gebhart/patrepeval huggingface dataset:
The pharmacokinetics and pharmacodynamics of docetaxel (DCTX) in Caucasian and African American patients with solid tumors (2004)

2043 Background: Increased oral clearance (CL/F) of drugs that are CYP3A and/or P-glycoprotein (P-gp) substrates has been reported in African-American (AA) compared to Caucasian (C) patients (pts). The primary study objective was to test the hypothesis that the pharmacokinetics and pharmacodynamics of DCTX, an intravenously administered substrate for CYP3A and P-gp, would be different between C and AA pts. Methods: DCTX population pharmacokinetics and pharmacodynamics were studied following a single intravenous dose of DCTX (75 or 100 mg/m2) in cancer pts. of C and AA ethnicity. Timed blood samples, using a published limited sampling regimen, were obtained. Clinical toxicity and absolute neutrophil count (ANC) were monitored on days 8, 15 and 22 post treatment. DCTX concentrations were measured by HPLC. A complete population pharmacokinetic analysis is being performed and genotyping for CYP3A and P-gp is ongoing using sequencing or polymerase chain reaction -restriction fragment length polymorphisms (PCR-RFLP). Results: 109 pts were enrolled into the study. There were 69 C (43M:26F) median age 61 yr (range 29–73) and 40 AA (26M:14F) median age 63 yr (range 38–81). Mean ± SD DCTX Cmax and C6h (all adjusted to 75 mg/m2dose) are shown in the table below. There was no difference in the percent reduction in ANC from baseline (mean ± SD; n) between C (81± 19%; n=43) and AA (75± 24%; n=20) when patients who received 75 mg/m2 DCTX were compared. Relationships between DCTX pharmacokinetics and CYP3A and P-gp genotype in the two ethninc groups are being explored. Conclusions: There was no apparent difference in DCTX pharmacokinetics or DCTX induced myelosuppression between cancer patients of either C or AA ethnicity. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis
General scaling limitations of ground-plane and isolated-object cloaks (2011)

We prove that, for arbitrary three-dimensional transformation-based invisibility cloaking of an object above a ground plane or of isolated objects, there are practical constraints that increase with the object size. In particular, we show that the cloak thickness must scale proportionally to the thickness of the object being cloaked, assuming bounded refractive indices, and that absorption discrepancies and other imperfections must scale inversely with the object thickness. For isolated objects, we also show that bounded refractive indices imply a lower bound on the effective cross section.
Characterisation of distributive mixing in thermoplastics compositions (1986)

Problems associated with assessment of mixture uniformity are discussed with particular reference to polymer compositions containing pigment additives. The use of automatic image analysis is described and shown to be a rapid means of quantifying distributive mixture quality in these materials. Results are presented which demonstrate the application of this technique to measurement of polymer mixing by twin-screw extrusion.
Structure and functional characterization of neuronal alpha 1E calcium channel subtypes. (1994)

We have cloned overlapping cDNAs encoding alpha 1E Ca2+ channel subunits from mouse and human brain. We observed that these alpha 1E transcripts were widely distributed in the central nervous system. We also demonstrated the existence of two variants of the human alpha 1E subunit. Comparison of the sequence of these alpha 1E subunits to those from other species suggests that at least four alternatively spliced variants of alpha 1E exist. Expression of human alpha 1E in HEK293 cells and Xenopus oocytes produced high voltage-activated Ca2+ currents that inactivated rapidly (tau approximately 20 ms at 0 mV). The size of the currents obtained were enhanced approximately 40-fold by co-expression with human neuronal alpha 2 and beta Ca2+ channel subunits. alpha 1E currents were insensitive to the drugs and toxins previously used to define other classes of voltage-activated Ca2+ channels. Thus, alpha 1E-mediated Ca2+ channels appear to be a pharmacologically distinct class of voltage-activated Ca2+ channels.
Thrombocytopenia and Acute Renal Failure in Puumala Hantavirus Infections (2004)

