BP Ratio Research Articles

A composite anode based on intercalation and conversion mechanism for high-rate lithium-ion batteries

To increase the specific capacity and cycle stability of lithium-ion batteries at high current density, we have investigated the anode materials. Among them, black phosphorus has attracted attention because of its large theoretical specific capacity (2596 mA h/g). However, the moderate conductivity of black phosphorus itself makes it less effective. The addition of graphite to form P-C and P-O-C bonds with black phosphorus enhances the performance of the battery cell. Lithium ions are primarily stored in black phosphorus-graphite layered structural materials via an intercalation mechanism, which improves electrochemical performance at tiny current density but is inadequate for charge/discharge cycling at high current density. In addition, lithium ions also can undergo conversion mechanism with metal oxide materials (e.g. Tungsten trioxide). While this conversion mechanism enables more stable battery cycling at high current density, the specific capacity remains insufficiently high. Higher charge/discharge specific capacity and long cycle stability of lithium-ion batteries at high current density can be realized by the joint action of the two mechanisms. In this work, black phosphorus, graphite, and tungsten trioxide (BP/G/WO3) composites are prepared by ball milling method. A comprehensive series of electrochemical analyses reveals that the BP/G/WO3-532 electrode (BP, graphite, and WO3 mass ratio of 5:3:2) exhibits the most substantial enhancement in the cycling stability of lithium-ion batteries. The anode exhibits a high specific capacity of 1463.1 mA h/g at 6 A/g and presents a retention capacity of 1159.8 mA h/g after 300 charge/discharge cycles, indicating a high cycle stability and fast reaction kinetics. This result is mainly attributed to the joint action of two mechanisms of composites.

Effects of shift work on sleep quality and cardiovascular function in Taiwanese police officers

ABSTRACT This study aimed to investigate the effects of shift work on sleep quality, cardiovascular function, and physical activity (PA) levels in Taiwanese police officers. Twenty-one male police officers aged 26.9 ± 4.1 years old located in Taipei voluntarily participated in this study. The participants completed the resting heart rate (HR) and hemodynamic variables (e.g. blood pressure, BP) before and after day-time (DTW) and night-time (NTW) shift work phases (5 working days and 2 resting days for each phase). Additionally, an actigraphy was administered to measure PA and sleep patterns in the last 3 working days. The average total sleep time and sleep efficiency were 278.5 ± 79. 6 min and 72.9 ± 10%, respectively, in the NTW phases, which were significantly lower than that in the DTW phases. A comparison of the PA characteristics between the two phases revealed that a lower proportion of moderate-vigorous PA (1.2 ± 0.8%) and a greater proportion of sedentary behaviour PA (74.8 ± 6.4%) was found in the NTW phases. The results of hemodynamic measures demonstrated that the police officers have significantly elevated systolic BP by 3.3% and diastolic BP by 3.9% after the NTW phases. Furthermore, the NTW phases exhibited a significantly higher percentage change ratio of systolic BP and diastolic BP compared to the DTW phases. Compared with the DTW phases, the NTW phase was significantly more likely to report higher decreasing parasympathetic-related HR variability with a range of −5.9% to −7.8%. In conclusion, night-time shift work resulted in negative physiological changes leading to adverse effects on the health and well-being of Taiwanese police officers.

Salivary cardiac-enriched FHL2-interacting protein is associated with higher diastolic-to-systolic-blood pressure ratio, sedentary time and center of pressure displacement in healthy 7-9 years old school-children.

