Miracle-dz/UniFAR-FTUs huggingface dataset:
Discovery of Escherichia coli methionyl-tRNA synthetase mutants for efficient labeling of proteins with azidonorleucine in vivo

Incorporation of noncanonical amino acids into cellular proteins often requires engineering new aminoacyl-tRNA synthetase activity into the cell. A screening strategy that relies on cell-surface display of reactive amino acid side-chains was used to identify a diverse set of methionyl-tRNA synthetase (MetRS) mutants that allow efficient incorporation of the methionine (Met) analog azidonorleucine (Anl). We demonstrate that the extent of cell-surface labeling in vivo is a good indicator of the rate of Anl activation by the MetRS variant harbored by the cell. By screening at low Anl concentrations in Met-supplemented media, MetRS variants with improved activities toward Anl and better discrimination against Met were identified.
Detecting Cortical Spreading Depolarization with Full Band Scalp Electroencephalography: An Illusion?

Introduction There is strong evidence suggesting detrimental effects of cortical spreading depolarization (CSD) in patients with acute ischemic stroke and severe traumatic brain injury. Previous studies implicated scalp electroencephalography (EEG) features to be correlates of CSD based on retrospective analysis of EEG epochs after having detected “CSD” in time aligned electrocorticography. We studied the feasibility of CSD detection in a prospective cohort study with continuous EEG in 18 patients with acute ischemic stroke and 18 with acute severe traumatic brain injury. Methods Full band EEG with 21 silver/silver chloride electrodes was started within 48 h since symptom onset. Five additional electrodes were used above the infarct. We visually analyzed all raw EEG data in epochs of 1 h. Inspection was directed at detection of the typical combination of CSD characteristics, i.e., (i) a large slow potential change (SPC) accompanied by a simultaneous amplitude depression of >1Hz activity, (ii) focal presentation, and (iii) spread reflected as appearance on neighboring electrodes with a delay. Results In 3,035 one-hour EEG epochs, infraslow activity (ISA) was present in half to three quarters of the registration time. Typically, activity was intermittent with amplitudes of 40–220 µV, approximately half was oscillatory. There was no specific spatial distribution. Relevant changes of ISA were always visible in multiple electrodes, and not focal, as expected in CSD. ISA appearing as “SPC” was mostly associated with an amplitude increase of faster activities, and never with suppression. In all patients, depressions of spontaneous brain activity occurred. However, these were not accompanied by simultaneous SPC, occurred simultaneously on all channels, and were not focal, let alone spread, as expected in CSD. Conclusion With full band scalp EEG in patients with cortical ischemic stroke or traumatic brain injury, we observed various ISA, probably modulating cortical excitability. However, we were unable to identify unambiguous characteristics of CSD.
The Pathogen of Frogs Amphibiocystidium ranae Is a Member of the Order Dermocystida in the Class Mesomycetozoea

ABSTRACT The pathogen of frogs Amphibiocystidium ranae was recently described as a new genus. Due to its spherical shape, containing hundred of endospores, it was thought to be closely related to the pathogens of fish, mammals, and birds known as Dermocystidium spp. , Rhinosporidium seeberi, and Sphaerothecum destruens in the Mesomycetozoea, but further studies were not conducted to confirm this relationship. To investigate its phylogenetic affinities, total genomic DNA was extracted from samples collected from infected frogs containing multiple cysts (sporangia) and endospores. The universal primers NS1 and NS8, used to amplify the 18S small-subunit rRNA by PCR, yielded ≈1,770-bp amplicons. Sequencing and basic local alignment search tool analyses indicated that the 18S small-subunit rRNA of A. ranae from both Rana esculenta and Rana lessonae was closely related to all of the above organisms. Our phylogenetic analysis placed this pathogen of frogs as the sister group to the genus Dermocystidium and closely related to Rhinosporidium. These data strongly supported the placement of the genus Amphibiocystidium within the mesomycetozoeans, which is in agreement with the phenotypic features that A. ranae shares with the other members of this class. Interestingly, during this study Dermocystidium percae did not group within the Dermocystidium spp. from fish; rather, it was found to be the sister group to Sphaerothecum destruens. This finding suggests that D. percae could well be a member of the genus Sphaerothecum or perhaps represents a new genus.
Supporting workers with disabilities: a scoping review of the role of human resource management in contemporary organisations

