Miracle-dz/UniFAR-FTUs huggingface dataset:
KpsC and KpsS are retaining 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) transferases involved in synthesis of bacterial capsules

Significance Capsules are bacterial surface structures used by many Gram-negative pathogens to evade the host immune system. They are comprised of long carbohydrate chains, called capsular polysaccharides (CPSs), which possess a lipid at one end. The lipid is connected to the CPS through an unusual linker consisting of five to nine residues of an acidic sugar 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo). This study identifies two conserved proteins from CPS assembly systems, KpsC and KpsS, as the enzymes that synthesize the Kdo linker on the terminal lipid. Synthesis of this terminal glycolipid was reconstituted in vitro using purified enzymes and a synthetic lipid acceptor. The data support a unique model for CPS biosynthesis and identify these enzymes as unique targets for antibacterial therapies. Capsular polysaccharides (CPSs) are high-molecular-mass cell-surface polysaccharides, that act as important virulence factors for many pathogenic bacteria. Several clinically important Gram-negative pathogens share similar systems for CPS biosynthesis and export; examples include Escherichia coli, Campylobacter jejuni, Haemophilus influenzae, Neisseria meningitidis, and Pasteurella multocida. Each CPS contains a serotype-specific repeat-unit structure, but the glycans all possess a lipid moiety at their reducing termini. In E. coli and N. meningitidis, the predominant lipid is a lysophosphatidylglycerol moiety that is attached to the repeat-unit domain of the CPS via multiple residues of 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo), referred to as a poly-Kdo linker. The Kdo residues are β-linked, suggesting that they are synthesized by retaining glycosyltransferases. To date, the only characterized Kdo transferases are the inverting enzymes that catalyze the α-linkages found in lipopolysaccharide. Here, we identify two conserved proteins from CPS assembly systems, KpsC and KpsS, as the β-Kdo-transferases and demonstrate in vitro reconstitution of poly-Kdo linker assembly on a fluorescent phosphatidylglycerol acceptor. KpsS adds the first Kdo residue, and this reaction product is then extended by KpsC. Cross-complementation experiments demonstrate that the E. coli and N. meningitidis protein homologs are functionally conserved.
HMGA1a: sequence‐specific RNA‐binding factor causing sporadic Alzheimer's disease‐linked exon skipping of presenilin‐2 pre‐mRNA

Aberrant exon 5 skipping of presenilin‐2 (PS2) pre‐mRNA produces a deleterious protein isoform PS2V, which is almost exclusively observed in the brains of sporadic Alzheimer's disease patients. PS2V over‐expression in vivo enhances susceptibility to various endoplasmic reticulum (ER) stresses and increases production of amyloid‐β peptides. We previously purified and identified high mobility group A protein 1a (HMGA1a) as a trans‐acting factor responsible for aberrant exon 5 skipping. Using heterologous pre‐mRNAs, here we demonstrate that a specific HMGA1a‐binding sequence in exon 5 adjacent to the 5′ splice site is necessary for HMGA1a to inactivate the 5′ splice site. An aberrant HMGA1a–U1 snRNP complex was detected on the HMGA1a‐binding site adjacent to the 5′ splice site during the early splicing reaction. A competitor 2′‐O‐methyl RNA (2′‐O‐Me RNA) consisting of the HMGA1a‐binding sequence markedly repressed exon 5 skipping of PS2 pre‐mRNA in vitro and in vivo. Finally, HMGA1a‐induced cell death under ER stress was prevented by transfection of the competitor 2′‐O‐Me RNA. These results provide insights into the molecular basis for PS2V‐associated neurodegenerative diseases that are initiated by specific RNA binding of HMGA1a.
A Time-to-Digital Converter Based on Time-Space Relationship