Cardiac-enriched FHL2-interacting protein (CEFIP) is a recently identified protein, first found in the z-disc of striated muscles, and related to cardiovascular diseases. Our objectives are: 1) to quantify CEFIP in saliva in healthy 7-9 years old school-children; and 2) to assess the associations of salivary CEFIP concentration and blood pressure, physical (in)activity and physical fitness in these children. A total of 72 children (7.6 ± 0.3 years) were included in the study, recruited in primary schools in Girona (Spain). A sandwich enzyme-linked immunosorbent assay was used (abx506878; Abbexa, United Kingdom) to quantify CEFIP in saliva. Anthropometric evaluation was performed [body mass, height and body mass index (BMI)]. Systolic and diastolic blood pressure were measured by means of an electronic oscillometer and the diastolic-to-systolic blood pressure ratio (D/S BP ratio) was calculated. Physical (in)activity [sedentary time and time spent in physical activity (PA)] were assessed by means of a triaxial Actigraph GT3X accelerometer (Actigraph, Pensacola, FL, USA) that children were instructed to wear for 24h during 7 conssecutive days. Finally, physical fitness (speed and agility, explosive power of legs, handgrip strength, flexibility and balance) were assessed through validated and standardized testing batteries. CEFIP was easily detected and measured in all saliva samples (mean concentration: 0.6 ± 0.2 pg/ml). Salivary CEFIP was positively associated with D/S BP ratio (r=0.305, p=0.010) and sedentary time (r=0.317, p=0.012), but negatively associated with PA in 7-9 years old school-children (r=-0.350, p=0.002). Furthermore, salivary CEFIP was related to lower level of balance i.e., higher center of pressure (CoP) displacement in these children (r=0.411, p<0.001). The associations of salivary CEFIP with D/S BP ratio (Beta=0.349, p=0.004), sedentary time (Beta=0.354, p=0.009) and CoP displacement (Beta=0.401, p=0.001), were maintained significant after adjustment for potential confounding variables such as age, gender and BMI in linear regression analyses. CEFIP can be easily assessed in saliva as a promising biomarker associated with cardiovascular health in 7-9 years old school-children. Interestingly, higher salivary CEFIP concentration was related to higher D/S BP ratio, more sedentary time and higher CoP displacement i.e., lower level of balance in these children.

Prognostic Significance of Blood Pressure at Rest and After Performing the Six-Minute Walk Test in Patients With Acute Heart Failure.

It remains unclear whether systolic (SBP) and diastolic (DBP) pressure and BP response after six-minute walk test (6MWT) are associated with adverse outcomes in patients with acute heart failure (AHF). We investigated these associations in 98 AHF patients (24.5% women; mean age, 70.5 years) enrolled in the ROSE trial (The Low-dose Dopamine or Low-dose Nesiritide in Acute Heart Failure with Renal Dysfunction). The primary endpoint consisted of any death or rehospitalization within 6 months after randomization. We computed hazard ratios (HRs) of the risks associated with 1-SD increase in post-exercise BP levels and BP ratios, calculated as BP immediately after 6MWT divided by BP before 6MWT. The BP before and after 6MWT averaged 110.6/117.5 mm Hg for SBP and 61.9/64.7 mm Hg for DBP. In multivariable-adjusted analyses including clinic BP measured at the same day of 6MWT, higher DBP after 6MWT was associated with lower risk of the primary endpoint (HR, 0.49; 95% confidence interval [CI], 0.26-0.95; P = 0.034). Both higher SBP and DBP immediately after 6MWT were associated with lower risk of 6-month mortality (HRs, 0.39/0.16; 95% CI, 0.17-0.90/0.065-0.40; P ≤ 0.026). The post-exercise SBP ratio was associated with the risk of 6-month mortality in multivariable-adjusted analyses (HR, 0.44; P = 0.023). Higher BP levels and BP ratios immediately after 6MWT conferred lower risk of adverse health outcomes. Our observations highlight that 6MWT-related BP level and response may refine risk estimates in patients hospitalized AHF and may help further investigation for the development of HF preventive strategies.

Combing of picogram level DNA equivalent to genomic DNA present in single human cell by self propelled droplet motion over a stable gradient surface

DNA combing is a powerful technique for studying replication profile, fork-directionality and fork velocity. At present, there is requirement of a methodology to comb DNA present in a single human cell for studying replication dynamics at early embryonic stage. In our study, a surface having dual characteristics i.e., affinity towards negatively charged single DNA molecules and a hydrophobic gradient for self propelled droplet motion of combing solution was developed. The surface was made by coating of TCOS (trichloro-octylsilane) by vapor diffusion on APTES (Aminopropyl-triethoxysilane) coated glass slides. A gradient surface having high deposition efficiency (DE) was developed on which 5 picogram DNA equivalent to genomic DNA present in one single human cell can be combed. The gradient surface was thermostable in nature having the ability to sustain boiling temperature for two hours and sustain anisotropy in 70 % ethanol for 80 h. Applicability for multiple runs was enhanced such that the surface can be used for 13–14 times. Factors associated with gradient surface are unidirectional movement of combing solution droplet over the gradient surface for combing straight DNA molecules and a longer gradient surface of more than 1 cm such that long size DNA molecules can be combed. Ellipsometry and contact angle hysteresis confirmed the presence of hydrophobic gradient. XPS (X-ray photoelectron spectroscopy) and FTIR (Fourier Transform Infrared Spectroscopy) confirmed the presence of characteristic affinity towards negatively charged DNA molecules on the gradient surface. Combing solution was optimized for increasing deposition efficiency and for increasing the applicability of gradient surface for multiple runs. High temperature of combing solution was found to increase Deposition Efficiency. Combing solution was also optimized for combing single DNA molecules over the gradient surface. Single DNA molecules were combed by reducing pH and lowering concentration of triton-X in the combing solution. Dye: bp ratio was optimized for high fluorescent intensity and low surface background.