This is a scoping review of literature on human resource management (HRM) and management practice that impacts on workers with physical, mental health and intellectual disabilities, employed or entering paid employment. The aim is to illuminate the use of HRM practices, managerial attitudes and employee outcomes in the disability literature. The methodological research framework commenced with seven databases and was supported with evidenced-based literature to find three main themes. Themes highlight the management and employer support for workers with disabilities, discrimination and attitudes towards employment of this cohort of workers, and performance and employment outcomes. As governments around the world seek to reduce welfare costs and increase the employment of people with disabilities this paper is timely. Overall, the paper contributes to a dearth of literature on the management of people with disabilities at the workplace to unpack the key barriers, challenges and trends, and develop a comprehensive research agenda.
A Highly Ca 2 (cid:1) -sensitive Pool of Granules Is Regulated by Glucose and Protein Kinases in Insulin-secreting INS-1 Cells

We have used membrane capacitance measurements and carbon-ﬁber amperometry to assay exocytosis triggered by photorelease of caged Ca 2 (cid:1) to directly measure the Ca 2 (cid:1) sensitivity of exocytosis from the INS-1 insulin-secreting cell line. We ﬁnd heterogeneity of the Ca 2 (cid:1) sensitivity of release in that a small proportion of granules makes up a highly Ca 2 (cid:1) -sensitive pool (HCSP), whereas the bulk of granules have a lower sensitivity to Ca 2 (cid:1) . A substantial HCSP remains after brief membrane depolarization, suggesting that the majority of granules with high sensitivity to Ca 2 (cid:1) are not located close to Ca 2 (cid:1) channels. The HCSP is enhanced in size by glucose, cAMP, and a phorbol ester, whereas the Ca 2 (cid:1) -sensitive rate constant of exocytosis from the HCSP is unaffected by cAMP and phorbol ester. The effects of cAMP and phorbol ester on the HCSP are mediated by PKA and PKC, respectively, because they can be blocked with speciﬁc protein kinase inhibitors. The size of the HCSP can be enhanced by glucose even in the presence of high concentrations of phorbol ester or cAMP, suggesting that glucose can increase granule pool sizes independently of activation of PKA or PKC. The effects of PKA and PKC on the size of the HCSP are not additive, suggesting they converge on a common mechanism. Carbon-ﬁber amperometry was used to assay quantal exocytosis of serotonin (5-HT) from insulin-containing granules following preincubation of INS-1 cells with 5-HT and a precursor. The amount or kinetics of release of 5-HT from each granule is not signiﬁcantly different between granules with higher or lower sensitivity to Ca 2 (cid:1) , suggesting that granules in these two pools do not differ in morphology or fusion kinetics. We conclude that glucose and second messengers can modulate insulin release triggered by a high-afﬁnity Ca 2 (cid:1) sensor that is poised to respond to modest, global elevations of [Ca 2 (cid:1) ] i .
Near-Optimal Approximation Rates for Distribution Free Learning with Exponentially, Mixing Observations

This paper derives the rate of convergence for the distribution free learning problem when the observation process is an exponentially strongly mixing (α-mixing with an exponential rate) Markov chain. If {z<sub>k</sub>}<sub>K=1</sub><sup>∞</sup> = {(x<sub>k</sub>, y<sub>k</sub>)}<sub>k=1</sub><sup>∞</sup> ⊂ x × Y ≡ Z is an exponentially strongly mixing Markov chain with stationary measure ρ, it is shown that the empirical estimate f<sub>z</sub> that minimizes the discrete quadratic risk satisfies the bound E<sub>z∈Z</sub><sup>m</sup> (∥ f<sub>ρ</sub> - f<sub>z</sub> ∥<sub>L2(ρx)</sub>) ≤ C (lna/a)<sup>r/(2r+1)</sup> where E<sub>z∈Z</sub><sup>m</sup> (·) is the expectation over the first m-steps of the chain, f<sub>ρ</sub> is the regressor function in L<sup>2</sup><sub>(ρX)</sub> associated with ρ, r is related to the abstract smoothness of the regressor, ρ<sub>X</sub> is the marginal measure associated with ρ, and a is the rate of concentration of the Markov chain.
Curcumin as a clinically-promising anti-cancer agent: pharmacokinetics and drug interactions

