Miracle-dz/UniFAR-FTUs huggingface dataset:
Canonical Wnt signaling is a positive regulator of mammalian cardiac progenitors

Guiding multipotent cells into distinct lineages and controlling their expansion remain fundamental challenges in developmental and stem cell biology. Members of the Wnt pathway control many pivotal embryonic events, often promoting self-renewal or expansion of progenitor cells. In contrast, canonical Wnt ligands are thought to negatively regulate cardiomyogenesis in several species. However, the cell-autonomous role of canonical Wnt signaling within precardiac mesoderm, through its obligatory transcriptional mediator, β-catenin, is unknown. Using tissue-specific in vivo genetic manipulation, we found that β-catenin is required for development of cardiac progenitors and is a positive regulator of proliferative expansion of such progenitor cells. At discrete windows of development in embryonic stem cells, activation of canonical Wnt signaling promoted expansion of cardiac progenitors after initial commitment and was required for cardiac differentiation. Together, these data provide in vivo and in vitro evidence that canonical Wnt signaling promotes the expansion of cardiac progenitors and differentiation of cardiomyocytes.
Self‐Powered Cardiac Pacemaker Enabled by Flexible Single Crystalline PMN‐PT Piezoelectric Energy Harvester

A flexible single-crystalline PMN-PT piezoelectric energy harvester is demonstrated to achieve a self-powered artificial cardiac pacemaker. The energy-harvesting device generates a short-circuit current of 0.223 mA and an open-circuit voltage of 8.2 V, which are enough not only to meet the standard for charging commercial batteries but also for stimulating the heart without an external power source.
Human brain imaging of nicotinic acetylcholine α4β2* receptors using [18F]Nifene: Selectivity, functional activity, toxicity, aging effects, gender effects, and extrathalamic pathways

Nicotinic acetylcholinergic receptors (nAChR's) have been implicated in several brain disorders, including addiction, Parkinson's disease, Alzheimer's disease and schizophrenia. Here we report in vitro selectivity and functional properties, toxicity in rats, in vivo evaluation in humans, and comparison across species of [18F]Nifene, a fast acting PET imaging agent for α4β2* nAChRs. Nifene had subnanomolar affinities for hα2β2 (0.34 nM), hα3β2 (0.80 nM) and hα4β2 (0.83 nM) nAChR but weaker (27–219 nM) for hβ4 nAChR subtypes and 169 nM for hα7 nAChR. In functional assays, Nifene (100 μM) exhibited 14% agonist and >50% antagonist characteristics. In 14‐day acute toxicity in rats, the maximum tolerated dose (MTD) and the no observed adverse effect level (NOAEL) were estimated to exceed 40 μg/kg/day (278 μg/m2/day). In human PET studies, [18F]Nifene (185 MBq; <0.10 μg) was well tolerated with no adverse effects. Distribution volume ratios (DVR) of [18F]Nifene in white matter thalamic radiations were ∼1.6 (anterior) and ∼1.5 (superior longitudinal fasciculus). Habenula known to contain α3β2 nAChR exhibited low levels of [18F]Nifene binding while the red nucleus with α2β2 nAChR had DVR ∼1.6–1.7. Females had higher [18F]Nifene binding in all brain regions, with thalamus showing >15% than males. No significant aging effect was observed in [18F]Nifene binding over 5 decades. In all species (mice, rats, monkeys, and humans) thalamus showed highest [18F]Nifene binding with reference region ratios >2 compared to extrathalamic regions. Our findings suggest that [18F]Nifene PET may be used to study α4β2* nAChRs in various CNS disorders and for translational research.
Sensitivity to Interaural Level and Envelope Time Differences of Two Bilateral Cochlear Implant Listeners Using Clinical Sound Processors

