Miracle-dz/UniFAR-FTUs huggingface dataset:
Computational protein design enables a novel one-carbon assimilation pathway

Significance This paper describes the development of a computationally designed enzyme that is the cornerstone of a novel metabolic pathway. This enzyme, formolase, performs a carboligation reaction, directly fixing one-carbon units into three-carbon units that feed into central metabolism. By combining formolase with several naturally occurring enzymes, we created a new carbon fixation pathway, the formolase pathway, which assimilates one-carbon units via formate. Unlike native carbon fixation pathways, this pathway is linear, not oxygen sensitive, and consists of a small number of thermodynamically favorable steps. We demonstrate in vitro pathway function as a proof of principle of how protein design in a pathway context can lead to new efficient metabolic pathways. We describe a computationally designed enzyme, formolase (FLS), which catalyzes the carboligation of three one-carbon formaldehyde molecules into one three-carbon dihydroxyacetone molecule. The existence of FLS enables the design of a new carbon fixation pathway, the formolase pathway, consisting of a small number of thermodynamically favorable chemical transformations that convert formate into a three-carbon sugar in central metabolism. The formolase pathway is predicted to use carbon more efficiently and with less backward flux than any naturally occurring one-carbon assimilation pathway. When supplemented with enzymes carrying out the other steps in the pathway, FLS converts formate into dihydroxyacetone phosphate and other central metabolites in vitro. These results demonstrate how modern protein engineering and design tools can facilitate the construction of a completely new biosynthetic pathway.
Predictive digital current programmed control

This paper explores predictive digital current programmed control for valley, peak or average current. The control laws are derived for the three basic converters: buck, boost, and buck-boost. It is found that for each variable of interest (valley, peak or average current) there is a choice of the appropriate pulse-width modulation method to achieve predictive digital current control without oscillation problems. The proposed digital control techniques can be used in a range of power conversion applications, including rectifiers with power factor correction (PFC). Very low current distortion meeting strict avionics requirements (400-800 Hz line frequency) is experimentally demonstrated on a digitally controlled boost PFC employing predictive average current programmed control.
Upper and lower limb functionality: are these compromised in obese children?

OBJECTIVE The aim of this study was to investigate the effects of obesity on upper and lower limb functional strength and power in children, and to determine whether the ability to perform the daily activity of rising from a chair was compromised in obese children. It was hypothesised that obese children would display less upper and lower limb functionality compared to their non-obese counterparts. METHODS Upper and lower limb strength and power of 43 obese children (aged 8.4 +/- 0.5 y, BMI 24.1 +/- 2.3 kg/m(-2)) and 43 non-obese controls (aged 8.4 +/- 0.5 y, BMI 16.9 +/- 0.4 kg/m(-2)) were assessed using age-appropriate field-based tests: arm push/pull ability; basketball throw; vertical jump (VJ), and standing long jump (SLJ) performance. Functional lower limb strength was assessed for 13 obese and 13 non-obese children by quantifying their chair rising ability. RESULTS Although obese children displayed significantly greater upper limb push (9.3 +/- 2.3 kg) and pull strength (9.6 +/- 3.0 kg) than their non-obese peers (push: 8.8 +/- 2.2 kg; pull: 8.8 +/- 2.3 kg; p < or = 0.05), their VJ (22.1 +/- 4.3 cm) and SLJ (94.6 +/- 12.8 cm) performance was significantly impaired relative to the non-obese children (VJ: 24.7 +/- 4.0 cm; SLJ: 101.7 +/- 14.0 cm; p < or = 0.05). Obese children spent significantly more time during all transfer phases of the chair rising task, compared to the non-obese children. CONCLUSIONS Lower limb functionality in young obese children is impeded when they move their greater body mass against gravity.
A Laboratory Method for Investigating Influences on Switching Attention to Task-Unrelated Imagery and Thought

