gebhart/patrepeval huggingface dataset:
A First-in-Human Phase I Study of Subcutaneous Outpatient Recombinant Human IL15 (rhIL15) in Adults with Advanced Solid Tumors (2017)

<b>Purpose:</b> Preclinical data established IL15 as a homeostatic factor and powerful stimulator of NK and CD8<sup>+</sup> T-cell function, the basis for clinical testing.<b>Experimental Design:</b> A first-in-human outpatient phase I dose escalation trial of subcutaneous (SC) rhIL15 was conducted in refractory solid tumor cancer patients. Therapy consisted of daily (Monday-Friday) subcutaneous injections of rhIL15 for two consecutive weeks (10 total doses/cycle). Clinical response was assessed by RECIST. Pharmacokinetics of rhIL15 and immune biomarkers were evaluated.<b>Results:</b> Nineteen patients were treated with rhIL15 at dose levels of 0.25, 0.5, 1, 2, and 3 mcg/kg/day. Fourteen patients completed ≥ 2 cycles of therapy that was well tolerated. One serious adverse event (SAE), grade 2 pancreatitis, required overnight hospitalization. Enrollment was halted after a patient receiving 3 mcg/kg/day developed a dose-limiting SAE of grade 3 cardiac chest pain associated with hypotension and increased troponin. No objective responses were observed; however, several patients had disease stabilization including a renal cell carcinoma patient who continued protocol treatment for 2 years. The treatment induced profound expansion of circulating NK cells, especially among the CD56<sup>bright</sup> subset. A proportional but less dramatic increase was found among circulating CD8<sup>+</sup> T cells with maximal 3-fold expansion for the 2 and 3 mcg/kg patients.<b>Conclusions:</b> SC rhIL15 treatment was well tolerated, producing substantial increases in circulating NK and CD8<sup>+</sup> T cells. This protocol establishes a safe outpatient SC rhIL15 regimen of 2 mcg/kg/day dosing amenable to self-injection and with potential as a combination immunotherapeutic agent. <i>Clin Cancer Res; 24(7); 1525-35. ©2017 AACR</i>.
Neuroendocrine neoplasm of the pancreas as a manifestation of familial isolated pituitary adenoma: A case report (2020)

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
Tuning Ionic Liquids for Simultaneous Dilution and Demulsification of Water-in-Bitumen Emulsions at Ambient Temperature (2019)

Abstract Thermal and flotation processes are widely used to produce bitumen from oil sand in Alberta. However, bitumen contains many surface-active components that tend to form water-in-oil emulsion stabilized by fines and/or asphaltenes. Although several demulsifiers have been proposed in the literature to treat such emulsions, these chemicals are sometimes not effective. We propose ionic liquids whose composition has been designed to enable effective treatment of these emulsions. Different ionic liquids were synthesized and tested for their efficiency in treating bitumen emulsion obtained from a field in Alberta. Ionic liquids tested are mixtures of organic bases with acids. Mixtures of ionic liquids and bitumen emulsion were prepared at several mass ratios. The two components were mixed under ambient conditions. After mixing, segregation of different components in the mixture was accelerated by centrifugation for rapid assessment of the degree of emulsion breaking. Optical microscopy, rheology, thermal gravimetric analysis, and viscosity measurements were used to assess the effect of ionic liquids on bitumen emulsions. The first set of ionic liquids with cations of different alkyl chain lengths were able to separate the water from the emulsion. However, these ionic liquids tend to form a gel when mixed with water. The number and length of alkyl chains proved critical for avoiding gel formation. Ionic liquids with multiple long chains on the cation were immiscible with the separated water. These ionic liquids were very efficient in diluting and demulsifying bitumen emulsion. The emulsion droplet sizes increased upon addition of the ionic liquid. The ionic liquid mixes into the bitumen phase released from the emulsion, yielding a viscosity at ambient temperature close to the pipeline specifications. This work demonstrates that ionic liquids can be tailored to break bitumen emulsions effectively without heat input. The process developed in this paper can replace current practice for the demulsification and dilution of bitumen emulsions, which requires the emulsion to be heated significantly. Hence the ionic liquid process reduces the heat requirements and hence greenhouse gas emissions.
Carbon-Coated Nickel Phosphide Nanosheets as Efficient Dual-Electrocatalyst for Overall Water Splitting (2016)