Nephropathia epidemica, caused by Puumala virus (PUUV) infection, is a form of hemorrhagic fever with renal syndrome of variable severity. Early prognostic markers for the severity of renal failure have not been established. We evaluated clinical and laboratory parameters of 15 consecutive patients with acute PUUV infection, which is endemic in the Alb-Danube region, South Germany. Severe renal failure (serum creatinine >620 micromol/L) was observed in seven patients; four required hemodialysis treatment. Low platelet count (<60 x 109/L), but not leukocyte count, C-reactive protein, or other parameters obtained at the initial evaluation, was significantly associated with subsequent severe renal failure (p = 0.004). Maximum serum creatinine was preceded by platelet count nadirs by a median of 4 days. Thrombocytopenia <60 x 109/L appears predictive of a severe course of acute renal failure in nephropathia epidemica, with potential value for risk-adapted clinical disease management.
Vapor Phase Growth of Stannic Oxide Single Crystals (1969)

Single crystals of stannic oxide, , of higher purity and with higher Hall mobility than any previously reported have been grown from the vapor using the reaction
Growth of small children managed with chronic peritoneal dialysis and nasogastric tube feedings: 203-month experience in 14 patients. (1990)

This 203-month experience with CPD and NG feedings in 14 small children weighing less than or equal to 10 kg at initiation of CPD for ESRD, provides evidence that CPD and vigorous nutritional therapy is effective in maintaining and improving growth until a successful renal transplant can be performed. Nutritional therapy should be initiated early, if possible when growth begins to decline even before the onset of ESRD and the need for CPD. Infants who are less than or equal to 4 months old at initiation of CPD are more likely to have a complicated clinical course and poor growth, despite the provision of CPD and vigorous nutritional support. More experience with this group of patients is needed to determine appropriate therapy.
Should a fistula first policy be revisited in elderly haemodialysis patients? (2018)

Life-sustaining haemodialysis requires a durable vascular access (VA) to the circulatory system. The ideal permanent VA must provide longevity for use with minimal complication rate and supply sufficient blood flow to deliver the prescribed dialysis dosage. Arteriovenous fistulas (AVFs) have been endorsed by many professional societies as the VA of choice. However, the high prevalence of comorbidities, particularly diabetes mellitus, peripheral vascular disease and arterial hypertension in elderly people, usually make VA creation more difficult in the elderly. Many of these patients may have an insufficient vasculature for AVF maturation. Furthermore, many AVFs created prior to the initiation of haemodialysis may never be used due to the competing risk of death before dialysis is required. As such, an arteriovenous graft and, in some cases, a central venous catheter, become a valid alternative form of VA. Consequently, there are multiple decision points that require careful reflection before an AVF is placed in the elderly. The traditional metrics of access patency, failure and infection are now being seen in a broader context that includes procedure burden, quality of life, patient preferences, morbidity, mortality and cost. This article of the European Dialysis (EUDIAL) Working Group of ERA-EDTA critically reviews the current evidence on VA in elderly haemodialysis patients and concludes that a pragmatic patient-centred approach is mandatory, thus considering the possibility that the AVF first approach should not be an absolute.
In vivo investigation of high-intensity focused ultrasound combined with thermally triggered chemotherapy for liver cancer treatment (2017)

High-Intensity Focused Ultrasound (HIFU) induces rapid tissue heating and mechanical disruption and also provides noninvasive release of chemotherapy from temperature-sensitive-liposomes (TSLs). We evaluated the combination of Sorafenib-loaded TSLs (SfTSLs) and HIFU via analysis of cell viability, tumor growth, and long-term survival. Liposomes were encapsulated with Sorafenib at 10μM with a glass transition temperature of 43°C. Hep3B human liver cancer cells were placed in PCR tubes to mimic dense tumor aggregates. Aggregates were treated with HIFU alone, SfTSLs alone, or SfTSLs + HIFU. HIFU exposure was applied for 30 seconds at acoustic output powers of 8.7 and 12W. Cell viability and proliferation were measured over 4 days post-treatment via AnnexinV/PI and WST-8 staining. Xenografted tumors were created via injection of 1.0×106 Hep3B cells within Matrigel into flanks of athymic-nude mice. Tumors at 8–10 mm were separated into the following groups: Control (sham), HIFU, SfTSLs, and SfTSLs + HIFU. Tumors were measured daily with endpoints at 5 days, 14 days, or long-term survival. Dissected tumors were H&amp;E stained and evaluated by a blinded pathologist. The in vitro data indicates that Hep3B cells exposed to SfTSLs + HIFU have a significantly lower viability and proliferation rate. Similarly, in vivo results show SfTSLs + HIFU reduces tumor growth and increases survival.
Process optimization of continuous gluconic acid fermentation by isolated yeast‐like strains of Aureobasidium pullulans (2005)

