Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of 5-week ethanol feeding on the liver of aldehyde dehydrogenase 2 knockout mice

Objective The polymorphism of aldehyde dehydrogenase 2 (ALDH2), denoted ALDH2*2, is very common in East Asian countries, and the mutated ALDH2 protein derived from ALDH2*2 lacks the ability of acetaldehyde metabolization. Our aim was to determine the consequences of the ALDH2 polymorphism on ethanol-administered liver tissue. Methods Aldh2+/+, +/−, and −/− mice were fed with ethanol solution and standard hard feed for 5 weeks. Results The serum alanine aminotransferase (ALT) level in the Aldh2−/− mice clearly decreased upon ethanol feeding, in contrast to Aldh2+/+ mice, in which the ALT level was unchanged. The levels of malondialdehyde, phospho extracellular signal-regulated kinase 2, and tumor necrosis factor-alpha in the liver tissue all correlated with the ALT level. Conclusion These findings suggest that ethanol intake in the presence of inactive ALDH2 decreases the serum ALT level following a decrease in oxidative stress and tumor necrosis factor-alpha secretion.
An amino acid code for β‐sheet packing structure

To understand the relationship between protein sequence and structure, this work extends the knob‐socket model in an investigation of β‐sheet packing. Over a comprehensive set of β‐sheet folds, the contacts between residues were used to identify packing cliques: sets of residues that all contact each other. These packing cliques were then classified based on size and contact order. From this analysis, the two types of four‐residue packing cliques necessary to describe β‐sheet packing were characterized. Both occur between two adjacent hydrogen bonded β‐strands. First, defining the secondary structure packing within β‐sheets, the combined socket or XY:HG pocket consists of four residues i, i+2 on one strand and j, j+2 on the other. Second, characterizing the tertiary packing between β‐sheets, the knob‐socket XY:H+B consists of a three‐residue XY:H socket (i, i+2 on one strand and j on the other) packed against a knob B residue (residue k distant in sequence). Depending on the packing depth of the knob B residue, two types of knob‐sockets are found: side‐chain and main‐chain sockets. The amino acid composition of the pockets and knob‐sockets reveal the sequence specificity of β‐sheet packing. For β‐sheet formation, the XY:HG pocket clearly shows sequence specificity of amino acids. For tertiary packing, the XY:H+B side‐chain and main‐chain sockets exhibit distinct amino acid preferences at each position. These relationships define an amino acid code for β‐sheet structure and provide an intuitive topological mapping of β‐sheet packing. Proteins 2014; 82:2128–2140. © 2014 Wiley Periodicals, Inc.
Suicidal ideation and suicide attempts among adult Danes

This study describes the prevalence of suicidal ideation and attempted suicide in a representative survey among adults in Denmark and gives the proportion of people reporting a suicide attempt that results in contact with the health care system. The data for the 1994 Danish national health interview survey were collected by personal interview and a self-administered questionnaire. A subsample of 1362 individuals participated in the part of the survey that addressed suicidal behaviour (64% of the random sample). The results show that 6.9% reported having had suicidal thoughts within the past year. Averaging across all age groups the overall prevalence of people reporting ever having made a suicide attempt was 3.4% and the one-year prevalence was 0.5%. Suicidal ideation was more prevalent among young people than among older people, whereas ever-attempted suicide showed no age gradient. Both suicidal ideation and ever-attempted suicide were more prevalent among economically inactive people (e.g. unemployed) and among unmarried or divorced people. We estimate that 50-60% of suicide attempts reported in a representative, national survey become known to the healthcare system.
Broken Bones, Bone Expediency Tools, and Bone Pseudotools: Lessons from the Blast Zone around Mount St. Helens, Washington

