Miracle-dz/UniFAR-FTUs huggingface dataset:
Phosphorylation of Endogenous Proteins by Adenosine 3′:5′‐Monophosphate‐Dependent Protein Kinase in Mouse Neuroblastoma Cells

Abstract: Increased intracellular adenosine 3′:5′‐monophosphate (cAMP) levels and activation of cAMP‐dependent protein kinases (ATP:protein phosphotransferase, EC 2.7.1.37) in vivo were correlated in mouse neuroblastoma cells grown in the presence of 1 mM‐6N.O2‐dibutyryl 3′:5′‐monophosphate (Bt2cAMP). The time course for activation showed that cAMP‐dependent protein kinases were activated by 30 min. A heat‐stable inhibitor protein inhibited a majority of activated cAMP‐dependent protein kinase. Activation of cAMP—dependent protein kinase caused additional phosphorylation of proteins when compared with untreated control cells, as demonstrated by endogenous phosphorylation of proteins in vitro using [γ‐32P]ATP and analysis by two—dimensional polyacrylamide gel electrophoresis. The phosphorylation data show selective phosphorylation of specific proteins by cAMP‐independent and cAMP‐dependent protein kinase. Among the proteins in the postmitochondrial supernatant fraction phosphorylated by cAMP‐dependent protein kinases, two proteins with a molecular weight of 43,000 were heavily phosphorylated. It is suggested that phosphorylation of cellular proteins by cAMP‐dependent protein kinases might be involved in the cAMP‐modulated biochemical changes in neuroblastoma cells.
Buckling profile of a thin rod embedded in a fractured biopolymer matrix

A thin elastic rod embedded in an elastic medium buckles into an exponentially decaying short wavelength profile under compressive loading beyond a critical value. In this study, we report a combined experimental and theoretical investigation of the buckling profile of a thin elastic rod embedded in an elastic gelatin biopolymer network when fracture of the network happens. Prior models have predicted the transverse displacement of the rod under a compressive force in a uniform viscoelastic medium, but it is assumed that the deformation is small and elastic. Thus they cannot capture the main features where there is plastic deformation. Here we use the energy principle to interpret and predict the buckling profile of the superelastic thin rod after fracture of the surrounding gelatin happens due to excessive lateral displacement of the rod in a gelatin medium. Preliminary results indicate that the modeling framework can be used to predict the buckling profile in experiments with certain improvements.
Identifying challenges of change impact analysis for software projects

Project changes are difficult since the impacts of the changes are not readily known in advance. Changing customer needs and technology are driving factors influencing project evolution. Consequently, there is a need to assess the impact of these changes on existing software systems. For safety-critical system, the changes can even introduce hazards to bug down the system, particularly for larger systems, it quickly become difficult to comprehend what impact of requirement change might have on the overall system or parts of the system. Impact analysis is identifying the potential impact of disruption caused by a change to one or more components in the requirement on other components. The significant behind impact analysis is to identify requirement elements that may be affected by the change. However, this paper deals with impact analysis approach during project changes and identifies issues of impact analysis and where change impact analysis applied during software development projects.
The five pillars of pain management.

SUMMARY The last 10-15 years have seen an increase in the use of opioids in chronic noncancer pain. The consequences of increased use only gradually became apparent. The five pillars of pain management were developed as a convenient mechanism for the management of chronic noncancer pain and to allow for a comprehensive approach to patient care. The mnemonic ADDOP was developed: 'A' pillar one - assessment including risk and symptom assessment; 'D' pillar two - defining and treating the underlying condition; 'D' pillar three - making a pain diagnosis and going down an established path of treatment; 'O' pillar four - other treatments embracing the biopsychosocial model and treating co-morbidities; 'P' pillar five - patient self-management, personal responsibility and patient education. Adopting this method will prevent the practitioner and the patient from being drowned in the 'swamp of pain management'. If in doubt, the five pillars should be revisited and reviewed in any patient in which problems arise. This article is a commentary based on the author's clinical experience and observations. The recommendations and generalizations are not based on a systemic review of controlled trials. The article adds to the research-based recommendations that have already been published (i.e., the 2010 Canadian guidelines) by highlighting some of the issues and events surrounding the use of opioids for chronic noncancer pain and the thinking that went into the need to develop such guidelines. However, the Canadian Guidelines address the opiate issue only. They do not look at other aspects of pain management. By contrast, the five pillars of pain management provides a framework for the use of other modalities, other medications and other nonpharmacologic treatment, and self-management techniques. The five pillars represent a counterpoint, and emphasizes the need for risk assessment and a multipronged, holistic approach to the patient with chronic pain.
1,3-Butadiene: III. Assessing carcinogenic modes of action

