DNA Sequence Evolution through Integral Value Transformations

In deciphering the DNA structures, evolutions and functions, Cellular Automata (CA) do have a significant role. DNA can be thought of as a one-dimensional multi-state CA, more precisely four states of CA namely A, T, C, and G which can be taken as numerals 0, 1, 2 and 3. Earlier, G.Ch. Sirakoulis et al reported the DNA structure, evolution and function through quaternary logic one dimensional CA and the authors have found the simulation results of DNA evolutions with the help of only four linear CA rules. The DNA sequences which are produced through the CA evolutions, however, are seen by our research team not to exist in the established databases of various genomes although the initial seed (initial global state of CA) was taken from the database. This problem motivated us to study the DNA evolutions from a more fundamental point of view. Parallel to the CA paradigm we have devised an enriched set of discrete transformations which have been named as Integral Value Transformations (IVT). Interestingly, on applying the IVT systematically, we have been able to show that each of the DNA sequences at various discrete time instances in IVT evolutions can be directly mapped to a specific DNA sequence existing in the database. This has been possible through our efforts of getting quantitative mathematical parameters of the DNA sequences involving Fractals. Thus we have at our disposal some transformational mechanism between one DNA to another

Understanding Genomic Evolution of Olfactory Receptors through Fractal and Mathematical Morphology

Fractals and Mathematical Morphology are immensely used to study many problems in different branches of science and technology including the domain of Biology. There are many more unrevealed facts and figures of genes and genome in Computational Biology. In this paper, our objective is to explore how the evolutionary network is associated among Human, Chimpanzee and Mouse with regards to their genomic information. We are about to explore their genomic evolution through the quantitative measures of fractals and morphology. We have considered olfactory receptors for our case study. These olfactory receptors do function in different species with subtle differences in the structures of DNA sequences. Those subtle differences can be exposed through intricate details of Fractals and Mathematical Morphology

Cervical Cancer in Women with Unhealthy Cervix in a Rural Population of a Developing Country

Background: Cervical cancer, the most common malignancy among Indian women, is the second most common and fi fth most fatal cancer in women world-wide.Aim: The study is aimed to determine the risk factors, incidence of cervical malignancy in women with grossly unhealthy cervix in a rural population and to get an overview of eff ectiveness of the existing screening programs.Subjects and Methods: This cross-sectional prospective pilot study was carried in a tertiary care hospital in a span of 6 months. A total of 300 females with grossly unhealthy cervix with suspicions of malignancy, who had never undergone cervical cytology or any other cervical neoplasia screening procedure, were included. Unaided visual inspection with Cusco’s speculum was performed followed by digital examination. Clinical staging was carried out in patients according to International Federation of Gynecology and Obstetrics (FIGO’S) Classifi cation. Cervical punch biopsy was taken under colposcopic guidance and histopathological examinations were done. Data were analyzed using SPSS, version 15.0 (Chicago Illinois, USA) and presented as simple percentages.Results: Among 300 females, 63.4% (190/300) were aged between 40 and 59 years. Nearly, 70.7% were illiterate and 52.6% had monthly family income between Rs. 2,000 and 5,000. Majority was married and 72.7% had parity between 1 and 3 and 58.7% had early marriages. Unaided visual examination of the women showed 62.7% of them had visible growth and 48.7% of them had bleeding erosions. Visible growths along with bleeding erosions were present in 11.3% cases. Histopathological examination of cervical biopsy specimens revealed mild, moderate and severe dysplasia in 14, 22 and 36 cases, respectively. A total of 212 patients had invasive squamous cell carcinoma. Only 16 patients had normal histopathology fi ndings. Nearly, 56.61% had Stage II disease; among them 27 had Stage IIa and 33 had Stage IIb disease, 26 patients had Stage I disease. Stage IIIa and IIIb have been found in 50 and 12 cases respectively. Four cases had cancer extending to urinary bladder and rectum (Stage IVa). Conclusions: Cervical carcinoma not only has a biomedical spectrum, but also has a wide cultural and socio-economic background. Extensive screening campaigns needs to be implemented with immediate eff ect to early diagnose cases to decrease the social burden of the disease.  Keywords: Africa, cervical cancer, screening procedure