Criteria for recognizing technological and use-wear modifications have been used to identify “bone expediency tools” by archaeologists who analyze bone assemblages recovered from sites where butchering of animals took place. These criteria are here reviewed and then used to identify bone pseudotools in cervid bone assemblages completely formed by non-human processes and recovered from the blast zone around the Mount St. Helens volcano in Washington. The procedures for identifying stone tools and bone tools share similar strengths and weaknesses that seem to originate with the logical criteria used for recognizing modifications to the objects under study. Less equivocal inferential identifications of bone objects as “tools” can be facilitated by turning to the problem of constructing testable hypotheses about the way patterns of use-wear modifications to bone tools can be expected to appear in the archaeological record.
On-line estimation of SPSG parameters using discrete Kalman filters

Diverse estimators are available for on-line parametric identification; among them the discrete Kalman filter (DKF) is the most popular. It can be used in its traditional form (DTKF) for linear systems or in its extended form (DEKF) when the system is nonlinear. Another interesting application of the discrete Kalman filter is when it is biased (DBKF). The consideration of the bias makes it possible to reduce the mean squared error (MSE) between measured and estimated values of the system state variable. Therefore the normalized MSE (NMSE) can be diminished as well. Likewise, standard deviation (STD) between real and estimated values of the parameter can be limited in the tolerable percentage. All these situations are discussed in this paper where the system under study is a salient-pole synchronous generator (SPSG). MATLAB codes and Simulink models are implemented to validate the different DKFs. Finally comparative study between continuous and discrete KFs is provided and which reveals the benefit of the DKF.
An unusual cause of chest pain.

(CHEST 2004; 125:1536 –1538) A 33-year-old Turkish Cypriot man living in the United Kingdom was seen in the emergency department for chest pain. He was aware of the pain for some weeks, and on the day of hospital admission it worsened significantly and radiated to the left arm and back. It was constant, not pleuritic, and settled spontaneously over a period of 3 h. He smoked heavily and worked as a catering manager. His weight was stable with no other symptoms. His medical history was significant for abdominal injury sustained at the age of 5 years in a hand grenade incident that resulted in the death of his brother. He underwent laparotomy with a splenectomy at that time. Clinical examination revealed several abdominal wall scars but was otherwise unremarkable. The chest radiograph obtained in the emergency department demonstrated a large, left-sided, pleuralbased mass adjacent to the costal margin with several small ipsilateral pleural nodules adjacent to the heart (Fig 1). Contrast enhanced CT confirmed the presence of multiple enhancing pleural nodules and masses confined to the left hemithorax. The largest of these measured 2 cm by 9 cm and corresponded to the large pleural mass seen on the chest radiograph (Fig 2). In addition, there were several small enhancing nodules in the left upper quadrant of the abdomen and several small metallic fragments in the abdominal wall (Fig 3). The spleen was absent. This pleural-based mass remained unchanged on an 8-week follow-up chest radiograph. A 99m Tc sulfur colloid scan was obtained to confirm the diagnosis. Abnormal uptake was demonstrated within the pleural and abdominal nodules (Fig 4).
Protein phosphorylation and cardiac function: cholinergic-adrenergic interaction.

OBJECTIVE The muscarinic inhibition of cyclic AMP (cAMP) mediated contractile effects may not only be the result of a reduction in cAMP levels, but may also involve cAMP linked protein phosphorylation in the heart. To show that a cholinergic agonist may antagonise the effects of agents that induce the cAMP signalling sequence at the level of protein phosphorylation, the effect of carbachol was investigated on the in vivo phosphorylation of phospholamban, troponin I, and a 15 kDa protein during positive inotropic intervention with isoprenaline, forskolin, and a phosphodiesterase inhibitor in the isolated rat heart. METHODS The contractile activity of the heart was monitored during drug administration, and the hearts were freeze clamped for assay of protein phosphorylation and metabolites [cAMP, cyclic guanosine monophosphase (cGMP), cAMP dependent protein kinase (cA-PK), and phosphorylase a]. For estimation of the amount of in vivo phosphorylation, a "back phosphorylation" method was used. RESULTS Carbachol attenuated in vivo phosphorylation, induced by cAMP increasing drugs, of all the phosphoproteins studied, whereas the accumulation of cAMP was not affected or was decreased to 61% after exposure to isoprenaline alone. In addition, the cAMP mediated phosphorylase a activation was completely reversed by carbachol. similarly, sodium nitroprusside reduced phosphorylation as well as the contractile force of the investigated phosphoproteins. CONCLUSIONS These data confirm the reduction of cAMP mediated cardiac protein phosphorylation by carbachol. The cholinergic antagonism may primarily involve cellular target systems distal to sites of cAMP generation. The observed similarity in the cardiac response to carbachol and sodium nitroprusside indicates a role of cGMP in the antiadrenergic action of carbachol in the myocardium.
Can We Talk Now ? Technology Selection for an Intelligent Status Tracking System

