Relative Peak Height Research Articles

Comparative analysis of thrombin generation platforms for patients with coagulation factor deficiencies: A comprehensive assessment

IntroductionThrombin generation assays (TGAs) assess the overall functionality of the hemostatic system and thereby provide a reflection of the hemostatic capacity of patients with disorders in this system. Currently, four (semi-)automated TGA platforms are available: the Calibrated Automated Thrombogram, Nijmegen Hemostasis Assay, ST Genesia and Ceveron s100. In this study, we compared their performance for detecting patients with congenital single coagulation factor deficiencies. Materials and methodsPooled patient samples, healthy control samples and normal pooled plasma were tested on all four platforms, using the available reagents that vary in tissue factor and phospholipid concentrations. The TGA parameters selected for analysis were peak height and thrombin potential. Results were normalized by using the calculated mean of healthy controls and a correction for between-run variation. Outcomes were presented as relative values, with the mean of healthy controls standardized to 100 %. ResultsAcross all platforms and reagents used, thrombin potentials and peak heights of samples with coagulation factor deficiencies were lower than those of healthy controls. Reagents designed for bleeding tendencies yielded the lowest values on all platforms (relative median peak height 19–32 %, relative median thrombin potential 19–45 %). Samples representing more severe coagulation factor deficiencies generally exhibited lower relative peak heights and thrombin potentials. ConclusionsThrombin generation assays prove effective in differentiating single coagulation factor deficient samples from healthy controls, with modest discrepancies observed between the platforms. Reagents designed for assessing bleeding tendencies, featuring the lowest tissue factor and phospholipid concentrations, emerged as the most suitable option for detecting coagulation factor deficiencies.

Evaluation of the Value of Perfusion-Weighted Magnetic Resonance Imaging in the Differential Diagnosis of Sellar and Parasellar Tumors.

The purpose of this study was to assess the value of perfusion-weighted imaging (PWI) in the differential diagnosis of sellar and parasellar tumors, as an additional sequence in the magnetic resonance imaging (MRI) protocol. Analysis was based on a substantial group of subjects and included 124 brain and pituitary MRI examinations with a dynamic susceptibility contrast (DSC) PWI sequence. The following perfusion parameters were determined for the tumors: relative cerebral blood volume (rCBV), relative peak height (rPH) and relative percentage of signal intensity recovery (rPSR). To ensure greater repeatability, each of the aforementioned parameters was calculated as: arithmetic mean of the values of the whole tumor, arithmetic mean of the maximum values on each axial slice within the tumor and maximum values derived from the whole tumor. In our study, we established that meningiomas compared to both non-functional and hormone-secreting pituitary adenomas (pituitary neuroendocrine tumors-PitNET) had significantly higher values of rCBV with cut-off points set at 3.45 and 3.54, respectively (mean rCBV). Additionally, meningiomas presented significantly higher maximum and mean maximum rPH values compared to adenomas. DSC PWI imaging adds significant value to conventional MRI examinations and can be helpful in differentiating equivocal pituitary tumors.

Comparison of genotyping and weight of evidence results when applying different genotyping strategies on samples from a DNA transfer experiment.

In this study, we assessed to what extent data on the subject of TPPR (transfer, persistence, prevalence, recovery) that are obtained through an older STR typing kit can be used in an activity-level evaluation for a case profiled with a more modern STR kit. Newer kits generally hold more loci and may show higher sensitivity especially when reduced reaction volumes are used, and this could increase the evidential value at the source level. On the other hand, the increased genotyping information may invoke a higher number of contributors in the weight of evidence calculations, which could affect the evidential values as well. An activity scenario well explored in earlier studies [1,2] was redone using volunteers with known DNA profiles. DNA extracts were analyzed with three different approaches, namely using the optimal DNA input for (1) an older and (2) a newer STR typing system, and (3) using a standard, volume-based input combined with replicate PCR analysis with only the newer STR kit. The genotyping results were analyzed for various aspects such as percentage detected alleles and relative peak height contribution for background and the contributors known to be involved in the activity. Next, source-level LRs were calculated and the same trends were observed with regard to inclusionary and exclusionary LRs for persons who had or had not been in direct contact with the sampled areas. We subsequently assessed the impact on the outcome of the activity-level evaluation in an exemplary case by applying the assigned probabilities to a Bayesian network. We infer that data from different STR kits can be combined in the activity-level evaluations.

