Miracle-dz/UniFAR-FTUs huggingface dataset:
Stimulation and inhibition of gastrointestinal propulsion induced by substance P and substance K in the rat

1 Substance P and substance K (neurokinin A) (dose range: 0.08–80 nmol kg−1) were tested for their effects on gastrointestinal propulsion in the rat. The peptides were given by intraperitoneal injection concurrently with the intragastric administration of a test meal containing charcoal and 51Cr. 2 Examination 3 min after the test meal showed that high doses of substance P (> 0.74 nmol kg−1) and substance K (> 8.8 nmol kg−1) inhibited gastric emptying and gastrointestinal transit. This inhibitory effect was changed to a stimulant effect by pretreatment of the rats with atropine (3.5 μmol kg−1). Guanethidine pretreatment (67 μmol kg−1) revealed a facilitatory effect of low doses of the two tachykinins (about 1 nmol kg−1) on gastrointestinal propulsion. 3 Examination 15 min after the test meal demonstrated that substance P (> 0.74 nmol kg−1) dose‐dependently enhanced gastrointestinal propulsion, an effect that was also seen after atropine pretreatment. Low doses of substance K (about 1 nmol kg−1) also stimulated gastrointestinal propulsion but this effect was abolished by atropine. In addition, atropine pretreatment revealed a stimulant effect of high doses of substance K (88 nmol kg−1) on gastric emptying. 4 These results show that the effects of substance P and substance K on gastrointestinal propulsion vary with dose and time and involve, at least partly, activation of the autonomic nervous system.
Structural dynamics in the C-terminal domain of calmodulin at low calcium levels.

Calmodulin undergoes Ca2+-induced structural rearrangements that are intimately coupled to the regulation of numerous cellular processes. The C-terminal domain of calmodulin has previously been observed to exhibit conformational exchange in the absence of Ca2+. Here, we characterize further the conformational dynamics in the presence of low concentrations of Ca2+ using 15N spin relaxation experiments. The analysis included 1H-15N dipolar/15N chemical shift anisotropy interference cross-correlation relaxation rates to improve the description of the exchange processes, as well as the picosecond to nanosecond dynamics. Conformational transitions on microsecond to millisecond time scales were revealed by exchange contributions to the transverse auto-relaxation rates. In order to separate the effects of Ca2+ exchange from intramolecular conformational exchange processes in the apo state, transverse auto-relaxation rates were measured at different concentrations of free Ca2+. The results reveal a Ca2+-dependent contribution due mainly to exchange between the apo and (Ca2+)1 states with an apparent Ca2+ off-rate of approximately 5115 s(-1), as well as Ca2+-independent contributions due to conformational exchange within the apo state. 15N chemical shift differences estimated from the exchange data suggest that the first Ca2+ binds preferentially to loop IV. Thus, characterization of chemical exchange as a function of Ca2+ concentration has enabled the extraction of unique information on the rapidly exchanging and weakly populated (<10 %) (Ca2+)1 state that is otherwise inaccessible to direct study due to strongly cooperative Ca2+ binding. The conformational exchange within the apo state appears to involve transitions between a predominantly populated closed conformation and a smaller population of more open conformations. The picosecond to nanosecond dynamics of the apo state are typical of a well-folded protein, with reduced amplitudes of motions in the helical segments, but with significant flexibility in the Ca2+-binding loops. Comparisons with order parameters for skeletal troponin C and calbindin D9k reveal key structural and dynamical differences that correlate with the different Ca2+-binding properties of these proteins.
Prolonged myelosuppression with clofarabine in the treatment of patients with relapsed or refractory, aggressive non-Hodgkin lymphoma

