Emerging evidence for CHFR as a cancer biomarker : from tumor biology to precision medicine

Novel insights in the biology of cancer have switched the paradigm of a "one-size-fits-all" cancer treatment to an individualized biology-driven treatment approach. In recent years, a diversity of biomarkers and targeted therapies has been discovered. Although these examples accentuate the promise of personalized cancer treatment, for most cancers and cancer subgroups no biomarkers and effective targeted therapy are available. The great majority of patients still receive unselected standard therapies with no use of their individual molecular characteristics. Better knowledge about the underlying tumor biology will lead the way toward personalized cancer treatment. In this review, we summarize the evidence for a promising cancer biomarker: checkpoint with forkhead and ring finger domains (CHFR). CHFR is a mitotic checkpoint and tumor suppressor gene, which is inactivated in a diverse group of solid malignancies, mostly by promoter CpG island methylation. CHFR inactivation has shown to be an indicator of poor prognosis and sensitivity to taxane-based chemotherapy. Here we summarize the current knowledge of altered CHFR expression in cancer, the impact on tumor biology and implications for personalized cancer treatment

The prevalence of mild to moderate distress in patients with end stage renal disease:results from a patient survey using the emotion thermometers in four hospital Trusts in the West Midlands, UK

Objectives To assess the prevalence of mild-To-moderate distress in patients with end-stage renal disease (ESRD) and determine the association between distress and patient characteristics. Design Cross-sectional survey using emotion thermometer and distress thermometer problem list. Setting Renal units in four hospital Trusts in the West Midlands, UK. Participants Adult patients with stage 5 chronic kidney disease who were: (1) On prerenal replacement therapy. (2) On dialysis for less than 2 years. (3) On dialysis for 2 years or more (4) With a functioning transplant. Outcomes The prevalence of mild-To-moderate distress, and the incidence of distress thermometer problems and patient support needs. Results In total, 1040/3730 surveys were returned (27.9%). A third of survey respondents met the criteria for mild-To-moderate distress (n=346; 33.3%). Prevalence was highest in patients on dialysis for 2 years or more (n=109/300; 36.3%) and lowest in transplant patients (n=118/404; 29.2%). Prevalence was significantly higher in younger versus older patients (χ 2 =14.33; p=0.0008), in women versus men (χ 2 =6.63; p=0.01) and in black and minority ethnic patients versus patients of white ethnicity (χ 2 =10.36; p=0.013). Over 40% of patients (n=141) reported needing support. More than 95% of patients reported physical problems and 91.9% reported at least one emotional problem. Conclusions Mild-To-moderate distress is common in patients with ESRD, and there may be substantial unmet support needs. Regular screening could help identify patients whose distress may otherwise remain undetected. Further research into differences in distress prevalence over time and at specific transitional points across the renal disease pathway is needed, as is work to determine how best to support patients requiring help.</p

Understanding the Reactivity of Dicalcium Silicate by Density Functional Theory

Ordinary Portland Cement (OPC) is a mixture consisting of various phases. Because of mineralogical complexity, the relationship between chemical reactivity of the mixture and each individual phase is still unanswered question. In this study, computational method based on Density Functional Theory (DFT) was applied to investigate the chemical reactivity of different polymorphs of dicalcium silicate crystals. At first, computationally generated dicalcium silicate crystals were geometrically optimized to achieve targeted convergence criteria for computing the total internal energy, lattice parameters, and atomic arrangement at 0K. The simulations performed explain well the thermodynamic stability as well as the synthesis temperatures of the different polymorphs of dicalcium silicate

Structural basis of functions of the mitochondrial cytochrome bc1 complex

AbstractThe crystal structure of the cytochrome bc1 complex (ubiquinol-cytochrome c reductase) from bovine heart submitochondria was determined at 2.9 Å resolution. The bc1 complex in crystal exists as a closely interacting dimer, suggesting that the dimer is a functional unit. Over half of the mass of the complex, including subunits core 1 and core 2, are on the matrix side of the membrane, while most of the cytochrome b subunit is located within the membrane. There are 13 transmembrane helices in each monomer, eight of them belonging to cytochrome b. Two large cavities are made of the transmembrane helices D, C, F and H in one monomer and helices D′ and E′ from the other monomer of cytochrome b, and the transmembrane helices of c1, iron-sulfur protein (ISP), and subunits 10 and 11. These cavities provide entrances for ubiquinone or inhibitor and connect the Qi pocket of one monomer and the Qo pocket of the other monomer. Ubiquinol made at the Qi site of one monomer can proceed to the nearby Qo site of the other monomer without having to leave the bc1 complex. The soluble parts of cytochrome c1 and ISP, including their redox prosthetic groups, are located on the cytoplasmic side of the membrane. The distances between the four redox centers in the complex have been determined, and the binding sites for several electron transfer inhibitors have been located. Structural analysis of the protein/inhibitor complexes revealed that the extramembrane domain of the Rieske iron-sulfur protein may undergo substantial movement during the catalytic cycle of the complex. The Rieske protein movement and the larger than expected distance between FeS and cytochrome c1 heme suggest that electron transfer reaction between FeS and cytochrome c1 may involve movements or conformational changes in the soluble domain of iron-sulfur protein. The inhibitory function of E-β-methoxyacrylate-stilbene and myxothiazol may result from the increase of mobility in ISP, whereas the function of stigmatellin and 5-undecyl-6-hydroxy-4,7-dioxobenzothiazole may result from the immobilization of ISP