Objectives: To assess the sensitivity of two bilateral cochlear implant users to interaural level and time differences (ILDs and ITDs) for various signals presented through the auxiliary inputs of clinical sound processors that discard fine timing information and only preserve envelope cues. Design: In a lateralization discrimination experiment, the just noticeable difference (JND) for ILDs and envelope ITDs was measured by means of an adaptive 2-AFC method. Different stimuli were used, including click trains at varying repetition rates, a speech fragment, and noise bursts. For one cochlear implant listener and one stimulus, the sensitivity to envelope ITDs was also determined with the method of constant stimuli. The dependency of ILD-JNDs on the interaural place difference was studied with stimulation at single electrode pairs by using sinusoidal input signals in combination with appropriate single-channel processor fittings. In a lateralization position experiment, subjects were required to use a visual pointer on a computer screen to indicate in-the-head positions for blocks of stimuli containing either ILD or ITD cues. All stimuli were loudness balanced (before applying ILD) and fed directly into the auxiliary inputs of the BTE processors (TEMPO+, Med-El Corp.). The automatic gain control and the processors’ microphones were deactivated. Results: Both cochlear implant listeners were highly sensitive to ILDs in all broadband stimuli used; JNDs approached those of normal-hearing listeners. Pitch-matched single electrode pairs showed significantly lower ILD-JNDs than pitch-mismatched electrode pairs. Envelope ITD-JNDs of cochlear implant listeners obtained with the adaptive method were substantially higher and showed a higher test-retest variability than waveform ITD-JNDs of normal-hearing control listeners and envelope ITD-JNDs of normal-hearing listeners reported in the literature for comparable signals. The envelope ITD-JNDs for the click trains were significantly lower than for the speech token or the noise bursts. The best envelope ITD-JND measured was ca. 250 &mgr;s for the click train at 100 cycles per sec. Direct measurement of the psychometric function for envelope ITD by the method of constant stimuli showed discrimination above chance level down to 150 &mgr;s. The lateralization position experiment showed that both ILDs and envelope ITDs can lead to monotonic changes in lateral percept. Conclusions: The two cochlear implant users tested showed strong effects of ILDs in various broadband stimuli with respect to JNDs as well as lateralization position. The high dependency of ILD-JNDs on the interaural pitch difference suggests the potential importance of pitch-matched assignment of electrodes in the two ears by the speech processors. Envelope ITDs appear to be more ambiguous cues than ILDs, as reflected by the higher and more variable JNDs compared with normal-hearing listeners. The envelope ITD-JNDs of cochlear implant listeners depended on the stimulus.
Alternative Translation Initiation of the Moloney Murine Leukemia Virus mRNA Controlled by Internal Ribosome Entry Involving the p57/PTB Splicing Factor (*)

Moloney murine leukemia virus (Mo-MuLV) genomic mRNA codes for two gag precursors by alternative initiations of translation. An AUG codon governs the synthesis of the retroviral capsid proteins precursor, whereas a CUG codon directs the synthesis of a glycosylated cell surface antigen, the gross cell surface antigen. Control of the relative synthesis of the two precursors is crucial for MuLV infectivity and pathology. Furthermore, the MuLV mRNA leader sequence is very long and should inhibit translation according to the classical scanning model. This suggests a different translation initiation mechanism allowing gag efficient expression. We demonstrate, by using bicistronic vectors expressed in COS-7 cells, that the Mo-MuLV mRNA leader drives translation initiation by internal ribosome entry. We have localized the internal ribosome entry site (IRES) between the two initiation codons. This 126 nucleotide long IRES implies an oligopyrimidine tract located 45 nucleotides upstream of AUG codon. UV cross-linking and affinity chromatography experiments show that the PTB/p57 splicing factor specifically interacts with this oligopyrimidine tract. The MuLV IRES controls alternative translation initiation by activating the capsid protein precursor expression. This gag translational enhancer could exist in other retroviruses.
Clonal origins of human breast cancer

Tumours are usually considered as the clonal progeny of single transformed cells. An X‐chromosome inactivation assay has been applied to exploring clonal relationships in human breast cancer. Analysis of X‐inactivation in DNA extracted from microdissected in situ and invasive breast carcinoma by Hpa II restriction and polymerase chain reaction (PCR) of the androgen receptor exon I CAG polymorphism confirmed monoclonality in 105/133 samples of carcinoma cells from 31/32 informative breast cancers. Clonality was identical in seven cases between in situ and invasive carcinoma. Unexpectedly, 4 of 12 cancers (33%) with two or more monoclonal samples available were mosaic (polyclonal) in respect of X‐chromosome inactivation between separate morphologically homogeneous tumour cell samples. Concordant clonality supports a common clonal origin of in situ and invasive breast cancers, but frequent apparently mosaic X‐inactivation in breast cancer cannot be explained by non‐tumour cell contamination. It is concluded that these carcinomas may be genuinely multiclonal. Possible mechanisms of multiclonality include simultaneous transformation of cell groups straddling X‐chromosome inactivation patch boundaries, tumour‐initiating mutations prior to X‐inactivation, or recruitment of bystander stem cells by DNA transfer from necrotic or apoptotic tumour cells. Collision of independent cancers appears implausible at this frequency. Further studies using independent analytical techniques are required to test the important possibility that a significant proportion of mammary carcinomas are not monoclonal. Copyright © 2001 John Wiley & Sons, Ltd.
Imaging and management of greater trochanteric pain syndrome

