Miracle-dz/UniFAR-FTUs huggingface dataset:
DNA Damage Response Proteins and Oxygen Modulate Prostaglandin E2 Growth Factor Release in Response to Low and High LET Ionizing Radiation

Common cancer therapies employ chemicals or radiation that damage DNA. Cancer and normal cells respond to DNA damage by activating complex networks of DNA damage sensor, signal transducer, and effector proteins that arrest cell cycle progression, and repair damaged DNA. If damage is severe enough, the DNA damage response (DDR) triggers programed cell death by apoptosis or other pathways. Caspase 3 is a protease that is activated upon damage and triggers apoptosis, and production of prostaglandin E2 (PGE2), a potent growth factor that can enhance growth of surviving cancer cells leading to accelerated tumor repopulation. Thus, dying tumor cells can promote growth of surviving tumor cells, a pathway aptly named Phoenix Rising. In the present study, we surveyed Phoenix Rising responses in a variety of normal and established cancer cell lines, and in cancer cell lines freshly derived from patients. We demonstrate that IR induces a Phoenix Rising response in many, but not all cell lines, and that PGE2 production generally correlates with enhanced growth of cells that survive irradiation, and of unirradiated cells co-cultured with irradiated cells. We show that PGE2 production is stimulated by low and high LET ionizing radiation, and can be enhanced or suppressed by inhibitors of key DDR proteins. PGE2 is produced downstream of caspase 3 and the cyclooxygenases COX1 and COX2, and we show that the pan COX1–2 inhibitor indomethacin blocks IR-induced PGE2 production in the presence or absence of DDR inhibitors. COX1–2 require oxygen for catalytic activity, and we further show that PGE2 production is markedly suppressed in cells cultured under low (1%) oxygen concentration. Thus, Phoenix Rising is most likely to cause repopulation of tumors with relatively high oxygen, but not in hypoxic tumors. This survey lays a foundation for future studies to further define tumor responses to radiation and inhibitors of the DDR and Phoenix Rising to enhance the efficacy of radiotherapy with the ultimate goal of precision medicine informed by deep understanding of specific tumor responses to radiation and adjunct chemotherapy targeting key factors in the DDR and Phoenix Rising pathways.
Octopaminergic modulation of contrast sensitivity

Sensory systems adapt to prolonged stimulation by decreasing their response to continuous stimuli. Whereas visual motion adaptation has traditionally been studied in immobilized animals, recent work indicates that the animal's behavioral state influences the response properties of higher-order motion vision-sensitive neurons. During insect flight octopamine is released, and pharmacological octopaminergic activation can induce a fictive locomotor state. In the insect optic ganglia, lobula plate tangential cells (LPTCs) spatially pool input from local elementary motion detectors (EMDs) that correlate luminosity changes from two spatially discrete inputs after delaying the signal from one. The LPTC velocity optimum thereby depends on the spatial separation of the inputs and on the EMD's delay properties. Recently it was shown that behavioral activity increases the LPTC velocity optimum, with modeling suggesting this to originate in the EMD's temporal delay filters. However, behavior induces an additional post-EMD effect: the LPTC membrane conductance increases in flying flies. To physiologically investigate the degree to which activity causes presynaptic and postsynaptic effects, we conducted intracellular recordings of Eristalis horizontal system (HS) neurons. We constructed contrast response functions before and after adaptation at different temporal frequencies, with and without the octopamine receptor agonist chlordimeform (CDM). We extracted three motion adaptation components, where two are likely to be generated presynaptically of the LPTCs, and one within them. We found that CDM affected the early, EMD-associated contrast gain reduction, temporal frequency dependently. However, a CDM-induced change of the HS membrane conductance disappeared during and after visual stimulation. This suggests that physical activity mainly affects motion adaptation presynaptically of LPTCs, whereas post-EMD effects have a minimal effect.
Primary structure of the human laminin A chain. Limited expression in human tissues.

