gebhart/patrepeval huggingface dataset:
New Perspectives on an Old Friend: Optimizing Carboplatin for the Treatment of Solid Tumors (1998)

BACKGROUND. Since its clinical introduction in 1981, carboplatin has proved a feasible alternative to cisplatin for the treatment of many solid tumors, especially ovarian cancer. Because the pharmacokinetics and, ultimately, the pharmacodynamics of carboplatin are highly dependent on the status of renal function, fixed dosing based on body surface area has led to carboplatin overdosing or, especially, underdosing. This has resulted in less than optimal treatment results compared with cisplatin in a variety of solid tumor types. Only in the past few years has the optimal dosing method for carboplatin-individualizing the dose (area under the concentration-versus-time curve [AUC]) rather than conventional use of body surface area-been adopted by clinical oncologists. METHODS. An extensive review of the oncology literature has been performed to update both carboplatin dosing guidelines as well as its present role in solid tumor chemotherapy. Initial efforts to devise a dosing formula for carboplatin focused on reducing myelotoxicity (especially thrombocytopenia). Subsequently, a simple formula was developed to adjust the carboplatin dose according to renal function. By targeting a carboplatin AUC rather than empirically dosing according to body surface area, doses of carboplatin can be individualized to fall within the drug's therapeutic index. RESULTS. The use of carboplatin dosing guidelines based on renal function has led to optimization of its pharmacodynamic effects both with respect to its safety profile and its ultimate impact on solid tumor response and patient survival. Since carboplatin has little neurotoxicity, it has become the platinum agent of choice in combination with paclitaxel for therapy of previously untreated ovarian cancer. Carboplatin plus etoposide and carboplatin plus paclitaxel have been studied in phase II and III trials, with the latter combination demonstrating improved activity against advanced non-small cell lung cancer. Additional trials in patients with other solid tumors have shown that carboplatin is more cost-effective and less toxic than cisplatin. CONCLUSIONS. Dosing based on renal function and a targeted serum AUC, rather than on body surface area, has resulted in the optimal utilization of carboplatin in cancer chemotherapy. Its predictable toxicity and clinical efficacy equivalent to cisplatin make carboplatin the drug of choice for selected tumor types.
How the spectre and meltdown hacks really worked (2019)

We're Used to Thinking of computer processors as orderly machines that proceed from one simple instruction to the next with complete regularity. But the truth is, that for decades now, they've been doing their tasks out of order and just guessing at what should come next. They're very good at it, of course. So good in fact, that this ability, called speculative execution, has underpinned much of the improvement in computing power during the last 25 years or so. But on 3 January 2018, the world learned that this trick, which had done so much for modern computing, was now one of its greatest vulnerabilities.
Hybrid Myelomas Producing Antibodies Against a Human Neuroblastoma Antigen Present on Fetal Brain (1979)

Spleen cells from mice immunized with a cultured human neuroblastoma were hybridized with the mouse plasmacytoma P3X63Ag8. Hybrid myelomas were screened for production of antibodies that reacted with human neuroblastomas but not with cells from other tissues. One of these hybridoma antibodies reacted with an antigen present on the six human neuroblastomas tested, one of two retinoblastomas, a glioblastoma, and fetal brain, but did not react with other tumors or tissues including adult human brain.
Viscous damping and spring force in periodic perforated planar microstructures when the Reynolds’ equation cannot be applied (2010)

A model of squeeze-film behavior is developed based on Stokes' equations for viscous, compressible isothermal flows. The flow domain is an axisymmetrical, unit cell approximation of a planar, periodic, perforated microstructure. The model is developed for cases when the lubrication approximation cannot be applied. The complex force generated by vibrations of the diaphragm driving the flow has two components: the damping force and the spring force. While for large frequencies the spring force dominates, at low (acoustical) frequencies the damping force is the most important part. The analytical approach developed here yields an explicit formula for both forces. In addition, using a finite element software package, the damping force is also obtained numerically. A comparison is made between the analytic result, numerical solution, and some experimental data found in the literature, which validates the analytic formula and provides compelling arguments about its value in designing microelectomechanical devices.
Per-O-Trimethylsilyl-α-L-Fucopyranosyl Iodide: A Novel Glycosylating Agent for Terminal α-L-Fucosylation (1996)