ABSTRACT Introduction: Curcumin has been extensively studied for its anti-cancer properties. While a diverse array of in vitro and preclinical research support the prospect of curcumin use as an anti-cancer therapeutic, most human studies have failed to meet the intended clinical expectation. Poor systemic availability of orally-administered curcumin may account for this disparity. Areas covered: This descriptive review aims to concisely summarise available clinical studies investigating curcumin pharmacokinetics when administered in different formulations. A critical analysis of pharmacokinetic- and pharmacodynamic-based interactions of curcumin with concomitantly administered drugs is also provided. Expert opinion: The encouraging clinical results of curcumin administration are currently limited to people with colorectal cancer, given that sufficient curcumin concentrations persist in colonic mucosa. Higher parent curcumin systemic exposure, which can be achieved by several newer formulations, has important implications for optimal treatment of cancers other than those in gastrointestinal tract. Curcumin-drug pharmacokinetic interactions are also almost exclusively in the enterocytes, owing to extensive first pass metabolism and poor curcumin bioavailability. Greater scope of these interactions, i.e. modulation of the systemic elimination of co-administered drugs, may be expected from more-bioavailable curcumin formulations. Further studies are still warranted, especially with newer formulations to support the inclusion of curcumin in cancer therapy regimens.
A Survey of Foot Types in Normal Females between the Ages of 18 and 30 Years*.

*This Study was funded in part by a grant from the Chicagoland Orthopaedic Physical Therapy study Group. The purpose of this study was to determine the incidence of forefoot varus, forefoot valgus, subtalar varus, subtalar valgus, and tibiofibular varum in healthy females between the ages of 18 and 30 years. Fifty-eight females had both lower extremities evaluated to determine their foot type. Chi-square testing was used to determine significance between extremities for both the forefoot and rearfoot deformity groups. The relationship between left or right extremities for forefoot or rearfoot deformities was not significant. The forefoot valgus deformity was the most common forefoot imbalance in this sample. Rearfoot varus was present in 97 (83.6%) of the feet surveyed. Eighteen (31%) of the subjects had a different forefoot or rearfoot foot type bilaterally.J Orthop Sports Phys Ther 1988;9(12):406-109.
Biological constrained learning of parameters in a recurrent neural network-based model of the primary visual cortex

Neurons in primary visual cortex (VI) optimally respond to stimuli with their preferred orientation. The response of neurons in VI is suppressed by iso-oriented neurons located in their surround. It is very important to understand the circuitry of center-surround interactions. Previous studies in this field followed the approach of postulating models inspired by neuroscience data. While previous models are only postulated, we adopted a strictly data-driven approach and trained a biologically constrained recurrent network model by using supervised learning methods. We have trained a recurrent neural network model constrained by selected biological and anatomical facts. The obtained model describes the near and far surround behavior and the synaptic weights obtained by training are biologically plausible.
Shifts of Bordetella pertussis Variants in Sweden from 1970 to 2003, during Three Periods Marked by Different Vaccination Programs

ABSTRACT The Swedish population of Bordetella pertussis strains was characterized from 1,247 isolates covering a whole-cell vaccine program up to 1979, a 17-year period without vaccination (1979 to 1996), and a period after the introduction of general vaccination among newborns with acellular pertussis vaccines (1997 to 2003). Strains were characterized by serotyping and genotyping of pertactin and ptxA and by means of pulsed-field gel electrophoresis (PFGE). With emphasis on vaccine-related markers, the vast majority of circulating strains were of nonvaccine type. There were shifts of serotype connected with shifts of vaccination program. Serotype Fim3 was most frequent during the periods with general vaccination schedules, whereas serotype Fim2 was predominant during the 17-year vaccine-free period. Pertactin 1 was predominant during the pertussis whole-cell (Pw) vaccine period but was thereafter replaced by prn2 and has not reappeared after the introduction of acellular pertussis (Pa) vaccines. ptxA (1) was predominant over all three decades. There was a significant difference in the distribution of serotypes between vaccinated and unvaccinated individuals, but not for pertactin. A few PFGE profiles were predominant over the years: BpSR25 (serotype Fim3 prn1/7) and BpSR18 (serotype Fim3 prn2) during the Pw period, BpSR1 (serotype Fim2 prn2) during the 17 years without general vaccination, and BpSR11 (serotype Fim3 prn2) after the reintroduction of general vaccination in 1996. Despite differences between the pertactin and toxin types of Pa vaccines and circulating strains, there is no evidence that there is a threat, i.e., the vaccination program so far has been effective against whooping cough, and there seems to be no impact on the effectiveness of the vaccination program from the bacterial polymorphism.
The Scavenger Receptor CD36 Downmodulates the Early Inflammatory Response while Enhancing Bacterial Phagocytosis during Pneumococcal Pneumonia

