Miracle-dz/UniFAR-FTUs huggingface dataset:
High-Throughput Screening for Small-Molecule Inhibitors of LARG-Stimulated RhoA Nucleotide Binding via a Novel Fluorescence Polarization Assay

Guanine nucleotide exchange factors (GEFs) stimulate guanine nucleotide exchange and the subsequent activation of Rho-family proteins in response to extracellular stimuli acting upon cytokine, tyrosine kinase, adhesion, integrin, and G-protein-coupled receptors (GPCRs). Upon Rho activation, several downstream events occur, such as morphological and cytoskeletal changes, motility, growth, survival, and gene transcription. The leukemia-associated RhoGEF (LARG) is a member of the regulators of G-protein signaling homology domain (RH) family of GEFs originally identified as a result of chromosomal translocation in acute myeloid leukemia. Using a novel fluorescence polarization guanine nucleotide-binding assay using BODIPY—Texas Red—GTPγS (BODIPY-TR-GTPγS), the authors performed a 10,000-compound high-throughput screen for inhibitors of LARG-stimulated RhoA nucleotide binding. Five compounds identified from the high-throughput screen were confirmed in a nonfluorescent radioactive guanine nucleotide-binding assay measuring LARG-stimulated [ 35S] GTPγS binding to RhoA, thus ruling out nonspecific fluorescent effects. All 5 compounds selectively inhibited LARG-stimulated RhoA [ 35S] GTPγS binding but had little to no effect on RhoA or Gα o [35S] GTPγS binding. Therefore, these 5 compounds should serve as promising starting points for the development of small-molecule inhibitors of LARG-mediated nucleotide exchange as both pharmacological tools and therapeutics. In addition, the fluorescence polarization guanine nucleotide-binding assay described here should serve as a useful approach for both high-throughput screening and general biological applications. (Journal of Biomolecular Screening 2009:161-172)
Decomposition of laser altimeter waveforms

The authors develop a method to decompose a laser altimeter return waveform into a series of components assuming that the position of each component within the waveform can be used to calculate the mean elevation of a specific reflecting surface within the laser footprint. For simplicity, they assume each component is Gaussian in nature. They estimate the number of Gaussian components from the number of inflection points of a smoothed copy of the laser waveform and obtain initial estimates of the Gaussian half-widths and positions from the positions of its consecutive inflection points. Initial amplitude estimates are obtained using a nonnegative least-squares method (LSM). To reduce the likelihood of fitting the background noise within the waveform and to minimize the number of Gaussians needed in the approximation, we rank the "importance" of each Gaussian in the decomposition using its initial half-width and amplitude estimates. The initial parameter estimates of all Gaussians ranked "important" are optimized using the Levenburg-Marquardt method. If the sum of the Gaussians does not approximate the return waveform to a prescribed accuracy, then additional Gaussians can be included in the optimization procedure or initial parameters can be recalculated. The Gaussian decomposition method is demonstrated on data collected by the airborne laser vegetation imaging sensor (LVIS) in October 1997 over the Sequoia National Forest, California.
The BpeAB-OprB Efflux Pump of Burkholderia pseudomallei 1026b Does Not Play a Role in Quorum Sensing, Virulence Factor Production, or Extrusion of Aminoglycosides but Is a Broad-Spectrum Drug Efflux System

ABSTRACT Most Burkholderia pseudomallei strains are intrinsically aminoglycoside resistant, mainly due to AmrAB-OprA-mediated efflux. Rare naturally occurring or genetically engineered mutants lacking this pump are aminoglycoside susceptible despite the fact that they also encode and express BpeAB-OprB, which was reported to mediate efflux of aminoglycosides in the Singapore strain KHW. To reassess the role of BpeAB-OprB in B. pseudomallei aminoglycoside resistance, we used mutants overexpressing or lacking this pump in either AmrAB-OprA-proficient or -deficient strain 1026b backgrounds. Our data show that BpeAB-OprB does not mediate efflux of aminoglycosides but is a multidrug efflux system which extrudes macrolides, fluoroquinolones, tetracyclines, acriflavine, and, to a lesser extent, chloramphenicol. Phylogenetically, BpeAB-OprB is closely related to Pseudomonas aeruginosa MexAB-OprM, which has a similar substrate spectrum. AmrAB-OprA is most closely related to MexXY, the only P. aeruginosa efflux pump known to extrude aminoglycosides. Since BpeAB-OprB in strain KHW was also implicated in playing a major role in export of acylated homoserine lactone (AHL) quorum-sensing molecules and in expression of diverse virulence factors, we explored whether this was also true in the strain 1026b background. The results showed that BpeAB-OprB was not required for AHL export, and mutants lacking this efflux system exhibited normal swimming motility and siderophore production, which were severely impaired in KHW bpeAB-oprB mutants. Biofilm formation was impaired in 1026b Δ(amrRAB-oprA) and Δ(amrRAB-oprA) Δ(bpeAB-oprB) mutants. At present, we do not know why our BpeAB-OprB susceptibility and virulence factor expression results with 1026b and its derivatives are different from those previously published for Singapore strain KHW.
C-Mannosylation and O-Fucosylation of the Thrombospondin Type 1 Module*

