Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of protons position in acid–base enzyme catalyzed reactions: The hepatitis C viral NS3 protease

General acid–base catalysis is a key element of the catalytic activity of most enzymes. Therefore, any explicit molecular modeling of enzyme‐catalyzed chemical reactions requires correct identification of protons location on the catalytic groups. In this work, we apply our quantum mechanical/self‐consistent reaction field in virtual solvent [QM/SCRF(VS)] method for identification of the position of protons shared by the enzyme catalytic groups and the polar groups of the inhibitor in a covalent tetrahedral complex (TC) of the hepatitis C virus NS3 protease with a peptidyl α‐ketoacid inhibitor. To identify the relevant protonation states, we have analyzed relative stabilities of R and S configurations of the TC that depend on the specific proton distribution over the polar groups and correlated it with experimental NMR and X‐ray crystallography data, both at low and neutral pH ranges. The tentative assignment of the single resonance in the 13C NMR spectrum of the hemiketal carbon at physiological pH to the S configuration of TC is confirmed. Both R and S configurations are equally stable at acidic pH in our modeling, in good agreement with the 13C NMR observation. Proteins 2004;9999:000–000. © 2004 Wiley‐Liss, Inc.
Prevalence and factors associated with human brucellosis in livestock professionals

ABSTRACT OBJECTIVE The objective of this study is to estimate the seroprevalence of human brucellosis in livestock professionals and analyze the factors associated with brucellosis focusing on sociodemographic variables and the variables of knowledge and practices related to the characteristics of the activities carried out in livestock. METHODS This is a cross-sectional seroepidemiological study with a population of 131 workers of butchers, slaughter rooms, and slaughterhouse and 192 breeders sampled randomly in Namibe province, Angola. The data were obtained from the collection of blood and use of questionnaires. The laboratory tests used were rose bengal and slow agglutination. The questionnaire allowed us to collect sociodemographic information and, specifically on brucellosis, it incorporated questions about knowledge, attitudes, and behaviors of livestock professionals. In addition to the descriptive statistical approach, we used the Chi-square test of independence, Fisher’s test, and logistic regression models, using a significance level of 10%. RESULTS The general weighted prevalence of brucellosis was 15.6% (95%CI 13.61–17.50), being it 5.3% in workers and 16.7% (95%CI 11.39–21.93) in breeders. The statistical significance was observed between human seroprevalence and category (worker and breeder) (p < 0.001) and education level (p = 0.032), start of activity (p = 0079), and service location (p = 0.055). In a multivariate context, the positive factor associated with brucellosis in professionals was the professional category (OR = 3.54; 95%CI 1.57–8.30, related to breeders in relation to workers). CONCLUSIONS Human brucellosis in livestock professionals is prevalent in Namibe province (15.6%), where the professional category was the most important factor. The seroprevalence levels detected are high when compared with those found in similar studies.
An epidemiological study of acute carbon monoxide poisoning in the West Midlands.

OBJECTIVES: To describe the epidemiology of carbon monoxide (CO) poisoning in a defined population, identifying those at greatest risk from acute poisoning resulting in admission to hospital or death. METHODS: A retrospective study with routinely collected information, set in the former West Midlands Regional Health Authority; population of 5.2 million. The data comprised 939 deaths and 701 hospital admissions due to CO poisoning between January 1988 to December 1994. The main outcome measures were age and sex standardised incidence rates (SIRs) for non-intentional, suicidal, and undetermined poisonings for health authorities and the linear relation with socioeconomic deprivation. RESULTS: Overall rate of non-intentional poisonings over the 7 year period was 7.6/100,000, an annual rate of 1.1/100,000. The 7 year rates were highest in people > or = 85; men 24.0/100,000 and women 19.7/100,000. For suicides the 7 year rate was 19.6/100,000, an annual rate of 2.8/100,000. The 7 year rates were highest for men of 35-39, 64.1/100,000, and for women aged 45-49, 15.3/100,000. None of the causes of poisoning were related to deprivation. Non-intentional poisonings showed a strong seasonal variation with the highest rates being recorded in the months October to March. Increased rates of poisoning were found in the rural districts of the West Midlands. There seems to have been a decline in suicides coinciding with the introduction of three way catalytic converters on cars. CONCLUSIONS: Elderly people and the very young are at the greatest risk from non-intentional CO poisoning and rates are highest in the winter months. Although deaths from non-intentional CO poisoning are declining nationally, in the West Midlands they have remained stable and hospital admissions are increasing. It is not solely an urban phenomenon with rates for non-intentional CO poisoning and suicides higher in the rural districts. Health authorities need to consider all populations in any prevention programme. Further work is needed to establish the extent of the burden of chronic CO poisoning and the impact of catalytic converters on suicides.
Using choice experiments to assess the costs of supplying carbon offsets in beef production systems

