Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of TGF-β Signaling Promotes Human Pancreatic β-Cell Replication

Diabetes is associated with loss of functional pancreatic β-cells, and restoration of β-cells is a major goal for regenerative therapies. Endogenous regeneration of β-cells via β-cell replication has the potential to restore cellular mass; however, pharmacological agents that promote regeneration or expansion of endogenous β-cells have been elusive. The regenerative capacity of β-cells declines rapidly with age, due to accumulation of p16INK4a, resulting in limited capacity for adult endocrine pancreas regeneration. Here, we show that transforming growth factor-β (TGF-β) signaling via Smad3 integrates with the trithorax complex to activate and maintain Ink4a expression to prevent β-cell replication. Importantly, inhibition of TGF-β signaling can result in repression of the Ink4a/Arf locus, resulting in increased β-cell replication in adult mice. Furthermore, small molecule inhibitors of the TGF-β pathway promote β-cell replication in human islets transplanted into NOD-scid IL-2Rgnull mice. These data reveal a novel role for TGF-β signaling in the regulation of the Ink4a/Arf locus and highlight the potential of using small molecule inhibitors of TGF-β signaling to promote human β-cell replication.
Root morphology, hydraulic conductivity and plant water relations of high-yielding rice grown under aerobic conditions.

BACKGROUND AND AIMS Increasing physical water scarcity is a major constraint for irrigated rice (Oryza sativa) production. 'Aerobic rice culture' aims to maximize yield per unit water input by growing plants in aerobic soil without flooding or puddling. The objective was to determine (a) the effect of water management on root morphology and hydraulic conductance, and (b) their roles in plant-water relationships and stomatal conductance in aerobic culture. METHODS Root system development, stomatal conductance (g(s)) and leaf water potential (Ψ(leaf)) were monitored in a high-yielding rice cultivar ('Takanari') under flooded and aerobic conditions at two soil moisture levels [nearly saturated (> -10 kPa) and mildly dry (> -30 kPa)] over 2 years. In an ancillary pot experiment, whole-plant hydraulic conductivity (soil-leaf hydraulic conductance; K(pa)) was measured under flooded and aerobic conditions. KEY RESULTS Adventitious root emergence and lateral root proliferation were restricted even under nearly saturated conditions, resulting in a 72-85 % reduction in total root length under aerobic culture conditions. Because of their reduced rooting size, plants grown under aerobic conditions tended to have lower K(pa) than plants grown under flooded conditions. Ψ(leaf) was always significantly lower in aerobic culture than in flooded culture, while g(s) was unchanged when the soil moisture was at around field capacity. g(s) was inevitably reduced when the soil water potential at 20-cm depth reached -20 kPa. CONCLUSIONS Unstable performance of rice in water-saving cultivations is often associated with reduction in Ψ(leaf). Ψ(leaf) may reduce even if K(pa) is not significantly changed, but the lower Ψ(leaf) would certainly occur in case K(pa) reduces as a result of lower water-uptake capacity under aerobic conditions. Rice performance in aerobic culture might be improved through genetic manipulation that promotes lateral root branching and rhizogenesis as well as deep rooting.
Study of the visual evoked magnetic field with the m-sequence technique.

