Miracle-dz/UniFAR-FTUs huggingface dataset:
Computational model predicts effective delivery of 188-Re-labeled melanin-binding antibody to metastatic melanoma tumors with wide range of melanin concentrations

Metastatic melanoma is almost always deadly and new methods of treatment are urgently needed. Recently, we established the feasibility of radioimmunotherapy (RIT) for experimental melanoma in mice using a 188-rhenium (188Re)-labeled monoclonal antibody (mAb) 6D2 (IgM) to melanin. Our objective was to determine the effects of varying tumor melanin concentration and of different diffusivities and lymphatic clearance rates of the normal tissue, on the absorbed dose to the tumor in simulated therapy, in preparation for a clinical trial of RIT for melanoma. Using finite element analysis (FEA), we created a pharmacokinetic model that describes melanin-targeting RIT of a melanoma micrometastasis (1.3-mm radius) imbedded in normal tissue (14.3-mm radius). Our method incorporates antibody plasma kinetics, transcapillary transport, interstitial diffusion, and lymphatic clearance. Michaelis–Menten kinetics was used to model mAb binding to tumor melanin for melanin concentrations of 76, 7.6, 0.76, 0.076, and 0.0076 μmol/l. An absorbed dose was calculated, after accounting for direct and crossfire irradiation, on the basis of a 7.4-GBq intravenous dose of 188Re-6D2. The results showed that penetration of mAb into the tumor was inversely proportional to tumor melanin concentration. Decreased diffusivity and increased lymphatic clearance of the surrounding normal tissue decreased the dose to the tumor. The formation of mAb–melanin complex was remarkably similar within a 1000-fold range of melanin concentration, resulting in total doses of 2840, 2820, 2710, and 1990 cGy being delivered to tumors with melanin concentrations of 76, 7.6, 0.76, and 0.076 μmol/l, respectively. In conclusion, RIT of metastatic melanoma can be effective over a wide range of tumor melanin concentrations. The results can be useful in the design of a clinical trial of melanin-targeting RIT in patients with metastatic melanoma.
Levobupivacaine for labor pain: appear good from Afar, but far too expensive (?)

1. Leeners B, Neumaier-Wagner P, Kuse S, Rath W. Smoking and the risk of developing hypertensive diseases in pregnancy: what is the effect on HELLP syndrome? Acta Obstet Gynecol Scand. 2006;/85:/1217 /24. 2. Conde-Agudelo A, Althabe F, Belizan JM, Kafury-Goeta AC. Cigarette smoking during pregnancy and risk of preeclampsia: a systematic review. Am J Obstet Gynecol. 1999;/181:/1026 /35. 3. Castles A, Adams EK, Melvin CL, Kelsch C, Boulton ML. Effects of smoking during pregnancy. Five meta-analyses. Am J Prev Med. 1999;/16:/208 /15. 4. Lindqvist PG, Marsal K. Moderate smoking during pregnancy is associated with a reduced risk of preeclampsia. Acta Obstet Gynecol Scand. 1999;/78:/693 /7. 5. Bainbridge SA, Sidle EH, Smith GN. Direct placental effects of cigarette smoke protect women from pre-eclampsia: the specific roles of carbon monoxide and antioxidant systems in the placenta. Med Hypoth. 2005;/64:/17 /27. 6. Bainbridge SA, Belkacemi L, Dickinson M, Graham CH, Smith GN. Carbon monoxide inhibits hypoxia/reoxygenationinduced apoptosis and secondary necrosis in syncytiotrophoblast. Am J Pathol. 2006;/169:/774 /83.
Mechanisms of the priming effect of lipopolysaccharides on the biosynthesis of leukotriene B4 in chemotactic peptide‐stimulated human neutrophils