A Simplified Method for Determining Blood-to-Plasma Ratios in vitro and ex vivo by Matrix Matching with Blank Blood or Plasma.

This work describes a simplified, 96-well plate method for determining the blood-to-plasma concentration ratio (BP ratio) for small molecules. The need for calibration curves was eliminated using a matrix-matching approach in which blood samples were mixed with blank plasma and plasma samples were mixed with blank blood. As a result, both blood- and plasma-origin samples shared an equivalent matrix ahead of bioanalysis. In the in vitro assay, identical sample matrices were achieved by using the same source of blank plasma and blood. In humans, a good correlation (R2 = 0.84) was observed between the data obtained in this matrix-matching method and literature values for 11 commercial compounds possessing a wide range of logD values across multiple chemical classes. In addition, this method showed good agreement with in vitro BP ratios for 10 proprietary compounds determined radiometrically (R2 = 0.72) in human and preclinical species. Finally, the in vitro matrix matching method compared favorably to BP ratios determined ex vivo for 13 proprietary and literature compounds (R2 = 0.87) in rat. This method, suitable for in vitro and ex vivo BP ratio determinations, is operationally efficient, robust, and a useful improvement upon previously published methods.

Serum gamma glutamyl transferase levels in metabolic syndrome in obese south Indian population

Background: Increased waist circumference in metabolic syndrome (MS), which reflects central obesity is associated with an increased risk of type 2 diabetes, dyslipidemia, hypertension and coronary vascular disease. Generation of free radicals in central obesity depletes intracellular glutathione, thereby induces release of gamma glutamyl transferase (GGT) into circulation. Elevated GGT levels could be a marker of high oxidative stress which is known to be associated with central obesity and metabolic syndrome. Hence the aim of this study was to determine the association of GGT levels with components of metabolic syndrome in obese South Indian population. Materials and methods: In this case control study conducted at Master Health Check (MHC) Department, Sri Ramachandra Medical College, study population included 60 obese subjects with metabolic syndrome (cases) and 60 non obese subjects (controls) of South Indian population who were non-smokers and non-alcoholics, between the ages of 30-50 years. Components of metabolic syndrome such as waist circumference, blood pressure, fasting plasma glucose, lipid profiles and GGT measured in both the groups. Data between cases and controls compared with unpaired student t-test. Pearson’s correlation was performed to find the association of GGT levels with other variables in Metabolic syndrome. Results: Serum GGT levels were significantly higher in metabolic syndrome patients (cases) than controls with p &lt; 0.0001. High levels of serum GGT were also associated with increase in BP and atherogenic lipid levels and ratios. Conclusion: Elevated serum GGT levels were significantly associated with components of metabolic syndrome in obese South Indian population.

Supply chain price variability under the buyback contract

ABSTRACT Supply chain price variability, also known as the “Bullwhip effect in Pricing (BP),” refers to the absorption or amplification of the variability of prices from one stage to another in a supply chain. This article derives analytical conditions that result in BP considering a buyback contract and conducts numerical simulations to gain further insights. For this, a joint price and replenishment setting newsvendor model with a wholesale-Stackelberg game is considered. Two demand types (linear and isoelastic) are analyzed along with uniformly and normally distributed additive and multiplicative uncertainties. The outcome of this research reveals that the main influential factors that affect BP are the structure and error type of the demand functions. Absorption (amplification) in price fluctuations occurs for linear (isoelastic) demand cases. Moreover, the price variances and BP ratios differ under the buyback and wholesale-price-only cases. The overall results help understand the fluctuation of market prices under various conditions.

