Structural Modification of the Immunosuppressants FK-506 and Ascomycin Using a Biological Approach

Bioconversion was utilized to conduct structural modification of the complex molecules FK-506 and ascomycin. Four interesting microbial reactions, regiospecific O-demethylation, glucosylation, hydroxylation, and phosphorylation, yielding various derivatives of the title compounds, were discovered from screening more than thousand microorganisms including bacteria, actinomycetes, and fungi. The isolated compounds were evaluated for a better understanding of structural and functional features responsible for their biological activity

Modified collection methods and quality of semen in Nigerian local turkeys (Meleagris gallopavo)

Semen collection in birds was initially achieved either via post-mortem drainage of the vas deferens or by cloacal retrieval after natural mating. Current techniques do not exclude stress and risk of injury during restraint or milking, especially in domestic turkeys. The present study was designed to develop more convenient methods of semen collection in turkeys. It involved five (n = 5) matured turkey toms weighing approximately 12 – 15 kg and two (n = 2) turkey hens. In the improved collection method, toms were stimulated by exposing them to hens, covered using a locally constructed wooden box. They were allowed to mount until there was evidence of ejaculatory response, demonstrated by increased abdominal pressure and cloacal contraction. After mounting, the tail feathers were lifted, and a collection vial was placed immediately below the cloaca to collect the ejaculates. In the modified abdominal massage, the turkey toms were restrained on sterna recumbency while the ejaculatory response was initiated by gently massaging the soft part of the abdomen and backward massage of the tail feathers. This is continued by rubbing either side of the cloaca till erection is achieved and semen is milked into a collection vial by gently squeezing the cloaca. Collections were made twice a week for four weeks using each method independently. The mean semen volume in the improved collection method was significantly (p < 0.05) higher than the modified abdominal massage. There was no significant (p > 0.05) difference in motility, abnormalities and concentration between both methods. The results from this study suggest that both collection methods were satisfactory for practical use and may offset some challenges associated with the most widely used abdominal massage technique of semen collection in turkeys

Object Goal Navigation with End-to-End Self-Supervision

A household robot should be able to navigate to target locations without requiring users to first annotate everything in their home. Current approaches to this object navigation challenge do not test on real robots and rely on expensive semantically labeled 3D meshes. In this work, our aim is an agent that builds self-supervised models of the world via exploration, the same as a child might. We propose an end-to-end self-supervised embodied agent that leverages exploration to train a semantic segmentation model of 3D objects, and uses those representations to learn an object navigation policy purely from self-labeled 3D meshes. The key insight is that embodied agents can leverage location consistency as a supervision signal - collecting images from different views/angles and applying contrastive learning to fine-tune a semantic segmentation model. In our experiments, we observe that our framework performs better than other self-supervised baselines and competitively with supervised baselines, in both simulation and when deployed in real houses

Novel VPS13B Mutations in Three Large Pakistani Cohen Syndrome Families Suggests a Baloch Variant with Autistic-Like Features.

BackgroundCohen Syndrome (COH1) is a rare autosomal recessive disorder, principally identified by ocular, neural and muscular deficits. We identified three large consanguineous Pakistani families with intellectual disability and in some cases with autistic traits.MethodsClinical assessments were performed in order to allow comparison of clinical features with other VPS13B mutations. Homozygosity mapping followed by whole exome sequencing and Sanger sequencing strategies were used to identify disease-related mutations.ResultsWe identified two novel homozygous deletion mutations in VPS13B, firstly a 1 bp deletion, NM_017890.4:c.6879delT; p.Phe2293Leufs*24, and secondly a deletion of exons 37-40, which co-segregate with affected status. In addition to COH1-related traits, autistic features were reported in a number of family members, contrasting with the "friendly" demeanour often associated with COH1. The c.6879delT mutation is present in two families from different regions of the country, but both from the Baloch sub-ethnic group, and with a shared haplotype, indicating a founder effect among the Baloch population.ConclusionWe suspect that the c.6879delT mutation may be a common cause of COH1 and similar phenotypes among the Baloch population. Additionally, most of the individuals with the c.6879delT mutation in these two families also present with autistic like traits, and suggests that this variant may lead to a distinct autistic-like COH1 subgroup

Securing Secure Aggregation: Mitigating Multi-Round Privacy Leakage in Federated Learning

Secure aggregation is a critical component in federated learning, which enables the server to learn the aggregate model of the users without observing their local models. Conventionally, secure aggregation algorithms focus only on ensuring the privacy of individual users in a single training round. We contend that such designs can lead to significant privacy leakages over multiple training rounds, due to partial user selection/participation at each round of federated learning. In fact, we empirically show that the conventional random user selection strategies for federated learning lead to leaking users\u27 individual models within number of rounds linear in the number of users. To address this challenge, we introduce a secure aggregation framework with multi-round privacy guarantees. In particular, we introduce a new metric to quantify the privacy guarantees of federated learning over multiple training rounds, and develop a structured user selection strategy that guarantees the long-term privacy of each user (over any number of training rounds). Our framework also carefully accounts for the fairness and the average number of participating users at each round. We perform several experiments on MNIST and CIFAR-10 datasets in the IID and the non-IID settings to demonstrate the performance improvement over the baseline algorithms, both in terms of privacy protection and test accuracy

Blended learning in undergraduate dental education: a global pilot study.

