gebhart/patrepeval huggingface dataset:
Continuous Separations with Microfabricated Electrophoresis−Electrochemical Array Detection (1996)

A novel electrochemical detection scheme for channel electrophoresis has been developed. A microfabricated array of individually addressed microelectrodes has been used as a site-specific amperometric detector for continuous separations in a buffer-filled rectangular channel. Continuous separations of picomole quantities of dopamine and catechol by channel electrophoresis with this new detection scheme have been demonstrated. Dopamine, an electroactive neurotransmitter, has been continuously monitored for 60 min with the electrochemical array detector. The new detection technique should allow dynamic chemical events in volume-limited microenvironments (i.e. single cells) to be examined with channel electrophoresis.
Sonic hedgehog contributes to oligodendrocyte specification in the mammalian forebrain (2001)

This study addresses the role of Sonic hedgehog (Shh) in promoting the generation of oligodendrocytes in the mouse telencephalon. We show that in the forebrain, expression of the early oligodendrocyte markers Olig2, plp/dm20 and PDGFR(alpha) corresponds to regions of Shh expression. To directly test if Shh can induce the development of oligodendrocytes within the telencephalon, we use retroviral vectors to ectopically express Shh within the mouse embryonic telencephalon. We find that infections with Shh-expressing retrovirus at embryonic day 9.5, result in ectopic Olig2 and PDGFR(alpha) expression by mid-embryogenesis. By postnatal day 21, cells expressing ectopic Shh overwhelmingly adopt an oligodendrocyte identity. To determine if the loss of telencephalic Shh correspondingly results in the loss of oligodendrocyte production, we studied Nkx2.1 mutant mice in which telencephalic expression of Shh is selectively lost. In accordance with Shh playing a role in oligodendrogenesis, within the medial ganglionic eminence of Nkx2.1 mutants, the early expression of PDGFR(alpha) is absent and the level of Olig2 expression is diminished in this region. In addition, in these same mutants, expression of both Shh and plp/dm20 is lost in the hypothalamus. Notably, in the prospective amygdala region where Shh expression persists in the Nkx2.1 mutant, the presence of plp/dm20 is unperturbed. Further supporting the idea that Shh is required for the in vivo establishment of early oligodendrocyte populations, expression of PDGFR(alpha) can be partially rescued by virally mediated expression of Shh in the Nkx2.1 mutant telencephalon. Interestingly, despite the apparent requirement for Shh for oligodendrocyte specification in vivo, all regions of either wild-type or Nkx2.1 mutant telencephalon are competent to produce oligodendrocytes in vitro. Furthermore, analysis of CNS tissue from Shh null animals definitively shows that, in vitro, Shh is not required for the generation of oligodendrocytes. We propose that oligodendrocyte specification is negatively regulated in vivo and that Shh generates oligodendrocytes by overcoming this inhibition. Furthermore, it appears that a Shh-independent pathway for generating oligodendrocytes exists.
Characterization of the Endothelium-Specific Murine Vascular Endothelial Growth Factor Receptor-2 (Flk-1) Promoter (1996)

Flk-1, a high-affinity signaling receptor for vascular endothelial growth factor (VEGF), is strongly and specifically expressed on endothelial cells during embryonic development of the vascular system and during tumor angiogenesis. Disruption of Flk-1 gene function has recently been shown to prevent completely endothelial cell differentiation during murine embryonic development. To gain insights into the mechanisms that regulate the endothelium-specific Flk-1 expression, we have isolated the 5'-flanking region of the murine Flk-1 gene. RNase protection and primer extension analyses revealed a single transcriptional start site located 299 bp upstream from the translational start site in an initiator-like pyrimidine-rich sequence. The 5'-flanking region is rich in GC residues and lacks a typical TATA or CAAT box. A luciferase reporter construct containing a fragment from nucleotides -1900 to +299 showed strong endothelium-specific activity in transfected bovine aortic endothelial cells. Deletion analyses revealed that endothelium-specific Flk-1 expression is stimulated by the 5'-untranslated region of the first exon, which contains an activating element between nucleotides +137 and +299. In addition, two endothelium-specific negative regulatory elements were identified between nucleotides -4100 and -623. Two strong general activating elements were present in the region between nucleotides -96 and -37, which contains one potential NF kappa B and three potential AP-2 binding sites. This study shows that Flk-1 expression in endothelial cells is mainly regulated by an endothelium-specific activating element in the long 5'-untranslated region of the first exon and by negative regulatory elements located further upstream.
Efficacy and Safety of ETC-1002, a Novel Investigational Low-Density Lipoprotein-Cholesterol–Lowering Therapy for the Treatment of Patients With Hypercholesterolemia and Type 2 Diabetes Mellitus (2014)