Interleukin-22/Interleukin-22 binding protein axis and oral contraceptive use in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is associated with alterations in gut microbiota. The cytokine interleukin-22 (IL-22) is produced by immune cells and closely linked to gut immunity, which is tightly controlled by its binding protein (IL-22BP). In this study, we aimed to assess whether IL-22/IL-22BP axis is altered in PCOS at baseline and in response to short-term oral contraceptive (OC) therapy. We have evaluated circulating concentrations of IL-22 and IL-22BP in serum samples of 63 PCOS patients and 39 age- and BMI-matched healthy controls. Blood samples were taken in the early follicular phase of a cycle and stored at -80 °C. Serum IL-22 and IL-22BP levels were measured by ELISA at baseline in both women with PCOS and controls, and after 3 months of OC use in PCOS group. IL-22/IL-22BP ratio was calculated in order to have a better reflection of IL-22 biological activity. At baseline, serum IL-22, IL-22BP concentrations and IL22/IL-22BP ratio were similar between women with PCOS and healthy controls. Three months of OC use along with general lifestyle advice resulted in a significant increase in IL-22/IL-22BP ratio in the PCOS group (62.4 [IQR:14.7-172.7] at baseline vs 73.8 [IQR:15.1-264.3] after OC use respectively p = 0.011). Results of this study show that women with PCOS have similar circulating concentrations of IL-22 and IL-22BP with healthy women and that short term oral contraception is associated with an increase in IL-22/IL-22BP ratio suggesting higher biological activity of the IL-22 system with OC use in PCOS.

Variation in blood pressure and heart rate of radiological technologists in worktime tracked by a wearable device: A preliminary study

The aim of this preliminary study was to measure the systolic BP (SBP) and diastolic BP (DBP) and heart rate (HR) of radiological technologists by WD, and evaluate variation among individuals by worktime, day of the week, job, and workplace. Measurements were obtained using a wristwatch-type WD with optical measurement technology that can measure SBP and DBP every 10 minutes and HR every 30 minutes. SBP, DBP, and HR data obtained at baseline and during work time were combined with the hours of work, day of the week, job, and workplace recorded by the participants in 8 consecutive weeks. We calculated the mean, the ratio to baseline and coefficient of variation [CV(%)] for SBP, DBP, and HR. SBP, DBP, and HR values were significantly higher during work hours than at baseline (p&lt;0.03). The ratio to baseline values ranged from 1.02 to 1.26 for SBP and from 1.07 to 1.30 for DBP. The ratio to baseline for SBP and DBP showed CV(%) of approximately 10% according to the day of the week and over the study period. For HR, ratio to baseline ranged from 0.95 to 1.29. The ratio of mean BP to baseline was &gt;1.2 at the time of starting work, middle and after lunch, and at 14:00. The ratio to baseline of SBP were 1.2 or more for irradiation, equipment accuracy control, registration of patient data, dose verification and conference time, and were also working in CT examination room, treatment planning room, linac room, and the office. CV(%) of BP and HR were generally stable for all workplaces. WD measurements of SBP, DBP, and HR were higher during working hours than at baseline and varied by the individuals, work time, job, and workplace. This method may enable evaluation of unconscious workload in individuals.

Superconductivity with large upper critical field in noncentrosymmetric Cr-bearing high-entropy alloys

A series of new Cr5+xMo35−xW12Re35Ru13C20 high-entropy alloys (HEAs) have been synthesized and characterized by x-ray diffraction, scanning electron microscopy, electrical resistivity, magnetic susceptibility and specific heat measurements. It is found that the HEAs adopt a noncentrosymmetric cubic β-Mn type structure and exhibit bulk superconductivity for 0 ≤x≤ 9. With increasing x, the cubic lattice parameter decreases from 6.7940(3) Å to 6.7516(3) Å. Meanwhile, the superconducting transition temperature Tc is suppressed from 5.49 K to 3.35 K due to the magnetic pair breaking caused by Cr moments. For all these noncentrosymmetric HEAs, the zero-temperature upper critical field Bc2(0) is comparable to the Pauli paramagnetic limit BP(0) = 1.86Tc. In particular, the Bc2(0)/BP(0) ratio reaches a maximum of ∼1.03 at x = 6, which is among the highest for β-Mn type superconductors.

Mortality and prognostic factors of Bullous Pemphigoid in a Moroccan population.

