Miracle-dz/UniFAR-FTUs huggingface dataset:
Insulin Inhibits LPS-Induced Signaling Pathways in Alveolar Macrophages

The systemic inflammatory response syndrome (SIRS) is triggered by lipopolysaccharide (LPS) from Gram-negative bacteria. Insulin was shown to have a protective role in SIRS related to sepsis. Lungs are particularly affected in this condition and provide a second wave of mediators/cytokines which amplifies SIRS. The aim of the present study was to investigate the effect of insulin on the signaling pathways elicited by LPS in alveolar macrophages (AMs) and its consequence in cellular response to LPS measured as production of tumor necrosis factor (TNF). To this purpose, resident AMs from male Wistar rats were obtained by lung lavage and stimulated by LPS (100 ng/mL). Insulin (1 mU/mL) was added 10 min before LPS. Activation (phosphorylation) of signaling molecules by LPS was analyzed by western blot, 30 min after LPS stimulation. TNF was measured in the AMs culture supernatants by bioassay using L-929 tumor cells. Relative to controls, LPS induced a significant increase in the activation of ERK (3.6-fold), p38 (4.4-fold), Tyr-326 Akt (4.7-fold), Ser-473 Akt (6.9-fold), PKCα (4.7-fold) and PKCδ (2.3-fold). Treatment of AMs with insulin before LPS stimulation, significantly reduced the activation of ERK (54%), p38 (48%), Tyr-326 Akt (64%), Ser-473 Akt (41%), PKCα (62%) and PKCδ (39%). LPS induced TNF production in AMs which was also inhibited by insulin (60%). These results show that insulin down-regulates MAPK, PI3K and PKCs and inhibits a downstream effect of LPS, TNF production, in rat AMs stimulated with LPS and suggest that the protective effect of insulin in sepsis could be through modulation of signal transduction pathways elicited by LPS in lung macrophages.
p53-related pathways and the molecular pathogenesis of melanoma

Cutaneous malignant melanoma (CMM) is a life-threatening cancer that can have a poor prognosis with high metastatic potential. Its incidence is rapidly increasing worldwide. Its molecular alterations involve multiple pathways, including those related to p53. Since 1981, more than 380 papers containing the terms ‘p53 and melanoma’ as key words in the Abstract have been published in the literature. However, in spite of these extensive investigations, a review of p53 and associated genes in CMM is still lacking. To remedy this issue, this review seeks to provide a brief overview of p53 and discuss the genes targeted along its related pathways.
Immunology of human schistosomiasis: off the beaten path

Reviews of the immunology of human schistosomiasis generally address the host's protective responses against infection or the factors associated with development of severe pathology. However, there is a growing recognition that the high number of patients expressing moderate morbidity, rather than the few patients with severe morbidity, accounts for the greatest public health impact of schistosomiasis. Therefore, other aspects of the host immune response that have received relatively little attention may actually provide pivotal answers in our understanding and management of the morbidity associated with human schistosomiasis. This review highlights lines of investigation that focus on how immune responses to schistosomiasis may affect schistosomiasis‐associated anaemia, alter susceptibility or disease progression during co‐infections, and influence effective execution of mass treatment programmes.
[Signal of the cytoplasmic regions of leukemia inhibitory factor receptor (LIFR) alpha-subunit and gp130 involves Stat3 activation in leukemic U937 cells].

OBJECTIVE In order to understand the mechanism of proliferation and differentiation of leukemia cells, we investigate the relation between the cytoplasmic regions LIFR alpha-subunit and gp130 and the transcription activator Stat3 in human leukemic U937 cells. METHODS The cytoplasmic domain was each truncated from the LIFR alpha-subunit and gp130. The truncated forms of LIFR alpha-subunit(gp190EX) and gp130 (gp130EX) which can compete with the wild type receptor for binding to leukemia inhibitory factor (LIF) were expressed on the membrane of U937 cells. The level of Stat 3 and its phosphorylation were estimated by immunoblotting. RESULTS The increased level of Stat3 and its decreased tyrosine phosphorylation were detected in each group of gp130EX and gp190EX as compared with that in the wild type receptor subunit group. CONCLUSION The cytoplasmic domains of both LIFR alpha subunit and gp130 involve the induction of Stat3 phosphorylation in U937 cells.
Synergistic relationship between changes in the pulse wave velocity and changes in the heart rate in middle-aged Japanese adults: a prospective study