Septic Abortion Managed in a Tertiary Hospital in West Bengal

Background: Septic abortion is still a challenging problem and a major cause of maternal mortality and morbidity in developing countries.Aim: The present study was conducted to estimate incidence, causes, risk factors, associated microorganisms, and treatment modalities of cases of septic abortion managed in a tertiary health care in West Bengal.Subjects and Methods: It was a cross‑sectional study carried out in Burdwan Medical College and Hospital in West Bengal between July 2011 and June 2012. On admission a thorough history was taken, examination was done, and investigations were carried. Depending on the examination findings the cases were grouped into three grades‑grade I: The infection localized in the uterus; grade II: The infection spread beyond the uterus to the parametrium, tubes, and ovaries or pelvic peritoneum; grade III: Generalized peritonitis and/or endotoxic shock or jaundice or acute renal failure. Statistical analysis was done by using Epi Info™ software (Version 3.5.1, CDC) after proper arrangement of all the data in tabular form and presented as simple percentage.Results: During the period, 1297 cases of abortion were admitted among which 107 were septic abortions, thus giving the incidence of the latter as 8.2% (107/1297). Forty‑three percent cases of septic abortion (46/107) were in grade I, 21.5% (23/107) in grade II, and 35.5% (38/107) in grade III. The modal age group of the patients was 15‑25 years (49.5%). Majority of the subjects were married (77.6%; 83/107) and multiparous (60.7%; 65/107). Similarly, most of them (71%; 76/107) were from low socioeconomic class. Ninety percent of the patients (96/107) had induced abortion. The common clinical features at presentation were pallor (88.8%; 95/107) and fever (86.0%; 92/107). Escherichia coli (62.6%; 67/107) and Klebsiella pneumonia (32.75%; 35/107) were the most common organism isolated. The case fatality from septic abortion in this study was 13.1% and the condition accounted for 15.4% of total maternal mortality within the period reviewed.Conclusion: The incidence of septic abortion in this study is relatively high, and majority of the cases resulted from attempted termination of pregnancy. It is a significant contributor to maternal mortality. Promotion of family planning and legalization of abortion services will go a long way in reducing the incidence of septic abortion and itsassociated complications. Keywords: Asia, management, maternal mortality, outcome, septic abortio

A Prospective Study of Doppler Velocimetry in Pregnancy-induced Hypertension in a Rural Population of a Developing Country

Background: Pregnancy-induced hypertension (PIH) remains a great challenge to obstetricians. Doppler velocimetry can detect fetal compromise much before other antepartum tests.Aim: The aim of this study is to detect the changes of uterine artery, umbilical artery and middle cerebral artery in PIH by Doppler velocimetry.Subjects and Methods: This prospective study was conducted on hundred subjects with PIH. Doppler studies were carried, and parameters recorded in uterine, umbilical and middle cerebral artery (MCA) were Systolic/Diastolic ratio, Resistance Index, Cerebro Placental Index (CPI). Fetal outcomes were monitored. Statistical analysis was performed using Epi InfoTM software (Version 3.5.1, CDC, Atlanta). Test for significance was done with student’s t-test and Chi-square where applicable. A P- value of<0.05 was considered as significant.Results: Among the 100 subjects, 76 (76%) of fetuses had abnormal and 24% normal umbilical artery Doppler velocimetry; 62% had abnormal and 38% normal MCA Doppler velocimetry; 64% fetuses had abnormal and 36% normal CPI. In 95% of subjects having abnormal umbilical Doppler studies, caesarean section had to be done for acute fetal distress. Incidence of caesarean section was 61% in abnormal MCA group and 63% in abnormal CPI group. Among 14 patients who had abnormal uterine artery Doppler, four developed pre-eclampsia, 2 IUGR. In patients with notches in uterine artery Doppler, 38% developed pre-eclampsia, 38% had IUGR, 13% babies were still born and 25% of newborns required NICU admission. In umbilical artery Doppler, when S/D ratio was abnormal, 60% developed pre-eclampsia, 40% had IUGR and 40% of newborns had to be admitted in NICU.Conclusion: Doppler study for fetal surveillance in pregnancy-induced hypertension is a very useful device and abnormal umbilical artery and uterine artery velocimetry seems to have worse pregnancy outcomes in the present study. Notch as a single parameter is the best indicator with highest sensitivity and positive predicative values. However, combination of parameters is the best indicator.  Keywords: Doppler study, fetomaternal outcome, pregnancy-induced hypertensio

CMOS integration of inkjet-printed graphene for humidity sensing.

We report on the integration of inkjet-printed graphene with a CMOS micro-electro-mechanical-system (MEMS) microhotplate for humidity sensing. The graphene ink is produced via ultrasonic assisted liquid phase exfoliation in isopropyl alcohol (IPA) using polyvinyl pyrrolidone (PVP) polymer as the stabilizer. We formulate inks with different graphene concentrations, which are then deposited through inkjet printing over predefined interdigitated gold electrodes on a CMOS microhotplate. The graphene flakes form a percolating network to render the resultant graphene-PVP thin film conductive, which varies in presence of humidity due to swelling of the hygroscopic PVP host. When the sensors are exposed to relative humidity ranging from 10-80%, we observe significant changes in resistance with increasing sensitivity from the amount of graphene in the inks. Our sensors show excellent repeatability and stability, over a period of several weeks. The location specific deposition of functional graphene ink onto a low cost CMOS platform has the potential for high volume, economic manufacturing and application as a new generation of miniature, low power humidity sensors for the internet of things.S.S. acknowledges Department of Science and Technology (DST), India for Ramanujan Fellowship to support the work (project no. SR/S2/RJN-104/2011). This work was (partly) supported through the EU FP7 project MSP (611887). T.H. acknowledges support from the Royal Academy of Engineering through a fellowship (Graphlex).This is the final version of the article. It was first available from NPG via http://dx.doi.org/10.1038/srep1737