Temperature dependence of nanoscale friction on topological insulator Bi2Se3 surfaces

The topological insulator Bi2Se3 is an insulator in the bulk and has unusual metallic surface states that consist of spin-polarized Dirac fermions. Although the electronic properties of topological insulators have been extensively studied, the friction characteristic that is a key factor for further applications is barely known. In this study, conductive friction force microscopy (c-FFM) in ultrahigh vacuum (UHV) conditions was used to probe the nanoscale friction on freshly cleaved Bi2Se3 planes (0001) as a function of surface temperature from 105.0 K to 300.0 K. The experimental results demonstrate a non-monotonic enhancement of dry friction, with distinct friction peaks emerging at K and K. While the widths of the friction peaks are nearly independent of the normal force, the relative peak height increases and the peak temperature decreases with normal load. We reveal that this anomalous friction behavior originates from the formation and rupture of multiple thermally activated sub-contacts, which is further confirmed by velocity dependence measurements. These results for multiple thermally activated sub-contact formation and rupture provide a deep insight into the frictional behaviors of Bi2Se3.

Correlation between dynamic susceptibility contrast perfusion MRI and genomic alterations in glioblastoma

To determine if dynamic susceptibility contrast perfusion MR imaging (DSC-pMRI) can predict significant genomic alterations in glioblastoma (GB). A total of 47 patients with treatment-naive GB (M/F: 23/24, mean age: 54years, age range: 20-90years) having DSC-pMRI with leakage correction and genomic analysis were reviewed. Mean relative cerebral blood volume (rCBV), maximum rCBV, relative percent signal recovery (rPSR), and relative peak height (rPH) were derived from T2* signal intensity-time curves by ROI analysis. Major genomic alterations of IDH1-132H, MGMT, p53, EGFR, ATRX, and PTEN status were correlated with DSC-pMRI-derived GB parameters. Statistical analysis was performed utilizing the independent-samples t-test, ROC (receiver operating characteristic) curve analysis, and multivariable stepwise regression model. rCBVmean and rCBVmax were significantly different in relation to the IDH1, MGMT, p53, and PTEN mutation status (all p < 0.05). The rPH of the p53 mutation-positive GBs (mean 5.8 ± 2.8) was significantly higher than those of the p53 mutation-negative GBs (mean 4.0 ± 1.5) (p = 0.022). Multivariable stepwise regression analysis revealed that the presence of IDH-1 mutation (B = - 2.81, p = 0.005) was associated with decreased rCBVmean; PTEN mutation (B = - 1.21, p = 0.003) and MGMT methylation (B = - 1.47, p = 0.038) were associated with decreased rCBVmax; and ATRX loss (B = - 1.05, p = 0.008) was associated with decreased rPH. Significant associations were identified between DSC-pMRI-derived parameters and major genomic alterations, including IDH-1 mutation, MGMT methylation, ATRX loss, and PTEN mutation status in GB.

Characterizing the structure of halo merger trees using a single parameter: the tree entropy

ABSTRACT Linking the properties of galaxies to the assembly history of their dark matter haloes is a central aim of galaxy evolution theory. This paper introduces a dimensionless parameter s ∈ [0, 1], the ‘tree entropy’, to parametrize the geometry of a halo’s entire mass assembly hierarchy, building on a generalization of Shannon’s information entropy. By construction, the minimum entropy (s = 0) corresponds to smoothly assembled haloes without any mergers. In contrast, the highest entropy (s = 1) represents haloes grown purely by equal-mass binary mergers. Using simulated merger trees extracted from the cosmological N-body simulation SURFS, we compute the natural distribution of s, a skewed bell curve peaking near s = 0.4. This distribution exhibits weak dependences on halo mass M and redshift z, which can be reduced to a single dependence on the relative peak height δc/σ(M, z) in the matter perturbation field. By exploring the correlations between s and global galaxy properties generated by the SHARK semi-analytic model, we find that s contains a significant amount of information on the morphology of galaxies – in fact more information than the spin, concentration, and assembly time of the halo. Therefore, the tree entropy provides an information-rich link between galaxies and their dark matter haloes.