Objectives Temporal associations between rates of increases in pulse wave velocity (PWV), a marker of arterial stiffness, and heart rate (HR) indices (baseline HR and changes in HR) as well as inflammatory markers were examined. Methods In 1795 apparently healthy Japanese individuals (mean age 39 ± 8 years old), brachial-ankle PWV (baPWV) and serum C-reactive protein (CRP) levels were measured at the baseline and at the end of a 5–6-year follow-up period. Results Heart rate at the baseline examination and changes in HR during the follow-up period were significantly associated with the corresponding changes in baPWV during the study period (nonstandardized co-efficient = 0.14, 95% confidential interval = 8.14 × 10−2–0.19, P < 0.01) even after the adjustment for atherogenic risk factors. When individuals were divided into four groups categorized by baseline HR (higher or lower than median HR) and increase/decrease in HR during the study period, serum CRP levels and atherogenic risk factors were significantly worse in the individuals with high baseline HR accompanied by increased HR during the study period. There was no significant relationship between the changes in the baPWV and the changes in the serum CRP levels. Even after the adjustment for confounding factors, changes in baPWV were significantly higher in this group than the other three groups (P < 0.01). Conclusions The study results suggest a synergistic role of high baseline HR and increase in HR during the study period in accelerating age-associated increases in PWV. Inflammation might not be a major factor for this relationship.
Fusobacterium nucleatum Activates the Immune Response through Retinoic Acid–Inducible Gene I

Retinoic acid–inducible gene I (RIG-I) is a cytosolic pattern recognition receptor involved in the sensing of RNA viruses and the initiation of antiviral responses. Fusobacterium nucleatum, a Gram-negative anaerobic bacterium associated with periodontal disease, is capable of invading cells. We hypothesized that F. nucleatum’s ability to invade cells allows the microorganism to activate the immune response through RIG-I. Bacterial invasion was found to be necessary for F. nucleatum–induced nuclear factor kappa B (NF-κB) activation. Following invasion of the human periodontal ligament fibroblast (PDLF), F. nucleatum was located in the cytosol. F. nucleatum infection led to an 80-fold increase in RIG-I expression. Silencing RIG-I in PDLF by siRNA led to a significant decrease of NF-κB activation and expression of proinflammatory genes. Additionally, F. nucleatum was able to secrete nucleic acids, and introduction of F. nucleatum RNA into PDLF led to a RIG-I-dependent activation of NF-κB. Our findings showed RIG-I to be involved in the recognition of F. nucleatum. The function of RIG-I is likely to be broad and not limited to sensing of viruses only. Hence, this receptor may play an important role in detecting invasive forms of oral pathogens and contribute to inflammation in periodontal tissues.
Computational analysis the influence of missense mutations upon protein structure and function

Distinguish harmful missense nucleotide substitutions from single nucleotide polymorphisms is a difficult problem usually to be accomplished through functional in vivo analyses. In this study, instead current biochemical methods, the effects of missense mutations upon protein structure and function were assayed by means of computational methods and information from the databases. For this order, the effects of new missense mutations in exon 5 of PTEN gene upon protein structure and function were examined. The gene coding for PTEN was identified and localized on chromosome region 10q23.3 as the tumor suppressor gene. The utilization of these methods were shown that c.319G>A and c.341T>G missense mutations that were recognized in patients with breast cancer and Cowden disease, could be pathogenic. This method could be use for analysis of missense mutation in others genes.
Chip-side-healing as a basis for robust bare-chip assemblies