Bullous pemphigoid is a common autoimmune blistering skin disease that is significantly associated with a high rate of morbidity and mortality. Our aim was to determine the 1-, 2- and 3-year mortality rate and standardized mortality ratio of BP in Moroccan patients, as well as to identify risk factors that influence survival both in the 1st and 3rd year of follow-up. All patients with BP diagnosed between January 2008 and December 2017 in a tertiary referral centre at the Mohammed V Military Hospital in Morocco were included retrospectively. The 1-year, 2-year and 3-year mortality rates of the cases were 25.8%, 32.3% and 43%, respectively. The median age of onset was 72 years (range, 64 ∼ 80 years), and 51 (54.8%) patients were men. The standardized mortality ratio of patients with BP was 2.6 times higher than that of age- and sex-matched members of the general Moroccan population. Besides advanced age, the presence of diabetes mellitus at the time of diagnosis was associated with increased 3-year mortality in multivariate analysis. This is the first study analysing the mortality rate of bullous pemphigoid in Morocco. Our findings confirm a high mortality rate for BP patients compared with the expected mortality rate for age- and sex-adjusted general Moroccan population. Risk factors for increased 3-year mortality include advanced age at the time of diagnosis and diabetes mellitus.

Diabetic nephropathy ameliorated in patients with normal home blood pressure compared to those with isolated high home systolic blood pressure: A 5-year prospective cohort study among patients with type 2 diabetes mellitus.

Background:Using normal home blood pressure (home BP) as a reference, isolated high home systolic blood pressure (IH-home SBP) increases the risk of diabetic nephropathy. However, whether diabetic nephropathy would improve among diabetic patients without IH-home SBP has not been previously assessed.Methods:This prospective 5-year cohort study of 264 patients with moderate or severe albuminuria investigated the effect of IH-home SBP or normal home BP on the risk of diabetic nephropathy in patients with type 2 diabetes mellitus. Improvement of diabetic nephropathy was defined as remission or regression from moderate or severe albuminuria to normal or mildly increased albuminuria.Results:Improvement of diabetic nephropathy was shown in 59 out of 264 patients during 5 years. The adjusted odds ratio (95% confidence interval) of normal home BP for improving diabetic nephropathy was 2.52 (1.01–5.99, p = 0.05).Conclusion:Normal home BP had relation to an improvement in diabetic nephropathy among type 2 diabetic patients with moderate and severe increased albuminuria in the observation period of 5 years. Good home BP control might be valuable to ameliorate diabetic nephropathy.

Manipulated and Improved Photoinduced Deformation Property of Photoresponsive Liquid Crystal Elastomers by Copolymerization.

Photoresponsive liquid crystal elastomers (LCEs) have aroused much attention due to their unique structures, properties, and potential applications. However, many reported photoresponsive LCEs show small photoinduced deformation with a slow deformation speed, which limits their application to a certain extent. In this article, multiple hydrogen bond component and biphenyl component was introduced into photoresponsive LCEs bearing cyanostilbene by copolymerization, and prepared a series of LCEs CSm-BPn (CS and BP means cyanostilbene and biphenyl component, respectively; m, n means the content ratio of CS and BP). All uniaxially oriented CSm-BPn fibers show photoinduced deformation behavior under 365nm UV light except for CS0-BP5. The introduction of hydrogen bond and the decrease of glass transition temperature realize large deformation and fast deformation speed. Besides, the properties of LCEs are successfully regulated by changing the content ratio of each component. What's more interesting is that the addition of appropriate amount of biphenyl can significantly improve and manipulate the deformation property of the CSm-BPn fibers. The maximum bending angle can reach 175° , and the whole photoinduced deformation process only takes 11 s. The photoresponsive LCEs with such large bending angle and fast deformation rate are rarely reported.

Impacts of Baobab (Adansonia digitata) Powder on the Poly(Butylene Succinate) Polymer Degradability to Form an Eco-Friendly Filler-Based Composite

Poly (butylene succinate) (PBS) is one of the most common biodegradable plastic polymers that has recently been used in the green environmental field. Enhancement of physicochemical characteristics of these polymers by using plant-based materials like Baobab (Adansonia digitata) will improve its industrial application. This study evaluated Baobab (Adansonia digitata) powder (BP) and PBS composites under various ratios (PBS/BP: 90/10, 80/20, 70/30, 60/40, and 50/50 wt%) for their thermo-mechanical and other physicochemical properties for the industrial application. The nanoscale morphological and elemental characterization were also measured by scanning electron microscope-dispersive X-ray spectroscopy (SEM-EDS). The results revealed that PBS/BP blends of 90/10 and 50/50 showed a significantly reduced melting temperature (Tm) up to 94°C (p &amp;lt; 0.05) compared to PBS (114°C). Also, the dynamic viscosity, storage modulus, and loss modulus showed a significant decrease with increasing the ratio of BP in PBS/BP composite, which confirmed faster degradation than the pure PBS. In conclusion, the novel PBS/BP biomaterial is recommended for use as a carbon source for denitrification processes, as an eco-friendly faster degradable natural filler-based polymer. Besides, they could be use in food packaging and biomedical industries.