Trimethylsilylation of L-Fucose, followed by reaction with TMS-I, yields in situ the per-O-trimethylsilyl-α-L-fucopyranosyl iodide (2) without chromatography. Compound 2, in the absence of a promoter, reacts with alcohols to give α-L-fucopyranosides in good yields (45-90%). The net result is that hydrogenation is not an essential final step in the synthesis of fucosides and that benzyl groups may be used as temporary protecting groups in oligosaccharide synthesis involving terminal fucosylation.
Oncolytic Adenovirus ICOVIR-7 in Patients with Advanced and Refractory Solid Tumors (2010)

Overall, objective evidence of antitumor activity was seen in 9 of 17 evaluable patients. In radiological analyses, 5 of 12 evaluable patients had stabilization or reduction in tumor size. These consisted of one partial response, two minor responses and two cases of stable disease, all occurring in patients who had progressive disease before treatment. In summary, ICOVIR-7 treatment is apparently safe, resulting in anticancer activity, and is therefore promising for further clinical testing.
G-Protein Coupled Receptor Signaling in Myocardium: Not for the Faint of Heart (2007)

Catecholamines, endothelin-1 and angiotensin II are among a diverse group of diffusible extracellular signals that regulate pump function of the heart by binding to G-protein coupled receptors (GPCR). When the body demands a temporary boost of power output or if temporary budgeting of resources is required, these signals can adjust heart rate and contractile strength to maintain continuous perfusion of all vascular beds with nutrient- and oxygen-rich blood. Given adequate time in the face of prolonged challenges, activation of GPCRs can also promote "remodeling of the heart" by increasing cell size, organ size, and chamber dimensions, or by varying tissue composition and altering the expression of protein isoforms controlling excitability and contractility. A common feature of heart disease is the state of chronic activation of GPCR signaling systems. Paradoxically, whereas acute activation is beneficial, chronic activation often contributes to further deterioration of cardiac performance. A better understanding of how chronic GPCR activation contributes to the development of heart disease is needed so that it can be translated into better prevention and therapeutic strategies in the clinic.
Alpha-power law MOSFET model and its applications to CMOS inverter delay and other formulas (1990)

An alpha -power-law MOS model that includes the carrier velocity saturation effect, which becomes prominent in short-channel MOSFETs, is introduced. The model is an extension of Shockley's square-law MOS model in the saturation region. Since the model is simple, it can be used to handle MOSFET circuits analytically and can predict the circuit behavior in the submicrometer region. Using the model, closed-form expressions for the delay, short-circuit power, and transition voltage of CMOS inverters are derived. The delay expression includes input waveform slope effects and parasitic drain/source resistance effects and can be used in simulation and/or optimization CAD tools. It is found that the CMOS inverter delay becomes less sensitive to the input waveform slope and that short-circuit dissipation increases as the carrier velocity saturation effect in short-channel MOSFETs gets more severe.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Prevalence of Hepatitis C Virus Genotypes in District Bannu, Khyber Pakhtunkhwa, Pakistan (2014)

Determination of an individual's hepatitis C virus (HCV) genotypes prior to antiviral therapy has become increasingly important for the clinical management and prognosis of HCV infection. Therefore, this study was conducted to investigate the prevalence of HCV genotypes in HCV infected patients of district Bannu in Khyber Pakhtunkhwa region of Pakistan. Serum samples of 117 seropositive patients were screened for HCV-RNA by using reverse transcriptase-nested polymerase chain reaction (RT-nested PCR) and then PCR positive samples were subjected to HCV genotyping. Out of 117 seropositive samples, 110 samples were found positive by PCR analysis. Genotype 3a was the most prevalent one detected in 38% of patients, followed by genotype 3b in 21% of patients, and then genotype 2a in 12% of patients. However 21% of HCV-PCR positive samples could not be genotyped by method used in this study. Genotype 3a was the most prevalent genotype in patients of all age groups and its prevalence was found high among patients with increasing age (>34 years). Moreover, genotypes 3a and 3b were found to be the most prevalent genotypes in patients with history of shaving by barbers, receiving multiple injections, and dental procedures. In conclusion there is need of further investigation of genotypes of HCV by using more sensitive assays and considering large sample size in district Bannu.
The master equations of mode-locking (2003)

