Sc Variants Research Articles

Experimental and numerical analysis of variable cross-section channel liquid cooling plate for server chips thermal management

Utilizing high-performance chips results in increased heat generation, necessitating more effective heat dissipation method. To address challenges in microchannel liquid cooling plates for server chips cooling the study presents the variable cross-section channel liquid cooling plate designs. To investigate the effect of channel structure on the performance of liquid cooling plate, two types of samples, one featuring side wall ribs and bottom cavities (SC) and the other featuring side wall ribs and bottom waves (SW), are evaluated through experimental analyses under various heating power and flow rate conditions. Comparing their performance to a conventional rectangular channel (RC) liquid cooling plate, their heat transfer and flow attributes were assessed. Finally numerical analysis was conducted to investigate the flow behavior inside the channel and extreme performance prediction were made using the numerical study. Results demonstrate that the SC and SW designs outperform the RC in terms of heat transfer capabilities, despite having the weaker flow characteristics. Under 300 W heat source power, the SW variants enable the heat source surface temperature to stay below 77.8 °C with a 194 mL/min flow rate. Notably, the SW variant showcases lower average heat source surface temperature and demonstrates lower pressure drop compared to the SC variant. As the flow rate increases, the heat transfer efficiency of the SW variant is further amplified while simultaneously highlighting the relatively suboptimal flow behavior of the SC variant. Predictive numerical models underscore that the SW variants offers improved thermal performance when subjected to high heat source power scenarios. Remarkably, under the heat source power of 500 W, a mere augmentation in flow rate proves sufficient to reduce the heat source temperature below the prescribed threshold value. The combination design of side wall ribs and bottom waves should enable a low cost, simple and high efficiency electronics cooling.

Climate-Smart Holistic Management System Criteria’s Effectiveness on Milk Production in Lithuania

One of the problematic sectors according to GHG (greenhouse gas) and ammonia (NH3) emission quantities is agriculture. Without endangering food production (and intensifying), GHG emissions come from all sources in animal husbandry. The aim of this study was to comprehensively reduce GHG emissions by applying a holistic process management model to one of the most popular cowsheds in Lithuania (260-seat boxing cowshed, cows are milked on site, computerized management of technological processes, productivity of 8600 kg of milk, barn system, and liquid manure). Considering the cow keeping technology applied on the farm, the equipment used, and the feed production and ration system, a model for the management of technological parameters of production processes was prepared for the farm. This model balanced trade-offs among animal welfare, cow productivity, production costs, and GHG and NH3 emissions. The aim of the research was the adaptation of the integrated model to fully control, manage, and optimize milk production processes through bio- and engineering innovations to implement climate-friendly feed production and feeding and feed rationing systems, to improve animal housing and working conditions, and to reduce GHG and NH3 emissions without increasing production costs. The environmental impact assessment was performed with SimaPro 9.1 process modeling software. Data from milk production, biomass cultivation, and feed preparation, transportation, and equipment were used from the Ecoinvent v3 database. Based on the LML-I calculation methodology, the effect of processes was determined. To quantify the potential emissions in the dairy farm, the emission factors were estimated using a life cycle assessment method per functional unit—1000 kg—of standardized milk. Grass silage, maize silage, and feed concentrate were found to account for the largest share of gas emissions—26.09% (107.39 kg CO2 eq. FU−1), 22.70% (93.44 kg CO2 eq. FU−1), and 21.85% (89.92 kg CO2 eq. FU−1) of the total CO2 emissions during the process, respectively. Considering the critical points of the classic SC scenario, the cultivation technology was adjusted, where 50% of N fertilizers were replaced by bioproducts (biological preparations). Both scenarios—classic SC (control variant) and Bio SC (variants using bioproducts)—were evaluated for comparison. The use of biopreparations in the categories reduced the environmental impact from 0.1% to 45.7% in dairy production technology grass silage, barley grain, hay production, and corn silage stocks. The carbon footprint of the sustainable bio-based milk production (0.393 kg CO2 eq. kg−1 FPCM (fat- and protein-adjusted milk)) was lower by 4.6% compared to the average Lithuanian classic dairy farm (0.412 kg CO2 eq. kg−1 FPCM). Based on this methodology, it is possible to assess many dairy farms and address critical points in an integrated way, which can help to improve the quality of dairy production and the environment.