http://www.clinicaltrials.gov. Unique identifier: NCT# 01607294.
Photothermal Heating Enabled by Plasmonic Nanostructures for Electrokinetic Manipulation and Sorting of Particles (2014)

Plasmonic nanostructures support strong electromagnetic field enhancement or optical "hot spots" that are accompanied by local heat generation. This heating effect is generally seen as an obstacle to stable trapping of particles on a plasmonic substrate. In this work, instead of treating the heating effect as a hindrance, we utilized the collective photoinduced heating of the nanostructure array for high-throughput trapping of particles on a plasmonic nanostructured substrate. The photoinduced heating of the nanostructures is combined with an ac electric field of less than 100 kHz, which results in creation of a strong electrothermal microfluidic flow. This flow rapidly transports suspended particles toward the plasmonic substrate, where they are captured by local electric field effects. This work is envisioned to have application in biosensing and surface-enhanced spectroscopies such as SERS.
Here, there, everywhere (2014)

mRNA localization and localized translation is a common mechanism that contributes to cell polarity and cellular asymmetry. In metazoan, mRNA transport participates in embryonic axis determination and neuronal plasticity. Since the mRNA localization process and its molecular machinery are rather complex in higher eukaryotes, the unicellular yeast Saccharomyces cerevisiae has become an attractive model to study mRNA localization. Although the focus has so far been on the mechanism of ASH1 mRNA transport, it has become evident that mRNA localization also assists in protein sorting to organelles, as well as in polarity establishment and maintenance. A diversity of different pathways has been identified that targets mRNA to their destination site, ranging from motor protein-dependent trafficking of translationally silenced mRNAs to co-translational targeting, in which mRNAs hitch-hike to organelles on ribosomes during nascent polypeptide chain elongation. The presence of these diverse pathways in yeast allows a systemic analysis of the contribution of mRNA localization to the physiology of a cell.
Initial Experience with Paclitaxel‐Coated Stents (2002)

Local delivery of immunosuppressive or antiproliferative agents using a drug-eluting stent is a new technology that is supposed to inhibit in-stent restenosis, thus providing a biological and mechanical solution. This technique is a very promising. To date, several agents have been used, including paclitaxel, QP-2, rapamycin, actinomycin D, dexamethason, tacrolimus, and everolimus. Several studies, published recently or still ongoing, have evaluated these drugs as to their release kinetics, effective dosage, safety in clinical practice, and benefit. These studies include: SCORE (paclitaxel derivative), TAXUS I-VI, ELUTES, ASPECT, DELIVER (paclitaxel), RAVEL, SIRIUS (sirolimus), ACTION (actinomycin), EVIDENT, PRESENT (tacrolimus), EMPEROR (dexamethason), and FUTURE (everolimus). Paclitaxel was one of the first stent-based antiproliferative agents under clinical investigation that provided profound inhibition of neointimal thickening depending on delivery duration and drug dosage. The randomized, multicenter SCORE trail (Quanam stent, paclitaxel-coated) enrolled 266 patients at 17 sites. At 6-month's follow-up, a drop of 83% in stent restenosis using the drug-eluting stent could be achieved (6.4% drug-eluting stent vs 36.9% control group), which was attributable to a remarkable decrease in intimal proliferation. Unfortunately, due to frequent stent thrombosis and side-branch occlusions, the reported 30-day MACE rate was 10.2%. The randomized TAXUS-I safety trial (BSC, NIRx, paclitaxel-coated) also demonstrated beneficial reduction of restenotic lesions at 6-month's follow-up (0% vs 10%) but was associated with the absence of thrombotic events presumably due to less drug dosage. The ongoing TAXUS II-VI trials are addressing additional insight regarding the efficacy of the TAXUS paclitaxel-eluting stent. ASPECT and ELUTES evaluated paclitaxel-coated stents (i.e., Cook and Supra G), including subgroups with different drug dosages. With respect to stent restenosis and neointimal proliferation, both studies demonstrated a clear dose response. The RAVEL and the SIRIUS trials evaluated sirolimus-coated stents (i.e., Cordis, Johnson & Johnson, and Bx VELOCITY stents). Results confirmed the beneficial findings regarding reduction of renarrowing using a drug-eluting stent without any major adverse effects. Although parameters such as drug toxicity, optimal drug dosage, or delayed endothelial healing still need to be evaluated, today's clinical experience indicates that drug-coated stents are extremely beneficial in the interventional treatment of coronary lesions.
Epidermal Growth Factor Receptor Inhibitors and Antiangiogenic Agents for the Treatment of Non-Small Cell Lung Cancer (2009)

