Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Homophenylalanine Biosynthetic Genes from the Cyanobacterium Nostoc punctiforme PCC73102 and Application to Its Microbial Production by Escherichia coli

ABSTRACT l-Homophenylalanine (l-Hph) is a useful chiral building block for synthesis of several drugs, including angiotensin-converting enzyme inhibitors and the novel proteasome inhibitor carfilzomib. While the chemoenzymatic route of synthesis is fully developed, we investigated microbial production of l-Hph to explore the possibility of a more efficient and sustainable approach to l-Hph production. We hypothesized that l-Hph is synthesized from l-Phe via a mechanism homologous to 3-methyl-2-oxobutanoic acid conversion to 4-methyl-2-oxopentanoic acid during leucine biosynthesis. Based on bioinformatics analysis, we found three putative homophenylalanine biosynthesis genes, hphA (Npun_F2464), hphB (Npun_F2457), and hphCD (Npun_F2458), in the cyanobacterium Nostoc punctiforme PCC73102, located around the gene cluster responsible for anabaenopeptin biosynthesis. We constructed Escherichia coli strains harboring hphABCD-expressing plasmids and achieved the fermentative production of l-Hph from l-Phe. To our knowledge, this is the first identification of the genes responsible for homophenylalanine synthesis in any organism. Furthermore, to improve the low conversion efficiency of the initial strain, we optimized the expression of hphA, hphB, and hphCD, which increased the yield to ∼630 mg/liter. The l-Hph biosynthesis and l-Leu biosynthesis genes from E. coli were also compared. This analysis revealed that HphB has comparatively relaxed substrate specificity and can perform the function of LeuB, but HphA and HphCD show tight substrate specificity and cannot complement the LeuA and LeuC/LeuD functions, and vice versa. Finally, the range of substrate tolerance of the l-Hph-producing strain was examined, which showed that m-fluorophenylalanine, o-fluorophenylalanine, and l-tyrosine were accepted as substrates and that the corresponding homoamino acids were generated.
Interactions of TLC1 (Which Encodes the RNA Subunit of Telomerase), TEL1, and MEC1 in Regulating Telomere Length in the Yeast Saccharomyces cerevisiae

ABSTRACT In the yeast Saccharomyces cerevisiae, chromosomes terminate with a repetitive sequence [poly(TG1–3)] 350 to 500 bp in length. Strains with a mutation of TEL1, a homolog of the human gene (ATM) mutated in patients with ataxia telangiectasia, have short but stable telomeric repeats. Mutations of TLC1 (encoding the RNA subunit of telomerase) result in strains that have continually shortening telomeres and a gradual loss of cell viability; survivors of senescence arise as a consequence of a Rad52p-dependent recombination events that amplify telomeric and subtelomeric repeats. We show that a mutation inMEC1 (a gene related in sequence to TEL1 andATM) reduces telomere length and that tel1 mec1double mutant strains have a senescent phenotype similar to that found in tlc1 strains. As observed in tlc1 strains, survivors of senescence in the tel1 mec1 strains occur by a Rad52p-dependent amplification of telomeric and subtelomeric repeats. In addition, we find that strains with both tel1 andtlc1 mutations have a delayed loss of cell viability compared to strains with the single tlc1 mutation. This result argues that the role of Tel1p in telomere maintenance is not solely a direct activation of telomerase.
Infection with a plasmid-free variant Chlamydia related to Chlamydia trachomatis identified by using multiple assays for nucleic acid detection

Clinical samples in transport media from 40 patients exhibiting pathologies potentially caused by Chlamydia trachomatis infection were analyzed for chlamydial nucleic acid, and the results were compared with those of culture. Chlamydial culture was performed by a shell vial centrifugation method with HeLa 229 host cells. Polymerase chain reaction (PCR) assays were used to detect either regions on a 7.5-kb plasmid characteristic of C. trachomatis (plasmid-PCR) or a segment of the 16S rRNA genes (rRNA-PCR). All PCR results were confirmed by hybridization with probes for the specific amplified products in either a Southern or a dot blot format. An RNase protection (RNP) assay was used to detect genus-specific chlamydial 16S rRNA directly from the clinical samples. The PCR assays detected C. trachomatis but not other bacteria, including Chlamydia spp. C. trachomatis was isolated from six samples which were positive by the rDNA-PCR and plasmid-PCR assays. Five of the culture-positive specimens were positive by the RNP assay. Twenty-two samples were negative by all criteria. Surprisingly, nine samples were positive by rRNA-PCR and RNP assays only. Nucleic acid sequencing of the rRNA-PCR-amplified products indicated a close relationship between the variants and C. trachomatis. The data may indicate an unrecognized process in C. trachomatis infection or that these patients were infected by a variant strain of C. trachomatis which lacks the C. trachomatis-specific plasmid.
Polarimetric SAR interferometry for forest application at P-band: Potentials and challenges

