k mer

Motivation: De novo transcriptome assembly is an integral part for many RNA-seq workflows. Common applications include sequencing of non-model organisms, cancer or meta transcriptomes. Most de novo transcriptome assemblers use the de Bruijn graph (DBG) as the underlying data structure. The quality of the assemblies produced by such assemblers is highly influenced by the exact word length k. As such no single kmer value leads to optimal results. Instead, DBGs over different kmer values are built and the assemblies are merged to improve sensitivity. However, no studies have investigated thoroughly the problem of automatically learning at which kmer value to stop the assembly. Instead a suboptimal selection of kmer values is often used in practice. Results: Here we investigate the contribution of a single kmer value in a multi-kmer based assembly approach. We find that a comparative clustering of related assemblies can be used to estimate the importance of an additional kmer assembly. Using a model fit based algorithm we predict the kmer value at which no further assemblies are necessary. Our approach is tested with different de novo assemblers for datasets with different coverage values and read lengths. Further, we suggest a simple post processing step that significantly improves the quality of multi-kmer assemblies. Conclusion: We provide an automatic method for limiting the number of kmer values without a significant loss in assembly quality but with savings in assembly time. This is a step forward to making multi-kmer methods more reliable and easier to use. Availability and Implementation:A general implementation of our approach can be found under: https://github.com/SchulzLab/KREATION. Supplementary information: Supplementary data are available at Bioinformatics online. Contact: [email protected]

Investigations on structural, optical, and impedance spectroscopy studies of titanium dioxide nanoparticles

This article explains a novel synthesis for producing titanium dioxide (TiO2) nanoparticles by a sol-gel technique using titanium tetraisopropoxide as a titanium source. The synthesized nanoparticles were analyzed using many measurements like X-ray diffraction (XRD), HRTEM, absorption UV spectroscopy, FTIR, and ac impedance spectroscopy. X-ray peaks were used to calculate the crystallite size and lattice strain by Williamson–Hall method. Crystallite size calculated from x-ray diffraction using the Scherrer equation gives an approximate size and cannot be used for measurements. TiO2 nanoparticles are found to possess a tetragonal structure with a crystalline size around 12 nm. Particle size was confirmed by HRTEM images. The optical studies response for the nanoparticles showed the possible visible absorption peaks for TiO2 nanoparticles are 323 nm. Bandgap energy (Eg) of the TiO2 nanoparticle calculated from UV visible absorption spectra is discussed, and the bandgap is 3.14 eV. FTIR spectra showed vibration bands of the Ti-O network. AC Conductivity properties of TiO2 nanoparticles are studied in the frequency range 1 to 8 MHz at varying temperatures. The conductivity of the TiO2 nanoparticle is found to be constant in the low angular frequency region. Dielectric parameters were analyzed at different temperatures and frequencies.                     KEY WORDS: Conductivity, Dielectric, Nanoparticles, Titanium dioxide, Structural studies   Bull. Chem. Soc. Ethiop. 2021, 35(1), 151-160. DOI: https://dx.doi.org/10.4314/bcse.v35i1.1

A Mixed-Methods Trial of Broad Band Noise and Nature Sounds for Tinnitus Therapy: Group and Individual Responses Modeled under the Adaptation Level Theory of Tinnitus

Objectives: A randomized cross-over trial in 18 participants tested the hypothesis that nature sounds, with unpredictable temporal characteristics and high valence would yield greater improvement in tinnitus than constant, emotionally neutral broadband noise.Study Design: The primary outcome measure was the Tinnitus Functional Index (TFI). Secondary measures were: loudness and annoyance ratings, loudness level matches, minimum masking levels, positive and negative emotionality, attention reaction and discrimination time, anxiety, depression and stress. Each sound was administered using MP3 players with earbuds for 8 continuous weeks, with a 3 week wash-out period before crossing over to the other treatment sound. Measurements were undertaken for each arm at sound fitting, 4 and 8 weeks after administration. Qualitative interviews were conducted at each of these appointments.Results: From a baseline TFI score of 41.3, sound therapy resulted in TFI scores at 8 weeks of 35.6; broadband noise resulted in significantly greater reduction (8.2 points) after 8 weeks of sound therapy use than nature sounds (3.2 points). The positive effect of sound on tinnitus was supported by secondary outcome measures of tinnitus, emotion, attention, and psychological state, but not interviews. Tinnitus loudness level match was higher for BBN at 8 weeks; while there was little change in loudness level matches for nature sounds. There was no change in minimum masking levels following sound therapy administration. Self-reported preference for one sound over another did not correlate with changes in tinnitus.Conclusions: Modeled under an adaptation level theory framework of tinnitus perception, the results indicate that the introduction of broadband noise shifts internal adaptation level weighting away from the tinnitus signal, reducing tinnitus magnitude. Nature sounds may modify the affective components of tinnitus via a secondary, residual pathway, but this appears to be less important for sound effectiveness. The different rates of adaptation to broadband noise and nature sound by the auditory system may explain the different tinnitus loudness level matches. In addition to group effects there also appears to be a great deal of individual variation. A sound therapy framework based on adaptation level theory is proposed that accounts for individual variation in preference and response to sound.Clinical Trial Registration:www.anzctr.org.au, identifier #12616000742471