1,3-Butadiene (BD) is a multisite carcinogen in laboratory rodents following lifetime exposure, with greater potency in the mouse than the rat, and is associated with an increase in leukemia mortality in highly exposed workers. Species differences in the formation of reactive metabolites underlie observed species differences in sensitivity to the carcinogenic effects of BD. The modes of action (MOAs) for human leukemia and rodent tumors are both likely related to mutagenic potencies of one or more of these metabolites. However, differences in the nature of genotoxic lesions associated with human leukemia and rodent tumors, along with their implications for risk assessment, require that they be discussed separately. The MOAs for BD are assessed in this review using the modified Hill criteria and human relevance framework. Key events in MOAs for human and rodent cancers are identified, along with important species differences and sources of nonlinearity for each event that can affect extrapolations made from high- to low-dose exposures. Because occupational exposures to BD have also included co-exposures to styrene and dimethyldithiocarbamide (DMDTC), potential interactions with BD carcinogenicity are also discussed. The MOAs for BD carcinogenesis will be used to guide key decisions made in the quantitative cancer dose-response assessment.
Generation of Virulence Factor Variants in Staphylococcus aureus Biofilms

ABSTRACT Several serious diseases are caused by biofilm-associated Staphylococcus aureus. Colonial variants occur in biofilms of other bacterial species, and S. aureus variants are frequently isolated from biofilm-associated infections. Thus, we studied the generation of variants with altered expression of virulence factors in S. aureus biofilms. We observed that the number of variants found in biofilms, as measured by hemolytic activity, varied for different strains. Further study of hemolytic activity and signaling by the accessory gene regulator (Agr) quorum-sensing system in one S. aureus strain revealed three primary biofilm subpopulations: nonhemolytic (Agr deficient), hemolytic (Agr positive), and hyperhemolytic (also Agr positive). The nonhemolytic variant became the numerically dominant subpopulation in the biofilm. The nonhemolytic variant phenotype was stable and heritable, indicating a genetic perturbation, whereas the hyperhemolytic phenotype was unstable, suggesting a phase variation. Transcription profiling revealed that expression of the agr locus and many extracellular virulence factors was repressed in the nonhemolytic variant. Expression of the agr-activating gene, sarU, was also repressed in the nonhemolytic variant, suggesting one potential regulatory pathway responsible for the Agr-deficient phenotype. We suggest that the development of these variants in biofilms may have important clinical implications.
Synthesis of controllers for symmetric systems

This article deals with supervisory control problem for coloured Petri (CP) nets. Considering a CP-net, we build a condensed version of the ordinary state-space, namely the symbolic reachability graph (SRG). This latter graph allows to cope with state-space explosion problem for symmetric systems. The control specification can be expressed in terms of either forbidden states or forbidden sequences of transitions. According to these specifications, we derive the controller by applying the theory of regions on the basis of the SRG. Thanks to expressiveness power of CP-nets, the obtained controller to be connected to the plant model is reduced to one single place.
Impressions of neurology and neurosurgery in the People's Republic of China

During July, 1979, the authors visited the neurological and neurosurgical services of eight major hospitals and associated medical schools in Peking, Tientsin, and Shanghai, and viewed many of their teaching and research facilities. From these visits and our discussions with the staffs of these units, we came away with the impressions reported here.
AIT-082 Is Neuroprotective against Kainate-Induced Neuronal Injury in Rats

