Miracle-dz/UniFAR-FTUs huggingface dataset:
Dose Escalation Study of No-Carrier-Added 131I-Metaiodobenzylguanidine for Relapsed or Refractory Neuroblastoma: New Approaches to Neuroblastoma Therapy Consortium Trial

131I-metaiodobenzylguanidine (MIBG) is specifically taken up in neuroblastoma, with a response rate of 20%–37% in relapsed disease. Nonradioactive carrier MIBG molecules inhibit uptake of 131I-MIBG, theoretically resulting in less tumor radiation and increased risk of cardiovascular toxicity. Our aim was to establish the maximum tolerated dose of no-carrier-added (NCA) 131I-MIBG, with secondary aims of assessing tumor and organ dosimetry and overall response. Methods: Eligible patients were 1–30 y old with resistant neuroblastoma, 131I-MIBG uptake, and cryopreserved hematopoietic stem cells. A diagnostic dose of NCA 131I-MIBG was followed by 3 dosimetry scans to assess radiation dose to critical organs and soft-tissue tumors. The treatment dose of NCA 131I-MIBG (specific activity, 165 MBq/μg) was adjusted as necessary on the basis of critical organ tolerance limits. Autologous hematopoietic stem cells were infused 14 d after therapy to abrogate prolonged myelosuppression. Response and toxicity were evaluated on day 60. The NCA 131I-MIBG was escalated from 444 to 777 MBq/kg (12–21 mCi/kg) using a 3 + 3 design. Dose-limiting toxicity (DLT) was failure to reconstitute neutrophils to greater than 500/μL within 28 d or platelets to greater than 20,000/μL within 56 d, or grade 3 or 4 nonhematologic toxicity by Common Terminology Criteria for Adverse Events (version 3.0) except for predefined exclusions. Results: Three patients each were evaluable at 444, 555, and 666 MBq/kg without DLT. The dose of 777 MBq/kg dose was not feasible because of organ dosimetry limits; however, 3 assigned patients were evaluable for a received dose of 666 MBq/kg, providing a total of 6 patients evaluable for toxicity at 666 MBq/kg without DLT. Mean whole-body radiation was 0.23 mGy/MBq, and mean organ doses were 0.92, 0.82, and 1.2 mGy/MBq of MIBG for the liver, lung, and kidney, respectively. Eight patients had 13 soft-tissue lesions with tumor-absorbed doses of 26–378 Gy. Four of 15 patients had a complete (n = 1) or partial (n = 3) response, 1 had a mixed response, 4 had stable disease, and 6 had progressive disease. Conclusion: NCA 131I-MIBG with autologous peripheral blood stem cell transplantation is feasible at 666 MBq/kg without significant nonhematologic toxicity and with promising activity.
Alternatives to the use of unequal voting rights : a propos the potential threat to their effectiveness as a takeover defense

Background: The origin of this study was the negotiations around a EU takeover directive, aimed at making the market for corporate control more open. One of the proposals was to neutralise shares carrying multiple rights in takeover situations when a potential acquirer obtains 75% of the total share capital. For many Swedish ownership groups, this would mean that the system of unequal voting rights, constituting an important defense to their control, would decrease in effectiveness. In the middle of writing this thesis, an EU agreement was finally reached, making the proposal voluntary to adopt. The imminent threat posed to the Swedish system faded, but has though not disappeared since the present rules anew will be brought under inspection in five years. Purpose: To give examples on potential tactics to adopt if unequal voting rights would risk to become neutralised in takeover situations, these tactics dependent on two different scenarios: (1) Present Swedish ownership structure is considered advantageous for the country and thus to be remained or (2) A more open market for takeovers is desired. Course of action: Interviews have been conducted with parties within Swedish trade and industry, partly in order to assess the value and necessity of the content of this thesis. Conclusion: The threat of an abolition of the unequal voting rights is not perceived as imminent by parties within Swedish trade and industry and few alternative resistance strategies are suggested. If current Swedish ownership structure is to be remained, the author proposes competition-reducing defenses, if a more open market for takeovers is aimed for, auction-inducing resistance strategies. The choice of how to proceed should depend on how afraid the Swedish Government and Swedish companies are of a change in present ownership structure.
Congenital Cyclic Neutropenia

tor (GM-CSF) and interleukin-1 (IL-3) . 7 These observations suggest that the G-CSF-responsive myeloid progenitors are defective in patients with cyclic neutropenia. In one study, the G-CSF receptors on the patients’ neutrophils were found to be normal with regard to both number and affinity.8 Oscillations of serum levels of cytokines were observed in a pregnant woman with congenital cyclic neutropenia.9 The G-CSF peaked at the nadir of neutropenia, while the tumor necrosis factor-a (TNF-a) and interleukin-6 fluctuated in-
Does Hedging Increase Firm Value? Comparing Premia for Hedging 'Big' Versus 'Small' Risks