Analysis of MUC4 expression in the prostatic adenocarcinoma and its pathological implications

Background: Expression of various types of mucins has been documented in several malignancies and seems to play a sentinel role in some epithelial malignancies. MUC1 and MUC4 are two transmembrane mucins that are involved in cell signalling events that drive the proliferation of cells. Therefore, mucins may be important biomarkers for early diagnosis and targeted therapy due to their frequently altered expression pattern in carcinomas. The objective of the study was to determine the expression pattern of MUC-4 in prostate cancer and to correlate the expression with clinicopathological parameters.Methods: Thirty cases of prostate carcinomas of different grades were selected from the case files of our institute for the study. Immunohistochemistry was done on all cases using monoclonal antibodies against MUC- 4 by the avidin biotin technique. The expression and pattern of staining were analyzed .Staining pattern in the adjacent benign areas were also noted.Results: Our study showed that expression of MUC4 was considerably down regulated in prostate cancer tissues when compared to normal or benign prostatic tissue. Few cases of prostate cancer showed a moderate staining while majority cases of adjacent normal areas were moderate to strongly positivity.Conclusions: The results of our study implies that MUC4 is down regulated in prostate cancer and this may be of significance for diagnostic application and tumor progression in prostate cancer. Since MUC4 is known to modulate HER2/ErbB2 signalling it may prospectively prove to be useful in prostate cancer therapy

Tetra-μ-chlorido-bis­(18-crown-6)platinum(II)dipotassium(I)

In the title compound, [K2PtCl4(C12H24O6)2], the PtII ion is located on an inversion centre and is coordinated by four Cl atoms, forming a square-planar geometry. The KI ion is coordinated by six O atoms of the crown ether and two bridging Cl atoms. The KI ion is displaced by 0.756 (2) Å from the mean plane of the six O atoms of the crown ether. The mol­ecules are connected by weak C—H⋯O hydrogen bonds, forming an infinite two-dimensional network parallel to the (10) plane. Intra- and inter­molecular C—H⋯Cl hydrogen bonds are also observed

Colectomy rate in steroid-refractory colitis initially responsive to cyclosporin: a long-term retrospective cohort study

BACKGROUND: There is consistent evidence that 50% of patients with acute, steroid-resistant flare of ulcerative colitis (UC) may achieve remission and avoid colectomy if treated with cyclosporin (CsA). However, follow-up of the responders has shown that most of them relapse and need surgery shortly after the response. We compared the records of our CsA-treated patients with those of other groups in order to help clarify this matter. METHODS: All patients admitted consecutively to our Unit with an attack of UC and treated with CsA between January 1991 and December 1999 were studied. Patients were begun on continuously-infused CsA at 2 mg/kg/day (1991–1996), or on NEORAL at an initial dose of 5 mg/kg/day (1996–1999). The maintenance treatment included oral CsA for 3–6 months with or without azathioprine (AZA). CsA failure was defined as a relapse requiring steroids with or without progression to colectomy; the cumulative probability of relapse/colectomy was assessed by Fisher's exact tests and Kaplan-Meier analysis. RESULTS: Among the patients, 39/61 (63%) initially responded. These 39 included a fatality and 4 drop-outs (unrelated to the side-effects of CsA), leaving 34 patients for the study. Of these, 61% and 35% were colectomy-free at 1 and 7 years, respectively; the corresponding figures were 80 and 60% respectively in the subset treated with AZA, but 47% and 15% in the AZA-untreated subgroup (p= 0.0007 at 7 years). Among the 34 patients, 44% were relapse-free at 1 year, but all had relapsed at 7 years (p = 0.0635). The overall resort to colectomy was 72%, while 19% of the patients remained colectomy-free. CONCLUSION: Sixty percent of a cohort of patients with steroid-refractory colitis responded to CsA and 60% of these responders retained the colon after 1 year. These figures fell to 35% at 7 years but improved to 60% on AZA. The overall need for colectomy remains high in these patients and toxicity must be monitored

An affinity-based scoring scheme for predicting DNA-binding activities of modularly assembled zinc-finger proteins

Zinc-finger proteins (ZFPs) have long been recognized for their potential to manipulate genetic information because they can be engineered to bind novel DNA targets. Individual zinc-finger domains (ZFDs) bind specific DNA triplet sequences; their apparent modularity has led some groups to propose methods that allow virtually any desired DNA motif to be targeted in vitro. In practice, however, ZFPs engineered using this ‘modular assembly’ approach do not always function well in vivo. Here we report a modular assembly scoring strategy that both identifies combinations of modules least likely to function efficiently in vivo and provides accurate estimates of their relative binding affinities in vitro. Predicted binding affinities for 53 ‘three-finger’ ZFPs, computed based on energy contributions of the constituent modules, were highly correlated (r = 0.80) with activity levels measured in bacterial two-hybrid assays. Moreover, Kd values for seven modularly assembled ZFPs and their intended targets, measured using fluorescence anisotropy, were also highly correlated with predictions (r = 0.91). We propose that success rates for ZFP modular assembly can be significantly improved by exploiting the score-based strategy described here