We evaluated the safety and efficacy of the purine nucleoside analogue, clofarabine, in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). Six patients with DLBCL (n = 5) or MCL (n = 1) and a median age of 68 years were treated with 40 mg/m2 clofarabine IV over 2 h for 5 days, repeated every 28 days, for 1–2 cycles. The overall response rate was 50% (complete response = 1, complete response unconfirmed = 1, partial response = 1). Median progression-free survival was 3.5 months (range 1.5–10 months) and the median overall survival was 7.8 months (range 3–31 months). Grade 3–4 neutropenia and thrombocytopenia was universal, with a median of 34 (range 19–55) and 77 (range 0–275) days required for neutrophil and platelet recovery. Grade 3 non-hematologic toxicities included transaminitis, febrile neutropenia, non-neutropenic infections and orthostatic hypotension. Further accrual to the study was terminated due to prolonged Grade 3–4 myelosuppression and orthostatic hypotension in five of six patients. Clofarabine exhibits evidence of single agent activity in relapsed or refractory DLBCL. However, further study with novel administration schedules that maintain this efficacy and limit toxicity is warranted.
Association Between SSRI Use and Hip Fractures and the Effect of Residual Confounding Bias in Claims Database Studies

Background: Although use of selective serotonin reuptake inhibitor (SSRI) antidepressants has been associated with hip fractures in claims data studies, it has been suggested that such results may be confounded by cognitive and functional status for which no information is available in claims data. Using survey data, we determined the magnitude of such bias and corrected the association between SSRI use and hip fractures accordingly. Methods: We used the Medicare Current Beneficiary Survey to determine the association between SSRI use and 5 potential confounding factors not measured in Medicare claims data: body mass index, smoking, activities of daily living score, cognitive impairment, and Rosow-Breslau physical impairment scale. For 7126 participants aged ≥65 years, we estimated the association between SSRI use and these potential confounders. Combined with literature estimates of the associations between confounders and hip fractures, we were able to compute the extent of residual confounding bias caused by a failure to adjust for these factors. Results: Comparing SSRI users with nonusers, there was considerable overestimation of an association with hip fractures if activities of daily living scores (+21.5% bias) or Rosow-Breslau impairment scales (+10.6%) are unmeasured in claims data. All 5 unmeasured confounders together resulted in net confounding of +9.6% (range: −0.3% to + 39%). After correction for this bias, the strength of association observed in claims data after bias correction (RR = 1.8; 95% CI = 1.5 to 2.1) was comparable to a recent clinical study (RR = 1.5; 0.6 to 3.8), but the claims data study achieved formal statistical significance due to its much large size (8239 vs. 288 hip fractures). Conclusions: Epidemiologic claims data studies tend to overestimate the relation between antidepressant use and hip fractures. However, after correcting for such bias, a significant association persists.
Current Application of β‐tricalcium Phosphate Composites in Orthopaedics

Presently, bioceramic materials have been extensively used in spinal surgery as bone grafts; however, there are some limitations for bioceramic materials. Calcium sulfate is rapidly absorbed in vivo, the degradation of which often occurs prior to the formation of new bones. Hydroxyapatite (HA) is hardly absorbed, which blocks the formation of new bones and remodeling, and results in poor local stability or permanent stress concentration. Only β‐tricalcium phosphate (β‐TCP) is relatively balanced between scaffold absorption and bone formation. And it is a good biodegradable ceramic material that could supply a large quantity of calcium ion and sulfate ion as well as scaffold structure for bone regeneration. However, the problem of single β‐TCP is lack of osteoinductivity and osteogenicity, which restricts its application. Therefore β‐TCP composite materials have been used in the field of orthopaedics in recent decades, which fully use excellent properties of other bone repairing materials, such as biodegradability, osteoinductivity, osteogenicity and osteoconductivity. These materials make up for the deficiencies of single β‐TCP and endow β‐TCP with more biological and physical properties.
Rapid diagnosis of drug-resistant TB using line probe assays: from evidence to policy

