Miracle-dz/UniFAR-FTUs huggingface dataset:
Evolution of Choice of Solubility and Dissolution Media After Two Decades of Biopharmaceutical Classification System

The introduction of the biopharmaceutics drug classification system (Biopharmaceutics Classification System (BCS)), in 1995, provided a simple way to describe the biopharmaceutics behavior of a drug. Solubility and permeability are among the major parameters, which determine the fraction dose absorbed of a drug substance and consequently its chances to be bioavailable. The purpose of this review is to summarize the evolution of the media used for determining solubility and dissolution and how this can be used in modern drug development. Over the years, physiologically adapted media and buffers were introduced with the intention to better predict the in vivo solubility and dissolution of drug substances. Water, buffer solutions, compendial media, micellar solubilization media, and biorelevant media are reviewed. At this time point, there is no universal medium available which can be used to predict every drug substance’s solubility or a drug product’s in vivo dissolution behavior. However, there have been many improvements and additions made to media to optimize their in vivo predictability; for example, the current phosphate concentrations in buffers seem to be too high to correlate with the carbonate buffer concentrations in vivo. Biorelevant media were updated to correlate them better with the composition of human intestinal fluids. The BCS was introduced into regulatory sciences as a scientific risk management tool to waive bioequivalence studies under certain conditions. Today’s different guidance documents define the dose-solubility ratio differently. As shown for amoxicillin, this can cause more confusion than certainty for globally operating companies. Harmonization of BCS guidelines is highly desirable.
Revealing Preferences Graphically: An Old Method Gets a New Tool Kit

Because uncertainty is endemic in a wide variety of economic circumstances, models of decision making under uncertainty play a key role in every field of economics. The standard model of decisions under uncertainty is based on von Neumann and Morgenstern Expected Utility Theory (EUT), so it is natural that experimentalists should want to test the empirical validity of the Savage axioms on which EUT is based. Empirical violations of EUT provoke intriguing questions about the rationality of individual behavior and, at the same time, raise criticisms about the status of the Savage axioms as the touchstone of rationality. These criticisms have generated the development of various theoretical alternatives to EUT, and the investigation of these theories has led to new empirical regularities. For the most part, these experimental investigations use several pairwise choices, a la Allais, to test EUT and its various alternatives, such as weighted utility, implicit expected utility, and prospect theory, among others. Each of these theories gives rise to indifference curves with distinctive shapes in some part of the Marschak-Machina probability triangle, so each theory can be tested against the others by choosing alternatives that the various theories rank differently. In these studies, the criterion used to evaluate a theory is the fraction of choices it predicts correctly. Generally speaking, experimental work has, on the one hand, collected only a few decisions from each subject and, on the other, presented subjects with a serious of choices, designed to compare the predictive abilities of competing theories or discover violations of specific axioms (Colin F. Camerer (1995) and Chris Starmer (2000) review the experimental and theoretical work that focuses on evaluating non-EUT theories). Although this practice is understandable given the purposes for which the experiments were designed, critics say that it limits the usefulness of the data for other purposes. First, while these experiments reveal that violations exist, they give us little sense of how important they are or how frequently they
Bilateral controller design based on transparency in the state convergence framework

This paper describes a new methodology for designing bilateral controllers based on transparency that applies a modified scheme of control by state of convergence. The design is based on modelling the behavior of the master and slave which regard state space equations, and also taking into account that perfect transparency cannot be reached. This methodology allows designing the controllers in order to obtain the convergence between the state of the master and the slave. Furthermore, it consequently provides a higher degree of transparency to the operator. The paper explains criteria in achieving convergence between the master and the slave, and so as with transparency on a steady state. A set of equations that calculate controller gains have been obtained by applying such criteria. In order to verify this new methodology, a master-slave system of 3 DoF have been used.
Comparison of fundamental frequency in Welsh and English in bilingual speech