A common problem in the workplace is determining how best to communicate with one another especially between mobile workers. This paper presents the results of a feasibility study and technology selection for a prototype intelligent status tracking system („CanWeTalkNow? ‟ or CWTN). CWTN is inspired by principles from Social Networking Services and makes use of various features from mobile devices (Apple iPhone initially) such as calendars and GPS to automatically populate status information so as to encourage uptake of CWTN. The Drools rule engine will be used to implement rules to determine the “best” means of communication between users. Server-side infrastructure would be deployed on Google App Engine, making use of free publically accessible infrastructure and authentication to address security concerns. Client-server communications will be via REST services using JSON format. The next phase of the project will be the development of the prototype using the selected technologies.
Constructing evolutionary algorithms for bilevel multiobjective optimization

We propose a procedure to construct evolutionary bilevel optimization algorithms based on recent theoretical advances that have established connections between bilevel optimization and multiobjective optimization. In the proposed procedure, a new algorithm is defined by integrating an evolutionary multiobjective optimization algorithm with a partial order that is compatible with bilevel optimization. The advantages of the procedure include the ability to harness the methodology of evolutionary multiobjective optimization for bilevel optimization and to systematically develop new algorithms for single-objective and multiobjective bilevel optimization. No regularity assumptions are used, which ensures maximal applicability of the optimization algorithms constructed by the procedure. The necessary theoretical foundation is developed and the steps of the procedure are illustrated with an example.
Abrogating chemotherapy-induced myelosuppression by recombinant granulocyte-macrophage colony-stimulating factor in patients with sarcoma: protection at the progenitor cell level.

PURPOSE The purpose of this study was to optimize the dose, schedule, and timing of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) administration that would best abrogate myelosuppression in patients with sarcoma. PATIENTS AND METHODS Sarcoma patients who had experienced severe myelosuppression after chemotherapy with Cytoxan (cyclophosphamide; Bristol-Myers Squibb Co, Evansville, IN), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and dacarbazine ([CyADIC], cycle 1) were eligible. GM-CSF was administered during a 14-day period until 1 week before cycle 2 of CyADIC and was resumed 2 days after cycle 2 completion. The schedule subsequently was modified to allow the earlier administration of GM-CSF in which CyADIC was compressed from 5 days to 3 days, and GM-CSF was administered immediately after the discontinuation of CyADIC in cycle 2. To understand better the impact of GM-CSF on bone marrow stem cells, the proliferative status of bone marrow progenitors was examined during treatment. To evaluate the effects of GM-CSF on effector cells, select functions of mature myeloid cells were also examined. RESULTS In the seven patients who were treated on the initial schedule, GM-CSF enhanced the rate of neutrophil recovery; however, severe neutropenia was not abrogated, By using the modified schedule in 17 patients, GM-CSF significantly reduced both the degree and the duration of neutropenia and myeloid (neutrophils, eosinophils, and monocytes) leukopenia. The mean neutrophil and mature myeloid nadir counts were 100/mm3 and 280/mm3 in cycle 1 and 290/mm3 and 1,540/mm3 in cycle 2 (P less than .01 and P less than .001). The duration of severe neutropenia (neutrophil count less than 500/mm3) and myeloid leukopenia (myeloid leukocyte count less than 1,000/mm3) were reduced from 6.2 and 6.8 days in cycle 1 to 2.8 and 1.4 days in cycle 2 (P less than .001). While 16 of 17 patients experienced severe myeloid leukopenia (less than 500/mm3) in cycle 1, only two of 17 experienced severe myeloid leukopenia in cycle 2 (P less than .001). Overall, severe neutropenia was abrogated in seven patients, which made them eligible for dose-escalation of Adriamycin. The fraction of cycling progenitors increased threefold on GM-CSF and decreased dramatically below the baseline within 1 day of GM-CSF discontinuation. CONCLUSIONS The modified schedule improved the beneficial effects of GM-CSF by enhancing myeloprotection and permitting dose-intensification of chemotherapy. The increased myeloid mass and quiescent progenitors at the initiation of chemotherapy suggest that GM-CSF might allow further chemotherapy dose-rate intensification by shortening the interval between courses.
Loss of sensory input increases the intrinsic excitability of layer 5 pyramidal neurons in rat barrel cortex

