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Background: Cutaneous metastases from colorectal cancer is a rare event. It indicates widely spread disease with poor prognosis. Case Report: A 40 years old male, diagnosed case of adenocarcinoma of the ascending colon, presented with multiple cutaneous nodules over the trunk, back and the legs. Histopathological examination of one of the cutaneous nodule showed deposits of signet ring cell carcinoma. Conclusion: Multiple cutaneous metastasis from signet ring cell carcinoma is uncommon. This entity should be recognized in patients of colonic primary as it depicts wide spread disease with poor prognosis.

The recognition of chemical and biological entities is an important step in biomedical, forensic, and environmental sciences. The generation of extremely sensitive and cost-effective sensors needs sophisticated equipment coupled with basic understanding of chemistry, biology, and material science. Nanoparticles especially noble metal nanoparticles (gold, silver) have drawn great attention in this area due to their distinctive physicochemical properties and can be used in constructing innovative identification and transduction process for chemical and biological sensors. The use of toxic chemicals in traditional synthesis restricts their use in the real samples. Thus, to overcome the limitation, green synthetic pathways of nanoparticles have gained tremendous attention, which provide some important features including easy fabrication and high biocompatibility. Herein, potential applications of green synthesized nanoparticles such as silver nanoparticles, gold nanoparticles, and carbon dots have been described.

Wilms tumor in children has cure rates of 90% at 5 years with a combined modality of treatment with surgery, chemotherapy and/or radiation. Wilms tumor recurs in 15–20% patients and almost all of them occur within 2 years of diagnosis. Late recurrence in Wilms tumor is rare with only a handful of case reports. No clear cut guidelines exist for management of recurrent Wilms tumor. The outcome with early and late relapses remain similar. Here we report a case of Wilms tumor presenting with recurrence 20 years after first diagnosis and review the literature on very late recurrences.

Noninvasive methods of detection of diseases are very important in the medical domain. Imaging modalities such as MRI are usually employed and present the state of the art. As of now, it is very widely used in the prognosis of heart diseases where tissue distribution is taken into account. This work exhibits multi-modal MRI to enable segmenting tissues in limb, which happens to be a crucial first step in analysis.

X-ray luminescent computed tomography (XLCT) is a promising new functional imaging modality based on computed tomography (CT). This imaging technique uses X-ray excitable nanophosphors to illuminate objects of interest in the visible spectrum. Though there are several validations of the underlying technology, none of them have addressed the issues of performance optimality for a given design of the imaging system. This study addresses the issue of obtaining best image quality through optimizing collimator width to balance the signal to noise ratio (SNR) and resolution. The results can be generalized as to any XLCT system employing a selective excitation scheme.

Overlapping of cervical cancerous cells and presence of debris, mucus and blood play a major issue in accurate segmentation of cells. Manual screening of overlapped cells in Pap smear slides is prone to error due to the complexity, high variation in shape and size and poor contrast of images. The automated system must be able to detect the nucleus and cytoplasm of clumped cells accurately as merging of cells is a characteristic of high stages of cervical cancer. In this paper, we propose a novel method to accurately segment the overlapping cells by dividing the whole image into many small non-overlapping pixel blocks, then extracting the texture features from Gray level co-occurrence matrix GLCM. The overlapped parts have a noticeable change in certain features which help us in selecting the area of interest which is marked explicitly and further the contours are marked using Independent level set method, accurately segmenting the cell nucleus and cytoplasm.

