Miracle-dz/UniFAR-FTUs huggingface dataset:
The impact of bright artificial white and ‘blue‐enriched’ light on sleep and circadian phase during the polar winter

Delayed sleep phase (and sometimes free‐run) is common in the Antarctic winter (no natural sunlight) and optimizing the artificial light conditions is desirable. This project evaluated sleep when using 17 000 K blue‐enriched lamps compared with standard white lamps (5000 K) for personal and communal illumination. Base personnel, 10 males, five females, 32.5 ± 8 years took part in the study. From 24 March to 21 September 2006 light exposure alternated between 4–5‐week periods of standard white (5000 K) and blue‐enriched lamps (17 000 K), with a 3‐week control before and after extra light. Sleep and light exposure were assessed by actigraphy and sleep diaries. General health (RAND 36‐item questionnaire) and circadian phase (urinary 6‐sulphatoxymelatonin rhythm) were evaluated at the end of each light condition. Direct comparison (rmanova) of blue‐enriched light with white light showed that sleep onset was earlier by 19 min (P = 0.022), and sleep latency tended to be shorter by 4 min (P = 0.065) with blue‐enriched light. Analysing all light conditions, control, blue and white, again provided evidence for greater efficiency of blue‐enriched light compared with white (P < 0.05), but with the best sleep timing, duration, efficiency and quality in control natural light conditions. Circadian phase was earlier on average in midwinter blue compared with midwinter white light by 45 min (P < 0.05). Light condition had no influence on general health. We conclude that the use of blue‐enriched light had some beneficial effects, notably earlier sleep, compared with standard white light during the polar winter.
Enhanced CREB phosphorylation in immature dentate gyrus granule cells precedes neurotrophin expression and indicates a specific role of CREB in granule cell differentiation

Differentiation and maturation of dentate gyrus granule cells requires coordinated interactions of numerous processes. These must be regulated by protein factors capable of integrating signals mediated through diverse signalling pathways. Such integrators of inter and intracellular physiological stimuli include the cAMP‐response element binding protein (CREB), a leucine‐zipper class transcription factor that is activated through phosphorylation. Neuronal activity and neurotrophic factors, known to be involved in granule cell differentiation, are major physiologic regulators of CREB function. To examine whether CREB may play a role in governing coordinated gene transcription during granule cell differentiation, we determined the spatial and temporal profiles of phosphorylated (activated) CREB throughout postnatal development in immature rat hippocampus. We demonstrate that CREB activation is confined to discrete, early stages of granule cell differentiation. In addition, CREB phosphorylation occurs prior to expression of the neurotrophins BDNF and NT‐3. These data indicate that in a signal transduction cascade connecting CREB and neurotrophins in the process of granule cell maturation, CREB is located upstream of neurotrophins. Importantly, CREB may be a critical component of the machinery regulating the coordinated transcription of genes contributing to the differentiation of granule cells and their integration into the dentate gyrus network.
Association of Brief Health Literacy Screening and Blood Pressure in Primary Care

Health literacy impacts health outcomes. However, the relationship to blood pressure is inconsistent. This study aimed to determine whether health literacy, assessed by clinic staff, is associated with blood pressure among patients with hypertension. The design was a cross-sectional study of a large sample of primary care patient encounters in 3 academic medical center clinics in Nashville, Tennessee. Health literacy was assessed using the Brief Health Literacy Screen, with higher scores indicating higher health literacy. Blood pressure was extracted from the electronic health record. Using 23,483 encounters in 10,644 patients, the authors examined the association of health literacy with blood pressure in multivariable analyses, adjusting for age, gender, race, education, and clinic location. Independent of educational attainment, 3-point increases in health literacy scores were associated with 0.74 mmHg higher systolic blood pressure (95% CI [0.38, 1.09]) and 0.30 mmHg higher diastolic blood pressure (95% CI [0.08, 0.51]). No interaction between education and health literacy was observed (p = .91). In this large primary care population of patients with hypertension, higher health literacy, as screened in clinical practice, was associated with a small increase in blood pressures. Future research is needed to explore this unexpected finding.
Association of Elevated C-reactive Protein Levels With an Impaired Prognosis in Patients With Surgically Treated Endometrial Cancer