cDNA clones for the human laminin A chain were isolated from libraries prepared from human gestational choriocarcinoma cell line (JAR) RNA. They cover approx. 8 kb from the 5'-end of the 9.5 kb mRNA coding for this protein. Our clones contain 94 nucleotide residues for the 5'-end untranslated region and 7885 nucleotide residues of coding sequence. The complete human laminin A chain contains a 17-amino acid-residue signal peptide and a 3058-residue A chain proper. The human laminin A chain has a distinct domain structure with numerous internal cysteine-rich repeats. The large globular domain G has five repeats, which have several conserved glycine and cysteine residues. Furthermore the A chain contains 20 internal cysteine-rich repeats present in tandem arrays in three separate clusters (domains IIIa, IIIb and V). Domain I + II has a predicted continuous alpha-helical structure characterized by heptad repeats and three domains (IVa, IVb and VI) are predicted to contain a number of beta-sheets and coiled-coil structures. Northern-blot analysis was used to study the laminin A chain expression in the JAR cell line, full-term placenta and newborn-human tissues (kidney, spleen, lung, heart muscle, psoas muscle and diaphragm muscle). The expression was detectable in newborn-human kidney and JAR cell line only. The overall amino acid sequence identity between human and mouse is 76%. The human chain has only one Arg-Gly-Asp (RGD) sequence, which is located in the long arm within domain G, whereas the single RGD sequence in the mouse chain is located in the short arm in domain IIIb. The degree of identity between the human laminin A chain sequence and the sequence available for merosin [Ehrig, Leivo, Argraves, Ruoslahti & Engvall (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 3264-3268] is about 41% and when conservative substitutions are included the degree of similarity is 54%.
The multi-rule partial sequenced route query

Trip planning search (TPS) represents an important class of queries in Geographic Information Systems (GIS). In many real-world applications, TPS requests are issued with a number of constraints. Unfortunately, most of these constrained TPS cannot be directly answered by any of the existing algorithms. By formulating each restriction into rules, we propose a novel form of route query, namely the multi-rule partial sequenced route (MRPSR) query. Our work provides a unified framework that also subsumes the well-known trip planning query (TPQ) and the optimal sequenced route (OSR) query. In this paper, we first prove that MRPSR is NP-hard and then present three heuristic algorithms to search for near-optimal solutions for the MRPSR query. Our extensive simulations show that all of the proposed algorithms can answer the MRPSR query effectively and efficiently. Using both real and synthetic datasets, we investigate the performance of our algorithms with the metrics of the route distance and the response time in terms of the percentage of the constrained points of interest (POI) categories. Compared to the LORD-based brute-force solution, the response times of our algorithms are remarkably reduced while the resulting route length is only slightly longer than the shortest route.
Behavioral determinants of brushing young children's teeth: implications for anticipatory guidance.

PURPOSE The purposes of this study were to identify parents' motivation, support, and barriers to twice daily tooth-brushing of infants and preschool-age children and to discover new approaches to encourage this important health behavior. METHODS Qualitative interviews were conducted with 44 rural parents about tooth-brushing habits and experiences. RESULTS Forty of 44 parents reported that they had begun to brush their child's teeth; 24 (55%) reported brushing twice a day or more. Parents who brushed twice a day, vs less often, were more likely to describe specific skills to overcome barriers; they expressed high self-efficacy and held high self-standards for brushing. Parents who brushed their children's teeth less than twice daily were more likely to: hold false beliefs about the benefits of twice daily tooth-brushing; report little normative pressure or social support for the behavior; have lower self-standards; describe more external constraints; and offer fewer ideas to overcome barriers. CONCLUSIONS The findings support an integrative framework in which barriers and support for parents' twice daily brushing of their young children's teeth are multiple and vary among individuals. Knowledge of behavioral determinants specific to individual parents could strengthen anticipatory guidance and recommendations about at-home oral hygiene of young children.
The Cluster File System: Integration of High Performance Communication and I/O in Clusters