Non-small cell lung cancer (NSCLC) is a major global health problem and represents the leading cause of cancer-related deaths worldwide. The majority of patients with NSCLC are diagnosed with advanced-stage disease, and the prognosis for such patients is poor. The currently approved cytotoxic chemotherapy is associated with substantial limitations in both efficacy and safety. The availability of agents targeted against the epidermal growth factor receptor (EGFR), as well as the antiangiogenic agent bevacizumab, have provided some clinical benefit. Nonetheless, the efficacy of these agents is also inadequate, and resistance has emerged as a clinical problem. Numerous novel targeted therapies are now in clinical development and may have potential for overcoming the limitations associated with currently available agents. In this article we review clinical data for molecular-targeted therapies in NSCLC, with emphasis on EGFR inhibitors and antiangiogenic agents.
Phorbol Ester Activation of a Proteolytic Cascade Capable of Activating Latent Transforming Growth Factor-β (2002)

12-O-Tetradecanoylphorbol-13-acetate (TPA) suppresses the proliferation of the human breast epithelial cell line MCF10A-Neo by initiating proteolytic processes that activate latent transforming growth factor (TGF)-beta in the serum used to supplement culture medium. Within 1 h of treatment, cultures accumulated an extracellular activity capable of cleaving a substrate for urokinase-type plasminogen activator (uPA) and tissue plasminogen activator (tPA). This activity was inhibited by plasminogen activator inhibitor-1 or antibodies to uPA but not tPA. Pro-uPA activation was preceded by dramatic changes in lysosome trafficking and the extracellular appearance of cathepsin B and beta-hexosaminidase but not cathepsins D or L. Co-treatment of cultures with the cathepsin B inhibitors CA-074 or Z-FA-FMK suppressed the cytostatic effects of TPA and activation of pro-uPA. In the absence of TPA, exogenously added cathepsin B activated pro-uPA and suppressed MCF10A-Neo proliferation. The cytostatic effects of both TPA and cathepsin B were suppressed in cells cultured in medium depleted of plasminogen/plasmin or supplemented with neutralizing TGF-beta antibody. Pretreatment with cycloheximide did not suppress the exocytosis of cathepsin B or the activation of pro-uPA. Hence, TPA activates signaling processes that trigger the exocytosis of a subpopulation of lysosomes/endosomes containing cathepsin B. Subsequently, extracellular cathepsin B initiates a proteolytic cascade involving uPA, plasminogen, and plasmin that activates serum-derived latent TGF-beta.
Vasopressin Therapy for Vasoplegic Syndrome Following Cardiopulmonary Bypass (2002)

High-dose vasopressin is effective in the treatment of the vasoplegic syndrome after cardiac operations employing cardiopulmonary bypass.
Acute Creatine Supplementation in Older Men (2000)