Low-cost and efficient electrocatalysts for overall water splitting are in high demand for a wide range of applications across renewable and clean energy. Here, we report a simple one-step synthesis of a three-dimensional (3D) carbon-coated Ni<sub>8</sub>P<sub>3</sub> nanosheet array as bifunctional catalyst for both hydrogen evolution reactions (HER) and oxygen evolution reactions (OER). The nanosheet array possesses low overpotentials, high current densities, and small Tafel slopes in both HER and OER and shows high electrocatalytic activities and long-term stability. The carbon layer with high electric conductivity serves not only as a protective layer to prevent Ni<sub>8</sub>P<sub>3</sub> dissolution but also as an active layer to decrease the electrocatalysis overpotential. The nanosheet array has HER outstanding activity in both acid and alkaline media. Its superior performance in OER can be due to the synergistic interaction at the Ni<sub>8</sub>P<sub>3</sub>/NiO<sub>x</sub> heterojunction. Furthermore, cell voltage as low as 1.65 V can achieve 10 mA cm<sup>-2</sup> current density for full water splitting in an alkaline water electrolyzer, indicating potential application of C@ Ni<sub>8</sub>P<sub>3</sub> as bifunctional catalyst for clean and renewable energy utilization.
Case Studies—Offshore Managed Pressure Drilling (2006)

Abstract Managed Pressure Drilling (MPD) technology has evolved on land drilling programs since the mid-sixties. However, it has been only fairly recently that the technology has found an important niche in the minds of offshore drilling decision-makers. With most of the world's remaining prospects for oil and gas being economically un-drillable with conventional-wisdom casing set points and fluids programs, MPD is now being viewed as a technology which can render a significant increase in economic drill-ability by reducing excessive drilling-related costs typically associated with conventional offshore drilling. This paper will define for the audience the two Categories (Reactive &amp; Proactive) and the Variations of MPD that are being currently practiced or will be practiced in the near future in marine environments: CBHP (Constant Bottomhole Pressure) PMCD (Pressurized Mud Cap Drilling) Dual Gradient (several methods) HSE (Returns Flow Control) Case studies will be presented which speak to MPD applications from both fixed (Jackup, platform) rigs with surface BOP stacks…and from floating rigs (moored semi-submersibles and DP Drillships) with subsea and surface BOP's. There will be an emphasis upon the "drilling trouble zones" benefits of MPD. Operator company objectives of practicing the variations of MPD will be detailed. Stances of various regulatory agencies will be briefly discussed.
Two Populations of AChR in Rat Myotubes Have Different Degradation Rates and Responses to cAMP (1993)

Acetylcholine receptors (AChRs) of rat muscle cells grown in culture for 4 days were labeled with 125I-alpha-bungarotoxin and their degradation rate measured. Two AChR populations, a rapidly degrading one (Rr,t1/2 approximately 1 day) and a slowly degrading one (Rs, t1/2 approximately 4 days) were identified at a ratio of approximately 9 to 1. The degradation rate of the Rs was slowed to a t1/2 of approximately 10 days by cAMP while that of the Rr remained unchanged. These data provide further evidence that two AChR populations with different degradation rates can exist in noninnervated muscle and that they can be further distinguished by their differing response to cAMP. We suggest that the two AChR populations seen in myotubes may be physiologically equivalent to the Rs and Rr components seen at the neuromuscular junction of denervated adult muscle and could thus provide a good model for characterizing the Rr and Rs AChRs.
<title>New recursive VLSI architectures for forward and inverse discrete cosine transform</title> (1996)

New recursive VLSI architectures for arbitrary length discrete cosine transform (DCT) and inverse DCT (IDCT) are presented. Compared with previous methods, the proposed approach saves N-1 adders but requires one additional delay element for the DCT implementation, and saves (N/2) multipliers for the IDCT. The reduction in elements results from identifying common computations in the processing that generates the transform components.
Growth of high‐In‐content InGaN multiple quantum disk nanocolumns on Si(111) by RF plasma‐assisted molecular‐beam epitaxy (2006)