Thought-intrusions, automatic inferences, and other unintended thought are beginning to play an important role in the study of psychiatric disease as well as normal thought processes. We examine one method for the study of task-unrelated imagery and thought (TUIT). TUIT likelihood was shown to be reliably measured over a wide range of vigilance tasks, to have high short-term and long-term test-retest reliability, and to be sensitive to information processing demands. Likelihood of TUITs was shown to be different as a function of aging, hyperactivity, time of the day, and level of depression. Thus, we now can reliably measure the influence of endogenous and exogenous influences on TUITs. In addition, TUIT measurement was proposed as a minimally interfering and natural second task for determining resource utilization in a primary task. Finally, this method was offered as a reliable approach to quantification of such mental states as obsessions and drug craving and addiction.
Nanolipodendrosome-loaded glatiramer acetate and myogenic differentiation 1 as augmentation therapeutic strategy approaches in muscular dystrophy

Backgrond Muscular dystrophies consist of a number of juvenile and adult forms of complex disorders which generally cause weakness or efficiency defects affecting skeletal muscles or, in some kinds, other types of tissues in all parts of the body are vastly affected. In previous studies, it was observed that along with muscular dystrophy, immune inflammation was caused by inflammatory cells invasion – like T lymphocyte markers (CD8+/CD4+). Inflammatory processes play a major part in muscular fibrosis in muscular dystrophy patients. Additionally, a significant decrease in amounts of two myogenic recovery factors (myogenic differentation 1 [MyoD] and myogenin) in animal models was observed. The drug glatiramer acetate causes anti-inflammatory cytokines to increase and T helper (Th) cells to induce, in an as yet unknown mechanism. MyoD recovery activity in muscular cells justifies using it alongside this drug. Methods In this study, a nanolipodendrosome carrier as a drug delivery system was designed. The purpose of the system was to maximize the delivery and efficiency of the two drug factors, MyoD and myogenin, and introduce them as novel therapeutic agents in muscular dystrophy phenotypic mice. The generation of new muscular cells was analyzed in SW1 mice. Then, immune system changes and probable side effects after injecting the nanodrug formulations were investigated. Results The loaded lipodendrimer nanocarrier with the candidate drug, in comparison with the nandrolone control drug, caused a significant increase in muscular mass, a reduction in CD4+/CD8+ inflammation markers, and no significant toxicity was observed. The results support the hypothesis that the nanolipodendrimer containing the two candidate drugs will probably be an efficient means to ameliorate muscular degeneration, and warrants further investigation.
Effect of Bottlenecking on Evolution of the Nonstructural Protein 3 Gene of Hepatitis C Virus during Sexually Transmitted Acute Resolving Infection

ABSTRACT Sexual partners of patients infected with the hepatitis C virus (HCV) often have detectable HCV-specific T-cell responses in the absence of seroconversion, suggesting unapparent, spontaneously resolving infection. To determine whether differences in the evolutionary potential of bottlenecked inoculum may explain the low rate of HCV persistence after sexual exposure, we have investigated changes in the entire HCV nonstructural 3 (NS3) gene over time in a chronic carrier and compared his viral quasispecies with that of the acute-phase isolate of his sexual partner, who developed acute resolving hepatitis C. The overall rate of accumulation of mutations, estimated by regression analysis of six consecutive consensus NS3 sequences over 8 years, was 1.5 × 10−3 mutations per site per year, with small intersample fluctuations related to changes in environmental conditions. Comparison of quasispecies parameters in one isolate of the chronic carrier with those of the acute-phase isolate of the infected partner revealed a higher heterogeneity and lower proportion of nonsynonymous mutations in the former. All NS3 sequences from the acute-phase isolate clustered with a single sequence from the chronic isolate, despite complete HLA mismatch between the patients, suggesting bottlenecking during transmission. The low risk of viral persistence after sexual exposure to HCV may be related to the selection of a limited number of viral particles carrying a particular combination of mutations which may further limit the potential of a relatively homogeneous quasispecies to rapidly diversify and overcome the immune response of the exposed host.
Process migration

