Focal cortical dysplasia (FCD) is one of the most common causes of drug resistant epilepsy. Our aim was to evaluate the role of presurgical noninvasive multimodality imaging techniques in selecting ...patients with refractory epilepsy and focal cortical dysplasia for epilepsy surgery and the influence of the imaging modalities on long-term seizure freedom.
We performed a retrospective analysis of data of 188 consecutive patients with FCD and refractory epilepsy with at least 2 years of postsurgery follow-up. Predictors of seizure freedom and the sensitivity of neuroimaging modalities were analyzed.
MR imaging showed clear-cut FCD in 136 (72.3%) patients. Interictal FDG-PET showed focal hypo-/hypermetabolism in 144 (76.6%); in 110 patients in whom ictal SPECT was performed, focal hyperperfusion was noted in 77 (70.3%). Focal resection was the most common surgery performed in 112 (59.6%). Histopathology revealed FCD type I in 102 (54.3%) patients. At last follow-up, 124 (66.0%) were seizure-free. Complete resection of FCD and type II FCD were predictors of seizure freedom. Localization of FCD on either MR imaging or PET or ictal SPECT had the highest sensitivity for seizure freedom at 97.5%. Among individual modalities, FDG-PET had the highest sensitivity (78.2%), followed by MR imaging (75.8%) and ictal SPECT (71.8%). The sensitivity of MR imaging to localize type I FCD (60.8%) was significantly lower than that for type II FCD (84.8%,
< .001). Among 37 patients with subtle MR imaging findings and a focal FDG-PET pattern, 30 patients had type I FCD.
During presurgical multimodality evaluation, localization of the extent of the epileptogenic zone in at least 2 imaging modalities helps achieve seizure freedom in about two-thirds of patients with refractory epilepsy due to FCD. FDG-PET is the most sensitive imaging modality for seizure freedom, especially in patients with type I FCD.
Bacterial lipopolysaccharides (LPS), also termed endotoxins, considered to be a major virulence factor, are responsible for the lethal effects and clinical manifestations of diseases in humans and ...animals. Higher animals are extremely sensitive to endotoxin even at low doses but lower vertebrates like fish are often resistant to endotoxic shock. Toll-like receptor (TLR)-4 is mainly involved in the activation of the immune system by LPS through the specific recognition of its endotoxin (Lipid A) moiety. Although several Toll-like receptors are present in fish, those molecules specifically involved in TLR-4 mediated endotoxin recognition have not been fully established in different fish species. Despite this, LPS has the potency to express cytokines, acute-phase proteins and also exerts immunological, pathological, physiological, immuno-endocrinological and neuro-immunological effects in several fish species. The immunostimulating effects of endotoxin by triggering various immune parameters such as T and B lymphocytes, macrophages, and complement systems have been established in teleosts. This article reviews the multiple biological effects of endotoxin which will further strengthen the knowledge among researchers on various aspects of endotoxin in lower vertebrates, particularly in the piscine system.
Hypersonic leading-edge separation is studied toward understanding the varying shock-related unsteadiness with freestream Reynolds number (
1.66
×
10
5
≤
Re
D
≤
5.85
×
10
5
) in the newly constructed ...hypersonic Ludwieg tunnel (HLT) at a freestream design Mach number of
M
∞
=
6.0
. An axisymmetric flat-face cylinder of base body diameter
D
=
35
mm is fitted with axial protrusions of different fineness (
d
/
D
=
0.1
,
0.2
,
0.26
,
0.34
at
L
/
D
=
1.4
) and slenderness (
L
/
D
=
0.7
,
1
,
1.4
,
1.9
at
d
/
D
=
0.2
) ratio to induce a wide range of leading-edge separation intensities. Qualitative and quantitative assessments are made using schlieren imaging, planar laser Rayleigh scattering, and unsteady pressure measurements. A well-known to-and-fro shock motion called pulsation and a flapping shock-shear layer oscillation is observed as
Re
D
changes. A shorter protrusion length (
L
/
D
=
0.7
), associated with pulsation, produces a pressure loading four orders higher than the cases with longer protrusion lengths associated with flapping. There exists a critical separation length (
L
/
D
≥
1.4
) beyond which the separated shear layer trips to turbulence and introduces fluctuations in the recirculation region as
Re
D
increases. The intensity of the separated turbulent shear layer is dampened by an order of magnitude, provided the reattachment angle is shallow by increasing the fineness ratio to
d
/
D
≥
0.34
. There also exists a set of critical geometrical parameters (
L
/
D
=
1
,
d
/
D
=
0.2
) for which the unsteady modes (pulsation and flapping) switch between themselves during successive runs, probably due to upstream fluctuations. From the modal analysis of the Rayleigh scattering images, the first four dominant modes that drive flapping are identified as translatory flapping, sinuous flapping, and large and small-scale shedding.