Assessment of a low-cost LED vein detection method: Initial proof of concept

Venepuncture is one of the most common invasive procedures in medical healthcare worldwide, however failure rates are still relatively high, particularly for paediatric, geriatric, darker skinned, and obese patients. Visualisation of the veins has been shown to decrease failure rates and can be achieved through trans-illumination, near infrared reflectance, or sonography. However, these techniques are either not reliable or very expensive, resulting in them not being commonly used in the clinical workplace. This paper develops a proof of concept low-cost LED vein detection device using photocurrent generated by LEDs in reverse bias. The prototype uses two emitting LEDs and one detecting LED to identify the location of a vein via trans-illuminance and reflectance. Various light intensities and wavelengths of the LEDs are tested in regard to resolution, noise, and signal peaks. A balance between system noise and resolution is identified for each LED in relation to the emitted intensity. No significant difference was observed in relative peak height when different wavelengths were used to identify the same superficial veins. The initial proof of concept proves the LED vein detection method and provides the foundation for further low-cost LED vein detection devices to be developed.

Diffusion and perfusion MR patterns of central nervous system lymphomas.

Central nervous system lymphomas (CNSLs) are rare tumors which may show variable appearance in standard magnetic resonance imaging (MRI) depending on their origin (primary or secondary) or patients' immunological status. The aim of the study was to analyze imaging patterns of different CNSLs, using diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI). Our material consisted of 16 CNSLs (14 primary, 2 secondary, 13 immunocompetent, 3 immunodeficient) which underwent magnetic resonance (MR) examinations including DWI and T2* dynamic susceptibility contrast (DSC) perfusion (without a preload in 13 cases, with a preload in 3 subjects). In DWI, apparent diffusion coefficient (ADC), and in PWI, parameters of relative cerebral blood volume (rCBV), relative peak height (rPH) and relative percentage of signal recovery (rPSR) were analyzed within the entire tumor (mean values) and in regions with minimal diffusion (ADCmin) and maximal perfusion values (rCBVmax, rPHmax, rPSRmax). All CNSLs showed low values of ADCmean (0.70 × 10-3), ADCmin (0.54 × 10-3), rCBVmean (0.80), rCBVmax (1.27), rPHmean (1.05), rPHmax (1.59), as well as high values of rPSRmean (1.99) and rPSRmax (2.41). There were no significant differences in rCBVmax, as well as in all ADC, rPH and rPSR values between primary and secondary CNSLs or between tumors in immunocompetent and immunodeficient patients. Dynamic susceptibility contrast PWI with a preload resulted in significantly higher rCBV, rPH and lower rPSR values. Despite various MR appearances, both primary and secondary CNSLs in immunocompetent and immunodeficient patients show very typical patterns of restricted diffusion and hypoperfusion with signal intensity curves returning above the baseline. Dynamic susceptibility contrast perfusion without a preload is recommended.

Recurrent brain tumor versus radiation necrosis; can dynamic susceptibility contrast (DSC) perfusion magnetic resonance imaging differentiate?

BackgroundAssessment of treatment response in patients with a brain tumor is paramount, as true tumor recurrence and radiation necrosis are similar looking on conventional MRI. PurposeTo evaluate the role of dynamic susceptibility contrast (DSC) perfusion magnetic resonance imaging in the differentiation between recurrent brain tumors and radiation necrosis. Material and MethodsTwenty patients with a history of operated primary brain tumors and postoperative radiotherapy with or without chemotherapy were enrolled in this prospective study having conventional MRI findings of enhancing lesion suspicious of being recurrence or radiation necrosis. All patients were examined by DSC-perfusion MRI. Definitive diagnosis was reached through either subsequent surgical biopsy or follow up over 6-12 months. ResultsFifteen patients (75%) were diagnosed as tumor recurrence and 5 patients as radiation necrosis (25%). The relative cerebral blood volume (rCBV) and relative peak height (rPH) were significantly higher (P < 0.05) in recurrent tumors than in radiation necrosis lesions. The rCBV and rPH thresholds in differentiating between them were 1.8 and 1.22 respectively with 87%, 93% sensitivity and 100% specificity for each respectively. ConclusionsDSC-perfusion MRI is a valuable non-invasive tool besides conventional MRI whenever available to differentiate between radiation injury changes and tumor recurrence.

The Importance of the Dissociation Rate in Ion Channel Blocking.

