Miracle-dz/UniFAR-FTUs huggingface dataset:
Cohesin's role in pluripotency and reprogramming

ABSTRACT Cohesin is required for ES cell self-renewal and iPS-mediated reprogramming of somatic cells. This may indicate a special role for cohesin in the regulation of pluripotency genes, perhaps by mediating long-range chromosomal interactions between gene regulatory elements. However, cohesin is also essential for genome integrity, and its depletion from cycling cells induces DNA damage responses. Hence, the failure of cohesin-depleted cells to establish or maintain pluripotency gene expression could be explained by a loss of long-range interactions or by DNA damage responses that undermine pluripotency gene expression. In recent work we began to disentangle these possibilities by analyzing reprogramming in the absence of cell division. These experiments showed that cohesin was not specifically required for reprogramming, and that the expression of most pluripotency genes was maintained when ES cells were acutely depleted of cohesin. Here we take this analysis to its logical conclusion by demonstrating that deliberately inflicted DNA damage - and the DNA damage that results from proliferation in the absence of cohesin - can directly interfere with pluripotency and reprogramming. The role of cohesin in pluripotency and reprogramming may therefore be best explained by essential cohesin functions in the cell cycle.
Participating in cardiac rehabilitation: a systematic review and meta-synthesis of qualitative data

Background: Participation in cardiac rehabilitation (CR) benefits patients with coronary heart disease (CHD), yet worldwide only some 15–30% of those eligible attend. To improve understanding of the reasons for poor participation we undertook a systematic review and meta-synthesis of the qualitative literature. Methods: Qualitative studies identifying patient barriers and enablers to attendance at CR were identified by searching multiple electronic databases, reference lists, relevant conference lists, grey literature, and keyword searching of the internet (1990–2010). Studies were selected if they included patients with CHD and reviewed experience or understanding about CR. Meta-synthesis was used to review the papers and to synthesize the data. Results: From 1165 papers, 34 unique studies were included after screening. These included 1213 patients from eight countries. Study methodology included interviews (n = 25), focus groups (n = 5), and mixed-methods (n = 4). Key reasons for not attending CR were physical barriers, such as lack of transport, or financial cost, and personal barriers, such as embarrassment about participation, or misunderstanding the reasons for onset of CHD or the purpose of CR. Conclusions: There is a vast amount of qualitative research which investigates patients’ reasons for non-attendance at CR. Key issues include system-level and patient-level barriers, which are potentially modifiable. Future research would best be directed at investigating strategies to overcome these barriers.
Acidification of pig slurry before separation to improve slurry management on farms

ABSTRACT Pig slurry, rich in plant nutrients such as nitrogen (N) and phosphorus (P), is generally applied to soil as organic fertilizer. However, costs related to slurry transport may limit its utilization to fields close to the farm, leading to significant N losses, namely ammonia (NH3) emissions. Slurry acidification, to minimize NH3 emissions, is a potential solution to this problem, while solid–liquid separation leads to a solid fraction (SF) – rich in organic matter (OM) and phosphorus – and a liquid fraction (LF) rich in soluble nutrients. We hypothesized that a combination of acidification and separation could affect the quality of the resulting fractions depending on the separation technique used. After acidification, the two most common techniques for separation, centrifugation (CF) and screw-press (SP), were applied. The main characteristics of the slurry fractions in terms of nutrient concentrations and speciation as well as the potential N mineralization (PNM) were analysed. Our results show SFs with improved properties, mostly N and PNM when acidification is performed before separation with both techniques. The PNM was significantly increased in LFs from both techniques after acidification. The concentration increased in LFs from SP with acidification; therefore, slurry acidification is recommended to avoid any N losses during the separation process with SP, while CF may not require such pretreatment. Acidification could allow the use of a cheaper technique such as SP relative to CF since it prevents NH3 emissions during the separation process and leads to more equilibrated fractions in terms of nutrient composition.
Basic helix-loop-helix transcription factors and regulation of alkaloid biosynthesis

