Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of the Arabidopsis RING-H2 Protein RBX1 in RUB Modification and SCF Function Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.003178.

The ubiquitin-related protein RUB/Nedd8 is conjugated to members of the cullin family of proteins in plants, animals, and fungi. In Arabidopsis, the RUB conjugation pathway consists of a heterodimeric E1 (AXR1-ECR1) and a RUB-E2 called RCE1. The cullin CUL1 is a subunit in SCF-type ubiquitin protein ligases (E3s), including the SCFTIR1 complex, which is required for response to the plant hormone auxin. Our previous studies showed that conjugation of RUB to CUL1 is required for normal SCFTIR1 function. The RING-H2 finger protein RBX1 is a subunit of SCF complexes in fungi and animals. The function of RBX1 is to bind the ubiquitin-conjugating enzyme E2 and bring it into close proximity with the E3 substrate. We have identified two Arabidopsis genes encoding RING-H2 proteins related to human RBX1. Studies of one of these proteins indicate that, as in animals and fungi, Arabidopsis RBX1 is an SCF subunit. Reduced RBX1 levels result in severe defects in growth and development. Overexpression of RBX1 increases RUB modification of CUL1. This effect is associated with reduced auxin response and severe growth defects similar to those observed in axr1 mutants. As in the axr1 mutants, RBX1 overexpression stabilizes the SCFTIR1 substrate AXR2/IAA7. The RBX1 protein is a component of SCF complexes in Arabidopsis. In addition to its direct role in SCF E3 ligase activity, RBX1 promotes the RUB modification of CUL1 and probably functions as an E3 ligase in the RUB pathway. Hypermodification of CUL1 disrupts SCFTIR1 function, suggesting that cycles of RUB conjugation and removal are important for SCF activity.
High-throughput flow cytometry for drug discovery

High-throughput flow cytometry exploits a novel many-samples/one-file approach to dramatically speed data acquisition, limit aspirated sample volume to as little as 2 μl/well and produce multisample data sets that facilitate automated analysis of samples in groups as well as individually. It has been successfully applied to both cell- and microsphere-based bioassays in 96- and 384-well formats, to screen tens-of-thousands of compounds and identify novel bioactive structures. High-content multiparametric analysis capabilities have been exploited for assay multiplexing, allowing the assessment of biologic selectivity and specificity to be an integral component of primary screens. These and other advances in the last decade have contributed to the application of flow cytometry as a uniquely powerful tool for probing biologic and chemical diversity and complex systems biology.
When Clocks Go Bad: Neurobehavioural Consequences of Disrupted Circadian Timing

Progress in unravelling the cellular and molecular basis of mammalian circadian regulation over the past decade has provided us with new avenues through which we can explore central nervous system disease. Deteriorations in measurable circadian output parameters, such as sleep/wake deficits and dysregulation of circulating hormone levels, are common features of most central nervous system disorders. At the core of the mammalian circadian system is a complex of molecular oscillations within the hypothalamic suprachiasmatic nucleus. These oscillations are modifiable by afferent signals from the environment, and integrated signals are subsequently conveyed to remote central neural circuits where specific output rhythms are regulated. Mutations in circadian genes in mice can disturb both molecular oscillations and measurable output rhythms. Moreover, systematic analysis of these mutants indicates that they can express an array of abnormal behavioural phenotypes that are intermediate signatures of central nervous system disorders. Furthermore, the response of these mutants to psychoactive drugs suggests that clock genes can modify a number of the brain’s critical neurotransmitter systems. This evidence has led to promising investigations into clock gene polymorphisms in psychiatric disease. Preliminary indications favour the systematic investigation of the contribution of circadian genes to central nervous system disease.
A new rule-based algorithm for identifying metabolic markers in prostate cancer using tandem mass spectrometry