COX1 gene and ITS-2 region: A comparative study of molecular diagnosis of Parabronema skrjabini in camels (Camelus dromedaries), Al-Najaf Province, Iraq

The current study was contributed to the analysis of the nucleotide sequence pattern of the nucleotide sequence of the tissue DNA isolates based on the Internal Transcribed Spacer ribosomal DNA (ITS2rDNA) gene and Cytochrome c oxidase subunit 1 mitochondrial DNA (COX1 mtDNA) using the traditional polymerase chain reaction (150 samples of abomasum collected directly from camel carcasses after working in Al-Najaf slaughterhouse from 1/10/2019 to 1/2/2020). ITS2rDNA were well suited for the prepared primer with size783 bp and identical ratio ranged 81.17-99.73% of the same species, as indicated a high similarity of the isolates taken from two-humped camels in China or less related to Parabronema skrjabini in sheep and goat. In addition, the study identified the number of the mutations within the four COX1 gene and ITS-2 region, which were the most conservative region of the host's species, supporting the concept of host specificity with Parabronema skrjabini. The COX1 gene and ITS-2 region applied to confirm the diagnosis using a universal primer, as it included eight isolates with a size of 689 bp, identical values were ranged from 84.99-98.02% depending on the multiple sequence alignment and showed an increase in the substitution level among isolates at an upper taxonomic level. Studying of the COX1 gene and ITS-2 region in Parabronema skrjabini demonstrated a significant relation in the cluster and an early common ancestor with isolates of the two-humped camel (China). As for the COX1 gene and ITS-2 region, the phylogenetic relationship supported the ribosomal gene results, especially with Habronema muscae or related species such as Habronema majus, Dirofilaria repens, Dipetalonema evansi, Setaria tundra, Cercopithifilaria sp towards the root node. Therefore, considering COX1 gene and ITS-2 region as an ideal tool in determining the phylogenetic history of the sequence maps, but less conservative mode than the ITS2 ribosome gene based to a taxonomic species level.

Pattern of Mutational Changes in Patients with Chronic Phase CML Who Are Treated with Frontline TKI and Transform to Blast Phase CML