This paper describes a time-to-digital converter based on time-space relationship to improve the measuring precision of time interval. A tapped transmission line of certain length is used as the delay line, which converts the measured time to length. The delay characteristics and electrical performance of two types of transmission lines, coaxial cable and microstrip, are analyzed, as well as the factors affecting the delay characteristics, such as loss and temperature. The coincidence detection of the delayed start signal and stop signal is so critical that a type of coincidence detection circuit is developed, of which the uncertainty is 14 ps. Buffer is used to enlarge the measurement range. The structure of the time-to-digital converter is also presented, of which the quantization error, integral nonlinearity error and random error is analyzed. An advantage of this kind of time-to-digital converter is easy to be integrated. Based on the CMOS technology, a chip is designed, and a simulation of the chip is performed, which presents 23 ps single-shot precision. As a demonstration of this principle, a prototype using the microstrip on a printed-circuit-board as delay line is realized with 108 ps single-shot precision.
Pharmacodynamics of the Antibacterial Effect and Emergence of Resistance to Tomopenem, Formerly RO4908463/CS-023, in an In Vitro Pharmacokinetic Model of Staphylococcus aureus Infection

ABSTRACT The antibacterial effects (ABE) of tomopenem (formerly RO4908463/CS-023) against seven Staphylococcus aureus strains (methicillin-resistant S. aureus [MRSA] strain tomopenem MICs, 0.5 to 16 mg/liter; methicillin-sensitive S. aureus [MSSA] strain tomopenem MIC, 0.06 mg/liter) were studied in an in vitro pharmacokinetic model. Initially, two human doses were simulated, 750 mg every 8 hours (8hly) and 1,500 mg 8hly intravenously, using S. aureus at a standard inoculum of 106 CFU/ml. There was a rapid clearance of bacteria from the model by 12 h after drug exposure with most strains. Clearance was not related to the tomopenem MIC. The ABE of these two tomopenem dose regimens were also tested at a high inoculum, 108 CFU/ml; in all simulations, there was a >4-log drop in viable count at 24 h. Strains were not cleared from the model at 108 CFU/ml, in contrast to what was seen for the standard inoculum. When the ABE of tomopenem at 750 mg 8hly was compared to those of vancomycin, tomopenem was seen to have a superior effect, as measured by the area under the bacterial kill curve at 24 h (AUBKC24) and 48 h (P < 0.05). Dose ranging studies were performed to provide time-above-MIC (T>MIC) drug exposures of 0 to 100% (8 to 10 doses per strain) with five MRSA/MSSA strains. The T>MIC for a 24-h bacteriostatic effect was 8% ± 5% (range, 1.3% to 15.4%); the T>MIC for a 4-log drop in viable count was 32% ± 18% (range, 12.8% to 36.2%). The T>MIC for a 90% maximum response using AUBKC24 as ABE was 24.9% ± 15.7%. Inoculum had little impact on T>MIC exposures for ABE. There was emergence of resistance to tomopenem in the dose ranging studies, with increased growth of subpopulations on plates containing tomopenem at 2× and 4× the MIC compared to what was seen for preexposure population analysis at T>MICs of <20%. The pharmacodynamics of tomopenem against S. aureus is similar to those of other members of the carbapenem class, with the exception that MRSA is included. These data indicate that tomopenem will have clinically useful activity against MRSA at T>MICs achievable in humans.
Design and optimization of new thyristors controlled reactors with zero harmonic content

This paper provides optimal design of new topologies of the thyristor controlled reactors TCR used in static VAR compensators systems SVC with zero harmonic content. The paper discusses the principle of operation of the new topologies which depends on thyristor switched reactors TSR. The objective function and its constrains to get optimal design of such topologies are suggested to get proper reactive power control with uniform distribution. The genetic algorithm GA is used to get the optimal design for each proposed topology. The developed designs are evaluated during reactive power development with zero harmonic content. Paper provides the ratings for each topology and suggests the possible modifications to adjust the design and minimize apparent power for reactors and switches.
DTMOS-Based Pulse Transformer Boost Converter With Complementary Charge Pump for Multisource Energy Harvesting