OBJECTIVE: To evaluate whether C-reactive protein (CRP) serum levels are associated with prognosis in surgically treated endometrial cancer. METHODS: In the present multicenter study, CRP serum levels were measured preoperatively in 403 surgically staged patients with endometrioid endometrial cancer. Results were correlated to clinical data. RESULTS: The mean (standard deviation) serum CRP level in patients with endometrial cancer was 1.0 (1.8) mg/dL. Serum CRP levels were associated with tumor stage (P=.01), but not with tumor grade (P=.8), lymph node involvement (P=.8), and age at diagnosis (P=.9). In a univariable survival analysis, serum CRP levels, tumor stage, tumor grade, and age at diagnosis were associated with disease-free and overall survival (all P <.001). In a multivariable Cox regression model, serum CRP levels (P=.001, P=.004), tumor stage (P <.001, P <.001), tumor grade (P=.02, P=.009), and age at diagnosis (P=.002, P=.001) were independent prognostic factors for disease-free and overall survival. CONCLUSION: Our results suggest that elevated serum CRP levels are associated with a less favorable prognosis in patients with surgically treated endometrial cancer. LEVEL OF EVIDENCE: II
A finite-time stability concept and conditions for finite-time and exponential stability of controlled nonlinear systems

This paper introduces a finite-time stability concept for nonlinear systems and the corresponding notion of stabilizability of controls. The concept generalizes previous finite-time stability as it requires that the state trajectory satisfies a given bound at some time instant in a certain interval, whereas previous notions considers that the system stays within that bound over the entire interval. Here, the bound on the trajectory may represent a region arbitrarily close to the origin, and thus it is in tune with situations where contractive trajectories are required. This feature allows us to relate the proposed concept with the usual exponential stability concept, and simultaneously, with the previous finite-time concepts, thus clarifying the relations among them. As regards to controlled systems, we derive a sufficient condition for stabilizability, with the interpretation that the size of the time interval demanded by the control to drive the trajectory into a specified region is in inverse proportion with the size of the region. Moreover, we present a simple moving horizon implementation for a stabilizing (in the new sense) control that provides an exponentially stable controlled system. For stationary controls we can connect stabilizability in the sense here with the classical exponential sense. We show that the control is exponentially stabilizing whenever it is finite-time stabilizing and stationary. An illustrative example is included
Potential Application of N-Carbamoyl-β-Alanine Amidohydrolase from Agrobacterium tumefaciens C58 for β-Amino Acid Production

ABSTRACT An N-carbamoyl-β-alanine amidohydrolase of industrial interest from Agrobacterium tumefaciens C58 (βcarAt) has been characterized. βcarAt is most active at 30°C and pH 8.0 with N-carbamoyl-β-alanine as a substrate. The purified enzyme is completely inactivated by the metal-chelating agent 8-hydroxyquinoline-5-sulfonic acid (HQSA), and activity is restored by the addition of divalent metal ions, such as Mn2+, Ni2+, and Co2+. The native enzyme is a homodimer with a molecular mass of 90 kDa from pH 5.5 to 9.0. The enzyme has a broad substrate spectrum and hydrolyzes nonsubstituted N-carbamoyl-α-, -β-, -γ-, and -δ-amino acids, with the greatest catalytic efficiency for N-carbamoyl-β-alanine. βcarAt also recognizes substrate analogues substituted with sulfonic and phosphonic acid groups to produce the β-amino acids taurine and ciliatine, respectively. βcarAt is able to produce monosubstituted β2- and β3-amino acids, showing better catalytic efficiency (kcat/Km) for the production of the former. For both types of monosubstituted substrates, the enzyme hydrolyzes N-carbamoyl-β-amino acids with a short aliphatic side chain better than those with aromatic rings. These properties make βcarAt an outstanding candidate for application in the biotechnology industry.
Evaluation of Donor-Specific Transfusion Sources: Unique Failure of Bone Marrow Cells to Induce Prolonged Skin Allograft Survival with Anti-CD154 Monoclonal Antibody