This paper presents the impact of simulation parameters according to the potential future space-borne mission BIOMASS (P-band) in polarimetric and interferometric SAR (Pol-InSAR) inverison performance. Forest height inversion is obtained from the simulated data sets (bandwidth, NESZ and ambiguities) generated from DLR E-SAR (Experimental Synthetic Aperture Radar) airborne SAR data. For this study two campaign data sets (BioSAR 2007 / INDREX-II) have been selected and investigated. The several comparative results of Pol-InSAR between airborne data and the simulated data (incl. bandwidth, NESZ and range/azimuth ambiguities) will be shown and discussed.
A Game Theoretic Framework for Call Admission Control in CDMA Mobile Multimedia Systems with Traffic Asymmetry between Uplink and Downlink

In code-division multiple-access (CDMA) mobile multimedia systems, call admission control (CAC) is essential to prevent overloading and ensure quality of service (QoS) requirement for each traffic class. While efficiency is an important performance issue in the mobile networks with multimedia services, the concept of fairness among services should also be considered. Game theory can provide an appropriate framework for formulating such fair and efficient CAC problem. In this paper, a selection method for fair-efficient threshold parameters of the CAC scheme in CDMA mobile multimedia systems with traffic asymmetry based on the framework of game theory is proposed. The proposed scheme provides fairness and efficiency in terms of uplink and downlink signal-to-interference ratio (SIR) for the 2 classes of traffic, and also guarantees the priority of class 0 calls over class 1 calls. Class 0 calls and class 1 calls are viewed as two players of a game. For the cooperative game, the arbitration schemes for the interpersonal comparisons of utility and the bargaining problem are investigated. In the aspect of the social welfare (total utility), the numerical results indicate that the Nash solution of the bargaining problem outperforms the equilibrium point of the noncooperative game and the solution of the interpersonal comparisons of utility due to its much higher total utility.
Infinite Loot Box: A Platform for Simulating Video Game Loot Boxes

Loot boxes are garnering increased attention in both the industry and media. One focal point of the discussion is whether loot boxes should be considered a form of gambling. While parallels can be drawn between loot boxes and random reward schedules, researchers have argued that the “glorification” aspect of loot boxes that have heightened player awareness (e.g., opening a box, a pack of cards, or spinning a wheel) of randomness is a relatively new trend in games. However, there is currently a dearth of empirical research on loot boxes. We make two contributions in this paper: 1) Infinite Loot Box, an open-source Unity platform for experimenting with loot boxes created from scratch; and 2) a 2 × 2 experiment (high/low visual effects × high/low audial effects; $N$ = 1235). We find that high audial effects significantly increase the number of loot boxes opened. Neither audial nor visual effects were found to significantly impact other variables. These contributions push forward our understanding of loot boxes and their contextual factors.
On the Circuit-Level Reliability Degradation Due to AC NBTI Stress

In this paper, an experimental analysis of the impact of dynamic negative bias temperature instability (NBTI) stress on the CMOS inverter dc response and temporal performance is presented. We analyzed the circuit behavior subjected to ac NBTI in the prospect to correlate the induced degradation with that seen at PMOS device level. The results revealed that, while ac NBTI-induced shift of the inverter features shows both voltage and temperature dependence, it does not always exhibit stress time dependence. Indeed, the time exponent n is found to depend on both voltage and temperature. The analysis of such behavior when correlated with the PMOS threshold shift points toward the coexistence of more than one physical mechanism behind the degradation, where one mechanism could dominate the other under certain stress conditions. Depending on these conditions, circuit lifetime could be more or less affected.
Evaluation of the potassium channel activator cromakalim (BRL 34915) as a bronchodilator in the guinea‐pig: comparison with nifedipine