PURPOSE Multifocally stimulated visual evoked magnetic field (VEF) examination with an m-sequence technique (multifocal VEF; mVEF) was studied, and the neural generators at peaks of mVEF were estimated in the visual cortex. METHODS Visual field stimulation was generated by a multifocal testing system with use of the m-sequence technique. The stimulation pattern covered a central area extending from 0.6 degrees to 10 degrees in radius outward from the center of four visual-field quadrants. The stimulation pattern was projected onto a screen by a liquid crystal projector. VEFs of 14 healthy adults were recorded with a 160-channel, whole-head-type magnetoencephalography (MEG) system. The output signals of 16 selected MEG sensors covering the occipital region were recorded for each subject with the multifocal testing system, and the second-order responses were calculated. The analyzed response data files were transferred to the MEG system, a single equivalent current dipole (ECD) was estimated to locate the neural generator, and the localization was superimposed onto the corresponding brain magnetic resonance image of the subject. RESULTS mVEFs showed three peak waves (N75m, P100m, N145m) in 75% of the subjects and two peak waves (N75m, N145m) in 25%. (N, P and m denote negative, positive, and magnetic fields, respectively.) Latencies of the first and the last peak were similar between the two kinds of peak waves. ECD examination showed more than 97% of goodness of fit at all peaks, and the relation between EDCs and the stimulated visual field coincided with a retinotopic organization that fit a cruciform model in all subjects. ECD depths from the occipital pole were similar to the depth expected from the human linear cortical magnification factor model in all subjects. Main neural generators of all mVEF components (N75m, P100m, N145m) were shown in the striate cortex (V1). CONCLUSIONS Testing the VEF with an m-sequence technique showed stable responses to simultaneous stimulation of four visual-field quadrants. Consistency of correlation of the estimated ECD with the known cortical organization of the primary visual cortex confirmed the reliability of this examination. The three mVEF peaks were thought to derive mainly from V1 activity.
Human ovarian cancer xenografts in nude mice: Characterization and analysis of antigen expression

We have characterized 13 different human ovarian cancer xenografts grown subcutaneously in nude mice. The tumor lines represented 5 histological subtypes: serous (4), mucinous (4), clear‐cell carcinoma (1), carcinosarcoma (1) and undifferentiated (3). The specific histology and the degree of differentiation resembled those of the original patients' tumors and were maintained upon serial transfer. Volume doubling times of the xenografts ranged from 3.5 to 15 days. The xenografts were also analyzed for their antigen expression using 20 monoclonal antibodies (MAbs) reactive with 15 tumor‐associated antigens. Immunohistochemical examination of tissue sections showed a positive reaction pattern with MAbs 115D8, 140C1, 139H2, 175C5, HMFG1 and HMFG2, each recognizing episialin, as well as with MAbs AUA1, 358.4. 32 and 199‐157 in xenografts of the serous, mucinous and clear‐cell carcinoma subtype. MAb OC125 was reactive with xenografts of the serous subtypes. Other antibodies, such as 494 and OV‐TL3 infrequently demonstrated positive reactions. Reactivity of all MAbs was low in the carcinosarcoma and undifferentiated tumor lines. With the exception of AUA1, 495 and I26E5, all MAbs revealed a heterogeneous staining pattern. MAbs against episialin and OC125 predominantly stained the apical site of the tumor cells. Strongest reactivity with almost all histological subtypes was observed with MAbs 115D8, 140C1, 139H2 and AUA1. In cases where we were able to compare the patients' tumor tissue with the respective xenografts, retention of antigen expression was demonstrated in each instance. Release of tumor‐associated antigens was shown for CA125 in 2 serous‐tumor lines, for CA15.3 in I serous‐tumor line, and for CEA in 3 lines of the mucinous subtype. This panel of human tumor xenografts could be a valuable tool to determine the potential usefulness of MAb‐guided therapy in ovarian cancer.
An Interferon α2 Mutant Optimized by Phage Display for IFNAR1 Binding Confers Specifically Enhanced Antitumor Activities*

All α-interferons (IFNα) bind the IFNAR1 receptor subunit with low affinity. Increasing the binding affinity was shown to specifically increase the antiproliferative potency of IFNα2. Here, we constructed a phage display library by randomizing three positions on IFNα2 previously shown to confer weak binding to IFNAR1. The tightest binding variant selected, comprised of mutations H57Y, E58N, and Q61S (YNS), was shown to bind IFNAR1 60-fold tighter compared with wild-type IFNα2, and 3-fold tighter compared with IFNβ. Binding of YNS to IFNAR2 was comparable with wild-type IFNα2. The YNS mutant conferred a 150-fold higher antiproliferative potency in WISH cells compared with wild-type IFNα2, whereas its antiviral activity was increased by only 3.5-fold. The high antiproliferative activity was related to an induction of apoptosis, as demonstrated by annexin V binding assays, and to specific gene induction, particularly TRAIL. To determine the potency of the YNS mutant in a xenograft cancer model, we injected it twice a week to nude mice carrying transplanted MDA231 human breast cancer cells. After 5 weeks, no tumors remained in mice treated with YNS, whereas most mice treated with wild-type IFNα2 showed visible tumors. Histological analysis of these tumors showed a significant anti-angiogenic effect of YNS, compared with wild-type IFNα2. This work demonstrates the application of detailed biophysical understanding in the process of protein engineering, yielding an interferon variant with highly increased biological potency.
Diisopropylammonium thiocyanate

