gebhart/patrepeval huggingface dataset:
Identification of -R-X-(X)-S/T-X3-S/T- as consensus sequence motif for autophosphorylation-dependent protein kinase. (1994)

To identify consensus sequence motif for a new family of protein kinase termed autophosphorylation-depend- ent protein serindthreonine kinase (auto-kinase), we have tested several synthetic peptides.The well established protein serinelthreonine kinases such as CAMPdependent protein kinase, Ca2+lcalmodulin-dependent protein kinase (CaM-kinase), and protein kinase C were found to be inactive toward phosphorylation of syntide-3 (RPFWASVPPSPSLSRHA), which turned out to be an excellent substrate only for auto-kinase, indicating that syntide-3 is a specific substrate for auto-kinase.Modification of syntide-3 to become RPRPASVPPSfl' did not affect the activity of auto-kinase.By contrast, autokinase became rather or almost inactive when the peptide was modified to become RPRPASVPPNGIFI"R/DI E/Y, indicating that amino acid number 10 in syntide-3 is crucial to the sequence motif recognized by auto-kinase.Phosphorylation of myelin basic protein (MBP) by autokinase revealed that auto-kinase predominantly phosphorylates MBP on one particular site with RT-T(p)HYGS as the phosphorylation site sequence, which could not be phosphorylated by any other reported MBP kinases including CAMP-dependent protein kinase, CaM-kinase, protein kinase C, mitogen-activated protein kinase, and kinase FNGSK-3.Taken together, the results provide initial evidence that -kg-X-(X)-Serfl'hr-X,-Ser/Thr-may represent a unique consensus sequence motif specifically recognized by autophosphorylationdependent protein kinase, a new family of multisubstratelmultifunctional protein serinelthreonine kinase.A new family of protein serinekhreonine kinase termed autophosphorylation-dependent protein kinase has been identified and characterized from mammalian nervous and non-nervous tissues (Yang et a l . ,1987a, 198713; Guo et al., 1993; Guo and Damuni, 1993).This protein kinase exists in an inactive form but can be activated in the presence of MgATP.The activation process involves an intramolecular autophosphorylation.The activated protein kinase becomes capable of phosphorylating several substrates including histones (Yang et al., 1987a), glycogen synthase (Yang et al., 1987b), protein phosphatase 2A (Guo et al., 1993; Guo and Damuni, 19931, and myelin basic
Flash photolysis study of a Friedel–Crafts alkylation. Reaction of the photogenerated 9-fluorenyl cation with aromatic compounds (1996)

A combination of flash photolysis and product analysis is employed to investigate the reaction of aromatic compounds (ArH) with the 9-fluorenyl cation (Fl+) photogenerated from 9-fluorenol in 1,1,1,3,3,3-hexafluoroisopropyl alcohol (HFIP). The availability of the photochemical route to Fl+ means that the reaction of a benzylic-type cation with ArH can be directly followed by flash photolysis. An additional feature with electron-rich ArH is that the cyclohexadienyl cation is observed to grow as Fl+ decays. Thus both cationic intermediates of a Friedel–Crafts alkylation are observed in the same experiment. The formation of the cyclohexadienyl cation is demonstrated to be reversible, or at least quasi-reversible, with the kinetic analysis furnishing absolute rate constants for the formation of this cation, as well as for its loss of H+ and Fl+. Values of kH:kD for benzene: [2H6]benzene and toluene: [2H8]toluene are ∼ 1.5 and demonstrate that Fl+ addition is at least partly reversible with these compounds as well. The Hammett ρ+ value obtained for a series of the less electron-rich ArH is –8, indicative of a transition state with considerable cyclohexadienyl cation character. Anisole shows a negative deviation from the Hammett correlation line, explained by the addition of Fl+ to ArH becoming encounter-controlled. This behaviour is dramatically illustrated in a comparison of data for Fl+ and Br2. For the less electron-rich ArH, rate constants for the two electrophiles are parallel. However, from m-xylene through pentamethylbenzene, the rate with Fl+ is unchanged, while the rate with Br2 increases over 1000-fold. The concept of encounter control with Fl+ is strongly supported by the absolute rate constants, which for the the electron-rich ArH are all in the range 1–2 × 109 dm3 mol–1 s–1, a magnitude typical of diffusion-controlled reactions. The electron-rich ArH also show no intermolecular selectivity since their reactions are encounter-controlled, but have a high intramolecular selectivity. It is suggested that a factor influencing the latter is the reversibility of formation of the cyclohexadienyl cation from the encounter complex.
Abnormal sensitization and temporal summation of second pain (wind-up) in patients with fibromyalgia syndrome (2001)