Greater trochanteric pain syndrome (GTPS) is a commonly diagnosed regional pain syndrome with a wide spectrum of aetiologies, reflecting the anatomy of the structures outside the hip joint capsule. There are five muscle tendons that insert on to the greater trochanter and three bursae in the region of the greater trochanter. The term GTPS includes tendinopathies, tendinous tears, bursal inflammation and effusion. There are a range of treatments and therapies depending on the specific diagnosis and severity of the condition. Many patients with GTPS can be successfully managed conservatively with weight loss and non-steroidal anti-inflammatory drugs. Patients suffering from more chronic pain can receive varying degrees of symptomatic relief with lateral hip corticosteroid and local anaesthetic injections. More severe refractory cases of GTPS can be treated with surgical intervention. It is therefore important to make the correct diagnosis to ensure that appropriate management can be implemented. The clinical features of GTPS however are often non-specific because common conditions such as lumbar radicular pain and hip joint osteoarthritis can present with an almost identical form of lateral hip pain. The various diagnostic imaging modalities have particular strengths and weaknesses with ultrasound being the best first-line investigation due to its availability, low cost, dynamic nature and ability to guide treatments such as steroid injections. MRI can be very helpful in the further investigation of patients in whom there is diagnostic uncertainty as to the cause of lateral hip pain and in whom specialist orthopaedic referral is being considered.
Roaming in Connecting Light: Practical Visible Light Communication Leveraging LED Sensing

Given the growing interests on using Commercial Off-The-Shelf (COTS) devices to implement Visible Light Communication (VLC) systems, there is a call for filling the gap between VLC standards and practical deployments. In particular, since LED-Camera VLC systems have shown a strong potential in covering large indoor areas due to the increasing pervasiveness of LED lighting systems and smartphones, providing roaming support to such a system has become an impending need. To this end, we propose RoCLight as a lightweight solution to this call. In order to have a proper feedback channel for roaming support, we innovate in converting part of the LED luminaires (already used as the VLC transmitters) into light sensors. By sensing the disturbance to the ambient diffuse reflection caused by user presence and mobility, RoCLight is able to adaptively handoff its transmissions from one luminaire to another, so as to keep up with user mobility and hence to offer an adequate roaming support. We implement RoCLight as a small-scale testbed with five LED luminaires spanning a length of 7.5 meters, and we conduct various evaluations on the roaming support capability of RoCLight based on this testbed; all our experiment results strongly demonstrate its promising performance.
Binding of High Density Lipoprotein (HDL) and Discoidal Reconstituted HDL to the HDL Receptor Scavenger Receptor Class B Type I*

The binding of apoA-I-containing ligands to the HDL receptor scavenger receptor class B type I (SR-BI) was characterized using two different assays. The first employed conventional binding or competition assays with125I-labeled ligands. The second is a new nonradioactive ligand binding assay, in which the receptor-associated ligand is detected by quantitative immunoblotting (“immunoreceptor assay”). Using both methods, we observed that theK d value for spherical HDL (density = 1.1–1.13 g/ml) was ∼16 μg of protein/ml, while the values for discoidal reconstituted HDL (rHDL) containing proapoA-I or plasma apoA-I were substantially lower (∼0.4–5 μg of protein/ml). We also observed reduced affinity and/or competition for spherical125I-HDL cell association by higher relative to lower density HDL and very poor competition by lipid-free apoA-I and pre-β-1 HDL. Deletion of either 58 carboxyl-terminal or 59 amino-terminal residues from apoA-I, relative to full-length control apoA-I, resulted in little or no change in the affinity of corresponding rHDL particles. However, rHDL particles containing a double mutant lacking both terminal domains competed poorly with spherical 125I-HDL for binding to SR-BI. These findings suggest an important role for apoA-I and its conformation/organization within particles in mediating HDL binding to SR-BI and indicate that the NH2 and COOH termini of apoA-I directly or indirectly contribute independently to binding to SR-BI.
Genesis of the novel epidemic Vibrio cholerae O139 strain: evidence for horizontal transfer of genes involved in polysaccharide synthesis.

