Showing papers by "Rajesh Kumar published in 2013"

TERT Promoter Mutations in Familial and Sporadic Melanoma

Abstract: Cutaneous melanoma occurs in both familial and sporadic forms. We investigated a melanoma-prone family through linkage analysis and high-throughput sequencing and identified a disease-segregating germline mutation in the promoter of the telomerase reverse transcriptase (TERT) gene, which encodes the catalytic subunit of telomerase. The mutation creates a new binding motif for Ets transcription factors and ternary complex factors (TCFs) near the transcription start and, in reporter gene assays, caused up to twofold increase in transcription. We then screened the TERT promoter in sporadic melanoma and observed recurrent ultraviolet signature somatic mutations in 125 of 168 (74%) of human cell lines derived from metastatic melanomas, 45 of 53 corresponding metastatic tumor tissues (85%), and 25 of 77 (33%) primary melanomas. The majority of those mutations occurred at two positions in the TERT promoter and also generated binding motifs for Ets/TCF transcription factors.

In Silico Approach for Predicting Toxicity of Peptides and Proteins

Abstract: Background: Over the past few decades, scientific research has been focused on developing peptide/protein-based therapies to treat various diseases. With the several advantages over small molecules, including high specificity, high penetration, ease of manufacturing, peptides have emerged as promising therapeutic molecules against many diseases. However, one of the bottlenecks in peptide/protein-based therapy is their toxicity. Therefore, in the present study, we developed in silico models for predicting toxicity of peptides and proteins. Description: We obtained toxic peptides having 35 or fewer residues from various databases for developing prediction models. Non-toxic or random peptides were obtained from SwissProt and TrEMBL. It was observed that certain residues like Cys, His, Asn, and Pro are abundant as well as preferred at various positions in toxic peptides. We developed models based on machine learning technique and quantitative matrix using various properties of peptides for predicting toxicity of peptides. The performance of dipeptide-based model in terms of accuracy was 94.50% with MCC 0.88. In addition, various motifs were extracted from the toxic peptides and this information was combined with dipeptide-based model for developing a hybrid model. In order to evaluate the over-optimization of the best model based on dipeptide composition, we evaluated its performance on independent datasets and achieved accuracy around 90%. Based on above study, a web server, ToxinPred has been developed, which would be helpful in predicting (i) toxicity or non-toxicity of peptides, (ii) minimum mutations in peptides for increasing or decreasing their toxicity, and (iii) toxic regions in proteins. Conclusion: ToxinPred is a unique in silico method of its kind, which will be useful in predicting toxicity of peptides/ proteins. In addition, it will be useful in designing least toxic peptides and discovering toxic regions in proteins. We hope that the development of ToxinPred will provide momentum to peptide/protein-based drug discovery (http://crdd.osdd.net/ raghava/toxinpred/).

Enhanced sensitivity of the LIGO gravitational wave detector by using squeezed states of light

Abstract: Nearly a century after Einstein first predicted the existence of gravitational waves, a global network of Earth-based gravitational wave observatories1, 2, 3, 4 is seeking to directly detect this faint radiation using precision laser interferometry. Photon shot noise, due to the quantum nature of light, imposes a fundamental limit on the attometre-level sensitivity of the kilometre-scale Michelson interferometers deployed for this task. Here, we inject squeezed states to improve the performance of one of the detectors of the Laser Interferometer Gravitational-Wave Observatory (LIGO) beyond the quantum noise limit, most notably in the frequency region down to 150 Hz, critically important for several astrophysical sources, with no deterioration of performance observed at any frequency. With the injection of squeezed states, this LIGO detector demonstrated the best broadband sensitivity to gravitational waves ever achieved, with important implications for observing the gravitational-wave Universe with unprecedented sensitivity.