I test whether hedging increases firm value by examining whether the premium for hedging a 'big' risk is larger than for a 'small' risk. I use a sample of firms in the oil and gas exploration and production (E\&P) business for the analysis and exploit the variation in exposure to hydrocarbon price volatility because of the firm's business activities to classify this risk as a big or small risk for each firm. Applying the methodology used in the existing literature to estimate the hedging premium, I find that hedging a 'big' risk is associated with lower firm value whereas hedging a 'small' risk is associated with higher firm value. Further, I find that hedging a 'big' ('small') risk is a proxy for bad (good) management or high (low) agency costs, and the apparent valuation effects of hedging are diminished after controlling for these factors. These results question whether hedging has a measurable impact on firm value.
4-Hydroxynonenal induces mitochondrial-mediated apoptosis and oxidative stress in SH-SY5Y human neuronal cells.

Excessive and sustained increases in oxidative stress and apoptosis have been implicated in the pathogenesis of many diseases. In this study, we demonstrated that 4-hydroxynonenal (4-HNE), a product of lipid peroxidation in a range of concentration (0.1-50 μM) showed cytotoxic effects on SH-SY5Y cell culture at a concentration >5 μM at 4 hr of exposure. 4-HNE dose dependently decreased cell viability and significantly promoted reactive oxygen species formation and enhanced oxidative stress as reflected in the increased level of lipid peroxidation and catalase activity and decreased glutathione peroxidase activity as well as glutathione levels. 4-HNE-induced oxidative stress was associated with increased transcriptional and translational expressions of Bax and p53 in SH-SY5Y cells. Mitochondrial-mediated apoptosis was confirmed by increased expression and activity of caspase-3. Our data demonstrate that 4-HNE induces neuronal cell death through abnormal expression of apoptotic markers (p53, Bax and caspase-3). Oxidative stress may be involved in the initial priming of SH-SY5Y cells to 4-HNE-induced cytotoxicity in vitro.
Effect of exercise on the proportion of unsaturated fatty acids in serum of untrained middle aged individuals.

OBJECTIVES: To examine whether prolonged moderate exercising by untrained middle aged individuals of both sexes affects the plasma ratio of unsaturated to saturated (U/S) fatty acids in the non-esterified fatty acid (NEFA) and triacylglycerol (TG) fractions. METHODS: Twenty two healthy untrained volunteers (eleven men and eleven pre-menopausal women), aged 35-55, exercised on bicycles at 50-55% maximal heart rate reserve (estimated 61% maximal oxygen uptake) for one hour. Pre- and post-exercise blood samples were analysed for lactate, glucose, glycerol, individual NEFAs and TG acyl groups, cholesterol, high density lipoprotein cholesterol, urea, cortisol, and testosterone. Biopsy specimens of adipose tissue were analysed for TG acyl group composition. RESULTS: Serum total NEFAs increased significantly whereas total TG decreased significantly in both sexes. Changes in individual fatty acids, in both the NEFA and TG fractions, generally paralleled changes in the total pool but were not proportionate. As a result, U/S NEFAs increased in both sexes, although significantly only in women. The shift was in the direction of the composition of the major source of blood NEFAs--that is, adipose tissue TG. U/S acyl groups of TG also increased in both sexes, although significantly only in men. CONCLUSIONS: Prolonged moderate exercise increases the U/S ratio of serum NEFAs and TG. This may add to the beneficial effects of exercise given the protective role of unsaturated fatty acids against coronary heart disease.
Large‐scale dynamics of the mesosphere and lower thermosphere: An analysis using the extended Canadian Middle Atmosphere Model