Abstract Self‐organized In x Ga 1– x N nanocolumns with high‐In‐contents of x = 0.86–1.0 and In 0.86 Ga 0.14 N/ In 0.79 Ga 0.21 N multiple quantum disk (MQD) nanocolumns were successfully grown on Si(111) substrates by rf plasma‐assisted molecular beam epitaxy. The In x Ga 1– x N nanocolumns showed room‐temperature photoluminescence (RT‐PL) emission and the emission peak wavelength varied from 1500 to 1920 nm with increasing In content from 0.86 to 1.0. The In 0.86 Ga 0.14 N/In 0.79 Ga 0.21 N MQD nanocolumns showed a satellite peak in X‐ray diffraction spectra that indicates the growth of a good periodic structure. RT‐PL emission was also observed and the emission peak wavelength shifted from 1450 to 1620 nm with changing In 0.86 Ga 0.14 N well layer thickness from 1.5 to 3.0 nm. (© 2006 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Prediction of hematologic toxicity after radioimmunotherapy with (131)I-labeled anticarcinoembryonic antigen monoclonal antibodies. (1999)

Red marrow dose, baseline blood counts, multiple bone or marrow (or both) metastases and recent chemotherapy are the most important factors related to hematologic toxicity after RAIT. This study provides a simple model for predicting myelotoxicity with reasonable accuracy in most patients. In addition, the identification of bone or marrow (or both) metastases and recent chemotherapy as significant factors for myelotoxicity may be important in the future design of clinical trials.
Enhanced Hole Injection in a Hybrid Organic–Inorganic Light-Emitting Diode (2008)

The operating mechanism, particularly the carrier injection mechanism, of a hybrid organic-inorganic light-emitting diode (HOILED) is reported. Asymmetric hole injection has been observed in a symmetric hole-only device, which has two identical interfaces between a conducting polymer and a metal oxide. A HOILED having a layer of molybdenum oxide (MoO3) deposited on a layer of poly(dioctylfluorene-alt-benzothiadiazole) (F8BT) demonstrated a markedly enhanced hole injection, four orders of magnitude higher on one side of the structure than on the other side. This enhanced hole injection is the considered to initiate the operation of the HOILED. X-ray photoelectron spectra (XPS) analysis revealed that Mo deposited on the surface of F8BT was reduced compared to that deposited Mo below the film of F8BT. It is suggested that a chemical interaction between the metal oxide and the organic material affects carrier injection.
The Medicinal Chemistry of Taxol (2021)

Natural products, including their semisynthetically modified or their synthetic analogues, have been valuable and abundant sources or leads for various drugs currently in clinical use. Undoubtedly, new and known naturally occurring substances will continue to play an important role in the future development of novel therapeutic agents. Natural products and related derivatives are also powerful agents for cancer chemotherapy. Examples include plant products such as the vinca alkaloids, camptothecins, derivatives of podophyllotoxin, and antitumor antibiotics such as the anthracyclines, mitomycin C, actinomycin D, bleomycins, and others.1 Taxol (1, Figure 1, NSC 125973, paclitaxel), first isolated in 1971 by Wani et al.2 from the bark of Taxus brevifolia and approved in December 1992 by the FDA for the treatment of drug refractory metastatic ovarian cancer, is yet another example demonstrating the importance of natural products as a source for the development of novel anticancer agents. It is also interesting to note that Taxol acts through a new and unique mechanism of action, promoting the formation and hyperstabilization of microtubules.3 Recently it has been suggested that the antitumor activity of Taxol may be influenced by additional effects. It was observed that Taxol induced the expression of tumor necrosis factor-α and interleukin-1 in macrophages,4–6 caused stimulation of MAP-2 kinase activity, and increased tyrosine phosphorylation.7,8 It was also reported that Taxol blocks processes essential for invasion and metastases in prostate tumor cells (PC-3 ML).9 Because of the multiple functions of microtubules in the regulation of cellular processes, in addition to their role in mitosis, it is conceivable that Taxol may find applications in therapeutic areas other than cancer chemotherapy. The recent 319finding that Taxol inhibits the progression of congenital polycystic kidney disease (PKD) in cpk mice indicates that Taxol may also be usful for the treatment of human PKD.10
An efficient and scalable synthesis of (2R,αS)‐3,4‐dihydro‐2‐[3‐(1,1,2,2‐tetrafluoroethoxy)phenyl]‐5‐[3‐(trifluoromethoxy)phenyl]‐α‐(trifluoromethyl)‐1(2H)‐quinolineethanol: A potent CETP inhibitor (2010)