Prospects for Observing and Localizing Gravitational-Wave Transients with Advanced LIGO, Advanced Virgo and KAGRA

Abstract: We present our current best estimate of the plausible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next several years, with the intention of providing information to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals for the third (O3), fourth (O4) and fifth observing (O5) runs, including the planned upgrades of the Advanced LIGO and Advanced Virgo detectors. We study the capability of the network to determine the sky location of the source for gravitational-wave signals from the inspiral of binary systems of compact objects, that is BNS, NSBH, and BBH systems. The ability to localize the sources is given as a sky-area probability, luminosity distance, and comoving volume. The median sky localization area (90\% credible region) is expected to be a few hundreds of square degrees for all types of binary systems during O3 with the Advanced LIGO and Virgo (HLV) network. The median sky localization area will improve to a few tens of square degrees during O4 with the Advanced LIGO, Virgo, and KAGRA (HLVK) network. We evaluate sensitivity and localization expectations for unmodeled signal searches, including the search for intermediate mass black hole binary mergers.

Role of plant hormones and their interplay in development and ripening of fleshy fruits

Abstract: Plant hormones have been extensively studied for their roles in the regulation of various aspects of plant development. However, in the last decade important new insights have been made into their action during development and ripening, in both dry and fleshy fruits. Emerging evidence suggests that relative functions of plant hormones are not restricted to a particular stage, and a complex network of more than one plant hormone is involved in controlling various aspects of fruit development. Though some areas are extensively covered, considerable gaps in our knowledge and understanding still exist in the control of hormonal networks and crosstalk between different hormones during fruit expansion, maturation, and various other aspects of ripening. Here, we evaluate the new knowledge on their relative roles during tomato fruit development with a view to understand their mechanism of action in fleshy fruits. For a better understanding, pertinent evidences available on hormonal crosstalk during fruit development in other species are also discussed. We envisage that such detailed knowledge will help design new strategies for effective manipulation of fruit ripening.

TERT promoter mutations in bladder cancer affect patient survival and disease recurrence through modification by a common polymorphism

Abstract: The telomerase reverse transcriptase (TERT) promoter, an important element of telomerase expression, has emerged as a target of cancer-specific mutations. Originally described in melanoma, the mutations in TERT promoter have been shown to be common in certain other tumor types that include glioblastoma, hepatocellular carcinoma, and bladder cancer. To fully define the occurrence and effect of the TERT promoter mutations, we investigated tumors from a well-characterized series of 327 patients with urothelial cell carcinoma of bladder. The somatic mutations, mainly at positions -124 and -146 bp from ATG start site that create binding motifs for E-twenty six/ternary complex factors (Ets/TCF), affected 65.4% of the tumors, with even distribution across different stages and grades. Our data showed that a common polymorphism rs2853669, within a preexisting Ets2 binding site in the TERT promoter, acts as a modifier of the effect of the mutations on survival and tumor recurrence. The patients with the mutations showed poor survival in the absence [hazard ratio (HR) 2.19, 95% confidence interval (CI) 1.02-4.70] but not in the presence (HR 0.42, 95% CI 0.18-1.01) of the variant allele of the polymorphism. The mutations in the absence of the variant allele were highly associated with the disease recurrence in patients with Tis, Ta, and T1 tumors (HR 1.85, 95% CI 1.11-3.08). The TERT promoter mutations are the most common somatic lesions in bladder cancer with clinical implications. The association of the mutations with patient survival and disease recurrence, subject to modification by a common polymorphism, can be a unique putative marker with individualized prognostic potential.