Thrombospondin-1 (TSP-1) is a multidomain protein that has been implicated in cell adhesion, motility, and growth. Some of these functions have been localized to the three thrombospondin type 1 repeats (TSRs), modules of ∼60 amino acids in length with conserved Cys and Trp residues. The Trp residues occur in WXXW patterns, which are the recognition motifs for protein C-mannosylation. This modification involves the attachment of an α-mannosyl residue to the C-2 atom of the first tryptophan. Analysis of human platelet TSP-1 revealed that Trp-368, -420, -423, and -480 are C-mannosylated. Mannosylation also occurred in recombinant, baculovirally expressed TSR modules from Sf9 and “High Five” cells, contradictory to earlier reports that such cells do not carry out this reaction. In the course of these studies it was appreciated that the TSRs in TSP-1 undergo a second form of unusual glycosylation. By using a novel mass spectrometric approach, it was found that Ser-377, Thr-432, and Thr-489 in the motif CSX(S/T)CG carry the O-linked disaccharide Glc-Fuc-O-Ser/Thr. This is the first protein in which such a disaccharide has been identified, although proteinO-fucosylation is well described in epidermal growth factor-like modules. Both C- andO-glycosylations take place on residues that have been implicated in the interaction of TSP-1 with glycosaminoglycans or other cellular receptors.
Insulator condition analysis for overhead distribution lines using combined wavelet support vector machine (SVM)

Condition analysis of overhead power distribution system insulators using combined support vector machine (SVM) and wavelet multi-resolution analysis (MRA) seems to be promising for distribution system monitoring (DSM) automation to cope with the increasing system complexity. Though system well-being analysis for engineering applications has been used mostly for electric power system reliability studies, the same principle has been extended for assessing the condition of insulators in a distribution system based on the extent of their damage. Video surveillance with fixed cameras provide the required images of power lines along with insulators at regular intervals and same is sent to a control room using remote terminal units (RTUs) for analysis. Not only the health of the insulators, but also the sagging of the lines, breakage of both insulators and lines can be captured with such cameras. This paper mainly focuses on application of wavelet-transform based feature extraction for digital image processing and SVM for subsequent condition analysis of insulators. The most significant contribution of the paper is to compute the condition indices for overhead power distribution line insulators to overcome difficulties related to vehicular applications in video surveillance. The results contained in this paper validate the efficacy of the proposed methodology for wide-scale applications in overhead power distribution system monitoring (DSM) automation.
The effects of compression gloves on hand symptoms and hand function in rheumatoid arthritis and hand osteoarthritis: a systematic review

Objective: to evaluate the effects of compression gloves in adults with rheumatoid arthritis and hand osteoarthritis. Data sources: Systematic review of randomized controlled trials identified from MEDLINE, CINAHL, AMED, PEDro, OT Seeker, The Cochrane Library, ISI Web of Knowledge, Science Direct and PubMed from their inceptions to January 2015. Review methods: Methodological quality of identified trials was evaluated using the PEDro scale by three independent assessors. Effects were summarized descriptively. Results: Four trials (n=8-24; total n=74), comparing night wear of full-length finger compression gloves with placebo gloves, were assessed. Three were of moderate (PEDro score 4-5) and one low (score 3) methodological quality. Effect sizes or standardized mean differences could not be calculated to compare trials due to poor data reporting. In rheumatoid arthritis, finger joint swelling was significantly reduced, but results for pain and stiffness were inconclusive and no differences in grip strength and dexterity were identified. One study reported similar effects in pain, stiffness and finger joint swelling from both compression and thermal placebo gloves. Only one study evaluated gloves in hand osteoarthritis (n=5) with no differences. Conclusions: All the trials identified were small with a high risk of Type I and II errors. Evidence for the effectiveness of compression gloves worn at night is inconclusive in rheumatoid arthritis and hand osteoarthritis.
Design consideration for the improved Class-D inverter topology