An energy-harvesting system that accommodates both discrete-time or continuous-time energy sources simultaneously is presented. The core dc-dc converter is a pulse transformer boost converter using dynamic threshold MOS transistor that self-starts at 36 mV-input voltage and generates bipolar output voltages up to ±2.5 V. Employing the dynamic body bias technique to the boost converter power transistor improves power efficiency at sub-300-mV input voltages up to two times over the identical transistor in a conventional configuration. At large harvested power, the source-to-body diode of the power transistor functions as an input voltage limiter. Dynamic threshold MOSFET (DTMOS) also increases transistor saturation current and output power compared to conventional transistors at similar input voltage. Instead of using a linear shunt regulator, excess power is dissipated by internal loss of a bipolar-clocked cross-coupled charge pump. An on-chip voltage-controlled oscillator, which generates clock frequency in proportion to the harvested power, and a unipolar-to-bipolar level shifter are included to drive the charge pump designed. The circuit prototypes are fabricated by using the UMC 0.13-μm CMOS process with the triple-well option.
The Styx IP-Core for ubiquitous network device interoperability

ASBTRACT Application level interoperability between ubiquitous networked communication devices (e.g. Mobile phones, PDA, CCD camera, etc.) poses many problems. In this paper we consider the issue of efficient application level access to resources on remote devices whilst achieving both network and distribution transparency. Provision of such transparency is difficult as lowresource devices are usually limited to one or two standard communication mediums (e.g. WiFi, Bluetooth, ZigBee). Thus, it is unlikely that an application node can communicate directly with all other nodes, with the requirement for some to act as intermediaries. Also, direct control of remote devices (potentially via some intermediary) in the same manner as local devices is not usually provided by conventional OSs. In this paper we consider the Styx protocol (from the Inferno OS) as a solution to these problems. Styx is defined to provide a file based interface to devices, within a namespace that provides distribution transparency (coping with intermediary devices). However, Styx currently is only available as software, requiring a OS (and CPU). We define and implement a (hardware) Styx IP-core Module 1 to provide both network and distribution transparency for applications that control physically remote devices. For lowresource devices, such an approach removes the need for a CPU (to execute a software OS and Styx implementation). The implementation of the hardware Styx IP-core (and subsequent demonstration) presented within the paper show the efficacy of this hardware Styx approach.
Inhibition of some human neutrophil functions by the cyclooxygenase inhibitor ketorolac tromethamine

Ketorolac tromethamine, a new nonsteroidal anti‐inflammatory agent of the pyrrolo‐pyrrole group, was assayed for inhibitory effects on polymorphonuclear leukocytes (PMN) in a variety of systems. Ketorolac inhibited PMN superoxide anion generation, lysozyme release, myeloperoxidase release, adherence to plastic surfaces, and chemotaxis in response to N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP) in a dose‐dependent manner. Ketorolac also inhibited phorbol myristate acetate‐stimulated adherence of PMN to bovine pulmonary artery endothelial cells. The drug inhibited lysozyme and myeloperoxidase release by PMN in response to C5a but failed to inhibit C5a stimulation of PMN in any of the other assays. Levels of ketorolac required to inhibit PMN function in most systems were in the range of 0.2 to 1.0 mg/ml, but chemotaxis to fMLP was inhibited by concentrations of ketorolac as low as 1 μg/ml. Ketorolac, currently the only nonsteroidal anti‐inflammatory drug available in a parenteral form may have therapeutic usefulness in a variety of conditions thought to be mediated in part by PMN, including sepsis.
Recurrence rates in endonasal surgery for polyposis.

OBJECTIVE To assess the prognostic factors of recurrence in a cohort of patients operated on for polyposis by means of endonasal endoscopic surgery. METHODS Prospective study of 227 patients operated on for polyposis in a single institution between 1993 and 2001. The mean follow-up period was 24 months (range 12 months to 60 months). Nine parameters were analysed to study their association with polyp recurrence: age, gender, smoking history, presence of asthma, allergy, non-steroidal anti-inflammatory drugs (NSAID) intolerance, recurrent sinusitis, previous nasal surgery, and polyp extension. Analysis of recurrences was accomplished using the Kaplan-Meier survival curves and differences were analysed using the log-rank test. The Cox proportional hazards model was used to estimate the effect of individual risk factors on polyp recurrence. A probability value of p < 0.05 was the level of significance selected. RESULTS During the study period, recurrences developed in 55 patients, giving a rate of 24%. In the univariate analysis, NSAID intolerance, asthma, revision surgery and polyp extension were associated with recidivism. The other mentioned factors did not attain statistical significance. However, the multivariate analysis demonstrated that only NSAID intolerance and asthma are independent predictive factors for recurrence. CONCLUSIONS Patients presenting NSAID intolerance or asthma are at risk for the development of recurrences after endonasal surgery for nasal polyposis.
Dictionary based inverted index for music information retrieval