Transcription factors of the basic Helix-Loop-Helix (bHLH) family play a central role in cell proliferation, determination, and differentiation. In plants, the regulatory functions of bHLHs in phenylpropanoid biosynthesis have been well established with regard to other interacting-proteins; i.e., MYB and WD40 repeat proteins. On the other hand, those in alkaloid biosynthesis are greatly limited due to the limited distribution of alkaloids in plant species. Recently, several groups have reported the regulatory functions of bHLH in alkaloid biosynthesis: novel CjbHLH1 in isoquinoline alkaloid biosynthesis in Coptis japonica, and Jasmonate-inducible MYC2-type bHLHs in nicotine-alkaloid biosynthesis in Nicotiana plants and indole alkaloid biosynthesis in Catharanthus roseus. We report here the JA-inducibility of CjbHLH1 and discuss the similarity and differences of non-MYC2-resemblant CjbHLH1 and MYC2-type bHLHs in nicotine and indole alkaloid biosynthesis.
Early vocabulary development in Mandarin (Putonghua) and Cantonese*

ABSTRACT Parent report instruments adapted from the MacArthur-Bates Communicative Development Inventories (CDI) examined vocabulary development in children aged 0 ; 8 to 2 ; 6 for two Chinese languages, Mandarin (n=1694) and Cantonese (n=1625). Parental reports suggested higher overall scores for Mandarin- than for Cantonese-speaking children from approximately 1 ; 4 onward. Factors relevant to the difference were only-child status, monolingual households and caregiver education. In addition to the comparison of vocabulary scores overall, the development of noun classifiers, grammatical function words common to the two languages, was assessed both in terms of the age and the vocabulary size at which these terms are acquired. Whereas age-based developmental trajectories again showed an advantage for Beijing children, Hong Kong children used classifiers when they had smaller vocabularies, reflecting the higher frequencies and greater precision of classifier use in adult Cantonese. The data speak to the importance of using not just age, but also vocabulary size, as a metric by which the acquisition of particular linguistic elements can be examined across languages.
Benefit of inpatient multidisciplinary rehabilitation up to 1 year after stroke.

OBJECTIVE To analyze the benefit of inpatient multidisciplinary rehabilitation up to 1 year after stroke. DESIGN Retrospective cohort study. SETTING Inpatient rehabilitation hospital in Japan. PARTICIPANTS A total of 1056 patients with stroke were divided into 3 groups based on the interval between stroke onset and admission to the rehabilitation hospital: group I, within 90 days (n=507, 48%); group II, 91 to 180 days (n=377, 36%); and group III, more than 180 days (n=172, 16%). INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Functional outcome (A to D; independent to totally dependent) in walking, affected upper extremity, and activities of daily living (ADLs) and discharge disposition. RESULTS Walking status improved in 70.9% of nonambulatory patients in group I, in 54.8% in group II, and in 43.9% in group III. Similarly, ADLs improved in 66.7% of the totally dependent patients in group I and in approximately 50% in groups II and III. Functional gain in those with a totally nonfunctional upper extremity at admission was poor (29.7%). Initial functional categories affected each outcome (P<.0001). On discharge, 73.8% in group I and approximately 60% in groups II and III went home. CONCLUSION Approximately half of all patients regained their abilities in walking and ADLs after inpatient multidisciplinary rehabilitation up to 1 year after stroke. However, there was considerable limitation in functional recovery of the affected upper extremity.
Transcription Activation by the Human Estrogen Receptor Subtypeβ (ERβ) Studied with ERβ and ERα Receptor Chimeras* *This work was supported by NIH Grants CA-18119 and CA-60514 (to B.S.K.).

We have studied the two estrogen receptor (ER) subtypes, ERα and ERβ, and chimeric constructs with ERα and ERβ to examine the bioactivities of these receptors and their responses to estrogen and antiestrogen ligands. Transcriptional activity of ERβ is highly dependent on cell/promoter context and on the nature of the ligand. ERβ activated significant levels of transcription in response to estrogens in certain cell types, but showed only moderate activity compared with ERα in others. Antiestrogens such as tamoxifen and 2-phenylbenzofuran, which show some agonistic activity with ERα, exhibit no agonistic activity with ERβ. Alteration of the amino-terminal A/B receptor domain can result in a dramatic change in cell type- and ligand-specific transcriptional activity of ERβ. Upon replacing the A/B domain of ERβ with the A/B domain of ERα, this receptor chimera not only exhibits an improved transcriptional response to estrogens, but also is now able to activate transcription upon treatment with these antiestrog.
Quantization-Based Approximate Nearest Neighbor Search with Optimized Multiple Residual Codebooks

SUMMARY Nearest neighbor search (NNS) among large-scale and high-dimensional vectors plays an important role in recent large-scale multimedia search applications. This paper proposes an optimized multiple codebook construction method for an approximate NNS scheme based on product quantization, where sets of residual sub-vectors are clustered according to their distribution and the codebooks for product quantization are constructed from these clusters. Our approach enables us to adaptively select the number of codebooks to be used by trading between the search accuracy and the amount of memory available.
Meeting the challenges and burdens associated with hereditary angioedema.