Introduction: R/R DLBCL patients who have received ≥2 lines of therapy, including those progressed post stem cell transplantation (SCT) or who are not candidates for SCT, have limited treatment options. Selinexor, a selective oral XPO1 inhibitor leads to nuclear accumulation and activation of tumor suppressor proteins and reductions in c-Myc and Bcl-2 oncogenes. Selinexor plus low dose dexamethasone (Sel-dex) was recently approved in relapsed/refractory myeloma in the United States based on data from the STORM study, wherein Sel-dex induced an overall response rate (ORR) of 26.2% in patients with penta-exposed, triple-class refractory multiple myeloma. We conducted the SADAL study to evaluate the efficacy and safety of single agent selinexor in patients with R/R DLBCL. In this patient population, selinexor demonstrated deep and durable responses with an overall response rate (ORR) of 28.3% including a 11.0% complete response (CR) rate. The median duration of response (DOR) was 9.2 months. In patients with CR, the DOR was 13.4 months. Here we evaluate the effect of prior therapy on the efficacy and safety of selinexor. Methods: SADAL is a multicenter, open-label study in R/R DLBCL patients with 2-5 prior lines of therapy, who may have progressed post SCT or are not candidates for SCT. Patients were stratified by subtype (germinal center B-cell or non-GCB) and treated with 60 mg selinexor BIW per 28-day cycle. The primary endpoint was ORR. Secondary endpoints included duration of response (DOR) and safety. We performed post-hoc analyses to compare outcomes based on the number (2 vs. >2) and type (SCT vs. no SCT) of prior lines of therapy received. Results: Of 127 patients, 83 (65%) received 2 prior lines of therapy and 43 (34%) received >2 prior lines of therapy. Thirty-six patients (28%) received prior SCT and 91 (72%) had no prior SCT. In general, patient demographic and baseline characteristics were well balanced in both subgroups. ORR was 30.1% vs. 25.6% (P=0.74) in patients with 2 vs >2 prior lines of therapy respectively. The CR rate was 10.8% in patients with 2 prior lines of therapy compared with 11.6% in patients with >2 prior lines of therapy (P=1.00). The median DOR was 9.2 months in patients with 2 prior lines of therapy compared with 8.4 months in those with >2 prior lines of therapy (P=0.64). Median progression free survival was 3.7 months and 1.9 months (P=0.37) and median overall survival was 11.0 months and 9.8 months (P=0.69) in patients with 2 and >2 prior lines of therapy respectively. In patients with prior SCT, the ORR was 44.4% compared with 22.0 % (P=0.02) in patients with no prior SCT. The CR rate was 16.7% in patients with prior SCT compared with 8.8% in patients with no prior SCT (P=0.34). The DOR was 8.4 months in patients with prior SCT and 9.2 months with no prior SCT (P=0.80). Median progression free survival was 5.9 months and 2.3 months (P=0.07) and median overall survival was 9.1 and 9.8 months (P=0.36) in patients with prior SCT and no prior SCT respectively. The most common related adverse events (AEs) [grade ≥3] included thrombocytopenia (2 prior lines: 36%, >2 prior lines: 42%; prior SCT: 58%, no prior SCT: 31%), neutropenia (2 prior lines: 19%, >2 lines: 23%; prior SCT: 25%, no prior SCT: 20%), and anemia (2 prior lines: 15%, >2 prior lines: 14%, prior SCT: 17%, no prior SCT: 14%). Treatment-related serious AEs were reported in 23%, 14%, 25%, and 19% of patients with 2 prior lines, >2 prior lines, prior SCT, and no prior SCT respectively. Conclusions: Single agent oral selinexor with its novel mechanism of action demonstrated deep and durable responses with no new safety signals regardless of prior therapy. Patients with 2 prior lines of therapy had a higher response rate (30.1% vs. 25.6%) compared with those with >2 prior lines of therapy. The greatest benefit, with an ORR of 44.4% was observed in patients with prior SCT. Collectively, these data support the clinical benefit of single agent selinexor and importantly in earlier lines of therapy. Further evaluation of selinexor in combination with other agents to improve outcomes in R/R DLBCL is ongoing. Disclosures Cavallo: Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Follows:Roche: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Goy:Astrazenca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Hackensack University Medical Center, RCCA: Employment; Pharmacyclics/Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants outside of the submitted work, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants outside of the submitted work; Takeda: Other: Grants outside of the submitted work; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants outside of the submitted work, Research Funding; Genentech: Other: Grants outside of the submitted work, Research Funding; University of Nebraska: Research Funding; Hakensackumc: Research Funding; COTA: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Other: leadership role for profit healthcare company. Casasnovas:Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses; Merck Sharp and Dohme: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Zijlstra:Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria. Choquet:Keocyt: Honoraria. Gurion:Roche: Consultancy. Hill:TG therapeutics: Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Research Funding; Kite: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Honoraria; Celegene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Takeda: Research Funding; Amgen: Research Funding. Jaeger:Novartis, Roche, Sandoz: Consultancy; AbbVie, Celgene, Gilead, Novartis, Roche, Takeda Millennium: Research Funding; Celgene, Roche, Janssen, Gilead, Novartis, MSD, AbbVie, Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen, AbbVie, Celgene, Eisai, Gilead, Janssen, Novartis, Roche, Takeda Millennium, MSD, BMS, Sanofi: Honoraria. Sancho:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sandoz: Consultancy; F. Hoffmann-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Other: Advisory board; Novartis: Honoraria; Kern Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Celltrion: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squib: Membership on an entity's Board of Directors or advisory committees. Schuster:Celgene: Speakers Bureau; Genentech: Speakers Bureau; Janssen: Speakers Bureau; Novartis: Speakers Bureau; Seattle Genetics: Speakers Bureau; Takeda: Speakers Bureau; Verastem: Speakers Bureau; Astellas: Speakers Bureau; Actinium: Research Funding; Incyte: Research Funding; Karyopharm Therapeutics: Research Funding; Morphosys: Research Funding; Nordic Nanovector: Research Funding; Pharmacyclics: Research Funding, Speakers Bureau; Rafael: Research Funding; F2G Ltd.: Research Funding; AbbVie: Speakers Bureau; Amgen: Speakers Bureau. Thieblemont:Roche: Honoraria, Research Funding; Gilead: Honoraria; Novartis: Honoraria; Kyte: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Cellectis: Membership on an entity's Board of Directors or advisory committees. Vassilakopoulos:Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene / GenesisPharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; WinMedica: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. McCarthy:Karyopharm Therapeutics: Employment, Equity Ownership. Ma:Karyopharm: Employment, Equity Ownership. Corona:Karyopharm Therapeutics: Employment, Equity Ownership. Saint-Martin:Karyopharm Therapeutics: Employment, Equity Ownership. Joshi:Karyopharm Therapeutics: Employment, Equity Ownership. Shah:Karyopharm Therapeutics: Employment, Equity Ownership. Van Den Neste:Gilead: Other: travel support. Canales:Sandoz: Honoraria; F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau; Celgene: Honoraria; Novartis: Honoraria; Takeda: Speakers Bureau; SOBI: Research Funding; iQone: Honoraria; Karyopharm: Honoraria; Gilead: Honoraria; Janssen: Honoraria, Speakers Bureau.