Background. Treatment with anti-CD154 monoclonal antibody (mAb) plus a donor-specific transfusion (DST) of spleen cells prolongs skin allograft survival in mice through a mechanism involving deletion of host alloreactive CD8+ T cells. It is unknown if other lymphohematopoietic cell populations can be used as a DST. Methods. Murine recipients of allogeneic skin grafts on day 0 were either untreated or given a DST on day −7 plus 4 doses of anti-CD154 mAb on days −7, −4, 0, and +4. Deletion of CD8+ alloreactive cells was measured using “synchimeric” CBA recipients, which circulate trace populations of TCR transgenic alloreactive CD8+ T cells. Results. Transfusion of splenocytes, thymocytes, lymph node cells, or buffy coat cells led to prolonged skin allograft survival in recipients treated with anti-CD154 mAb. In contrast, bone marrow DST failed to delete host alloreactive CD8+ T cells and was associated with brief skin allograft survival. Transfusions consisting of bone marrow-derived dendritic cells or a mixture of splenocytes and bone marrow cells were also ineffective. Conclusions. Donor-specific transfusions of splenocytes, thymocytes, lymph node cells, or buffy coat cells can prolong skin allograft survival in recipients treated with costimulation blockade. Bone marrow cells fail to serve this function, in part by failing to delete host alloreactive CD8+ T cells, and they may actively interfere with the function of a spleen cell DST. The data suggest that transplantation tolerance induction protocols that incorporate bone marrow cells to serve as a DST may not be effective.
Natural Variant of Collagen-Like Protein A in Serotype M3 Group A Streptococcus Increases Adherence and Decreases Invasive Potential

ABSTRACT Group A Streptococcus (GAS) predominantly exists as a colonizer of the human oropharynx that occasionally breaches epithelial barriers to cause invasive diseases. Despite the frequency of GAS carriage, few investigations into the contributory molecular mechanisms exist. To this end, we identified a naturally occurring polymorphism in the gene encoding the streptococcal collagen-like protein A (SclA) in GAS carrier strains. All previously sequenced invasive serotype M3 GAS possess a premature stop codon in the sclA gene truncating the protein. The carrier polymorphism is predicted to restore SclA function and was infrequently identified by targeted DNA sequencing in invasive strains of the same serotype. We demonstrate that a strain with the carrier sclA allele expressed a full-length SclA protein, while the strain with the invasive sclA allele expressed a truncated variant. An isoallelic mutant invasive strain with the carrier sclA allele exhibited decreased virulence in a mouse model of invasive disease and decreased multiplication in human blood. Further, the isoallelic invasive strain with the carrier sclA allele persisted in the mouse nasopharynx and had increased adherence to cultured epithelial cells. Repair of the premature stop codon in the invasive sclA allele restored the ability to bind the extracellular matrix proteins laminin and cellular fibronectin. These data demonstrate that a mutation in GAS carrier strains increases adherence and decreases virulence and suggest selection against increased adherence in GAS invasive isolates.
Binocular function during unequal monocular input

The fine task of stereoscopic depth discrimination in human subjects requires a functional binocular system. Behavioral investigations show that relatively small binocular abnormalities can diminish stereoscopic acuity. Clinical evaluations are consistent with this observation. Neurons in visual cortex represent the first stage of processing of the binocular system. Cells at this level are generally acutely sensitive to differences in relative depth. However, an apparent paradox in previous work demonstrates that tuning for binocular disparities remains relatively constant even when large contrast differences are imposed between left and right eye stimuli. This implies a range of neural binocular function that is at odds with behavioral findings. To explore this inconsistency, we have conducted psychophysical tests by which human subjects view vertical sinusoidal gratings drifting in opposite directions to left and right eyes. If the opposite drifting gratings are integrated in visual cortex, as wave theory and neurophysiological data predict, the subjects should perceive a fused stationary grating that is counter‐phasing in place. However, this behavioral combination may not occur if there are differences in contrast and therefore signal strength between left and right eye stimuli. As expected for the control condition, our results show fused counter‐phase perception for equal inter‐ocular grating contrasts. Our experimental tests show a striking retention of counter‐phase perception even for relatively large differences in inter‐ocular contrast. This finding demonstrates that binocular integration, although relatively coarse, can occur during substantial differences in left and right eye signal strength.
Role for the Chlamydial Type III Secretion Apparatus in Host Cytokine Expression

