A comparison between the time-domain and the frequency-domain diakoptic methods of solving field problems by transmission-line modelling

The nature and significance of time-domain approximations needed for a diakoptic solution using transmission-line modelling (TLM) are examined. Truncation, filtering and repeated convolution of time responses result in severe restrictions in the accuracy of time-domain diakoptics. The frequency-domain diakoptic method has several advantages, including speed and simplicity, and warrants further study.     

THZ531 Induces a State of BRCAness in Multiple Myeloma Cells: Synthetic Lethality with Combination Treatment of THZ 531 with DNA Repair Inhibitors

Multiple myeloma (MM) is a hematological disease marked by abnormal growth of B cells in bone marrow. Inherent chromosomal instability and DNA damage are major hallmarks of MM, which implicates an aberrant DNA repair mechanism. Studies have implicated a role for CDK12 in the control of expression of DNA damage response genes. In this study, we examined the effect of a small molecule inhibitor of CDK12–THZ531 on MM cells. Treatment of MM cells with THZ531 led to heightened cell death accompanied by an extensive effect on gene expression changes. In particular, we observed downregulation of genes involved in DNA repair pathways. With this insight, we extended our study to identify synthetic lethal mechanisms that could be exploited for the treatment of MM cells. Combination of THZ531 with either DNA-PK inhibitor (KU-0060648) or PARP inhibitor (Olaparib) led to synergistic cell death. In addition, combination treatment of THZ531 with Olaparib significantly reduced tumor burden in animal models. Our findings suggest that using a CDK12 inhibitor in combination with other DNA repair inhibitors may establish an effective therapeutic regimen to benefit myeloma patients.     

Histamine H4 Receptor Agonism Induces Antitumor Effects in Human T-Cell Lymphoma

The discovery of the human histamine H4 receptor (H4R) has contributed to our understanding of the role of histamine in numerous physiological and pathological conditions, including tumor development and progression. The lymph nodes of patients with malignant lymphomas have shown to contain high levels of histamine, however, less is known regarding the expression and function of the H4R in T-cell lymphoma (TCL). In this work we demonstrate the expression of H4R isoforms (mRNA and protein) in three human aggressive TCL (OCI-Ly12, Karpas 299, and HuT78). Histamine and specific H4R agonists (VUF8430 and JNJ28610244) significantly reduced cell viability in a dose-dependent manner (p < 0.05). The combined treatment with the H4R antagonist (JNJ7777120, 10 µM) reversed the effects of the H4R ligands. Importantly, we screened a drug repurposing library of 433 FDA-approved compounds (1 μM) in combination with histamine (10 μM) in Hut78 cells. Histamine produced a favorable antitumor effect with 18 of these compounds, including the histone deacetylase inhibitor panobinostat. Apoptosis, proliferation, and oxidative stress studies confirmed the antitumoral effects of the combination. We conclude that the H4R is expressed in TCL, and it is involved in histamine-mediated responses.     

Microbial and chemical assessment of regions within New Orleans, LA impacted by Hurricane Katrina

The city of New Orleans, LA was severely impacted by flooding and wind damage following landfall of Hurricane Katrina in August 2005. The city's drinking water infrastructure was severely compromised and massive amounts of sediment were redeposited throughout the flooded region. Thousands of homes were water-damaged resulting in the rapid growth of mold. In September and October 2005 a convenience sample of selected homes, tap water, surface water, and sediment within New Orleans was assessed for mold contamination, microbial contamination, and heavy metal concentrations. At selected sites, indoor mold spore concentrations were compared to outdoor concentrations. The purpose of this study was to conduct a baseline environmental assessment in an effort to identify public health threats caused by wind and flood damage. Surface waters contained high concentrations of bacterial indicators whereas no bacteria were detected in tap water, even from taps containing no chlorine residual. Sediment samples contained concentrations of lead and arsenic similarto pre-Katrina concentrations. Outdoor total spore (sp) concentrations ranged from >6500 to 84 713 sp/m(3). Indoor concentrations ranged from 6142 to 735 123 sp/m(3). For the 13 locations with matched indoor/ outdoor samples, the mean indoor/outdoor spore ratio was 4.11 (ranging from 0.27 to >11.44). Inside 5 of the 13 homes, total spore counts/m(3) exceeded 100 000, with measurements in the moldiest home exceeding 700 000 sp/ m(3). In conclusion, surface waters had high concentrations of bacterial contamination but no bacterial indicators were present in tap water. Sediment samples did not have appreciable increases in lead or arsenic. Flooded homes, however, contained substantial concentrations of mold which could present a public health exposure route to individuals repopulating and restoring the City of New Orleans.     