The characteristics and the superiority of the efficient snubber network for Class-D series resonant inverters are addressed in detail by comparison with conventional snubbers, i.e., the lossless capacitive snubber and the RC snubber, with respect to switching losses, overvoltage stresses, high-frequency resonant current stresses, and overall efficiency. Also, the optimal design scheme for it is considered and the analytical equations are derived in order to provide a straightforward and easy-to-design tool. The validity of the theoretical description is verified by testing on a 29-kHz MOSFET Class-D series resonant inverter rated at 1.2 kW.
A predictive current control of voltage source inverters for common-mode current attenuation

The development of distributed generation (DG) systems has led to the increasing use of voltage source inverters. However, step-changes in the modulated voltage can produce dangerous peak common-mode currents (CMCs), which can interfere with the power system ground and cause detrimental effects on other equipment. In this paper, the root cause of CMCs is explored and analyzed. After this, a new method which combines of a modified inverter topology and a predictive current control scheme is developed. The test results show that the proposed method effectively controls the load current while the CMCs can be reduced significantly.
Degradation of poly-L-lactide. Part 2: Increased temperature accelerated degradation

Abstract Poly-L-lactide (PLLA) is one of the most significant members of a group of polymers regarded as bioresorbable. The degradation of PLLA proceeds through hydrolysis of the ester linkages in the polymer's backbone; however, the time for the complete resorption of orthopaedic devices manufactured from PLLA is known to be in excess of five years in a normal physiological environment. To evaluate the degradation of PLLA in an accelerated time period, PLLA pellets were processed by compression moulding into tensile test specimens, prior to being sterilized by ethylene oxide gas (EtO) and degraded in a phosphate-buffered solution (PBS) at both 50 °C and 70 °C. On retrieval, at predetermined time intervals, procedures were used to evaluate the material's molecular weight, crystallinity, mechanical strength, and thermal properties. The results from this study suggest that at both 50 °C and 70 °C, degradation proceeds by a very similar mechanism to that observed at 37 °C in vitro and in vivo. The degradation models developed also confirmed the dependence of mass loss, melting temperature, and glass transition temperature (Tg) on the polymer's molecular weight throughout degradation. Although increased temperature appears to be a suitable method for accelerating the degradation of PLLA, relative to its physiological degradation rate, concerns still remain over the validity of testing above the polymer's Tg and the significance of autocatalysis at increased temperatures.
FIDS: an intelligent financial Web news articles digest system

In this paper, we present a system called FIDS (Financial Information Digest System), which can digest online financial news automatically. Compared to previous approaches, FIDS is unique in the way that it can understand news articles in different domains simultaneously. These domains are all concerned with financial news. The system is able to integrate the information from different articles by conducting automatic content-based classification and information item extraction. Moreover, it allows one to perform cross-validation on their contents. As a result, users can have access to more complete information which otherwise would be scattered in different articles.
pH-controlled change of the metal coordination in a dicopper(II) complex of the ligand H-BPMP: crystal structures, magnetic properties, and catecholase activity.