MOTIVATION Prostate cancer is the most prevalent tumor in males and its incidence is expected to increase as the population ages. Prostate cancer is treatable by excision if detected at an early enough stage. The challenges of early diagnosis require the discovery of novel biomarkers and tools for prostate cancer management. RESULTS We developed a novel feature selection algorithm termed as associative voting (AV) for identifying biomarker candidates in prostate cancer data measured via targeted metabolite profiling MS/MS analysis. We benchmarked our algorithm against two standard entropy-based and correlation-based feature selection methods [Information Gain (IG) and ReliefF (RF)] and observed that, on a variety of classification tasks in prostate cancer diagnosis, our algorithm identified subsets of biomarker candidates that are both smaller and show higher discriminatory power than the subsets identified by IG and RF. A literature study confirms that the highest ranked biomarker candidates identified by AV have independently been identified as important factors in prostate cancer development. AVAILABILITY The algorithm can be downloaded from the following http://biomed.umit. at/page.cfm? pageid=516.
Implementation of a Sliding-Mode Controller With an Integral Function and Fuzzy Gain Value for the Electrical Drive With an Elastic Joint

This paper presents a modified sliding-mode structure implemented for the speed control of a two-mass drive. A characteristic feature of the presented control method is the higher rank of the switching function caused by the application of an integral element (sliding mode with an integral function control). The proposed control system is a combination of a sliding-mode controller and a linear controller. Furthermore, to eliminate the chattering phenomenon related to the sliding-mode control, a switching function with a variable slope based on the fuzzy system is implemented. This solution ensures the robustness and dynamics of a two-mass drive better than with a linear speed controller. The main stages of the design methodology of the presented speed control structure are described in the initial sections of this paper. In the subsequent sections, simulation and experimental tests for the proposed control structure are presented and discussed.
Use of mathematical models for estimating the shelf‐life of cornflakes in flexible packaging

The objective of this work was to evaluate three different mathematical models (linear, middle point and logarithm interval) to predict the stability of commercial cornflakes in flexible packages. The limiting factor for cornflakes' shelf‐life was gain of moisture from the external environment, which caused loss of crispness and thus was unacceptable to the consumer. It was concluded that both middle point and logarithm interval methods are suitable for estimating the stability of cornflakes with a good approximation. The accuracy of these two methods depends on the precision of the experimental points of the sorption isotherms. The best fit to adjust the moisture isotherm was the GAB model. Knowledge of the mode of deterioration of the product and the sensory critical moisture content were fundamental to understanding and setting up the limits to confirm the models. Copyright © 2005 John Wiley & Sons, Ltd.
In vivo measured joint friction in hip implants during walking after a short rest

Introduction It has been suspected that friction in hip implants is higher when walking is initiated after a resting period than during continuous movement. It cannot be excluded that such increased initial moments endanger the cup fixation in the acetabulum, overstress the taper connections in the implant or increase wear. To assess these risks, the contact forces, friction moments and friction coefficients in the joint were measured in vivo in ten subjects. Instrumented hip joint implants with telemetric data transmission were used to access the contact loads between the cup and head during the first steps of walking after a short rest. Results The analysis demonstrated that the contact force is not increased during the first step. The friction moment in the joint, however, is much higher during the first step than during continuous walking. The moment increases throughout the gait cycle were 32% to 143% on average and up to 621% individually. The high initial moments will probably not increase wear by much in the joint. However, comparisons with literature data on the fixation resistance of the cup against moments made clear that the stability can be endangered. This risk is highest during the first postoperative months for cementless cups with insufficient under-reaming. The high moments after a break can also put taper connections between the head and neck and neck and shaft at a higher risk. Discussion During continuous walking, the friction moments individually were extremely varied by factors of 4 to 10. Much of this difference is presumably caused by the varying lubrication properties of the synovia. These large moment variations can possibly lead to friction-induced temperature increases during walking, which are higher than the 43.1°C which have previously been observed in a group of only five subjects.
Cumulative UV radiation dose and outcome in clinical practice: effectiveness of trioxsalen bath PUVA with minimal UVA exposure

Background: The cumulative artificial ultraviolet (UV) exposure dose of dermatological patients was prospectively monitored in clinical conditions for a total of 2 years (August 1997 – July 1999). We focused on whole body UV treatments, i.e. the trioxsalen (TMP) bath PUVA, the broad‐band UVB, and the UVA plus UVB phototherapy.
Identification of Porphyromonas gingivalis components that mediate its interactions with fibronectin