In the title molecular salt, C6H16N+·NCS−, the cation possesses approximate local twofold rotation symmetry. One of its NH atoms forms a hydrogen bond to a thiocyanate N atom and the other to a thiocyanate S atom. This results in [001] chains of alternating cations and anions.
Joint Torque and Mechanical Power of Lower Extremity and Its Relevance to Hamstring Strain during Sprint Running

The aim of this study was to quantify the contributions of lower extremity joint torques and the mechanical power of lower extremity muscle groups to further elucidate the loadings on hamstring and the mechanics of its injury. Eight national-level male sprinters performed maximum-velocity sprint running on a synthetic track. The 3D kinematic data and ground reaction force (GRF) were collected synchronously. Intersegmental dynamics approach was used to analyze the lower extremity joint torques and power changes in the lower extremity joint muscle groups. During sprinting, the GRF during the stance phase and the motion-dependent torques (MDT) during the swing phase had a major effect on the lower extremity movements and muscle groups. Specifically, during the stance phase, torque produced and work performed by the hip and knee muscles were generally used to counteract the GRF. During the swing phase, the role of the muscle torque changed to mainly counteract the effect of MDT to control the movement direction of the lower extremity. Meanwhile, during the initial stance and late swing phases, the passive torques, namely, the ground reaction torques and MDT produced by the GRF and the inertial movement of the segments of the lower extremity, applied greater stress to the hamstring muscles.
Variation in conception rates following synchronization of estrus with melengestrol acetate and prostaglandin F2 alpha.

Beef cows and heifers (n = 263) at three locations that were exhibiting estrous cycle either were fed . 5 mg/d melengestrol acetate (MGA) for 7 d and administered prostaglandin F2 alpha (25 mg, i.m.) on the last day of MGA feeding or were untreated. State of the estrous cycle at the beginning of the experiment was determined based on estrous detection and (or) progesterone concentrations in pretreatment blood samples. Estrous was checked twice daily for 30 d posttreatment. Animals were artificially inseminated approximately 12 h after detection of estrus. A synchronized estrus (less than 7 d posttreatment) was detected in 72% of the treated animals. More animals in the treated group became pregnant during the first 7 d of breeding, but their conception rate was lower than that of animals in the control group (P less than .05). Conception rate (36%) was reduced among treated animals when MGA feeding began late (d 14 to 20) in the estrous cycle. Conversely, the conception rate (66%) of treated animals fed MGA beginning earlier in the cycle was not different from that of control animals (73%; treatment x stage of cycle; P less than .05).
HoloCollab: a shared virtual platform for physical assembly training using spatially-aware head-mounted displays

Today's industrial jobs require a skilled and trained workforce as tasks such as maintenance, service, and repair are becoming more complicated and more demanding. Therefore, both education and training for executing these tasks are becoming more important. Usually training is conducted on-site at designated training facilities with physical hardware. However, on-site hands-on training can be expensive as it requires designated training facilities that have to be maintained and need to be traveled to. With Augmented Reality (AR) becoming a substantial part of modern day manufacturing, using AR-based systems to train new workforces is becoming increasingly popular. In this paper, we investigate different training environments that use AR-based support during workforce training. We draw the design space for a shared collaborative AR-based learning space, and present the concept and implementation of HoloCollab which combines having a scalable virtual representation of an industrial scenario, such as assembly, with the benefit of having a trainer on-site with a trainee.
Analysis of major antigens of Haemophilus (Actinobacillus) pleuropneumoniae and related organisms