ABSTRACT In many important human pathogens, such as Shigella and Salmonella spp. , the bacterial type III secretion (T3S) apparatus is required to initiate inflammation via activation of caspase-1- or NF-κB-dependent genes. Using an ex vivo infection model, the goal of the present study was to determine whether the chlamydial T3S apparatus also modulates the host inflammatory response. Infections of mouse peritoneal macrophages were performed with Chlamydia muridarum, and the expression of inflammatory cytokines was monitored by quantitative reverse transcription-PCR and enzyme-linked immunosorbent assay. Since there is no current genetic system for Chlamydia spp. , blockade of T3S was accomplished pharmacologically using a T3S inhibitor called INP0007. It has been previously shown that INP0007 also blocks chlamydial growth in vitro and that the addition of exogenous iron completely reverses this deficit. The addition of iron to INP0007-treated C. muridarum-infected macrophages not only restored chlamydial growth deficit caused by INP0007 but also led to a multi-inclusion phenotype. Overall, T3S inhibition led to decreased interleukin-6 (IL-6), IL-1β, and CXCL10, whereas the tumor necrosis factor alpha levels were unchanged. Rescue of chlamydial growth by addition of iron sulfate did not restore cytokine production, implying that the decreased expression of many cytokines during infection was dependent on T3S and not solely on growth. In addition, the observation that the greatest effects of INP0007 were seen at late time points during infection suggests that a temporally regulated T3S effector protein(s) may be triggering the host cytokine response.
Ciz1 promotes mammalian DNA replication

Using a cell-free system that reconstitutes initiation of mammalian DNA replication, we identified a cyclin A-responsive protein, p21Cip1-interacting zinc finger protein 1 (Ciz1). In cell-free experiments, Ciz1 protein increases the number of nuclei that initiate DNA replication, and in intact cells GFP-tagged Ciz1 stimulates DNA synthesis, in both a wild-type and a p21Cip1 null background. Furthermore, mutation of a putative cyclin-dependent kinase phosphorylation site at threonines 191/2 alters Ciz1 activity in vitro, indicating that this site plays a role in regulating Ciz1. Consistent with a role in DNA replication, endogenous Ciz1 is present in nuclear foci that co-localize with PCNA during S phase, and targeted depletion of Ciz1 transcripts restrains cell proliferation by inhibiting entry to S phase. Ciz1-depleted cells accumulate with chromatin bound Mcm3 and PCNA but fail to synthesize DNA efficiently. These cell-based and cell-free experiments suggest that Ciz1 functions to promote DNA replication after replication complex formation. Finally, alternatively spliced forms of Ciz1 occur in embryonic cells from mouse and man, raising the possibility that Ciz1 splicing contributes to the regulation of DNA replication during development.
Cardiac Rehabilitation Wait Times: EFFECT ON ENROLLMENT

PURPOSE: Cardiac rehabilitation (CR) is a proven effective means for secondary prevention of coronary heart disease. Timely access to CR services is key to promoting patient participation and ensuring optimal patient outcomes. Despite wait time benchmarks having been established, research regarding how long patients wait to enter CR following referral receipt is limited. The aim of this study was to (a) describe wait times from CR referral to intake assessment and (b) examine the association of wait time to CR enrollment rates. METHODS: Wait time from date of CR referral to date of intake assessment was calculated in days for 599 participants referred to CR from 2006 to 2009 inclusive. A descriptive examination of sociodemographic and clinical characteristics was performed, followed by logistic regression analysis to assess the wait time by enrollment relationship. RESULTS: Median wait time from referral receipt to CR intake was 42.0 days. Wait time had a negative effect on CR enrollment, such that for every 1-day increment in wait time, patients were 1% less likely to enroll. CONCLUSIONS: The time that patients wait to enroll in CR may affect the number of patients who choose to attend, and longer wait times may mean fewer patients will benefit from CR participation. Programs should be encouraged to undertake quality improvement initiatives to ensure wait times are not negatively impacting patient enrollment and ultimately preventing patients from benefiting from CR participation. Further research is needed to establish evidence-based wait time benchmarks and interventions to promote timely access to CR services.
Ethanol production by immobilized Saccharomyces cerevisiae, Saccharomyces uvarum, and Zymomonas mobilis