In silico approaches for designing highly effective cell penetrating peptides

Abstract: Background: Cell penetrating peptides have gained much recognition as a versatile transport vehicle for the intracellular delivery of wide range of cargoes (i.e. oligonucelotides, small molecules, proteins, etc.), that otherwise lack bioavailability, thus offering great potential as future therapeutics. Keeping in mind the therapeutic importance of these peptides, we have developed in silico methods for the prediction of cell penetrating peptides, which can be used for rapid screening of such peptides prior to their synthesis. Methods: In the present study, support vector machine (SVM)-based models have been developed for predicting and designing highly effective cell penetrating peptides. Various features like amino acid composition, dipeptide composition, binary profile of patterns, and physicochemical properties have been used as input features. The main dataset used in this study consists of 708 peptides. In addition, we have identified various motifs in cell penetrating peptides, and used these motifs for developing a hybrid prediction model. Performance of our method was evaluated on an independent dataset and also compared with that of the existing methods. Results: In cell penetrating peptides, certain residues (e.g. Arg, Lys, Pro, Trp, Leu, and Ala) are preferred at specific locations. Thus, it was possible to discriminate cell-penetrating peptides from non-cell penetrating peptides based on amino acid composition. All models were evaluated using five-fold cross-validation technique. We have achieved a maximum accuracy of 97.40% using the hybrid model that combines motif information and binary profile of the peptides. On independent dataset, we achieved maximum accuracy of 81.31% with MCC of 0.63. Conclusion: The present study demonstrates that features like amino acid composition, binary profile of patterns and motifs, can be used to train an SVM classifier that can predict cell penetrating peptides with higher accuracy. The hybrid model described in this study achieved more accuracy than the previous methods and thus may complement the existing methods. Based on the above study, a user- friendly web server CellPPD has been developed to help the biologists, where a user can predict and design CPPs with much ease. CellPPD web server is freely accessible at http://crdd.osdd.net/raghava/cellppd/.

In Silico Models for Designing and Discovering Novel Anticancer Peptides

Abstract: Bioinformatics Centre, CSIR-Institute of Microbial Technology, Chandigarh-160036, India. Use of therapeutic peptides in cancer therapy has been receiving considerable attention in the recent years. Present study describes the development of computational models for predicting and discovering novel anticancer peptides. Preliminary analysis revealed that Cys, Gly, Ile, Lys, and Trp are dominated at various positions in anticancer peptides. Support vector machine models were developed using amino acid composition and binary profiles as input features on main dataset that contains experimentally validated anticancer peptides and random peptides derived from SwissProt database. In addition, models were developed on alternate dataset that contains antimicrobial peptides instead of random peptides. Binary profiles-based model achieved maximum accuracy 91.44% with MCC 0.83. We have developed a webserver, which would be helpful in: (i) predicting minimum mutations required for improving anticancer potency; (ii) virtual screening of peptides for discovering novel anticancer peptides, and (iii) scanning natural proteins for identification of anticancer peptides (http://crdd.osdd.net/raghava/anticp/).

Parameter estimation for compact binary coalescence signals with the first generation gravitational-wave detector network

Abstract: Compact binary systems with neutron stars or black holes are one of the most promising sources for ground-based gravitational-wave detectors. Gravitational radiation encodes rich information about source physics; thus parameter estimation and model selection are crucial analysis steps for any detection candidate events. Detailed models of the anticipated waveforms enable inference on several parameters, such as component masses, spins, sky location and distance, that are essential for new astrophysical studies of these sources. However, accurate measurements of these parameters and discrimination of models describing the underlying physics are complicated by artifacts in the data, uncertainties in the waveform models and in the calibration of the detectors. Here we report such measurements on a selection of simulated signals added either in hardware or software to the data collected by the two LIGO instruments and the Virgo detector during their most recent joint science run, including a "blind injection'' where the signal was not initially revealed to the collaboration. We exemplify the ability to extract information about the source physics on signals that cover the neutron-star and black-hole binary parameter space over the component mass range 1M(circle dot)-25M(circle dot) and the full range of spin parameters. The cases reported in this study provide a snapshot of the status of parameter estimation in preparation for the operation of advanced detectors.