Growing concerns about the spread of multidrug-resistant tuberculosis (MDR-TB) and the emergence of extensively drug-resistant TB have triggered substantial interest in the development and application of rapid tests for the detection of drug-resistant TB. Molecular assays to detect gene mutations that signal drug resistance are widely recognized as being most suited for rapid diagnosis. Among molecular assays, line probe assays have shown great promise. Currently, two line probe assays are commercially available: the INNO-LiPA® Rif. TB kit (Innogenetics NV, Gent, Belgium) and the GenoType® MTBDRplus assay (Hain Lifescience GmbH, Nehren, Germany). Evidence from a systematic review suggests that INNO-LiPA is a highly sensitive and specific test for the detection of rifampicin resistance in culture isolates. The test, however, appeared to have relatively lower sensitivity when used directly on clinical specimens. Another meta-analysis showed that the GenoType MTBDR assays had excellent accuracy for rifampicin resistance, even when used directly on clinical specimens. While specificity was excellent for isoniazid, sensitivity estimates were modest and variable. Based on evidence and expert opinion, the WHO recently endorsed the use of molecular line probe assays for rapid screening of patients at risk of MDR-TB. Special initiatives have been announced to make these assays accessible and affordable for countries with high MDR-TB prevalence. With strong evidence and new policy directives, the stage is now set for the use of rapid tests for MDR-TB diagnosis. Whether molecular tools, such as line probe assays, will actually make a clinical and public-health impact remains to be determined.
A Novel Soybean Dirigent Gene GmDIR22 Contributes to Promotion of Lignan Biosynthesis and Enhances Resistance to Phytophthora sojae

Phytophthora root and stem rot caused by the oomycete pathogen Phytophthora sojae is a destructive disease of soybean worldwide. Plant dirigent proteins (DIR) are proposed to have roles in biosynthesis of either lignan or lignin-like molecules, and are important for defense responses, secondary metabolism, and pathogen resistance. In the present work, a novel DIR gene expressed sequence tag is identified as up-regulated in the highly resistant soybean cultivar ‘Suinong 10’ inoculated with P. sojae. The full length cDNA is isolated using rapid amplification of cDNA ends, and designated GmDIR22 (GenBank accession no. HQ_993047). The full length GmDIR22 is 789 bp and contains a 567 bp open reading frame encoding a polypeptide of 188 amino acids. The sequence analysis indicated that GmDIR22 contains a conserved dirigent domain at amino acid residues 43–187. The quantitative real-time reverse transcription PCR demonstrated that soybean GmDIR22 mRNA is expressed most highly in stems, followed by roots and leaves. The treatments with stresses demonstrated that GmDIR22 is significantly induced by P. sojae and gibberellic acid (GA3), and also responds to salicylic acid, methyl jasmonic acid, and abscisic acid. The GmDIR22 is targeted to the cytomembrane when transiently expressed in Arabidopsis protoplasts. Moreover, The GmDIR22 recombinant protein purified from Escherichia coli could effectively direct E-coniferyl alcohol coupling into lignan (+)-pinoresinol. Accordingly, the overexpression of GmDIR22 in transgenic soybean increased total lignan accumulation. Moreover, the lignan extracts from GmDIR22 transgenic plants effectively inhibits P. sojae hyphal growth. Furthermore, the transgenic overexpression of GmDIR22 in the susceptible soybean cultivar ‘Dongnong 50’ enhances its resistance to P. sojae. Collectively, these data suggested that the primary role of GmDIR22 is probably involved in the regulation of lignan biosynthesis, and which contributes to resistance to P. sojae.
Thromboresistance of alkali- and heat-treated titanium metal formed with apatite.

Fibrin deposition and platelet adhesion onto alkali- and heat-treated titanium metal (AH-Ti), alkali- and water-treated titanium metal (Wa-Ti), and alkali- and heat-treated titanium metal formed with apatite (Ap-Ti) in simulated body fluid (SBF) were evaluated by exposure to anticoagulated blood or washed platelet suspension (WPS) under static conditions and subsequent observation with scanning electron microscopy (SEM). The results were compared with those for commercially pure titanium metal (cp-Ti). Thrombus formation on AH-Ti and Wa-Ti, which were exposed to heparinized whole blood for 1 h, was significantly less than that on cp-Ti, on which pronounced depositions of fibrin-erythrocytes and lymphocytes were observed. No thrombus was observed on Ap-Ti, possibly because of a high adsorption of heparin. Morphological change of platelets attached to surfaces via adsorbed plasma proteins was found to a significant extent on AH-Ti and Wa-Ti exposed to WPS. However, there was almost no difference between cp-Ti and Ap-Ti in round morphology of adherent platelets. These findings suggested that Ap-Ti exhibits stronger antithrombogenic characteristics than cp-Ti and other materials examined in heparinized blood.
How does the minimum wage affect employment statuses of youths?: evidence of Indonesia