Although individuals with fibromyalgia syndrome (FMS) consistently report wide-spread pain, clear evidence of structural abnormalities or other sources of chronic stimulation of pain afferents in the involved body areas is lacking. Without convincing evidence for peripheral tissue abnormalities in FMS patients, it seems likely that a central pathophysiological process is at least partly responsible for FMS, as is the case for many chronic pain conditions. Therefore, the present study sought to obtain psychophysical evidence for the possibility that input to central nociceptive pathways is abnormally processed in individuals with long standing FMS. In particular, temporal summation of pain (wind-up) was assessed, using series of repetitive thermal stimulation of the glabrous skin of the hands. Although wind-up was evoked both in control and FMS subjects, clear differences were observed. The perceived magnitude of the sensory response to the first stimulus within a series was greater for FMS subjects compared to controls, as was the amount of temporal summation within a series. Within series of stimuli, FMS subjects reported increases in sensory magnitude to painful levels for interstimulus intervals of 2-5 s, but pain was evoked infrequently at intervals greater than 2 s for control subjects. Following the last stimulus in a series, after-sensations were greater in magnitude, lasted longer and were more frequently painful in FMS subjects. These results have multiple implications for the general characterization of pain in FMS and for an understanding of the underlying pathophysiological basis.
A high-sensitivity polyimide capacitive relative humidity sensor for monitoring anodically bonded hermetic micropackages (2001)

This paper presents the design, fabrication and complete characterization of a high-sensitivity polyimide-based humidity sensor for monitoring internal humidity level in anodically bonded hermetic micropackages. This capacitive sensor is 1 mm on a side and utilizes CU1512 polyimide film with a thickness in the range from 300 /spl Aring/ to 1200 /spl Aring/ sandwiched between two metal electrodes to sense moisture. The measured sensitivity for a sensor with a 1200-/spl Aring/-thick film is 0.86 pF/%RH, and for a 300-/spl Aring/-thick sensor is 3.4 pF/%RH. The sensor has been exposed to and survived a one-hour test at 400/spl deg/C, which is the temperature typically used to perform anodic bonding. Measurements show a drift of less than 1% RH at 50% RH and 37/spl deg/C for 48 h, and a hysteresis of <2% RH over a range from 30 to 70% RH for a 1200-/spl Aring/-thick polyimide film sensor. The measured breakdown voltage of the sensor (1200 /spl Aring/ thick) exceeds 20 V and agrees well with other results.
Agitation and pain assessment using digital imaging (2009)

Pain assessment in patients who are unable to verbally communicate with medical staff is a challenging problem in patient critical care. The fundamental limitations in sedation and pain assessment in the intensive care unit (ICU) stem from subjective assessment criteria, rather than quantifiable, measurable data for ICU sedation and analgesia. This often results in poor quality and inconsistent treatment of patient agitation and pain from nurse to nurse. Recent advancements in pattern recognition techniques using a relevance vector machine algorithm can assist medical staff in assessing sedation and pain by constantly monitoring the patient and providing the clinician with quantifiable data for ICU sedation. In this paper, we show that the pain intensity assessment given by a computer classifier has a strong correlation with the pain intensity assessed by expert and non-expert human examiners.
Multicenter Evaluation of a Sequence-Based Protocol for Subtyping Shiga Toxins and Standardizing Stx Nomenclature (2012)

