Miracle-dz/UniFAR-FTUs huggingface dataset:
Experimental pencil beam kernels derivation for 3D dose calculation in flattening filter free modulated fields

This paper presents a method to obtain the pencil-beam kernels that characterize a megavoltage photon beam generated in a flattening filter free (FFF) linear accelerator (linac) by deconvolution from experimental measurements at different depths. The formalism is applied to perform independent dose calculations in modulated fields. In our previous work a formalism was developed for ideal flat fluences exiting the linac’s head. That framework could not deal with spatially varying energy fluences, so any deviation from the ideal flat fluence was treated as a perturbation. The present work addresses the necessity of implementing an exact analysis where any spatially varying fluence can be used such as those encountered in FFF beams. A major improvement introduced here is to handle the actual fluence in the deconvolution procedure. We studied the uncertainties associated to the kernel derivation with this method. Several Kodak EDR2 radiographic films were irradiated with a 10 MV FFF photon beam from two linacs from different vendors, at the depths of 5, 10, 15, and 20cm in polystyrene (RW3 water-equivalent phantom, PTW Freiburg, Germany). The irradiation field was a 50mm diameter circular field, collimated with a lead block. The 3D kernel for a FFF beam was obtained by deconvolution using the Hankel transform. A correction on the low dose part of the kernel was performed to reproduce accurately the experimental output factors. Error uncertainty in the kernel derivation procedure was estimated to be within 0.2%. Eighteen modulated fields used clinically in different treatment localizations were irradiated at four measurement depths (total of fifty-four film measurements). Comparison through the gamma-index to their corresponding calculated absolute dose distributions showed a number of passing points (3%, 3mm) mostly above 99%. This new procedure is more reliable and robust than the previous one. Its ability to perform accurate independent dose calculations was demonstrated.
Dissociation of 5' AMP-activated protein kinase activation and glucose uptake stimulation by mitochondrial uncoupling and hyperosmolar stress: differential sensitivities to intracellular Ca2+ and protein kinase C inhibition.

2,4-dinitrophenol (DNP) compromises ATP production within the cell by disrupting the mitochondrial electron transport chain. The resulting loss of ATP leads to an increase in glucose uptake for anaerobic generation of ATP. In L6 skeletal muscle cells, DNP increases the rate of glucose uptake by twofold. We previously showed that DNP increases cell surface levels of glucose transporter 4 (GLUT4) and hexose uptake via a Ca2+-sensitive and conventional protein kinase C (cPKC)-dependent mechanism. Recently, 5' AMP-activated protein kinase (AMPK) has been proposed to mediate the stimulation of glucose uptake by energy stressors such as exercise and hypoxia. Changes in Ca2+ and cPKC have also been invoked in the stimulation of glucose uptake by exercise and hypoxia. Here we examine whether changes in cytosolic Ca2+ or cPKC lead to activation of AMPK. We show that treatment of L6 cells with DNP (0.5 mM) or hyperosmolar stress (mannitol, 0.6 M) increased AMPK activity by 3.5-fold. AMPK activation peaked by 10-15 min prior to maximal stimulation of glucose uptake. Intracellular Ca2+ chelation and cPKC inhibition prior to treatment with DNP and hyperosmolarity significantly reduced cell surface GLUT4 levels and hexose uptake but had no effect on AMPK activation. These results illustrate a break in the relationship between AMPK activation and glucose uptake in skeletal muscle cells. Activation of AMPK does not suffice to stimulate glucose uptake in response to DNP and hyperosmolarity.
Successful Use and Dosing of Bivalirudin After Temporary Total Artificial Heart Implantation: A Case Series