Porphyromonas (Bacteroides) gingivalis W12 binds and degrades human plasma fibronectin. In the presence of the protease inhibitor N-alpha-p-tosyl-L-lysyl chloromethyl ketone, P. gingivalis cells accumulated substantial amounts of 125I-fibronectin as a function of incubation time. Fibronectin binding was specific, reversible, and saturable. The Kd for the reaction was estimated to be on the order of 100 nM, and there was an average of 3.5 x 10(3) fibronectin binding sites per cell. Unlabeled fibronectin inhibited the binding of 125I-fibronectin to bacteria; however, fibrinogen was an even more efficient inhibitor of 125I-fibronectin binding. Unrelated proteins were without effect on fibronectin binding. A fibronectin-binding component (Mr, 150,000) was identified in sodium dodecyl sulfate-solubilized P. gingivalis. Fibronectin was degraded into discrete peptides by P. gingivalis W12. The degradation of fibronectin was inhibited by N-alpha-p-tosyl-L-lysyl chloromethyl ketone. Two P. gingivalis components (Mrs, 120,000 and 150,000) degraded fibronectin in substrate-containing gels following sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In a previous study (M. S. Lantz, R. D. Allen, T. A. Vail, L. M. Switalski, and M. Hook, J. Bacteriol. 173:495-504, 1991), we found that the same strain of P. gingivalis bound and subsequently degraded human fibrinogen via apparently distinct cell surface components of molecular sizes similar to those of components now implicated in the binding and degradation of fibronectin. These results raise the possibility that the two ligands are recognized and modified by the same components on P. gingivalis W12. In support of this hypothesis, unlabeled fibrinogen effectively inhibited the binding of 125I-fibronectin to bacteria and blocked 125I-fibronectin binding to a P. gingivalis ligand-binding component (Mr, 150,000 immobilized on a nitrocellulose membrane.
Computational tameness of classical non-causal models

We show that the computational power of the non-causal circuit model, i.e. the circuit model where the assumption of a global causal order is replaced by the assumption of logical consistency, is completely characterized by the complexity class UP∩coUP. An example of a problem in that class is factorization. Our result implies that classical deterministic closed timelike curves (CTCs) cannot efficiently solve problems that lie outside of that class. Thus, in stark contrast to other CTC models, these CTCs cannot efficiently solve NP-complete problems, unless NP=UP∩coUP=coNP, which lets their existence in nature appear less implausible. This result gives a new characterization of UP∩coUP in terms of fixed points.
Development of Micromachined Probes for Bio-Nano Applications

Development of Micromachined Probes for Bio-Nano Applications. (August 2009) Murat Kaya Yapici, B.S., Texas A&M University Chair of Advisory Committee: Dr. Jun Zou The most commonly known macro scale probing devices are simply comprised of metallic leads used for measuring electrical signals. On the other hand, micromachined probing devices are realized using microfabrication techniques and are capable of providing very fine, micro/nano scale interaction with matter; along with a broad range of applications made possible by incorporating MEMS sensing and actuation techniques. Micromachined probes consist of a well-defined tip structure that determines the interaction space, and a transduction mechanism that could be used for sensing a change, imparting external stimuli or manipulating matter. Several micromachined probes intended for biological and nanotechnology applications were fabricated, characterized and tested. Probes were developed under two major categories. The first category consists of Micro Electromagnetic Probes for biological applications such as single cell, particle, droplet manipulation and neuron stimulation applications; whereas the second category targets novel Scanning Probe topologies suitable for direct nanopatterning, variable resolution scanning probe/dip-pen nanolithography, and biomechanics applications. The functionality and versatility of micromachined probes for a broad range of micro and nanotechnology applications is successfully demonstrated throughout the five different probes/applications that were studied. It is believed that, the unique advantages of precise positioning capability, confinement of interaction as determined by the probe tip geometry, and special sensor/actuator mechanisms incorporated through MEMS technologies will render micromachined probes as indispensable tools for microsystems and nanotechnology studies.
Structure-Function Similarities between a Plant Receptor-like Kinase and the Human Interleukin-1 Receptor-associated Kinase-4*