Saccharomyces cerevisiae NRRL Y‐2034, S, uvarum NRRL Y‐1347, and Zymomonas mobilis NRRL B‐806 each were separately immobilized in a Ca‐alginate matrix and incubated in the presence of a free‐flowing and continuous 1, 3, 5, 10, or 20% (w/w) glucose solution. In general, the yeast cells, converted 100percnt; of the 1, 3, and 5% glucose to alcohol within 48 h and maintained such a conversion rate for at least two weeks. The bacterium converted ca. 90% (w/w) of the 1, 3, and 5% glucose to alcohol continuously for one week. However, both the yeast and bacterium were inhibited in the highest glucose (20% w/w) solution. All of the immobilized cultures produced some alcohol for at least 14 days. Immobilized S. cerevisiae was the best alcohol producer of all of the glucose concentrations; the yeast yielded 4.7 g ethanol/100 g solution within 72 h in the 10% glucose solution. After 7–8 days in the 10% solution, S. cerevisiae produced ethanol at 100% of theoretical yield (5.0 g ethanol/100 g solution), with a gradual decrease in alcohol production by 14 days. Immobillized S. uvarum produced a maximum of 4.0 g ethanol/100 g solution within 2 days and then declined to ca. 1.0 g ethanol/100 g solution after 7 days continuous fermentation in the 10% glucose solution. Zymomonas mobilis reached its maximum ethanol production at 4 days (4.7 g/100 g solution), and then diminished similarly to S. uvarum. The development of a multiple disk shaft eliminated the problem both of uneven distribution of alginate‐encapsulated cells and of glucose channeling within the continuous‐flow fermentor column. This invention improved alcohol production about threefold for the yeast cells.
An Update on Candida tropicalis Based on Basic and Clinical Approaches

Candida tropicalis has emerged as one of the most important Candida species. It has been widely considered the second most virulent Candida species, only preceded by C. albicans. Besides, this species has been recognized as a very strong biofilm producer, surpassing C. albicans in most of the studies. In addition, it produces a wide range of other virulence factors, including: adhesion to buccal epithelial and endothelial cells; the secretion of lytic enzymes, such as proteinases, phospholipases, and hemolysins, bud-to-hyphae transition (also called morphogenesis) and the phenomenon called phenotypic switching. This is a species very closely related to C. albicans and has been easily identified with both phenotypic and molecular methods. In addition, no cryptic sibling species were yet described in the literature, what is contradictory to some other medically important Candida species. C. tropicalis is a clinically relevant species and may be the second or third etiological agent of candidemia, specifically in Latin American countries and Asia. Antifungal resistance to the azoles, polyenes, and echinocandins has already been described. Apart from all these characteristics, C. tropicalis has been considered an osmotolerant microorganism and this ability to survive to high salt concentration may be important for fungal persistence in saline environments. This physiological characteristic makes this species suitable for use in biotechnology processes. Here we describe an update of C. tropicalis, focusing on all these previously mentioned subjects.
Evidence for a role for protein tyrosine phosphatase in the control of ion release from the guard cell vacuole in stomatal closure

Protein tyrosine phosphatases (PTPases) exist in plants, but their role in plant signaling processes is unknown. One of the most important signaling networks in plants concerns the regulation of stomatal aperture, by which closure of stomatal pores restricts water loss in dry conditions, a process essential for plant survival. Closure is achieved by reduction in guard cell volume as a consequence of net efflux of potassium salt at both plasmalemma and tonoplast. To test whether protein tyrosine phosphorylation has any role in guard cell signaling processes, the effects on stomatal aperture and on guard cell K(Rb) fluxes of a number of specific inhibitors of PTPases have been investigated. Stomatal closure induced by abscisic acid, high external Ca2+, hydrogen peroxide, and dark were all prevented by one such inhibitor, phenylarsine oxide, which added to closed stomata promoted reopening. Flux measurements with 86Rb+ identified the efflux across the tonoplast as the sensitive process, implying that protein tyrosine dephosphorylation must occur at or downstream of the Ca2+ signal responsible for triggering ion efflux from the vacuole. There was no inhibition of efflux at the plasmalemma. A second inhibitor of PTPases, 3,4 dephosphatin, gave very similar effects, inhibiting closure induced by abscisic acid, high external Ca2+, and dark, and promoting reopening if added to closed stomata. Again, the efflux of K(Rb) at the tonoplast was the sensitive process. These results provide clear evidence for the involvement of PTPases in a major signaling network in plants.