Sirtuin1: A Promising Serum Protein Marker for Early Detection of Alzheimer’s Disease

Abstract: Sirtuin (SIRT) pathway has a crucial role in Alzheimer’s disease (AD). The present study evaluated the alterations in serum sirtuin1 (SIRT1) concentration in healthy individuals (young and old) and patients with AD and mild cognitive impairment (MCI). Blood samples were collected from 40 AD and 9 MCI patients as cases and 22 young healthy adults and 22 healthy elderly individuals as controls. Serum SIRT1 was estimated by Surface Plasmon Resonance (SPR), Western Blot and Enzyme Linked Immunosorbent Assay (ELISA). A significant (p<0.0001) decline in SIRT1 concentration was observed in patients with AD (2.27±0.46 ng/µl) and MCI (3.64±0.15 ng/µl) compared to healthy elderly individuals (4.82±0.4 ng/µl). The serum SIRT1 concentration in healthy elderly was also significantly lower (p<0.0001) compared to young healthy controls (8.16±0.87 ng/µl). This study, first of its kind, has demonstrated, decline in serum concentration of SIRT1 in healthy individuals as they age. In patients with AD and MCI the decline was even more pronounced, which provides an opportunity to develop this protein as a predictive marker of AD in early stages with suitable cut off values.

Search for gravitational waves from binary black hole inspiral, merger and ringdown in LIGO-Virgo Data from 2009-2010

Abstract: We report a search for gravitational waves from the inspiral, merger and ringdown of binary black holes (BBH) with total mass between 25 and 100 solar masses, in data taken at the LIGO and Virgo observatories between July 7, 2009 and October 20, 2010. The maximum sensitive distance of the detectors over this period for a (20, 20)M-circle dot coalescence was 300 Mpc. No gravitational wave signals were found. We thus report upper limits on the astrophysical coalescence rates of BBH as a function of the component masses for nonspinning components, and also evaluate the dependence of the search sensitivity on component spins aligned with the orbital angular momentum. We find an upper limit at 90% confidence on the coalescence rate of BBH with nonspinning components of mass between 19 and 28M(circle dot) of 3:3 x 10(-7) mergers Mpc(-3) yr(-1).

CancerDR: Cancer Drug Resistance Database

Abstract: Cancer therapies are limited by the development of drug resistance, and mutations in drug targets is one of the main reasons for developing acquired resistance. The adequate knowledge of these mutations in drug targets would help to design effective personalized therapies. Keeping this in mind, we have developed a database "CancerDR", which provides information of 148 anti-cancer drugs, and their pharmacological profiling across 952 cancer cell lines. CancerDR provides comprehensive information about each drug target that includes; (i) sequence of natural variants, (ii) mutations, (iii) tertiary structure, and (iv) alignment profile of mutants/variants. A number of web-based tools have been integrated in CancerDR. This database will be very useful for identification of genetic alterations in genes encoding drug targets, and in turn the residues responsible for drug resistance. CancerDR allows user to identify promiscuous drug molecules that can kill wide range of cancer cells. CancerDR is freely accessible at http://crdd.osdd.net/raghava/cancerdr/

Einstein@Home all-sky search for periodic gravitational waves in LIGO S5 data

Abstract: This paper presents results of an all-sky search for periodic gravitational waves in the frequency range [50, 1190] Hz and with frequency derivative range of similar to[-20, 1.1] x 10(-10) Hz s(-1) for the fifth LIGO science run (S5). The search uses a noncoherent Hough-transform method to combine the information from coherent searches on time scales of about one day. Because these searches are very computationally intensive, they have been carried out with the Einstein@Home volunteer distributed computing project. Postprocessing identifies eight candidate signals; deeper follow-up studies rule them out. Hence, since no gravitational wave signals have been found, we report upper limits on the intrinsic gravitational wave strain amplitude h(0). For example, in the 0.5 Hz-wide band at 152.5 Hz, we can exclude the presence of signals with h(0) greater than 7.6 x 10(-25) at a 90% confidence level. This search is about a factor 3 more sensitive than the previous Einstein@Home search of early S5 LIGO data.

Somatic mutations in exocrine pancreatic tumors: association with patient survival.

