Miracle-dz/UniFAR-FTUs huggingface dataset:
Primary central nervous system diffuse large B-cell lymphoma in the immunocompetent: Immunophenotypic subtypes and Epstein-Barr virus association

Introduction: Primary central nervous system diffuse large B-cell lymphoma (PCNSL DLBCL) in the immunocompetent is an uncommon tumor that has an activated B-cell immunophenotype resembling germinal center exit B cells. They also differ from primary central nervous diffuse large B-cell lymphomas in the immunocompromised as they show no association with the Epstein-Barr virus. Objective: To determine if immunophenotypic subtyping of PCNS DLBCL from Asian subcontinent are also different similar to its systemic counterpart is unclear, as there are only limited studies from Asia, and none from India. Material and Methods: The immunohistochemical profile of 24 South Indian patients with primary central nervous system diffuse large B-cell lymphoma was studied using germinal center markers – CD10 and Bcl-6, and activation markers – MUM1 and CD138, which are markers for late/post germinal centre B cells. Insitu hybridization for EBV genome and LMP1 by immunohistochemistry was carried out in all cases to determine association with EBV. Results: Centroblastic morphology and uniform activated B-cell phenotype with positivity for MUM1 was seen in 91.6% of tumors. Co-expression of Bcl-6 and MUM1 was evident in 50%, which is more frequent than in systemic diffuse large B-cell lymphomas. All cases were negative for Epstein-Barr virus using EBER in-situ hybridization and LMP1 immunohistochemistry. Conclusion: Primary diffuse large B-cell lymphoma in the immunocompetent is a distinct clinicopathological entity with centroblastic morphology, a uniform activated B-cell immunophenotype that is not associated with the Epstein-Barr virus regardless of geographic origin.
A novel approach for the designing of controller for the Wind Energy Conversion System

Many innovations has been done for optimal utilization of various energy resources, nowadays many limitations are increasing on non-renewables due to their depletion and adverse environmental effects. Wind is one of the most important inexhaustible sources. As technologies are advancing, efficient use of wind like resources is also increasing. Doubly-fed Induction Generator (DFIG) based system is one of the best available in the market due to its various advantages; it is of utmost need that these systems should be well-controlled as intermittent nature of wind depletes the power quality. In the present work novel approach to control the mechanical input to the induction generator has been proposed and the results are presented. From the results obtained it is observed that there is considerable improvement in the small signal stability of the Wind Energy Conversion System (WECS). After comparing the various control system parameters there are considerable improvement in peak time, rise time, settling time and overshoot.
Regulation of flowering time by SPL10/MED25 module in Arabidopsis.

Several SPL (SQUAMASA PROMOTER BINDING PROTEIN-LIKE) transcription factors are involved in plant developmental transition from vegetative to reproductive growth. However, the function of SPL10 in regulating floral transition is largely unknown. It is also not known which Mediator subunit mediates SPL10 transcriptional activity. Here, we used over-expression lines and knockout mutants to examine the role of SPL10 in flowering time regulation and we investigated possible interactions of SPL10 with several mediator subunits in vitro and in vivo. Plants overexpressing SPL10 showed precocious flowering whereas the triple loss-of-function mutants of SPL10 and its two homologous genes, SPL2 and SPL11, flowered late compared to WT plants. We found that SPL10 interacts with MED25, a subunit of the Mediator complex, which bridges transcription factors and RNA polymerase II to facilitate transcription initiation. Genetic analysis showed that MED25 acts downstream of SPL10 to execute SPL10-regulated floral transition. Furthermore, SPL10 was required for MED25 association with the promoters of two target genes, FUL and LFY. We provide evidence that SPL10 recruits MED25 to the promoter of target genes to regulate flowering time. Our results on the SPL10/MED25 module are relevant to the molecular mechanism of other SPL family members. This article is protected by copyright. All rights reserved.
C-MYC and BCL2: Correlation between Protein Over-Expression and Gene Translocation and Impact on Outcome in Diffuse Large B Cell Lymphoma