In this paper, we report on the experiences in designing a portable parallel file system for clusters. The file system offers to the applications an interface compliant with MPI-IO, the I/O interface of the MPI-2 standard. The file system implementation relies upon MPI for internal coordination and communication. This guarantees high performance and portability over a wide range of hardware and software cluster platforms. The internal architecture of the file system has been designed to allow rapid prototyping and experimentation of novel strategies for managing parallel I/O in a cluster environment. The discussion of the file system design and early implementation is completed with basic performance measures confirming the potential of the approach.
Acute neurologic dysfunction after high‐dose etoposide therapy for malignant glioma

Etopside (VP‐16–213) has been used in the treatment of many solid tumors and hematologic malignancies. When used in high doses and in conjunction with autologous bone marrow transplantation, this agent has activity against several treatment‐resistant cancers including malignant glioma. In six of eight patients (75%) who we treated for recurrent or resistant glioma, sudden severe neurologic deterioration occurred. This developed a median of 9 days after initiation of high‐dose etoposide therapy. Significant clinical manifestations have included confusion, papilledema, somnolence, exacerbation of motor deficits, and sharp increase in seizure activity. These abnormalities resolved rapidly after initiation of high‐dose intravenous dexamethasone therapy. In all patients, computerized tomographic (CT) brain scans demonstrated stability in tumor size and peritumor edema when compared with pretransplant scans. This complication appears to represent a significant new toxicity of high‐dose etoposide therapy for malignant glioma.
Chronic obstructive pulmonary disease: a slowly progressive cardiovascular disease masked by its pulmonary effects?

This editorial refers to ‘Airflow obstruction, lung function, and risk of incident heart failure: the Atherosclerotic Risk in Communities (ARIC) study’ by S.K. Agarwal et al., published in this issue on pages 414–422 and ‘Clinical characteristics and outcomes of hospitalized heart failure patients with systolic dysfunction and chronic obstructive pulmonary disease: findings from OPTIMIZE-HF’ by R.J. Mentz et al., published in this issue on pages 395–403.
Conditioned medium increases the rate of neurite elongation: separation of this activity from the substratum-bound inducer of neurite outgrowth

Heart cell-conditioned medium supports extensive neurite outgrowth from dissociated parasympathetic neurons of the chicken embryo ciliary ganglion. We have shown previously that neurite outgrowth in this system depends on the deposition of a substratum-conditioning factor from conditioned medium onto the polyornithine culture substratum. However, in the presence of only the substratum-bound material, neurite outgrowth is never as extensive as in whole conditioned medium. The present report demonstrates that a different and soluble component of conditioned medium is required to achieve the rates of neurite elongation normally observed in whole conditioned medium. This second component, while unable by itself to support neurite outgrowth, is able to increase the rate of neurite elongation approximately 3-fold within 30 to 60 min of its addition. This conclusion is based on direct time- lapse observations of the rate of elongation of individual neurites before and after the addition of fractions of conditioned medium previously depleted of the substratum-conditioning factor. Correlated with the effect of such fractions of conditioned medium on the rate of neurite elongation is a change in the morphology of the growth cones, which become larger and more spread. The activity of the soluble, elongation-promoting component of conditioned medium is nondialyzable and is sensitive to treatments known to affect proteins, such as repeated freeze-thawing, heating, and trypsinization. Fractions of conditioned medium which contain the elongation-promoting activity also contain all of the survival factor for parasympathetic neurons previously shown to be present in heart cell-conditioned medium. The methods described here represent a convenient new assay which we have used recently to demonstrate elongation-promoting factors with neuronal specificity in extracts of rat hippocampus.
Accelerometer Placement for Posture Recognition and Fall Detection