Understanding the relationships between the rates and dynamics of current wave forms under voltage clamp conditions is essential for understanding phenomena such as state-dependence and use-dependence, which are fundamental for the action of drugs used as anti-epileptics, anti-arrhythmics, and anesthetics. In the present study, we mathematically analyze models of blocking mechanisms. In previous experimental studies of potassium channels we have shown that the effect of local anesthetics can be explained by binding to channels in the open state. We therefore here examine models that describe the effect of a blocking drug that binds to a non-inactivating channel in its open state. Such binding induces an inactivation-like current decay at higher potential steps. The amplitude of the induced peak depends on voltage and concentration of blocking drug. In the present study, using analytical methods, we (i) derive a criterion for the existence of a peak in the open probability time evolution for a model with an arbitrary number of closed states, (ii) derive formula for the relative height of the peak amplitude, and (iii) determine the voltage dependence of the relative peak height. Two findings are apparent: (1) the dissociation (unbinding) rate constant is important for the existence of a peak in the current waveform, while the association (binding) rate constant is not, and (2) for a peak to exist it suffices that the dissociation rate must be smaller than the absolute value of all eigenvalues to the kinetic matrix describing the model.

High pressure processing of beet extract complexed with anionic polysaccharides enhances red color thermal stability at low pH

High pressure processing (HPP; 600 MPa; 3 min; 25 °C) of beet root powder slurries complexed (1:1) with locust bean gum (LBG), sodium alginate, or gum arabic was assessed for its’ ability to affect the thermal stability of the red color presented by betalain pigments therein. HPP treated beet extract solutions alone did not show improved color stability during thermal treatment (50 and 80 °C) at pH 3, while those complexed with the anionic polysaccharides, alginate and gum arabic had dramatically improved color stability following HPP treatment compared to controls. The HPP treated complexes, particularly those with gum arabic, additionally maintained their red color through six weeks of unbuffered cold storage. The HPP treated LBG (neutral mannan gum) complexes also showed improved color stability at low pH although not as robust as the anionic polysaccharide complexes at high elevated temperatures. The improved color stability appears to be independent of any impact HPP may have on the beet extract solution alone. Measurement of the pigment complex zeta-potentials showed a reduction in LBG-beet root complex (least improved stability) negativity and an increase in the gum arabic-beet complex (most improved stability) negativity following HPP. ATR-IR spectroscopy showed relative peak height increases near wavenumbers 990 and 920 cm−1 following HPP for the beet extract alone and the tested complexes. This observation could suggest an increased exposure of pigment aromatic rings occurs with high pressure treatment. Furthermore, DPPH scavenging activity associated with the beet extract solutions was not dramatically reduced by polysaccharide complexation nor HPP treatment. The data suggest combined polysaccharide complexation and HPP can add much needed low-pH red color thermal stability to betalain containing solutions without adversely affecting the beneficial antioxidant potential of the pigments.

Detection of protonated non-Watson-Crick base pairs using electrospray ionization mass spectrometry.

Many studies have shown that protonated nucleic acid base pairs are involved in a wide variety of nucleic acid structures. However, little information is available on relative stability of hemiprotonated self- and non-self-dimers at monomer level. We used electrospray ionization mass spectrometry (ESI-MS) to evaluate the relative stability under various concentrations of hydrogen ion. These enable conjecture of the formation of protonated non-Watson-Crick base pairs based on DNA and RNA base sequence. In the present study, we observed that ESI-MS peaks corresponded to respective self-dimers for all examined nucleosides except for adenosine. Peak heights depended on the concentration of hydrogen ion. The ESI-MS peak heights of the hemiprotonated cytidine dimers and the hemiprotonated thymidine dimer sharply increased with increased concentration of hydrogen ion, suggesting direct participation of hydrogen ion in dimer formations. In ESI-MS measurements of the solutions containing adenosine, cytidine, thymidine and guanosine, we observed protonated cytidine-guanosine dimer (CH+-G) and protonated cytidine-thymidine dimer (CH+-T) in addition to hemiprotonated cytidine-cytidine dimer (CH+-C) with following relative peak height, (CH+-C) > (CH+-G) ≈ (CH+-T) > (CH+-A). Additionally, in the ESI-MS measurements of solutions containing adenosine, thymidine and guanosine, we observed a considerable amount of protonated adenosine-guanosine (AH+-G) and protonated adenosine-thymidine (AH+-T).