This study was focused on the optimization of a new fermentation process for continuous gluconic acid production by the isolated yeast-like strain Aureobasidium pullulans DSM 7085 (isolate 70). Operational fermentation parameters were optimized in chemostat cultures, using a defined glucose medium. Different optima were found for growth and gluconic acid production for each set of operation parameters. Highest productivity was recorded at pH values between 6.5 and 7.0 and temperatures between 29 and 31 degrees C. A gluconic acid concentration higher than 230 g/L was continuously produced at residence times of 12 h. A steady state extracellular gluconic acid concentration of 234 g/L was measured at pH 6.5. 122% air saturation yielded the highest volumetric productivity and product concentration. The biomass-specific productivity increased steadily upon raising air saturation. An intracellular gluconic acid concentration of about 159 g/L (0.83 mol) was determined at 31 degrees C. This is to be compared with an extracellular concentration of 223 g/L (1.16 mol), which indicates the possible existence of an active transport system for gluconic acid secretion, or the presence of extracellular glucose oxidizing enzymes. The new process provides significant advantages over the traditional discontinuous fungi operations. The process control becomes easier, thus offering stable product quality and quantity.
The Millimeter Wave Spectrum of Estragole and Verbenone (2012)

Author Institution: Department of Chemistry, University of Leicester, Leicester, LE1 7RH, United Kingdom; School of Chemistry, Monash University, 3800, Victoria, Australia
Multicenter Evaluation of a Standardized Protocol for Rest and Acetazolamide Cerebral Blood Flow Assessment Using a Quantitative SPECT Reconstruction Program and Split-Dose (2010)

SPECT can provide valuable diagnostic and treatment response information in large-scale multicenter clinical trials. However, SPECT has been limited in providing consistent quantitative functional parametric values across the centers, largely because of a lack of standardized procedures to correct for attenuation and scatter. Recently, a novel software package has been developed to reconstruct quantitative SPECT images and assess cerebral blood flow (CBF) at rest and after acetazolamide challenge from a single SPECT session. This study was aimed at validating this technique at different institutions with a variety of SPECT devices and imaging protocols. Methods: Twelve participating institutions obtained a series of SPECT scans on physical phantoms and clinical patients. The phantom experiments included the assessment of septal penetration for each collimator used and of the accuracy of the reconstructed images. Clinical studies were divided into 3 protocols, including intrainstitutional reproducibility, a comparison with PET, and rest–rest study consistency. The results from 46 successful studies were analyzed. Results: Activity concentration estimation (Bq/mL) in the reconstructed SPECT images of a uniform cylindric phantom showed an interinstitution variation of 65.1%, with a systematic underestimation of concentration by 12.5%. CBF values were reproducible both at rest and after acetazolamide on the basis of repeated studies in the same patient (mean 6 SD difference, 20.4 6 5.2 mL/min/100 g, n 5 44). CBF values were also consistent with those determined using PET (26.1 6 5.1 mL/min/100 g, n 5 6). Conclusion: This study demonstrates that SPECT can quantitatively provide physiologic functional images of rest and acetazolamide challenge CBF, using a quantitative reconstruction software package.
P3432Coronary artery calcium score is of limited sensitivity in detecting subclinical atherosclerosis in young individuals with family history of coronary artery disease (2019)