Phylogenetic analysis has previously shown that plant receptor-like kinases (RLKs) are monophyletic with respect to the kinase domain and share an evolutionary origin with the animal interleukin-1 receptor-associated kinase/Pelle-soluble kinases. The lysin motif domain-containing receptor-like kinase-3 (LYK3) of the legume Medicago truncatula shows 33% amino acid sequence identity with human IRAK-4 over the kinase domain. Using the structure of this animal kinase as a template, homology modeling revealed that the plant RLK contains structural features particular to this group of kinases, including the tyrosine gatekeeper and the N-terminal extension α-helix B. Functional analysis revealed the importance of these conserved features for kinase activity and suggests that kinase activity is essential for the biological role of LYK3 in the establishment of the root nodule nitrogen-fixing symbiosis with rhizobia bacteria. The kinase domain of LYK3 has dual serine/threonine and tyrosine specificity, and mass spectrometry analysis identified seven serine, eight threonine, and one tyrosine residue as autophosphorylation sites in vitro. Three activation loop serine/threonine residues are required for biological activity, and molecular dynamics simulations suggest that Thr-475 is the prototypical phosphorylated residue that interacts with the conserved arginine in the catalytic loop, whereas Ser-471 and Thr-472 may be secondary sites. A threonine in the juxtamembrane region and two threonines in the C-terminal lobe of the kinase domain are important for biological but not kinase activity. We present evidence that the structure-function similarities that we have identified between LYK3 and IRAK-4 may be more widely applicable to plant RLKs in general.
Experimental Investigations on Mechanical Properties of Cenosphere/MWCNT Reinforced Polymer Nanocomposites

Utilization of cenosphere in polymeric composites made the composite lighter and cost effective. Howeverthere is need to further enhance the strength and stiffness of these polymer composites. Multiwalled Carbon nanotubes (MWCNT) can be effectively used as secondary reinforcement material in polymer based composites due to their superlative mechanical properties which enhance strength and stiffness of the composites. In this work, mechanical properties of Cenosphere/MWCNT reinforced epoxy nano composites are investigated experimentally. The composites were fabricated using uniform dispersion of MWCNT and cenosphere in epoxy resin by ultrasonic energy method, with the percentage of MWCNT varied from 0.1 to 0.5 wt% of epoxy. The specimens were tested for flexural, tensile and impact properties as per ASTM standards. It was observed that good flexural and tensile properties were found for 0.1 to 0.2 wt% of MWCNT and composite with 0.5 wt% exhibits higher impact strength.
Synergistic Interaction of Rnf8 and p53 in the Protection against Genomic Instability and Tumorigenesis

Rnf8 is an E3 ubiquitin ligase that plays a key role in the DNA damage response as well as in the maintenance of telomeres and chromatin remodeling. Rnf8−/− mice exhibit developmental defects and increased susceptibility to tumorigenesis. We observed that levels of p53, a central regulator of the cellular response to DNA damage, increased in Rnf8−/− mice in a tissue- and cell type–specific manner. To investigate the role of the p53-pathway inactivation on the phenotype observed in Rnf8−/− mice, we have generated Rnf8−/−p53−/− mice. Double-knockout mice showed similar growth retardation defects and impaired class switch recombination compared to Rnf8−/− mice. In contrast, loss of p53 fully rescued the increased apoptosis and reduced number of thymocytes and splenocytes in Rnf8−/− mice. Similarly, the senescence phenotype of Rnf8−/− mouse embryonic fibroblasts was rescued in p53 null background. Rnf8−/−p53−/− cells displayed defective cell cycle checkpoints and DNA double-strand break repair. In addition, Rnf8−/−p53−/− mice had increased levels of genomic instability and a remarkably elevated tumor incidence compared to either Rnf8−/− or p53−/− mice. Altogether, the data in this study highlight the importance of p53-pathway activation upon loss of Rnf8, suggesting that Rnf8 and p53 functionally interact to protect against genomic instability and tumorigenesis.
Is memory disaggregation feasible? A case study with Spark SQL