The dinucleating ligand 2,6-bis[(bis(2-pyridylmethyl)amino)methyl]-4-methylphenol (H-BPMP) has been used to synthesize the three dinuclear Cu(II) complexes [Cu2(BPMP)(OH)][ClO4](2). 0.5C4H8O (1), [Cu2(BPMP)(H2O)2](ClO4)(3). 4H2O (2), and [Cu2(H-BPMP)][(ClO4)4]. 2CH3CN (3). X-ray diffraction studies reveal that 1 is a mu-hydroxo, mu-phenoxo complex, 2 a diaqua, mu-phenoxo complex, and 3 a binuclear complex with Cu-Cu distances of 2.96, 4.32, and 6.92 A, respectively. Magnetization measurements reveal that 1 is moderately antiferromagnetically coupled while 2 and 3 are essentially uncoupled. The electronic spectra in acetonitrile or in water solutions give results in accordance with the solid-state structures. 1 is EPR-silent, in agreement with the antiferromagnetic coupling between the two copper atoms. The X-band spectrum of powdered 2 is consistent with a tetragonally elongated square pyramid geometry around the Cu(II) ions, in accordance with the solid-state structure, while the spectrum in frozen solution suggests a change in the coordination geometry. The EPR spectra of 3 corroborate the solid-state and UV-visible studies. The 1H NMR spectra also lead to observations in accordance with the conclusions from other spectroscopies. The electrochemical behavior of 1 and 2 in acetonitrile or in water solutions shows that the first reduction (Cu(II)Cu(II)-Cu(II)Cu(I) redox couple) is reversible and the second (formation of Cu(I)Cu(I) irreversible. In water, 1 and 2 are reversibly interconverted upon acid/base titration (pK 4.95). In basic medium a new species, 4, is reversibly formed (pK 12.0), identified as the bishydroxo complex. Only 1 exhibits catecholase activity (oxidation of 3,5-di-tert-butylcatechol to the corresponding quinone, vmax = 1.1 x 10(-6) M-1 s-1 and KM = 1.49 mM). The results indicate that the pH dependence of the catalytic abilities of the complexes is related to changes in the coordination sphere of the metal centers.
How Does China's New Labour Contract Law Affect Floating Workers?

China's new Labour Contract Law took effect in January 2008 and required firms to give migrant workers written contracts, strengthened labour protections for workers and contained penalties for firms that did not follow the labour code. This article uses survey data of migrant workers in the Pearl River Delta before and after the law, and a retrospective question on when workers received their first labour contract to assess the effects of the law on labour outcomes. The evidence shows that the new law increased the percentage of migrant workers with written contracts, which in turn raised social insurance coverage, reduced the likelihood of wage arrears and raised the likelihood that workers had a union at their workplace.
SDN-Based DDoS Attack Detection with Cross-Plane Collaboration and Lightweight Flow Monitoring

Distributed Denial of Service (DDoS) attacks are one of the biggest concerns for security professionals. Traditional DDoS attack detection mechanisms are based on middle-box devices or SDN controllers, which either lack network-wide monitoring information or suffer with serious southbound communication overhead and detection delay. In this paper, we propose a SDN-based DDoS attack detection framework with cross-plane collaboration called OverWatch, which performs a two-stage granularity filtering procedure between coarse-grained detection data plane and fine- grained detection control plane for abnormal flows. It leverages computational capabilities that currently underutilized on OpenFlow switches to shrink the detection range for fine-grained DDoS attack detections. In OverWatch, we propose a lightweight flow monitoring algorithm to capture the key features of DDoS attack traffics on the data plane by polling the values of counters in OpenFlow switches. Experiments are conducted in an evaluating network with a FPGA-based OpenFlow switch prototype and the Ryu controller, which reveal that our proposed OverWatch framework and flow monitoring algorithm can greatly improve the detection efficiency, as well as reduce the detection delay and southbound communication overhead.
Steptolaelaps (Acarina: Laelaptidae) a new genus of mites parasitic on neotropical rodents.

Among the collections made by the author in 1953 as part of a study of the parasitic mites of Mexico were many robust, active acarines from pocket mice, Liomys spp. These have been identified as Laelaps liomydis Grant. Through the courtesy of Lieutenant Colonel Robert Traub a collection of parasitic mites from Venezuela was made available for study and comparison with the Mexican fauna. Among these were numerous specimens from Heteromys and other rodents which represent a new species of mite closely related to L. liomydis. Study of these forms was facilitated by the loan of the allotype male and a female specimen of L. liomydis by C. Donald Grant, and the loan of a cotype of Liponysella madagascariensis (Hirst) by the British Museum of Natural History. Identifications of Mexican mammals were made by Drs. Bernardo Villa R. and Seth Benson. Dr. E. W. Jameson, Jr. kindly offered helpful comments on the manuscript. It is the author's belief that L. liomydis and the new species described here represent a new genus. Grant (in litt.) agrees with this interpretation.
Hospitalized Cases of Child Abuse in America: Who, What, When, and Where