Development of the cortical map is experience dependent, with different critical periods in different cortical layers. Previous work in rodent barrel cortex indicates that sensory deprivation leads to changes in synaptic transmission and plasticity in layer 2/3 and 4. Here, we studied the impact of sensory deprivation on the intrinsic properties of layer 5 pyramidal neurons located in rat barrel cortex using simultaneous somatic and dendritic recording. Sensory deprivation was achieved by clipping all the whiskers on one side of the snout. Loss of sensory input did not change somatic active and resting membrane properties, and did not influence dendritic action potential (AP) backpropagation. In contrast, sensory deprivation led to an increase in the percentage of layer 5 pyramidal neurons showing burst firing. This was associated with a reduction in the threshold for generation of dendritic calcium spikes during high‐frequency AP trains. Cell‐attached recordings were used to assess changes in the properties and expression of dendritic HCN channels. These experiments indicated that sensory deprivation caused a decrease in HCN channel density in distal regions of the apical dendrite. To assess the contribution of HCN down‐regulation on the observed increase in dendritic excitability following sensory deprivation, we investigated the impact of blocking HCN channels. Block of HCN channels removed differences in dendritic calcium electrogenesis between control and deprived neurons. In conclusion, these observations indicate that sensory loss leads to increased dendritic excitability of cortical layer 5 pyramidal neurons. Furthermore, they suggest that increased dendritic calcium electrogenesis following sensory deprivation is mediated in part via down‐regulation of dendritic HCN channels.
MULTIPLE FORMS OF ENZYMES: TISSUE, ONTOGENETIC, AND SPECIES SPECIFIC PATTERNS.

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Molecular and prospective phenotypic characterization of a pedigree with familial Alzheimer's disease and a missense mutation in codon 717 of the β‐amyloid precursor protein gene

We present prospective clinical and neuropathologic details of a pedigree segregating familial Alzheimer's disease (FAD) associated with a mutation (G→A substitution) at nucleotide 2149 in exon 17 of the amyloid precursor protein (APP) gene. This mutation, which is predicted to cause the missense substitution of isoleucine for valine at codon 717 of APP, cosegregated perfectly with the FAD trait (lod score = 3.49 at = 0.00). The earliest clinical manifestations of the disease relate to deficits in memory function, cognitive processing speed, and attention to complex cognitive sets. These changes occurred in the absence of changes in nonmemory language and visuospatial functions. The neuropathologic features of FAD associated with the APP717 mutation in this family include severe neuronal loss, abundant neurofibrillary tangles, amyloid plaques, and amyloid angiopathy. These results provide independent confirmation that mutations in the APP gene are linked to the FAD trait in some families.
Therapeutics , Targets , and Chemical Biology EGFR-Activating Mutations Correlate with a Fanconi Anemia – likeCellular Phenotype That Includes PARP Inhibitor Sensitivity

