Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanism of the Maturation Process of SARS-CoV 3CL Protease

Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel human coronavirus. Viral maturation requires a main protease (3CLpro) to cleave the virus-encoded polyproteins. We report here that the 3CLpro containing additional N- and/or C-terminal segments of the polyprotein sequences undergoes autoprocessing and yields the mature protease in vitro. The dimeric three-dimensional structure of the C145A mutant protease shows that the active site of one protomer binds with the C-terminal six amino acids of the protomer from another asymmetric unit, mimicking the product-bound form and suggesting a possible mechanism for maturation. The P1 pocket of the active site binds the Gln side chain specifically, and the P2 and P4 sites are clustered together to accommodate large hydrophobic side chains. The tagged C145A mutant protein served as a substrate for the wild-type protease, and the N terminus was first digested (55-fold faster) at the Gln-1-Ser1 site followed by the C-terminal cleavage at the Gln306-Gly307 site. Analytical ultracentrifuge of the quaternary structures of the tagged and mature proteases reveals the remarkably tighter dimer formation for the mature enzyme (Kd = 0.35 nm) than for the mutant (C145A) containing 10 extra N-terminal (Kd = 17.2 nm) or C-terminal amino acids (Kd = 5.6 nm). The data indicate that immature 3CLpro can form dimer enabling it to undergo autoprocessing to yield the mature enzyme, which further serves as a seed for facilitated maturation. Taken together, this study provides insights into the maturation process of the SARS 3CLpro from the polyprotein and design of new structure-based inhibitors.
The normal type Ia SN 2003hv out to very late phases

Aims. We study a thermonuclear supernova (SN), emphasizing very late phases. Methods. An extensive dataset for SN 2003hv that covers the flux evolution from maximum light to day +786 is presented. This includes 82 epochs of optical imaging, 24 epochs of near-infrared (NIR) imaging, and 10 epochs of optical spectroscopy. These data are combined with published nebular-phase IR spectra, and the observations are compared to model light curves and synthetic nebular spectra. Results. SN 2003hv is a normal Type Ia supernova (SN Ia) with photometric and spectroscopic properties consistent with its rarely observed B-band decline-rate parameter, Δm15(B) = 1.61 ± 0.02. The blueshift of the most isolated [Fe ii] lines in the nebular-phase optical spectrum appears consistent with those observed in the IR at similar epochs. At late times there is a prevalent color evolution from the optical toward the NIR bands. We present the latest-ever detection of a SN Ia in the NIR in Hubble Space Telescope images. The study of the ultraviolet/optical/infrared (UVOIR) light curve reveals that a substantial fraction of the flux is “missing” at late times. Between 300 and 700 days past maximum brightness, the UVOIR light curve declines linearly following the decay of radioactive 56 Co, assuming full and instantaneous positron trapping. At 700 days we detect a possible slowdown of the decline in optical-bands, mainly in the V-band. Conclusions. The data are incompatible with a dramatic infrared catastrophe (IRC). However, the idea that an IRC occurred in the densest regions before 350 days can explain the missing flux from the UVOIR wavelengths and the flat-topped profiles in the NIR. We argue that such a scenario is possible if the ejecta are clumpy. The observations suggest that positrons are most likely trapped in the ejecta.
Inhibition by Brain Natriuretic Peptide of Vasopressin Neurons in the Supraoptic Nucleus and Neurons in the Region of the Anteroventral Third Ventricle in Rat Hypothalamic Slice Preparations