Abstract Introduction Family history of premature coronary artery disease (CAD) is known to predispose individuals to adverse CAD events, often at a younger age. Current risk stratification strategy is suboptimal, as up to 50% of individuals were considered “low-risk” prior to their first presentation of myocardial infarction. Coronary artery calcium score (CACS) is a marker of atherosclerosis and provides incremental value in risk stratification. However, the utility of CACS may be limited in younger patients as they often have non-calcified atherosclerotic plaques. In this study, we evaluate the sensitivity of CACS in detecting subclinical atherosclerosis in different age groups. Method From 310 referrals to a specialized unit in the management of early atherosclerosis, 222 individuals with a family history of premature CAD (defined as CAD events in first-degree family members, male&lt;55 and female&lt;65) and aged between 35 and 55 were enrolled for assessment of their CAD risks. Individuals with possible, probably or definite familial hypercholesterolemia were excluded. In addition to clinical and risk factor evaluation, cardiac CT and CACS were performed in select individuals, at the discretion of the treating physician. Results Of the 141 (59% male, mean age 45.9±6.0 year) individuals that completed clinical evaluation, 65 (73% male, mean age 47.4±6.9 years) have subclinical atherosclerosis (defined by the presence of atherosclerotic plaques in any of the coronary artery segments in cardiac CT). Of them, 52 have CACS&gt;0, giving an overall sensitivity of 80%. The breakdown by age group is shown in table 1. The sensitivity of CACS in detecting subclinical atherosclerosis is quite modest in younger individuals (60% in individuals &lt;45 year-old) but improves with patient age (&gt;85% in &gt;45 years). Table 1. Sensitivity of CACS in different age groups Age group True Positive Fast Negative Sensitivity N (CAC+ CTCA+) (CAC+ CTCA−) (%) &lt;40 6 4 60 10 41–45 7 4 55 11 46–50 19 3 86 22 51–55 20 1 95 21 Conclusion In younger individuals (&lt;45 years) with family history of premature CAD, CACS is of limited sensitivity in detecting subclinical atherosclerosis, and should not be used to rule out CAD. Further studies are warranted.
Interaction of tumor and normal blood cells with ethylene oxide and propylene oxide block copolymers (1999)

Ethylene oxide and propylene oxide block copolymers (pluronics) are widely known as agents that promote drug penetration across biological barriers. We have studied the interaction of normal and malignant blood cells with pluronics L61 and P85 that have different hydrophobicity. SP2/0 myeloma cells accumulated pluronics while normal cells adsorb most of the polymer on the surface. Interaction of pluronics with cells resulted in drastic changes of membrane microviscosity. Tumor cell membrane microviscosity decreased after pluronics adsorption, in contrast to normal cells, whose membrane microviscosity was enhanced. We suppose that sensitivity of tumor cell membrane microviscosity to the pluronics action correlates with its permeability for molecular substances.
Site‐specific receptor methylation of FrzCD in Myxococcus xanthus is controlled by a tetra‐trico peptide repeat (TPR) containing regulatory domain of the FrzF methyltransferase (2008)

Myxococcus xanthus is a gliding bacterium with a complex life cycle that includes swarming, predation and fruiting body formation. Directed movements in M. xanthus are regulated by the Frz chemosensory system, which controls cell reversals. The Frz pathway requires the activity of FrzCD, a cytoplasmic methyl-accepting chemotaxis protein, and FrzF, a methyltransferase (CheR) containing an additional domain with three tetra trico-peptide repeats (TPRs). To investigate the role of the TPRs in FrzCD methylation, we used full-length FrzF and FrzF lacking its TPRs (FrzF(CheR)) to methylate FrzCD in vitro. FrzF methylated FrzCD on a single residue, E182, while FrzF(CheR) methylated FrzCD on three residues, E168, E175 and E182, indicating that the TPRs regulate site-specific methylation. E168 and E182 were predicted consensus methylation sites, but E175 is methylated on an HE pair. To determine the roles of these sites in vivo, we substituted each methylatable glutamate with either an aspartate or an alanine residue and determined the impact of the point mutants on single cell reversals, swarming and fruiting body formation. Single, double and triple methylation site mutants revealed that each site played a unique role in M. xanthus behaviour and that the pattern of receptor methylation determined receptor activity. This work also shows that methylation can both activate and inactivate the receptor.
Observation of biological objects using an optical diffraction tomographic microscope (2000)