The temporary total artificial heart (TAH‐t) has emerged as an effective bridge to transplantation for individuals with biventricular failure. Implantation of a TAH‐t creates a hypercoagulable state requiring a multidrug approach that includes low‐dose unfractionated heparin (UFH) in order to minimize thromboembolism. A concern with UFH is the development of heparin‐dependent antibodies, which develop in up to 50% of patients receiving the drug as part of cardiopulmonary bypass. If UFH therapy continues postoperatively, the risk of heparin‐induced thrombocytopenia approaches 3%. Small investigations have demonstrated that bivalirudin, given as a bolus of 0.75–1 mg/kg followed by an infusion at 1.75‐2.5 mg/kg/hour, is an effective alternative to UFH for therapeutic anticoagulation during coronary artery bypass surgery, valve replacement, or both. We describe a series of five adults (age range 24–58 yrs) who received bivalirudin as an alternative to low‐dose UFH after TAH‐t implantation. None of the patients had documented heparin‐induced thrombocytopenia. Treatment was started at the discretion of the treating physician, and adjustments were based principally on the results of thromboelastography. Additional general monitoring included activated partial thromboplastin time, prothrombin time, international normalized ratio, fibrinogen, D‐dimer, platelet count, hemoglobin, hematocrit, and platelet aggregation studies. Bivalirudin therapy was continued until successful warfarin implementation. All five patients received bivalirudin in addition to standard antithrombotic therapy. Bivalirudin treatment started at a dosage of 0.005 or 0.01 mg/kg/hour with titration to maintain normocoagulability, which occurred (without concomitant warfarin therapy) within the dosage range of 0.01‐0.02 mg/kg/hour. Duration of TAH‐t implantation was a mean of 38.8 days (range 25–60 days), and bivalirudin was continued for a mean of 15.2 days (range 7–24 days). No major hemorrhagic events occurred during treatment, and all patients successfully transitioned to warfarin therapy. Low‐dose bivalirudin, as an alternative to UFH, maintained normocoagulability after TAH‐t implantation. Further investigation is warranted to define the role and dosing of bivalirudin in this situation.
The thiol reagent, thimerosal, irreversibly inhibits meiosis reinitiation in mouse oocyte when applied during a very early and narrow temporal window: A pharmacological analysis

The effect of the sulfhydryl reagent, thimerosal (TMS) on meiosis resumption in germinal vesicle (GV)‐stage denuded mouse oocytes was studied. It irreversibly inhibits both GV breakdown (GVBD) and the first polar body (pb1) extrusion in concentration‐ and time‐dependent manners, the most striking result being the very early and narrow temporal window during which denuded primary oocytes released from their follicle are susceptible to a pulse of the drug. This inhibition is bypassed by dithiothreitol (DTT) with an efficiency declining with time, while thiosalicylic acid (TA), an analog of TMS devoid of the mercury atom, has no effect on meiosis reinitiation. These results strongly suggest that the inhibitory effect of TMS is a consequence of its sulfhydryl group oxidising activity. The molecular target(s) of this inhibitory oxidation should however be identified. In contrast to DTT, okadaic acid (OA), known to bypass the inhibitory effect of drugs interfering with protein kinase activities, only induces chromatin condensation and GVBD in TMS‐pulsed oocytes with a delay of about 8 hr as compared to the control situation. This confirms that a very early thiol oxidation induced by TMS exerts a much more dramatic effect on resumption on meiosis than any pharmacological manipulation of protein kinase activities leading to activation of MPF. Mol. Reprod. Dev. 65: 454–461, 2003. © 2003 Wiley‐Liss, Inc.
Thyroid hormone promotes insulin‐induced glucose uptake by enhancing Akt phosphorylation and VAMP2 translocation in 3T3‐L1 adipocytes