Introduction: CML patients (pts) who transform to blast phase (CML-BP) or accelerated phase (AP) from a chronic phase (CML-CP) have a poor prognosis and exhibit a poor response to therapy with TKI. Increased usage of newer TKI's has remarkably reduced the incidence of CML-BP, however, the genetic mechanisms involved in the transformation remain unclear. In this study, using paired whole-exome sequencing, we compared the pattern of gene mutations and chromosomal allelic imbalances (CAI) between CML-CP and CML-BP in patients who received front-line TKI therapy.Methods: We analysed 13 CML patients who received front-line TKI therapy in CML-CP and eventually transformed to CML-BP. In 7 of 13 patients, sufficient DNA was available for sequencing both at the time of CP and AP/BP while in the remaining 6 patients, DNA was only available at 1 time point, either BP (n=4) or CP (n=2). Whole exome sequencing (WES) was performed using Agilent exome capture kit on Illumina HiSeq. For exome mutation analysis, read alignment was done using BWA and GATK, and variants were called using GATK's UnifiedGenotyper. CAI profiles were generated using hapLOHseq. For CAI, chromosomal arm events were called if they spanned at least 20% of the genomic region of a chromosomal arm. Somatic status was assigned to variants after filtering for potential germline variants using variants identified in the ExAC project. For assessing biological processes driving each cancer's mutation profile, mutation signatures were deconvoluted using the R package deconstructSigs into a set of previously identified, weighted set of COSMIC mutation signatures. For reporting of specific mutations, only somatic variants reported in the COSMIC database were selected.Results: The median age of the study group at the time of BP was 54 years (range, 24 to 73); 53% were male. Seven pts had e13a2 and 6 had e14a2 BCR-ABL transcripts. Eleven pts (85%) were treated with imatinib and 2 pts received nilotinib as their initial therapy. The median time to transformation to BP was 19 months (range, 3.5-63). The immunophenotype of blasts was myeloid in 9 (69%), lymphoid in 3 (23%) and mixed lineage in 1 pts (8%). The cytogenetic abnormalities detected by conventional karyotyping at the time of BP included: classic Ph alone in 5 pts, 2 pts each with variant Ph, double Ph and isochromosome 17q and one pt each had inversion 3 and another with cryptic Ph. The median OS was 16 months; 9 pts had died at the time of last follow up. Both CML-CP and CML-BP samples exhibited deficiencies in DNA-mismatch repair and DNA double-strand break repair through mutation signature analyses. The median number of mutations at the time of BP was 374. The most frequently mutated genes detected exclusively during BP included ABL1 and RUNX1 . ABL1 mutation was significantly associated with CML-BP (5/10; p=0.012). Similarly suggests that RUNX1 mutation may be associated with CML-BP (4/10) although not at statistical significance (p=0.14; odds ratio of CML-BP = 6 (95% CI: 0.46 - 359). CAI profiles show that BP samples have increased genomic instability. CAI was frequent at the time of BP. CAI was significantly associated with BP (8/10; p = 0.0019; odds ratio of BP = 30 (95% CI: 2.3 - 1911). Chromosomes 7 and 8 were the most frequently altered chromosomes (each altered in 3/10 BP samples) while 0/3 (0%) AP and 1/8 (12.5%) CP samples had CAI. Gene mutation results are shown in Figure 1.Conclusions: Bypaired exome sequencing of CML patients who received frontline TKI therapy, our analyses suggest that CML-BP is associated with (1) acquisition of additional gene mutations during BP, frequently in ABL1 and RUNX1 and (2) increased chromosomal instability. Defects in DNA mismatch repair and double-strand break repair were identified in all CML phases. This may suggest that these deficient repair processes, evident in the CP phase, are early contributors to the transition to CML-BP. This hypothesis is supported by the increased chromosomal instability observed in the BP samples that may result from these cellular defects. As such, identification of these repair deficiencies may have an early predictive potential in detecting CML patients who can potentially transform to blast phase. We are performing additional studies using targeted NGS and WES in samples that did not undergo BP transformation to substantiate these hypotheses. Further studies are needed to explore the modalities to target these alterations in CML. [Display omitted] DisclosuresKantarjian:Delta-Fly Pharma: Research Funding; Novartis: Research Funding; ARIAD: Research Funding; Amgen: Research Funding; Bristol-Meyers Squibb: Research Funding; Pfizer: Research Funding. Jabbour:Bristol-Myers Squibb: Consultancy. Cortes:Novartis Pharmaceuticals Corporation: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; ImmunoGen: Consultancy, Research Funding; ARIAD: Consultancy, Research Funding; Sun Pharma: Research Funding; BMS: Consultancy, Research Funding; Teva: Research Funding.

Synthesis and characterization of poly(phthalazinone ether ketone ketone) copolymers with 4,4′-dihydroxybiphenyls

Meta-poly(phthalazinone ether ketone ketone) copolymers with 4,4′-dihydroxybiphenyls (meta-PPBEKK) was synthesized with 4,4′-dihydroxybiphenyls (BP), 1,3-bis(4-fluorobenzoyl)benzene (meta-DFKK) and 4-(4-hydroxyphenyl)-2,3-diazaphthalene-1-one (DHPZ). The copolymers are high-temperature resistant and have good solubility in many solvents. With increasing molar ratio of BP to meta-DFKK from 0 to 0.2, the addition of BP improves number-average molecular masses, intrinsic viscosity, mechanical properties and fluidity of meta-PPBEKKs. When the molar ratio of BP to meta-DFKK is 0.2, the intrinsic viscosity reaches 1.14 dL g−1, the number-average molecular mass reaches 44700 g mol−1, the maximum thermal elongation ratio reaches 14 with strength of 127.1 MPa and Young’s modulus of 2.4 GPa. With increasing molar ratio of BP to meta-DFKK from 0 to 0.2, meta-PPBEKKs have improved comprehensive properties, and make sense in many fields.