4-[[3-(1,6-dihydro-6-oxo-9-purin-9-yl)-1-oxopropyl]amino]benzoic acid (AIT-082) is an hypoxanthine derivative that stimulates in vitro neurite outgrowth and the production of adenosine and neurotrophins from astrocytes. These effects may predict an in vivo neuroprotective activity of the drug. Thus, we evaluated whether AIT-082 protected against a long-term excitotoxicity of hippocampal neurons following status epilepticus induced in rats by i.p. injection of kainate (12 mg/kg). The epileptogenic effect of kainate was evaluated by monitoring behavioral signs and by electroencephalographic (EEG) recording (80% of the animals showed status epilepticus with a latency of 96.8 +/- 7.4 min starting from the injection). In surviving rats (40% of the injected animals) the neurotoxic effect was evaluated by measuring glutamic acid decarboxylase (GAD) activity, as an index of loss of hippocampal GABAergic neurons, by evaluating the body weight after 7 days and by histological examination of hippocampi. The GAD activity was reduced by 44 +/- 8%, and neuronal loss (about 70%) was found in the CA3c, the CA1 area, and in the dentate gyrus. A single dose of diazepam (20 mg/kg; i.p., 20 min before the kainate injection) almost completely inhibited both seizures and neurotoxicity, ensuring survival of animals. AIT-082 (60 mg/kg/day; i.p., for 7 days, starting from 20 min before the kainate injection) did not modify the seizures caused by kainate but, like diazepam, it decreased kainate-induced mortality, the reduction of GAD activity, and the loss of hippocampal neurons. These data confirm that AIT-082 is of potential interest for the experimental therapy of neurodegenerative disorders.
ATX-101 (deoxycholic acid injection) for reduction of submental fat

ABSTRACT Introduction: The shape and contour of the chin and neck play an important role in facial esthetics. As such, excess fat within the submental area (double chin) can negatively affect facial esthetics and body image. Common treatments for submental contouring include invasive procedures such as surgical rejuvenation and targeted liposuction. Energy devices (lasers, radiofrequency, and ultrasound) may be used to improve submental skin laxity while cryolipolysis was recently cleared in the United States for use in the submental area. However, ATX-101 (deoxycholic acid injection) is the only injectable drug approved in the United States and Canada for reduction of submental fat. Areas covered: The efficacy and safety of ATX-101 have been extensively evaluated in a global clinical development program including multiple Phase I/II studies and four large Phase III trials. Available data from ATX-101 trials are reviewed. Expert commentary: Injectables have been well established for facial rejuvenation. Extending injectable treatment into the chin and neck is a major advance for nonsurgical cosmetic correction. Overall, the evidence supports ATX-101 as a safe and effective, minimally invasive treatment alternative for reduction of submental fat that will provide a major tool for the esthetic physician.
Regulation of Expression of Cloned Bacteriophage T4 Late Gene 23