The purpose of this study was to test a hypothesis that T3 promotes glucose uptake via enhancing insulin‐induced Akt phosphorylation and VAMP2 translocation in 3T3‐L1 adipocytes. T3 significantly enhanced insulin‐induced phosphorylation of Akt, cytoplasma to cell membrane translocations of vesicle‐associated membrane protein 2 (VAMP2) and glucose transporter 4 (GLUT4), and glucose uptake in adipocytes. Akt inhibitor X abolished the promoting effects of T3, suggesting that Akt activation is essential for T3 to enhance these insulin‐induced events in adipocytes. Knockdown of VAMP2 using siRNA abrogated the effects of T3 on insulin‐induced GLUT4 translocation and glucose uptake, suggesting that VAMP2 is an important mediator of these processes. These data suggest that T3 may promote glucose uptake via enhancing insulin‐induced phosphorylation of Akt and subsequent translocations of VAMP2 and GLUT4 in 3T3‐L1 adipocytes. Akt phosphorylation is necessary for the promoting effects of T3 on insulin‐stimulated VAMP2 translocation. Further, VAMP2 is essential for T3 to increase insulin‐stimulated translocation of GLUT4 and subsequent uptake of glucose in adipocytes. J. Cell. Physiol. 226: 2625–2632, 2011. © 2010 Wiley‐Liss, Inc.
Neural tube defects induced by folate deficiency in mutant curly tail (Grhl3) embryos are associated with alteration in folate one-carbon metabolism but are unlikely to result from diminished methylation.

BACKGROUND Folate one-carbon metabolism has been implicated as a determinant of susceptibility to neural tube defects (NTDs), owing to the preventive effect of maternal folic acid supplementation and the higher risk associated with markers of diminished folate status. METHODS Folate one-carbon metabolism was compared in curly tail (ct/ct) and genetically matched congenic (+(ct)/+(ct)) mouse strains using the deoxyuridine suppression test in embryonic fibroblast cells and by quantifying s-adenosylmethionine (SAM) and s-adenosylhomocysteine (SAH) in embryos using liquid chromatography tandem mass spectrometry. A possible genetic interaction between curly tail and a null allele of 5,10-methylenetetrahydrofolate reductase (MTHFR) was investigated by generation of compound mutant embryos. RESULTS There was no deficit in thymidylate biosynthesis in ct/ct cells, but incorporation of exogenous thymidine was lower than in +(ct)/+(ct) cells. In +(ct)/+(ct) embryos the SAM/SAH ratio was diminished by dietary folate deficiency and normalized by folic acid or myo-inositol treatment, in association with prevention of NTDs. In contrast, folate deficiency caused a significant increase in the SAM/SAH ratio in ct/ct embryos. Loss of MTHFR function in curly tail embryos significantly reduced the SAM/SAH ratio but did not cause cranial NTDs or alter the frequency of caudal NTDs. CONCLUSIONS Curly tail fibroblasts and embryos, in which Grhl3 expression is reduced, display alterations in one-carbon metabolism, particularly in the response to folate deficiency, compared to genetically matched congenic controls in which Grhl3 is unaffected. However, unlike folate deficiency, diminished methylation potential appears to be insufficient to cause cranial NTDs in the curly tail strain, nor does it increase the frequency of caudal NTDs.
Frequency Selective Buildings Through Frequency Selective Surfaces

This paper proposes the deployment of frequency selective surfaces (FSS) in indoor wireless environments and investigates their effect on radio wave propagation. FSS can be deployed to selectively confine radio propagation in indoor areas, by artificially increasing the radio transmission loss naturally caused by building walls. FSS can also be used to channel radio signals into other areas of interest. Simulations and measurements have been carried out in order to verify the frequency selectivity of the FSS. Practical considerations regarding the deployment of FSS on building walls and the separation distance between the FSS and the supporting wall have been also investigated. Finally, a controlled, small-scale indoor environment has been constructed and measured in an anechoic chamber in order to practically verify this approach through the usage of ray tracing techniques.
Probing membrane proteins using atomic force microscopy

To gain insights into how biological molecules function, advanced technologies enabling imaging, sensing, and actuating single molecules are required. The atomic force microscope (AFM) would be one of novel potential tools for these tasks. In this study, techniques and efforts using AFM to probe biomolecules are introduced and reviewed. The state‐of‐art techniques for characterizing specific single receptor using the functionalized AFM tip are discussed. An example of studying the angiotensin II type 1 (AT1) receptors expressed in sensory neuronal cells by AFM with a functionalized tip is given. Perspectives for identifying and characterizing specific individual membrane proteins using AFM in living cells are provided. Given that many diseases have their roots at the molecular scale and are best understood as a malfunctioning biological nanomachines, the prospects of these unique techniques in basic biomedical research or in clinical practice are beyond our imagination. J. Cell. Biochem. 97: 1191–1197, 2006. © 2006 Wiley‐Liss, Inc.
Annual Report Readability and Stock Liquidity