The extended Canadian Middle Atmosphere Model is used to investigate the large-scale dynamics of the mesosphere and lower thermosphere (MLT). It is shown that the 4-day wave is substantially amplified in southern polar winter in the presence of instabilities arising from strong vertical shears in the MLT zonal mean zonal winds brought about by parameterized nonorographic gravity wave drag. A weaker 4-day wave in northern polar winter is attributed to the weaker wind shears that result from weaker parameterized wave drag. The 2-day wave also exhibits a strong dependence on zonal wind shears, in agreement with previous modeling studies. In the equatorial upper mesosphere, the migrating diurnal tide provides most of the resolved westward wave forcing, which varies semiannually in conjunction with the tide itself; resolved forcing by eastward traveling disturbances is dominated by smaller scales. Nonmigrating tides and other planetary-scale waves play only a minor role in the zonal mean zonal momentum budget in the tropics at these heights. Resolved waves are shown to play a significant role in the zonal mean meridional momentum budget in the MLT, impacting significantly on gradient wind balance. Balance fails at low latitudes as a result of a strong Reynolds stress associated with the migrating diurnal tide, an effect which is most pronounced at equinox when the tide is strongest. Resolved and parameterized waves account for most of the imbalance at higher latitudes in summer. This results in the gradient wind underestimating the actual eastward wind reversal by up to 40%.
Prescribing practices in a population-based HIV postexposure prophylaxis program

Objectives To characterize factors associated with being prescribed triple or double postexposure prophylaxis (PEP) against HIV in a population-based program. Methods Individuals potentially exposed to HIV received a 5 day starter kit of either double or triple antiretroviral PEP between April 1999 and November 2000 and did/did not receive the remaining 23 days PEP. Data were collected through dispensation of kits. Logistic regression identified characteristics independently associated with being prescribed triple therapy starter kits and with any 23 day follow-up. Results Of 2064 people receiving 5 day PEP [403 (20%) triple and 1661 (80%) double], 590 (29%) received 23 day follow-up. Independently associated with being prescribed triple therapy starter kits were being male [adjusted odds ratio (AOR) 1.38; 95% confidence interval (CI) 1.10–1.74;P = 0.006), occupational mucocutaneous injuries (AOR 1.70; 95% CI, 1.14–2.55;P = 0.010), and community needlesticks (AOR 2.04; 95% CI, 1.54–2.69;P < 0.001). Independently associated with being prescribed the 23 day follow-up were being male (AOR 1.24; 95% CI, 1.00–1.53;P = 0.04), community mucocutaneous incidents (AOR 2.83; 95% CI, 1.41–5.70;P = 0.004), community needlesticks (AOR 1.75; 95% CI, 1.33–2.29;P < 0.001), and having received triple therapy as the starter kit (AOR 2.61; 95% CI, 2.07–3.29;P < 0.001). Conclusions Being prescribed triple therapy starter PEP was associated with being male and with experiencing an occupational mucocutaneous or community needlestick injury. Receiving the remaining 23 days PEP was associated with being male, experiencing a community mucocutaneous or needlestick injury, and triple therapy as the initial 5 day starter PEP.
Systematic Approach to Optimization of Submicron Particle Agglomeration Using Ionic-Wind-Assisted Pre-Charger

ABSTRACTElectric agglomeration is the process in which particles are charged in electric fields and coagulate, which is enhanced by electric force or turbulence. The collection efficiency of submicron particles is improved, which can be a solution to submicron particle abatement in traditional electrostatic precipitators (ESPs), by using a pre-charger to increase median particle diameter and realizing particle pre-charging. In this study, a laboratory bipolar pre-charger with a perforated plate between discharging regions was designed to examine ionic-wind-assisted charge-induced agglomeration, and an ESP was arranged afterwards to collect the fine particles. Experiments were conducted to investigate submicron particle charging, agglomeration characteristics, and collection efficiency. Results indicated that a pre-charger with proper discharging voltage match and plate porosity can optimize particle agglomeration and improve collection efficiency by about 12% compared with the results obtained without a pre-charger. An optimal solution was achieved and a collecting efficiency of 96%–98% was obtained for all sizes by utilizing the turbulence caused by ionic wind and optimizing the experimental operation conditions.
Homeobox gene mutations and brain-stem developmental disorders: learning from knockout mice

Analysis of mice that carry targeted inactivations of Hox, Nkx and Phox2 homeobox genes revealed their involvement in regional patterning of brain-stem territories, in specification of neuronal identity, in establishment of appropriate patterns of connectivity and in control of neurotransmission. The specific abnormalities generated by such mutations may provide clues to the genetic basis and cellular mechanisms that are involved in human brain-stem developmental disorders.
A new hydrogen peroxide--based medical-device detergent with germicidal properties: comparison with enzymatic cleaners.