Summary form only given. The theory of active mode-locking was first formulated by Kuizenga and Siegman. The master equation of passive mode-locking with a fast saturable absorber was set up by Haus. For a while, the subsequent master equation describing mode-locking with a slow saturable absorber held sway, since ultrashort pulses ran into the relaxation rate of the saturable absorber. Mode-locking by artificial saturable absorbers, such as KLM (Kerr Lens Modelocking) and Additive Pulse Modelocking (AFM) is well described by the master equation with a fast saturable absorber, complemented by self-phase modulation as done by Martinez et al.
Prevention of Nephrotoxicity of Cisplatin by Repeated Oral Administration of Ebselen in Rats (2000)

The ability of ebselen, which exhibits glutathione peroxidase (GSH-Px)-like activity, to prevent cisplatin (CDDP)-induced nephrotoxicity was examined in rats. CDDP (6 mg/kg [20 micromol/kg] body weight) was injected intraperitoneally. In subgroups, daily ebselen doses of 2.75 (10 micromol), 5.5 (20 micromol), or 11.0 mg (40 micromol)/kg body weight were administrated orally 1 hour prior to CDDP treatment. Treatment with CDDP alone resulted in significantly increased plasma creatinine (Cr) and blood urea nitrogen (BUN) levels. Repeated administration of 5.5 and 11.0 mg/kg ebselen prevented the CDDP-induced elevation of plasma Cr and BUN levels and protected against kidney damage. Relative to controls, rat that received CDDP treatment displayed a decreased ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG), an indicator directly related to oxidative stress, and elevated malondialdehyde (MDA) levels in the kidney. In comparison with controls, activity of GSH-Px activity, which antioxidant enzyme, was also reduced in the kidney of rats treated with CDDP. Repeated administration of 5.5 or 11.0 mg/kg ebselen prevented CDDP-induced alteration of GSH/GSSG ratios, MDA levels, and GSH-Px activity; however, no protection against CDDP was observed with administration of 2.75 mg/kg ebselen. Effective protection of CDDP-induced nephrotoxicity with ebselen was observed only when the molar amount of each daily ebselen treatment equaled or exceeded
Separate nuclear genes encode sarcomere-specific and ubiquitous human mitochondrial creatine kinase isoenzymes. (1990)

Creatine kinase (EC 2.7.3.2) isoenzymes play a central role in energy transduction. Nuclear genes encode creatine kinase subunits from muscle, brain, and mitochondria (MtCK). We have recently isolated a cDNA clone encoding MtCK from a human placental library which is expressed in many human tissues (Haas, R. C., Korenfeld, C., Zhang, Z., Perryman, B., Roman, D., and Strauss, A. W. (1989) J. Biol. Chem. 264, 2890-2897). With nontranslated and coding region probes, we demonstrated by RNA blot analysis that the MtCK mRNA in sarcomeric muscle is distinct from this placenta-derived, ubiquitous MtCK cDNA. To compare these different mRNAs, a MtCK cDNA clone was isolated from a human heart library and characterized by complete nucleotide sequence analysis. The chemically determined NH2-terminal 26 residues of purified human heart MtCK protein are identical to those predicted from this sarcomeric MtCK cDNA. The human sarcomeric and ubiquitous cDNAs share 73% nucleotide and 80% predicted amino acid sequence identities, but have less than 66% identity with the cytosolic creatine kinases. The sarcomeric MtCK cDNA encodes a 419-amino acid protein which contains a 39-residue transit peptide essential for mitochondrial import. Primer extension analysis predicts a 348-base pair 5'-nontranslated region. RNA blot analysis demonstrates that heart-derived MtCK is sarcomere-specific, but the ubiquitous MtCK mRNA is expressed in most tissues. Thus, separate nuclear genes encode two closely related, tissue-specific isoenzymes of MtCK. Our finding that multiple genes encode different mitochondrial protein isoenzymes is rare.
Transaction Network, Telephones, and Terminals: The Switched Network Transaction Telephone System (1978)