The hypothesis of this study was that short term creatine (Cr) ingestion in older individuals would increase body mass and exercise performance, as has been shown in younger subjects. Seventeen males 60-78 years old were randomly placed into two groups, Cr and placebo (P), and supplemented in double-blind fashion for 5 days. Subjects ingested either 5 g of Cr plus 1 g of sucrose 4x per day or 6 g of a sucrose placebo 4x per day. Isometric strength of the elbow flexors was assessed using a modified preacher bench attached to a strain gauge. Isokinetic exercise performance was assessed using an intermittent fatigue test of the knee extensors. Subjects performed 3 sets of 30 repetitions with 60 sec rest between sets. There was a small (0.5 kg) but statistically significant increase in body mass (p < 0.05) in the Cr group after supplementation. There was a significant overall interaction between groups in isokinetic performance from pre to post supplementation (group x time x set, p < 0.05). However, analysis of the groups separately revealed that the subjects in the Cr group demonstrated a small non-significant increase in isokinetic performance while subjects in the P group demonstrated a small non-significant performance decrement. There was no significant difference in isometric strength between groups from pre to post supplementation. These data suggest that acute oral Cr supplementation does not increase isometric strength and only produces small increases in isokinetic performance and body mass in men over the age of 60.
Plasmonic sensors based on nano-holes: technology and integration (2008)

Surface plasmon resonance sensors are a popular technology for the optical detection of surface adsorption, for applications ranging from drug-development to pathogen detection. Here, we will discuss the integration of nano-hole arrays to provide high-sensitivity detection, with a lower detection limit, speed and cost. Calculations will be presented that suggest that in-hole detection is more sensitive than detecting binding from the surface around the nano-holes. In-hole detection also has the benefit of increased speed due to rapid diffusive transport, yet it provides the challenge of microfluidic/nanofluidic integration. We will outline our recent efforts to produce nano-hole arrays with through-hole detection.
A factor present in fetal calf serum enhances oncogene-induced transformation of rodent fibroblasts. (1987)

Our previous studies indicated that addition of the tumor promoters 12-O-tetradecanoylphorbol-13-acetate (TPA) or teleocidin to Dulbecco modified Eagle medium supplemented with calf serum enhanced T24-induced focus formation in both the murine C3H 10T1/2 and rat 6 embryo fibroblast cell lines. In the present studies we have found that fetal calf serum (FCS) is more potent than 12-O-tetradecanoylphorbol-13-acetate in enhancing T24-induced focus formation, in terms of the number and size of the foci, in both C3H 10T1/2 and rat 6 cells. Time course studies indicate that FCS can exert this enhancing effect when it is added several days after the transfection with T24 DNA. In rat 6 cells, an 11-fold increase in T24-induced focus formation occurred when the transfected cultures were maintained for only 1 day in 5% FCS, starting 4 days after the transfection. Several known growth factors, including epidermal growth factor, transforming growth factors alpha and beta, insulin, and platelet-derived growth factor, did not enhance T24-induced transformation in these cell systems. Fractionation studies indicate that the factor present in FCS has a molecular weight of about 1,300, is not lipid soluble, and is acid, base, and heat stable. These findings suggest that a factor(s) normally present in serum may enhance the emergence of tumor cells in vivo, by acting in concert with an activated oncogene, during the multistage carcinogenic process.
Proposal for an international end to end protocol (1976)

article Free Access Share on Proposal for an international end to end protocol Authors: V. Cerf Stanford University, USA Stanford University, USAView Profile , A. McKenzie Bolt Beranek and Newman Inc. Bolt Beranek and Newman Inc.View Profile , R. Scantlebury National Physical Laboratory, UK National Physical Laboratory, UKView Profile , H. Zimmermann IRIA, France IRIA, FranceView Profile Authors Info & Claims ACM SIGCOMM Computer Communication ReviewVolume 6Issue 1January 1976 pp 63–89https://doi.org/10.1145/1015828.1015832Published:01 January 1976Publication History 21citation346DownloadsMetricsTotal Citations21Total Downloads346Last 12 Months50Last 6 weeks7 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my Alerts New Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Surface-Plasmon-One-Electron Decay and its Observation in Photoemission (1970)

Evidence for the decay of surface plasmons into one-electron excitations has been obtained in photoemission measurements from a slightly roughened surface of aluminum. A simple theory has been developed which explains the resultant photoyield in terms of both the drop in reflectance resulting from roughness-aided plasmon coupling, and the relative penetration depth of the fields associated with these excited plasmons.
Room-temperature continuous-wave operation of InGaN multi-quantum-well structure laser diodes with a lifetime of 27 hours (1997)