Comparison of HLA DQA1 and DQB1 Genes by Multiplex Ligation-Dependent Probe Amplification and Next Generation Sequencing Technologies for Celiac Disease Risk Determination

Introduction: Celiac disease is a systemic autoimmune disease with chronic gastrointestinal disorder caused by intolerance to gluten proteins. The most dominant genetic risk factors are the specific genotypes encoding the Human Leukocyte Antigen (HLA) class II molecule genes, DQA1 and DQB1. The DQ2.5 variant (DQA1*05/DQB1*02 alleles) is present in 90-95% of patients with celiac disease. The DQ8 variant (DQA1*03/DQB1*0302) and DQ2.2 variant (DQA1*02/DQB1*02) are found in most of the remaining patients. A positive test is indicative of genetic susceptibility but does not necessarily mean disease development. A negative test has a more significant value because gluten intolerance rarely occurs in the absence of specific HLA predisposing alleles. In the current study we compared Multiplex Ligation-dependent Probe Amplification (MLPA) and Next Generation Sequencing (NGS) technologies for identifying Celiac disease risk HLA alleles. Methods: DNA was extracted from either saliva or whole-blood archival samples obtained from commercial vendors using Qiagen DNA mini extraction kits. MLPA assay probe mix designed to detect the HLA alleles implicated in Celiac disease consists of 29 specific fluorescent labeled amplification products. The PCR products are separated by capillary gel electrophoresis on the ABI 3500 Genetic Analyzer yielding a specific electropherogram. Based on the presence and relative height of individual probe, as compared to the relative probe peak height in various reference samples, the HLA allele in the patient sample was determined. For Next Generation sequencing assay, long range PCR products of HLA DQA1 and DQB1 genes were pooled to prepare bar coded NGS libraries. Equimolar pools of the barcoded libraries were sequenced on the Illumina MiSeq platform by paired end 151 bp sequencing. Demultiplexed FASTQ files were aligned to HLA variant database and genotypes were identified. Results: A total of 26 samples with different HLA variants were analyzed by both MLPA and NGS assay panel. The samples included DQ2.5, DQ8, DQ2.2, both heterozygous and homozygous variants, negatives and positive control cell line DNA samples. Data is summarized in Table 1. There was 100% concordance between the two technologies in determining the Celiac disease risk alleles. DNA dilution studies showed that both technologies were optimal with a minimum of 40 ng of DNA input. The workflow for MLPA was simple with sample to data generation completed within 24 hours. NGS assay was laborious with highly technical library preparation, sequencing and data analysis with sample to data in 48 hours. However, NGS technology results in a high resolution genotyping whereas MLPA assay is limited to 5 alleles of DQA1 and DQB1 genes.Table: Table. HLA DQA1 and DQB1 genotyping data summary- MLPA and NGS dataConclusion: Both methods are reliable and efficient to provide necessary information for celiac disease risk evaluation. In the future if high resolution HLA genotyping is needed, NGS may be more applicable.

STRAPS v1.0: evaluating a methodology for predicting electron impact ionisation mass spectra for the aerosol mass spectrometer