Abstract: KRAS mutations are major factors involved in initiation and maintenance of pancreatic tumors. The impact of different mutations on patient survival has not been clearly defined. We screened tumors from 171 pancreatic cancer patients for mutations in KRAS and CDKN2A genes. Mutations in KRAS were detected in 134 tumors, with 131 in codon 12 and only 3 in codon 61. The GGT>GAT (G12D) was the most frequent mutation and was present in 60% (80/134). Deletions and mutations in CDKN2A were detected in 43 tumors. Analysis showed that KRAS mutations were associated with reduced patient survival in both malignant exocrine and ductal adenocarcinomas (PDAC). Patients with PDACs that had KRAS mutations showed a median survival of 17 months compared to 30 months for those without mutations (log-rank P = 0.07) with a multivariate hazard ratio (HR) of 2.19 (95% CI 1.09-4.42). The patients with G12D mutation showed a median survival of 16 months (log-rank-test P = 0.03) and an associated multivariate HR 2.42 (95% CI 1.14-2.67). Although, the association of survival in PDAC patients with CDKN2A aberrations in tumors was not statistically significant, the sub-group of patients with concomitant KRAS mutations and CDKN2A alterations in tumors were associated with a median survival of 13.5 months compared to 22 months without mutation (log-rank-test P = 0.02) and a corresponding HR of 3.07 (95% CI 1.33-7.10). Our results are indicative of an association between mutational status and survival in PDAC patients, which if confirmed in subsequent studies can have potential clinical application. (Less)

18F-FDOPA PET/CT for detection of recurrence in patients with glioma: prospective comparison with 18F-FDG PET/CT.

Abstract: Differentiation between recurrence and radiation necrosis in patients with glioma is crucial, since the two entities have completely different management and prognosis. The purpose of the present study was to compare the efficacies of 18F-FDG PET/CT and 3,4-dihydroxy-6-[18F]fluoro-phenylalanine (18F-FDOPA) PET/CT in detection of recurrent gliomas. A total of 28 patients (age 38.82 ± 1.25 years; 85.7 % men) with histopathologically proven glioma with clinical/imaging suspicion of recurrence were evaluated using 18F-FDG PET/CT and 18F-FDOPA PET/CT. 18F-FDG PET/CT and 18F-FDOPA PET/CT images were evaluated qualitatively and semiquantitatively. The combination of clinical follow-up, repeat imaging and/or biopsy (when available) was taken as the reference standard. Based on the reference standard, 21 patients were positive and 7 were negative for tumour recurrence. The sensitivity, specificity and accuracy of 18F-FDG PET/CT were 47.6 %, 100 % and 60.7 %, respectively, and those of 18F-FDOPA PET/CT were 100 %, 85.7 % and 96.4 %, respectively. The results of 18F-FDG PET/CT and 18F-FDOPA PET/CT were concordant in 57.1 % of patients (16 of 28) and discordant in 42.9 % (12 of 28). The difference in the findings between 18F-FDG PET/CT and 18F-FDOPA PET/CT was significant (P = 0.0005, McNemar’s test). The difference was significant for low-grade tumours (P = 0.0039) but not for high-grade tumours (P = 0.250). 18F-FDOPA PET/CT is highly sensitive and specific for detection of recurrence in glioma patients. It is superior to 18F-FDG PET/CT for this purpose and is especially advantageous in patients with low-grade gliomas.

Diuretic 18F-FDG PET/CT imaging for detection and locoregional staging of urinary bladder cancer: prospective evaluation of a novel technique.