Abstract magnified image An efficient and scalable synthesis of the potent CETP inhibitor, (2 R ,α S )‐3,4‐dihydro‐2‐[3‐(1,1,2,2‐tetrafluoroethoxy)phenyl]‐5‐[3‐(trifluoromethoxy)phenyl]‐α‐(trifluoromethyl)‐1(2 H )‐quinolineethanol 1, is described. One of the important intermediates, tetrahydroquinoline 10, was readily prepared by reductive cyclization of nitroketone 9 in high yield. Asymmetric synthesis of 10 with high enantiomeric excess (&lt;80% ee) was also developed. J. Heterocyclic Chem., (2010).
The pressure drop along rectangular microchannels containing bubbles (2007)

This paper derives the difference in pressure between the beginning and the end of a rectangular microchannel through which a flowing liquid (water, with or without surfactant, and mixtures of water and glycerol) carries bubbles that contact all four walls of the channel. It uses an indirect method to derive the pressure in the channel. The pressure drop depends predominantly on the number of bubbles in the channel at both low and high concentrations of surfactant. At intermediate concentrations of surfactant, if the channel contains bubbles (of the same or different lengths), the total, aggregated length of the bubbles in the channel is the dominant contributor to the pressure drop. The difference between these two cases stems from increased flow of liquid through the "gutters"-the regions of the system bounded by the curved body of the bubble and the corners of the channel-in the presence of intermediate concentrations of surfactant. This paper presents a systematic and quantitative investigation of the influence of surfactants on the flow of fluids in microchannels containing bubbles. It derives the contributions to the overall pressure drop from three regions of the channel: (i) the slugs of liquid between the bubbles (and separated from the bubbles), in which liquid flows as though no bubbles were present; (ii) the gutters along the corners of the microchannels; and (iii) the curved caps at the ends of the bubble.
Impact of the vent size in the feedback-path and occlusion-effect in hearing aids (2014)

Occlusion-effect and acoustic feedback are common complaints of the hearing aid user. The occlusion-effect is described as an annoying quality of the user's own voice that sounds hollow or boomy, while feedback instability results in an unpleasant loud continuous tone. Despite the availability of high performance feedback cancellers, severe to profound losses require large amplification and, as a result, certain degree of occlusion to minimize feedback. The smaller the vent, the greater is the feedback-path attenuation as well the increase in the occlusion-effect. This work presents a method to measure paired transfer functions for the feedback-path and occlusion-system. Such results, not presented in literature before, relate concomitantly the feedback-path and occlusion-system characteristics with the vent diameter. Results indicate power variations of up to 10 dB for both feedback-path and occlusion-system in the 0 to 3mm vent diameter range. Such a result should be taken into consideration in the design of feedback cancellers as well in fitting procedures.
Studies on the Catalytic Mechanism of a Glutamic Peptidase (2010)

Scytalidoglutamic peptidase (SGP) is the prototype of fungal glutamic peptidases that are characteristically pepstatin insensitive. These enzymes have a unique catalytic dyad comprised of Gln(53) and Glu(136) that activate a bound water molecule for nucleophilic attack on the carbonyl carbon atom of the scissile peptide bond. The hydrolysis by SGP at peptide bonds with proline in the P(1)' position is a rare event among peptidases that we investigated using the series of fluorescence resonance energy transfer peptides, Abz-KLXPSKQ-EDDnp, compared with the series Abz-KLXSSKQ-EDDnp. The preference observed in these two series for Phe and His over Leu, Ile, Val, Arg, and Lys, seems to be related to the structure of the S(1) subsite of SGP. These results and the pH profiles of SGP activity showed that its S(1) subsite can accommodate the benzyl group of Phe at pH 4 as well as the positively charged imidazolium group of His. In the pH range 2 to 7, SGP maintains its structure and activity, but at pH 8 or higher it is irreversibly denatured. The intrinsic fluorescence of the Trp residues of SGP were sensitive to the titration of carboxyl groups having low pK values; this can be attributed to the buried Asp(57) and/or Asp(43) as described in SGP three-dimensional structure. The solvent kinetic isotope effects and the proton inventory experiments support a mechanism for the glutamic peptidase SGP that involves the nucleophilic attack of the general base (Glu(136)) activated water, and establish a fundamental role of the S(1) subsite interactions in promoting catalysis.
Role of nitric oxide in gut ischemia-reperfusion-induced hepatic microvascular dysfunction (1997)