Aims
To assess glutathione (GSH) biosynthesis ability and activity of dependent enzymes in food‐grade lactic acid bacteria (LAB) and correlating with genomic information on GSH system in LAB.
Methods ...and Results
Whole‐genome sequences of 26 food‐grade LAB were screened for the presence/absence of a set of genes involved in de novo GSH system. Multiple strains of Streptococcus thermophilus (37), Lactobacillus casei (37), Lactobacillus rhamnosus (4), Lactobacillus paracasei (8) Lactobacillus plantarum (23) and Lactobacillus fermentum (22) were screened for biochemical evidence of the GSH system. Multiple sequence analysis of GshF sequences was carried out for comparing the genomic signatures between GSH‐producing and nonproducing species.
Conclusions
Streptococcus thermophilus was found to have de novo GSH biosynthesis as well as import ability. Lactobacillus sp. were negative for GSH synthesis but could import it from the medium. All the species exhibited prolific GSH reductase and peroxidase activity. Sequence analysis revealed the absence of key amino acid residues as well as a truncated N‐terminal region in lactobacilli.
Significance and Impact of the Study
The study provides a comprehensive view on the status of an important antioxidative system (the GSH system) in LAB and is expected to serve as a primer for future work on the mechanistic role of GSH in the group.
Peptide materials have a wide array of functions, from tissue engineering and surface coatings to catalysis and sensing. Tuning the sequence of amino acids that comprise the peptide modulates peptide ...functionality, but a small increase in sequence length leads to a dramatic increase in the number of peptide candidates. Traditionally, peptide design is guided by human expertise and intuition and typically yields fewer than ten peptides per study, but these approaches are not easily scalable and are susceptible to human bias. Here we introduce a machine learning workflow-AI-expert-that combines Monte Carlo tree search and random forest with molecular dynamics simulations to develop a fully autonomous computational search engine to discover peptide sequences with high potential for self-assembly. We demonstrate the efficacy of the AI-expert to efficiently search large spaces of tripeptides and pentapeptides. The predictability of AI-expert performs on par or better than our human experts and suggests several non-intuitive sequences with high self-assembly propensity, outlining its potential to overcome human bias and accelerate peptide discovery.
The iron formation of Bonai-Keonjhar belt, Keonjhar district of Odisha comprises a promising horizon of Banded Iron Formation (BIF) which is situated in the western flank of North Odisha Iron Ore ...Craton (NOIC). In this investigation, major, trace and REE chemistry of the Banded Iron Formation of the area are utilized to interpret the source of metals and to explain the origin and depositional environment of the BIF. Petrographic study indicates that the BIF belongs to the oxide facies iron formation consisting mainly of iron oxide (hematite) mesobands arranged alternating with silica/quartz mesobands. Bedded layers, banding structures of quartz and hematite along with their diagenetic growth indicate a sedimentary depositional milieu for BIF. The geochemical analysis data reveal that the BIF is mainly composed of Fe
2
O
3
and SiO
2
, which constitute more than 97% of the bulk composition. Low concentration of Al
2
O
3
, TiO
2
and trace HFSEs (high field strength elements) showing that BIFs are relatively detritus free chemical sediments. The chondrite normalized REE pattern display positive Eu and negative Ce anomalies which suggest the source of Fe and silica was the result of deep ocean hydrothermal activity admixture with seawater.
Endocrine-resistant HR+/HER2- breast cancer (BC) and triple-negative BC (TNBC) are of interest for molecularly informed treatment due to their aggressive natures and limited treatment profiles. ...Patients of African Ancestry (AA) experience higher rates of TNBC and mortality than European Ancestry (EA) patients, despite lower overall BC incidence. Here, we compare the molecular landscapes of AA and EA patients with HR+/HER2- BC and TNBC in a real-world cohort to promote equity in precision oncology by illuminating the heterogeneity of potentially druggable genomic and transcriptomic pathways.
De-identified records from patients with TNBC or HR+/HER2- BC in the Tempus Database were randomly selected (N = 5000), with most having stage IV disease. Mutations, gene expression, and transcriptional signatures were evaluated from next-generation sequencing data. Genetic ancestry was estimated from DNA-seq. Differences in mutational prevalence, gene expression, and transcriptional signatures between AA and EA were compared. EA patients were used as the reference population for log fold-changes (logFC) in expression.