When Shiga toxin-producing Escherichia coli (STEC) strains emerged as agents of human disease, two types of toxin were identified: Shiga toxin type 1 (Stx1) (almost identical to Shiga toxin produced by Shigella dysenteriae type 1) and the immunologically distinct type 2 (Stx2). Subsequently, numerous STEC strains have been characterized that express toxins with variations in amino acid sequence, some of which confer unique biological properties. These variants were grouped within the Stx1 or Stx2 type and often assigned names to indicate that they were not identical in sequence or phenotype to the main Stx1 or Stx2 type. A lack of specificity or consistency in toxin nomenclature has led to much confusion in the characterization of STEC strains. Because serious outcomes of infection have been attributed to certain Stx subtypes and less so with others, we sought to better define the toxin subtypes within the main Stx1 and Stx2 types. We compared the levels of relatedness of 285 valid sequence variants of Stx1 and Stx2 and identified common sequences characteristic of each of three Stx/Stx1 and seven Stx2 subtypes. A novel, simple PCR subtyping method was developed, independently tested on a battery of 48 prototypic STEC strains, and improved at six clinical and research centers to test the reproducibility, sensitivity, and specificity of the PCR. Using a consistent schema for nomenclature of the Stx toxins and stx genes by phylogenetic sequence-based relatedness of the holotoxin proteins, we developed a typing approach that should obviate the need to bioassay each newly described toxin and that predicts important biological characteristics.
A family of small inducible proteins secreted by leukocytes are members of a new superfamily that includes leukocyte and fibroblast-derived inflammatory agents, growth factors, and indicators of various activation processes. (1989)

We have isolated and characterized four cDNA clones that encode mRNA expressed more abundantly in Con A-activated mouse helper T cells than by resting T cells. One mRNA encoded a approximately 14-kDa protein with a hydrophobic N-terminal sequence and was abundantly expressed by the Th 2 subset of Th cells, but was not expressed by Th 1 cells. The remaining three mRNA encoded related approximately 8-kDa secreted proteins that are part of a family of small, secreted, and inducible mouse and human proteins. This family of proteins is itself distantly related to another family of growth and inflammatory factors that are associated with various lymphoid and fibroblast activation phenomena. One of the small, inducible, secreted proteins has a predicted mature N terminus identical to that of the previously described macrophage inflammatory protein.
MYC-driven accumulation of 2-hydroxyglutarate is associated with breast cancer prognosis (2013)

Metabolic profiling of cancer cells has recently been established as a promising tool for the development of therapies and identification of cancer biomarkers. Here we characterized the metabolomic profile of human breast tumors and uncovered intrinsic metabolite signatures in these tumors using an untargeted discovery approach and validation of key metabolites. The oncometabolite 2-hydroxyglutarate (2HG) accumulated at high levels in a subset of tumors and human breast cancer cell lines. We discovered an association between increased 2HG levels and MYC pathway activation in breast cancer, and further corroborated this relationship using MYC overexpression and knockdown in human mammary epithelial and breast cancer cells. Further analyses revealed globally increased DNA methylation in 2HG-high tumors and identified a tumor subtype with high tissue 2HG and a distinct DNA methylation pattern that was associated with poor prognosis and occurred with higher frequency in African-American patients. Tumors of this subtype had a stem cell-like transcriptional signature and tended to overexpress glutaminase, suggestive of a functional relationship between glutamine and 2HG metabolism in breast cancer. Accordingly, 13C-labeled glutamine was incorporated into 2HG in cells with aberrant 2HG accumulation, whereas pharmacologic and siRNA-mediated glutaminase inhibition reduced 2HG levels. Our findings implicate 2HG as a candidate breast cancer oncometabolite associated with MYC activation and poor prognosis.
A class of self-healing ring architectures for SONET network applications (2002)