The study presents the results of cross-linguistic differences in speaking fundamental frequency in Welsh and English in bilinguals’ speech. The findings established significant cross-linguistic differences between pitch profiles of Welsh and English. Welsh is produced with wider pitch span. The increase in F0 span is achieved by higher F0 maxima in tone units. This result is not dependent on differences in anatomical constitution of the speakers. These differences are consistent across female bilinguals. The detected within-speaker differences in pitch profiles can be attributed to sociolinguistic factors.
Visualization of Building Models and Factual Data integrated by CityGML

Focus of this paper lies on the enrichment of 3D models with features extracted from IR images and on the integration of factual data, multiple image textures, and meta data into a semantically-geometrical model. In the last year CityGML was developed to capture geometric data and links to textures images as well as factual data and meta data of 3D city models. Multiple textures given by, e.g. different sensors (visual and IR) or taken at different time to record the thermal behaviour of a building, can not be considered in CityGML. But, due to the open source individual extensions can be easily integrated. Open source viewer like Aristoteles has to be adapted to explore the scene and to visualize these different features and data.
Analysis of bacteriophage SP82 major "early" in vitro transcripts

A restriction map was constructed for the 17.5-kilobase SalI C fragment of SP82 DNA. Unfractionated SP82 DNA, the SalI C fragment, and restriction fragments derived from SalI-C were used as templates for in vitro synthesis by the Bacillus subtilis RNA polymerase, and the resulting transcripts were analyzed by gel electrophoresis. Comparison of the RNA species obtained from SalI-C with those produced from unfractionated DNA indicated that most of the RNAs and all of the major transcripts originate from the SalI C fragment; this fragment contains one copy of the terminally redundant portion of the genome. Seven major transcripts, a bidirectional terminator site, and 5 of the 13 minor transcripts were located within the 13-kilobase redundant region. The binding of polymerase to fragments of DNA produced by digestion of SalI-C with HpaII and HhaI was used to identify promoter-bearing regions within SalI-C.
The structure of adrenodoxin reductase of mitochondrial P450 systems: electron transfer for steroid biosynthesis.

Adrenodoxin reductase is a monomeric 51 kDa flavoenzyme that is involved in the biosynthesis of all steroid hormones. The structure of the native bovine enzyme was determined at 2.8 A resolution, and the structure of the respective recombinant enzyme at 1.7 A resolution. Adrenodoxin reductase receives a two-electron package from NADPH and converts it to two single electrons that are transferred via adrenodoxin to all mitochondrial cytochromes P 450. The structure suggests how the observed flavin semiquinone is stabilized. A striking feature is the asymmetric charge distribution, which most likely controls the approach of the electron carrier adrenodoxin. A model for the interaction is proposed. Adrenodoxin reductase shows clear sequence homology to half a dozen proteins identified in genome analysis projects, but neither sequence nor structural homology to established, functionally related electron transferases. Yet, the structure revealed a relationship to the disulfide oxidoreductases, permitting the assignment of the NADP-binding site.
Determinants of Manual Dexterity in Young Adults