Abstract. Our ability to model the chemical and thermodynamic processes that lead to secondary organic aerosol (SOA) formation is thought to be hampered by the complexity of the system. While there are fundamental models now available that can simulate the tens of thousands of reactions thought to take place, validation against experiments is highly challenging. Techniques capable of identifying individual molecules such as chromatography are generally only capable of quantifying a subset of the material present, making it unsuitable for a carbon budget analysis. Integrative analytical methods such as the Aerosol Mass Spectrometer (AMS) are capable of quantifying all mass, but because of their inability to isolate individual molecules, comparisons have been limited to simple data products such as total organic mass and the O : C ratio. More detailed comparisons could be made if more of the mass spectral information could be used, but because a discrete inversion of AMS data is not possible, this activity requires a system of predicting mass spectra based on molecular composition. In this proof-of-concept study, the ability to train supervised methods to predict electron impact ionisation (EI) mass spectra for the AMS is evaluated. Supervised Training Regression for the Arbitrary Prediction of Spectra (STRAPS) is not built from first principles. A methodology is constructed whereby the presence of specific mass-to-charge ratio (m∕z) channels is fitted as a function of molecular structure before the relative peak height for each channel is similarly fitted using a range of regression methods. The widely used AMS mass spectral database is used as a basis for this, using unit mass resolution spectra of laboratory standards. Key to the fitting process is choice of structural information, or molecular fingerprint. Our approach relies on using supervised methods to automatically optimise the relationship between spectral characteristics and these molecular fingerprints. Therefore, any internal mechanisms or instrument features impacting on fragmentation are implicitly accounted for in the fitted model. Whilst one might expect a collection of keys specifically designed according to EI fragmentation principles to offer a robust basis, the suitability of a range of commonly available fingerprints is evaluated. Using available fingerprints in isolation, initial results suggest the generic public MACCS fingerprints provide the most accurate trained model when combined with both decision trees and random forests, with median cosine angles of 0.94–0.97 between modelled and measured spectra. There is some sensitivity to choice of fingerprint, but most sensitivity is in choice of regression technique. Support vector machines perform the worst, with median values of 0.78–0.85 and lower ranges approaching 0.4, depending on the fingerprint used. More detailed analysis of modelled versus mass spectra demonstrates important composition-dependent sensitivities on a compound-by-compound basis. This is further demonstrated when we apply the trained methods to a model α-pinene SOA system, using output from the GECKO-A model. This shows that use of a generic fingerprint referred to as FP4 and one designed for vapour pressure predictions (Nanoolal) gives plausible mass spectra, whilst the use of the MACCS keys in isolation performs poorly in this application, demonstrating the need for evaluating model performance against other SOA systems rather than existing laboratory databases on single compounds. Given the limited number of compounds used within the AMS training dataset, it is difficult to prescribe which combination of approach would lead to a robust generic model across all expected compositions. Nonetheless, the study demonstrates the use of a methodology that would be improved with more training data, fingerprints designed explicitly for fragmentation mechanisms occurring within the AMS, and data from additional mixed systems for further validation. To facilitate further development of the method, including application to other instruments, the model code for re-training is provided via a public Github and Zenodo software repository.

Improving the retrieval of solar-induced chlorophyll fluorescence at canopy level by modeling the relative peak height of the apparent reflectance

Recently, a great number of algorithms have been used in connection with the retrieval of solar-induced chlorophyll fluorescence (SIF) with the aim of detecting the physiological status of vegetation. In these SIF retrieval algorithms, methods based on Fraunhofer line discrimination (FLD) are widely used. However, all these FLD-based methods require that assumptions are made about the shape of the real reflectance around the absorption bands. These assumptions are a significant source of error in the retrieval of SIF and mean that satisfactory results at the O2-B band cannot be obtained if the spectral resolution (SR) is relatively coarse. In order to enable more accurate SIF retrieval at the O2-B band at canopy level, we have developed an alternative solution that uses a statistical empirical model to retrieve the SIF inside the absorption band, bypassing the assumptions about the shape of the real reflectance made in the FLD-based methods. In the proposed approach, called the reflectance height method (RHM), a model of the relative peak height of the apparent reflectance using two variables including the absorption depth of the irradiance and the gradient of the smoothed reflectance around the absorption bands is constructed using simulated training samples covering the most commonly occurring vegetation conditions. Validation of the RHM using both simulations and in situ observations showed that the RHM can effectively improve the SIF retrieval accuracy at the O2-B band at canopy level compared to traditional FLD-based methods, especially for cases using sensors with relatively coarse SR (SR≥1 nm) and high signal-to-noise ratio (SNR) (SNR≥1000).

Quantitative determination of two polymorphic forms of imatinib mesylate in a drug substance and tablet formulation by X-ray powder diffraction, differential scanning calorimetry and attenuated total reflectance Fourier transform infrared spectroscopy