The goal of this study was to explain the priming effect of lipopolysaccharides (LPS) in human polymorphonuclear leukocytes on leukotriene B4 (LTB4) biosynthesis after stimulation with the receptor‐mediated agonist formyl‐methionyl‐leucylphenylalanine (fMLP). This priming effect for LTB4 biosynthesis was maximal after a 30 min preincubation with LPS but was lost when incubations were extended to 90 min or longer. Priming with LPS resulted in an enhanced maximal activation of 5‐lipoxygenase (5‐ to 15‐fold above unprimed cells) as well as a prolonged activation of the enzyme after stimulation with fMLP compared to that measured in unprimed cells. The activation of 5‐lipoxygenase was associated with its translocation to the nuclear fraction of the cell after stimulation of LPS‐primed cells but not of unprimed cells. Priming of cells with LPS also resulted in an enhanced capacity (fivefold increase) for arachidonic acid (AA) release after stimulation with fMLP compared to unprimed cells as measured by mass spectrometry. This release of AA was very efficiently blocked in a dose‐dependent manner by the 85 kDa cytosolic phospholipase A2 (PLA2) inhibitor MAFP (IC50 = 10nM) but not by the 14 kDa secretory PLA2 inhibitor SB 203347 (up to 5 µM), indicating that the 85 kDa cPLA2 is the PLA2 responsible for AA release in response to receptor‐mediated agonists. In accord with inhibitor studies, the LPS‐mediated phosphorylation of cPLA2 followed the same kinetics as the priming for AA release, and a measurable fMLP‐induced translocation of cPLA2 was observed only in primed cells. As with AA release and LTB4 biosynthesis, both the phosphorylation and capacity to translocate cPLA2 were reversed when the preincubation period with LPS was extended to 120 min. These results explain some of the cellular events responsible for the potentiation and subsequent decline of functional responses of human polymorphonuclear leukocytes recruited to inflammatory foci. —Surette, M. E. , Dallaire, N. , Jean, N. , Picard, S. , Borgeat, P. Mechanisms of the priming effect of lipopolysaccharides on the biosynthesis of leukotriene B4 in chemotactic peptide‐stimulated human neutrophils. FASEB J. 12, 1521–1531 (1998)
Depressive symptoms, perceived stress, self-efficacy, and outcome expectations: Predict fitness among adolescents with obesity

The objective of the present study was to test if outcome expectancy mediated the relationship between fitness and self-efficacy, perceived stress, and depressive symptoms.Adolescents with obesity (n = 228) completed measures of perceived stress and depressive symptoms at baseline, self-efficacy and outcome expectancy at baseline and 3 months, and fitness at baseline and 6 months. Structural equation modeling was used to analyze the data. Results showed that self-efficacy was positively associated with fitness via outcome expectancies. For females, fewer depressive symptoms were linked to fitness via self-efficacy and outcome expectancies. Exercise interventions that enhance exercise self-efficacy, outcome expectancy, and reduce depressive symptoms may increase fitness.
PRO-ART: enabling requirements pre-traceability

Requirements traceability is essential for developing software systems of high quality. Whereas the traceability of the refinement, deployment, and use of a requirement is called post-traceability, the traceability of a requirement back to its origin is named pre-traceability. We present a requirements engineering environment, called PRO-ART, which enables requirements pre-traceability, PRO-ART is based on three main contributions: a three-dimensional framework for requirements engineering which defines the kind of information to be recorded; a trace-repository for structuring the trace information and enabling selective trace retrieval; a novel tool interoperability approach which enables (almost) automated trace capture. In addition, we report on experiences made with the first prototypical implementation of PRO-ART and the resulting redesign and re-implementation, called PRO-ART 2.0, which mainly addresses scalability problems faced with in real applications.
Clinically Important Drug Interactions Potentially Involving Mechanism-based Inhibition of Cytochrome P450 3A4 and the Role of Therapeutic Drug Monitoring