We examine the effect of annual report textual complexity on firms’ stock liquidity. Using techniques from computational linguistics, we predict and find that less readable filings are associated with lower stock liquidity. Our study provides evidence that difficult-to-read annual reports hinders investor’s ability to process and analyze information contained in corporate annual reports, reducing thereby their willingness to trade which decreases stock liquidity. Our findings are robust to a battery of sensitivity tests, including endogeneity, use of alternative regression techniques, and use of alternative liquidity and readability proxies.
Capacity-approaching signals for the scalar Gaussian channel

We consider the scalar Gaussian channel with power constraint P. A gap exists between the channel capacity and the highest achievable rate of equiprobable uniformly spaced signal. Several approaches enable to overcome this limitation such as constellations with non-uniform probability or constellation shaping. In this short paper, we focus on constellation shaping. We present a method to construct one-dimensional constellations with equiprobable signaling that achieve the Gaussian capacity as the number of signal points goes to infinity.
Naloxone--does over-antagonism matter? Evidence of iatrogenic harm after emergency treatment of heroin/opioid overdose.

AIM To analyse drug users' views and experiences of naloxone during emergency resuscitation after illicit opiate overdose to identify (i) any evidence of harm caused by excessive naloxone dosing ('over-antagonism'); and (ii) implications for the medical administration of naloxone within contemporary emergency settings. DESIGN Re-analysis of a large qualitative data set comprising 70 face-to-face interviews conducted within a few hours of heroin/opioid overdose occurring, observations from hospital settings and a further 130 interviews with illicit opiate users. Data were generated between 1997 and 1999. SETTING Emergency departments, drug services and pharmacies in two Scottish cities. PARTICIPANTS Two hundred illicit opiate users: 131 males and 69 females. FINDINGS Participants had limited knowledge of naloxone and its pharmacology, yet described it routinely in negative terms and were critical of its medical administration. In particular, they complained that naloxone induced acute withdrawal symptoms, causing patients to refuse treatment, become aggressive, discharge themselves from hospital and take additional street drugs to counter the naloxone effects. Participants believed that hospital staff should administer naloxone selectively and cautiously, and prescribe counter-naloxone medication if dosing precipitated withdrawals. In contrast, observational data indicated that participants did not always know that they had received naloxone and hospital doctors did not necessarily administer it incautiously. CONCLUSIONS Opiate users in urban Scotland repeatedly report harm caused by naloxone over-antagonism, although this is not evident in observational data. The concept of contemporary legend (a form of folklore that can be based on fact and provides a means of communicating and negotiating anxiety) helps to explain why naloxone has such a feared reputation among opiate users.
Extracellular Activation of Unitary Excitatory Synapses Between Hippocampal CA3 and CA1 Pyramidal Cells

The possibility of regular activation of unitary excitatory synapses on hippocampal CA1 cells by electrical stimulation of Schaffer collaterals was explored in the rat. The amplitude of the excitatory postsynaptic currents (EPSCs) and failures in response to a range of stimulation intensities around the threshold for the smallest detectable EPSC were analysed. After an abrupt appearance of EPSCs in response to increasing stimulation strength, both EPSC amplitude and failure rate could reach a plateau where increasing stimulation intensity did not cause additional responses. This was interpreted as a regular activation of mainly a single axon. Statistical methods showed, however, that only 12 out of ∼50 experiments using threshold stimulation were without significant contamination from additional fibres. In this subset of experiments, upper limits for contamination from other fibres were estimated by using bootstrapping methods. More than 90% of the responses were probably due to faithful activation of a single axon, assuming that the density of axons connecting to one target cell is relatively homogeneous. This result makes the described method suitable for examining some aspects of the transmission between individual hippocampal cells.
Cyclodextrin Aldehydes are Oxidase Mimics