Background: Due to lack of availability of gene expression profiling (GEP) for most developing countries and clinicians; the immunohistochemistry (IHC) is mostly used in the clinical application. The aim of our study is to check the possibility of using IHC to detect MYC and BCL2 in our patients with diffuse large B-cell lymphoma (DLBCL) instead of GEP to stratify them into high and low-risk groups. This will help in a proper treatment choice of subsequent improvement in the survival outcome. Method: During the study period, 90 DLBCL patients were eligible. MYC and BCL2 evaluated by IHC and gene rearrangement by real-time PCR (RT-PCR) and correlated with clinical-pathological features and survival. Results: Through IHC, the expression of MYC, BCL2, and double expression was detected in 35.6%, 46.7% and 30% of patients, respectively. While by RT-PCR, it was 4.53±0.74 for MYC compared with 2.18±0.78 for BCL-2. Most patients with BCL2+/MYC+; double-expressor and double-hit lymphomas (DEL and DHL) had high stage (III, IV), more extra-nodal involvement, (P value <0.001) and intermediate to high International Prognostic Index (IPI) risk profile (P-value <0.001). The median overall survival was 14 months and 6 months for DEL and DHL, respectively. While all patients with DHL died during the follow-up period, the median PFS were only 2 months for DEL. There was a statistically significant correlation between mRNA of MYC and BCL2 with their protein expression (p<0.001). Conclusion: Our results confirmed the unique characters and poor outcome associated with DEL and DHL mandated the need for more intense therapy and not the standard protocol. Moreover, the significant correlation between protein overexpression and gene rearrangement may open the door for the possibility to use IHC instead of RT-PCR in developing countries.
The role of type III collagen in family members of patients with abdominal aortic aneurysms.

OBJECTIVES type III collagen is responsible for the tensile strength of the aorta-wall. To determine if genetic defect in the type III collagen production is associated with familial clustering of AAA. METHODS fifty-six patients with AAA and 82 first-degree family members participated. The medical and family histories were obtained. All these relatives were screened by ultrasound for AAA. In 58 relatives of 20 families, skin biopsies were taken for protein analysis to measure type III collagen production in cultured fibroblasts. RESULTS only one new AAA was detected in a brother of a patient. Four other relatives were already known with AAA. Three AAA patients had a type III collagen deficiency, but type III collagen was normal in all family members. CONCLUSION type III collagen deficiency does not appear to be an aetiological factor in the development of AAA.
Comparative lipidomic studies of Scenedesmus sp. (Chlorophyceae) and Cylindrotheca closterium (Bacillariophyceae) reveal their differences in lipid production under nitrogen starvation

Microalgae are a promising resource for the highly sustainable production of various biomaterials (food and feed), high‐value biochemicals, or biofuels. However, factors influencing the valued lipid production from oleaginous algae require a more detailed investigation. This study elucidates the variations in lipid metabolites between a marine diatom (Cylindrotheca closterium) and a freshwater green alga (Scenedesmus sp.) under nitrogen starvation at the molecular species level, with emphasis on triacylglycerols using liquid chromatography–electrospray ionization mass spectrometry techniques. A comprehensive analysis was carried out by comparing the changes in total lipids, growth kinetics, fatty acid compositions, and glycerolipid profiles at the molecular species level at different time points of nitrogen starvation. A total of 60 and 72 triacylglycerol molecular species, along with numerous other polar lipids, were identified in Scenedesmus sp. and C. closterium, respectively, providing the most abundant triacylglycerol profiles for these two species. During nitrogen starvation, more triacylglycerol of Scenedesmus sp. was synthesized via the “eukaryotic pathway” in the endoplasmic reticulum, whereas the increase in triacylglycerol in C. closterium was mainly a result of the “prokaryotic pathway” in the chloroplasts after 96 h of nitrogen starvation. The distinct responses of lipid synthesis to nitrogen starvation exhibited by the two species indicate different strategies of lipid accumulation, notably triacylglycerols, in green algae and diatoms. Scenedesmus sp. and Cylindrotheca closterium could serve as excellent candidates for the mass production of biofuels or polyunsaturated fatty acids for nutraceutical purposes.
Preliminary Work Towards Finding Proteins as Potential Vaccine Candidates for Vibrio cholerae Pakistani Isolates through Reverse Vaccinology