Only Vibrio cholerae strains of serotype O1 are known to cause epidemics, while non‐O1 strains are associated with sporadic cases of cholera. It was therefore unexpected that the recent cholera epidemic in Asia was caused by a non‐O1 strain with the serotype O139. We provide evidence that O139 arose from a strain closely related to the causative agent of the present cholera pandemic, V. cholerae O1 El Tor, by acquisition of novel DNA which was inserted into, and replaced part of, the O antigen gene cluster of the recipient strain. Part of the novel DNA was sequenced and two open reading frames (otnA and otnB) were observed, the products of which showed homology to proteins involved in capsule and O antigen synthesis, respectively. This suggests that the otnAB DNA determines the distinct antigenic properties of the O139 cell surface. The otnAB DNA was not detected in O1 strains, but was present in two non‐O1 V. cholerae strains with serotypes O69 and O141. In the O69 and O139 strains the otnAB genes were located proximate to the putative insertion sequence (IS) element rfbQRS, which is associated with O antigen synthesis genes in O1 strains, and may have played a role in the insertion of the otnAB DNA in the recipient chromosome. Our results suggest that the O139 strain arose by horizontal gene transfer between a non‐O1 and an O1 strain. The acquired DNA has altered the antigenic properties of the recipient O1 strain, providing a selective advantage in a region where a large part of the population is immune to O1 strains. (ABSTRACT TRUNCATED AT 250 WORDS)
Temporal variation in case fatality of acute myocardial infarction in Finland

Background. Previous studies have suggested that seasonal variation and weather conditions have an influence on the incidence and mortality of acute myocardial infarction (AMI). The influence of these factors on AMI case fatality is less studied. Aims. The aim of this study was to examine the temporal variation of AMI case fatality and the effect of daily weather conditions on it. Methods. We analysed death registry and hospital discharge data from all men and women (n=7328) with their first AMI occurrence in the seven largest cities in Finland in the years 1983, 1988, and 1993, aged 25 to 74 years. Results. The mean annual 28-day case fatality was 44%. We found significant weekly and monthly variation of case fatality (P<0.001). The December holiday season had the highest case fatality throughout the year in women and men aged 65–74 years (P<0.05). The highest weekly case fatality was on Sundays; it differed significantly from the rest of the weekdays only for the oldest age-group (64–74) (P<0.01). Conclusions. There is significant weekly and monthly variation in case fatality of AMI. The highest case fatality risk for AMI is during the Christmas season and on Sundays. Weather conditions were not found to have an effect on the case fatality.
On Development and Democracy: The Willing and Unwilling Goers

This article argues that the question of what comes first between development and democracy is a settled question: each is a standalone though not an isolated phenomenon. The analysis put forth, therefore, is an attempt to comprehend some of the dynamics when the two phenomena interact. It is the article‘s contention that the force which seems to propel and relate the two is the very urge of the people to participate in the developmental and democratic process of their societies. In the final analysis, the article maintains that nowhere in the world have the two phenomena (development and democracy) ever been achieved or received on a silver plate. The powers that be must use their authority to guide even to the point of coercing the Unwilling Goers‘ to significantly participate in the development and democratic process of their communities. Key words · Development · Democracy · Nation-building · East Asia · Uganda
Implementing the undergraduate mini‐CEX: a tailored approach at Southampton University

Objectives The mini‐clinical evaluation exercise (mini‐CEX) is widely used in the UK to assess clinical competence, but there is little evidence regarding its implementation in the undergraduate setting. This study aimed to estimate the validity and reliability of the undergraduate mini‐CEX and discuss the challenges involved in its implementation.
Polarization Color Imaging System for On‐Line Quantitative Evaluation of Facial Skin Lesions