During their life cycles, semiconductor devices are exposed to different mechanical loads as a result of assembly and packaging processes as well as by stresses due to environmental conditions during operation. Especially, in modern applications like high temperature sensors the die-strength and the fracture resistance of the used semiconductor are important factors for the system reliability. They often develop high stresses in the chips. The die-strength is considerably influenced by the wafer dicing because of process-induced damages, which are generated at the side walls of chips. Chip-side-healing (CSH) is a term for the selective removal of dicing damages with the aim to increase the die-strength. In this work, two new CSH-processes are evaluated. The first one uses xenon difluoride (XeF2) as the etching medium and the second process works with fluorine radicals to remove the damages. Both processes can remove all of the dicing damages. After the CSH the bending strength was nearly four times higher than without the aforementioned processes. In comparison to six common dicing techniques, diamond-scribing, water-jet-laser-dicing, stealth-dicing, blade-dicing, deep-reactive-ion-etching and thermal-laser-separation, CSH shows better potential to increase the thermal-mechanical reliability of semiconductors.
Amygdala Automaticity in Emotional Processing

Abstract: The question addressed in this paper is whether the human amygdala processes threat‐related stimuli independent of selective attention. This is considered from a functional neuroimaging perspective, describing studies in normal volunteers and patients with brain lesions. The conclusion is that the evidence for such automaticity is strong, indicating that important distinctions exist between emotion and other forms of cognition.
In vivo control of endosomal architecture by class II‐associated invariant chain and cathepsin S

The invariant chain (Ii) is a chaperone that regulates assembly and transport of class II MHC molecules. In the absence of the lysosomal protease cathepsin S (CatS), degradation of Ii is impaired and an Ii remnant that extends from the N terminus to about residue 110 accumulates in class II MHC‐positive endosomal compartments, which are enlarged in size and lack multivesicular morphology. In primary B cells examined in vitro and in lymph nodes examined by immuno‐electron microscopy, CatS controls architecture of class II‐positive endosomal compartments. In a compound mutant mouse that lacks both CatS and Ii, the normal size of endosomes in class II‐positive cells is restored, although internal endosomal membranes are absent. Proper degradation of Ii is thus essential for normal endosomal morphology in antigen‐presenting cells in vivo.
Aortic valve replacement reduces valvuloarterial impedance but does not affect systemic arterial compliance in elderly men with degenerative calcific trileaflet aortic valve stenosis.

OBJECTIVE Standard methods of quantifying aortic valve stenosis (AS), which focus entirely on the valve itself, do not adequately characterize the magnitude, predict the onset, progression, and severity of symptoms, or identify the incidence of subsequent adverse events. Valvuloarterial impedance (Z(va)) is an index of global left ventricular (LV) afterload that incorporates valvular and arterial loads. The authors tested the hypothesis that aortic valve replacement (AVR) reduces Z(va) but does not affect the arterial component of LV afterload in elderly patients with degenerative calcific trileaflet AS. DESIGN Observational study. SETTING Veterans affairs medical center. PARTICIPANTS Eight elderly (age, 79 ± 4 years) men with moderate-to-severe AS and normal preoperative LV function (ejection fraction, 61% ± 9%) scheduled for AVR with or without coronary artery bypass graft surgery were studied after institutional review board approval. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS A comprehensive TEE examination was performed during isoflurane-fentanyl-rocuronium anesthesia. Doppler echocardiography was used to measure pressure gradients across the aortic valve, stroke volume (continuity equation), and aortic valve area using standard techniques. Z(va) was determined as (systolic arterial pressure+mean gradient)/stroke volume index. Energy loss index was calculated as (aortic area × aortic valve area)/([aortic area--aortic valve area]× body surface area). The stroke work loss was obtained as (mean gradient × 100/[systolic arterial pressure+mean gradient]). The ratio of stroke volume index to pulse pressure was used to measure systemic arterial compliance. Z(va), energy loss index, stroke work loss, and systemic arterial compliance were assessed before and 15 minutes after cardiopulmonary bypass. Systemic and pulmonary hemodynamics (invasive catheters) were similar after versus before AVR. Aortic valve area increased significantly (p<0.05) with AVR (0.92 ± 0.26 cm(2) to 1.94 ± 0.35 cm(2)), concomitant with decreases in peak and mean gradients (60 ± 17 mmHg to 15 ± 8 mmHg and 38 ± 11 mmHg to 8 ± 5 mmHg, respectively) and peak blood flow velocity (3.9 ± 0.5 m · s(-1) to 1.9 ± 0.5 m · s(-1)). AVR reduced Z(va) (4.6 ± 1.0 mmHg · mL(-1) · m(-2) to 3.5 ± 0.3 mmHg · mL(-1) · m(-2)) and improved energy loss index (0.55 ± 0.16 cm(2) · m(-2) to 1.58 ± 0.48 cm(2) · m(-2)) concomitant with a decline in stroke work loss (25% ± 6% to 7% ± 4%), but systemic arterial compliance remained unchanged (0.63 ± 0.13 compared with 0.70 ± 0.12 mL · mmHg(-1)· m(-2)). CONCLUSION The current results showed that AVR acutely reduced Zva, improved energy loss index, and decreased stroke work loss, but did not affect systemic arterial compliance in elderly men with degenerative calcific trileaflet AS.
Lower urinary tract symptoms (LUTS) after renal transplant in non‐urologic anuric patients