Cytochrome P450 (CYP) 3A4 is the most abundant enzyme of CYPs in the liver and gut that metabolizes approximately 50% currently available drugs. A number of important drugs have been identified as substrates, inducers, and/or inhibitors of CYP3A4. The substrates of CYP3A4 considerably overlap with those of P-glycoprotein. Both CYP3A4 and P-glycoprotein are subject to inhibition and induction by a number of factors. Mechanism-based inhibition of CYP3A4 is characterized by NADPH-, time-, and concentration-dependent enzyme inactivation occurring when some xenobiotics or drugs are converted by CYPs to reactive metabolites. Such an inhibition of CYP3A4 is caused by chemical modification of the heme, the protein, or both as a result of covalent binding of modified heme to the protein. To date, the identified clinically important mechanism-based CYP3A4 inhibitors mainly include macrolide antibiotics (eg, clarithromycin and erythromycin), anti-HIV agents (eg, ritonavir and delavirdine), antidepressants (eg, fluoxetine and fluvoxamine), calcium channel blockers (eg, verapamil and diltiazem), steroids and their modulators (eg, gestodene and mifepristone), and several herbal and dietary components. The inactivation of CYP3A4 by drugs often causes unfavorable and long-lasting drug-drug interactions and probably fatal toxicity, depending on many factors associated with the enzyme, drugs, and the patients. Clinicians are encouraged to have a sound knowledge of drug-induced, mechanism-based CYP3A4 inhibition; take proper cautions, and perform close monitoring for possible drug interactions when using drugs that are mechanism-based CYP3A4 inhibitors. To minimize drug-drug interactions involving mechanism-based CYP3A4 inhibition, it is necessary to choose safe drug combination regimens, adjust drug dosages appropriately, and conduct therapeutic drug monitoring for drugs with narrow therapeutic indices.
Secure Multiuser MIMO Downlink Transmission Via Precoding-Aided Spatial Modulation

This letter generalizes the precoding-aided spatial modulation (PSM) to a multiuser (MU) downlink scenario. With precoding vectors elaborately designed, a proposed MU-PSM scheme has the capability to resist a multiple antenna eavesdropper. Specifically, signal precoding matrices (SPMs) are designed to cancel the MU interference and modulate partial information bits on the indices of receive antennas. To improve physical layer security, scrambling on SPMs is conceived to construct a fast-varying precoding matrix, which contributes to the degradation at Eve's blind estimation and detection. Moreover, issues of detection algorithms and a lower bound of secrecy rate are addressed to verify security enhancement in the proposed scheme.
Millimeter-wave phase-coded CW MIMO radar using zero-correlation-zone sequence sets

We present a phase-coded continuous-wave (CW) multiple-input multiple-output (MIMO) radar approach based on code-division multiplexing. We use zero-correlation-zone (ZCZ) sequence sets to separate at the receivers signals from multiple transmitters. In particular, our approach uses equidistantly shifted almost-perfect autocorrelation sequences for efficient implementation. We carried out measurements using a software-defined radar platform with 16 MIMO channels to demonstrate the capability of the proposed approach.
Assessment of physical demands and comparison of multiple exposure definitions in a repetitive sawmill job: board edger operator

The primary objectives of the study were to 1) describe the physical exposures in a sawmill job with a high incidence of upper extremity musculoskeletal injuries in terms of multiple measures of posture, exertion and frequency (with varying definitions) and 2) to examine the comparability of those definitions. Surface electromyography and electrogoniometry were used to quantify the muscle demands and joint motions. Fourteen board edger operators from two sawmill facilities participated. All exposure assessments, with the exception of surface EMG measurements, were performed on the production lines. EMG measurements were performed within the facility in a location removed from the production line. The measurements showed that, on average, ranges of motions of 59, 102 and 84 degrees respectively in the planes of wrist radial/ulnar deviation, flexion/extension and pronation/supination were required to perform the job. Significant differences (p < .001) were observed between ranges of motion defined by peak postures and those due to peak postures required to perform the primary task only. Performance of the primary task required an average of 32% of maximum voluntary contraction from the forearm muscles assessed. Repetitions per day ranged, on average, from 2,015 to 9,365. Incidence of reported upper extremity musculoskeletal injuries in the two facilities assessed was found to be higher with the greater total exposure. However, examination of the trend with a standardized measure of injury incidence was not possible.
EFFECTS OF ACIDOSIS OR ALKALOSIS ON THE ACTIONS OF NIFEDIPINE ON EXCITATION‐CONTRACTION COUPLING IN THE RAT TAIL ARTERY

1. The clinical success of calcium channel blockers in the management of organ ischaemia is less than theoretically anticipated. Blood gas/pH changes are associated with organ ischaemia; therefore, we studied the possibility that pH changes could alter the pharmacological effects of the calcium channel blocker nifedipine on rat tail artery contracted by either noradrenaline (NA) or potassium.
Corona ions from powerlines and increased exposure to pollutant aerosols.