Several investigations on DNA-based nucleic acid sensors performed in the past few years point toward the requirement of an alternative nucleic acid that can detect target DNA strands more efficiently, i.e., with higher sensitivity and selectivity, and can be more robust compared to the DNA sensor probes. Locked nucleic acid (LNA), a conformationally restricted DNA analogue, is potentially a better alternative than DNA, since it is nuclease-resistant, it can form a more stable duplex with DNA in a sequence-specific manner, and it interacts less with substrate surface due to presence of a rigid backbone. In this work, we probed solid-phase dehybridization of ssDNA targets from densely packed fully modified ssLNA probes immobilized onto a gold(111) surface by fluorescence-based measurement of the "on-surface" melting temperatures. We find that mismatch discrimination can be clearly improved by applying the surface-tethered LNA probes, in comparison to the corresponding DNA probes. We show that concentration as well as type of cation (monovalent and polyvalent) can significantly influence thermal stability of the surface-confined LNA-DNA duplexes, the nature of concentration dependence contradicting the solution phase behavior. Since the ionic setting influenced the fully matched duplexes more strongly than the singly mismatched duplexes, the mismatch discrimination ability of the surface-confined LNA probes could be controlled by ionic modulations. To our knowledge, this is the first report on ionic regulation of melting behavior of surface-confined LNA-DNA duplexes.