It is not entirely clear whether or not atrial natriuretic peptide (ANP) directly inhibits vasopressin neurons in the supraoptic nucleus (SON) and paraventricular nucleus. Recently, a novel peptide, brain natriuretic peptide (BMP), which has been isolated from the brain, has been shown to have a similar action to ANP on the regulation of vasopressin release. Intracerebroventricular injection of both BNP and ANP inhibits stimulus‐evoked increases of plasma vasopressin level. The present study was undertaken: 1) to investigate whether BNP affects the activity of neurons in the region of the anteroventral third ventricle (AV3V) and SON which are involved in the control of body fluid homeostasis and blood pressure regulation, 2) to reassess effects of ANP on SON neurons, and 3) to test whether BNP exerts its effects by mechanisms which are different from those of ANP. Extracellular recordings were made from 213 AV3V and 110 SON spontaneously firing neurons in the rat coronal hypothalamic slice preparation. Of the AV3V neurons tested, BNP inhibited 86 (40%) and excited 2 (1%) while 125 neurons remained unaffected. A dose‐response relationship was obtained for 7 AV3V neurons at different BNP concentrations ranging from 10−11 M to 10−6 M; the firing rates of all 7 neurons decreased. The threshold concentration to evoke inhibitory responses was approximately 10−10M in the AV3V. When BNP and ANP were applied to the same neuron, most AV3V neurons which were inhibited by BNP were also inhibited by ANP and the neurons which were unaffected by BNP were also unaffected by ANP. Thus, these two peptides probably have a similar action on AV3V neurons. When BNP and angiotensin II were applied to a group of 60 neurons in the AV3V, most of the responsive neurons showed either inhibitory responses to BNP or excitatory responses to angiotensin II. Both BNP and ANP were applied to a group of 110 SON neurons: BNP (10 −7 M) inhibited 52 (75%) of 69 phasic (putative vasopressin) neurons, while BNP affected none of the 41 non‐phasic (putative oxytocin) neurons. By contrast, ANP inhibited only 20 (29%) of 69 phasic neurons tested but it also had no effect on 41 non‐phasic neurons tested. Our results are consistent with the suggestion that BNP is involved in the regulation of vasopressin release by acting on SON neurons and AV3V neurons.
Antimicrobial Assessment of Resins from Calophyllum Antillanum and Calophyllum Inophyllum

The Calophyllum genus is well‐known for its antimicrobial and cytotoxic activities, and therefore, we analyzed these biological activities for resins of Calophyllum antillanum and Calophyllum inophyllum growing in Cuba. C. antillanum resins showed a potent activity against Plasmodium falciparum (IC50 = 0.3 ± 0.1 µg/mL), while its cytotoxicity against MRC‐5 cells was much lower (IC50 = 21.6 ± 1.1 µg/mL). In contrary, the resin of C. inophyllum showed an unspecific activity. The presence of apetalic acid, isoapetalic acid, calolongic acid, pinetoric acid I, pinetoric acid II, isocalolongic acid, pinetoric acid III, and isopinetoric acid III in C. antillanum resins was also confirmed. These results demonstrated for the first time the potential activity of C. antillanum resins against P. falciparum. Copyright © 2015 John Wiley & Sons, Ltd.
Randomized Trial of an Inhibitor of Formation of Advanced Glycation End Products in Diabetic Nephropathy

Background/Aims: Pimagedine inhibits the formation of advanced glycation end products and slows the progression of diabetic complications in experimental models. This study was undertaken to determine if pimagedine ameliorates nephropathy in type 1 (insulin-dependent) diabetes mellitus. Methods: This was a randomized, double-masked, placebo-controlled study performed in 690 patients with type 1 diabetes mellitus, nephropathy, and retinopathy. The patients received twice daily dosing with placebo, pimagedine 150 mg, or pimagedine 300 mg for 2–4 years. The primary end point was the time to doubling of serum creatinine; the secondary end points included evaluations of proteinuria, kidney function, and retinopathy. Results: Serum creatinine doubled in 26% (61/236) of the placebo-treated patients and in 20% (91/454) of those who received pimagedine (p = 0.099). The estimated glomerular filtration rate decreased more slowly in the pimagedine-treated patients with a 36-month decrease from baseline of 6.26 ml/min/1.73 m2 as compared with 9.80 ml/min/1.73 m2 in the placebo-treated patients (p = 0.05), and pimagedine reduced the 24-hour total urinary proteinuria. (The mean reduction from baseline at month 36 was 732 mg/24 h at the low dose and 329 mg/24 h at the high dose as compared with 35 mg/24 h in the placebo group; p ≤ 0.001.) Fewer pimagedine-treated patients with baseline and end point evaluations (31/324; 10%) as compared with those receiving placebo (16%; 28/179) experienced a three-step or greater progression of the retinopathy (Early Treatment of Diabetic Retinopathy Study) score (p = 0.030). Three patients receiving high-dose pimagedine but none receiving low-dose treatment developed glomerulonephritis. Conclusions: While this study did not demonstrate a statistically significant beneficial effect of pimagedine on the progression of overt nephropathy resulting from type 1 diabetes, it is noteworthy in providing the first clinical proof of the concept that inhibiting advanced glycation end product formation can result in a clinically important attenuation of the serious complications of type 1 diabetes mellitus.
V-ATPase Inhibitors in Cancer Treatment and Their Implication in Multidrug Resistance in Oral Squamous Cell Carcinoma