1 The potential of the potassium channel activator, cromakalim (BRL 34915), as a bronchodilator has been evaluated in guinea‐pig models in comparison with nifedipine. Some effects of the compounds on guinea‐pig tracheal spirals have been studied in an attempt to elucidate their different efficacies in vivo. 2 When given by the intraduodenal route to anaesthetized guinea‐pigs, cromakalim (3 and 10 mg kg−1) inhibited 5‐hydroxytryptamine (5‐HT)‐induced bronchospasm for at least 60 min. When given by the i.v. route, the dose of cromakalim producing 50% inhibition of the 5‐HT response was 84 μg kg−1. Nifedipine failed to show any protective effect up to 100 μg kg−1, i.v. and was lethal at higher dose levels. 3 Cromakalim protected conscious guinea‐pigs from asphyxic collapse in response to histamine aerosol. The maximal effect occurred 60 min following oral dosing, with 2.5 mg kg−1 providing complete protection for almost half of the animals. Nifedipine had only a weak protective effect even at a high dose level of 50 mg kg−1, p.o. 4 Cromakalim prolonged the time before convulsive cough in response to an antigen challenge in actively sensitized guinea‐pigs. Its minimum protective dose was 1 mg kg−1, p.o. Nifedipine (50 mg kg−1, p.o.) was ineffective. 5 Cromakalim inhibited both spontaneous and prostaglandin E2‐induced tone in guinea‐pig isolated tracheal spirals with IC50 values, relative to the maximum inhibition achieved by isoprenaline (10−3m), of 1.1 × 10−6m and 8.9 × 10−7m, respectively. Its maximal effect was 89% of that produced by isoprenaline. Removal of the epithelium did not influence its activity. Studies using the two enantiomers showed that the activity of cromakalim resided almost entirely in the (−)‐enantiomer. 6 Nifedipine (2 × 10−5 m) achieved only 49% of the relaxant effect of 10−3 m isoprenaline in isolated tracheal spirals. Addition of cromakalim (10−5 m) at the end of the nifedipine concentration‐response experiment caused further relaxation to 94% of the effect of isoprenaline. 7 It is concluded that cromakalim has greater potential than nifedipine as a bronchodilator. It appears that opening of potassium channels, with consequent hyperpolarization and stabilization of the membrane potential, prevents calcium entering the cytosol through routes that are unaffected by calcium entry blockers.
Are the Performance Based Logistics Prophets Using Science or Alchemy to Create Life-Cycle Affordability? Using Theory to Predict the Efficacy of Performance Based Logistics

Abstract : Numerous studies have provided evidence that performance-based logistics (PBL) can control cost and improve performance. The success -- and failure -- of PBL strategies suggest the need to position the PBL research domain into a fabric of theory. Just as engineering theories predict the reliability of a new armored vehicle, economic and business theories provide a framework that explains the efficacy of PBL. This article describes the underlying theoretical fabric of PBL. Armed with a framework grounded in theory, senior leaders can make science-based decisions to explain, predict, refine, and advocate for affordability-enhancing, life-cycle governance structures by leveraging the critical success factors of PBL.
Automatic off‐resonance correction in spiral imaging with piecewise linear autofocus

Off‐resonance generates blurring artifacts in spiral images. Applications that often utilize spiral trajectories, such as fine‐resolution imaging and rapid scanning, typically preclude the measurement of accurate field maps needed for effective off‐resonance correction. Automatic deblurring, or autofocus, algorithms have been developed to estimate the field map directly from the corrupted data prior to off‐resonance correction, eliminating the need for field map measurements. These algorithms rely in whole or in part on optimizing an objective function, and suffer from problems related to the accurate minimization and utility of the function. Here, a new method is presented to correct off‐resonance blurring automatically without an objective function using a piecewise linear framework. Local linear field maps are estimated with a combination of k‐space spectral analysis and mapdrift, an image feature‐based correlation technique, for subsequent piecewise linear deblurring. This approach enables field map estimation without optimization, provides accurate off‐resonance correction, is suitable for low signal‐to‐noise ratio and fine‐resolution applications, and does not require access to the raw data. Deblurred images from fine‐resolution spiral scans of a phantom and healthy volunteers at 3T show that the proposed method can be superior to conventional autofocus and comparable to field map‐based correction. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.
A Novel 3D Geometric Algorithm for Aircraft Autonomous Collision Avoidance