Imatinib has been identified as a tyrosine kinase inhibitor that selectively inhibits the Abl tyrosine kinases, including Bcr-Abl. The active substance used in drug product is the mesylate salt form of imatinib, a phenylaminopyrimidine derivative and chemically named as N-(3-(4-(pyridin-3-yl) pyrimidin-2-ylamino)-4-methylphenyl)-4-((4-methylpiperazin-1-yl) methyl)-benzamide methanesulfonic acid salt. It exhibits many polymorphic forms and most stable and commercialized polymorphs are known as α and β forms. Molecules in α and β polymorphic forms exhibit significant conformational differences due to their different intra- and intermolecular interactions, which stabilize their molecular conformations and affect their physicochemical properties such as bulk density, melting point, solubility, stability, and processability. The manufacturing process of a drug tablet included granulation, compression, coating, and drying may cause polymorphic conversions. Therefore, polymorphic content of the drug substance should be controlled during quality control and stability testing. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) methods were evaluated for determination of the polymorphic content of the drug substance and drug product; and PXRD was the most accurate technique and selected as preferred method and validated. Prior to development of a quantification method, pure α and β polymorphs were characterized and used throughout the method development and validation studies. Mixtures with different ratios of α and β forms were scanned using X-ray diffractometer with a scan rate of 0.250°/min over an angular range of 19.5–21.0° 2θ and the peak heights for characteristic peak of β form at 20.5±0.2° 2θ diffraction angle were used to generate a calibration curve. The detection limit of β polymorph in α form imatinib mesylate tablets was found as 4% and the linear regression analysis data for the calibration plots showed good linear relationship with correlation coefficient of 0.992 with respect to relative peak height in the concentration range of 12–75wt% β form containing tablet mixtures. The obtained results at each stage of the validation study proved that the method is specific, repeatable, precise and accurate, and could be used for determination of β polymorph content in tablets produced by using α polymorph of imatinib mesylate. The developed PXRD quantification method was used to monitor the polymorphic purity of α form drug substance and corresponding drug products during the quality control analyses and stability studies, and the results indicated that α form was stable and not converted to β form during the manufacturing process and stability period.

Glacial cirques and the relationship between equilibrium line altitudes and mountain range height

Research Article| January 01, 2015 Glacial cirques and the relationship between equilibrium line altitudes and mountain range height Sara Gran Mitchell; Sara Gran Mitchell 1Department of Biology, College of the Holy Cross, P.O. Box B, 1 College Street, Worcester, Massachusetts 01610, USA Search for other works by this author on: GSW Google Scholar Elizabeth E. Humphries Elizabeth E. Humphries 2Department of Geological Sciences, University of North Carolina–Chapel Hill, 104 South Road, Campus Box #3315, Chapel Hill, North Carolina 27599, USA Search for other works by this author on: GSW Google Scholar Author and Article Information Sara Gran Mitchell 1Department of Biology, College of the Holy Cross, P.O. Box B, 1 College Street, Worcester, Massachusetts 01610, USA Elizabeth E. Humphries 2Department of Geological Sciences, University of North Carolina–Chapel Hill, 104 South Road, Campus Box #3315, Chapel Hill, North Carolina 27599, USA Publisher: Geological Society of America Received: 13 Aug 2014 Revision Received: 16 Oct 2014 Accepted: 19 Oct 2014 First Online: 09 Mar 2017 Online ISSN: 1943-2682 Print ISSN: 0091-7613 © 2014 Geological Society of America Geology (2015) 43 (1): 35–38. https://doi.org/10.1130/G36180.1 Article history Received: 13 Aug 2014 Revision Received: 16 Oct 2014 Accepted: 19 Oct 2014 First Online: 09 Mar 2017 Cite View This Citation Add to Citation Manager Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Search Site Citation Sara Gran Mitchell, Elizabeth E. Humphries; Glacial cirques and the relationship between equilibrium line altitudes and mountain range height. Geology 2015;; 43 (1): 35–38. doi: https://doi.org/10.1130/G36180.1 Download citation file: Ris (Zotero) Refmanager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentBy SocietyGeology Search Advanced Search Abstract A global GIS- and literature-based analysis of the altitude and relief of more than 14,000 ice-free glacial cirques in 56 study areas ranging from 69°N to 77°S shows that average cirque floor altitudes vary with latitude in a zone centered on the Quaternary average equilibrium line altitude (QA-ELA). In addition, relief above cirque floors averages 346 ± 107 m, and is rarely >600 m. In regions where ice-free cirques are abundant, cirque relief is independent of modern precipitation rates, tectonic regime, and relative peak height, limiting peaks to within a fixed distance above the QA-ELA and thus causing them to also parallel the ELA. We propose a physical process model where, under suitable geologic and tectonic conditions, climate exerts a first-order control on mountain range height. In this model, glacial erosion excavates a zone of cirques with floors centered on the QA-ELA, while climate-driven weathering processes on adjacent slopes limit the peaks to within a few hundred meters above this zone. You do not have access to this content, please speak to your institutional administrator if you feel you should have access.