This paper presents an approach to fall detection with accelerometers that exploits posture recognition to identify postures that may be the result of a fall. Posture recognition as a standalone task was also studied. Nine placements of up to four sensors were considered: on the waist, chest, thigh and ankle. The results are compared to the results of a system using ultra wide band location sensors on a scenario consisting of events difficult to recognize as falls or non-falls. Three accelerometers proved sufficient to correctly recognize all the events except one(a slow fall). The location-based system was comparable to two accelerometers, except that it was able to recognize the slow fall because it resulted in lying outside the bed, whose location was known to the system. One accelerometer was able to recognize only the most clear-cut fall. Two accelerometers achieved over 90% accuracy of posture recognition, which was better than the location-based system. Chest and waist accelerometers proved best at both tasks, with the chest accelerometer having a slight advantage in posture recognition.
The Antiwear Behavior of TCP in Different Atmospheres and Different Base Stocks

TCP, as an antiwear and EP agent, has been studied in different hydrocarbon base stocks and in different atmospheres. It is much less effective in base stocks containing condensed-ring aromatics and in atmospheres of high relative humidity. Although the exact mechanism of TCP's action is still not clear, it does not appear to involve a prior hydrolysis to acid phosphate. Also, TCP is just as effective, relative to the base stock, in an inert atmosphere as in air. Presented as an American Society of Lubrication Engineers paper at the ASLE/ASME Lubrication Conference held in Houston, Texas, October 14–16, 1969
Selection of Candidate Reference Genes for Gene Expression Analysis in Kentucky Bluegrass (Poa pratensis L.) under Abiotic Stress

Kentucky bluegrass (Poa pratensis L.) belong to Gramineae and is widely used in lawns, golf courses, landscapes, and sport fields as a prominent cool-season grass. Gene expression patterns during different stages of plant development can provide clues toward the understanding of its biological functions. The selection and validation of reference genes are the first steps in any real-time quantitative PCR gene expression study. Therefore, suitable reference genes are necessary for obtaining reliable results in real-time quantitative PCR analyses of Kentucky bluegrass. In the present study, 9 candidate reference genes were chosen, and their expression stability in the leaves and roots of Kentucky bluegrass under different stresses (drought, salt, heat, and cold) were evaluated using the GeNorm, NormFinder, BestKeeper, and RefFinder programs. The results showed that the expression stability of the candidate reference genes was dependent on the experimental conditions. The combination of SAM with GAPDH was the most stable in leaves under salt stress and cold stress, while TUB combined with ACT or GAPDH was stable in roots under salt or cold stress, respectively. ACT and SAM maintained stable expression in drought-treated leaves, and GAPDH combined with ACT was stable in drought-treated roots. SAM and TUB exhibited stable expression in heat-treated leaves. ACT and RPL were stable in heat-treated roots. In addition, the expression patterns of PpFEH in response to drought and cold stress were used to confirm the reliability of the selected reference genes, indicating that the use of an inappropriate reference gene as the internal control will cause erroneous results. This work is the first study on the expression stability of reference genes in Kentucky bluegrass and will be particularly useful in the selection of stress-tolerance genes and the identification of the molecular mechanisms conferring stress tolerance in this species.
Activation of the Epstein-Barr virus replicative cycle by human herpesvirus 6