The parameters governing the activity of the cloned T4 gene 23, which codes for the major T4 head protein, were analyzed. Suppressor-negative bacteria carrying wild-type T4 gene 23 cloned into plasmid pCR1 or pBR322 were infected with T4 gene 23 amber phage also carrying mutations in the following genes: (i) denA and denB (to prevent breakdown of plasmid DNA after infection) and (ii) denA, denB, and, in addition, 56 (to generate newly replicated DNA containing dCMP) and alc/unf (because mutations in this last gene allow late genes to be expressed in cytosine-containing T4 DNA). Bacteria infected with these phage were labeled with 14C-amino acids at various times after infection, and the labeled proteins were separated by one-dimensional gel electrophoresis so that the synthesis of plasmid-coded gp23 could be compared with the synthesis of other, chromosome-coded T4 late proteins. We analyzed the effects of additional mutations that inactivate DNA replication proteins (genes 32 and 43), an RNA polymerase-binding protein (gene 55), type II topoisomerase (gene 52), and an exonuclease function involved in recombination (gene 46) on the synthesis of plasmid-coded gp23 in relation to chromosome-coded T4 late proteins. In the denA:denB:56:alc/unf genetic background, the phage chromosome-borne late genes followed the same regulatory rules (with respect to DNA replication and gp55 action) as in the denA:denB genetic background. The plasmid-carried gene 23 was also under gp55 control, but was less sensitive than the chromosomal late genes to perturbations of DNA replication. Synthesis of plasmid-coded gp23 was greatly inhibited when both the type II T4 topoisomerase and the host's DNA gyrase are inactivated. Synthesis of gp23 was also substantially affected by a mutation in gene 46, but less strongly than in the denA:denB genetic background. These observations are interpreted as follows. The plasmid-borne T4 gene 23 is primarily expressed from a late promoter. Expression of gene 23 from this late promoter responds to an activation event which involves some structural alteration of DNA. In these respects, the requirements for expressing the plasmid-borne gene 23 and chromosomal late genes are very similar (although in the denA:denB:56:alc/unf genetic background, there are significant quantitative differences). For the plasmid-borne gene 23, activation involves the T4 gp46, a protein which is required for DNA recombination. However, for the reasons presented in the accompanying paper (Jacobs et al., J. Virol. 39:31-45, 1981), we conclude that the activation of gene 23 does not require a complete breakage-reunion event which transposes that gene to a later promoter on the phage chromosome. Ways in which gp46 may actually be involved in late promoter activation on the plasmid are discussed.
Histopathological findings in chronic tendon disorders

Tendon injuries and other tendon disorders represent a common diagnostic and therapeutic challenge in sports medicine, resulting in chronic and long‐lasting problems. Tissue degeneration is a common finding in many sports‐related tendon complaints. In the great majority of spontaneous tendon ruptures, chronic degenerative changes are seen at the rupture site of the tendon (1). Systemic diseases and diseases specifically deteriorating the normal structure of the tendon (i.e. foreign bodies, and metabolic, inherited and infectious tendon diseases) are only rarely the cause of tendon pathology. Inherited diseases, such as various hereditary diseases with disturbed collagen metabolism and characteristic pathological structural alterations (Ehlers‐Danlos syndrome, Marfani syndrome, homocystinuria (ochronosis)), represent approximately 1% of the causes of chronic tendon complaints (2), whereas foreign bodies are somewhat more common and are found in less than 10% of all chronic tendon problems (1). Rheumatoid arthritis and sarcoidosis are typical systemic diseases that cause chronic inflammation in tendon and peritendinous tissues. Altogether, these ‘specific’disorders represented less than 2% of the pathological alterations found in the histological analysis of more than 1000 spontaneously ruptured tendons (1, 3, 4). In this material, degenerative changes were seen in a great majority of the tendons, indicating that aspontaneous tendon rupture is a typical clinical end‐state manifestationof a degenerative process in the tendon tissue. The role of overuse in the pathogenesis of chronic tendon injuries and disorders is not completely understood. It has been speculated that when tendon is overused, it becomes fatigued and loses its basal reparative ability, the repetitive microtraumatic processes thus overwhelming the ability of the tendon cells to repair the fiber damage. The intensive repetitive activity, which often is eccentric by nature, may lead to cumulative microtrauma which further weakens the collagen cross‐linking, non‐collagenous matrix, and vascular elements of the tendon. Overuse has also been speculated to cause chronic tendon problems, by disturbing the micro‐ and macrovasculature of the tendon and resulting in insufficiency in the local blood circulation. Decreased blood flow simultaneous with an increased activity may result in local tissue hypoxia, impaired nutrition and energy metabolism, and together these factors are likely to play an important role in the sequence of events leading to tendon degeneration (4). A sedentary lifestyle has been proposed as a main reason for poor basal circulation of the tendon, and presumably is at least partly responsible for the high number of tendon problems in people with a sedentary lifestyle who occasionally take part in high physical activity sports events.
Quantitative Comparison of Growth-associated Protein-43 and Substance P in Ulcerative Colitis

