Miracle-dz/UniFAR-FTUs huggingface dataset:
Rapid intramolecular coupling of active sites in the pyruvate dehydrogenase complex of Escherichia coli: mechanism for rate enhancement in a multimeric structure.

In the absence of CoA and presence of pyruvate, the lipoic acid residues covalently bound to the lipoate acetyltransferase core component (acetyl-CoA:dihydrolipoate S-acetyltransferase, EC 2.3.1.12) of the pyruvate dehydrogenase multienzyme complex of Escherichia coli become reductively acetylated. A study of a series of reassembled complexes varying only in their content of pyruvate decarboxylase [pyruvate:lipoate-oxidoreductase (decarboxylating and acceptor-acetylating) EC 1.2. 4.1] showed that the initial direct reductive acetylation of lipoic acid residues can be followed by extensive intramolecular transacetylation reaction between lipoic acid residues on neighboring polypeptide chains of the lipoate acetyltransferase core [Bates, D. L. , Danson, M. J., Hale, G. , Hooper, E. A. & Perham, R. N. (1977) Nature (London) 268, 313-316]. Pulsed-quenched-flow measurements of the rates of the acetylation reactions in the various complexes now demonstrate that the intramolecular transacetylation reactions are not rate-determining in the normal reaction mechanism of the enzyme. There is therefore the potential for rapid multiple coupling of active sites in the lipoate acetyltransferase core. The rate constant for the overall complex reaction, measured by stopped-flow fluorimetry, is found to be approximately twice that for the reductive acetylation reaction measured by pulsed-quenched flow. This result could mean that CoA is an allosteric stimulator of the reductive acetylation part of the overall reaction or that there are two active sites on each chain of the lipoate acetyltransferase component working in parallel. A system of rapid functional connection of active sites in a multienzyme complex ensures that sequential reactions can be successfully coupled even under conditions of low substrate concentrations for the different steps. The substantial rate enhancement thus achieved offers a plausible explanation for the unusual complexity of the quaternary structure of the enzyme.
Aetiological relationships of nasal mucus cyclic nucleotides in patients with taste and smell dysfunction

Aims The authors previously demonstrated that nasal mucus cyclic adenosine 3′, 5′-monophosphate (cAMP) and cyclic 3′, 5′-guanosine monophosphate (cGMP) were lower in patients with smell and taste dysfunction than in normal individuals. To learn more about these differences this study related levels of nasal mucus cAMP and cGMP in patients with smell and taste dysfunction to the aetiology of their sensory loss and compared these results with those in normal individuals. Methods Nasal mucus cAMP and cGMP levels in patients with smell loss (hyposmia) were calculated after assembling data into aetiological groups. Levels were compared with each clinical group, with the entire patient group and with normal individuals. Data were obtained from initial values among patients with hyposmia who participated in a clinical trial of treatment with the phosphodiesterase inhibitor theophylline. Results Nasal mucus cyclic nucleotides in the entire patient group before treatment were below normal as previously demonstrated. Stratification by aetiology revealed differences not previously apparent. In some groups levels of cAMP and cGMP were below normal, some were similar to normal and some were above the normal mean. Conclusions As nasal mucus cyclic nucleotides relate to the growth and development of olfactory epithelial cells these results indicate there are differential alterations in nasal mucus cAMP and cGMP related to the aetiology of smell and taste dysfunction.
Darwin's clinical relevance

‘‘Evolution is the dominant fact of biology,’’ stated Nobel laureate and codiscoverer of the structure of DNA, James D. Watson at a recent meeting at the University of Chicago. Although there has been a great deal of interest in the evolution of cancer, it has been focused primarily on preclinical events; however, these concepts apply as well to the clinical manifestations of cancer. To design a strategy for cancer management, one must have a model of the disease. For such a model to be useful it must be consistent with what we already know, especially with what Watson describes as ‘‘the dominant fact of biology. ’’ We must understand what evolutionary theory both states and implies before we can apply it in the clinic. What follows is a discussion of the clinical relevance of evolutionary concepts as they bear on the development of a cancer, its natural history and prognosis, and to determining appropriate therapeutic strategies.
Logistic regression models for predicting intraventricular haemorrhage in preterm infants using respiratory and blood pressure signals