ATPases are enzyme systems that originated in a common ancestor and are distributed universally among all organisms. There are three types of ATPases: those found in archaea (A-ATPases), synthases (F-APTases), and vacuole or vacuolar ATPases (V-ATPases) (Nelson, Nelson 1989). They are essential for life and have in common the fact that they create an electrochemical ion gradient across the membrane to hydrolyze or synthesize ATP. Structurally, they are enzymatic complexes that work as molecular rotary motors. ATPases are formed by two domains, a hydrophobic domain (A0, V0, and F0) and a hydrophilic domain (A1, V1, and F1) connected by a central axis and either one or two lateral axes. In this chapter, we are going to discuss V-ATPases.
Population differences in levels of linkage disequilibrium in the wild

Information about the levels of linkage disequilibrium (LD) in wild animal populations is still limited, and this is true particularly with respect to possible interpopulation variation in the levels of LD. We compared the levels and extent of LD at the genome‐wide scale in three Siberian jay (Perisoreus infaustus) populations, two of which (Kuusamo and Ylläs) represented outbred populations within the main distribution area of the species, whereas the third (Suupohja) was a semi‐isolated, partially inbred population at the margin of the species’ distribution area. Although extensive long‐range LD (>20 cM) was observed in all three populations, LD generally decayed to background levels at a distance of 1–5 cM or c. 200–600 kb. The degree and extent of LD differed markedly between populations but aligned closely with both observed levels of within‐population genetic variation and expectations based on population history. The levels of LD were highest in the most inbred population with strong population substructure (Suupohja), compared with the two outbred populations. Furthermore, the decay of LD with increasing distance was slower in Suupohja, compared with the other two populations. By demonstrating that levels of LD can vary greatly over relatively short geographical distances within a species, these results suggest that prospects for association mapping differ from population to population. In this example, the prospects are best in the Suupohja population, given that minimized marker genotyping and a minimum marker spacing of 1–5 cM (c. 200–600 kb) would be sufficient for a whole genome scan for detecting QTL.
Feasibility of Body-Centric Systems Using Passive Textile RFID Tags

Recent progresses in the design of wearable RFID-tag antennas stimulate the idea of passive body-centric systems, wherein the required power to drive the wearable tags is directly scavenged from the interrogation signal emitted by the reader unit. While active body-centric links have been extensively investigated, the feasibility of passive systems is still questionable, due to the poor sensitivity of the tags and due to the modest reading distances. This paper describes a systematic measurement campaign involving low-profile wearable textile tags in the UHF RFID band. It was demonstrated that both on-body and off-body links are affordable, with a power budget fully compliant with the available technology and the safety standards. The experiments permitted identifying the most-efficient tag placements, and proposing some quantitative and general guidelines useful to characterize and design this kind of new system.
Physical limitations on antennas — isoperimetric inequalities and the effect of metamaterials

In this paper, physical limitations on antennas are presented based on the holomorphic properties of the forward scattering dyadic. As a direct consequence of causality and energy conservation, a forward dispersion relation for the extinction cross section is established, and isoperimetric inequalities for the partial realized gain and partial directivity are derived for antennas of arbitrary shape. Closed-form expressions for the prolate and oblate spheroids are compared with Chu 's classical result for the sphere, and the effect of invoking metamaterials in the antenna design is discussed. The theory is illustrated by numerical simulations of a monopole antenna with a finite ground plane.
Improving timing characteristics through Semi-Random Net Reordering