A population-based approach for gene prioritization in understanding complex traits.

Gene prioritization is the process of determining which variants and genes identified in genetic analyses are likely to cause a disease or a variation in a phenotype. For many genes, neither in vitro nor in vivo testing is available, thus assessing their pathogenic role could be challenging, leading to false-positive or false-negative results. In this paper, we propose an innovative score of gene prioritization based on the population of interest. We introduce the concept of singleton-cohort variants (SC variant), a variant that has allele count equal to one in the cohort under study. The difference between the normalized count of SC variants in the coding region and the normalized count of SC variants in the non-coding region should give a hint regarding the level of constraints for that gene in a specific population. This scoring system is negative when there are constraints that allow the presence of SC variants only in the non-coding region; on the contrary, it is positive when there are no constraints. A complimentary score is the sum of SC variants normalized count in both coding and non-coding regions, which could be used as a proxy of positive or strong purifying selection in a specific population. Our methodology showed a high level of constraining for genes such as USP34 in all subpopulations tested (1000 Gdataset). In contrast, some genes showed a high negative score only in specific populations, e.g., MYT1L in Europeans, UBR5 in East Asians, and FBXO11 in Africans.

Biophysical and Biochemical Characterization of Avian Secretory Component Provides Structural Insights into the Evolution of the Polymeric Ig Receptor.

The polymeric Ig receptor (pIgR) transports polymeric Abs across epithelia to the mucosa, where proteolytic cleavage releases the ectodomain (secretory component [SC]) as an integral component of secretory Abs, or as an unliganded protein that can mediate interactions with bacteria. SC is conserved among vertebrates, but domain organization is variable: mammalian SC has five domains (D1-D5), whereas avian, amphibian, and reptilian SC lack the D2 domain, and fish SC lacks domains D2-D4. In this study, we used double electron-electron resonance spectroscopy and surface plasmon resonance binding studies to characterize the structure, dynamics, and ligand binding properties of avian SC, avian SC domain variants, and a human SC (hSC) variant lacking the D2 domain. These experiments demonstrated that, unlike hSC, which adopts a compact or "closed" domain arrangement, unliganded avian SC is flexible and exists in both closed and open states, suggesting that the mammalian SC D2 domain stabilizes the closed conformation observed for hSC D1-D5. Experiments also demonstrated that avian and mammalian pIgR share related, but distinct, mechanisms of ligand binding. Together, our data reveal differences in the molecular recognition mechanisms associated with evolutionary changes in the pIgR protein.

BHLH proteins involved in Drosophila neurogenesis are mutually regulated at the level of stability.

Proneural bHLH activators are expressed in all neuroectodermal regions prefiguring events of central and peripheral neurogenesis. Drosophila Sc is a prototypical proneural activator that heterodimerizes with the E-protein Daughterless (Da) and is antagonized by, among others, the E(spl) repressors. We determined parameters that regulate Sc stability in Drosophila S2 cells. We found that Sc is a very labile phosphoprotein and its turnover takes place via at least three proteasome-dependent mechanisms. (i) When Sc is in excess of Da, its degradation is promoted via its transactivation domain (TAD). (ii) In a DNA-bound Da/Sc heterodimer, Sc degradation is promoted via an SPTSS phosphorylation motif and the AD1 TAD of Da; Da is spared in the process. (iii) When E(spl)m7 is expressed, it complexes with Sc or Da/Sc and promotes their degradation in a manner that requires the corepressor Groucho and the Sc SPTSS motif. Da/Sc reciprocally promotes E(spl)m7 degradation. Since E(spl)m7 is a direct target of Notch, the mutual destabilization of Sc and E(spl) may contribute in part to the highly conserved anti-neural activity of Notch. Sc variants lacking the SPTSS motif are dramatically stabilized and are hyperactive in transgenic flies. Our results propose a novel mechanism of regulation of neurogenesis, involving the stability of key players in the process.