Background and Objective: Vibrio cholerae continues to emerge as a dangerous pathogen because of increasing resistance to a number of antibiotics. This paper provides a solution to emerging antibiotic resistance by introducing novel proteins as vaccine candidates against cholera. Materials and Methods: Vibrio cholerae genome versatility is a hurdle for developing a vaccine to combat diarrhoeal infection, so its core gene information was used to determine a potential vaccine candidate. Whole genome sequence data of more than 100 Vibrio cholerae strains were used simultaneously to get core genome information. The VacSol pipeline based on reverse vaccinology was selected to address the problem of safe, cheap, temperature-stable, and effective vaccine candidates which can be used for vaccine development against Vibrio cholerae. VacSol screens vaccine candidates using integrated, well-known, and robust algorithms/tools for proteome analysis. The proteomes of the pathogens were initially screened to predict homology using BLASTp. Proteomes that are non-homologous to humans are then subjected to a predictor for localization. Helicer predicts transmembrane helices for the protein. Proteins failing to comply with the set parameters were filtered at each step, and finally, 11 proteins were filtered as vaccine candidates. Results: This selected group of vaccine candidates consists of proteins from almost all structural parts of Vibrio cholerae. Their blast results show that this filtered group includes flagellin A protein, a protein from the Zn transporter system, a lipocarrier outer membrane protein, a peptidoglycan-associated protein, a DNA-binding protein, a chemotaxis protein, a tRNA Pseuriudine synthase A, and two selected proteins, which were beta lactamases. The last two uncharacterized proteins possess 100% similarity to V. albensis and Enterobacter, respectively. Tertiary structure and active site determination show a large number of pockets on each protein. Conclusions: The most interesting finding of this study is that 10 proteins out of 11 filtered proteins are introduced as novel potential vaccine candidates. These novel vaccine candidates can result in the development of cost-effective and broad-spectrum vaccines which can be used in countries where cholera is a major contributor to diarrheal disease.
Channel Estimation Based on Linear Filtering Least Square in OFDM Systems

—Orthogonal Frequency Division Multiplexing (OFDM) has been a popular scheme for digital communication systems, which is widely used in digital television and audio broadcasting, wireless networks, powerline networks, and the Fourth Generation (4G) mobile communications. In OFDM scheme, channel estimation is a necessary technique for improving the system’s performance. Linear Least Square (LLS) and Linear Filtering LS (LFLS) channel estimation methods are proposed in this paper. The LLS channel estimation method can improve the accuracy of channel estimation based on timedomain threshold. The LFLS channel estimation method can effectively suppress the Additive White Gaussian Noise (AWGN) by the linear filter. Simulation results are shown to verify the effectiveness of the proposed LFLS channel estimation method. Compared with LS and LLS channel estimation methods in CP-OFDM system, the LFLS channel estimation method can suppress the noise effectively through the appropriate linear filter in time domain and provide superior system performance over multipath channel conditions.
Causal relationship between years of education and the occurrence of rheumatoid arthritis