In patients with lung cancer whose tumors harbor activating mutations in the EGF receptor (EGFR), increased responses to platinum-based chemotherapies are seen compared with wild-type cancers. However, the mechanisms underlying this association have remained elusive. Here, we describe a cellular phenotype of cross-linker sensitivity in a subset of EGFR-mutant lung cancer cell lines that is reminiscent of the defects seen in cells impaired in the Fanconi anemia pathway, including a pronouncedG2–Mcell-cycle arrest and chromosomal radial formation. We identified a defect downstream of FANCD2 at the level of recruitment of FAN1 nuclease and DNA interstrand cross-link (ICL) unhooking. The effect of EGFRmutation was epistatic with FANCD2. Consistent with the known role of FANCD2 in promoting RAD51 foci formation and homologous recombination repair (HRR), EGFR-mutant cells also exhibited an impaired RAD51 foci response to ICLs, but not to DNAdouble-strand breaks. EGFR kinase inhibition affected RAD51 foci formation neither in EGFR-mutant nor wild-type cells. In contrast, EGFR depletion or overexpression of mutant EGFR in wild-type cells suppressed RAD51 foci, suggesting an EGFR kinase-independent regulation of DNA repair. Interestingly, EGFR-mutant cells treated with the PARP inhibitor olaparib also displayed decreased FAN1 foci induction, coupled with a putative block in a late HRR step. As a result, EGFR-mutant lung cancer cells exhibited olaparib sensitivity in vitro and in vivo. Our findings provide insight into the mechanisms of cisplatin and PARP inhibitor sensitivity of EGFR-mutant cells, yielding potential therapeutic opportunities for further treatment individualization in this genetically defined subset of lung cancer. Cancer Res; 73(20); 6254–63. 2013 AACR.
Realization of a general LED lighting system based on a novel Power Line Communication technology

LED is regarded as one of the best potential light sources for next-generation lighting. In LED applications, Power Line Communication (PLC) is one of the popular communication techniques, which is used to control the complex lighting system. In this paper, a general LED lighting system based on a novel PLC technology, which is named as P-BUS, is presented. It is made up of four main parts: the master controller, the slave controller which controls the LED module, the DC-DC module and ancillary devices. The communication mode, protocol architecture, circuit structure and frame definition of P-BUS technique are covered and discussed. The control method of the system is introduced. Compared with other communication methods, the proposed P-BUS has many advantages such as fewer communication wires and components, simpler circuit topology and strong interference rejection. A prototype is given to show the advantages of the proposed solution and global system performance is also analyzed.
Evidence for sedimenting particles as the origin of the microbial community in a coastal marine sediment

The origin of the microbial community in a coastal marine sediment was investigated by examining the physical, chemical, and microbial characteristics of the sedimenting particles in Halifax Harbor, Canada. Particles were collected using particle interceptor traps placed on the sediment surface. The measured rate of particle accumulation compared to the sediment accumulation rate indicates that over 85 % of the dry weight of the particles is removed (including resuspension) or solubilized before deposition as sediment. Active decomposition is facilitated by the large microbial community present. The particles are heavily colonized by both bacteria (109 gl ) and protozoa (106 g' ) before they reach the sediment such that the microbial communities of the sinking particles and sediment-water interface are nearly indistinguishable. The particles and sediment are also similar with respect to community growth rates and carbon, nitrogen, and ATP content. Artificial sediment cores inserted into the sediment and left in place for 1 yr were colonized only to a depth of 4 cm. The data indicate that an extensive microbial community is already established on particles before they become sediment and that in situ sediment colonization is not necessary for the establishment of the sediment microbial community.
Impact of timing mismatch in multicarrier spectral-slicing transmission system using single coherent receiver

In this paper, we investigate the impact of timing mismatch among different sub-bands on the performance of a multicarrier spectral-slicing OFDM system with a single coherent receiver, both in the back-to-back configuration and long-distance fiber transmission. Two different timing mismatch models, namely linear timing error and Gaussian timing error, are introduced and investigated. Furthermore, the trade-off between nonlinear performance penalty and timing mismatch induced performance penalty under the impact of the number of subcarriers is investigated for the first time.