This paper presents a novel decision-making algorithm for pair wise non-cooperative aircraft mid-air collision avoidance. An analytical solution for this control problem, based on a three dimensional geometric approach, is derived. It does not require the solution of any programming problem, thus resulting suitable for real-time applications. Moreover, the availability of an analytical solution allows the application of well assessed control analysis and synthesis techniques in order to improve stability and performance robustness. The proposed algorithm performs optimal avoidance maneuvers, both in the horizontal and vertical plane, by minimizing aircraft deviation from its nominal trajectory. Its effectiveness has been proved via numerical simulations, in proper conflict scenarios which take into account aircraft dynamics and on-board sensors limitations
Fibrinogen-Fibrin Degradation Product Levels in Different Types of Intravascular Haemolysis

To examine the possibility that intravascular haemolysis may lead to intravascular coagulation we have compared the degree of fibrin deposition, as measured by levels of serum fibrinogen-fibrin degradation products (F.D.P.), in two different types of intravascular haemolysis associated with red cell fragmentation. F.D. P. levels in 56 patients with intravascular haemolysis secondary to prosthetic heart valves were compared with those in 18 patients who had microangiopathic haemolytic anaemia (M.H.A.) associated with malignant hypertension or renal disease. F.D. P. levels were raised in almost all the patients with M.H. A. , and this group had significantly higher levels than any of the valve replacement groups. In contrast, in the prosthetic valve patients F.D. P. levels were usually normal and bore no relation to the degree of haemolysis. It is suggested that in the absence of other precipitating factors intravascular haemolysis will not initiate intravascular coagulation. In M.H. A. , while the intravascular haemolysis appears to be a consequence of an underlying intravascular coagulation, it is likely that persistence of the coagulation disturbance is related more to factors such as small vessel damage than to the release of any thromboplastic substances from fragmented red cells.
Role of oxidative stress in a rat model of radiation-induced erectile dysfunction.

INTRODUCTION Chronic oxidative stress is one of the major factors playing an important role in radiation-induced normal tissue injury. However, the role of oxidative stress in radiation-induced erectile dysfunction (ED) has not been fully investigated. Aims. To investigate role of oxidative stress after prostate-confined irradiation in a rat model of radiation-induced ED. METHODS Fifty-four young adult male rats (10-12 weeks of age) were divided into age-matched sham radiotherapy (RT) and RT groups. Irradiated animals received prostate-confined radiation in a single 20 Gy fraction. MAIN OUTCOME MEASURES Intracavernous pressure (ICP) measurements with cavernous nerve electrical stimulation were conducted at 2, 4, and 9 weeks following RT. The protein expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits (Nox4 and gp91(phox)), markers of oxidative DNA damage (8-hydroxy-2'-deoxyguanosine [8-OHdG]), lipid peroxidation (4-hydroxynonenal [4HNE]), and inflammatory response including inducible nitric oxide synthase, macrophage activation (ED-1), and nitrotyrosine, and endogenous antioxidant defense by nuclear factor erythroid 2-related factor (Nrf2) were evaluated in irradiated prostate tissue and corpora cavernosa (CC). In addition, we investigated the relationships between results of ICP/mean arterial pressure (MAP) ratios and expression level of oxidative stress markers. RESULTS In the RT group, hemodynamic functional studies demonstrated a significant time-dependent decrease in ICP. Increased expression of Nox4, gp91(phox), 8-OHdG, and 4HNE were observed in the prostate and CC after RT. Similarly, expressions of inflammatory markers were significantly increased. There was a trend for increased Nrf2 after 4 weeks. ICP/MAP ratio negatively correlated with higher expression level of oxidative markers. CONCLUSION NADPH oxidase activation and chronic oxidative stress were observed in irradiated prostate tissue and CC, which correlated with lower ICP/MAP ratio. Persistent inflammatory responses were also found in both tissues after RT. These findings suggest that oxidative stress plays a crucial role in the development of radiation-induced ED.
Silver nanoparticles decorated nanoporous gold for surface-enhanced Raman scattering