The aim of this study was to compare immunoreactivities for substance P with other enteric neuropeptides and GAP-43, a general marker for enteric nerves, in normal human colon and in different stages of ulcerative colitis. Tissue samples from normal colon and regions of ulcerative colitis colon were obtained at surgery and immunostained for substance P, vasoactive intestinal polypeptide (VIP), somatostatin, calcitonin gene-related peptide (CGRP), enkephalin, galanin, GAP-43, and neuron-specific enolase (NSE). Visual examination and semiquantitative analysis revealed a clear increase in the immunoreactivity for substance P in ulcerative colitis, whereas no differences were observed in the distribution of the other peptides. Therefore, quantitative analysis was performed only for substance P immunoreactivity in the lamina propria, circular muscle layer, and myenteric ganglia. In the lamina propria, the score of total intensity of substance P immunoreactivity was 0.55 ± 0.15 (mean ± SEM) in normal colon, 1.30 ± 0.35 (p = 0.087) in least affected colon, and 2.22 ± 0.28 (p < 0.001) in moderately affected colon, whereas no significant differences were observed in immunoreactivities for GAP-43. Similar results were obtained for the mean substance P- or GAP-43-immunoreactive area. In the circular muscle layer, the number, density, total intensity, and perimeter of substance P- and GAP-43-immunoreactive fibers were essentially similar in normal colon, and in mild or moderately affected colon. We conclude that ulcerative colitis does not change the density of gut innervation as a whole. However, the density of substance P-containing nerves is specifically increased, probably due to increased peptide synthesis leading to better visibility of the fibers.
Limit Cycle Oscillation Reduction for Digital Low Dropout Regulators

The digital low dropout regulator (D-LDO) has drawn significant attention recently for its low-voltage operation and process-scalability. However, the D-LDO inherently suffers from limit cycle oscillation (LCO). To address this issue, the modes and amplitudes of LCO are calculated in this work and verified by SPICE simulation in a 65-nm CMOS process. An LCO reduction technique for the D-LDO is then proposed, by adding two unit power transistors in parallel with the main power MOS array as a feedforward path. This technique sets the LCO mode to 1 and effectively reduces the ripple amplitude for a wide (0.5-20 mA) load current range. When compared with the dead-zone scheme, this technique minimizes LCO with negligible circuit complexity and design difficulty.
Specification of SUMO1- and SUMO2-interacting Motifs*

SUMO proteins are ubiquitin-related modifiers implicated in the regulation of gene transcription, cell cycle, DNA repair, and protein localization. The molecular mechanisms by which the sumoylation of target proteins regulates diverse cellular functions remain poorly understood. Here we report isolation and characterization of SUMO1- and SUMO2-binding motifs. Using yeast two-hybrid system, bioinformatics, and NMR spectroscopy we define a common SUMO-interacting motif (SIM) and map its binding surfaces on SUMO1 and SUMO2. This motif forms a β-strand that could bind in parallel or antiparallel orientation to the β2-strand of SUMO due to the environment of the hydrophobic core. A negative charge imposed by a stretch of neighboring acidic amino acids and/or phosphorylated serine residues determines its specificity in binding to distinct SUMO paralogues and can modulate the spatial orientation of SUMO-SIM interactions.
Estimating the electromechanical oscillation characteristics of power system based on measured ambient data utilizing stochastic subspace method

Estimating low-frequency oscillation modes and the corresponding mode shapes based on ambient data from WAMS measurements has a promising prospect of application in power system analysis and control. The present approaches estimate the modes and mode shapes respectively, which greatly reduce the computational efficiency. Besides, there is no good solution for the problem of discriminating real modes from the spurious ones caused by numerical error. A method based on stochastic subspace method was proposed in this paper. By choosing the angle measurements of all buses as input signals for the method, the modes and simultaneously the corresponding mode shapes of any bus can be estimated conveniently. By introducing the idea of reference channels, the computation complexity was substantially reduced without decreasing the accuracy. Stabilization diagrams technique was introduced to discriminate the real modes from the spurious ones. The test case based on the IEEE-118 system indicated that the method proposed is satisfying in respect of both computational efficiency and accuracy of results.