The continuous-wave (cw) operation of InGaN multi-quantum-well structure laser diodes (LDs) was demonstrated at room temperature (RT) with a lifetime of 27 h. The threshold current and the voltage of the LDs were 80 mA and 5.5 V, respectively. The threshold current density was 3.6 kA/cm2. Longitudinal modes with a mode separation of 0.042 nm were observed under cw operation at RT. When the temperature of the LDs was varied, large mode hopping of the emission wavelength was observed between adjacent quantum well or quantum dot subbands. The carrier lifetime and the threshold carrier density were estimated to be 10 ns and 2×1020/cm3, respectively.
Targeted disruption of the mouse αA-crystallin gene induces cataract and cytoplasmic inclusion bodies containing the small heat shock protein αB-crystallin (1997)

alpha A-crystallin (alpha A) and alpha B-crystallin (alpha B) are among the predominant proteins of the vertebrate eye lens. In vitro, the alpha-crystallins, which are isolated together as a high molecular mass aggregate, exhibit a number of properties, the most interesting of which is their ability to function as molecular chaperones for other proteins. Here we begin to examine the in vivo functions of alpha-crystallin by generating mice with a targeted disruption of the alpha A gene. Mice that are homozygous for the disrupted allele produce no detectable alpha A in their lenses, based on protein gel electrophoresis and immunoblot analysis. Initially, the alpha A-deficient lenses appear structurally normal, but they are smaller than the lenses of wild-type littermates. alpha A-/- lenses develop an opacification that starts in the nucleus and progresses to a general opacification with age. Light and transmission electron microscopy reveal the presence of dense inclusion bodies in the central lens fiber cells. The inclusions react strongly with antibodies to alpha B but not significantly with antibodies to beta- or gamma-crystallins. In addition, immunoblot analyses demonstrate that a significant portion of the alpha B in alpha A-/- lenses shifts into the insoluble fraction. These studies suggest that alpha A is essential for maintaining lens transparency, possibly by ensuring that alpha B or proteins closely associated with this small heat shock protein remain soluble.
Quantitative Structure−Activity Relationships among Macrolide Antibacterial Agents:  In Vitro and in Vivo Potency against Pasteurella multocida (1997)

Quantitative structure-activity relationships have been found among macrolide antibacterial agents in their potencies against the bacterial pathogen Pasteurella multocida both in vitro and in mouse infections. To obtain these relationships we measured, among other things, the pK(a)'s and log P's of 15 known macrolides of diverse structures. Among these compounds, in vitro potency [log(1/MIC)] is a function of log P, log D, and CMR (R = 0.86). In vivo potency is a function of the higher pK(a), the HPLC chromatographic capacity factor log k', log(1/MIC) and pNF (R = 0.93). pNF is defined as the negative logarithm of the fraction of neutral drug molecules present in aqueous solution at pH 7.4. The same physical properties were determined for 14 macrolides not used in developing the original QSAR models. Using the in vivo model, we calculated the mouse protection potency ranges for these new compounds. Ten estimates agreed with those observed, three were lower by a half-order of magnitude, and one was calculated to be active in the range of 15-50 mg/kg, but in fact was not active at 50 mg/kg, the highest level tested. When these new compounds were combined with the original 15, and the QSAR's updated, the new equations for the in vitro and in vivo potencies were essentially the same as those originally found. Hence, the physical properties indicated above are major determinants of macrolide antibacterial potencies.
Communication in a three-layered conducting media with a vertical magnetic dipole (1980)

The problem of communication in the sea has been considered by many writers. They regarded the sea as a two-layered media, and the bottom of the sea has not been included. However, the effect of the sea bottom cannot be neglected in some situations, for example in the case of a low frequency, a shallow sea, and the access of a transmitter or receiver to the sea bottom. The effect of the sea bottom on radio wave propagation is ascertained theoretically, and it will act as an important part in such cases. Considering a three-layered sea, the multipath reflection and multilateral waves that cannot be generated in a two-layered media are obtained.
Key green chemistry research areas—a perspective from pharmaceutical manufacturers (2007)

In 2005, the ACS Green Chemistry Institute (GCI) and the global pharmaceutical corporations developed the ACS GCI Pharmaceutical Roundtable to encourage the integration of green chemistry and green engineering into the pharmaceutical industry. The Roundtable has developed a list of key research areas. The purpose of this perspective is to summarise how that list was agreed, provide an assessment of the current state of the art in those areas and to highlight areas for future improvement.