BACKGROUND The objective of this study was to evaluate the efficacy of the cleaning and bacterial killing ability of a new non-enzyme-based formulation (killing detergent solution [KDS]) compared with commercially available enzymatic detergents that included Metrizyme (Metrex Research Division of Sybron Canada Ltd. Morrisburg, Ontario) and Gzyme (Germiphene Corp, Brantford, Ontario). KDS is a hydrogen peroxide-based detergent formulation that combines cleaning efficacy with the ability to kill microorganisms. The KDS formulation helps ensure the protection of the health care worker from infectious risk during the soaking and cleaning stages of medical device reprocessing and reduces the bioburden on devices before sterilization/disinfection. METHODS Test organisms that included Enterococcus faecalis, Salmonella choleraesuis, Staphylococcus aureus, and Pseudomonas aeruginosa were suspended in artificial test soil (ATS-B; patent submitted), inoculated at 10(6) colonyforming units per carrier and dried overnight before detergent exposure. The ATS-B mimics the blood, protein, carbohydrate, and endotoxin levels of patient-used medical devices. Plastic lumen carriers and a flexible colonoscope were used for surface and simulated-use testing, respectively. RESULTS The results for the microbial challenge dried onto polyvinyl chloride (PVC) carriers demonstrated that the ability of KDS to remove protein, blood, carbohydrate, and endotoxin from surface test carriers was as effective as the enzyme detergents that were evaluated. Furthermore, KDS was able to effect approximately a 5-Log(10) reduction in microbial loads with a 3-minute exposure at room temperature, whereas none of the other detergents were as effective. In simulated-use testing of a soiled colonoscope, KDS was significantly better at ensuring microbial killing compared with Gzyme and Metrizyme and was equivalent to the enzymatic detergents in cleaning ability. CONCLUSIONS In summary the KDS has excellent microbial-killing ability in 3-minute exposures at room temperature and cleans as well as the existing enzymatic detergent formulations that were tested.
Mitogenome evolution in the last surviving woolly mammoth population reveals neutral and functional consequences of small population size

The onset of the Holocene was associated with a global temperature increase, which led to a rise in sea levels and isolation of the last surviving population of woolly mammoths on Wrangel Island. Understanding what happened with the population's genetic diversity at the time of the isolation and during the ensuing 6000 years can help clarify the effects of bottlenecks and subsequent limited population sizes in species approaching extinction. Previous genetic studies have highlighted questions about how the Holocene Wrangel population was established and how the isolation event affected genetic diversity. Here, we generated high‐quality mitogenomes from 21 radiocarbon‐dated woolly mammoths to compare the ancestral large and genetically diverse Late Pleistocene Siberian population and the small Holocene Wrangel population. Our results indicate that mitogenome diversity was reduced to one single haplotype at the time of the isolation, and thus that the Holocene Wrangel Island population was established by a single maternal lineage. Moreover, we show that the ensuing small effective population size coincided with fixation of a nonsynonymous mutation, and a comparative analysis of mutation rates suggests that the evolutionary rate was accelerated in the Holocene population. These results suggest that isolation on Wrangel Island led to an increase in the frequency of deleterious genetic variation, and thus are consistent with the hypothesis that strong genetic drift in small populations leads to purifying selection being less effective in removing deleterious mutations.
Lesion location matters: The relationships between white matter hyperintensities on cognition in the healthy elderly

White matter hyperintensities (WMH) are associated with cognitive decline. We aimed to identify the spatial specificity of WMH impact on cognition in non-demented, healthy elderly. We quantified WMH volume among healthy participants of a community dwelling cohort (n = 702, age range 60 – 82 years, mean age = 69.5 years, 46% female) and investigated the effects of WMH on cognition and behavior, specifically for executive function, memory, and motor speed performance. Lesion location influenced their effect on cognition and behavior: Frontal WMH in the proximity of the frontal ventricles mainly affected executive function and parieto-temporal WMH in the proximity of the posterior horns deteriorated memory, while WMH in the upper deep white matter—including the corticospinal tract—compromised motor speed performance. This study exposes the subtle and subclinical yet detrimental effects of WMH on cognition in healthy elderly, and strongly suggests a causal influence of WMH on cognition by demonstrating the spatial specificity of these effects.
Gating and conduction of nano-channel forming proteins: a computational approach