Raman spectra are considered as signatures of matter and have been widely used to identify several classes of materials. The development of mobile spectrometers further extends applications of Raman spectroscopy, and both indoor/outdoor and in vivo/in vitro measurements have been evaluated on site. However, the finite detection level restricts its application in high density matters. Here we report a facile silver nanoparticle decorated nanoporous gold (NanoAg@NPG) substrate, which can provide high enhancement of the Raman signal from nearby molecules by 785 nm photoexcitation. This enhancement is attributed to the abundant Raman-active nanogaps constructed by adjacent nanoparticles and also by the NPG ligaments and adhered nanoparticles. This NanoAg@NPG substrate shows great potential as a reproducible and quantifiable near infrared surface-enhanced Raman scattering probe for various targets, since it performs well in the so-called biological window which can avoid autofluorescence and absorption either from targets or surroundings in the visible optical region.
The early chain of care and risk of death in acute stroke in relation to the priority given at the dispatch centre: A multicentre observational study

Background: The early chain of care is critical for stroke patients. The most important part is the so-called ’system delay’ i.e. the delay time from call to the emergency medical services until a diagnosis is established (computer tomography). Aim: The purpose of this study was to relate the initial priority level given by the dispatch centre to the early chain of care in acute stroke and to short-term and long-term mortality. Methods: All patients hospitalised with the first and the final diagnosis of acute stroke, 15 December 2010–15 April 2011, were recruited across nine hospitals, each hospital with a stroke care unit. Results: In all, 897 stroke patients were included. Priority at the dispatch centre: 54% received highest priority 1, 41% priority 2 and 5% priority 3. Median system delay from call to emergency medical services until diagnosis by computer tomography was 2 h and 52 min, 4 h and 49 min and 6 h and 33 min respectively in the three priority groups (p<0.0001). There was a similarly strong association between priority level at the dispatch centre and system delay to arrival in a hospital ward, suspicion of stroke by the emergency medical services nurse as well as the physician on hospital admission and the proportion of patients given thrombolysis. Mortality during the subsequent 30 days was 22% among patients with priority 1 and 14% among patients with priority 2. Conclusion: Patients given a lower priority level at the dispatch centre had the longest system delay. Although many of these patients died, the risk of death was highest among those given the highest priority.
Acute sodium arsenite treatment induces Cyp2a5 but not Cyp1a1 in the C57Bl/6 mouse in a tissue (kidney) selective manner

Modulation of hepatic and extrahepatic detoxication enzymes Cyp1a1, Cyp2a5, glutathione S‐transferse Ya (GSTYa) and NAD(P)H:quinone oxidoreductase (QOR) dependent catalytic activity and mRNA levels were investigated at 1, 2, or 4 days in liver, lung, or kidney of male, adult CD57 Bl/6 mice treated sc with a single dose (85 μmol/kg) of sodium arsenite (As3+). Maximum decreases of total hepatic cytochrome P450 (CYP) monooxygenase content and catalytic activities, occurring at 24 h, corresponded with maximum increases of heme oxygenase (HO‐1) in all tissues, as well as maximum plasma total bilirubin. Extrahepatic increases in CYP were observed only in non‐AHR dependent isozymes in the kidney, where both Cyp2a5 mRNA and catalytic activity increased maximally 24 h after treatment. In contrast, no significant changes in Cyp2b1/2‐dependent PROD or mRNA activity and decreases in Cyp1a1‐dependent‐EROD activity were noted 1, 2, or 4 days after treatment. Increases in QOR catalytic activities were observed in all tissues examined with increased mRNA in kidney. On the other hand, GSTYa catalytic activity and mRNA increases were only detected in kidney. This study demonstrates the differential modulation of CYP, QOR, and GST‐Ya, important drug metabolizing enzymes after acute As3+ administration. The induction of Cyp2a5, QOR, and GSTYa catalytic activity and gene expression occurred primarily in kidney during or shortly after conditions of oxidant stress. © 2002 Wiley Periodicals, Inc. J Biochem Mol Toxicol 16:96–106, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/jbt.10023