Process migration is the act of transferring a process between two machines. It enables dynamic load distribution, fault resilience, eased system administration, and data access locality. Despite these goals and ongoing research efforts, migration has not achieved widespread use. With the increasing deployment of distributed systems in general, and distributed operating systems in particular, process migration is again receiving more attention in both research and product development. As high-performance facilities shift from supercomputers to networks of workstations, and with the ever-increasing role of the World Wide Web, we expect migration to play a more important role and eventually to be widely adopted. This survey reviews the field of process migration by summarizing the key concepts and giving an overview of the most important implementations. Design and implementation issues of process migration are analyzed in general, and then revisited for each of the case studies described: MOSIX, Sprite, Mach, and Load Sharing Facility. The benefits and drawbacks of process migration depend on the details of implementation and, therefore, this paper focuses on practical matters. This survey will help in understanding the potentials of process migration and why it has not caught on.
Biodelignification of Lemon Grass and Citronella Bagasse by White-Rot Fungi

Twelve white-rot fungi were grown in solid-state culture on lemon grass (Cymbopogon citratus) and citronella (Cymbopogon winterianus) bagasse. The two lignocellulosic substrates had 11% permanganate lignin and a holocellulose fraction of 58%. After 5 to 6 weeks at 20°C, nine fungi produced a solid residue from lemon grass with a higher in vitro dry matter enzyme digestibility than the original bagasse; seven did the same for citronella. The best fungus for both substrates was Bondarzewia berkeleyi; it increased the in vitro dry matter enzyme digestibility to 22 and 24% for lemon grass and citronella, respectively. The increases were correlated with weight loss and lignin loss. All fungi decreased lignin contents: 36% of the original value for lemon grass and 28% for citronella. Practically all fungi showed a preference for hemicellulose over cellulose.
Migratory Status Is Not Related to the Susceptibility to HPAIV H5N1 in an Insectivorous Passerine Species

Migratory birds have evolved elaborate physiological adaptations to travelling, the implications for their susceptibility to avian influenza are however unknown. Three groups of stonechats (Saxicola torquata) from (I) strongly migrating, (II) weakly migrating and (III) non-migrating populations were experimentally infected with HPAIV H5N1. The different bird groups of this insectivorous passerine species were infected in autumn, when the migrating populations clearly exhibit migratory restlessness. Following infection, all animals succumbed to the disease from 3 through 7 days post inoculation. Viral shedding, antigen distribution in tissues, and survival time did not differ between the three populations. However, notably, endothelial tropism of the HPAIV infection was exclusively seen in the group of resident birds. In conclusion, our data document for the first time the high susceptibility of an insectivorous passerine species to H5N1 infection, and the epidemiological role of these passerine birds is probably limited due to their high sensitivity to HPAIV H5N1 infection. Despite pronounced inherited differences in migratory status, the groups were generally indistinguishable in their susceptibility, survival time, clinical symptoms and viral shedding. Nevertheless, the migratory status partly influenced pathogenesis in the way of viral tropism.
Localization of AMPA‐selective glutamate receptors in the auditory brainstem of the barn owl

AMPA receptor subunit‐specific antibodies were used to determine if the distribution of excitatory amino acid receptors in the owl's auditory brainstem and midbrain nuclei reflected specializations for temporal processing. Each auditory nucleus displays characteristic levels of immunostaining for the AMPA receptor subunits GluR1–4, with high levels of the subtypes which exhibit rapid desensitization (GluR4 and 2/3). In the auditory brainstem, levels of GluR2/3 and GluR4 were very high in the cochlear nucleus magnocellularis and the nucleus laminaris. The different cell types of the cochlear nucleus angularis and the superior olive were characterized by heterogeneous GluR2/3 and 4 immunostaining. GluR1 levels were very low or undetectable. In the lemniscal nuclei, most neurons contained low levels of GluR1, and dense GluR2/3 and GluR4 immunoreactivity, with high levels of GluR4 in the dendrites. Levels of GluR4 were higher in the anterior portion of the ventral nucleus of the lateral lemniscus. The divisions of the inferior colliculus could be distinguished on the basis of GluR1–4 immunoreactivity, with high levels of GluR4 and moderate levels of GluR1 in the external nucleus. No major differences were observed between the pathways for encoding time and sound level cues. J. Comp. Neurol. 378:239–253, 1997. © 1997 Wiley‐Liss, Inc.
Effects of enzyme supplementation on oral absorption of ciprofloxacin in patients with cystic fibrosis