It is significant to analyze the dental images in order to improve and quantify medical images for correct diagnosis. Caries or cavity is one of the most prevalent diseases of the teeth. Dentists are putting the best effort to identify the problem at an earlier stage. The proposed method used in this paper is focused on the challenges faced during the root canal edge extraction from dental radiographic images, which is a major problem besides cavity detection and extraction. The image processing techniques helps to identify the caries that provide dentists with the precise results of the area affected by the caries. The proposed methodology consists of preprocessing of bitewing radiographic images using top hat bottom hat transformation followed by the sharpening filter for edge enhancement. This combinational approach provides qualitative and quantitative assessment to dentists on the presence of cavity. The caries are extracted by some morphological tools to grade the severity on the basis of some metric values. Preparatory experiments show the significance of the proposed method to extract cavity and grade its effect on the tooth.

Automatic identification of bird species based on the chirping sounds of birds was experimented using feature extraction method and classification based on support vector machines (SVMs). The proposed technique followed the extraction of cepstral features on mel scale of each audio recording from the collected standard database. Extracted mel frequency cepstral coefficients (MFCCs) formed a feature matrix. This feature matrix was then trained and tested for efficient recognition of audio events from audio test signals. 70% of the whole database was used for training purpose while the reamaining 30% for testing of samples. The classifier achieved upto 89.4% accuracy on a data set containing four species, commonly found in India.

A number of reports have been made in recent times on label-free detection of nucleic acid sequences. However, most of these studies deal with ensemble measurements, therefore lacking in molecular level resolution. These assays have usually employed ssDNA sensor probes, and often suffered from problems of irreproducibility and poor sequence-selectivity. Herein, the applicability of surface-anchored single stranded locked nucleic acid (ssLNA) probes has been assessed in the detection of target DNA sequences, as an alternative to the DNA-based assay. Importantly, the effectiveness of the LNA-based assay in identifying different types of single nucleobase mismatches has been tested. Since the duplex melting temperature is an indicator of duplex stability, the ensemble on-surface Tm values of the surface-confined LNA-DNA duplexes have been compared to the duplex unbinding force values obtained from atomic force spectroscopy (AFS) experiments. A common mismatch discrimination pattern elicited by both the ensemble and the molecular level AFS approach could be identified. Apart from quantitative delineation of the different types of mismatches, the label-free AFS analysis confirms different degrees of efficiency of the purine and pyrimidine bases, present on the LNA backbone, in discriminating different nucleobase mismatch types. Importantly, the LNA-based AFS analysis can distinguish between the disease-relevant gene fragments, e.g., multidrug-resistant Mycobacterium tuberculosis (MTB) mutation, and the wild type. Since LNA probes are nuclease-resistant, these findings could potentially pave way to diagnostic applications of the LNA-based AFS assay.

In this paper the use of an evolutionary computational algorithm such Differential Evolution have been studied for their use in feature selection problems. Feature selection is rapidly increasing in importance due to the exponential increase in the size of datasets. The dimensionality problem arising due to these large datasets can be dealt with by using feature selection, which provides a multitude of advantages when it comes to datasets. The advantages have been discussed in the paper. The use of Differential Evolution in this regard is a novel approach and provides us with comparable results with existing algorithms like GA. This paper also deals with the approach that involves changing the mutation scheme to allow for conversion to binary before selecting the features.