Novel probiotic-fermented milk with angiotensin I-converting enzyme inhibitory peptides produced by Bifidobacterium bifidum MF 20/5

In previous research, we have demonstrated that Bifidobacterium bifidum MF 20/5 fermented milk possessed stronger angiotensin converting enzyme (ACE) inhibitory activity than other lactic acid bacteria, including Lactobacillus helveticus DSM 13137, which produces the hypotensive casokinins Ile-Pro-Pro (IPP) and Val-Pro-Pro (VPP). The aim of this study is to investigate the ACE-inhibitory peptides released in B. bifidum MF 20/5 fermented milk. The novel ACE-inhibitory peptide LVYPFP (IC₅₀ = 132 μM) is reported here for the first time. Additionally, other bioactive peptides such as the ACE-inhibitor LPLP (IC₅₀ = 703 μM), and the antioxidant VLPVPQK were identified. Moreover, the peptide and amino acid profiles, the ACE-inhibitory activity (ACEi), pH, and degree of hydrolysis of the fermented milk were determined and compared with those obtained in milk fermented by L. helveticus DSM 13137. The sequences of the major bioactive peptides present in fermented milk of B. bifidum and L. helveticus were identified and quantified. B. bifidum released a larger amount of peptides than L. helveticus but no IPP or VPP were detected in B. bifidum fermented milk. Also the lactotripeptide concentrations and ACEi were higher in L. helveticus fermented milk when the pH was maintained at 4.6. This may represent a technical advantage for B. bifidum that reduces the pH at a slow enough rate to facilitate the peptide generation without the need for pH control. Thus these findings show the potential for the use of this probiotic strain to produce fermented milk with a wider range of health benefits including reduction of blood pressure.     

Terephthalic acid synthesis at higher concentrations in high‐temperature liquid water. 2. Eliminating undesired byproducts

We synthesized terephthalic acid (TPA) from p‐xylene at an initial concentration above its solubility limit in high‐temperature liquid water (HTW). The nominal p‐xylene loading at the reaction conditions was 0.4 mol L^?1, which is the highest reported to date for generation of high TPA yields (>70 mol %) in HTW. The presence of two liquid phases during the reaction did not appear to accelerate the rate, unlike behavior reported for some other organic reactions done “on water” at lower temperatures. Adding oxygen gas in a large increment during synthesis produced a black liquid and a black solid byproduct, which is a previously undocumented problem. Adding oxygen in smaller increments prevented formation of the liquid and solid byproducts and also provided high selectivities (90 mol %) and yields (>70 mol %) of TPA. These results demonstrate the feasibility of HTW as a medium for TPA synthesis at p‐xylene concentrations even higher than its solubility limit. © 2009 American Institute of Chemical Engineers AIChE J, 2009     

Characterization of products from fast and isothermal hydrothermal liquefaction of microalgae

We investigated nonisothermal (fast) and nominally isothermal hydrothermal liquefaction (HTL) of Nannochloropsis sp. microalgae for the production of biocrude. Biocrude yields ranged from 36 to 45 wt % (dry weight), with fast HTL with low mass loading giving the highest yield. This condition also gave the biocrude with the lowest heating value, which indicates there are compromises to be made between biocrude quantity and quality. The aqueous phase and biocrude product fractions were characterized using elemental analysis and Fourier transform ion cyclotron resonance mass spectrometry (FT‐ICR MS). This detailed level of analysis identified more than 30,000 unique molecular products. The aqueous phase products included compounds with the same molecular formulae as known herbicides, which may inform efforts in genetic engineering of algae and/or bacteria for cultivation on the aqueous phase. This detailed molecular‐level characterization provides some clues regarding the types of reactions that may take place during HTL. © 2016 American Institute of Chemical Engineers AIChE J, 62: 815–828, 2016     

The effect of dietary supplementation with eicosapentaenoic acid on the phospholipid and fatty acid composition of erythrocytes of marmoset

Adult male marmoset monkeys were fed eicosapentaenoic acid (20∶5n−3) as the ethyl ester in diets containing either 32% (reference diet, no added cholesterol) or 7% (atherogenic diet with 0.2% added cholesterol) linoleic acid (18∶2n−6) for 30 wk. No changes were seen in the level of phosphatidylcholine (PC) or phosphatidylethanolamine (PE) but minor changes were observed in both the sphingomyelin (SPM) and phosphatidylinositol plus phosphatidylserine (PI+PS) fractions of erythrocyte lipids. The extent of total n−3 fatty acid incorporation into membrane lipids was higher in atherogenic diets (polyunsaturated/monounsaturated/saturated (P/M/S) ratio 0.2∶0.6∶1.0) than reference diets (P/M/S ratio 1∶1∶1) and this was true for both PE (33.4±1.0%vs 24.3±1.1%) and PC (9.3±0.5%vs 4.9±0.3%). Although suitable controls for cholesterol effects were not included in the study, earlier results obtained with marmosets lead us to believe such effects were probably small. Regardless of basic diet (atherogenic, reference), 20∶5n−3 was preferentially incorporated into PE (10.8±0.2%, 6.0±0.02%) while smaller amounts were incorporated into PC (6.9±0.4%, 3.2±0.2%). The major n−3 polyunsaturated fatty acid found in PE in response to dietary 20∶5n−3 was the elongation metabolite 22∶5n−3 in both the atherogenic (17.7±0.7%) and reference (14.3±1.0%) dietary groups; 22∶6n−3 levels were less affected by diet (4.7±0.3% and 3.9±0.2%, respectively). The results can be interpreted to indicate an inverse relationship between the amount of dietary 18∶2n−6 and incorporation of 20∶5n−3 into erythrocyte membrane phospholipids regardless of whether the major dietary n−3 fatty acid was α-linolenate (18∶3n−3) or 20∶5n−3. This interpretation is supported by theoretical calculations.