The overall objective of this study was to assess the contribution of an altered bioavailability of nitric oxide (NO) to the leukocyte adhesion and hypoxic stress elicited in the liver by gut ischemia-reperfusion (I/R). The accumulation of leukocytes, number of nonperfused sinusoids (NPS), and NADH autofluorescence were monitored (by intravital microscopy) in mouse liver after 15 min of superior mesenteric artery occlusion and 60 min of reperfusion. Leukostasis, NPS, and NADH autofluorescence (indicating hypoxia) were all increased in the liver at 60 min after gut I/R. The NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) exaggerated the liver leukostasis elicited by gut I/R, responses that were prevented by coadministration of L-arginine. The NO donor diethylenetriamine-NO (DETA-NO) and L-arginine were both effective in attenuating the gut I/R-induced leukostasis and increased NADH autofluorescence, whereas neither DETA nor D-arginine exerted a protective action. These findings indicate that NO is an important determinant of the liver leukostasis, impaired sinusoidal perfusion, and tissue hypoxia elicited by gut I/R.
Obesity: A crisis of growing proportions (2002)

Childhood obesity is a condition characterized by an imbalance between energy consumed and energy expended. A variety of factors that are unique to our modern day western society lead to the increasing prevalence of childhood obesity. The ease and volume of food supply, high calorie density, convenience foods, convenience transportation, sedentary lifestyle, school system issues, and perceptions of unsafe neighbourhoods all contribute to this increase in obesity. Consequences of childhood obesity are now known to carry health risks for childhood, as well as greater health risks in adulthood. A societal approach to solving this problem is necessary. The paediatrician's role as an advocate in society is vital. On an individual basis, paediatricians can help to identify these patterns early and prevent them by providing basic nutritional advice to the child and parents at an early stage.
Three-dimensional structure of laser-modified Ti6Al4V and bone interface revealed with STEM tomography (2011)

The Ti6Al4V titanium alloy is one of the most routinely used materials in implant technologies. It is a suitable biomaterial due to its intrinsic mechanical properties, the excellent biocompatibility of its native surface titanium-dioxide layer, and its ability to osseointegrate. The early interaction between an implant’s surface and bone is a leading factor for implant success, where multiple surface properties contribute to improved bone anchorage. An important parameter is surface topography, both on the micron and nanoscale. Laser-modification has been performed in the thread valleys of Ti6Al4V screws to alter their surface chemistry and topography to form a nanostructured surface titanium-dioxide. Since the valley regions are associated with increased bone formation kinetics and influential to implant bonding, the modified screws may exhibit enhanced bone attachment. In order to understand the underlying mechanisms and structure of the interface to nanostructured implant surfaces, characterization techniques with sufficient resolution are needed. Z-contrast electron tomography offers the possibility to explore the interfacial structure with high-resolution in three-dimensions. Furthermore, by operating in STEM mode, artifacts arising from diffraction contrast in the crystalline implant are avoided, while a high-degree of compositional contrast is maintained in the bone matrix. The aim of the present paper was to evaluate Z-contrast electron tomography as a tool to analyze the bone interface to a nanostructured implant surface. Implants were placed in the rabbit tibia and removed with surrounding bone after 8 weeks. Focused ion beam (FIB) was used to prepare specimens for transmission electron microscopy (TEM). Elemental analysis with energy dispersive x-ray spectroscopy (EDXS) over the implant-bone interface confirms the intermixing of bone apatite and titanium dioxide. This was further substantiated with three-dimensional reconstructions created from Z-contrast electron tomograms. Collagen fibers of the surrounding bone appear to have been laid down parallel to the implant surface. Accordingly, visualization of the laser-modified interface with nanoscale three-dimensional resolution, as offered by Z-contrast electron tomography, gives new insights into bone bonding mechanisms between roughened titanium-dioxide surfaces and bone.