Despite the decline in mortality rates for extremely preterm infants, intraventricular haemorrhage (IVH) remains a threat to their survival. In this study, we sought to explore logistic regression models for predicting IVH as they would be applied in a clinical setting, using features derived from respiratory and blood pressure signals. Calculated predictors included mean (μ) and the short- and long-term scaling exponents (α1, α2) from detrended fluctuation analysis. The model fitted with short-term scaling exponent (α1) of the beat-to-beat diastolic blood pressure (DBP) exhibited an area under receiver-operator characteristic curve (AUC) of 0.788 (0.62, 0.96), with a sensitivity of approximately 0.875 at a specificity of 0.75. Of the multivariable models explored, the highest AUC was 0.831 (0.66, 1.00), combining μDBP with α1 of the beat-to-beat systolic blood pressure (SBP).
Vibration Model and Analysis of Three-Member Telescopic Boom with Hydraulic Cylinder for its radius Change

In this paper, the free vibration problem of a system consisting of a three-member type telescopic boom of the laboratory crane, the hydraulic cylinder of crane radius change and the elastic support system has been presented. The model has been formulated in order to represent the vibrations in the lifting plane of the laboratory crane. The transverse vibrations of the boom, longitudinal and transverse vibrations of the hydraulic cylinder have been considered in the coupled model of the system taking into account the elasticity of the support system. In the computational model, the analyzed system has been replaced by the discrete-continuous model. The free vibration problem of the analyzed system is formulated and solved on the basis of Lagrange multiplier formalism. The experimental modal analysis is done and the genetic algorithm worked out with the aim of identifying spring constants of the support system elements. The analysis of the influence of the hydraulic cylinder and the length of the telescopic boom on the free vibration frequencies is carried out on the basis of the identified vibration model of the considered system. The examples of the experimental and numerical results are presented.
El sueño de Elie Metchnikoff: evaluación funcional de nuevas cepas de probióticos

Un gran numero de evidencias cientificas demuestran que, las bacterias lacticas ejercen numerosos efectos beneficiosos para la salud tales como la mejora de la intolerancia a la lactosa, la prevencion y atenuacion de infecciones intestinales, alergias y enfermedades inflamatorias intestinales, efectos inmunomoduladores. Estos estudios, han demostrado la singularidad de cada cepa, indicando la necesidad de estudiar las caracteristicas propias de cada una de forma que, su seleccion para una determinada aplicacion este basada en sus propiedades particulares y en las condiciones de salud del consumidor al que vaya dirigido su consumo. Recientemente se ha demostrado que la leche materna no es esteril, sino mas bien constituye una fuente excelente y continua de bacterias que seran transferidas al bebe a traves de la lactancia para iniciar su propia microbiota intestinal. Entre las bacterias comunmente aisladas de la leche materna se encuentran representantes de los generos estafilococos, estreptococos, lactococos, enterococos y lactobacilos. La presencia de bacterias lacticas en la leche materna con efectos probioticos podria explicar, al menos en parte, la menor incidencia de infecciones o alergias en ninos amamantados en comparacion con los alimentados con formulas infantiles. Por tanto, la leche materna es una fuente excelente de bacterias para buscar nuevas cepas con un destacado potencial probiotico que puedan ser aplicadas en humanos. Tras un proceso de seleccion que contemplo aspectos de seguridad, funcionalidad y tecnologicos, se seleccionaron 4 cepas con las que se llevo a cabo una evaluacion preclinica y clinica del efecto probiotico de las cepas Hereditum® con el fin de demostrar su eficacia y, determinar las posibles aplicaciones tanto en nutricion infantil como en la de adultos, asi como, en el campo de la prevencion y tratamiento de ciertas enfermedades. Con este fin se plantearon los siguientes objetivos que se han desarrollado en la presente Tesis Doctoral: 1. Demostrar la tolerancia y seguridad de las cepas Hereditum® en modelos animales, utilizando dosis superiores a las dosis habitualmente consumidas por humanos, con el fin de evaluar su seguridad en humanos. 2. Validacion preclinica de las cepas Hereditum® en animales de experimentacion que, demuestren la eficacia de los probioticos in vivo y permitan caracterizar las propiedades probioticas de cada cepa en particular con el fin de definir las aplicaciones mas adecuadas para cada una de ellas. 3. Validacion clinica de las cepas Hereditum®. Demostrar la funcionalidad de cada cepa en la poblacion a la que se vaya a dirigir su consumo ya sea en individuos sanos o enfermos.
TEXTURE SEGMENTATION BY EVIDENCE GATHERING 3 2 Background 2 . 1 Local Binary Patterns