Objective To search out whether or not years of education is causally related to rheumatoid arthritis (RA). Method We conducted a two-sample Mendelian randomisation (MR) analysis employing inverse-variance weighted (IVW), weighted median and MR-Egger regression analysis. We chose statistic data of years of education from the UK Biobank genome-wide association studies (GWASs) (n=293 723) as the exposure and a meta-analysis of GWASs of RA with autoantibody (n=5539) and European controls (n=20 169) as the outcome. Results We selected a total of 49 single nucleotide polymorphisms as instrumental variables (IVs). The IVW method instructed an inverse causative relationship between years of education and RA (β=− 0.039, SE=0.283, p=0.008). MR-Egger regression test showed that directional pleiotropy seems not to bias the MR results (intercept=0.028; p=0.358). MR-Egger analysis demonstrated no causative relationship between RA and years of education (β=− 2.320, SE=1.709, p=0.181). However, the weighted median approach indicated a causative association between RA and years of education (β=−0.950, SE=0.355, p=0.008). Conclusions The MR analysis supported a potential inverse causative relationship between years of education and development of RA.
AhR Activation in Pharmaceutical Development: Applying Liver Gene Expression Biomarker Thresholds to Identify Doses Associated with Tumorigenic Risks in Rats.

Aryl hydrocarbon receptor (AhR) activation is associated with carcinogenicity of non-genotoxic AhR-activating carcinogens such as 2, 3, 7, 8-tetrachlorodibenzodioxin (TCDD), and is often observed with drug candidate molecules in development and raises safety concerns. As downstream effectors of AhR signaling, the expression and activity of Cyp1a1 and Cyp1a2 genes are commonly monitored as evidence of AhR activation to inform carcinogenic risk of compounds in question. However, many marketed drugs and phytochemicals are reported to induce these Cyps modestly and are not associated with dioxin-like toxicity or carcinogenicity. We hypothesized that a threshold of AhR activation needs to be surpassed in a sustained manner in order for the dioxin-like toxicity to manifest, and a simple liver gene expression signature based on Cyp1a1 and Cyp1a2 from a short-term rat study could be used to assess AhR activation strength and differentiate tumorigenic dose levels from non-tumorigenic ones. To test this hypothesis, short term studies were conducted in Wistar Han rats with two AhR-activating carcinogens (TCDD and PCB126) at minimally carcinogenic and non-carcinogenic dose levels, and three AhR-activating non-carcinogens (omeprazole, mexiletine, and canagliflozin) at the top doses used in their reported 2-year rat carcinogenicity studies. A threshold of AhR activation was identified in rat liver that separated a meaningful "tumorigenic-strength AhR signal" from a statistically-significant AhR activation signal that was not associated with dioxin-like carcinogenicity. These studies also confirmed the importance of the sustainability of AhR activation for carcinogenic potential. A sustained activation of AhR above the threshold could thus be used in early pharmaceutical development to identify dose levels of drug candidates expected to exhibit dioxin-like carcinogenic potential.
Extending the chimeric receptor-based T-cell targeting strategy to solid tumors

The adoptive transfer of T cells expressing chimeric antigen receptors (CARs) has emerged as a promising immunotherapeutic strategy against cancer. Administering CAR-expressing T cells in combination with agents that promote the expression of CAR targets or optimize T-cell function within the tumor microenvironment may further improve the therapeutic potential of this approach.
Histone deacetylase 4 promotes type I interferon signaling, restricts DNA viruses, and is degraded via vaccinia virus protein C6