This paper explores the feasibility of entirely disaggregated memory from compute and storage for a particular, widely deployed workload, Spark SQL [9] analytics queries. We measure the empirical rate at which records are processed and calculate the effective memory bandwidth utilized based on the sizes of the columns accessed in the query. Our findings contradict conventional wisdom: not only is memory disaggregation possible under this workload, but achievable with already available, commercial network technology. Beyond this finding, we also recommend changes that can be made to Spark SQL to improve its ability to support memory disaggregation.
An overview of the cutaneous porphyrias

This is an overview of the cutaneous porphyrias. It is a narrative review based on the published literature and my personal experience; it is not based on a formal systematic search of the literature. The cutaneous porphyrias are a diverse group of conditions due to inherited or acquired enzyme defects in the porphyrin–haem biosynthetic pathway. All the cutaneous porphyrias can have (either as a consequence of the porphyria or as part of the cause of the porphyria) involvement of other organs as well as the skin. The single commonest cutaneous porphyria in most parts of the world is acquired porphyria cutanea tarda, which is usually due to chronic liver disease and liver iron overload. The next most common cutaneous porphyria, erythropoietic protoporphyria, is an inherited disorder in which the accumulation of bile-excreted protoporphyrin can cause gallstones and, rarely, liver disease. Some of the porphyrias that cause blistering (usually bullae) and fragility (clinically and histologically identical to porphyria cutanea tarda) can also be associated with acute neurovisceral porphyria attacks, particularly variegate porphyria and hereditary coproporphyria. Management of porphyria cutanea tarda mainly consists of visible-light photoprotection measures while awaiting the effects of treating the underlying liver disease (if possible) and treatments to reduce serum iron and porphyrin levels. In erythropoietic protoporphyria, the underlying cause can be resolved only with a bone marrow transplant (which is rarely justifiable in this condition), so management consists particularly of visible-light photoprotection and, in some countries, narrowband ultraviolet B phototherapy. Afamelanotide is a promising and newly available treatment for erythropoietic protoporphyria and has been approved in Europe since 2014.
Serologic identification of the human secondary B cell antigens. Correlations between function, genetics, and structure

The secondary B cell (SB) antigens are polymorphic HLA-linked antigens on human B cells and macrophages that are identified by primed T cell responses but are genetically distinct from the HLA-DR, MB, and MT antigens. Serologic identification of the SB molecule, using the monoclonal antibody ILR1, now makes it possible to correlate the function of these determinants in human T cell recognition with an Ia- like molecular structure and a genetic locus that marks a new HLA subregion. Three lines of evidence indicate that the ILR1 molecule identifies an epitope on some alleles of the SB gene: (a) the polymorphism of ILR1 -reactivity in the population correlates with SB2 SB3; (b) T cell proliferative response to SB2 and SB3 are specifically inhibited by ILR1; and (c) ILR1 reactivity is exactly concordant with the expression of SB2 in a panel of HLA-deletion mutant lymphoblastoid cell line. Together with previous studies, these results indicate that the SB antigens are on Ia-like molecules. Furthermore, the serologic studies of HLA-deletion mutant cell lines demonstrate that there are two HLA regions centromeric to HLA-B controlling expression of Ia-like molecules: a region toward HLA-B that controls expression of HLA-DR, and a region toward GLO that controls expression of SB.
A low-noise self-calibrating dynamic comparator for high-speed ADCs

This paper presents a low offset voltage, low noise dynamic latched comparator using a self-calibrating technique. The new calibration technique does not require any amplifiers for the offset voltage cancellation and quiescent current. It achieves low offset voltage of 1.69 mV at 1 sigma in low power consumption, while 13.7 mV is measured without calibration. Furthermore the proposed comparator requires only one phase clock while conventionally two phase clocks were required leading to relaxed clock. Moreover, a low input noise of 0.6 mV at 1 sigma, three times lower than the conventional one, is obtained. Prototype comparators are realized in 90 nm 10M1P CMOS technology. Experimental and simulated results show that the comparator achieves 1.69 mV offset at 250 MHz operating, while dissipating 40 muW/GHz ( 20 fJ/conv. ) from a 1.0 V supply.