Outer membrane protein (OMP)-enriched extracts and whole-cell protein preparations of Haemophilus (Actinobacillus) pleuropneumoniae and related organisms were examined by polyacrylamide gel electrophoresis and immunoblotting. Both the OMP-enriched and whole-cell protein profiles of Actinobacillus suis, A. pleuropneumoniae (NAD-independent biovar), A. lignieresii, and Pasteurella haemolytica were very similar to those of H. pleuropneumoniae serotypes 1 to 8. Antisera prepared against H. pleuropneumoniae typically recognized three major OMP antigens with approximate molecular weights of 17,000 (17K), 32K, and 42K in immunoblots of H. pleuropneumoniae serotypes 1 to 8, Actinobacillus spp. , and P. haemolytica. Antisera prepared against Actinobacillus spp. and Haemophilus sp. "minor group" also recognized these 17K, 32K, and 42K antigens. Using absorbed sera, we demonstrated that the 17K antigen had an epitope (or epitopes) common to all the gram-negative organisms examined, including Escherichia coli. The 32K and 42K antigens had epitopes common to members of the family Pasteurellaceae but, in the case of the 32K antigen, also contained unique epitopes. These results provide a basis for understanding the lack of specificity of serodiagnostic tests for H. pleuropneumoniae infection and provide another line of evidence for the association of H. pleuropneumoniae with the genus Actinobacillus.
Plasmid pKM101 encodes two nonhomologous antirestriction proteins (ArdA and ArdB) whose expression is controlled by homologous regulatory sequences

The IncN plasmid pKM101 (a derivative of R46) encodes the antirestriction protein ArdB (alleviation of restriction of DNA) in addition to another antirestriction protein, ArdA, described previously. The relevant gene, ardB, was located in the leading region of pKM101, about 7 kb from oriT. The nucleotide sequence of ardB was determined, and an appropriate polypeptide was identified in maxicells of Escherichia coli. Like ArdA, ArdB efficiently inhibits restriction by members of the three known families of type I systems of E. coli and only slightly affects the type II enzyme, EcoRI. However, in contrast to ArdA, ArdB is ineffective against the modification activity of the type I (EcoK) system. Comparison of deduced amino acid sequences of ArdA and ArdB revealed only one small region of similarity (nine residues), suggesting that this region may be somehow involved in the interaction with the type I restriction systems. We also found that the expression of both ardA and ardB genes is controlled jointly by two pKM101-encoded proteins, ArdK and ArdR, with molecular weights of about 15,000 and 20,000, respectively. The finding that the sequences immediately upstream of ardA and ardB share about 94% identity over 218 bp suggests that their expression may be controlled by ArdK and ArdR at the transcriptional level. Deletion studies and promoter probe analysis of these sequences revealed the regions responsible for the action of ArdK and ArdR as regulatory proteins. We propose that both types of antirestriction proteins may play a pivotal role in overcoming the host restriction barrier by self-transmissible broad-host-range plasmids. It seems likely that the ardKR-dependent regulatory system serves in this case as a genetic switch that controls the expression of plasmid-encoded antirestriction functions during mating.
Dynamic expression of broad-complex isoforms mediates temporal control of an ecdysteroid target gene at the onset of Drosophila metamorphosis.