The time to complete a test of manual dexterity (Grooved Pegboard Test) increases with advancing age due to changes in force steadiness, muscle strength, and cognitive function. However, the relative significance of these predictors among healthy young adults remains unknown. PURPOSE: To identify predictor variables that can explain the variance in the time that it takes young adults to complete the Grooved Pegboard Test. It was hypothesized that an expanded set of force steadiness tests, as well an assessment of cognitive function, would predict a significant amount of the variance in pegboard times. METHODS: Twenty-seven young adults (23.8 ± 4.0 years) performed three trials of the Grooved Pegboard Test with the right (dominant) hand. Strength was measured during handgrip, wrist extension, pinch, and index finger abduction tasks. Force steadiness measurements were made at 5% and 10% of maximum during traditional one-joint tests (wrist extension, index finger abduction, and pinch) as well as during novel two-joint tests (wrist extension combined with either index finger abduction or pinch). Cognitive function was assessed using a test of reaction time. RESULTS: 1) Time to complete the Grooved Pegboard Test was 52.5 ± 4.8 s (mean ± SD). 2) Force steadiness was worse for two-joint tests (3.78 ± 1.23%) than one-joint tests (2.50 ± 0.71%, P < 0.001). 3) Force steadiness was negatively correlated with pegboard times in 13 of 14 tests (e.g., wrist extension at 10%, r = -0.452, P < 0.01). 4) Pegboard times were not significantly correlation with reaction time or any measure of strength. 5) Multiple regression analysis explained 37% of the variance in the time to complete the Grooved Pegboard Test using a model containing a single one-joint test and two of the two-joint force steadiness tests of force steadiness. CONCLUSIONS: The use of an expanded set of steadiness tests significantly improved the ability to predict pegboard times among young adults. Nonetheless, a substantial amount of the variance in the pegboard times for young adults remains unexplained.
On the basis number of the direct product of graphs

The basis number b(G )o f ag raphG is defined to be the least integer d such that G has a d-fold basis for its cycle space. In this paper we: give an upper bound of the basis number of the direct product of trees; classify the trees with respect to the basis number of the direct product of trees and paths of order greater than or equal to 5; give an upper bound of the basis number of the direct product of bipartite graphs; and investigate the basis number of the direct product of a bipartite graph and a cycle.
Consensus statements and recommended clinical procedures regarding contemporary surgical and radiographic techniques in implant dentistry.

Successful dental implant rehabilitation requires accurate preoperative planning of the surgical intervention based on prosthodontic considerations and validated treatment methods. The introduction and widespread use of cross-sectional imaging in implant dentistry using cone beam computed tomography (CBCT) over the last decade has enabled clinicians to diagnose and evaluate the jaws in three dimensions before and after insertion of dental implants, thus replacing computed tomography (CT) as the standard of care. Furthermore, computer-guided implant surgery uses data from cross-sectional imaging derived from CBCT scans on a routine basis. Considering rapid changes in science and clinical practice, the first two systematic reviews in this group by Bornstein et al and Tahmaseb et al have centered their focused questions on these topics.
DAMS: distributed adaptive metaheuristic selection

We present a distributed algorithm, Select Best and Mutate (SBM), in the Distributed Adaptive Metaheuristic Selection (DAMS) framework. DAMS is dedicated to adaptive optimization in distributed environments. Given a set of metaheuristics, the goal of DAMS is to coordinate their local execution on distributed nodes in order to optimize the global performance of the distributed system. DAMS is based on three-layer architecture allowing nodes to decide distributively what local information to communicate, and what metaheuristic to apply while the optimization process is in progress. SBM is a simple, yet efficient, adaptive distributed algorithm using an exploitation component allowing nodes to select the metaheuristic with the best locally observed performance, and an exploration component allowing nodes to detect the metaheuristic with the actual best performance. SBM features are analyzed from both a parallel and an adaptive point of view, and its efficiency is demonstrated through experimentations and comparisons with other adaptive strategies (sequential and distributed).
Isolation and structural characterization of the Leishmania donovani kinetoplastid membrane protein-11, a major immunoreactive membrane glycoprotein.