Differentiation of hemangioblastomas from pilocytic astrocytomas using 3-T magnetic resonance perfusion-weighted imaging and MR spectroscopy.

Hemangioblastomas and pilocytic astrocytomas (PAs) present similar imaging features on conventional MR imaging, making differential diagnosis a challenge. The purpose of this study was to evaluate the usefulness of dynamic susceptibility-weighted contrast-enhanced perfusion-weighted imaging (DSC-PWI) and proton MR spectroscopic imaging in the differentiation of hemangioblastomas and PAs. A 3.0-T MR imaging unit was used to perform DSC-PWI and conventional MR imaging on 14 patients with hemangioblastomas and 22 patients with PAs. Four patients with hemangioblastomas and 10 PA patients also underwent proton MR spectroscopy. Parameters of relative peak height (rPH) and relative percentage of signal intensity recovery (rPSR) were acquired by DSC-PWI and variables of N-acetylaspasrtate (NAA)/creatine (Cr), choline (Cho)/Cr, and lactate-lipid (Lac-Lip)/Cr by MR spectroscopy. The sensitivity, specificity, and the area under the receiver operating characteristic curve of all analyzed parameters at respective cutoff values were determined. Higher rPH but lower rPSR values were detected in hemangioblastomas compared to PAs. The NAA/Cr ratio was significantly lower in hemangioblastomas compared with PAs. The threshold values ≥3.2 for rPH provide sensitivity, specificity, positive predictive values, and negative predictive values of 85.7, 95.5, 92.3, and 91.3%, respectively, for differentiating hemangioblastomas from PAs. The optimal threshold values were ≤0.9 for rPSR and ≤1.5 for NAA/Cr ratios in tumor. Significantly higher rPH and lower NAA/Cr were seen in patients with hemangioblastomas when compared with PA patients, suggesting that DSC-PWI and proton MR spectroscopy are helpful in the characterization and differentiation of these two types of tumors.

The impact of disorder on charge transport in three dimensional quantum dot resonant tunneling structures

Efficient iso-entropic energy filtering of electronic waves can be realized through nanostructures with three dimensional confinement, such as quantum dot resonant tunneling structures. Large-area deployment of such structures is useful for energy selective contacts but such configuration is susceptible to structural disorders. In this work, the transport properties of quantum-dot-based wide-area resonant tunneling structures, subject to realistic disorder mechanisms, are studied. Positional variations of the quantum dots are shown to reduce the resonant transmission peaks while size variations in the device are shown to reduce as well as broaden the peaks. Increased quantum dot size distribution also results in a peak shift to lower energy which is attributed to large dots dominating transmission. A decrease in barrier thickness reduces the relative peak height while the overall transmission increases dramatically due to lower “series resistance.” While any shift away from ideality can be intuitively expected to reduce the resonance peak, quantification allows better understanding of the tolerances required for fabricating structures based on resonant tunneling phenomena.

The application of portable microchip electrophoresis for the screening and comparative analysis of synthetic cathinone seizures

Variation in the chemical composition of illicit tablets and powders is common among samples within a given drug seizure. Using microchip electrophoresis (ME), multiple tablets can be screened in a cost-effective and timely manner. This method could be used in conjunction with reporting methods that focus solely on statistical sampling to infer homogeneity or otherwise of a larger subset of tablets. Some frequently observed synthetic cathinones, often present in illicit tablets seized in New Zealand, were chosen for analysis. An ME device (Agilent Bioanalyzer 2100) was used to electrophoretically separate synthetic cathinones. The background electrolyte was composed of a 50mM sodium tetraborate buffer with 50mM sodium dodecyl sulphate at pH 9.66. Analytes were derivatised prior to analysis for 3min at 90°C, employing fluorescein isothiocyanate isomer I (FITC). A characteristic fluorescent profile was obtained for each tablet, in terms of the number of constituents, relative peak height ratios and migration times. The repeatability of the developed method was assessed for a wide range of tablets and relative standard deviations of 0.4–5.2% and 1.6–5.5% were calculated for migration times and peak height ratios, respectively. The use of microchip tablet profiles in the forensic case comparison of illicit drug seizure samples in realistic scenarios is discussed.