Stated preference experiments have been used successfully to value non-market amenities such as biodiversity and aesthetics (Ballweg, 2013; Horne, 2006). These experiments have predominantly been applied to estimating how much consumers would be willing to contribute to preserving some natural feature, that is their demand for either use or non-use values of an environmental asset. The supply of carbon offsets from agricultural land has many of the same characteristics as these amenities but also represents a possible alternative (or complementary) enterprise for private agricultural landholders. The supply of carbon offsets from agricultural land in Australia has previously been estimated based on biophysical characteristics and using bioeconomic modelling but the resulting models do not necessarily reflect the underlying preferences of landholders for supplying offsets. This paper reports the use of stated preference techniques to estimate the cost of supply of a carbon offset enterprise on land currently under cattle production. Specifically the value to be estimated is landholders’ willingness to accept (WTA) a payment to reduce cattle production in favour of producing carbon offsets. The results showed that both landholder and contract conditions were significant in determining preferences for producing carbon offsets as well as the influence of bounded rationality, hyperbolic discounting and inertia on preferences.
Categorizing the severity of pain using questions from the 2012 National Health Interview Survey

Background Based on qualitative and mixed-method approaches, Miller and Loeb have proposed a coding system that combines questions on pain persistence and bothersomeness to create discrete categories of increasing pain severity for use in large population-based surveys. In the current analyses, using data from the 2012 National Health Interview Survey, we quantitatively assess the pain category definitions proposed by Miller and Loeb and compare this original definition to ten alternative definitions. Methods Using multivariate analysis of variance, each definition was related simultaneously to four dependent measures – the Kessler 6 score for measuring psychological distress, the number of health-related bed-disability days, the number of visits to a health professional, and the number of emergency room visits. Following the protocol of Serlin et al, the definition yielding the largest F score was considered the optimal definition. Results The Miller and Loeb definition produced the largest F value (185.87), followed consecutively by several alternative definitions #5 (184.17), #10 (180.95), and #9 (179.5). A nearly identical ordering was found when looking at the mean F value generated from 100 random samples. We also examined the frequencies with which each alternative definition achieved the optimal F value over the 100 random samples. Only two definitions had achieved the optimal F value >5% of the time: the Miller and Loeb definition was optimal 46% of the time, while alternative definition #5 was optimal 41% of the time. Similar results were seen in subpopulations with back pain and joint pain. Conclusion Additional support was provided for the Miller and Loeb coding of pain persistence and bothersomeness to produce discrete categories of increasing pain severity. This two-question coding scheme may prove to be a viable option for assessing pain severity in clinical settings where clinician time and patient burden are limiting factors.
Initiation of Poliovirus Negative-Strand RNA Synthesis Requires Precursor Forms of P2 Proteins