With the rapid progress in data storage and communication technology, there has been an explosive growth of music information. As the traditional metadata-based search engine can not provide natural and intuitive way to retrieve music, content-based music information retrieval has been attracting more and more attention and is becoming a popular research topic over the past decades. How to organize and search large scale music collections is one of the most fundamental challenging research problems. In this paper we introduce an inverted index approach well known in text information retrieval to organize and index music collections. According to musical form structure and repetition rule of musical themes, repeating patterns can be regarded as representation for musical themes. Statistical result indicates repeating patterns follow Zipf's law on a given music database. Music melodies are segmented into phrases based on musical dictionary composed of repeating patterns, and added into inverted index with necessary music information. Experimental results reveal that proposed index method outperforms the compared method greatly with much less storage space.
Tumourigenic characteristics of embryonal carcinoma cells as a model for studying tumour progression of human embryonic stem cells

The objective of this study was to compare tumourigenic characteristics of human embryonic stem cells (HESCs) and embryonal carcinoma cells (ECCs) to identify a robust and simple model for studying certain aspects of cell transformation and tumourigenesis, in tumour progression of HESCs.
Mechanisms of first and second pain in the peripheral and central nervous systems.

Brief (< 2.0 sec) noxious heat pulses (peak temp = 51.5°C) programmed by a computer and generated by a contact thermode produced first and second pain in human subjects. Measurements of reaction time confirmed that these first and second pains were related to the conduction of impulses in A heat nociceptive and C polymodal nociceptive afferents respectively. Estimates of psychophysical magnitude showed that when four identical heat pulses were applied to the same spot on the hand (interstimulus interval 80 sec), the first pain progressively decreased in perceived intensity whereas the second pain increased with interstimulus intervals of 3 sec or less. The first pain did not decrease if the location of the thermode was changed between each stimulus whereas the summation of the second pain increased under these conditions. Identical trains of noxious heat pulses partially suppressed the responses of A and of C nociceptive afferents. These psychophysical observations and physiologic records indicate that the temporal suppression of heat-induced first pain is related to the suppression of A heat nociceptors and that prolonged temporal summation of second pain is related to summation within the central nervous system. A heat nociceptive afferents and C polymodal nociceptive afferents converge on two types of spinothalamic tract neurons: (1) wide dynamic-range neurons that receive input from non-nociceptive and nociceptive afferents. and (2) nociceptive-specific neurons. Since both types show summation of responses to repeated C fiber stimulation, they can account for summation of second pain.
Increased expression of GLUT-4 and hexokinase in rat epitrochlearis muscles exposed to AICAR in vitro.

Exercise acutely stimulates muscle glucose transport and also brings about an adaptive increase in the capacity of muscle for glucose uptake by inducing increases in GLUT-4 and hexokinase. (1) Recent studies have provided evidence that activation of AMP protein kinase (AMPK) is involved in the stimulation of glucose transport by exercise. The purpose of this study was to determine whether activation of AMPK is also involved in mediating the adaptive increases in GLUT-4 and hexokinase. To this end, we examined the effect of incubating rat epitrochlearis muscles in culture medium for 18 h in the presence or absence of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), which enters cells and is converted to the AMP analog ZMP, thus activating AMPK. Exposure of muscles to 0.5 mM AICAR in vitro for 18 h resulted in an approximately 50% increase in GLUT-4 protein and an approximately 80% increase in hexokinase. This finding provides strong evidence in support of the hypothesis that the activation of AMPK that occurs in muscle during exercise is involved in mediating the adaptive increases in GLUT-4 and hexokinase.
Striding Out With Parkinson Disease: Evidence-Based Physical Therapy for Gait Disorders