The effect of pancreatic enzyme supplementation on the absorption of an oral dose of 250 mg of ciprofloxacin was studied in six patients with cystic fibrosis in a crossover design. The time to achieve maximum serum concentration was slightly reduced upon coadministration of pancreatic enzymes. There were no significant differences in peak concentration, elimination half-life, and area under the concentration-time curve.
SL‐401 and SL‐501, targeted therapeutics directed at the interleukin‐3 receptor, inhibit the growth of leukaemic cells and stem cells in advanced phase chronic myeloid leukaemia

While imatinib and other tyrosine kinase inhibitors (TKIs) are highly efficacious in the treatment of chronic myeloid leukaemia (CML), some patients become refractory to these therapies. After confirming that interleukin‐3 receptor (IL3R, CD123) is highly expressed on CD34+/CD38− BCR‐ABL1+ CML stem cells, we investigated whether targeting IL3R with diphtheria toxin (DT)‐IL3 fusion proteins SL‐401 (DT388‐IL3) and SL‐501 (DT388‐IL3[K116W]) could eradicate these stem cells. SL‐401 and SL‐501 inhibited cell growth and induced apoptosis in the KBM5 cell line and its TKI‐resistant KBM5‐STI subline. Combinations of imatinib with these agents increased apoptosis in KBM5 and in primary CML cells. In six primary CML samples, including CML cells harbouring the ABL1 T315I mutation, SL‐401 and SL‐501 decreased the absolute numbers of viable CD34+/CD38−/CD123+ CML progenitor cells by inducing apoptosis. IL3‐targeting agents reduced clonogenic growth and diminished the fraction of primitive long‐term culture‐initiating cells in samples from patients with advanced phase CML that were resistant to TKIs or harboured an ABL1 mutation. Survival was also extended in a mouse model of primary TKI‐resistant CML blast crisis. These data suggest that the DT‐IL3 fusion proteins, SL‐401 and SL‐501, deplete CML stem cells and may increase the effectiveness of current CML treatment, which principally targets tumour bulk.
Hepatitis C Virus NS5A Protein Interacts with Phosphatidylinositol 4-Kinase Type IIIα and Regulates Viral Propagation*

Hepatitis C Virus (HCV) nonstructural 5A (NS5A) is a pleiotropic protein involved in viral RNA replication and modulation of the cellular physiology in HCV-infected cells. To elucidate the mechanisms of the HCV life cycle, we identified cellular factors interacting with the NS5A protein in HCV-infected cells. Huh7.5 cells were electroporated with HCV Jc1 RNA. Cellular factors associated with HCV NS5A were identified by immunoprecipitation with Dynabead-conjugated NS5A antibody and LC-MS/MS. Phosphatidylinositol 4-kinase type IIIα (PI4KIIIα) was identified as a binding partner for the NS5A protein. NS5A derived from both genotypes 1b and 2a interacted with PI4KIIIα. NS5A interacted with PI4KIIIα through amino acids 401–600 of PI4KIIIα and domain I of NS5A. Interference of the protein interaction between NS5A and PI4KIIIα decreased HCV propagation. Knockdown of PI4KIIIα significantly reduced HCV replication in Huh7 cells harboring the subgenomic replicon and in Huh7.5 cells infected with cell culture grown virus (HCVcc). Silencing of PI4KIIIα further inhibited HCV release into the tissue culture medium. NS5A may recruit PI4KIIIα to the HCV RNA replication complex. These data suggest that PI4KIIIα is an essential host factor that supports HCV proliferation and therefore PI4KIIIα may be a legitimate target for anti-HCV therapy.
Intracellular consequences of SOS1 deficiency during salt stress