ABSTRACT The replication proteins encoded in the P2 region of the poliovirus genome induce extensive rearrangement of cellular membranes into vesicles and are a required component of viral RNA replication complexes. To identify distinct viral protein(s) from the P2 region of the genome that were required to form functional RNA replication complexes, the P2 proteins were expressed in addition to P3 in HeLa S10 translation-RNA replication reactions. Membrane-associated preinitiation replication complexes were isolated from these reactions and used to measure negative-strand synthesis. The formation of replication complexes capable of initiating negative-strand synthesis was observed when either P23 or when P2 and P3 were expressed in the HeLa S10 translation-replication reactions. The amount of negative-strand RNA synthesized with P2 and P3 was approximately 50% of that observed with P23. Negative-strand synthesis was not observed when the processed forms of the P2 proteins (e.g., 2A, 2B, 2C, 2AB, and 2BC) were used in various combinations in place of P2. In contrast, the expression of 2A and 2BCP3 supported negative-strand synthesis at the same level observed with P23. Therefore, functional replication complexes were formed in reaction mixtures that contained either 2A and 2BCP3 or P2 and P3. Genetic complementation analysis of P23 RNA that contained a lethal mutation in 2C confirmed these results. The expression of 2BCP3 in trans restored the replication of P23-2C(P131N) RNA to wild-type levels. The expression of P2 and P3 also complemented the replication of this mutant RNA, although very inefficiently. Complementation was not observed in reactions that contained P2 alone, 2BC, or 2C. Based on these results, we propose that RNA replication complexes are initially formed with the primary cleavage products of P23 (i.e., P2 and P3 or 2A and 2BCP3), and that 2A and 2BCP3 are preferentially used in this process.
Arterial stiffness is increased in patients with inflammatory bowel disease

Background and aims: Recent studies have reported early atherosclerosis in patients with inflammatory bowel disease (IBD). In these patients, the chronic low-grade inflammation may predispose to vascular remodelling and arterial stiffening. We aimed at studying arterial stiffness in IBD patients. Methods: Thirty-two IBD patients without cardiovascular risk factors and 32 matched controls were enrolled (age 19–49 years). SphygmoCor device (AtCor Medical, Sydney, Australia) was used to measure carotid–femoral and carotid–radial (muscular artery) pulse wave velocity (PWV), augmentation index and central blood pressure. Results: Carotid–femoral PWV was higher in IBD patients than in controls (6.6 ± 1.4 vs. 6.0 ± 0.8 m/s, respectively, P < 0.05), as well as carotid–radial PWV (8.5 ± 1.2 vs. 7.2 ± 1.0 m/s, P < 0.001). Central pulse pressure was higher in IBD than in controls (32 ± 6 vs. 28 ± 7 mmHg, P < 0.05). Aging was an important determinant of carotid–femoral PWV in both groups and carotid–radial PWV only in IBD patients. In fully adjusted model performed in both groups of patients considered as a whole, age was positively associated with carotid–femoral PWV [R2 = 0.10; +0.05 m/s per 1 year of aging, 95% confidence interval (CI) 0.01–0.08 m/s, P < 0.05], as well as IBD (R2 = 0.10; +0.72 m/s if IBD present, 95% CI 0.19–1.26 m/s, P < 0.05). In IBD patients, carotid–radial PWV was positively associated with the disease duration (R2 = 0.20; +0.11 m/s per 1 year of aging, 95% CI 0.03–0.19 m/s, P < 0.05). Conclusion: Arterial stiffness is increased in patients with IBD independently of conventional cardiovascular risk factors.
Potential Growth of the Spanish Economy

This paper presents an estimate of the Spanish economy’s potential growth. This estimate is based on a production function methodology that includes certain refi nements on previous versions and generates less procyclical potential output growth estimates than those traditionally considered in the literature. As a result, the (positive) output gap estimated in expansions is higher and that estimated in recessions is lower. According to these results, given the available population projections and under the assumption that total factor productivity (TFP) and structural unemployment will behave in line with historical patterns, the Spanish economy’s potential growth is expected to recover gradually over the coming years but, in line with projections by international organisations, to lower rates than those in the expansion period. However, per capita growth rates fully recover to the pre-crisis levels, which highlights the importance of population projections in shaping the Spanish potential growth.
A Slow Clearing, Fibrin-Specific, PAI-1 Resistant Variant of t-PA (T103N, KHRR 296-299 AAAA)