Abstract 1322: Development and performance of a formalin-damaged multiplexed DNA tumor mutation FFPE reference material

Abstract Tumor profiling often begins with a tissue biopsy that is formalin fixed and paraffin embedded (FFPE), a process that introduces various kinds of damage in the nucleic acids found in the tissue, however FFPE reference materials that closely mimic the damage profile of patient samples are lacking. Depurination, depyrimidination, deamination, oxidation, nicks, and double strand breaks may be found in DNA extracted from FFPE tissue, despite the use of extraction kits that attempt to repair some of this damage. We have developed a formalin-damaged, multiplexed biosynthetic reference material, Seraseq® FFPE Tumor DNA, to mimic this type of damage found in patient samples to create a more patient-like control. Biosynthetic DNA containing 24 cancer variants of interest were pooled in equivalent concentrations and introduced into the GM24385 reference cell line (Coriell) to simulate SNVs, indels, and structural rearrangements. Full length, allele-specific copies of ERBB2, MET, and MYC were also introduced to create copy number amplifications (CNV). Engineered cells were diluted to achieve desired allele frequencies and copy numbers as determined by digital PCR. The cells were processed with a proprietary FFPE protocol that mimics the damage seen in patient samples. Various FFPE extraction kits were used to isolate DNA and the amount of damage was assessed using the KAPA hgDNA Quantification &amp; QC Kit. Allele frequencies and copy numbers were determined by digital PCR, the Archer VariantPlex Solid Tumor assay, and the Illumina TruSight Tumor 170 assay. DNA extractions of the FFPE reference material with the Qiagen QIAamp DNA FFPE Tissue Kit and the Promega Maxwell RSC FFPE DNA Kit yielded similar amounts (&amp;gt;200 ng per curl). All 24 variants were detected close to the 5-10% targeted allele frequency range and CNVs were within 5-10 total copies by dPCR. Similar results were observed with the TST170 assay. The quality as measured by Q120 bp/Q41 bp ratio using the KAPA hgDNA Quantification &amp; QC Kit of the FFPE extracted damaged DNA was reduced by ~33% compared to non-damaged DNA extracted from FFPE, closer to the quality seen for some patient samples while still maintaining good amplifiability in downstream processes. The Seraseq FFPE Tumor DNA Reference Material performs as designed in digital PCR, amplicon-based, and hybrid capture-based NGS assays. It can be used in full process assay development and validation, bioinformatics pipeline optimization, and as a positive control in clinical research. The biosynthetic manufacturing approach allows for multiplexing of customizable variants and adjustable DNA damage. Citation Format: Dana J. Ruminski Lowe, Deepika Philkana, Catherine Huang, Matthew G. Butler, Omoshile Clement, Bharathi Anekella. Development and performance of a formalin-damaged multiplexed DNA tumor mutation FFPE reference material [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1322.

The Impact of Spironolactone on Markers of Myocardial Oxidative Status, Inflammation and Remodeling in Hyperthyroid Rats.

Hyperthyroidism promotes the development and progression of cardiovascular diseases (CVD). Aldosterone, a key mediator of myocardial inflammation, oxidative stress and fibrosis, may be activated in hyperthyroidism. To assess the impact of hyperthyroidism on aldosterone levels and myocardial oxidative status, inflammatory and fibrotic markers in hyperthyroid rats, and to test if the use of spironolactone (an aldosterone antagonist) attenuates these changes. Adult Wistar rats were randomly distributed into 4 groups; controls, spironolactone treated rats (Spir, 50mg/kg/day), hyperthyroid rats (Hyper, daily intraperitoneal levothyroxine 0.3mg/kg/day), and spironolactone treated hyperthyroid rats (Hyper+Spir) for 4 weeks. Blood pressure (Bp), and levels of serum and myocardial aldosterone, oxidants/antioxidants, inflammatory and fibrotic markers were measured. Levothyroxine increased serum thyroid hormones and increased Bp, heart rate and heart to bodyweight ratio. Relative to control, serum aldosterone levels were increased in Hyper and Hyper+ Spir groups. In parallel, cardiac lipid peroxides and serum endothelin-1 were increased whereas cardiac superoxide dismutase, catalase, glutathione, and matrix metalloproteinase -2 were reduced in the Hyper group. Spironolactone decreased serum thyroid hormones and improved cardiac lipid peroxides and metalloproteinase -2 levels. The use of spironolactone decreased serum nitrite levels and increased cardiac SOD and glutathione. Cardiac levels of aldosterone, endothelin-1, transforming growth factor-beta and nitrite were similar among all groups. Hyperthyroid status was associated with an increase in aldosterone and oxidant/ inflammatory biomarkers. The use of spironolactone enhanced antioxidant defenses. Aldosterone antagonists may serve as potential drugs to attenuate the development of cardiac disease in hyperthyroidism.