from mitogen-stimulated spleen cells, and the library was screened by differential plaque hybridization. A cDNA clone was isolated that detected a 1.4-kilobase mRNA that accumulated dramatically in response to the spleen cell conditioned medium. The 1.4-kilobase mRNA encodes a predicted protein of 98 amino acids, designated CRG-2, molecular weight (Mr) 10,781, with a 21-residue signal peptide. The amino acid sequence indicates that CRG-2 is a member of the platelet factor 4 family (PF4) of cytokines. The CRG-2 mRNA was induced by alpha-, beta-, and gamma-interferons (IFNs) and by lipopolysaccharide. In response to IFN-gamma, the CRG-2 mRNA level reached a peak between 3 and 6 h. The accumulation of CRG-2 mRNA was not blocked by cycloheximide. Among the known members of the PF4 family, CRG-2 is most closely related to the interferon-inducible human protein IP-10. The 5'-flanking region of the crg-2 gene was isolated, and comparisons between crg-2 and IP-10 genes, mRNAs, and proteins reveal conserved features of possible functional importance. CRG-2 may play a role in host defense, particularly in the response to viral infection.
Chronic low level complement activation within the eye is controlled by intraocular complement regulatory proteins. (2000)

The results suggest that the complement system is continuously active at a low level in the normal eye and is tightly regulated by intraocular complement regulatory proteins.
Fibroblasts as sentinel cells. Synthesis of chemokines and regulation of inflammation. (1997)

In this commentary, we have suggested that the fibroblast should be considered a sentinel cell. This concept is based on the fibroblast's ability to function both as a structural element and as a vital immunoregulatory cell. In some tissues, these capabilities may be ascribable to subsets of fibroblasts, rather than to some of the general fibroblast populations. The pioneering research of Xia et al, as well as that of others, highlights the need to explore the importance of fibroblasts as playing critical roles in disease. Emerging concepts regarding tissue-specific fibroblasts and fibroblast heterogeneity need to be considered in studies of their biosynthetic capabilities. Of special importance is the recent insight that the NF kappa B/RelB family of transcription proteins have apparently different regulatory roles in fibroblasts and hematopoietic cells. Therefore, with regard to therapeutic strategies targeting molecules such as RelB, caution should be exercised as their interruption may have very different consequences in macrophages compared with fibroblasts. For example, inhibition of RelB in macrophages may well prevent enhanced chemokine expression, whereas in fibroblasts, a critical governor for preventing chemokine expression would be lost. Overall, this could lead to exacerbation of inflammation rather than to an attenuation of the process.
A survey of 178 NF-Y binding CCAAT boxes (1998)

The CCAAT box is one of the most common elements in eukaryotic promoters, found in the forward or reverse orientation. Among the various DNA binding proteins that interact with this sequence, only NF-Y (CBF, HAP2/3/4/5) has been shown to absolutely require all 5 nt. Analysis of a database with 178 bona fide NF-Y binding sites in 96 unrelated promoters confirms this need and points to specific additional flanking nucleotides (C, Pu, Pu on the 5'-side and C/G, A/G, G,A/C, G on the 3'-side) required for efficient binding. The frequency of CCAAT boxes appears to be relatively higher in TATA-less promoters, particularly in the reverse ATTGG orientation. In TATA-containing promoters the CCAAT box is preferentially located in the -80/-100 region (mean position -89) and is not found nearer to the Start site than -50. In TATA-less promoters it is usually closer to the +1 signal (at -66 on average) and is sometimes present in proximity to the Cap site. The consensus and location of NF-Y binding sites parallel almost perfectly a previous general statistical study on CCAAT boxes in 502 unrelated promoters. This is an indication that NF-Y is the major, if not the sole, CCAAT box recognizing protein and that it might serve different roles in TATA-containing and TATA-less promoters.
Sequence and Function of LuxU: a Two-Component Phosphorelay Protein That Regulates Quorum Sensing in Vibrio harveyi (1999)

ABSTRACT Vibrio harveyi regulates the expression of bioluminescence ( lux ) in response to cell density, a phenomenon known as quorum sensing. In V. harveyi , two independent quorum-sensing systems exist, and each produces, detects, and responds to a specific cell density-dependent autoinducer signal. The autoinducers are recognized by two-component hybrid sensor kinases called LuxN and LuxQ, and sensory information from both systems is transduced by a phosphorelay mechanism to the response regulator protein LuxO. Genetic evidence suggests that LuxO-phosphate negatively regulates the expression of luminescence at low cell density in the absence of autoinducers. At high cell density, interaction of the sensors with their cognate autoinducers results in dephosphorylation and inactivation of the LuxO repressor. In the present report, we show that LuxN and LuxQ channel sensory information to LuxO via a newly identified phosphorelay protein that we have named LuxU. LuxU shows sequence similarity to other described phosphorelay proteins, including BvgS, ArcB, and Ypd1. A critical His residue (His 58) of LuxU is required for phosphorelay function.
Intravenous RNA Interference Gene Therapy Targeting the Human Epidermal Growth Factor Receptor Prolongs Survival in Intracranial Brain Cancer (2004)

Weekly i.v. nonviral RNAi gene therapy directed against the human EGFR is a new therapeutic approach to silencing oncogenic genes in solid cancers. This is enabled with a nonviral gene transfer technology that delivers liposome-encapsulated plasmid DNA across cellular barriers with receptor-specific targeting ligands.