Summary Site directed mutagenesis was used to construct a t-PA variant that contains an additional glycosylation site in the first kringle domain (T103N) combined with a tetra-alanine substitution in the protease domain (KHRR 296-299 AAAA). This combination variant has a plasma clearance rate that is 4.5-fold slower in rats and 5.4-fold slower in rabbits than t-PA. It is also less than one tenth as active as t-PA towards plasminogen in the presence of fibrinogen, and has approximately twice the normal activity in the presence of fibrin. It shows substantial resistance to the fast acting inhibitor, plasminogen activator inhibitor-1 (PAI-1), requiring a 10-fold greater molar excess of PAI-1 to reduce its activity by 50%, compared to t-PA. This is the result of a reduction of nearly 100-fold in the second order rate constant for PAI-1 inactivation. These results show that it is possible to combine mutations in different domains of t-PA to construct a variant which is simultaneously slower clearing, less reactive towards plasminogen in the absence of a fibrin clot, and resistant to inactivation by PAI-1.
Surface characterization by atomic force microscopy of sterilized PLGA microspheres

Atomic force microscopy (AFM) is recognized a suitable and powerful technique for surface and morphological analysis. Even if until now this technique has not been frequently used in the pharmaceutical field, it can contribute to an accurate morphologic characterization of microspheres and nanospheres. In this work, atomic force microscopy has been used to perform the surface characterization of sterilized microspheres. The aim is to investigate the morphologic modifications induced by gamma irradiation on poly(lactide-co-glycolide) microspheres loaded with ovalbumin and to compare the results obtained by AFM to those obtained by scanning electron microscopy (SEM). The results obtained show that, with respect to SEM, AFM can give some additional information regarding the modifications induced by γ-irradiation on microspheres surface morphology. The significant changes in surface roughness after irradiation are indicative of damage due to γ-irradiation. The unchanged surface roughness values calculated for microspheres containing PEG in their matrix, suggest that this polymer exerts a protective effect towards γ-irradiation.
Price Limits and Volatility: A New Approach and Some New Empirical Evidence from the Tokyo Stock Exchange

This study aims to examine regularities of price limit hits for stocks listed in the TSE. Regularities of limit hits have not been examined before. The results show an increase of limit hits on Monday and Tuesday. These results of limit hits are consistent with the existing literature for the day-of-the-week effect of stock returns carried out on Japan. This indicates that such patterns of price limit hits are not all due to noise trading. The results also show that high limit hit occurrences are associated with high volatility and low limit hit occurrences are associated with low volatility.
Novel Functions of Small Conductance Ca2+-activated K+ Channel in Enhanced Cell Proliferation by ATP in Brain Endothelial Cells*

Brain capillary endothelial cells (BCECs) form the blood-brain barrier (BBB), which is essential for maintaining homeostasis of the brain. Net cellular turnover, which results from the balance between cell death and proliferation, is important in maintaining BBB homeostasis. Here we report a novel mechanism that underlies ATP-induced cell proliferation in t-BBEC 117, a cell line derived from bovine brain endothelial cells. Application of 0.1-30 μm ATP to t-BBEC 117 concentration-dependently increased intracellular Ca2+ concentration ([Ca2+]i) in two phases: an initial transient phase and a later and smaller sustained one. These two phases of [Ca2+]i rise were mainly due to Ca2+ release and sustained Ca2+ influx, respectively. The pretreatment with apamin, a selective blocker of small conductance Ca2+-activated K+ channels (SK), significantly reduced both the [Ca2+]i increase and K+ current induced by ATP. Transcripts corresponding to P2Yx, SK2, and transient receptor potential channels were detected in t-BBEC 117. Knock down of SK2 protein, which was the predominant Ca2+-activated K+ channel expressed in t-BBEC 117, by siRNA significantly reduced both the sustained phase of the [Ca2+]i rise and the K+ current induced by ATP. Cell proliferation was increased significantly by the presence of the stable ATP analogue ATPγS. This effect was blunted by UCL1684, a synthesized SK blocker. In conclusion, in brain endothelial cells ATP-induced [Ca2+]i rise activates SK2 current, and the subsequent membrane hyperpolarization enhances Ca2+ entry presumably through transient receptor potential channels. This positive feedback mechanism can account for the augmented cell proliferation by ATP.
Single element correction in sorting algorithms with minimum delay overhead