CD36 is a scavenger receptor that exhibits pleiotropic functions, including adhesion to thrombospondin, inhibition of angiogenesis, transport of long-chain fatty acids, and clearance of apoptotic cells. In addition, it has been implicated in the host immune response because it acts as a coreceptor for TLR2 and plays a role in Staphylococcus aureus infection. However, its role in other Gram-positive bacterial infections is unclear. In this study, using mice deficient in CD36, we sought to examine the role of CD36 in pneumococcal pneumonia, a major cause of morbidity and mortality worldwide. We show that CD36 is expressed on both alveolar macrophages and respiratory epithelial cells. Early in infection, CD36−/− mice have an exaggerated inflammatory response compared with wild-type littermate controls. In vitro studies using CD36−/− primary cells confirm the enhanced early inflammation in response to S. pneumoniae and its lipoteichoic acid, demonstrate that S. pneumoniae binds to cells via its phosphocholine residues, and suggest a role for CD36 in reducing inflammation induced by the phosphocholine residues of pneumococcal lipoteichoic acid. Later in infection, although CD36−/− mice exhibit impaired bacterial clearance, owing to a decreased capacity of CD36−/− macrophages to phagocytose S. pneumoniae, minor effects on mortality occur, in comparison with those in wild-type littermate control mice. These data show that CD36 contributes to the pulmonary host response during S. pneumoniae infection by virtue of its ability to act as a phagocytic receptor and as a modulator of the early innate immune response.
Epinephrine Impairs Lipid Resuscitation from Bupivacaine Overdose: A Threshold Effect

Background:Lipid emulsion infusion reverses local anesthetic-induced cardiac toxicity, but the effect of adding epinephrine has not been studied. We compared escalating doses of epinephrine on recovery with lipid infusion in a rat model of bupivacaine overdose. Methods:Rats anesthetized with isoflurane received an IV bolus of 20 mg/kg bupivacaine, producing asystole (zero time) in all animals. Ventilation (100% oxygen) and chest compressions were started immediately, and at 3 min the rats received one of six IV treatments (n = 5 for all groups): 5 ml/kg saline followed by infusion for 2 min at 1.0 ml · kg−1 · min−1, and a second 5 ml/kg bolus at 5 min; or the same bolus and infusion treatment using 30% lipid emulsion plus a single injection of epinephrine at one of five doses: 0 (lipid control), 1, 2.5, 10, or 25 mcg/kg. An electrocardiogram and arterial pressure were monitored continuously, and arterial blood gas was measured at 7.5 and 15 min. Results:Epinephrine improved initial return of spontaneous circulation (rate-pressure product > 30% baseline) but only 3 of 5 rats at 10 mcg/kg and 1 of 5 rats at 25 mcg/kg sustained return of spontaneous circulation by 15 min. Lipid alone resulted in slower but more sustained recovery. Epinephrine doses above a threshold near 10 mcg/kg increased lactate, worsened acidosis, and resulted in poor recovery at 15 min, as compared with lipid controls. There was tight correlation of epinephrine dose to serum lactate at 15 min. Conclusions:Epinephrine over a threshold dose near 10 mcg/kg impairs lipid resuscitation from bupivacaine overdose, possibly by inducing hyperlactatemia.
Adding expressiveness to musical messages