A new approach to texture segmentation is presented which uses Local Binary Pattern data to provide evidence from which pixels can be classified into texture classes. The proposed algorithm, which we contend to be the first use of evidence gathering in the field of texture classification, uses Generalised Hough Transform style R-tables as unique descriptors for each texture class and an accumulator is used to store votes for each texture class. Tests on the Brodatz database and Berkeley Segmentation Dataset have shown that our algorithm provides excellent results; an average of 86.9% was achieved over 50 tests on 27 Brodatz textures compared with 80.3% achieved by segmentation by histogram comparison centred on each pixel. In addition, our results provide noticeably smoother texture boundaries and reduced noise within texture regions. The concept is also a “higher order” texture descriptor, whereby the arrangement of texture elements is used for classification as well as the frequency of occurrence that is featured in standard texture operators. This results in a unique descriptor for each texture class based on the structure of texture elements within the image, which leads to a homogeneous segmentation, in boundary and area, of texture by this new technique.
Simplification improves understanding of informed consent information in clinical trials regardless of health literacy level

Background: This study evaluated the effect of a simplified informed consent form for clinical trials on the understanding and efficacy of informed consent information across health literacy levels. Methods: A total of 150 participants were randomly assigned to one of two groups and provided with either standard or simplified consent forms for a cancer clinical trial. The features of the simplified informed consent form included plain language, short sentences, diagrams, pictures, and bullet points. Results: Levels of objective and subjective understanding were significantly higher in participants provided with simplified informed consent forms relative to those provided with standard informed consent forms. The interaction effects between type of consent form and health literacy level on objective and subjective understanding were nonsignificant. Conclusion: Simplified informed consent was effective in enhancing participant’s subjective and objective understanding regardless of health literacy.
Causation and the Price of Transitivity

Revisant sa propore critique de la transitivite de la causation, l'A. se propose de resoudre le probleme de l'incompatibilite entre la transitivite et la these de la dependance contrefactuelle par la reconnaissance de differents types de relation causale. Mettant en evidence la structure court-circuitee des contrexemples opposes a la transitivite par D. Lewis, l'A. definit par le terme de changement de position (switch) toute interaction d'un evenement avec une autre structure causale, et en tire les consequences du point de vue de la methodologie et de la metaphysique de la causation.
Performance of FHSS multiple-access networks using MFSK modulation

The main concern of this paper is to estimate the symbol error probabilities of synchronous and asynchronous frequency-hop spread-spectrum multiple-access (FHSS-MA) networks through semi-analytic Monte Carlo simulations. We concentrate on systems transmitting one M-ary (M/spl ges/2) FSK modulated symbol per hop with noncoherent demodulation. The usual practice when analyzing the performance of such networks is to upper-bound the probability of symbol error when a hop is hit by K/sup '//spl ges/1 interfering users with (M-1)/M or 1. Previous work on the derivation of accurate approximations to this probability for the case when M=2 has indicated that the aforementioned bound not only gives excessively pessimistic results but may also lead to wrong tradeoff decisions. Using the simulated values for the error probabilities, we show that a similar argument holds for the cases when M>2 as well. Also, by employing a normalized throughput measure that takes into account the bandwidth and time expansion associated with the modulation order M, we find that there exists an optimum value of M that achieves the maximum possible throughput for the cases when binary and M-ary error correcting codes are employed. Throughput results are also given for the case when the signals from the active users in the network suffer from independent Rayleigh fading.
Is there a role for mammary stem cells in inflammatory breast carcinoma?

