Transferable neural networks for enhanced sampling of protein dynamics

Variational auto-encoder frameworks have demonstrated success in reducing complex nonlinear dynamics in molecular simulation to a single non-linear embedding. In this work, we illustrate how this non-linear latent embedding can be used as a collective variable for enhanced sampling, and present a simple modification that allows us to rapidly perform sampling in multiple related systems. We first demonstrate our method is able to describe the effects of force field changes in capped alanine dipeptide after learning a model using AMBER99. We further provide a simple extension to variational dynamics encoders that allows the model to be trained in a more efficient manner on larger systems by encoding the outputs of a linear transformation using time-structure based independent component analysis (tICA). Using this technique, we show how such a model trained for one protein, the WW domain, can efficiently be transferred to perform enhanced sampling on a related mutant protein, the GTT mutation. This method shows promise for its ability to rapidly sample related systems using a single transferable collective variable and is generally applicable to sets of related simulations, enabling us to probe the effects of variation in increasingly large systems of biophysical interest.Comment: 20 pages, 10 figure

Increase in germination and plating efficiency of Neurospora crassa microconidia by amino acid supplementation

A major difficulty that has limited the use of uninucleate microconidia in genetic research is their low and erratic germination. We found that the supplementation of sorbose plating medium by amino acids, notably aspartic acid and methionine, markedly improved germination and plating efficiency of microconidia of mcm and pe fl genotypes of N. crassa. The plating efficiency of mcm microconidia in amino acid supplemented medium was comparable to macroconidia

Determination Of Aerosol Optical Thickness From Spectral Sky Transmittance.

The objective of this study is to test the feasibility of the proposed technique for retrieving spectral aerosol optical thickness (AOT) from the spectral transmittance measurements. The measurements have been acquired around Penang Island, Malaysia. Ground-based measurements were made with a handheld spectroradiometer. The measured spectral transmittance data were then converted to AOT values 6 spectral bands between 400 and 900 nm. Spectral AOT maps were generated using Kriging interpolation method for the 6 spectral bands. Air quality map was produced using this technique

Remote Sensing Of Turbidity Mapping From Digital Camera Imagery.

A complete set of normal digital camera data and ground-based measurements are used to test an algorithm for retrieval of turbidity distribution in the Prai Estuary, Penang, Malaysia

PM10 Retrieval From Spectroradiometer Measurements.

This study attempts to determine the aerosol optical thickness (AOT) from spectroradiometer data. The spectroradiometer is used to measure the atmospheric transmittances in a wide spectrum over Penang Island, Malaysia

Bacterial ventriculoperitoneal shunt infections: changing trends in antimicrobial susceptibility, a 7-year retrospective study from Pakistan

BACKGROUND: Ventriculoperitoneal (VP) shunt infections in adults represent a severe complication and make treatment more challenging. Therefore, drug susceptibility patterns are crucial for therapeutic decisions and infection control in neurosurgical centers. This 7-year retrospective study aimed to identify the bacteria responsible for adult VP shunt infections and determine their drug susceptibility patterns. METHODS: This single-center study was performed from 2015 to 2021 in Lahore, Pakistan, and included CSF cultures from VP shunt infections. Demographic data, causative organisms, and antimicrobial susceptibility testing results were collected. Multivariate analysis of variance (MANOVA) and two-sample t-tests were used to analyze and compare the antibiotic sensitivity trends over the study period. RESULTS: 14,473 isolates recovered from 13,937 CSF samples of VP shunt infections were identified and analyzed for their susceptibility patterns to antimicrobials. The proportion of Gram-negative and Gram-positive bacteria were 11,030 (76%) and 3443 (24)%, respectively. The predominant bacteria were Acinetobacter species (n = 5898, 41%), followed by Pseudomonas species (n = 2368, 16%) and coagulase-negative Staphylococcus (CoNS) (n = 1880, 13%). 100% of Staphylococcus aureus (S.aureus) and CoNS were sensitive to vancomycin and linezolid (n = 2580). However, 52% of S. aureus (719/1,343) were methicillin-resistant Staphylococcus aureus (MRSA). Acinetobacter showed maximum sensitivity to meropenem at 69% (2759/4768). Pseudomonas was 80% (1385/1863 sensitive to piperacillin-tazobactam, Escherichia coli (E. coli) showed 72% to amikacin (748/1055), while Klebsiella spp. was 57% (574/1170) sensitive to piperacillin-tazobactam. The sensitivity of piperacillin-tazobactam and meropenem for Gram-negative bacteria decreased significantly (p < 0.05) over 7 years, with 92.2% and 88.91% sensitive in 2015 and 66.7% and 62.8% sensitive in 2021, respectively. CONCLUSION: The significant decrease in the effectiveness of carbapenem and beta-lactam/beta-lactamase inhibitor combination drugs for the common Gram-negative causative agents of VP shunt infections suggests that alternative antibiotics such as colistin, fosfomycin, ceftazidime/avibactam, ceftolozane/tazobactam, and tigecycline should be considered and in consequence included in testing panels. Additionally, it is recommended to adopt care bundles for the prevention of VP shunt infection

High-Frequency Jet Ventilation During Cryoablation of Small Renal Tumours

AIM: To evaluate the effect of high-frequency jet ventilation (HFJV) in place of standard intermittent positive-pressure ventilation (IPPV) on procedure duration, patient radiation dose, complication rates, and outcomes during CT-guided cryoablation of small renal tumours. MATERIALS AND METHODS: One hundred consecutive CT-guided cryoablation procedures to treat small renal tumours under general anaesthesia were evaluated-50 with standard IPPV and 50 after the introduction of HFJV as standard practice. Anaesthesia and procedural times, ionising radiation dose, complications, and 1-month post-treatment outcomes were collected. RESULTS: HFJV was feasible and safe in all cases. Mean procedure time and total anaesthetic time were shorter with HFJV (p = <0.0001). The number of required CT acquisitions (p = 0.0002) and total procedure patient radiation dose (p = 0.0027) were also lower in the HFJV group compared with the IPPV group. There were a total of four complications of Clavien-Dindo classification 3 or above-three in the IPPV group and one in the HFJV group. At 1-month follow-up, two cases (both in the IPPV group) demonstrated subtotal treatment. Both cases were subsequently successfully retreated with cryoablation. CONCLUSION: By reducing target tumour motion during CT-guided renal cryoablation, HFJV can reduce procedure times and exposure to ionising radiation. HFJV provides an important adjunct to complex image-guided interventions, with potential to improve safety and treatment outcomes