BACKGROUND A number of studies have been performed for accurate evaluation of chromophores in skin lesions. Qualitative methods are subjective and cause user-dependent error in evaluation. Quantitative methods have limitations for widely distributed skin lesions due to poor spatial resolution, potential skin blanching, and difficulty in relocating identical sites for subsequent measurements and analysis. OBJECTIVE The objective was to develop a new imaging modality that provides both qualitative and quantitative methods to evaluate widely distributed skin lesions. METHODS We have developed a prototype polarization color imaging system named “DermaVision,” which provides quantitative on-line image analysis of polarization color images. Herein, we describe the hardware and software of DermaVision in terms of its performance and usefulness for dermatologic applications. RESULTS Polarization color images were successfully acquired from patients with vascular or pigmented skin lesions. The erythema and melanin index images were successfully computed and quantitatively confirmed the degree of erythema and pigmentation in the skin lesions. CONCLUSION We believe that DermaVision can be a useful auxiliary tool in dermatology because it simultaneously provides both qualitative and quantitative images of skin lesions.
Study on learning motivation for innovative talents of local normal universities

Abstract In order to improve the learning of innovative talents, the paper organically combine the learning motivation and self-efficacy, in a typical representative of the local normal universities as an example, with a total of 4305 undergraduates, analyzed the relationship between surface motivation and deep motivation, the relationship between learning motivation and self-efficacy, learning time and self-efficacy, and academic performance self-assessment and learning motivation & self-efficacy. Based on the above empirical research, this paper provides reference on the improvement of learning motivation for students of local colleges and universities.
Analgesic effects of preincisional administration of dextromethorphan and tenoxicam following laparoscopic cholecystectomy

Background: Pre‐incisional treatment with either N‐methyl‐D‐aspartate (NMDA) receptor antagonists or non‐steroidal anti‐inflammatory drugs (NSAIDs) improves postoperative pain relief. This study examines the effect on postlaparoscopic cholecystectomy (LC) pain of a combination of dextromethorphan (DM), a NMDA‐receptor antagonist, and tenoxicam, a NSAID, given preoperatively.
Biological vs. conventional combination treatment and work loss in early rheumatoid arthritis: a randomized trial.

IMPORTANCE The introduction of biological tumor necrosis factor inhibitors has improved the treatment of rheumatoid arthritis (RA) but at a substantial cost. These drugs have been shown to lead to superior radiological outcomes compared with a combination of conventional disease-modifying antirheumatic drugs over 2 years. OBJECTIVE To investigate whether radiological superiority translates into better work loss outcomes. DESIGN, SETTING, AND PARTICIPANTS Multicenter, 2-arm, parallel, randomized, active-controlled, open-label trial. Patients with early RA (symptom duration <1 year) were recruited from 15 rheumatology clinics in Sweden from October 1, 2002, through December 31, 2005. The study population was restricted to working-age patients (aged <63 years). INTERVENTIONS Patients who did not achieve low disease activity after 3 to 4 months of methotrexate therapy were randomized to receive additional biological treatment with infliximab or conventional combination treatment with sulfasalazine plus hydroxychloroquine. MAIN OUTCOMES AND MEASURES Monthly sick leave and disability pension days 21 months after randomization retrieved from the nationwide Swedish Social Insurance Office register. Main analyses were by intention to treat, including all patients, and adjusted for baseline sick leave and disability pension. RESULTS Of 204 eligible patients, 105 were randomized to biological and 99 to conventional treatment. Seven patients in the biological and 4 in the conventional treatment group never received the study drug, and 72 and 52 patients, respectively, followed the study per protocol for 21 months. The baseline mean (SD) work loss was 17 (13) d/mo (median, 16 d/mo) in both groups (mean difference, 0.6 d/mo; 95% CI, -3.0 to 3.9). The mean changes in work loss at 21 months were -4.9 d/mo in the biological and -6.2 d/mo in the conventional treatment group (adjusted mean difference, 1.6 d/mo; 95% CI, -1.2 to 4.4). Including only patients receiving at least 1 dose of assigned treatment, the adjusted mean difference was 1.5 d/mo (95% CI, -1.5 to 4.4), and in per-protocol analysis the adjusted mean difference was 0.3 d/mo (95% CI, -2.8 to 3.8). CONCLUSIONS AND RELEVANCE The radiological superiority of biological compared with conventional combination therapy did not translate into better work loss outcomes in patients with early RA who had experienced an insufficient response to methotrexate. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00764725.