Metamorphosis in Drosophila melanogaster is orchestrated by the steroid hormone ecdysone, which triggers a cascade of primary-response transcriptional regulators and secondary effector genes during the third larval instar and prepupal periods of development. The early ecdysone-response Broad-Complex (BR-C) gene, a key regulator of this cascade, is defined by three complementing functions (rbp, br, and 2Bc) and encodes several distinct zinc-finger-containing isoforms (Z1 to Z4). Using isoform-specific polyclonal antibodies we observe in the fat body a switch in BR-C isoform expression from the Z2 to the other three isoforms during the third instar. We show that the 2Bc(+) function that corresponds presumably to the Z3 isoform is required for the larval fat body-specific expression of a transgenic construct (AE) in which the lacZ gene is under the control of the ecdysone-regulated enhancer and minimal promoter of the fat body protein 1 (Fbp1) gene. Using hs(BR-C) transgenes, we demonstrate that overexpression of Z1, Z3, or Z4, but not Z2, is able to rescue AE activity with faithful tissue specificity in a BR-C null (npr1) genetic context, demonstrating a partial functional redundancy between Z1, Z3, and Z4 isoforms. We also show that continuous overexpression of Z2 during the third instar represses AE, while conversely, expression of Z3 earlier than its normal onset induces precocious expression of the construct. This finding establishes a tight correlation between the dynamic pattern of expression of the BR-C isoforms and their individual repressive or inductive roles in AE regulation. Altogether our results demonstrate that the balance between BR-C protein isoforms in the fat body mediates, in part, the precise timing of the ecdysone activation of the AE construct but does not modulate its tissue specificity.
Proteome analysis of polyacrylamide gel‐separated proteins visualized by reversible negative staining using imidazole‐zinc salts

Identification and characterization of proteins isolated from natural sources by polyacrylamide gel electrophoresis has become a routine technique. However, efficient sample proteolysis and subsequent peptide extraction is still problematic. Here, we present an improved protocol for the rapid detection of polyacrylamide gel‐separated proteins, in situ protein modification, proteolytic digestion and peptide extraction for subsequent protein identification and characterization by capillary high‐performance liquid chromatography/tandem mass spectrometry. This simple technique employs the rapid imidazole‐zinc reverse stain, in‐gel S‐pyridylethylation and proteolytic digestion of microcrushed polyacrylamide gel pieces with proteases. This technique obviates the need for buffer exchange or gel lyophilisation due to all of the sample manipulation steps being carried out at near neutral pH and thus lends itself readily to automation.
Healthy lifestyle behaviours are positively and independently associated with academic achievement: An analysis of self-reported data from a nationally representative sample of Canadian early adolescents

Introduction The lifestyle behaviours of early adolescents, including diet, physical activity, sleep, and screen usage, are well established contributors to health. These behaviours have also been shown to be associated with academic achievement. Poor academic achievement can additionally contribute to poorer health over the lifespan. This study aims to characterize the associations between health behaviours and self-reported academic achievement. Methods Data from the 2014 Canadian Health Behaviour in School-Aged Children Study (n = 28,608, ages 11–15) were analyzed. Students provided self-report of academic achievement, diet, physical activity, sleep duration, recreational screen time usage, height, weight, and socioeconomic status. Multi-level logistic regression was used to assess the relationship of lifestyle behaviours and body weight status with academic achievement while considering sex, age, and socioeconomic status as potential confounders. Results All health behaviours exhibited independent associations with academic achievement. Frequent consumption of vegetables and fruits, breakfast and dinner with family and regular physical activity were positively associated with higher levels of academic achievement, while frequent consumption of junk food, not meeting sleep recommendations, and overweight and obesity were negatively associated with high academic achievement. Conclusions The present findings demonstrate that lifestyle behaviours are associated with academic achievement, potentially identifying these lifestyle behaviours as effective targets to improve academic achievement in early adolescents. These findings also justify investments in school-based health promotion initiatives.
Background odour induces adaptation and sensitization of olfactory receptors in the antennae of houseflies

Abstract The presence of background odour was found to have a small but significant effect on the sensitivity of the antennal olfactory system of houseflies, Musca domestica Linnaeus (Diptera: Muscidae), to new pulses of odour. We show that cross‐adaptation and cross‐sensitization between a background odour of (±)‐1‐octen‐3‐ol and pulses of (±)‐1‐octen‐3‐ol, 2‐pentanone and R‐(+)‐limonene can occur, confirming that olfactory receptor cells are sensitive to different odours. Background odour can increase the responses to low concentration odour pulses and decrease the responses to higher concentration odour pulses. It is suggested that background odour has a larger effect on olfactory receptor cells that respond with a tonic increase of spike frequency, giving information about the level of odour concentration, i.e. the ‘static’ environment. Cells that respond in a phasic way only provide information on the dynamics of the olfactory environment.