Castagnetti M, Zhapa E, Berrettini A, Ghirardo G, Murer L, Zanon GF, Rigamonti W. Lower urinary tract symptoms (LUTS) after renal transplant in non‐urologic anuric patients. Pediatr Transplantation 2010: 14:859–862. © 2010 John Wiley & Sons A/S.
A COST OF REPRODUCTION IN DROSOPHILA MELANOGASTER: STRESS SUSCEPTIBILITY

Abstract Little is known about physiological mechanisms that underlie the cost of reproduction. We tested the hypothesis that stress susceptibility is a cost of reproduction. In one test of our hypothesis, Drosophila melanogaster females were exposed to a juvenile hormone analog (methoprene) to stimulate egg production followed by stress assays. A sterile stock of D. melanogaster was employed as a control for reproduction. Exposure of fertile females to methoprene resulted in an increase in female reproduction and increased susceptibility to oxidative stress and starvation (compared to solvent controls). Sterile females did not exhibit a decrease in stress resistance. Mating also stimulated egg production. As a second test of our hypothesis, mated females were compared to virgin females. Mated fertile females were relatively susceptible to oxidative stress, but this relationship was not evident when mated and virgin sterile females were compared. The results of the present study support the hypothesis that stress susceptibility is a cost of reproduction. Corresponding Editor: T. Mousseau
Five-dimensional supergravity and the hyperbolic Kac–Moody algebra GH2

Motivated by the recent analysis of the E10 sigma model for the study of M-theory, we study a one-dimensional sigma model associated with the hyperbolic Kac–Moody algebra GH2 and its link to pure supergravity, which closely resembles in many ways D = 11 supergravity. The bosonic equations of motion and the Bianchi identity for D = 5 pure supergravity match the equations of the level ℓ ⩽ 3 truncation of the GH2 sigma model up to higher level terms, just as they do for the D = 11 case. We also compute low level root and outer multiplicities in the A3 decomposition, and indeed find singlets at ℓ = 4k, k = 2, 3, … corresponding to the scaling of ERk+1 terms, although the missing singlet at ℓ = 4 remains a puzzle.
Two-dimensional coordination of guidance and adaptive radiated waveform for interception and rendezvous problems

We present an algorithm that allows an interceptor aircraft equipped with an airborne radar to meet another air target (the intercepted) by developing a guidance law and automatically adapting and optimising the transmitted waveform on a pulse to pulse basis. The algorithm uses a Kalman filter to predict the relative position and speed of the interceptor with respect to the target. The transmitted waveform is automatically selected based on its ambiguity function and accuracy properties along the approaching path. For each pulse, the interceptor predicts its position and velocity with respect to the target, takes a measurement of range and radial velocity and, with the Kalman filter, refines the relative range and range rate estimates. These are fed into a Linear Quadratic Gaussian (LQG) controller that ensures the interceptor reaches the target automatically and successfully with minimum error and with the minimum guidance energy consumption.
The Earliest Signs of Alzheimer's Disease