Synchronous optical network (SONET) technology has made high-speed self-healing ring (SHR) architectures practical and economical. The SHR architectures can be divided into two basic classes: bidirectional SHR (B-SHR) and unidirectional SHR (U-SHR). The cost and capacity tradeoffs between B-SHRs and U-SHRs depend strongly on the application, the network size, and the demand pattern. B-SHRs with four fibers can be operated under today's operations environment without a significant change. However, U-SHRs using a path protection switching method may ease intervendor compatibility problems and can be implemented on a timely basis without changing the well-defined SONET APS protocol. The selection of appropriate SONET SHR architectures will depend on the operating telephone companies' economic analysis, emphasis on a multivendor environment, SHR implementation time frame, and standards progress on making change to support a bidirectional ring architecture.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Demonstration of local protein synthesis within dendrites using a new cell culture system that permits the isolation of living axons and dendrites from their cell bodies. (1992)

The presence of polyribosomes within dendrites suggests a capability for local dendritic protein synthesis. However, local synthesis is difficult to evaluate because of rapid somatodendritic protein transport. The present study describes a two-surfaced culture system that allowed the separation of living axons and dendrites from their cell bodies of origin. Because this system eliminates the transport of proteins produced in the cell body, it was possible to study the extent of dendritic protein synthesis directly. Hippocampal neurons were plated on a Nucleopore polycarbonate membrane that was mounted on a thick matrix of proteins (Matrigel) fixed on a coverslip. As the neurons grew, axons and dendrites grew through the membrane into the Matrigel. To evaluate local protein synthesis within dendrites, the membrane with the cell bodies was removed, leaving a dense array of transected dendrites and axons on the coverslip with few contaminant cell bodies. Absence of cell bodies was confirmed by staining with the nuclear stain Hoechst 33258. Coverslips with isolated neurites were pulse labeled with 3H-leucine for 30 min, and fixed for autoradiography to identify sites of protein synthesis. Autoradiographic analyses revealed that isolated dendrites (immunochemically identified using antibodies against MAP2) became heavily labeled, whereas axons exhibited little if any labeling. The labeling was essentially eliminated when the neurites were pulse labeled with 3H-leucine in the presence of puromycin, whereas labeling was affected only minimally by chloramphenicol. The puromycin-sensitive incorporation of 3H-leucine in dendrites demonstrates that the polyribosomes previously described are active in protein synthesis. This system will allow a characterization of synthetic activity within isolated neurites and provide a new approach to identifying proteins that are produced within dendrites.
Modelling spinal circuitry involved in locomotor pattern generation: insights from deletions during fictive locomotion (2006)

The mammalian spinal cord contains a locomotor central pattern generator (CPG) that can produce alternating rhythmic activity of flexor and extensor motoneurones in the absence of rhythmic input and proprioceptive feedback. During such fictive locomotor activity in decerebrate cats, spontaneous omissions of activity occur simultaneously in multiple agonist motoneurone pools for a number of cycles. During these 'deletions', antagonist motoneurone pools usually become tonically active but may also continue to be rhythmic. The rhythmic activity that re-emerges following a deletion is often not phase shifted. This suggests that some neuronal mechanism can maintain the locomotor period when motoneurone activity fails. To account for these observations, a simplified computational model of the spinal circuitry has been developed in which the locomotor CPG consists of two levels: a half-centre rhythm generator (RG) and a pattern formation (PF) network, with reciprocal inhibitory interactions between antagonist neural populations at each level. The model represents a network of interacting neural populations with single interneurones and motoneurones described in the Hodgkin-Huxley style. The model reproduces the range of locomotor periods and phase durations observed during real locomotion in adult cats and permits independent control of the level of motoneurone activity and of step cycle timing. By altering the excitability of neural populations within the PF network, the model can reproduce deletions in which motoneurone activity fails but the phase of locomotor oscillations is maintained. The model also suggests criteria for the functional identification of spinal interneurones involved in the mammalian locomotor pattern generation.
Antinociceptive Profile of Hodgkinsine (2000)