Locked nucleic acid (LNA) is a conformationally restricted nucleic acid analogue, which is potentially a better alternative than DNA for application in the nucleic acid based biosensor technologies, due to its efficient and sequence-specific DNA/RNA detection capability and lack of molecule-surface interaction on solid surfaces, compared to DNA. We report, for the first time, a straightforward way (based on simple immersion method) of generating an ordered self-assembled LNA monolayer, which is bioactive, onto a gold(111) surface. This layer is capable of giving rise to a stronger DNA recognition signal (4-4.5 times) than its DNA counterpart, and importantly, it can differentiate between a fully complementary DNA target and that having a single base mismatch, where the mismatch discrimination ratio is almost two times compared to the ratio relevant in case of DNA-based detection. We have presented high-resolution atomic force microscopy (AFM) topographs of the well-defined one-dimensional LNA molecular ordering (few hundred nanometers long) and of the two-dimensional ordered assembly formed over a large area (7 μm × 7 μm) due to parallel positioning of the one-dimensional ordered arrangements. The effects of different parameters such as LNA concentration and incubation time on LNA self-assembly have been investigated. Further, reflection absorption infrared (RAIR) spectroscopy has been applied to obtain information about the orientation of the surface-immobilized LNA molecules for the first time. It has been found that the LNA molecules undergo an orientational transition from the "lying down" to the "upright" configuration in a time scale of few hours.

Two wire tandem submerged arc welding process facilitates high rate of joint filling with little increase in the overall rate of heat input due to the simultaneous deposition from two electrode wires. Since the lead wire is usually connected to a DC welding arc and the trail wire to a pulsed AC arc, the tandem process requires appropriate selection of a large number of process variables. A quantitative understanding of the effect of the welding conditions on weld joint dimensions and weld thermal cycle is difficult through experimental studies only. Here we present a three-dimensional heat transfer analysis based on finite element method using two independent volumetric heat sources to account for heat input from two welding arcs. The shapes of the heat sources are estimated based on the original joint geometry and welding conditions. The results show that the trail wire current pulses significantly influences the reinforcement height and weld width while lead wire current affects the depth of penetration. For a constant trail wire effective current, increase in the negative pulse time results in greater reinforcement height and reduced weld width with very little influence on the cooling rate and weld strength. In contrast, increase in trail wire negative current pulse increases both reinforcement height and weld width while reduces cooling rate and weld strength.

Electromechanical above-knee prosthetics are widely available, and are reliant on repetitive knee movements of fixed length/angle. This work explores the viability of developing adaptive movements on existing prototypes, through embedded controls from 8051-class 8-bit microcontroller units (MCUs). The system includes an integrated goniometer, intended for measuring the knee angle of the sound limb. The phase delay is subsequently processed to bring about kinematic coordination in the proposed echo-controlled prosthetic.

To the Editor:We present two leukemia patients whose blood group changed during the course of their treatment. The first case was a 17-y-old boy with acute myeloid leukemia (AML) whose blood group at presentation was O Rhesus positive (O Rh + ve). After 2 cycles of induction chemotherapy his disease was in remission, however, his blood group changed to A Rh + ve. He subsequently received A Rh + ve blood products without any transfusion reactions. The patient continues to be in remission and his blood group still remains A Rh + ve. The second case was an 11-y-old boy with acute lymphoblastic leukemia (ALL) whose blood group at presentation in March 2011was B Rh negative (B Rh-ve). However, his blood group changed to B Rh + ve when he relapsed in May 2015, only to revert back a month later to B Rh-ve after he attained remission with chemotherapy. The patient’s blood group changed back to B Rh + ve after 2 mo in August 2015 when his disease relapsed again. In both the cases the patients’ blood groups were determined by their disease remission status. The ABO blood group genes encode glycosyl transferase enzymes which modify the carbohydrate content of the blood group antigens on the red blood cell (RBC) surface and determine the blood group of an individual [1]. The mechanism underlying blood group change in leukemia is not clear as was seen in our patients. It has been proposed that in some leukemic patients’ epigenetic modification of the promoter ofABO gene in RBCs by leukemic cells leads to its suppression and consequent alteration in the blood group [2]. ABO blood group changes have been more commonly described in AML than in other hematological malignancies [3, 4]. However, most of these changes are subtle and detected on molecular studies and not detected on routine blood group typing [3]. Blood group changes have been identified prior to the diagnosis of underlying leukemia and also have shown to herald leukemia relapse [5]. These two cases are being highlighted to alert and educate the pediatricians about the rare possibility of change in blood group in leukemic patients during treatment or disease relapse.