Significance Histone deacetylases (HDACs) are regulators of host gene expression. HDAC4 is shown here to have an important role in type I interferon (IFN) signaling. Here, multiple cell lines lacking HDAC4 had impaired responses to IFN-α and were rescued by reintroduction of HDAC4. The biological significance of HDAC4 was demonstrated by the enhanced replication and spread of two DNA viruses, vaccinia virus (VACV) and herpes simplex virus type I, in HDAC4−/− cells, and their diminished replication when HDAC4 was overexpressed. Furthermore, HDAC4 was targeted for proteasomal degradation early after infection with VACV, and VACV protein C6, an inhibitor of type I IFN signaling, was necessary and sufficient for this degradation. In summary, HDAC4 is a restriction factor for large DNA viruses. Interferons (IFNs) represent an important host defense against viruses. Type I IFNs induce JAK-STAT signaling and expression of IFN-stimulated genes (ISGs), which mediate antiviral activity. Histone deacetylases (HDACs) perform multiple functions in regulating gene expression and some class I HDACs and the class IV HDAC, HDAC11, influence type I IFN signaling. Here, HDAC4, a class II HDAC, is shown to promote type I IFN signaling and coprecipitate with STAT2. Pharmacological inhibition of class II HDAC activity, or knockout of HDAC4 from HEK-293T and HeLa cells, caused a defective response to IFN-α. This defect in HDAC4−/− cells was rescued by reintroduction of HDAC4 or catalytically inactive HDAC4, but not HDAC1 or HDAC5. ChIP analysis showed HDAC4 was recruited to ISG promoters following IFN stimulation and was needed for binding of STAT2 to these promoters. The biological importance of HDAC4 as a virus restriction factor was illustrated by the observations that (i) the replication and spread of vaccinia virus (VACV) and herpes simplex virus type 1 (HSV-1) were enhanced in HDAC4−/− cells and inhibited by overexpression of HDAC4; and (ii) HDAC4 is targeted for proteasomal degradation during VACV infection by VACV protein C6, a multifunctional IFN antagonist that coprecipitates with HDAC4 and is necessary and sufficient for HDAC4 degradation.
Thomas M. Jessell (1951-2019)

ABSTRACT Thomas M. Jessell died on April 28, 2019. Tom revolutionized our understanding of the mechanisms through which neuronal cell type identities are programmed during development to dictate their function in the adult nervous system. Here, we (two former postdocs from his lab) remember some of his most important scientific contributions and how these changed the way we now understand and think about neuronal circuits controlling movement. Summary: Silvia Arber and James Briscoe look back at the life and career of Thomas M. Jessell who revolutionized our understanding of the mechanisms controlling neural tube development and circuit formation.
MATERNAL AND FETAL INFECTION

Although their incidence varies among populations, maternal-fetal infections are increasingly recognized to be among the most common causes of maternal and perinatal morbidity. The use of new techniques, including nucleic acid hybridization and direct fetal or trophoblastic cell sampling, continues to accelerate our knowledge of the epidemiology, microbiology, and immunology, as well as means to diagnose, treat, and prevent individual congenitally transmitted infections. Given the number and complexity of these infections, only selected aspects of recent advances are presented.
Software Ecosystems A Sytematic Literature Review

Software ecosystems are sets of software solutions functioning as a unit, enabling actors to automate activities and transactions. Arguably, software ecosystems are gaining importance with the advent of, e.g., the Google Android, Apple iOS, and Salesforce.com ecosystems. However, there exists no systematic overview of the research done on software ecosystems from a software engineering perspective. We performed a systematic literature review of software ecosystem research, analyzing 59 papers on the subject taken from a gross collection of 212. Our main conclusions are that while research on software ecosystems is increasing there is a) little consensus on what constitutes a software ecosystem, b) few analytical models of software ecosystems exist, and c) little research is done in the context of real-world ecosystems.
Temporal optimization of quality during video compression

Recent VQM developments have provided a set of methods for evaluating the relative subjective quality of a treated video segment compared to the original video. In this paper we intend to optimize the subjective quality of multi-segment video sequence for a given global bitrate constraint, by adjusting some basic compression parameters such as the Quantization Parameter, the frame rate and the image size along the video sequence. An optimal resource allocation algorithm has been designed to efficiently allocate the global video bit-budget to the different shots (i.e. segments), depending on the content of shots, by using 2 different optimizing criteria: maximize the minimum perceived quality over the sequence of shots, and maximize the average perceived quality over the sequence. We have studied the impact of such an approach on more than 800 shots extracted from 15 videos of different content. kw]Video Quality Measure