A novel membrane molecule, previously observed to be co-isolated with lipophosphoglycan and called lipophosphoglycan-associated protein, has been detected in Leishmania donovani promastigotes and amastigotes. This kinetoplastid membrane protein (KMP-11) has been purified by preparative SDS/PAGE after organic solvent extraction of promastigote membranes. Isoelectric-focusing experiments indicated that this was an acidic protein with an isoelectric point of 4.8. Immunoblot analysis of subcellular fractions, together with 125I-labelling experiments, showed this molecule to be associated with the promastigote cell surface membrane. KMP-11 was expressed at a copy number similar to that of lipophosphoglycan (1 x 10(6)-2 x 10(6) molecules per cell), making this glycoprotein one of the major features on the parasite cell surface. The primary structure, less a blocked N-terminal region, was determined by automated Edman degradation of peptides derived from CNBr or enzymic fragmentation. Several post-translational modifications were also found during these studies, including an O-linked oligosaccharide and an NG-monomethylarginine functionality which was verified by m.s. Finally, a set of sequential synthetic peptides was made based on the established partial sequence allowing structural determination of two distinct antibody-binding sites for the monoclonal antibodies L98 and L157.
Coffee consumption and mortality in a 14-year follow-up of an elderly northern Finnish population

The present study assessed the relationship between coffee consumption and mortality in a home-dwelling elderly population. A population-based cohort of 817 men and women born in 1920 or earlier and living in northern Finland provided complete data on daily coffee consumption and other variables at the baseline examination in 1991–1992. Deaths were monitored through to the end of 2005 by national death certificates, resulting in 6960 person-years of follow-up. Hazard rate ratios for mortality by daily coffee intake were estimated by Poisson regression models adjusted for some known predictors of mortality. During 14·5 years of follow-up, 623 deaths occurred. The total mortality rate was inversely related to the number of cups (average volume, 125 ml) of coffee consumed daily. After adjustment for age, sub-period of follow-up, sex, marital status, basic educational level, previous occupational group, current smoking, BMI, history of myocardial infarction, self-rated health and presence of diabetes, cognitive impairment or physical disability, the estimated relative risk reduction of total mortality per an increment of one more cup of coffee per d reported at baseline was 4 (95 % CI 0, 8) %. The observed associations between coffee consumption and mortality from CVD, cancer, and other or unknown causes, respectively, were qualitatively similar to that of total mortality but the estimates were less precise. The effect of coffee consumption at baseline appeared to attenuate after 10 years since the start of follow-up. The present study provides evidence for daily (caffeine-containing) coffee intake being inversely associated with mortality in the elderly.
The Proportion of Anemia Associated with Iron Deficiency in Low, Medium, and High Human Development Index Countries: A Systematic Analysis of National Surveys

Iron deficiency is commonly assumed to cause half of all cases of anemias, with hereditary blood disorders and infections such as hookworm and malaria being the other major causes. In countries ranked as low, medium, and high by the Human Development Index, we conducted a systematic review of nationally representative surveys that reported the prevalence of iron deficiency, iron deficiency anemia, and anemia among pre-school children and non-pregnant women of reproductive age. Using random effects meta-analyses techniques, data from 23 countries for pre-school children and non-pregnant women of reproductive age was pooled, and the proportion of anemia attributable to iron deficiency was estimated by region, inflammation exposure, anemia prevalence, and urban/rural setting. For pre-school children and non-pregnant women of reproductive age, the proportion of anemia associated with iron deficiency was 25.0% (95% CI: 18.0, 32.0) and 37.0% (95% CI: 28.0, 46.0), respectively. The proportion of anemia associated with iron deficiency was lower in countries where anemia prevalence was >40%, especially in rural populations (14% for pre-school children; 16% for non-pregnant women of reproductive age), and in countries with very high inflammation exposure (20% for pre-school children; 25% for non-pregnant women of reproductive age). Despite large heterogeneity, our analyses suggest that the proportion of anemia associated with iron deficiency is lower than the previously assumed 50% in countries with low, medium, or high Human Development Index ranking. Anemia-reduction strategies and programs should be based on an analysis of country-specific data, as iron deficiency may not always be the key determinant of anemia.
Every Step You Take, I’ll Be Watching You: Practical StepAuth-Entication of RFID Paths