This work discusses the Semi-Random Net Reordering (SRNR) technique as a means to improve signal integrity and predictability of timing characteristics for wide signal busses. SRNR is able to reduce induced noise, signal propagation delay, signal transition speed, and their variations amongst the different wires comprising the bus. SRNR produces a faster routing structure that is more uniformly behaved. It has the advantage of zero cost and applicability under the strictest routing methodologies.
ADVENTITIOUS INTERCONVERSION OF cis‐ AND trans‐UROCANIC ACID BY LABORATORY LIGHT

Urocanic acid (UCA) is a chromophore in the stratum corneum. Ultraviolet radiation (ultraviolet B) has been shown to suppress mammalian cell‐mediated immunity. The photoisomerization of trans‐UCA to cis‐UCA was proposed as the initiator of the suppression process. Cis‐urocanic acid has been demonstrated to suppress immunity by a variety of experiments. Investigators should be aware that laboratory illumination may be capable of interconverting trans‐UCA and cis‐UCA during experimental manipulations. This possible inadvertent contamination of one isomer by the other may influence results. We demonstrated that fluorescent lamps, daylight, sunlight and incandescent lamps were able to bring about isomerization. Window glass and container materials of plastic and clear glass did not filter out effective wavelengths, but three commercial plastic diffusers on fluorescent fixtures prevented the isomerization. Because the molar extinction coefficient (ɛ) for cis‐UCA is less than that of trans‐UCA, we have exposed 0.1 mMtrans‐UCA to ambient light and monitored the change in absorbance. A method is given to calculate the percentage of trans and cis isomers from the absorbance at 277 nm when the initial purity and absorbance are known. Using this procedure, we validated the molar extinction coefficient of cis‐UCA.
Key roles in intranet implementation: the conquest and the aftermath

Intranet technology has been rapidly adopted by many organizations. From being a largely unknown technology prior to the mid-1990s, numerous organizations today have implemented or are currently implementing intranets. The intranet implementation processes of three large organizations in two countries were studied over a period of 5 years. In particular, the paper investigates the role players who spearheaded the intranet implementations in these organizations. Five interrelated roles during the intranet implementation process are identified: the technology champion, organizational sponsor, intranet coordinator, intranet developer and content provider. In the light of the nature of intranet technology, each respective role is analysed in terms of its significance, key challenges and interrelationships during the implementation process. The paper further examines the dynamics of these roles in the aftermath of implementation as the technology becomes embedded in routine organizational activity.
Fine pitch Cu wire bond process for integrated circuit devices for high volume production

Wire bonding is the most applied technology to realize an electric chip-to-package interconnection and to provide electrical paths from and to the substrate for power and signal distribution. Established in the 1970s, wire bonding has been well documented and researched as a result of continuous process improvement and through the development of sophisticated, automated equipment over the years, [1-2].
Bounded Rational Heterogeneous Agents in Artificial Stock Markets: Literature Review and Research Direction

—In this paper, we provided a literature survey on the artiﬁcial stock problem (ASM). The paper began by exploring the complexity of the stock market and the needs for ASM. ASM aims to investigate the link between individual behaviors (micro level) and ﬁnancial market dynamics (macro level). The variety of patterns at the macro level is a function of the AFM complexity. The ﬁnancial market system is a complex system where the relationship between the micro and macro level cannot be captured analytically. Computational approaches, such as simulation, are expected to comprehend this connection. Agent-based simulation is a simulation technique commonly used to build AFMs. The paper proceeds by discussing the components of the ASM. We consider the roles of behavioral ﬁnance (BF) alongside the traditionally risk-averse assumption in the construction of agent’s attributes. Also, the inﬂuence of social networks in the developing of agents interactions is addressed. Network topologies such as a small world, distance-based, and scale-free networks may be utilized to outline economic collaborations. In addition, the primary methods for developing agents learning and adaptive abilities have been summarized. These incorporated approach such as Genetic Algorithm, Genetic Programming, Artiﬁcial neural network and Reinforcement Learning. In addition, the most common statistical properties (the stylized facts) of stock that are used for calibration and validation of ASM are discussed. Besides, we have reviewed the major related previous studies and categorize the utilized approaches as a part of these studies. Finally, research directions and potential research questions are argued. The research directions of ASM may focus on the macro level by analyzing the market dynamic or on the micro level by investigating the wealth distributions of the agents.
Role of the Deafness Dystonia Peptide 1 (DDP1) in Import of Human Tim23 into the Inner Membrane of Mitochondria*