A low delay overhead technique for the correction of errors affecting sorting algorithms, based on the use of Hamming code, is presented. Given the number of values to be sorted the expected Hamming check bits (as SUMs) are calculated, and a checker technique performs single error correction with lower delay overhead than classic approaches based on algorithm redundancy. The proposed technique has been applied to the well known bubble sorting with different sets of values to be sorted and the comparison of the resulting overhead with that imposed by the classic duplication with comparison and triple modular redundancy techniques shows that it requires lower delay overhead while providing enhanced error correction capabilities.
Accuracy vs. complexity trade-off in simulations of future wireless networks

As wireless networks shift towards denser deployments, simulations take longer time to run and consume more resources. Simulation of the physical (PHY) layer is particularly time consuming and, as such, its implementation requires the use of abstracted models with low computational complexity, in order to provide accurate results in reasonable time. Although Mutual Information Effective SINR Mapping (MIESM) is commonly used as the standard method to abstract the PHY layer, the popular "modified Shannon's equation" - proposed by Mogensen et al. - has been gaining ground as a simpler and lighter implementation of the PHY layer in System Level (SL) simulations. This paper aims at comparing MIESM and the modified Shannon's formula for SL simulators in terms of accuracy and computational complexity. Results show that Shannon's method proves beneficial for networks with a large number of users, as it is less complex and allows us to reduce up to 30 times the simulation time required by the PHY layer abstraction. On the other hand, the accuracy is in the range of 80-87% for the instantaneous throughput compared to MIESM; the accuracy improves up to 95% for the time-averaged user throughput. In scenarios involving fast-varying channels, the modified Shannon's formula needs to be calibrated considering the actual user speed; in this case, accuracy of 90% can be achieved for a user speed of 60kmph.
Volumetric assessment of the space between the posterior hyaloid and internal limiting membrane using SD-OCT

The purpose of this study was to measure, for clinical and surgical utility, the distance between the posterior hyaloid and the internal limiting membrane using a spectral domain optical-coherence tomography (SD-OCT) device. Eight eyes of eight patients with subclinical partial posterior vitreous detachment (PPVD) with vitreomacular traction syndrome were examined with SD-OCT. To quantify the vitreoretinal distance, the basic applications of SD-OCT (Spectralis HRA+OCT Heidelberg Engineering) were modified. We conducted a topographic study of the entire posterior pole by defining new maps, each generated from 19 raster scans. We obtained maps that represent the space between the residual vitreous and retina, expressed numerically and on a colour spectrum, and overlapped them on a posterior pole photograph. We also created a single map of the entire posterior pole. The mean PPVD volume in the eight eyes was 104.87±5.25 mm3. This study produced detailed maps of the vitreoretinal distance, which may facilitate the study of the clinical progression of PPVD. In case of surgery the maps may help to accurately determine where surgical manipulation is needed safely apart from the retina. These maps could also assist in the assessment of pharmacological vitreolysis efficacy.
(−)-β-Caryophyllene, a CB2 Receptor-Selective Phytocannabinoid, Suppresses Motor Paralysis and Neuroinflammation in a Murine Model of Multiple Sclerosis

(−)-β-caryophyllene (BCP), a cannabinoid receptor type 2 (CB2)-selective phytocannabinoid, has already been shown in precedent literature to exhibit both anti-inflammatory and analgesic effects in mouse models of inflammatory and neuropathic pain. Herein, we endeavored to investigate the therapeutic potential of BCP on experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). Furthermore, we sought to demonstrate some of the mechanisms that underlie the modulation BCP exerts on autoimmune activated T cells, the pro-inflammatory scenery of the central nervous system (CNS), and demyelination. Our findings demonstrate that BCP significantly ameliorates both the clinical and pathological parameters of EAE. In addition, data hereby presented indicates that mechanisms underlying BCP immunomodulatory effect seems to be linked to its ability to inhibit microglial cells, CD4+ and CD8+ T lymphocytes, as well as protein expression of pro-inflammatory cytokines. Furthermore, it diminished axonal demyelination and modulated Th1/Treg immune balance through the activation of CB2 receptor. Altogether, our study represents significant implications for clinical research and strongly supports the effectiveness of BCP as a novel molecule to target in the development of effective therapeutic agents for MS.