Insufficient clarity of definition of the clinical features in the earliest stages of developing Alzheimer's disease (AD) has impeded the execution of clinical and biologic studies into this major public health problem. Defining the earliest signs of a disease with such an insidious onset can prove to be a most elusive task, particularly in a disease whose very nature renders the patients' self-report unreliable. We therefore administered a structured interview to the close family caregivers of 83 patients with probable AD, in order to investigate the earliest perceived signs of illness in the patients. In 44 (53%) of patients, the earliest objective sign of change was not memory impairment. The initial sign of change was of a psychiatric type in 27 (32.5%); of a neurologic type in nine (10.9%); and of a noncoping type in eight (9.6%). Such nonmemory signs, as perceived by caregivers, preceded objective memory impairment by a mean of 1.8 years. In 39 patients (47%), memory impairment was the initial perceived sign of illness. These findings suggest thatthe earliest clinical manifestations of AD may, in many cases, significantly predate objective signs of memory impairment.
A Novel Approach to Evaluate Incremental Transmission Losses

During the past thirty years, the evaluation of incremental losses in transmission systems has been widespread around the world encompassing a fundamental task in order to solve the well-known economic dispatch problem. Nowadays, incremental losses or computation of penalty factors has gained a new relevance allocating transmission losses among market participants being integrated in the spot pricing model. Nevertheless, vagueness in power injections from load demand and renewable resources has a fundamental influence on transmission incre- mental losses, and consequently affecting spot prices of the energy. This paper presents a new method to compute Incremental Transmission Loss (ITL) factors taking into account the effect of uncertainty on power injections due to measurement errors or future estimation. Fuzzy Set Theory is applied to deal with vagueness of information about power injections. The proposed technique provides a broad spectrum of feasibility of incremental losses in order to perform operational planning tasks by Transmission System Operators or network regulators. A 3-bus system is used to illustrate the proposed methodology.
Explanation of the crystallization rate of amorphous nifedipine and phenobarbital from their molecular mobility as measured by (13)C nuclear magnetic resonance relaxation time and the relaxation time obtained from the heating rate dependence of the glass transition temperature.

To gain further insight into the effect of molecular mobility on the crystallization rate of amorphous drugs, the mean relaxation times of amorphous nifedipine and phenobarbital were calculated based on the Adam-Gibbs-Vogel (AGV) equation, using the parameters D, T(0), and T(f), derived from the heating rate dependence of the glass transition temperature (T(g)) of the amorphous drugs and heat capacity of the drugs in the amorphous and crystalline states. These relaxation times were compared with the crystallization rate of amorphous nifedipine and phenobarbital reported previously. The spin-lattice relaxation time (T(1)) and the spin-lattice relaxation time in the rotating frame (T(1rho)) of phenobarbital and nifedipine carbons were also determined. The temperature dependence of the crystallization rate of nifedipine and phenobarbital on the T(g) was coincident with that of the mean relaxation time calculated according to the AGV equation within experimental error, indicating that the crystallization of nifedipine and phenobarbital is largely correlated with molecular mobility at the temperatures studied. A (13)C nuclear magnetic resonance relaxation study indicated that the molecular motion of nifedipine and phenobarbital in the mid-kHz frequency range became significant at temperatures higher than T(g)-20 and T(g), respectively.
Mutant of simian virus 40 large T-antigen that is defective for viral DNA synthesis, but competent for transformation of cultured rat cells

A mutant was isolated which demonstrates that the transforming activity of simian virus 40 large T-antigen is separable from its function in viral DNA replication. The mutant, SVR9D, is nonconditionally defective for viral DNA synthesis, but competent at wild-type level for morphological transformation of cultured rat cells. The lytic growth defect in SVR9D is complemented by the simian virus 40 A gene product present in the transformed CV1 cell line, COS1. The lesion in SVR9D DNA was mapped genetically by marker rescue of plaque formation and localized to a 214-base-pair segment of the viral genome bounded by nucleotide numbers 4100 and 4314. DNA sequence analysis showed the mutation to be an adenine-to-guanine transition at nucleotide number 4178. This change predicts a lysine-to-glutamic acid amino acid change at residue number 214 of the mutant large T-antigen polypeptide.