PURPOSE Because little is known about the burden of illness associated with hereditary angioedema (HAE), this article reviews the challenges in identifying and managing this rare disease and its humanistic and economic burdens. DESIGN We identified studies examining the burdens associated with HAE. Conducting larger studies using claims analyses for HAE is particularly challenging, owing to the rarity of the disease in health plans and to diagnostic/coding challenges. Because the data have been limited, larger surveys of patients have been conducted. They are explored here. METHODOLOGY We searched for studies addressing attack characterization, acute treatment, chronic disease management, adverse events, psychosocial burden, effect on work, and patient costs. PRINCIPAL FINDINGS HAE may result in physical and/or psychological disability because of the lack of effective treatments and the unpredictability of symptom severity. The reported average annual total costs per patient are approximately $42,000, ranging from approximately $14,000 for mild cases to approximately $96,000 for severe disease. It is not known how much of this is paid by the patients, although it can be assumed that it is substantial for some. CONCLUSION The appropriate use of disease-specific treatments for HAE may improve patients' quality of life and reduce HAE-associated morbidity and mortality while also reducing costs associated with hospitalizations and other interventions. Future cost-effectiveness studies are needed to examine these issues. Disease-specific agents are expected to significantly change the HAE treatment paradigm in the United States and dramatically improve the efficacy of medical care for these patients.
Oral Presentation

ObjectiveTo study the effect of proinsulin misfolding on insulin signalling in β cells. Methods C57BL/KsJ‐LepR db/db and db/m mice were used for analysis of insulin signalling, including measurement of the phospho‐insulin receptor (p‐IR) and phospho‐AKT (P‐AKT) levels, precursor of insulin receptor (proIR) levels, and marker of endoplasmic reticulum (ER) stress phospho‐eIF2a in the liver, skeletal muscle, and pancreatic islets. The folding of proinsulin was also evaluated. The effects of ER stress on insulin signalling were examined in β cells treated with the ER stress inducer thapsigargin. The effects of misfolded proinsulin on the processing and maturation of the insulin receptor precursor and insulin signalling were examined in HEK293T cells cotransfected with plasmids encoding the insulin receptor and diabetes‐inducing mutant proinsulin‐C(A7)Y. Abnormal interactions between the misfolded mutant proinsulin and insulin receptor precursor were evaluated by coimmunoprecipitation. Results 1. db/db mice showed a decrease in p‐AKT in the liver, skeletal muscle, and pancreatic islets. 2. In db/db islets, proinsulin misfolding was increased, which may account for defects in the processing and maturation of proIR and insulin signalling. 3. ER stress impaired insulin signalling but did not affect the processing and maturation of proIR. 4. The diabetes‐inducing mutant proinsulin interacted abnormally with proIR and impaired proIR processing, maturation, and signalling. Conclusions Insulin resistance existed not only in insulin target tissues but also in pancreatic islets. Proinsulin misfolding was increased in db/ db mice. Misfolded proinsulin impaired proIR maturation and its signalling in β cells, which may contribute to β cell failure and the development of diabetes in db/db mice.
Comparative studies with various substrains of Mycobacterium bovis BCG on the production of an antigenic protein, MPB70

A protein, isolated and purified from the unheated culture filtrate of Mycobacterium bovis BCG (substrain Tokyo 172) and designated MPB70, elicited a delayed skin reaction in guinea pigs sensitized with viable cells of BCG but not in those sensitized with heat-killed cells. The skin reaction reached the maximum 4 to 8 weeks after the inoculation of the BCG and then decreased gradually, resulting in conversion to negative after 20 weeks, whereas the skin reaction to purified protein derivative (PPD) continued to be positive. Guinea pigs immunized with viable cells of various substrains of BCG were skin tested with MPB70 and PPD. Guinea pigs immunized with the BCG substrain Tokyo 172 and the substrain Moreau (Brazil) showed strong delayed skin reactions to both MPB70 and PPD. On the other hand, guinea pigs immunized with the Pasteur substrain 1173P2, the Glaxo substrain 1077, the Copenhagen substrain 1331, the Tice substrain, or the Beijing substrain 64-42 showed negative skin reactions to MPB70, whereas they were strongly positive to PPD. In a two-dimensional acrylamide gel electrophoretic analysis of proteins from the culture filtrates of the BCG substrains, the culture filtrates of the Tokyo and Moreau substrains showed the spot of MPB70 on the gel slabs, whereas those of the other BCG substrains did not.
Pilotprojekt zur verbesserten Lungendeposition durch ein neues Verfahren der nasalen Inhalation