Stem cells are pluripotent cells, with a large replicative potential, which perform normal physiological functions such as tissue renewal and damage repair. However, because of their long lifespan and high replicative potential, stem cells are ideal targets to accumulate multiple mutations. Therefore, they can be regarded as being responsible for the initiation of tumor formation. In the past, numerous studies have shown that the presence of an elaborate stem cell compartment within a tumor is associated with aggressive tumor cell behavior, frequent formation of metastases, resistance to therapy, and poor patient survival. From this perspective, tumors from patients with inflammatory breast cancer (IBC), an aggressive breast cancer subtype with a dismal clinical course, are most likely to be associated with stem cell biology. To date, this hypothesis is corroborated by evidence resulting from in vitro and in vivo experiments. Both gene and microRNA expression profiles highlighted several stem cell‐specific signal transduction pathways that are hyperactivated in IBC. Also, these stem cell‐specific signal transduction pathways seem to converge in the activation of nuclear factor‐kappa B, a molecular hallmark of IBC, and induction of epithelial‐to‐mesenchymal transition. Recently, the latter mechanism was identified as a prerequisite for the induction of stem cell characteristics in breast cancer cells. Cancer 2010;116(11 suppl):2794–805. © 2010 American Cancer Society.
Contribution of 6p24 to Non-syndromic Cleft Lip and Palate in a Malay Population

Non-syndromic cleft lip, with or without cleft palate, is a heterogeneous, complex disease with a high incidence in the Asian population. Several association studies have been done on cleft candidate genes, but no reports have been published thus far on the Orofacial Cleft 1 (OFC1) genomic region in an Asian population. This study investigated the association between the OFC1 genomic region and non-syndromic cleft lip with or without cleft palate in 90 Malay father–mother–offspring trios. Results showed a preferential over-transmission of a 101-bp allele of marker D6S470 in the allele- and haplotype-based transmission disequilibrium test (TDT), as well as an excess of maternal transmission. However, no significant p-value was found for a maternal genotype effect in a log-linear model, although single and double doses of the 101-bp allele showed a slightly increased cleft risk (RR = 1.37, 95% CI, 0.527-3.4, p-value = 0.516). Carrying two copies of the 101-bp allele was significantly associated with an increased cleft risk (RR = 2.53, 95% CI, 1.06-6.12, p-value = 0.035). In conclusion, we report evidence of the contribution of the OFC1 genomic region to the etiology of clefts in a Malay population.
Microarray Analysis of Aeromonas hydrophila Cytotoxic Enterotoxin-Treated Murine Primary Macrophages

ABSTRACT We performed microarray analyses of murine peritoneal macrophages to examine cellular transcriptional responses to a cytotoxic enterotoxin of Aeromonas hydrophila. While 66% of altered genes were common to both primary macrophages and the murine macrophage cell line RAW 264.7, Act caused expression changes of 28 genes specifically in murine peritoneal macrophages.
Depression and risk of suicide in patients with obsessive-compulsive disorder: A hospital-based study