Purpose - – The purpose of this paper is to examine the effects of minimum wage on youth employment across employment statuses in Indonesia. This study uses the National Labour Force Survey (Sakernas) from 2010 to 2012. Design/methodology/approach - – This study uses a multinomial logit model to see the youth distribution across different employment status changes as a result of an increase in the minimum wage. Five categories of youth employment statuses are examined including self-employed; unpaid family workers; paid employees in the covered sector; paid employees in the uncovered sectors; and unemployed. The model is examined separately for urban and rural areas, as well as for the male and female youth labour market. Findings - – The results generally suggest that an increase in minimum wage decrease the probability of youth being employed in the covered sector, i.e. paid employment in the covered sector and increase the probability of youth being employed in the uncovered sectors, including self-employed, unpaid family workers, and paid employment in the uncovered sectors. This study indicates a displacement effect for youths from the covered sector into the uncovered sector as suggested by the two-sector model. The specific results are different across urban and rural labour markets, as well as across males and females. Originality/value - – Compared to the developed country studies, the studies on the effects of minimum wage on youth employment in developing countries is relatively limited. The sample from Indonesian labour market with a large informal sector has never been used for these purposes. This study also contributes to the literature by using the particular definition of the covered-uncovered sector to the Indonesian labour market based on the employment status and individual wage data.
Enhanced release of calcium phosphate additives from bioresorbable orthopaedic devices using irradiation technology is non-beneficial in a rabbit model

Objectives Bioresorbable orthopaedic devices with calcium phosphate (CaP) fillers are commercially available on the assumption that increased calcium (Ca) locally drives new bone formation, but the clinical benefits are unknown. Electron beam (EB) irradiation of polymer devices has been shown to enhance the release of Ca. The aims of this study were to: 1) establish the biological safety of EB surface-modified bioresorbable devices; 2) test the release kinetics of CaP from a polymer device; and 3) establish any subsequent beneficial effects on bone repair in vivo. Methods ActivaScrew Interference (Bioretec Ltd, Tampere, Finland) and poly(L-lactide-co-glycolide) (PLGA) orthopaedic screws containing 10 wt% β-tricalcium phosphate (β-TCP) underwent EB treatment. In vitro degradation over 36 weeks was investigated by recording mass loss, pH change, and Ca release. Implant performance was investigated in vivo over 36 weeks using a lapine femoral condyle model. Bone growth and osteoclast activity were assessed by histology and enzyme histochemistry. Results Calcium release doubled in the EB-treated group before returning to a level seen in untreated samples at 28 weeks. Extensive bone growth was observed around the perimeter of all implant types, along with limited osteoclastic activity. No statistically significant differences between comparative groups was identified. Conclusion The higher than normal dose of EB used for surface modification did not adversely affect tissue response around implants in vivo. Surprisingly, incorporation of β-TCP and the subsequent accelerated release of Ca had no significant effect on in vivo implant performance, calling into question the clinical evidence base for these commercially available devices. Cite this article: I. Palmer, S. A. Clarke, F. J Buchanan. Enhanced release of calcium phosphate additives from bioresorbable orthopaedic devices using irradiation technology is non-beneficial in a rabbit model: An animal study. Bone Joint Res 2019;8:266–274. DOI: 10.1302/2046-3758.86. BJR-2018-0224.R2.
Placing the Effect? Gleaning Insights into the Relationship between Citizens’ Use of E-Government and Trust in Government

Abstract The effects of e-government on citizens’ trust in government are unclear. This study intends to address this lack of clarity by proposing a novel conceptual framework that can be used to explicate the processes tying e-government use to trust in government. This framework is centred upon citizens’ propensity to trust, perceptions of public sector performance, and trust in government. Citizens’ use of e-government is then argued to strengthen relationships in this framework. The validity of this framework is tested using data collected in 2012 from citizens of Seoul, South Korea. In general, the results offer partial support for the proposed framework. However, the strength of e-government’s influence decreases with more frequent use of information coming from government websites. Implications for effective practice are discussed.
The 5′ proximal helix of 16S rRNA is involved in the binding of streptomycin to the ribosome