Targeted Methylation and Gene Silencing of VEGF-A in Human Cells by Using a Designed Dnmt3a–Dnmt3L Single-Chain Fusion Protein with Increased DNA Methylation Activity

The C-terminal domain of the Dnmt3a de novo DNA methyltransferase (Dnmt3a-C) forms a complex with the C-terminal domain of Dnmt3L, which stimulates its catalytic activity. We generated and characterized single-chain (sc) fusion proteins of both these domains with linker lengths between 16 and 30 amino acid residues. The purified sc proteins showed about 10-fold higher DNA methylation activities than Dnmt3a-C in vitro and were more active in bacterial cells as well. After fusing the Dnmt3a-3L sc enzyme to an artificial zinc-finger protein targeting the vascular endothelial cell growth factor A (VEGF-A) promoter, we demonstrate successful targeting of DNA methylation to the VEGF-A promoter in human cells and observed that almost complete methylation of 12 CpG sites in the gene promoter could be achieved. Targeted methylation by the Dnmt3a-3L sc enzymes was about twofold higher than that of Dnmt3a-C, indicating that Dnmt3a-3L sc variants are more efficient as catalytic modules in chimeric DNA methyltransfeases than Dnmt3a-C. Targeted methylation of the VEGF-A promoter with the Dnmt3a-3L sc variant led to a strong silencing of VEGF-A expression, indicating that the artificial DNA methylation of an endogenous promoter is a powerful strategy to achieve silencing of the corresponding gene in human cells.

The Ability ofAneurinibacillus migulanus(Bacillus brevis) To Produce the Antibiotic Gramicidin S Is Correlated with Phenotype Variation

Phenotype instability of bacterial strains can cause significant problems in biotechnological applications, since industrially useful properties may be lost. Here we report such degenerative dissociation for Aneurinibacillus migulanus (formerly known as Bacillus brevis) an established producer of the antimicrobial peptide gramicidin S (GS). Phenotypic variations within and between various strains maintained in different culture collections are demonstrated. The type strain, ATCC 9999, consists of six colony morphology variants, R, RC, RP, RT, SC, and SP, which were isolated and characterized as pure cultures. Correlations between colony morphology, growth, GS production, spore formation, and resistance to their own antimicrobial peptide were established in this study. We found the original R form to be the best producer, followed by RC, RP, and RT, while SC and SP yielded no GS at all. Currently available ATCC 9999(T) contains only 2% of the original R producer and is dominated by the newly described phenotypes RC and RP. No original R form is detected in the nominally equivalent strain DSM 2895(T) (=ATCC 9999(T)), which grows only as SC and SP phenotypes and has thus completely lost its value as a peptide producer. Two other strains from the same collection, DSM 5668 and DSM 5759, contain the unproductive SC variant and the GS-producing RC form, respectively. We describe the growth and maintenance conditions that stabilize certain colony phenotypes and reduce the degree of degenerative dissociation, thus providing a recommendation for how to revert the nonproducing smooth phenotypes to the valuable GS-producing rough ones.

Single-chain Tet transregulators.

We demonstrate here that the Tet repressor (TetR), a dimeric allosterical regulatory protein, can be converted to a fully functional monomer when connected by a 29 amino acid linker. TetR-based transregulators are widely used to regulate gene expression in eukaryotes. They can be fused to form single-chain (sc) Tet transregulators with two TetR moieties and one eukaryotic regulatory domain. Sc variants of transactivator and transsilencer exhibit the same regulatory properties as their respective dimeric counterparts in human cell lines. In particular, the reverse 'tet-on' phenotype of rtTA variants is also present in the sc variants. Coexpression of a reverse transactivator and sc transsilencer leads to reduced background expression and shows full activation upon induction. The data demonstrate that sc Tet transregulators exhibit the phenotype of their respective dimers and lack functional interference when coexpressed in the same cell.

New Views of Sickle Cell Disease Pathophysiology and Treatment.

This review addresses several areas of concern in the care of patients with sickle cell disease. In Sections I and II, the fundamental pathogenetic mechanisms of sickle cell disease and their clinical consequences are discussed. Dr. Narla presents the evidence for abnormal cell adhesiveness by SS cells and Dr. Rosse examines the role of the increased whole blood viscosity. In Section III, Dr. Petz reviews common and uncommon alloimmune consequences of transfusion in sickle cell disease and discusses the diagnosis and management of sickle cell patients with hyperhemolysis after transfusion. In Section IV, Dr. Steinberg gives an update on the use of hydroxyurea in the treatment of sickle cell disease, including the SC and S-beta thalassemia variants.