In June of 1972, an AT&T/BTL project team was formed to determine the evolving communication needs of the financial and retail industries as they moved to implement electronic funds transfer systems. The Bell System response occurred in three phases. The first phase introduced the Transaction I telephone, 407B data sets, and the Transaction Telephone Test Line Station in order to provide a simple means of evolving from the widespread manual-entry/audio-response systems into automatic-entry/audio-response systems. The second phase expanded our system offering to include Transaction II telephone, 407C data sets, and an upgraded Transaction Telephone Test Line Station. The third phase introduced the Transaction printer, which provided a simple means of generating receipts at the terminal location under control of the data center computer. This paper describes the resulting Switched Network Transaction Telephone System and the individual products of which it is built.
Phagocytosis by rabbit polymorphonuclear leukocytes: The effect of albumin and polyamino acids on latex uptake (1977)

Abstract Albumin in low concentrations (0.001–0.01 weight percent) was found to be an effective inhibitor of phagocytosis of polystyrene latex beads by rabbit polymorphonuclear leukocytes. Polyglutamic acid proved to be an inhibitor of latex uptake at even lower concentrations. Polylysine stimulates phagocytosis, maximal stimulation occurring at 0.002% polylysine. These findings are discussed with reference to the surface properties of latex particles and leukocytes, and particularly with reference to electrostatic interactions in phagocytosis.
Regional Electroporation of Single Cardiac Myocytes in a Focused Electric Field (2009)

There is now a significant interest in being able to locate single cells within geometrically defined regions of a microfluidic chip and to gain intracellular access through the local electroporation of the cell membrane. This paper describes the microfabrication of electroporation devices which can enable the regional electroporation of adult ventricular myocytes, in order to lower the local electrical resistance of the cell membrane. Initially three different devices, designed to suit the characteristic geometry of the cardiomyocyte, were investigated (all three designs serve to focus the electric field to selected regions of the cell). We demonstrate that one of these three devices revealed the sequence of cellular responses to field strengths of increasing magnitudes, namely, cell contraction, hypercontraction, and lysis. This same device required a reduced threshold voltage for each of these events, including in particular membrane breakdown. We were not only able to show the gradual regional increase in the electric conductivity of the cell membrane but were also able to avoid changes in the local intra- and extracellular pH (by preventing the local generation of protons at the electrode surface, as a consequence of the reduced threshold voltage). The paper provides evidence for new strategies for achieving robust and reproducible regional electroporation, a technique which, in future, may be used for the insertion of large molecular weight molecules (including genes) as well as for on-chip voltage clamping of the primary adult cardiomyocyte.
Hyperosmolarity inhibits galactosyl receptor-mediated but not fluid phase endocytosis in isolated rat hepatocytes (1989)

We have investigated the effects of hyperosmolarity induced by sucrose on the fluid phase endocytosis of the fluorescent dye lucifer yellow CH (LY) and the endocytosis of 125I-asialo-orosomucoid (ASOR) by the galactosyl receptor system in isolated rat hepatocytes. Continuous uptake of LY by cells at 37 degrees C is biphasic, occurs for 3-4 h, and then plateaus. Permeabilized cells or crude membranes do not bind LY at 4 or 37 degrees C. Intact cells also do not accumulate LY at 4 degrees C. The rate and extent of LY accumulation are concentration- and energy-dependent, and internalized LY is released from permeabilized cells. Efflux of internalized LY from washed cells is also biphasic and occurs with halftimes of approximately 38 and 82 min. LY is taken up into vesicles throughout the cytoplasm and the perinuclear region with a distribution pattern typical of the endocytic pathway. LY, therefore, behaves as a fluid phase marker in hepatocytes. LY has no effect on the uptake of 125I-ASOR at 37 degrees C. The rate of LY uptake by cells in suspension is not affected for at least 30 min by up to 0.2 M sucrose. The rate of endocytosis of 125I-ASOR, however, is progressively inhibited by increasing the osmolality of the medium with sucrose (greater than 98% with 0.2 M sucrose; Oka and Weigel (1988) J. Cell. Biochem. 36, 169-183). Hyperosmolarity completely inhibits endocytosis of 125I-ASOR by the galactosyl receptor, whereas fluid phase endocytosis of LY is unaffected. Cultured hepatocytes contained about 100 coated pits/mm of apical membrane length as assessed by transmission electron microscopy. In the presence of 0.4 M sucrose, only 17 coated pits/mm of membrane were observed, an 83% decrease. Only a few percent of the total cellular fluid phase uptake in hepatocytes is due to the coated pit endocytic pathway. We conclude that the fluid phase and receptor-mediated endocytic processes must operate via two separate pathways.
WiBreathe: Estimating respiration rate using wireless signals in natural settings in the home (2015)