AIMS: To explore the global trends in blended learning in undergraduate dental education during the COVID pandemic and during the recovery phase by engaging with the students and faculty and evaluate the implications for dental education in the post-COVID era. METHODS: It was a pilot cross-sectional study which employed a convenience sampling technique to recruit representatives of dental faculty and undergraduate students in 80 dental institutions globally. A previously validated questionnaire consisting of a combination of closed and open-ended items was used for data collection. Responses to these online questionnaires were processed and analysed using the R statistical computing environment. RESULTS: A total of 320 dental students and 169 faculty members from 47 different dental institutions participated in the study. Video and Live Online Tutorials were considered to be the most effective method of online learning followed by online question banks by both groups. Significant differences were noted between faculty and students regarding time spent and effectiveness of online teaching and learning, respectively, both before and after the start of COVID. The results highlight the faculty need to engage more closely with the students to address their learning needs. Finally, the participants provided several recommendations regarding the future development of teaching and learning strategies as well as assessments in the post-pandemic era. CONCLUSIONS: This is the first study which explores blended learning in dental education with participants from multiple institutions in different regions of the globe. Compared to the faculty, students considered online learning to be less interactive and preferred learning activities and all assessments to be delivered face-to-face. The results underscore the need to adapt teaching practices to suit the learning needs of the students

Synthesis and in vitro antiproliferative activity of new 1-phenyl-3-(4-(pyridin-3-yl)phenyl)urea scaffold-based compounds

A new series of 1-phenyl-3-(4-(pyridin-3-yl)phenyl)urea derivatives were synthesized and subjected to in vitro antiproliferative screening against National Cancer Institute (NCI)-60 human cancer cell lines of nine different cancer types. Fourteen compounds 5a-n were synthesized with three different solvent exposure moieties (4-hydroxylmethylpiperidinyl and trimethoxyphenyloxy and 4-hydroxyethylpiperazine) attached to the core structure. Substituents with different π and σ values were added on the terminal phenyl group. Compounds 5a-e with a 4-hydroxymethylpiperidine moiety showed broad-spectrum antiproliferative activity with higher mean percentage inhibition values over the 60-cell line panel at 10 µM concentration. Compound 5a elicited lethal rather than inhibition effects on SK-MEL-5 melanoma cell line, 786-0, A498, RXF 393 renal cancer cell lines, and MDA-MB-468 breast cancer cell line. Two compounds, 5a and 5d showed promising mean growth inhibitions and thus were further tested at five-dose mode to determine median inhibitory concentration (IC50) values. The data revealed that urea compounds 5a and 5d are the most active derivatives, with significant efficacies and superior potencies than paclitaxel in 21 different cancer cell lines belonging particularly to renal cancer and melanoma cell lines. Moreover, 5a and 5d had superior potencies than gefitinib in 38 and 34 cancer cell lines, respectively, particularly colon cancer, breast cancer and melanoma cell lines

Using Combined Morphological, Allometric and Molecular Approaches to Identify Species of the Genus Raillietiella (Pentastomida)

Taxonomic studies of parasites can be severely compromised if the host species affects parasite morphology; an uncritical analysis might recognize multiple taxa simply because of phenotypically plastic responses of parasite morphology to host physiology. Pentastomids of the genus Raillietiella are endoparasitic crustaceans primarily infecting the respiratory system of carnivorous reptiles, but also recorded from bufonid anurans. The delineation of pentastomids at the generic level is clear, but the taxonomic status of many species is not. We collected raillietiellids from lungs of the invasive cane toad (Rhinella marina), the invasive Asian house gecko (Hemidactylus frenatus), and a native tree frog (Litoria caerulea) in tropical Australia, and employed a combination of genetic analyses, and traditional and novel morphological methods to clarify their identity. Conventional analyses of parasite morphology (which focus on raw values of morphological traits) revealed two discrete clusters in terms of pentastome hook size, implying two different species of pentastomes: one from toads and a tree frog (Raillietiella indica) and another from lizards (Raillietiella frenatus). However, these clusters disappeared in allometric analyses that took pentastome body size into account, suggesting that only a single pentastome taxon may be involved. Our molecular data revealed no genetic differences between parasites in toads versus lizards, confirming that there was only one species: R. frenatus. This pentastome (previously known only from lizards) clearly is also capable of maturing in anurans. Our analyses show that the morphological features used in pentastomid taxonomy change as the parasite transitions through developmental stages in the definitive host. To facilitate valid descriptions of new species of pentastomes, future taxonomic work should include both morphological measurements (incorporating quantitative measures of body size and hook bluntness) and molecular data

Evaluating indoor positioning systems in a shopping mall : the lessons learned from the IPIN 2018 competition

The Indoor Positioning and Indoor Navigation (IPIN) conference holds an annual competition in which indoor localization systems from different research groups worldwide are evaluated empirically. The objective of this competition is to establish a systematic evaluation methodology with rigorous metrics both for real-time (on-site) and post-processing (off-site) situations, in a realistic environment unfamiliar to the prototype developers. For the IPIN 2018 conference, this competition was held on September 22nd, 2018, in Atlantis, a large shopping mall in Nantes (France). Four competition tracks (two on-site and two off-site) were designed. They consisted of several 1 km routes traversing several floors of the mall. Along these paths, 180 points were topographically surveyed with a 10 cm accuracy, to serve as ground truth landmarks, combining theodolite measurements, differential global navigation satellite system (GNSS) and 3D scanner systems. 34 teams effectively competed. The accuracy score corresponds to the third quartile (75th percentile) of an error metric that combines the horizontal positioning error and the floor detection. The best results for the on-site tracks showed an accuracy score of 11.70 m (Track 1) and 5.50 m (Track 2), while the best results for the off-site tracks showed an accuracy score of 0.90 m (Track 3) and 1.30 m (Track 4). These results showed that it is possible to obtain high accuracy indoor positioning solutions in large, realistic environments using wearable light-weight sensors without deploying any beacon. This paper describes the organization work of the tracks, analyzes the methodology used to quantify the results, reviews the lessons learned from the competition and discusses its future