Background: Orthopaedic surgeons need to recognize features of child abuse. The purpose of this study was to identify common characteristics of child abuse and to delineate features of physical injury cases that would raise concern for child abuse. Methods: A nationally representative sample of all pediatric inpatient discharges for calendar years 1997, 2000, and 2003 was queried for physical injury diagnoses. Cases were identified as those with a diagnosis of child abuse and controls were those without the diagnosis of child abuse. Incidence of coded child abuse and a comparison of rates across time, demographics, and injury pattern were determined. Cases were compared with controls, and relative risks for coded child abuse were computed using the generalized linear model specifying the Poisson distribution and a log link. Results: There were 665,195 physical injury cases identified. Of these, 11,554 (1.74%) had a diagnosis of child abuse. Fracture requiring orthopaedic management was present in 28% of the child abuse cases. The 3 strongest demographic predictors of coded child abuse were age younger than 1 year, age 1 to younger than 2 years, and Medicaid as primary payer with adjusted relative risks of 11.46, 3.07, and 1.99, respectively. Winter and weekday presentation were significantly higher for coded child abuse. Fractures with the greatest adjusted relative risks for coded child abuse were rib or sternum (5.34) and scapula (3.22). Pelvic fracture was the only fracture significant for lowered adjusted relative risk of coded child abuse. Conclusions: This study shows that young age continues to be a strong predictor of child abuse in the setting of physical injury. Supporting features include Medicaid as primary payer and winter or weekday presentation. Orthopaedists should be particularly aware of child abuse as 28% of cases had a fracture requiring orthopaedic management. Level of Evidence: Prognostic Study, Level III (case-control study).
Prevention of intracardiac/pulmonary thrombosis during liver transplantation.

inserted the day prior to surgery:using bupivacaine, fentanyl, andadrenalin) or patient-controlled IVmorphine analgesia during the im-mediate postoperative period. Peri-operative care was standardized(all patients underwent general an-esthesia and received a mediansternotomy). When the two groupswere compared, the only differencewas a shorter time to postoperativetracheal extubation in patients re-ceiving thoracic epidural analgesia(2.3 vs 7.3 h). Absolutely no dif-ferences were observed regardingpostoperative analgesia (at rest andduring cough), degree of sedation,lung volumes (forced vital capacity,forced vital capacity at one second,peak expiratory flow), degree of am-bulation, global quality of recoveryscore (including all five domains),cardiac morbidity, renal morbidity,neurologic outcome, intensive careunit stay, or hospital length of stay.As reports describing seriouscomplications or lack of clinicalbenefits increase, the question mustbe asked: Is it time to abandonthoracic epidural techniques in pa-tients undergoing cardiac surgery?
Combinatorial Nullstellensatz

The Combinatorial Nullstellensatz is a theorem about the roots of a polynomial. It is related to Hilbert’s Nullstellensatz. Established in 1996 by Alon et al. [4] and generalized in 1999 by Alon [2], the Combinatorial Nullstellensatz is a powerful tool that allows the use of polynomials to solve problems in number theory and graph theory. This article introduces the Combinatorial Nullstellensatz, along with a proof and some of its applications. We also compare the Combinatorial Nullstellensatz to Hilbert’s Nullstellensatz.
Isolation and characterization of OmpC porin mutants with altered pore properties

The LamB protein is normally required for the uptake of maltodextrins. Starting with a LamB- OmpF- strain, we have isolated mutants that will grow on maltodextrins. The mutation conferring the Dex+ phenotype in the majority of these mutants has been mapped to the ompC locus. These mutants, unlike LamB- OmpF- strains, grew on maltotriose and maltotetraose, but not on maltopentaose, and showed a significantly higher rate of [14C]maltose uptake than the parent strain did. In addition, these mutants showed increased sensitivity to certain beta-lactam antibiotics and sodium dodecyl sulfate, but did not exhibit an increase in sensitivity to other antibiotics and detergents. The nucleotide sequence of these mutants has been determined. In all cases, residue 74 (arginine) of the mature OmpC protein was affected. The results suggest that this region of the OmpC protein is involved in the pore domain and that the alterations lead to an increased pore size.