Abstract: Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (FDG) has been used with limited success in the past in primary diagnosis and locoregional staging of urinary bladder cancer, mainly because of the pharmacokinetics of renal excretion of 18F-FDG. In the present prospective study, we have evaluated the potential application of diuretic 18F-FDG PET/CT in improving detection and locoregional staging of urinary bladder tumours. Twenty-five patients suspected of having primary carcinoma of the urinary bladder were evaluated prospectively for diagnosis and staging. All of these 25 patients underwent conventional contrast-enhanced computed tomography (CECT) of the abdomen/pelvis and whole-body diuretic 18F-FDG PET/CT. In addition, pelvic PET/CT images were obtained using the special technique of forced diuresis using intravenous furosemide (20–40 mg). Of the 25 patients, 10 underwent radical cystectomy and 15 underwent transurethral resection of the bladder tumour (TURBT). Results of CECT and diuretic 18F-FDG PET/CT were compared considering histopathology as a reference standard. Of the 25 patients, CECT detected a primary tumour in 23 (sensitivity 92 %), while 18F-FDG PET/CT was positive in 24 patients (sensitivity 96 %). Mean size and maximum standardized uptake value of the bladder tumours were 3.33 cm (range 1.6–6.2) and 5.3 (range 1.3–11.7), respectively. Of the 25 patients, only 10 patients underwent radical cystectomy based on disease status on TURBT. Among those ten patients, nine had locoregional metastases. Among the nine patients who had positive lymph nodes for metastasis on histopathology, CECT and PET/CT scan had a sensitivity of 44 and 78 %, respectively. 18F-FDG PET/CT was found to be superior to CECT in the detection of the primary tumour and locoregional staging (p < 0.05). Diuretic 18F-FDG PET/CT is highly sensitive and specific and plays an important role in improving detection of the primary tumour and locoregional staging of urinary bladder tumours. Diuretic 18F-FDG PET/CT demonstrated a higher diagnostic value when compared with CECT in these patients.

Comparison between autologous noncultured extracted hair follicle outer root sheath cell suspension and autologous noncultured epidermal cell suspension in the treatment of stable vitiligo: a randomized study

Abstract: Summary Background Vitiligo is an acquired disorder of pigmentation caused by loss of epidermal melanocytes. Autologous noncultured epidermal cell suspension (NCES) and autologous noncultured extracted hair follicle outer root sheath cell suspension (NCORSHFS) are important surgical modalities for the treatment of stable vitiligo. Objectives To compare NCES and NCORSHFS for producing repigmentation in stable vitiligo. Methods We randomized 30 patients with 47 stable vitiligo lesions into two groups. Patients in group 1 were treated with NCES, and those in group 2 with NCORSHFS. They were evaluated 16 weeks postsurgery for the extent of repigmentation, colour match, change in Dermatology Life Quality Index (DLQI) score and patient satisfaction. Results The extent of repigmentation was excellent (90–100% repigmentation) in 83% of lesions in the NCES group and 65% of lesions in the NCORSHFS group (P = 0·154). Repigmentation ≥ 75% (good repigmentation) was observed in 92% of lesions in the NCES group and 78% of lesions in the NCORSHFS group (P = 0·425). There was a significant improvement in DLQI score in both the groups, but the mean decrease among groups did not differ significantly (P = 0·244). However, patients in the NCES group were significantly more satisfied than the patients in the NCORSHFS group. No significant difference was seen in colour match and pattern of repigmentation. Adverse effects were minimal. Conclusions Both NCES and NCORSHFS are safe and effective techniques with comparable efficacy. To the best of our knowledge, this is the first study directly comparing two different cellular techniques.

Directed search for continuous gravitational waves from the Galactic center

Abstract: We present the results of a directed search for continuous gravitational waves from unknown, isolated neutron stars in the Galactic Center region, performed on two years of data from LIGO's fifth science run from two LIGO detectors. The search uses a semi-coherent approach, analyzing coherently 630 segments, each spanning 11.5 hours, and then incoherently combining the results of the single segments. It covers gravitational wave frequencies in a range from 78 to 496 Hz and a frequency-dependent range of first order spindown values down to -7.86 x 10^-8 Hz/s at the highest frequency. No gravitational waves were detected. We place 90% confidence upper limits on the gravitational wave amplitude of sources at the Galactic Center. Placing 90% confidence upper limits on the gravitational wave amplitude of sources at the Galactic Center, we reach ~3.35x10^-25 for frequencies near 150 Hz. These upper limits are the most constraining to date for a large-parameter-space search for continuous gravitational wave signals.