Zusammenfassung Einleitung: lnhalativ applizierte Medikamente können ihre Wirkung nur dann besonders effektiv entfalten, wenn sie bis in die mittleren und kleinen Atemwege gelangen. Das vorgestellte Verfahren kombiniert eine transnasale Aerosolapplikation mit einer pneumatischen Schienung der kleinen Atemwege. Methode: Bei 7 Patienten mit COPD im Stadium II und III nach GOLD erfolgte eine transnasale Inhalation eines in Wasser gelösten radiopharmakologischen Marker-Präparats bei einer mittleren Partikelgröße von 5,5 µm. Bei allen Patienten wurden in einem Abstand von mindestens 70 Stunden zwei unterschiedliche Applikationsmethoden angewandt. Bei der ersten („passiv“) inhalierte der Patient transnasal durch ein offenes Schlauchsystem, bei der zweiten („aktiv“) erfolgte eine Inhalation mit Atmungsunterstützung durch positiven Atemwegsdruck (pneumatische Schienung). Die planaren Szintigramme der Lunge sowie des Ganzkörpers wurden angefertigt, um die Verteilung der Aerosolteilchen zu detektieren. Ergebnisse: Bei der unter nichtinvasiver druckunterstützter Atmung („aktiv“) durchgeführten transnasalen Inhalation kommt es, im Vergleich zur „passiven“ Inhalation, zu einer erhöhten Deposition des Aerosols in der Lunge. Darüber hinaus konnte bei der „aktiven“ und „passiven“ Inhalation ein Nachweis von Aerosolpartikeln in der Lungenperipherie bei verhältnismäßig großen Aerosolteilchen (5,5 µm) beobachtet werden. Diskussion: Die Ergebnisse belegen, dass die Kombination aus transnasaler Inhalation und nichtinvasiver druckunterstützender Beatmung (pneumatische Schienung) zu einer deutlich verbesserten Partikeldeposition in der Lunge führt.
Light-Induced Expression of a MYB Gene Regulates Anthocyanin Biosynthesis in Red Apples1

Anthocyanins are secondary metabolites found in higher plants that contribute to the colors of flowers and fruits. In apples (Malus domestica Borkh.), several steps of the anthocyanin pathway are coordinately regulated, suggesting control by common transcription factors. A gene encoding an R2R3 MYB transcription factor was isolated from apple (cv Cripps' Pink) and designated MdMYB1. Analysis of the deduced amino acid sequence suggests that this gene encodes an ortholog of anthocyanin regulators in other plants. The expression of MdMYB1 in both Arabidopsis (Arabidopsis thaliana) plants and cultured grape cells induced the ectopic synthesis of anthocyanin. In the grape (Vitis vinifera) cells MdMYB1 stimulated transcription from the promoters of two apple genes encoding anthocyanin biosynthetic enzymes. In ripening apple fruit the transcription of MdMYB1 was correlated with anthocyanin synthesis in red skin sectors of fruit. When dark-grown fruit were exposed to sunlight, MdMYB1 transcript levels increased over several days, correlating with anthocyanin synthesis in the skin. MdMYB1 gene transcripts were more abundant in red skin apple cultivars compared to non-red skin cultivars. Several polymorphisms were identified in the promoter of MdMYB1. A derived cleaved amplified polymorphic sequence marker designed to one of these polymorphisms segregated with the inheritance of skin color in progeny from a cross of an unnamed red skin selection (a sibling of Cripps' Pink) and the non-red skin cultivar Golden Delicious. We conclude that MdMYB1 coordinately regulates genes in the anthocyanin pathway and the expression level of this regulator is the genetic basis for apple skin color.
A temperature‐sensitive expression system based on the Geobacillus stearothermophilus NRS 2004/3a sgsE surface‐layer gene promoter