A system to add expressiveness to musical messages has been developed, starting from the results of acoustic and perceptual analyses. The system allows to obtain different performances, by modifying the acoustic parameters of a given neutral performance. The modification of the input performance is performed by a model that uses the hierarchical segmentation of the musical organization. For every hierarchical level, opportune curves are applied to the principal acoustic parameters. Level's self-similarity is the main criteria to construct the curves. The modular structure of the system defines an open architecture, where the rendering steps can be realized both with synthesis and post-processing techniques. Different synthesis techniques, like FM, physical models or wavetable have been explored.
Cell Death Mechanisms Following Traumatic Brain Injury

Neuronal and glial cell death and traumatic axonal injury contribute to the overall pathology of traumatic brain injury (TBI) in both humans and animals. In both head‐injured humans and following experimental brain injury, dying neural cells exhibit either an apoptotic or a necrotic morphology. Apoptotic and necrotic neurons have been identified within contusions in the acute post‐traumatic period, and in regions remote from the site of impact in the days and weeks after trauma, while degenerating oligodendrocytes and astrocytes have been observed within injured white matter tracts. We review and compare the regional and temporal patterns of apoptotic and necrotic cell death following TBI and the possible mechanisms underlying trauma‐induced cell death. While excitatory amino acids, increases in intracellular calcium and free radicals can all cause cells to undergo apoptosis, in vitro studies have determined that neural cells can undergo apoptosis via many other pathways. It is generally accepted that a shift in the balance between pro‐ and anti‐apoptotic protein factors towards the expression of proteins that promote death may be one mechanism underlying apoptotic cell death. The effect of TBI on cellular expression of survival promoting‐proteins such as Bcl‐2, Bcl‐xL, and extracellular signal‐regulated kinases, and death‐inducing proteins such as Bax, c‐Jun N‐terminal kinase, tumor‐suppressor gene, p53, and the calpain and caspase families of proteases are reviewed. In light of pharmacologic strategies that have been devised to reduce the extent of apoptotic cell death in animal models of TBI, our review also considers whether apoptosis may serve a protective role in the injured brain. Together, these observations suggest that cell death mechanisms may be representative of a continuum between apoptotic and necrotic pathways.
Evaluation of BACTEC 9240 blood culture system by using high-volume aerobic resin media

The BACTEC 9240 blood culture system (Becton Dickinson Diagnostic Instrument Systems, Sparks, Md.) is one of three automated, continuous-monitoring systems that is widely used in clinical laboratories. The BACTEC 9240 was compared with the BACTEC NR 660 for the detection of organisms and bacteremic episodes; time to detection of positive cultures; number of false-positive and false-negative cultures; and time needed to load, process, and perform quality control functions by using high-volume aerobic media. Blood specimens (5,282) were inoculated in equal volumes (5 to 10 ml per bottle) into BACTEC Plus Aerobic/F (9240 system) and BACTEC Plus NR26 (660 system) bottles. Clinically significant isolates were detected in 6.6% of cultures, representing 348 microorganisms and 216 bacteremic episodes. Two hundred forty-eight microorganisms were detected by both systems, 48 by the 9240 only and 52 by the 660 only (P = not significant). Of the bacteremic episodes, 158 were detected by both systems, 27 by the 9240 only and 31 by the 660 only (P = not significant). Analysis of data by month revealed equivalent recovery rates for both systems, with the exception of a 30-day period at one study site during which the 660 system detected significantly more microorganisms. Following a proprietary hardware design retrofit of the 9240 instrument, detection rates were again equivalent for the remaining three months at this study site. Positive cultures detected by both systems were detected an average of 4.3 h faster by the 9240 system (21 versus 25.3 h). The numbers of false-positive cultures for the 9240 and 660 systems were 40 (1.0%) and 9 ( < 1.0%), respectively. The numbers of false-negative cultures were five for the 9240 system and three for the 660 system. The 9240 system required 23 s less technologist time per bottle to operate during the 5-day protocol. In conclusion, the BACTEC 9240 used with high-volume Aerobic/F medium is equivalent to the BACTEC 660 used with high volume NR26 medium for the detection of microorganisms and bacteremic episodes. In addition, the 9240 system detects positive cultures more rapidly than the 660 system but requires further evaluation to ensure reliability of instrument components.