This paper proposes a novel method for design of optimized inset-fed patch antennas using genetic algorithm. A patch antenna is thereby designed and the results were simulated to verify the resonating frequency against desired frequency, and the radiation pattern. It is a demonstration of how genetic algorithm can be used to optimize a patch antenna in accordance with various requirements and scenarios, with lower computational complexity resource utilization. The results obtained during simulation are quite promising to initiate antenna development using genetic algorithm to provide heuristic selection of designs, which best fit the purpose of antenna usage.

Achieving high gain resonating antenna at a prerequisite frequency is a real time problem. A Microstrip patch antenna is highly dependent on its designing. Although theoretically it is possible to find out the parameters for a particular frequency, the outcome is not always accurate. Since this process of combining sets of parameters is time consuming, using optimization algorithms seems a plausible option. Differential Evolution uses real parameters and uses the difference in the vectors to scan the contours of the fitness function. The function used to find the minima is the impedance function as a resonance is obtained when the impedance of antenna matches the input impedance. Unlike DE, Particle swarm optimization defines a set of locations and velocities of the members of vector array, using parallel search techniques starting with many vectors from initial position and communicating amongst themselves to find the global optima. On the other hand, Bacterial Foraging Optimization algorithm, despite being a swarm based algorithm, uses a different approach imitating the behavior of a bacteria at different situations. Although each algorithm is fed with the exact same parameters, the outcomes are strikingly different. Each algorithm optimizes the problem of resonating patch in its own way and time

The recent emergence of on-surface LNA-based assays as potentially better alternatives over DNA-based approaches, due to enhanced sensitivity and target specificity, raises the need for the precise identification of the factors that control the performance of these assays. In this work, we investigated whether the probe density of fully modified ssLNA probes on the gold(111) surface could influence the target recognition capacity of the LNA sensing layer and illustrated simple means to control it, primarily by adjusting the salt concentration, nature of the cation, and pH of the immobilization buffer. It was observed that monovalent Na(+) could more effectively control the sensor probe density compared to bivalent Mg(2+), leading to better target recognition. Interestingly, unlike in the case of ssDNA sensor probes, the target recognition efficiency of the LNA layer at the optimum probe density was found to be almost spacer-independent, probably due to the rigidity of the LNA backbone. The optimized LNA sensor layer could discriminate single base mismatches, detect a minimum target DNA concentration of 5 nM, and sense a significant level of hybridization within a time scale of a few minutes. To our knowledge, for the first time, we identify the factors that control the on-surface LNA probe density for maximizing the performance of the LNA sensing layer.

Unambiguous identification of single base mismatches in nucleic acid sequences is of great importance in nucleic acid detection assays. However, ambiguities are often encountered with, and therefore, a strategy for attaining substantially large enhancement of mismatch discrimination has been worked upon in this study. Short single-stranded peptide nucleic acid (PNA) and deoxyribonucleic acid (DNA) sensor probes that are immobilized onto gold nanoparticle (AuNP) modified Au(111) surface have been applied for target DNA detection. It will be shown that while both PNA and the analogous DNA probes exhibit generally better target detection abilities on the AuNP-modified Au(111) surface (elicited from fluorescence-based measurement of on-surface Tm values), compared to the bare Au(111) surface, PNA supersedes DNA, for all sizes of AuNPs (10, 50, and 90 nm) applied, with the difference being quite drastic in the case of the smallest 10 nm AuNP. It is found that while the AuNP curvature plays a pivotal role in target detection abilities of the PNA probes, the changes in the surface roughness caused by AuNP treatment do not exert any significant influence. This study also presents a means for preparing PNA-AuNP hybrids without altering PNA functionality and without AuNP aggregation by working with the surface-affixed AuNPs.