PURPOSE To investigate corona ions emitted from high-voltage powerlines and assess their effects on exposure to environmental pollutant aerosols. MATERIALS AND METHODS The charge density of ions in air required to produce a given change in the observed DC field at ground level was calculated. A DC field mill meter was used to map the DC fields near 132, 275 and 400 kV powerlines. RESULTS The Earth's natural DC field of around approximately 100 Vm(-1) was significantly modified near powerlines in 8 out of 14 cases. Typically, downwind of the powerlines the field direction was reversed giving values to -340 V m(-1). In one case, the effect extended more than 500 m from a 275 kV line. DISCUSSION These results can be analysed in terms of the charge density present. This analysis suggests that typically 2000 excess negative charges per cm3 are required to match the measured DC fields. Such space charge will result in unipolar aerosol charging in excess of the normal bipolar steady state charge distribution of pollutant aerosols. This may lead to increased lung deposition on inhalation.
General Formulation for Modeling Bandpass Filters with Finite Quality Factors and Resistive Couplings

Insertion loss can considerably affect the shape of bandpass filters. This effect can be broken down into two different aspects: the finite quality factor of each cavity and the resistive coupling between resonators. This paper presents a general model that can be used to predict the behavior of bandpass filters presenting insertion losses. A technique to extract the required values is also presented for two coupled resonators and the source/load coupling. Finally an inductive post rectangular waveguide bandpass filter is modeled with the proposed technique. The results agree with the full wave simulation obtained from a commercial package.
Synaptic 5′-Nucleotidase Activity Reflects Lesion-Induced Sprouting within the Adult Rat Dentate Gyrus

In development, the ectoenzyme 5'-nucleotidase marks maturing cerebellar and cortical synapses, but it is localized in glial cells in the normal, adult nervous system. With a histochemical lead technique, we have now investigated its localization during reactive synaptogenesis in the dentate gyrus of adult rats deprived of entorhinal afferents. A band of enhanced 5'-nucleotidase reaction product was present in the outer portions of the dentate molecular layer between 5 and 75 days after destruction of the ipsilateral entorhinal cortex. At the ultrastructural level, 5'-nucleotidase-positive microglia and degenerating axon terminals were numerous within this band during the first postoperative week. Between Days 7 and 75, intact synapses were found that exhibited 5'-nucleotidase reaction product in their clefts. Astrocytic labeling was abundant. No enzyme-positive synapses and few labeled glial elements were present in the control molecular layer. Conspicuous 5'-nucleotidase activity within synaptic clefts of mossy fiber terminals was present between Postoperative Days 10 and 40 on the operated side, but the staining was sporadic on the control side. We conclude that 5'-nucleotidase is associated with lesion-induced synaptic remodeling in the dentate gyrus. The band of 5'-nucleotidase reaction product within the outer molecular layer corresponds to the zone where the lesioned entorhinal fibers degenerate and where other afferents sprout. Here, the transient appearance of 5'-nucleotidase within synaptic clefts parallels the time course of synaptic reinnervation. The enzyme is also indicative of the sprouting response of mossy fiber terminals. Functional properties of 5'-nucleotidase in purinergic neuromodulation and cellular adhesion may be relevant for the generation and plasticity of synaptic contacts.
Flexible Piezoelectric Energy Harvesting Circuit With Printable Supercapacitor and Diodes

We report a flexible energy harvesting circuit fabricated by roll-to-roll compatible, solution-processable methods. The circuit incorporates a supercapacitor fabricated from a viscous carbon nanotube dispersion, printed Schottky diodes, and a piezoelectric element. Used low-temperature materials enabled component integration on poly(ethylene terephthalate) substrate. The supercapacitor was built with a paper separator and an aqueous NaCl electrolyte. Together with carbon-based electrodes, these materials translated into a disposable and environmentally safe electronic device. The energy harvested from mechanical movement was used to drive a commercial electrochromic display.
Effects of site-specific acetylation on omega-conotoxin GVIA binding and function.