After applying inclusion criteria, 3433 samples were evaluated (n = 623 AA and n = 2810 EA). Observed patterns of dysregulated pathways demonstrated significant heterogeneity among the two groups. Notably, PIK3CA mutations were significantly lower in AA HR+/HER2- tumors (AA = 34% vs. EA = 42%, P < 0.05) and the overall cohort (AA = 28% vs. EA = 37%, P = 2.08e-05). Conversely, KMT2C mutation was significantly more frequent in AA than EA TNBC (23% vs. 12%, P < 0.05) and HR+/HER2- (24% vs. 15%, P = 3e-03) tumors. Across all subtypes and stages, over 8000 genes were differentially expressed between the two ancestral groups including RPL10 (logFC = 2.26, P = 1.70e-162), HSPA1A (logFC = - 2.73, P = 2.43e-49), ATRX (logFC = - 1.93, P = 5.89e-83), and NUTM2F (logFC = 2.28, P = 3.22e-196). Ten differentially expressed gene sets were identified among stage IV HR+/HER2- tumors, of which four were considered relevant to BC treatment and were significantly enriched in EA: ERBB2_UP.V1_UP (P = 3.95e-06), LTE2_UP.V1_UP (P = 2.90e-05), HALLMARK_FATTY_ACID_METABOLISM (P = 0.0073), and HALLMARK_ANDROGEN_RESPONSE (P = 0.0074).
We observed significant differences in mutational spectra, gene expression, and relevant transcriptional signatures between patients with genetically determined African and European ancestries, particularly within the HR+/HER2- BC and TNBC subtypes. These findings could guide future development of treatment strategies by providing opportunities for biomarker-informed research and, ultimately, clinical decisions for precision oncology care in diverse populations.
Abstract Aeromonas hydrophila is a Gram-negative bacteria associated with many disease conditions of aquatic animals. Two rough attenuated variants were derived from two smooth virulent types of this ...bacterium by continuous passage separately in laboratory over a period of 8 years in brain–heart infusion agar. These variants were checked to be rough lipopolysaccharides (LPS) types and attenuated since they neither produced any disease nor mortality in the injected fishes. The immunogenic potential of these variants remained unaltered as compared to parent smooth types and fish immunized with these variants resisted the infection and mortality upon cross challenge. Because of their intact immunogenic potential and loss of virulence, they may be used as candidates for fish immunization.
An experimental investigation of the application of biodiesel (recycled cooking fat and vegetable oil) on small marine craft diesel engines was completed. The tests were performed on Perkins 404C-22 ...(Marinised) in Boat No. 1 (Fair Countess) and on Nanni Diesel 3.100HE in Boat No. 2 (Aimee 2). The tests were designed and carried out in accordance with the standardised test procedure described in ISO 8178-4 Test Cycle E5. The performance and gaseous emissions of the tested engines were compared and analysed. The test results show that the power output for both trial engines operating with biodiesel were comparable to that fuelled with fossil diesel, but with an increase in fuel consumptions. The NO
x
emissions were found to be reduced when fuelled with biodiesel. The CO emissions were found to be lower when the engines operated at higher loads using biodiesel.
River-training structures, such as spur dikes, are effective engineered methods used to protect banks and improve aquatic habitat. This paper reports the development and application of a ...two-dimensional depth-averaged hydrodynamic model to simulate suspended sediment concentration distribution in a groyne field. The governing equations of flow hydrodynamic model are depth-averaged two-dimensional Reynold’s averaged momentum equations and continuity equation in which the density of sediment laden-flow varies with the concentration of suspended sediment. The depth-averaged two-dimensional convection and diffusion equation was solved to obtain the depth-averaged suspended sediment concentration. The source term is the difference between suspended sediment entrainment and deposition from bed surface. One laboratory experiment was chosen to verify the simulated flow field around a groyne, and the other to verify the suspended sediment concentration distribution in a meandering channel. Then, the model utility was demonstrated in a field case study focusing on the confluence of the Kankakee and Iroquois Rivers in Illinois, United States, to simulate the distribution of suspended sediment concentration around spur dikes. Results demonstrated that the depth-averaged, two-dimensional model can approximately simulate the flow hydrodynamic field and concentration of suspended sediment. Spur dikes can be used to effectively relocate suspended sediment in alluvial channels.
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