The sgsE gene coding for the S‐layer (surface layer) protein in the thermophilic Gram‐positive bacterium Geobacillus stearothermophilus NRS 2004/3a is strongly induced when the culture is shifted from optimal (55 °C) to maximally tolerable growth temperature (67 °C). Here, we investigated the regulation of the sgsE promoter in G. stearothermophilus and tested the function of this promoter in Bacillus subtilis. We used EGFP (enhanced green fluorescent protein) reporter constructs and found that the sgsE promoter has very low basal activity at 28 °C, but is approx. 20‐fold induced by elevated growth temperatures (37 and 45 °C). The promoter confers high expression levels, as EGFP mRNA levels at 45 °C were approx. 120‐fold more abundant than mRNA levels of the cat (chloramphenicol resistance) gene, which was transcribed from a constitutive promoter on the same plasmid. In fluorescence‐microscopic and Western‐blot analysis, the EGFP protein was barely detectable at 28 °C, whereas intermediate and high levels were detected at 37 and 45 °C respectively. The potential to tune expression levels of genes driven by the sgsE promoter in B. subtilis by simple temperature adjustments presents a considerable potential for its future use as high‐yield protein expression system for B. subtilis.
Infectivity and persistence of an outbreak strain of Salmonella enterica serotype Typhimurium DT160 for house sparrows (Passer domesticus) in New Zealand

Abstract AIM: To examine the infective dose, incubation period and disease progression of an isolate of Salmonella enterica serotype Typhimurium definitive type 160 (DT160) originating from a naturally-infected house sparrow (Passer domesticus) during an outbreak of the disease in New Zealand. METHODS: Thirty-six house sparrows captured from the wild and free of Salmonella spp were divided into six groups of six birds, housed individually, and inoculated orally with phosphate buffered saline (PBS) or 101, 102, 103, 105, 2 × 108 colony forming units (cfu) of the outbreak strain of S. Typhimurium DT160. The birds were observed for 10 days for clinical signs and/or mortality, and faecal samples were collected to determine excretion of S. Typhimurium. The birds were eutha- nised 11 days post-inoculation (p.i.) and a wide range of tissue samples were collected for histopathological examination, and culture and typing of Salmonella spp. Macro-restriction profiling by pulsed-field gel electrophoresis (PFGE) using XbaI was performed for the epidemiological typing of S. Typhimurium DT160 isolates. RESULTS: Mortality in house sparrows inoculated with S. Typhimurium DT160 was dose-dependent, and 2/6 birds inoculated with 105 cfu and all six birds inoculated with 2 × 108 cfu died during the study. Infected sparrows displayed few clinical signs, apart from diarrhoea and/or polyuria, fluffed plumage, and sitting on the floor of the cage. Faecal excretion of DT160 occurred briefly in two birds inoculated with 102 cfu and four birds inoculated with 103 cfu, on most days in five birds inoculated with 105 cfu, and continuously in six birds inoculated with 2 × 108 cfu. DT160 was isolated from the livers of three birds which received 103 cfu, five birds dosed with 105 cfu, and all six birds given 2 × 108 cfu. Following necropsy, histopathological lesions similar to those seen in the natural disease were observed in the liver or spleen of three birds which received 103 cfu, and all birds dosed with ≥105 cfu. CONCLUSION: The results indicate that an isolate of S. Typhimurium DT60 originating from house sparrows in New Zealand is pathogenic to these birds and that the response is dose- dependent. The persistence and excretion of the pathogen may last for at least 10 days. This confirms that sparrows infected with DT160 could be a source of infection to humans and other in-contact animals.
Prognosis of wire bond lift-off fault of an IGBT based on multisensory approach

The safe and continuous operation of the power switches of the inverter units is vital in assisting the functioning of the inverter units. This paper proposes an algorithm for the condition monitoring and prognosis of wire-bond fault in an IGBT- extensively used power switch in inverter systems. The proposed algorithm employs both on-state collector emitter voltage and collector current in the estimation of IGBT junction temperature. These two signals complement each other as thermal sensitive electrical parameters and results in better estimation of junction temperature. This algorithm has integrated a stochastic method and Coffin Manson model to introduce criticality matrix which is used to determine the necessity for IGBT replacement. Both simulation result and experiment data verified the proposed. The proposed algorithm has the scope to be further modified for the condition monitoring of a more complex system in the future.