There has been a search for alternative nucleic acids that can be more effectively used in nucleic acid detection technologies compared to the DNA probes. Peptide nucleic acid (PNA), which contains a non-ionic peptidic backbone, offers such possibilities since it is nuclease-resistant, it binds to DNA with high affinity, and it can be readily self-assembled onto solid substrates, e.g., gold(111), with a molecular backbone orientation away from the substrate. Although application of PNA as a sensor probe has been exemplified, so far there is little or no account of the ionic modulation of single base mismatch discrimination capacity of surface-tethered PNA probes. Herein, we report "on-surface" melting temperatures of PNA-DNA duplexes formed on gold(111) surface, as obtained from fluorescence measurements. We show that surface-tethered PNA forms a stabler duplex than DNA, and is more effective in single base mismatch discrimination than DNA. Importantly, although PNA backbone is non-ionic, variation in the ionic components in hybridization buffer, i.e., varying concentration of monovalent sodium ion, and the nature of anion and the cation, exhibits clear effects on the mismatch discrimination capacity of PNA probes. In general, with decreasing cation concentration, PNA-DNA duplexes are stabilized and mismatch discrimination capacity of the PNA probes is enhanced. The stabilizing/destabilizing effects of anions are found to follow the Hofmeister series, emphasizing the importance of hydrophobic interaction between nucleobases for stability of the PNA-DNA duplexes. Interestingly, the nature of ionic dependence of "on-surface" mismatch detection ability of PNA probes differs significantly from the "solution" behavior of these probes.

Two brothers aged 14 and 17 years presented in our emergency department with complaints of fever and yellowish discoloration of eyes and urine for 6 and 10 days, respectively. They had similar clinical presentation, examination findings, laboratory biochemical derangements and positive results for rapid tests of Plasmodium falciparum and vivax species along with IgMEnzyme-linked immunosorbent assay (ELISA) test for hepatitis A virus. They also showed similar response to therapy and improved simultaneously within two to three days. This suggests the role of immunogenetics in modifying the natural course of disease. Moreover, triple infection by these hepatotropic pathogens lead to a presentation that is much more severe than that caused by either of them alone. This could only be explained by a synergistic interaction between these pathogens. This case foretells that co-infections with two or more hepatotropic pathogens require immediate attention with an aggressive management and role of immunogenetics along with co-infections in altering the phenotypic expression of a disease. Key words: Plasmodium falciparum, Plasmodium vivax

Training on micro- and nano- computed tomography (CT) scanners has been traditionally conducted via extensive practice on the instrument. This entails presence of an instructor to guide through the training procedure, until reasonable experience is attained. Modern tomographic instruments being expensive to maintain, the operational costs escalates with increasing number of training conducted. In a pioneering approach, the technical know-how to operate such equipment has been partly imparted via virtual reality environment running on the Second Life grid. The experimentation has indicated a reduction of the total training time. The authors hope that in the long run, such techniques will aid in significant reduction of instruction time and costs associated with training.

Alopecia is a rare manifestation of Hodgkin's disease. It may be due to follicular destruction due to direct infiltration by the disease, or it may be a secondary or paraneoplastic manifestation. In this patient, hair loss, diffuse yperpigmentation, and generalized itching preceded other manifestations of the disease. The pattern of hair loss was diffuse and generalized in nature involving scalp, eyebrows, axilla, and groin. Subsequently, the patient was diagnosed to be a case of Hodgkin's lymphoma, based on clinical and histopathological features. Earlier reports on alopecia accompanying Hodgkin's disease have also been discussed. This case highlights the importance of keeping a high suspicion of an underlying malignancy in patients presenting with such cutaneous manifestations.