Single mutations at the end of the 5′ proximal helix and in the 915 region (13UåA or C; 914AåU or G), and double mutations (13UåA and 914Aå U; 13UåC and 914AåG) were constructed into Escherichia coli 16S ribosomal RNA. The mutations were introduced into an expression plasmid containing the rrnB operon under the transcriptional control of the temperature‐inducible λPL promoter. None of the mutant 16S rRNAs affected cell growth when expressed. Ribosomes extracted after induction of expression of the mutant 16S rRNAs were assayed for their capacity to bind the error‐inducing drug streptomycin and for translational misreading in the presence of streptomycin. All mutations impaired the binding of streptomycin, and consequently its capacity to stimulate misreading. Our results demonstrate the involvement of the 5′ proximal helix of 16S rRNA in the binding of streptomycin and confirm the participation of the 915 region. They do not support a previous suggestion [Leclerc, D. and Brakier‐Gingras, L. (1991) FEBS Lett, Vol. 279, pp. 171–174] that base pairing between nucleotides 13 and 914 stabilizes the binding of streptomycin. — Pinard, R. , Payant, C. , Melançon, P., and Brakier‐Gingras, L. The 5′ proximal helix of 16S rRNA is involved in the binding of streptomycin to the ribosome. FASEB J. 7: 173‐176; 1993.
Leadership and Motivation for Public Goods Contributions

Results from a leader-follower public goods game are presented. An individual, when randomlyselected to make a contribution knowing that others will observe the selection, gives more than one does in the simultaneous-move public goods game. Followers adopt a quasi-matching strategy where they systematically donate less than the leader, but contribute more when the leader does and contribute less when the leader free rides. The net result is increased provision of a public good when contributions are sequential. The results highlight that psychological preferences, rather than solely social preferences, can explain behavior.
Optimal time points sampling in pathway modelling

Modelling cellular dynamics based on experimental data is at the heart of system biology. Considerable progress has been made to dynamic pathway modelling as well as the related parameter estimation. However, few of them gives consideration for the issue of optimal sampling time selection for parameter estimation. Time course experiments in molecular biology rarely produce large and accurate data sets and the experiments involved are usually time consuming and expensive. Therefore, to approximate parameters for models with only few available sampling data is of significant practical value. For signal transduction, the sampling intervals are usually not evenly distributed and are based on heuristics. In the paper, we investigate an approach to guide the process of selecting time points in an optimal way to minimize the variance of parameter estimates. In the method, we first formulate the problem to a nonlinear constrained optimization problem by maximum likelihood estimation. We then modify and apply a quantum-inspired evolutionary algorithm, which combines the advantages of both quantum computing and evolutionary computing, to solve the optimization problem. The new algorithm does not suffer from the morass of selecting good initial values and being stuck into local optimum as usually accompanied with the conventional numerical optimization techniques. The simulation results indicate the soundness of the new method.
Decreasing perinatal mortality in placental abruption

Objective. To study perinatal mortality associated with placental abruption. Design. Retrospective population study using the Finnish Hospital Discharge Register and Medical Birth Register data. Setting. Finland, 1987–2005. Population. Pregnancies with placental abruption and all other births without placental abruption. Methods. The national Hospital Discharge Register and Medical Birth Register were used to identify all pregnancies with placental abruption. Demographic data and delivery outcomes were collected retrospectively. Perinatal mortality associated with placental abruption was compared with that in other births. Potential risk factors were analysed. Main outcome measures. Perinatal mortality in placental abruption. Results. The study consisted of 618 735 women with 1.14 million pregnancies, 4336 of whom had placental abruption. Overall perinatal mortality with abruption was 119 per 1000 births. Placental abruption explained 7% of all perinatal deaths. The mortality among singleton births (125 per 1000) was higher than among multiple births (40 per 1000). The majority of deaths (77%) occurred in utero. Singleton perinatal mortality with abruption decreased from 173 per 1000 in 1987–1990 to 98 per 1000 in 2000–2005 (p < 0.001). In singleton births at <32 gestational weeks, overall perinatal mortality was high (345 per 1000) and was not increased by placental abruption. Prematurity, low birthweight, male fetal sex and maternal smoking were independent risk factors for placental abruption‐related perinatal mortality. Conclusions. Although mortality associated with placental abruption decreased during the study period, placental abruption still remains an important cause of perinatal mortality.