Chemical modification of omega-conotoxin GVIA (omega-CgTXGVIA) was performed using nonsaturating concentrations of acetic anhydride to generate seven distinct derivatives. Following separation of these peptides using reverse-phase HPLC (RP-HPLC), their individual molecular weights were determined using fast bombardment mass spectrometry (FAB-MS). Three peptides contained a single acetylated amino group, three possessed two acetylated amino groups, and the last contained three acetylations. For each peptide, the specific site of acetylation was confirmed using a scheme of tryptic digestion, under nonreducing conditions, followed by RP-HPLC and FAB-MS. Biological profiles for each peptide were obtained by analyzing their capacity to displace native 125I-omega-CgTx GVIA binding to rat hippocampal membranes and to block K(+)-stimulated 45Ca2+ influx into chick brain synaptosomes. The data indicate that successive additions of acetyl moieties to omega-CgTx GVIA lead to a loss of both binding affinity and Ca2+ influx inhibitory potency. Within the monoacetylated series, acetylation of the amino terminal of Cys-1, as compared to the epsilon-amino group of either Lys-2 or Lys-24, leads to the greatest shift in potency. In summary, these results indicate that basic (i.e., primary amino) groups, which are brought into close proximity as a result of disulfide bridging, are important in the functional blockade of neuronal Ca2+ channels by omega-CgTx GVIA.
Third sector primary health care in New Zealand.

AIMS To describe key organisational characteristics of selected third sector (non-profit and non-government) primary health care organisations. METHODS Data were collected, in 1997 and 1998, from 15 third sector primary care organisations that were members of a network of third sector primary care providers, Health Care Aotearoa (HCA). Data were collected by face-to-face interviews of managers and key informants using a semi-structured interview schedule, and from practice computer information systems. RESULTS Overall the populations served were young: only 4% of patients were aged 65 years or older, and the ethnicity profile was highly atypical, with 21.8% European, 36% Maori, 22.7% Pacific Island, 12% other, and 7.5% not stated. Community services card holding rates were higher than recorded in other studies, and registered patients tended to live in highly deprived areas. HCA organisations had high patient to doctor ratios, in general over 2000:1, and there were significant differences in management structures between HCA practices and more traditional general practice. CONCLUSIONS Third sector organisations provide services for populations that are disadvantaged in many respects. It is likely that New Zealand will continue to develop a diverse range of primary care organisational arrangements. Effort is now required to measure quality and effectiveness of services provided by different primary care organisations serving comparable populations.
Contrast Enhancement and Histopathological Findings in Vestibular Schwannoma

Changes of contrast uptake are considered to indicate the efficacy of therapy in irradiated vestibular schwannomas. We present a case of a large vestibular schwannoma with heterogeneous contrast uptake on MRI. Using neuronavigation, histological samples were obtained during surgery from an area with homogeneous contrast uptake and from a central tumor portion without contrast enhancement on MRI. Intraoperative investigation found no evidence of necrotic tumor, and histopathological examination revealed an active tumor in both sections, with no central necrosis. This finding illustrates the surgical experience that " necrotic tumor areas " on MRI may not be consistent with intraoperative findings. Lack of contrast uptake in previously irradiated schwannomas may not be indicative of effective radiotherapy.
Bayesian Model Choice in Cumulative Link Ordinal Regression Models

The use of the proportional odds (PO) model for ordinal regression is ubiquitous in the literature. If the assumption of parallel lines does not hold for the data, then an alternative is to specify a non-proportional odds (NPO) model, where the regression parameters are allowed to vary depending on the level of the response. However, it is often difficult to fit these models, and challenges regarding model choice and fitting are further compounded if there are a large number of explanatory variables. We make two contributions towards tackling these issues: firstly, we develop a Bayesian method for fitting these models, that ensures the stochastic ordering conditions hold for an arbitrary finite range of the explanatory variables, allowing NPO models to be fitted to any observed data set. Secondly, we use reversible-jump Markov chain Monte Carlo to allow the model to choose between PO and NPO structures for each explanatory variable, and show how variable selection can be incorporated. These methods can be adapted for any monotonic increasing link functions. We illustrate the utility of these approaches on novel data from a longitudinal study of individual-level risk factors affecting body condition score in a dog population in Zenzele, South Africa.