A mutation of AtSOS1 (Salt Overly Sensitive 1), a plasma membrane Na+/H+-antiporter in Arabidopsis thaliana, leads to a salt-sensitive phenotype accompanied by the death of root cells under salt stress. Intracellular events and changes in gene expression were compared during a non-lethal salt stress between the wild type and a representative SOS1 mutant, atsos1-1, by confocal microscopy using ion-specific fluorophores and by quantitative RT-PCR. In addition to the higher accumulation of sodium ions, atsos1-1 showed inhibition of endocytosis, abnormalities in vacuolar shape and function, and changes in intracellular pH compared to the wild type in root tip cells under stress. Quantitative RT-PCR revealed a dramatically faster and higher induction of root-specific Ca2+ transporters, including several CAXs and CNGCs, and the drastic down-regulation of genes involved in pH-homeostasis and membrane potential maintenance. Differential regulation of genes for functions in intracellular protein trafficking in atsos1-1 was also observed. The results suggested roles of the SOS1 protein, in addition to its function as a Na+/H+ antiporter, whose disruption affected membrane traffic and vacuolar functions possibly by controlling pH homeostasis in root cells.
Route Discovery Protocol for Energy Efficient Networks With MIMO Links

We propose a reactive route discovery protocol for energy efficient transmission in a wireless multihop network with multiple input multiple output (MIMO) channels. We focus on networks consisting of MIMO nodes that use time division scheduling where the source needs to transmit a certain amount of data to the destination in a fixed amount of time. We show how the intermediate nodes find the route distributively. This protocol takes into account the quality of the MIMO channels and allocates power to them so that the end-to-end transmission energy is minimized. The resulting protocol is easy to implement and provides the most energy efficient route and the power allocation for the data transmission. We perform simulations on Rayleigh-fading channels to show the significant energy benefits of the proposed route discovery protocol against a dynamic source routing (DSR)-based routing protocol with optimal power allocation.
Prediction of Cryogen Leak Rate through Damaged Composite Laminates

The structural weight of a cryogenic propellant tank for reusable launch vehicles (RLV) can be effectively reduced by the use of advanced composite materials. However, microscopic damage such as transverse matrix cracks (TMC) and delaminations are prone to develop in composites well below the load levels that would result in mechanical failure. This microscopic damage leads to a leakage path for the fuel. The leakage is influenced by many factors, including pressure gradients, microcrack density, connectivity of the cracks, residual stresses from manufacture, service-induced stresses from thermal and mechanical loads, and composite stacking sequence. It is expected that there is a direct relationship between leakage and damage opening but the connectivity of matrix cracks is also a major factor affecting the leakage. In this article, the leakage rate through the damage network is discussed based on earlier studies for the opening of damage paths due to TMC and delamination, including the TMC intersection area. In order to examine the leakage process, numerical simulations are performed using the computational fluid dynamics software (FLUENT) and the effective conductance of the leakage paths is estimated. A simplified model is also developed to predict the effective conductance. The flow resistance in the TMC and the resistance of the TMC intersection area are accounted for in the calculation of the effective conductance of the leakage path through the entire laminate using the simplified model. Comparisons between the numerical solution for a five-ply composite with interconnected leakage paths and the prediction of the simplified model are presented for gaseous hydrogen flow through the thickness of the composite at room and cryogenic temperatures.
Active Probing to Classify Internet Address Blocks ( poster abstract )

Previous Internet topology studies mostly focused on ASand router-level topologies [1,2,4,8,9], providing insight into AS relationships and interdomain routing. However, relatively little is known today about the demographics of Internet edge hosts and the use of the IPv4 address space. Since the transition to classless routing [3], external observers have only limited view into how IP address blocks are allocated, managed, and used. Only recently have researchers tried to characterize address usage [11], with a methodology limited to addresses used by clients. In this poster we begin to explore the potential of active probing and external classification of address block usage. Our work makes three assumptions: a significant number of Internet addresses will respond to external probes, some patterns of repeated probes correspond can indicate different address usage, and contiguous addresses are often used for similar purposes. While there are cases where these assumptions do not hold, in recent work we study probing effectiveness with ICMP and TCP, showing they detect the majority of used addresses [5]. In this poster we expand on the second hypothesis, using probe results to study address allocation strategies and to infer address usage (always be occupied or not in use, use by stable or frequently inaccessible hosts, etc.). In ongoing work we are evaluating the accuracy of this approach and these assumptions; in this poster we suggest this as a promising new direction for research. We expand on the goals of this research, the applications of classification, and our preliminary results below.