Age- and gender-based comorbidity categories in general practitioner and pulmonology patients with COPD

Chronic obstructive pulmonary disease (COPD) is a debilitating medical condition often accompanied by multiple chronic conditions. COPD is more frequent among older adults and affects both genders. The aim of the current cross-sectional survey was to characterize chronic comorbidities stratified by gender and age among patients with COPD under the care of general practitioners (GP) and pulmonologists, using real-world patient data. A total of 7966 COPD patients (women: 45%) with more than 5 years of the observation period in the practice were examined using 60 different Chronic comorbid conditions (CCC) and Elixhauser measures. More than 9 in 10 patients had at least one, and 51.7% had more than three comorbidities. No gender difference was found in the number of comorbidities. However, men had higher Elixhauser-van Walraven index scores than women, and the types of comorbidities differed by gender. An increasing number of comorbidities was seen with aging but the patients in their 30s and 40s also had a high number of comorbidities. Moreover, GP patients had a higher number and a wider array of documented comorbidities than pulmonology patients did. Psychological comorbidities were common in all patients, but particularly among younger patients. These findings around gender- and age-stratified comorbidities under the care of GPs and pulmonologists have implications for the choice of data provenience for decision-making analysis and treatment selection and success

Efficient Arithmetic on ARM-NEON and Its Application for High-Speed RSA Implementation

Advanced modern processors support Single Instruction Multiple Data (SIMD) instructions (e.g. Intel-AVX, ARM-NEON) and a massive body of research on vector-parallel implementations of modular arithmetic, which are crucial components for modern public-key cryptography ranging from RSA, ElGamal, DSA and ECC, have been conducted. In this paper, we introduce a novel Double Operand Scanning (DOS) method to speed-up multi-precision squaring with non-redundant representations on SIMD architecture. The DOS technique partly doubles the operands and computes the squaring operation without Read-After-Write (RAW) dependencies between source and destination variables. Furthermore, we presented Karatsuba Cascade Operand Scanning (KCOS) multiplication and Karatsuba Double Operand Scanning (KDOS) squaring by adopting additive and subtractive Karatsuba\u27s methods, respectively. The proposed multiplication and squaring methods are compatible with separated Montgomery algorithms and these are highly efficient for RSA crypto system. Finally, our proposed multiplication/squaring, separated Montgomery multiplication/squaring and RSA encryption outperform the best-known results by 22/41\%, 25/33\% and 30\% on the Cortex-A15 platform

Efficient Ring-LWE Encryption on 8-bit AVR Processors

Public-key cryptography based on the ``ring-variant\u27\u27 of the Learning with Errors (ring-LWE) problem is both efficient and believed to remain secure in a post-quantum world. In this paper, we introduce a carefully-optimized implementation of a ring-LWE encryption scheme for 8-bit AVR processors like the ATxmega128. Our research contributions include several optimizations for the Number Theoretic Transform (NTT) used for polynomial multiplication. More concretely, we describe the Move-and-Add (MA) and the Shift-Add-Multiply-Subtract-Subtract (SAMS2) technique to speed up the performance-critical multiplication and modular reduction of coefficients, respectively. We take advantage of incompletely-reduced intermediate results to minimize the total number of reduction operations and use a special coefficient-storage method to decrease the RAM footprint of NTT multiplications. In addition, we propose a byte-wise scanning strategy to improve the performance of a discrete Gaussian sampler based on the Knuth-Yao random walk algorithm. For medium-term security, our ring-LWE implementation needs 590k, 672k, and 276k clock cycles for key-generation, encryption, and decryption, respectively. On the other hand, for long-term security, the execution time of key-generation, encryption, and decryption amount to 2.2M, 2.6M, and 686k cycles, respectively. These results set new speed records for ring-LWE encryption on an 8-bit processor and outperform related RSA and ECC implementations by an order of magnitude