The Drosophila speciation factor HMR localizes to genomic insulator sites

Hybrid incompatibility between Drosophila melanogaster and D. simulans is caused by a lethal interaction of the proteins encoded by the Hmr and Lhr genes. In D. melanogaster the loss of HMR results in mitotic defects, an increase in transcription of transposable elements and a deregulation of heterochromatic genes. To better understand the molecular mechanisms that mediate HMR's function, we measured genome-wide localization of HMR in D. melanogaster tissue culture cells by chromatin immunoprecipitation. Interestingly, we find HMR localizing to genomic insulator sites that can be classified into two groups. One group belongs to gypsy insulators and another one borders HP1a bound regions at active genes. The transcription of the latter group genes is strongly affected in larvae and ovaries of Hmr mutant flies. Our data suggest a novel link between HMR and insulator proteins, a finding that implicates a potential role for genome organization in the formation of species

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Workload Control in Flow Shops with Bottleneck Shifting and Process Time Variability

Manufacturing industries struggle to devise precise planning and scheduling solutions due to unpredictable business situations. Additionally, uncertainties in production such as machine breakdowns, labour absenteeism, cycle time deviations, etc., would further deteriorate production plans and lead to uncertainty in decision-making processes. Flow shops with bottlenecks are particularly susceptible to these disturbances. Moreover, the random variations in cycle time variations can cause the bottleneck to shift between different stages. Literature indicates that conventional job release methods are ineffective in addressing these difficulties. In contrast, workload control methods would provide better solutions. Hence, a flow shop model has been developed and simulated using the variables like process time variations and bottleneck shifting on the discrete-event simulation software. The flow shop model incorporates realistic shop characteristics which are subjected to random process time variations, so as to assess the performance. The outcomes of the experimentation demonstrate that order release methods play a pivotal role in improving the performance of flow shops in more volatile situations

In vitro evaluation of anti oxidant activity and estimation of total flavonoids in seeds of Psoralea corylifolia plant extracts

The present study aims at in-vitro evaluation of anti oxidant activity of n-hexane and ethyl acetate extracts of seeds of Psoralea corylifolia. For evaluating this study  1, 1-diphenyl-2-picryl-hydrazyl (DPPH) method and reducing power method was used.For DPPH method Butylated Hydroxy Anisole (BHA) was used as a positive control and for  Reducing power method ascorbic acid  was used as a standard reducing agent. All the analysis was made with the use of UV-Visible Spectrophotometer. The content of total flavonoids was measured spectrophotometrically by using the aluminium chloride colorimetric assay where catechin was used as a standard. The extracts showed good DPPH radical scavenging activity and reducing power activity which was found to increase with the increasing concentration of the extracts. The total flavonoid content was found to be 73.09 mg CE/100g. Ethyl acetate extract of Psoralea corylifolia showed more prominent activity when compared to n-hexane extract which could be attributed to the presence of flavonoid content.The study could be further extended to isolate and characterize phytoconstituents from these extracts

Antidiabetic Activity Of Cassia auriculata Seeds In Alloxan Induced Diabetic Rats

The petroleum ether (40-60 ºC), chloroform, ethyl acetate, ethanol and aqueous extracts of Cassia auriculata seeds, obtained by soxhlet extraction method were evaluated for antidiabetic activity using alloxan (60 mg/kg through tail vein) induced hypoglycemic rats on acute and prolonged treatment. The potency of extracts was compared with that of standard tolbutamide (250 mg/kg body weight, p.o.). Petroleum ether and ethyl acetate extracts showed highly significant (

Outcomes of toric intraocular lens realignment surgery done using slit-lamp method and wavefront aberrometry method

Purpose: To compare the slit-lamp method and wavefront aberrometry method based on outcomes of toric realignment surgeries. Settings: Tertiary care ophthalmic hospital. Design: Retrospective study. Methods: This study included all eyes undergoing toric intraocular lens (TIOL) realignment surgery between January 2019 and December 2021 for which TIOL axis assessment by slit-lamp method and wavefront aberrometry method was available. Data were retrieved from electronic medical records, and we documented demographics, uncorrected visual acuity (UCVA), subjective refraction, and TIOL axis by slit-lamp and wavefront aberrometry methods on postoperative day 1 and day 14. In patients with misalignment, TIOL was realigned to the original position in group 1 (27 patients) and to an axis based on calculations provided by wavefront aberrometer in group 2 (25 patients). Post-realignment surgery, UCVA, subjective refraction, and TIOL axis by slit-lamp and wavefront aberrometry methods were assessed and analyzed. Results: We analyzed 52 eyes and found that the mean preoperative misalignment with the slit-lamp method (44.9° ±20.0°) and wavefront aberrometry (47.1° ±19.5°) was similar. The corresponding degrees of misalignment post-TIOL repositioning surgeries were 5.2° ±5.2° (slit-lamp method) and 4.7° ±5.1° (wavefront aberrometry) (P = 0.615). Both groups showed significant improvement in median log of minimum angle of resolution (logMAR) UCVA and reduction in median refractive cylinder. Conclusions: Slit-lamp method is as good as wavefront aberrometer method to assess TIOL axis. Toric realignment surgery is found to be safe, and realigning TIOL based on either slit-lamp method or wavefront aberrometer method equally improved UCVA and decreased residual refractive cylinder