Tim8 and Tim13 of yeast belong to a family of evolutionary conserved zinc finger proteins that are organized in hetero-oligomeric complexes in the mitochondrial intermembrane space. Mutations in DDP1 (deafness dystonia peptide 1), the human homolog of Tim8, are associated with the Mohr-Tranebjaerg syndrome, a progressive neurodegenerative disorder. We show that DDP1 acts with human Tim13 in a complex in the intermembrane space. The DDP1·hTim13 complex is in direct contact with translocation intermediates of human Tim23 in mammalian mitochondria. The human DDP1·hTim13 complex complements the function of the TIM8·13 complex in yeast and facilitates import of yeast and human Tim23. Thus, the pathomechanism underlying the Mohr-Tranebjaerg syndrome may involve an impaired biogenesis of the human TIM23 complex causing severe pleiotropic mitochondrial dysfunction.
A Sepic based high step-up DC-DC converter integrating coupled inductor for renewable energy applications

A novel Sepic based high step-up DC-DC converter is presented in this paper. A coupled inductor with three windings is employed in the proposed converter to achieve high voltage gain. In order to recycle the energy stored in the leakage inductor of the coupled inductor, a passive voltage clamp is used. The voltage of the main switch is clamped by this passive voltage clamp. Therefore, the voltage stress of the main switch is low which causes a low on-resistance (RDS-on) switch to be used which reduces conduction loss and increases the efficiency. The steady state analysis of the proposed converter is discussed. Finally, the simulation results are prepared to justify the validity of the analysis.
Evaluating the Effectiveness of the Kids Living Fit™Program: A Comparative Study

After-school programs can be implemented by school nurses to facilitate healthy lifestyle choices in children with the goal of decreasing obesity. Kids Living Fit™(KLF), an after-school program designed by community hospital nurses, was implemented in elementary schools and focused on best lifestyle choices regarding foods consumed and activities chosen for children in grades 2 through 5. Study measures included comparison of body mass index (BMI) percentiles for age and gender and waist circumference between two self-selected groups composing a total sample size of 185 participants: the KLF intervention group (n =80) and the no-intervention/ contrast group (n =105). The 12-week intervention included a weekly fitness program and monthly dietitian presentations. Participants completed food and activity diaries and wore pedometers. In pairwise comparisons, the KLF group had a significant decrease in BMI percentile between baseline and follow-up (−2.3%) compared with the contrast group. The KLF group also demonstrated a smaller increase in waist circumference than the contrast group.
A population-based study of quantitative sensory testing in adolescents with and without chronic pain

Abstract Quantitative sensory testing (QST) has been used to characterize pain sensitivity in individuals with and without pain conditions. Research remains limited in pediatric populations, hindering the ability to expand the utility of QST toward its potential application in clinical settings and clinical predictive value. The aims of this study were to examine pain sensitivity using QST in adolescents with chronic pain compared to adolescents without chronic pain and identify predictors of pain sensitivity. A population-based study conducted from 2010 to 2011 provided data on 941 adolescents, 197 were classified as having chronic pain and 744 were classified without chronic pain. Self-reported data on pain characteristics, psychological functioning, and QST responses were examined. The findings revealed lower pressure pain threshold and tolerance on the trapezius (P's = 0.03) in adolescents with chronic pain compared to adolescents without chronic pain, but no differences on heat or cold-pressor pain tasks. Female sex (P's = 0.02) and poorer psychological functioning (P's = 0.02) emerged as significant predictors of greater pain sensitivity across all pain modalities. Exploratory analyses revealed several associations between clinical pain characteristics and QST responses within the chronic pain cohort. Findings from this large pediatric sample provide comprehensive data that could serve as normative data on QST responses in adolescents with and without chronic pain. These findings lay the groundwork toward developing future QST research and study protocols in pediatric populations, taking into consideration sex and psychological distress.