Monitoring conformational changes in ion channels is essential to understand their gating mechanism. Here, we explore the structural dynamics of four outer membrane proteins with different structures and functions in the slowest nonzero modes of vibration. Normal mode analysis was performed on the modified elastic network model of channel in the membrane. According to our results, when membrane proteins were analyzed in the dominant mode, the composed pores, TolC and α-hemolysin showed large motions at the intramembrane β-barrel region while, in other porins, OmpA and OmpF, largest motions observed in the region of external flexible loops. A criterion based on equipartition theorem was used to measure the possible amplitude of vibration in channel forming proteins. The current approach complements theoretical and experimental techniques including HOLE, Molecular Dynamics (MD), and voltage clamp used to address the channel’s structure and dynamics and provides the means to conduct a theoretical simultaneous study of the structure and function of the channel. An animated interactive 3D complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:3
A methodology for company valuation

xv Chapter 1 The Valuation Framework.1 1.1 Basic Idea . 2 1.2 Replication of Contingent Claims.3 1.3 Dynamic Programming.14 1.4 Real Option Valuation.23 Chapter 2 The Company Valuation Algorithm . 31 2.1 The Basic Algorithm.31 2.1.1 Derivation of the Algorithm.32 2.1.2 First Example of the Basic Company Valuation Algorithm.36 2.1.3 Comparison to Other Approaches.43 2.2 The Real Option Extension.47 2.2.1 Derivation of the Real Option Company Valuation Algorithm.51 2.2.2 1. Example of the Real Option Company Valuation Algorithm . 54 2.3 Extension to Multiple Time Steps.62 2.3. 1 2. Example of the Real Option Company Valuation Algorithm . 62
Perception of Verticality in Patients with Primary Headache Disorders

OBJECTIVE: Migraine is associated with several vestibular syndromes, and vestibular syndromes can cause tilt of the subjective visual vertical (SVV). MATERIALS and METHODS: Caloric tests, cervical vestibular evoked myogenic potentials (cVEMPs), and SVV deviations were studied in a group, including 20 patients with migraine without aura (MoA), 24 patients with vestibular migraine (VM), 20 patients with tension-type headache (TTH), and 30 healthy controls. SVV deviations were measured using a translucent bucket. The procedure was repeated 10 times, and the mean SVV deviation was calculated for each subject. RESULTS: Apart from 5 patients with VM, the caloric test results were normal. cVEMP latencies, amplitudes, and SVV deviation values measured from the patient groups were not statistically different from the healthy controls. Despite not having differences in the average SVV deviation compared to controls, patients with migraine, either associated with vertigo or not, had significantly larger variability in their SVV measurements when all 10 test trials were taken into consideration. CONCLUSION: The larger variability of SVV measurements in our patients with migraine has also been reported in a previous study. It is difficult to inter pret this finding as evidence of vestibular dysfunction involving the otolithic pathways. Cognitive processes affecting the awareness of body orientation seem to be a more reasonable explanation. On the other hand, the bucket method is an easily performed, reliable bedside test to study SVV.
Mapping of brain tumor metabolites with proton MR spectroscopic imaging: clinical relevance.

Brain tumor metabolism was studied with hydrogen-1 magnetic resonance spectroscopy and positron emission tomography with fluorine-18 fluorodeoxyglucose in 50 patients. N-acetylaspartate (NAA) was generally decreased in tumors and radiation necrosis but was somewhat preserved at neoplasm margins. Choline was increased in most solid tumors. Solid high-grade gliomas had higher normalized choline values than did solid low-grade gliomas (P < .02), but the normalized choline value was not a discriminator of tumor grade, since necrotic high-grade lesions had reduced choline values. Serial studies in one case showed an increase in choline as the glioma underwent malignant degeneration. Choline values were lower in chronic radiation necrosis than in solid anaplastic tumors (P < .001). In two cases studied before and after treatment, clinical improvement and a reduction in choline followed therapy. Lactate is more likely to be found in high-grade gliomas, but its presence is not a reliable indicator of malignancy.