Sensing respiration rate has many applications in monitoring various health conditions, such as sleep apnea and chronic obstructive pulmonary disease. In this paper, we present WiBreathe, a wireless, high fidelity and non-invasive breathing monitor that leverages wireless signals at 2.4 GHz to estimate an individual's respiration rate. Our work extends past approaches of using wireless signals for respiratory monitoring by using only a single transmitter-receiver pair at the same frequency range of commodity Wi-Fi signals to estimate the respiratory rate of an individual. This is done irrespective of whether they are in line of sight or not (e.g., through walls). Furthermore, we demonstrate the capability of WiBreathe in detecting multiple people and by extension, their respiration rates. We evaluate our approach in various natural environments and show that we can track breathing with the accuracy of 1.54 breaths per minute when compared to a clinical respiratory chest band.
Solubilization of active GLP‐1 (7–36)amide receptors from RINm5F plasma membranes (1992)

Glucagon-like peptide-1 (7-36)amide (GLP-1 (7-36)amide) represents a physiologically important incretin in mammals including man. Receptors for GLP-1 (7-36)amide have been described in RINm5F cells. We have solubilized active GLP-1(7-36)amide receptors from RINm5F cell membranes utilizing the detergents octyl-beta-glucoside and CHAPS; Triton X-100 and Lubrol PX were ineffective. Binding of radiolabeled GLP-1(7-36)amide to the solubilized receptor was inhibited concentration-dependently by addition of unlabeled peptide. Scatchard analysis of binding data revealed a single class of binding sites with Kd = 0.26 +/- 0.03 nM and Bmax = 65.4 +/- 21.24 fmol/mg of protein for the membrane-bound receptor and Kd = 22.54 +/- 4.42 microM and Bmax = 3.9 +/- 0.79 pmol/mg of protein for the solubilized receptor. The binding of the radiolabel to the solubilized receptor was dependent both on the concentrations of mono- and divalent cations and the protein/detergent ratio in the incubation buffer. The membrane bound receptor is sensitive to guanine-nucleotides, however neither GTP-gamma-S nor GDP-beta-S affected binding of labeled peptide to solubilized receptor. These data indicate that the solubilized receptor may have lost association with its G-protein. In conclusion, the here presented protocol allows solubilization of the GLP-1(7-36)amide receptor in a functional state, and opens up the possibility for further molecular characterization of the receptor protein.
Cellular mechanisms of atherogenesis and the effects of nitric oxide (1992)

The cellular mechanisms leading to atherosclerosis are becoming more clearly defined. In response to hypercholesterolemia, an endothelial alteration or dysfunction occurs that precipitates monocyte adherence and infiltration. The specific alterations that lead to this initial event in atherogenesis are under intense study. A number of cytokines, adhesive molecules, and chemoattractants play an important role in this process. The reduced elaboration of antiatherogenic molecules may also be involved. Endothelium-derived relaxing factor, or nitric oxide, may be one such molecule. This substance, derived from the amino acid L-arginine, has potent antiplatelet and antiproliferative properties. More recently, it has been shown that this substance also inhibits interaction of leukocytes with the vessel wall. The influence of this factor is known to be reduced in hypercholesterolemic states, and this abnormality may promote atherogenesis. Restoration of nitric oxide activity appears to inhibit atherogenesis. This new finding may lead to new therapeutic approaches to atherosclerosis.
Functional heterogeneity of human memory CD4 + T cell clones primed by pathogens or vaccines (2014)

Distinct types of CD4(+) T cells protect the host against different classes of pathogens. However, it is unclear whether a given pathogen induces a single type of polarized T cell. By combining antigenic stimulation and T cell receptor deep sequencing, we found that human pathogen- and vaccine-specific T helper 1 (T(H)1), T(H)2, and T(H)17 memory cells have different frequencies but comparable diversity and comprise not only clones polarized toward a single fate, but also clones whose progeny have acquired multiple fates. Single naïve T cells primed by a pathogen in vitro could also give rise to multiple fates. Our results unravel an unexpected degree of interclonal and intraclonal functional heterogeneity of the human T cell response and suggest that polarized responses result from preferential expansion rather than priming.