To further understand the mechanism of analgesic activity and structural requirements of pyrrolidinoindoline alkaloids identified in Psychotria colorata, we here report the analgesic activity of the trimer hodgkinsine on thermal and chemical models of analgesia. Results show that hodgkinsine produces a dose-dependent naloxone reversible analgesic effect in thermal models of nociception, suggesting that activation of opioid receptors participates in hodgkinsine's mode of action. Hodgkinsine shows a potent dose-dependent analgesic activity against capsaicin-induced pain, indicating the participation of NMDA receptors in hodgkinsine-induced analgesia. Such a dual mechanism of action may be of interest for developing innovative analgesics.
IL-13-Induced Airway Hyperreactivity During Respiratory Syncytial Virus Infection Is STAT6 Dependent (2001)

Airway damage and hyperreactivity induced during respiratory syncytial virus (RSV) infection can have a prolonged effect in infants and young children. These infections can alter the long-term function of the lung and may lead to severe asthma-like responses. In these studies, the role of IL-13 in inducing and maintaining a prolonged airway hyperreactivity response was examined using a mouse model of primary RSV infection. Using this model, there was evidence of significant airway epithelial cell damage and sloughing, along with mucus production. The airway hyperreactivity response was significantly increased by 8 days postinfection, peaked during days 10-12, and began to resolve by day 14. When the local production of Th1- and Th2-associated cytokines was examined, there was a significant increase, primarily in IL-13, as the viral response progressed. Treatment of RSV-infected mice with anti-IL-13 substantially inhibited airway hyperreactivity. Anti-IL-4 treatment had no effect on the RSV-induced responses. Interestingly, when IL-13 was neutralized, an early increase in IL-12 production was observed within the lungs, as was a significantly lower level of viral Ags, suggesting that IL-13 may be regulating an important antiviral pathway. The examination of RSV-induced airway hyperreactivity in STAT6(-/-) mice demonstrated a significant attenuation of the response, similar to the anti-IL-13 treatment. In addition, STAT6(-/-) mice had a significant alteration of mucus-producing cells in the airway. Altogether, these studies suggest that a primary factor leading to chronic RSV-induced airway dysfunction may be the inappropriate production of IL-13.
Paid Consulting in Ontario Colleges of Applied Arts and Technology (1992)

A survey of faculty participation in paid consulting arrangements in Ontario Colleges of Applied Arts and Technology reveals that 34% were involved in at least one project during a specified one-year period. There was significant variation in participation by division of academic appointment and by gender. The authors suggest that further research should be undertaken concerning the nature and role of paid consulting in community colleges. A number of basic questions are raised in an attempt to induce further study on this important topic.
Sensitivity and specificity: twin goals of proteomics assays. Can they be combined? (2013)

A major ambition of proteomics is the provision of assays that can diagnose disease and monitor therapies. These assays are required to be sensitive and specific for individual proteins, and in most cases to quantify more than one protein in the same sample. The two main technologies currently used for proteomics assays are based on mass spectrometry and panels of affinity molecules such as antibodies. In the first part of this review the most sensitive existing assays based on these technologies are described and compared with the gold standard of ELISA. Analytical sensitivity is defined and related to the limit of detection, and analytical specificity is defined and shown to depend on molecular proofreading steps, similar to those applied in living systems whenever there is a need for high fidelity. It is shown that at present neither mass spectrometry nor panels of affinity molecules offer the necessary combination of sensitivity and specificity required for multiplexed assays. In the second part of this review the growing numbers of assays that use additional proofreading steps to combine sensitivity with specificity are described. These include assays based on proximity ligation and slow off-rate modified aptamers. Finally the review considers what improvements might be possible in the near future, and concludes that further development of proteomics assays incorporating advanced proofreading steps are most likely to provide the necessary combination of sensitivity and specificity, without incurring high development costs.