Convenient screening for hemoglobin variants by using the Diamat HPLC system

Hemolysates from 102 different patients previously assessed for the presence of hemoglobin variants by cellulose acetate electrophoresis were reanalyzed with the Diamat, a microprocessor-controlled step-gradient HPLC technique designed to determine glycohemoglobin (Hgb A1c). This pool contained 81 abnormal specimens, each with one of seven different variant abnormalities. In all cases the HPLC technique correctly detected the presence or absence of a variant. The common S trait gave a large peak immediately after Hgb A, and the SS and SC variants gave clearly abnormal patterns, caused in part by the absence of Hgb A. The pattern from EE variants was distinguished by the appearance of the glycated fraction Hgb E1c, which is eluted at 4.7 instead of 4.2 min, whereas the AE pattern had two glycated peaks. Hemoglobins F, "fast", S, and C were discerned by the presence of a major peak at 3, 5.2, 6.5, and 7.5 min, respectively. The findings suggest that the Diamat is a convenient tool to detect and help diagnose variants in a screening pool.

High-performance liquid chromatography of human hemoglobins on a new cation exchanger

We have investigated the use of a high-performance liquid chromatographic (HPLC) column packed with a unique weak cation exchanger prepared by coating silica with poly(aspartic acid) for hemoglobin analysis. The complete separation of hemoglobin Bart's F, A0, A2, S, C, D, E, G, SG, Winnipeg and Sealy was achieved by gradient elution within 30 min. The high resolution made it possible to distinguish hemoglobin variants such as Bart's, AC, AD, AE, AG, AS, ASG, CC, SC, SS, Winnipeg, Sealy and β-chain variants with thalassemia such as S/β+, S/β0 and S(C)-β+ thalassemia. Comparison of DEAE-cellulose column chromatography and our HPLC method for the quantitation of hemoglobin A2 yielded a good correlation. Hemoglobins A2, C and E are completely resolved on PolyCAT A columns in contrast to both cellulose acetate clectrophoresis and DEAE-cellulose column chromatography. The high resolution of the system and the accuracy of the method combined with complete automation make this procedure useful for diagnosis of hemoglobin disorders in both a research and clinical laboratory environment.

Variation of Colony Morphology Reflecting Fimbriation in Moraxella Bovis and Two Reference Strains of M. Nonliquefaciens

Five strains of Moraxella bovis were studied and found to yield distinct colony types with respect to agar corrosion and formation of corroding spreading zones. The types were largely similar to those of M. kingii, although some morphological differences were observed. Distinctly corroding clones, with more or less pronounced spreading colonies (SC type), were isolated from all strains. These isolates were all strongly fimbriated, as observed by electron microscopy. The fimbriae had a diameter of 65–85 Å. Another colony form, without corrosion and spreading (N type), was also observed in all strains. Electron microscopical preparations from these colonies revealed no fimbriae, or only occasional fimbriae, possibly of slightly different appearance, could be detected. With varying frequency, from none observed to about one in 10,000 colonies, N type populations revealed the intracolonial occurrence of fimbriated SC variants by partial change of colony morphology after a few days of incubation. Spontaneous variation from SC to N, accompanied by loss of fimbriation, was also observed. When 12–30 hr old SC colonies were subcultivated, less than one in 10,000 progeny colonies were usually observed to be of the N type, whereas older colonies sometimes revealed a high percentage of N variants in the progeny. A colony type intermediate between N and SC (NSC type) was occasionally seen, with relatively weak agar corrosion and spreading, and with an apparently slightly reduced degree of fimbriation, as compared with the SC type. The intermediate phenotype was unstable, however, showing an irregular tendency to produce progeny of a more corroding and spreading morphology. Two reference strains (including the neotype) of M. nonliquefaciens were studied and revealed fimbriae‐associated colony type differentiation slightly different from previously examined strains of this species and from M. bovis.