A prototype of a tomographic microscope has bene realized, which uses phase-shifting holography to sense the wave diffracted by an object. The observed object is successively illuminated by a series of about 1000 plane waves. Each diffracted wave yields a part of the frequency representation of the object, and superposition of these parts yields a 3D frequency representation. An inverse Fourier transform yields the 3D spatial representation, from which sections, projections or stereoscopic images can be extracted. This prototype has been used to image a variety of biological samples. Images show a resolution limit of about a quarter of a wavelength and a depth of field of about 40 microns. Important factors for the understanding of image characteristics include horizontal and vertical resolution, ability to image horizontal and/or vertical surfaces, ability to distinguish variations of refractive index from variations of absorptivity. These and other imaging characteristics of the tomographic microscope are discussed on the basis of a set of images of biological samples. The connection between characteristics of a three-dimensional image and its frequency representation is explained. Influence of an object's characteristics (thickness, refractive index, ...) on image quality is described. Possible improvements and their impact on image quality is also discussed.
Freeze‐drying of raw beef. III.—Influence of some packaging and some storage variables (1968)

Abstract Minimisation of oxygen exposure of freeze‐dried raw beef before packaging and during storage was studied in multifactorial experiments for its effect on the quality of the product, as was the effect of storage time and temperature, intramuscular fat content, and different head‐space gas compositions. Exposure of the freeze‐dried meat to the air before packaging under nitrogen, which is commercial practice today, clearly shortened storage life, particularly of meat with a high fat content. The effect could be counteracted by the application of an oxygen scavenging system, which proved effective at initial head‐space oxygen levels as high as 4%. The use of carbon dioxide in the head‐space reduced product quality compared with nitrogen or the hydrogen‐nitrogen mixture employed in the oxygen scavenging system. The red meat colour as well as quality as a whole was much better preserved by cold storage and particularly frozen storage, by packaging without pre‐exposure to the atmosphere or by using an oxygen scavenging system based on the reaction of oxygen with hydrogen over a palladium catalyst enclosed in the package. Of these methods, refrigerated storage is probably not a realistic solution under present commercial conditions.
Wide single-mode tuning in quantum cascade lasers with asymmetric Mach-Zehnder interferometer type cavities with separately biased arms (2013)

We report on the experimental demonstration of a widely tunable single mode quantum cascade laser with Asymmetric Mach-Zehnder (AMZ) interferometer type cavities with separately biased arms. Current and, consequently, temperature tuning of the two arms of the AMZ type cavity resulted in a single mode tuning range of 20 cm−1 at 80 K in continuous-wave mode operation, a ten-fold improvement from the lasers under a single bias current. In addition, we also observed a five fold increase in the tuning rate as compared to the AMZ cavities controlled by one bias current.
New loading algorithms for adaptive SS-MC-MA systems over power-line channels (2005)

International audience
RNA profiles reveal signatures of future health and disease in pregnancy (2022)

Maternal morbidity and mortality continue to rise, and pre-eclampsia is a major driver of this burden<sup>1</sup>. Yet the ability to assess underlying pathophysiology before clinical presentation to enable identification of pregnancies at risk remains elusive. Here we demonstrate the ability of plasma cell-free RNA (cfRNA) to reveal patterns of normal pregnancy progression and determine the risk of developing pre-eclampsia months before clinical presentation. Our results centre on comprehensive transcriptome data from eight independent prospectively collected cohorts comprising 1,840 racially diverse pregnancies and retrospective analysis of 2,539 banked plasma samples. The pre-eclampsia data include 524 samples (72 cases and 452 non-cases) from two diverse independent cohorts collected 14.5 weeks (s.d., 4.5 weeks) before delivery. We show that cfRNA signatures from a single blood draw can track pregnancy progression at the placental, maternal and fetal levels and can robustly predict pre-eclampsia, with a sensitivity of 75% and a positive predictive value of 32.3% (s.d., 3%), which is superior to the state-of-the-art method<sup>2</sup>. cfRNA signatures of normal pregnancy progression and pre-eclampsia are independent of clinical factors, such as maternal age, body mass index and race, which cumulatively account for less than 1% of model variance. Further, the cfRNA signature for pre-eclampsia contains gene features linked to biological processes implicated in the underlying pathophysiology of pre-eclampsia.