Hydropericardium syndrome: current state and future developments.

Abstract: Hydropericardium syndrome (HPS) is a highly infectious disease caused by fowl adenovirus serotype 4 (FAV-4) affecting poultry, especially broiler birds. The disease was initially reported from Angara Goth, Pakistan, and then from India during 1994, in the poultry belt of Jammu and Kashmir, and thereafter, from almost all parts of the country, causing heavy economic losses to the poultry industry. The disease occurs predominantly in broilers of the age group of 3-5 weeks, characterized by sudden onset of high mortality up to 80 %. The causative agent of HPS is fowl adenovirus 4, which is a member of the species Fowl Adenovirus C, genus Aviadenovirus, family Adenoviridae [60]. FAV-4 is non-enveloped and icosahedral in shape, measuring 70-90 nm in size and containing a linear dsDNA of approximately 45 kb in size as its genome. The livers of affected birds show necrotic foci and basophilic intranuclear inclusion bodies in the hepatocytes. The disease can be diagnosed from its gross and microscopic changes in the liver and by various serological tests, such as agar gel immunodiffusion, counterimmunoelectrophoresis, indirect haemagglutination, fluorescent antibody techniques, and ELISA. In the past few years, PCR has been used as a rapid diagnostic tool for the detection of fowl adenoviruses. The disease has been brought under control by the use of formalin-inactivated, attenuated or live vaccines in experimentally infected birds. Advancement in the field of computational immunology accelerates knowledge acquisition and simultaneously reduces the time and effort involved in screening potential epitopes, leading toward the development of epitope-based vaccines.

Occupational Exposure to Ultraviolet Radiation and Risk of Non-Melanoma Skin Cancer in a Multinational European Study

Abstract: Background: Studies suggest that ambient sunlight plays an important role in the pathogenesis of non-melanoma skin cancers (NMSC). However, there is ongoing controversy regarding the relevance of occupational exposure to natural and artificial ultraviolet radiation (UV) radiation. Objectives: We investigated potential associations between natural and artificial UV radiation exposure at work with NMSC in a case-control study conducted in Hungary, Romania, and Slovakia. Methods: Occupational exposures were classified by expert assessment for 527 controls and 618 NMSC cases (515 basal cell carcinoma, BCC). Covariate information was collected via interview and multiple logistic regression models were used to assess associations between UV exposure and NMSC. Results: Lifetime prevalence of occupational exposure in the participants was 13% for natural UV radiation and 7% for artificial UV radiation. Significant negative associations between occupational exposure to natural UV radiation and NMSC were detected for all who had ever been exposed (odds ratio (OR) 0.47, 95% confidence interval (CI) 0.27–0.80); similar results were detected using a semi-quantitative metric of cumulative exposure. The effects were modified by skin complexion, with significantly decreased risks of BCC among participants with light skin complexion. No associations were observed in relation to occupational artificial UV radiation exposure.

Computational approach for designing tumor homing peptides

Abstract: Tumor homing peptides are small peptides that home specifically to tumor and tumor associated microenvironment i.e. tumor vasculature, after systemic delivery. Keeping in mind the huge therapeutic importance of these peptides, we have made an attempt to analyze and predict tumor homing peptides. It was observed that certain types of residues are preferred in tumor homing peptides. Therefore, we developed support vector machine based models for predicting tumor homing peptides using amino acid composition and binary profiles of peptides. Amino acid composition, dipeptide composition and binary profile-based models achieved a maximum accuracy of 86.56%, 82.03%, and 84.19% respectively. These methods have been implemented in a user-friendly web server, TumorHPD. We anticipate that this method will be helpful to design novel tumor homing peptides. TumorHPD web server is freely accessible at http://crdd.osdd.net/raghava/tumorhpd/.