Association between mid-wall late gadolinium enhancement and sudden cardiac death in patients with dilated cardiomyopathy and mild and moderate left ventricular systolic dysfunction

Background—Current guidelines only recommend the use of an implantable cardioverter defibrillator (ICD) in patients with dilated cardiomyopathy (DCM) for the primary prevention of sudden cardiac death (SCD) in those with a left ventricular ejection fraction (LVEF)35%. Patients with a LVEF>35% also have low competing risks of death from non-sudden causes. Therefore, those at high-risk of SCD may gain longevity from successful ICD therapy. We investigated whether late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) identified patients with DCM without severe LV systolic dysfunction at high-risk of SCD. Methods—We prospectively investigated the association between mid-wall late gadolinium enhancement (LGE) and the pre-specified primary composite outcome of SCD or aborted SCD amongst consecutive referrals with DCM and a LVEF≥40% to our center between January 2000 and December 2011, who did not have a pre-existing indication for ICD implantation. Results—Of 399 patients (145 women, median age 50 years, median LVEF 50%, 25.3% with LGE) followed for a median of 4.6 years, 18 of 101 (17.8%) patients with LGE reached the pre-specified end-point, compared to 7 of 298 (2.3%) without (HR 9.2; 95% CI 3.9-21.8; p5% compared to those without LGE were 10.6 (95%CI 3.9-29.4), 4.9 (95% CI 1.3-18.9) and 11.8 (95% CI 4.3-32.3) respectively. Conclusions—Mid-wall LGE identifies a group of patients with DCM and LVEF≥40% at increased risk of SCD and low-risk of non-sudden death who may benefit from ICD implantation

Blockade of insulin-like growth factors increases efficacy of paclitaxel in metastatic breast cancer.

Breast cancer remains the leading cause of cancer death in women owing to metastasis and the development of resistance to established therapies. Macrophages are the most abundant immune cells in the breast tumor microenvironment and can both inhibit and support cancer progression. Thus, gaining a better understanding of how macrophages support cancer could lead to the development of more effective therapies. In this study, we find that breast cancer-associated macrophages express high levels of insulin-like growth factors 1 and 2 (IGFs) and are the main source of IGFs within both primary and metastatic tumors. In total, 75% of breast cancer patients show activation of insulin/IGF-1 receptor signaling and this correlates with increased macrophage infiltration and advanced tumor stage. In patients with invasive breast cancer, activation of Insulin/IGF-1 receptors increased to 87%. Blocking IGF in combination with paclitaxel, a chemotherapeutic agent commonly used to treat breast cancer, showed a significant reduction in tumor cell proliferation and lung metastasis in pre-clinical breast cancer models compared to paclitaxel monotherapy. Our findings provide the rationale for further developing the combination of paclitaxel with IGF blockers for the treatment of invasive breast cancer, and Insulin/IGF1R activation and IGF+ stroma cells as potential biomarker candidates for further evaluation

Styrene maleic acid recovers proteins from mammalian cells and tissues while avoiding significant cell death.

Detection of protein biomarkers is an important tool for medical diagnostics, typically exploiting concentration of particular biomarkers or biomarker release from tissues. We sought to establish whether proteins not normally released by living cells can be extracted without harming cells, with a view to extending this into biomarker harvest for medical diagnosis and other applications. Styrene maleic acid (SMA) is a polymer that extracts nanodiscs of biological membranes (containing membrane proteins) from cells. Hitherto it has been used to harvest SMA-lipid-membrane protein particles (SMALP) for biochemical study, by destroying the living cellular specimen. In this study, we applied SMA at low concentration to human primary cardiovascular cells and rat vascular tissue, to 'biopsy' cell proteins while avoiding significant reductions in cell viability. SMA at 6.25 parts per million harvested proteins from cells and tissues without causing significant release of cytosolic dye (calcein) or reduction in cell viability at 24 and 72 hours post-SMA (MTT assay). A wide range of proteins were recovered (20-200 kDa) and a number identified by mass spectrometry: this confirmed protein recovery from plasma membrane, intracellular membranes and cell cytosol without associated cell death. These data demonstrate the feasibility of non-lethally sampling proteins from cells, greatly extending our sampling capability, which could yield new physiological and/or pathological biomarkers