One common attribute of herpesviruses is the ability to establish latent, life-long infections. The role of virus-virus interaction in viral reactivation between or among herpesviruses has not been studied. Preliminary experiments in our laboratory had indicated that infection of Epstein-Barr virus (EBV) genome-positive human lymphoid cell lines with human herpesvirus 6 (HHV-6) results in EBV reactivation in these cells. To further our knowledge of this complex phenomenon, we investigated the effect of HHV-6 infection on expression of the viral lytic cycle proteins of EBV. Our results indicate that HHV-6 upregulates, by up to 10-fold, expression of the immediate-early Zebra antigen and the diffuse and restricted (85 kDa) early antigens (EA-D and EA-R, respectively) in both EBV producer and nonproducer cell lines (i.e., P3HR1, Akata, and Raji). Maximal EA-D induction was observed at 72 h post-HHV-6 infection. Furthermore, expression of late EBV gene products, namely, the viral capsid antigen (125 kDa) and viral membrane glycoprotein gp350, was also increased in EBV producer cells (P3HR1 and Akata) following infection by HHV-6. By using dual-color membrane immunofluorescence, it was found that most of the cells expressing viral membrane glycoprotein gp350 were also positive for HHV-6 antigens, suggesting a direct effect of HHV-6 replication on induction of the EBV replicative cycle. No expression of late EBV antigens was observed in Raji cells following infection by HHV-6, implying a lack of functional complementation between the deleted form of EBV found in Raji cells and the superinfecting HHV-6. The susceptibility of the cell lines to infection by HHV-6 correlated with increased expression of various EBV proteins in that B95-8 cells, which are not susceptible to HHV-6 infection, did not show an increase in expression of EBV antigens following treatment with HHV-6. Moreover, UV light-irradiated or heat-inactivated HHV-6 had no upregulating effect on the Zebra antigen or EA-D in Raji cells, indicating that infectious virus is required for the observed effects of HHV-6 on these EBV products. These results show that HHV-6, another lymphotropic human herpesvirus, can activate EBV replication and may thus contribute to the pathogenesis of EBV-associated diseases.
Effects of angiotensin II on the pericyte‐containing microvasculature of the rat retina

The aim of this study was to identify the mechanisms by which angiotensin II alters the physiology of the pericyte‐containing microvasculature of the retina. Despite evidence that this vasoactive signal regulates capillary perfusion by inducing abluminal pericytes to contract and thereby microvascular lumens to constrict, little is known about the events linking angiotensin exposure with pericyte contraction. Here, using microvessels freshly isolated from the adult rat retina, we monitored pericyte currents via perforated‐patch pipettes, measured pericyte calcium levels with fura‐2 and visualized pericyte contractions and lumen constrictions by time‐lapse photography. We found that angiotensin activates nonspecific cation (NSC) and calcium‐activated chloride channels; the opening of these channels induces a depolarization that is sufficient to activate the voltage‐dependent calcium channels (VDCCs) expressed in the retinal microvasculature. Associated with these changes in ion channel activity, intracellular calcium levels rise, pericytes contract and microvascular lumens narrow. Our experiments revealed that an influx of calcium through the NSC channels is an essential step linking the activation of AT1 angiotensin receptors with pericyte contraction. Although not required in order for angiotensin to induce pericytes to contract, calcium entry via VDCCs serves to enhance the contractile response of these cells. In addition to activating nonspecific cation, calcium‐activated chloride and voltage‐dependent calcium channels, angiotensin II also causes the functional uncoupling of pericytes from their microvascular neighbours. This inhibition of gap junction‐mediated intercellular communication suggests a previously unappreciated complexity in the spatiotemporal dynamics of the microvascular response to angiotensin II.
Matrix metalloproteinases and cardiovascular disease.

This editorial refers to ‘Prognostic value of tissue inhibitor of metalloproteinase-1 for cardiovascular death among patients with cardiovascular disease: results from the AtheroGene study’† by E. Lubos et al . , on page 150 Matrix metalloproteinases (MMPs) are a group of endopeptidases with capacity to cleave components of extracellular matrix, such as collagen and elastin.1 The ability to modify the tissues is important for several aspects of normal and abnormal physiology. Approximately 20 different MMPs are identified, and they can be subdivided into different groups according to which components of the extracellular matrix they degrade. MMPs are secreted in a latent proform and require activation for proteolytic activity. The activity of MMPs is normally low in healthy tissue, but the increased expression and activity of several MMPs in a range of pathological processes, such as inflammation and ventricular remodelling after myocardial infarction, might indicate that they play a role in the pathophysiology and progression of atherosclerotic disease. The activity of MMPs is tightly regulated at gene transcription level and is also regulated by their secretion in an inactive zymogen form that requires extracellular activation and co-secretion of the tissue inhibitors of metalloproteinases (TIMPs). 2 In healthy humans, MMP-2 and the … *Corresponding author. Tel: +46 8 585 800; fax: +46 8 585 867 10. E-mail address : stefan.agewall{at}karolinska.se