Background: Obsessive Compulsive Disorder (OCD) is a chronic, distressing, anxiety disorder associated with significant functional impairment. Patient with OCD often suffer from one or more co-morbid disorders. Major depression has been the most common co-morbid syndrome. Comorbid Axis I disorders along with increased severity of comorbid depressive and anxiety symptoms, increased severity of obsessions, feelings of hopelessness and past history of suicide attempts have been associated with worsening levels of suicidality in OCD (Angelakis I, Gooding P., 2015). As per data Thirty-six percent of the patients of OCD report lifetime suicidal thoughts and 11% have a history of attempted suicide(Torres AR, Ramos-Cerqueira AT, et al, 2011). There is a reasonable probability that the patient of OCD have suicidal thoughts, plans or actually attempt suicide. Aim: To assess depression and suicidality in OCD patients. Method: This study was conducted on 50 patients diagnosed with OCD as per ICD 10 criteria, both outpatient & indoor, from department of psychiatry, Dayanand Medical College & Hospital, Ludhiana, Punjab, India. A socio-demographic proforma (containing demographic details), Hamilton Depression Rating & Scale, Columbia suicide severity rating scale (CSSRS) & Yale Brown Obsessive Compulsive Scale Symptom Checklist (YBOCS) were administered. Results: Mild depression was found out to be 40% whereas 16% were suffering from moderate depression and 10% and 14% had severe and very severe depression respectively. Suicidal ideation was found in 52 % of patients.16% of patients had history of actual attempt. Data showed that 70% of females had suicidal ideations. It was also found that in cases of severe and very severe depression associated with OCD all the patients had suicidal ideations as compared to 35% in mild and 87.5% in moderate depressive patients. It was found that 40% of severe depressive and 28.57% of very severe depressive patients had attempted suicide one or more times during the course of illness. Also suicidality was found to be maximum in those with symptoms of cleanliness and contamination (57%) followed by religious obsessions (45%), sexual obsessions (33%), repeated rituals (31%) and other obsessions like need to touch, ask (26%) respectively. Conclusion: OCD is associated with high risk not only depression but also of suicidal behavior. It is vital that patients of OCD undergo detailed assessment for suicide risk and associated depression. Aggressive treatment of depression may be warranted to modify the risk of suicide. Behavioral and cognitive techniques along with pharmacotherapy should be used to target co-existing depressive symptoms so as to decrease morbidity and mortality.
Outcome of surgical treatment of synchronous liver metastases from colorectal cancer.

BACKGROUND We retrospectively identified the prognostic factors in cases of synchronous liver metastases from colorectal cancer and established a clinical strategy at our institution. METHODS One hundred eight patients with hepatic metastases from colorectal cancer underwent a first radical hepatic resection. Of these, 67 were diagnosed with hepatic synchronous metastases from colorectal primaries (S group) and 41 were diagnosed with metachronous metastases (M group). Hepatic lesions were diagnosed concurrently with the primary lesions in 45 of the 67 patients in the S group. Of these 45 patients, 37 underwent synchronous hepatectomy (SH group) and 8 underwent metachronous hepatectomy (MH group). RESULTS The overall 3-, 5- and 10-year survival rates were 51.4%, 41.6%, and 30.9%, respectively. There were no significant differences between the S and M groups in overall survival. Univariate analysis of the S group revealed significant differences in survival based on tumor factor, pathological lymph node metastases of the primary tumor, and the tumor-free margin. There were no significant differences between the SH and MH groups in overall survival. CONCLUSIONS Patients with synchronous liver metastases from colorectal cancer should undergo radical resection of the primary lesion and simultaneous hepatectomy with an adequate tumor-free margin as a standard surgical course.
The Role of Metals in Ischemia/Reperfusion Injury of the Liver

Based on current information, we have described the role that metals play in potentiating and ameliorating liver I/R injury. To date, most of the data have focused on the deleterious effects of free iron in mediating I/R injury. Several therapeutic strategies have proven useful in animal models to counteract the effect of iron as a potentiator of I/R injury. These approaches have predominantly centered on the role of iron chelation using DFO and DFO conjugates. The data suggest that chelation of iron may prove useful in preventing I/R injury such as occurs in liver transplantation. Indeed, enough data are now available to initiate and support clinical trials (e.g., addition of DFO conjugates to explant storage solutions). The role of copper, however, is less well defined. Copper is important for the function of copper-zinc SOD. However, free copper may be as injurious as free iron. Further studies are needed to clarify the role of copper in I/R-induced hepatocellular necrosis. Selenium has a well-defined antioxidant role as part of GSH peroxidase (GSH antioxidant pathway). More recent data suggest that selenium may also act as an antioxidant through selenoprotein P, but the role of selenoprotein P in I/R injury remains to be defined. Finally, zinc appears to function as an antioxidant in less well-defined pathways. Further studies are needed to identify the fundamental mechanisms by which zinc may ameliorate oxidative damage during I/R injury. These data demonstrate that metals play a critical role in I/R injury of the liver and remain a fruitful area for investigation and development of therapeutic strategies.