Cyclodextrins containing 6‐aldehyde groups were found to catalyse oxidation of aminophenols in the presence of hydrogen peroxide. The catalysis followed Michaelis–Menten kinetics and is related to the catalysis previously observed with cyclodextrin ketones. A range of different cyclodextrin aldehydes were prepared containing one, two or more aldehydes at the primary rim (6‐positions) or a ethoxy‐2‐al or propoxy‐3‐al at the secondary rim. 2‐O‐ethoxy‐2‐al‐β‐cyclodextrin (22) was found to be the best catalyst. The aldehydes are in many cases better catalysts than the ketones, because of their powerful covalent binding of hydrogen peroxide.
Global assays of hemostasis

Purpose of reviewThere exists an imbalance between our understanding of the physiology of the blood coagulation process and the translation of this understanding into useful assays for clinical application. As technology advances, the capabilities for merging the two areas have become more attainable. Global assays have advanced our understanding of the dynamics of the blood coagulation process beyond end point assays and are at the forefront of implementation in the clinic. Recent findingsWe will review recent advances in the main global assays with a focus on thrombin generation that have potential for clinical utility. These assays include direct (thrombogram, whole blood, purified systems) and indirect empirical measures of thrombin generation (thromboelastography) and mechanism-based computational models that use plasma composition data from individuals to generate thrombin generation profiles. SummaryEmpirical thrombin generation assays (direct and indirect) and computational modeling of thrombin generation have greatly advanced our understanding of the hemostatic balance. Implementation of these types of assays and visualization approaches in the clinic will potentially provide a basis for the development of individualized patient care. Advances in both empirical and computational global assays have made the goal of predicting precrisis changes in an individual's hemostatic state one step closer.
Lower extremity static and dynamic relationships with rearfoot motion in gait.

Twenty nonsymptomatic subjects were assessed while walking at a photoelectronically monitored place (2 +/- 0.1 m.s-1) using high speed cinematography (200 Hz) to record the rearfoot motion in the frontal plane, and electrogoniometry (100 Hz) to measure joint kinematics in the lower extremity. The foot type of the subjects was determined statically by using a podiascope and digitization techniques. The results demonstrated that no foot type variables contributed significantly to the variance in either rearfoot angle at foot strike or maximum rearfoot angle (p > 0.05). Regression equations were developed using kinematic variables: rearfoot angle at foot strike = 3.81 + (0.06*time to hip internal rotation) - (0.46*tibia internal rotation) + (0.14*plantarflexion); (R = 0.87, SE = 1.23 degrees); maximum rearfoot angle = 4.02 + (0.52*hip internal rotation) - (0.11*time to hip internal rotation); (R = 0.66, SE = 2.07 degrees). This study identifies hip joint movements as being the most significant contributors to prediction of rearfoot angles produced during walking.
Identification of anhydroecgonine methyl ester N-oxide, a new metabolite of anhydroecgonine methyl ester, using electrospray mass spectrometry.

Cocaine is transformed into hepatotoxic metabolites through oxidative pathways. For anhydroecgonine methyl ester (AEME), the main constituent in crack smoke, the oxidative metabolism has not been studied. Therefore, incubation of AEME with rat liver microsomes was performed and a metabolite of AEME, anhydroecgonine methyl ester N-oxide (AEMENO), was identified. The chemical structure of this new metabolite was confirmed by synthesis and by comparative interpretation of electrospray multiple-stage mass spectra, which were obtained in the positive ion mode. This metabolite was also detected in whole blood, serum and urine samples from crack users. The application of liquid chromatography/electrospray mass spectrometry or nanoelectrospray mass spectrometry was necessary because AEMENO is susceptible to thermal degradation during gas chromatographic/mass spectrometric analysis. This study demonstrated that AEMENO is produced by rat hepatic microsomal metabolism in vitro and is present in body fluids from crack users.