Although Parkinson disease (PD) is common throughout the world, the evidence for physical therapy interventions that enable long-term improvement in walking is still emerging. This article critiques the major physical therapy approaches related to gait rehabilitation in people with PD: compensatory strategies, motor skill learning, management of secondary sequelae, and education to optimize physical activity and reduce falls. The emphasis of this review is on gait specifically, although balance and falls are of direct importance to gait and are addressed in that context. Although the researchers who have provided the evidence for these approaches grounded their studies on different theoretical paradigms, each approach is argued to have a valid place in the comprehensive management of PD generally and of gait in particular. The optimal mix of interventions for each individual varies according to the stage of disease progression and the patient's preferred form of exercise, capacity for learning, and age.
Trafficking of Normal Stem Cells and Metastasis of Cancer Stem Cells Involve Similar Mechanisms: Pivotal Role of the SDF‐1–CXCR4 Axis

The α‐chemokine stromal‐derived factor (SDF)‐1 and the G‐protein–coupled seven‐span transmembrane receptor CXCR4 axis regulates the trafficking of various cell types. In this review, we present the concept that the SDF‐1–CXCR4 axis is a master regulator of trafficking of both normal and cancer stem cells. Supporting this is growing evidence that SDF‐1 plays a pivotal role in the regulation of trafficking of normal hematopoietic stem cells (HSCs) and their homing/retention in bone marrow. Moreover, functional CXCR4 is also expressed on nonhematopoietic tissue‐committed stem/progenitor cells (TCSCs); hence, the SDF‐1–CXCR4 axis emerges as a pivotal regulator of trafficking of various types of stem cells in the body. Furthermore, because most if not all malignancies originate in the stem/progenitor cell compartment, cancer stem cells also express CXCR4 on their surface and, as a result, the SDF‐1–CXCR4 axis is also involved in directing their trafficking/metastasis to organs that highly express SDF‐1 (e.g., lymph nodes, lungs, liver, and bones). Hence, we postulate that the metastasis of cancer stem cells and trafficking of normal stem cells involve similar mechanisms, and we discuss here the common molecular mechanisms involved in these processes. Finally, the responsiveness of CXCR4+ normal and malignant stem cells to an SDF‐1 gradient may be regulated positively/primed by several small molecules related to inflammation which enhance incorporation of CXCR4 into membrane lipid rafts, or may be inhibited/blocked by small CXCR4 antagonist peptides. Consequently, strategies aimed at modulating the SDF‐1–CXCR4 axis could have important clinical applications both in regenerative medicine to deliver normal stem cells to the tissues/organs and in clinical hematology/oncology to inhibit metastasis of cancer stem cells.
Genetic and Hormonal Regulation of Chlorophyll Degradation during Maturation of Seeds with Green Embryos

The embryos of some angiosperms (usually referred to as chloroembryos) contain chlorophylls during the whole period of embryogenesis. Developing embryos have photochemically active chloroplasts and are able to produce assimilates, further converted in reserve biopolymers, whereas at the late steps of embryogenesis, seeds undergo dehydration, degradation of chlorophylls, transformation of chloroplast in storage plastids, and enter the dormancy period. However, in some seeds, the process of chlorophyll degradation remains incomplete. These residual chlorophylls compromise the quality of seed material in terms of viability, nutritional value, and shelf life, and represent a serious challenge for breeders and farmers. The mechanisms of chlorophyll degradation during seed maturation are still not completely understood, and only during the recent decades the main pathways and corresponding enzymes could be characterized. Among the identified players, the enzymes of pheophorbide a oxygenase pathway and the proteins encoded by STAY GREEN (SGR) genes are the principle ones. On the biochemical level, abscisic acid (ABA) is the main regulator of seed chlorophyll degradation, mediating activity of corresponding catabolic enzymes on the transcriptional level. In general, a deep insight in the mechanisms of chlorophyll degradation is required to develop the approaches for production of chlorophyll-free high quality seeds.