Path authentication thwarts counterfeits in RFID-based supply chains. Its motivation is that tagged products taking invalid paths are likely faked and injected by adversaries at certain supply chain partners/steps. Existing solutions are path-grained in that they simply regard a product as genuine if it takes any valid path. Furthermore, they enforce distributed authentication by offloading the sets of valid paths to some or all steps from a centralized issuer. This not only imposes network and storage overhead but also leaks transaction privacy. We present StepAuth, the first step-grained path authentication protocol that is practically efficient for authenticating products with strict path bindings. We encode a path into a secret with minimum path visibility disclosure between adjacent steps. Carrying the secret, a product has to go through steps in the exact order as in the designated path to pass authentication. StepAuth enforces no tag computation and enables each step to locally verify path secrets without pre-offloaded valid-path sets. Toward an even higher security guarantee, StepAuth can hinder an adversary capable of compromising all steps from forging valid secrets. We make StepAuth practically efficient by taking advantage of nested encryption and hybrid encryption. To achieve a 128-b security for a practically long path of 100 steps, StepAuth generates a secret around 10 KB, which can be well supported by high-memory EPC Gen2 tags. Such secrets take StepAuth less than 1 s to encode and around 10 ms to verify.
Earthworm symbiont Verminephrobacter eiseniae mediates natural transformation within host egg capsules using type IV pili

The dense microbial communities commonly associated with plants and animals should offer many opportunities for horizontal gene transfer through described mechanisms of DNA exchange including natural transformation (NT). However, studies of the significance of NT have focused primarily on pathogens. The study presented here demonstrates highly efficient DNA exchange by NT in a common symbiont of earthworms. The obligate bacterial symbiont Verminephrobacter eiseniae is a member of a microbial consortium of the earthworm Eisenia fetida that is transmitted into the egg capsules to colonize the embryonic worms. In the study presented here, by testing for transformants under different conditions in culture, we demonstrate that V. eiseniae can incorporate free DNA from the environment, that competency is regulated by environmental factors, and that it is sequence specific. Mutations in the type IV pili of V. eiseniae resulted in loss of DNA uptake, implicating the type IV pilus (TFP) apparatus in DNA uptake. Furthermore, injection of DNA carrying antibiotic-resistance genes into egg capsules resulted in transformants within the capsule, demonstrating the relevance of DNA uptake within the earthworm system. The ability to take up species-specific DNA from the environment may explain the maintenance of the relatively large, intact genome of this long-associated obligate symbiont, and provides a mechanism for acquisition of foreign genes within the earthworm system.
B Cells Are Essential for Moderating the Inflammatory Response and Controlling Bacterial Multiplication in a Mouse Model of Vaccination against Chlamydophila abortus Infection

ABSTRACT The use of inactivated vaccines associated with suitable adjuvants has been demonstrated to confer a good level of protection against Chlamydophila abortus. However, the basis of the immune protective response induced by these vaccines has been poorly studied. B cells act as an immune regulatory population during primary infection by C. abortus. Thus, it was considered of interest to study the role of B cells in an infection after immunization with a killed vaccine. For this, C57BL/6 and B-cell-deficient mice were immunized with a killed vaccine against C. abortus using QS-21 as the adjuvant. After challenge, the course of infection was established by analysis of morbidity, C. abortus burden in the liver, and histopathological changes. The immune response induced was studied by real-time PCR techniques. Experiments involving transfer of immune serum from vaccinated or previously infected mice were also carried out. The lack of B cells reduced the protection conferred by the QS-21 adjuvant vaccine. Vaccinated B-cell-deficient mice showed a 1,000-fold-greater bacterial burden in the liver than their wild-type counterparts. Obvious differences existed in the liver, where a severe neutrophilic reaction and extended areas of necrosis were observed with vaccinated B-cell-deficient mice. An analysis of the immune response pointed to a significant increase in inflammatory cytokines and chemokines and the deficient production of transforming growth factor beta. The transfer of antibodies restored the level of protection. This study demonstrates that B cells play a crucial role in controlling C. abortus multiplication and prevent an exacerbated inflammatory response.