Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitative Model Calculation of the Time-dependent Protoporphyrin IX Concentration in Normal Human Epidermis After Delivery of ALA by Passive Topical Application or Iontophoresis¶

Abstract We present a mathematical layer model to quantitatively calculate the diffusion of 5-aminolevulinic acid (ALA) in the skin in vivo, its uptake into the cells and its conversion to protoporphyrin IX (PpIX) and subsequently to heme. The model is a modification and extension of a recently presented three-compartment model. The diffusion of ALA in the skin (epidermis, dermis) is described by the time-dependent diffusion equation, and the sink in this equation accounts for ALA uptake in the cells. As boundary conditions, we use the ALA flux across the human stratum corneum (SC) in vitro during passive or iontophoretic ALA delivery as measured in vitro. Besides the diffusion equation, the model includes three additional equations, similar in form to those of the three-compartment model but with a different interpretation. Our additional equations are supposed to describe, respectively, the conversion of ALA in the cytoplasm to some intermediate compound in the mitochondria and the conversion of the latter to PpIX and of PpIX to heme. The first conversion is a process of the Michaelis–Menten type, the other two are first-order rate processes. When fitted to the published data of PpIX fluorescence from normal human skin following iontophoresis of ALA, the model yields the tissue concentration of PpIX as a function of time after ALA application. The computed concentrations are in good agreement with the published phototoxic concentrations of PpIX in the tissues obtained from extraction. The model parameters obtained from the fit are subsequently used to compute the PpIX concentration in normal human skin after 4 h topical application of 10, 20 and 40% ALA. This again yields the PpIX concentrations in tissue, in good agreement with the published values. The saturation of the PpIX concentration as a function of applied ALA concentration is calculated and agrees with clinical observations on the effectiveness of photodynamic therapy. Photobleaching is simulated, with subsequent resynthesis of PpIX in qualitative agreement with experiment. Finally, the model predicts that only 2.5–3.5% of the ALA entering the skin after passing the SC is converted to PpIX. The layered model is a considerable simplification of real skin, but its successful qualitative and quantitative reproduction of experimental data may encourage further studies to test and refine the model to improve our understanding of the kinetics of ALA and the synthesis of PpIX in the skin.
Micro-Clusters and Networks: The Growth of Tourism

Introduction (Ewen J. Michael) Issues In Regional Development (C. Michael Hall and Ewen J. Michael) Development And Cluster Theory (Ewen J. Michael) Micro-Clusters In Tourism (Ewen J. Michael) The Role Of Networks (Paul Lynch and Alison Morrison) Micro-Clusters: Antiques, Retailing And Business Practice (Ewen J. Michael) Wine Tourism Networks And Clusters - Co-Operation And Barriers In New Zealand (Richard Mitchell and Chrissy Schreiber) Networks: Comparing Community Experiences (Laila Gibson and Paul Lynch) A Path For Policy (C. Michael Hall and Ewen J. Michael) The Contribution Of The Micro-Cluster Approach (C. Michael Hall, Paul Lynch, Ewen J. Michael and Richard Mitchell ).
Effects of curing temperature and superplasticizer on workability and compressive strength of self-compacting geopolymer concrete

This experimental work focuses on the effects of super plasticizer and curing temperature on the workability and compressive strength of self-compacting geopolymer concrete (SCGC). SCGC is an improved way of concreting execution that does not require compaction and is made by complete elimination of ordinary portland cement content. The parameters investigated were superplasticizer (SP) dosage and curing temperature. SCGC were synthesized from low calcium fly ash, activated by combinations of sodium hydroxide and sodium silicate solutions, and by incorporation of superplasticizer for self compactability. The SP dosages were 3%, 4%, 5%, 6% and 7% and the different curing temperatures were 60°C, 70°C, 80°C and 90°C. The effects of SP dosage on workability properties such as filling ability, passing ability and resistance to segregation were evaluated. The fresh properties were measured using slump flow, T-50 V-funnel, L-Box and J-ring test methods. The essential workability requirements for self compactability according to European Federation of National Associations Representing Producers and Applicators of Specialist Building Products for Concrete (EFNARC) were satisfied. Results showed that the workability and compressive strength improved with the increase in Super plasticizer dosage. An increase in strength was observed with the increase in curing temperature up to 70°C. However, the strength decreased when the curing temperature increased beyond 70°C. The compressive strength of 51.52MPa was obtained for SCGC with SP dosage of 6% and cured at 70°C oven temperature.
D‐type cyclin expression is decreased and p21 and p27 CDK inhibitor expression is increased when tsBN462 CCG1/TAFII250 mutant cells arrest in G1 at the restrictive temperature

Background: The tsBN462 temperature‐sensitive mutant hamster cell line exhibits cell cycle arrest and apoptosis at the restrictive temperature of 39.5 °C, due to a point mutation in the CCG1/TAFII 250 gene, which encodes a component of the general transcription factor TFIID.
Down-regulation of Monocyte Tissue Factor Mediated by Tissue Factor Pathway Inhibitor and the Low Density Lipoprotein Receptor-related Protein*

Inflammatory mediators like bacterial lipopolysaccharide induce monocytes to express tissue factor (TF), the cell-surface protein that triggers the blood clotting cascade in hemostasis and thrombotic disease. The physiologic ligand for TF is the serine protease, factor VIIa (FVIIa), and the resulting bimolecular enzyme, TF/FVIIa, can be reversibly inhibited by tissue factor pathway inhibitor (TFPI). Culturing monocytic cells in the presence of both FVIIa and TFPI caused down-regulation of TF expression via reducing its half-life. To exert this effect, FVIIa had to be competent to bind both TF and TFPI, and TFPI had to contain the C-terminal domain required for binding to other cell-surface receptors, including the low density lipoprotein receptor-related protein (LRP). TF down-regulation by FVIIa plus TFPI was abrogated by the 39-kDa receptor-associated protein, which blocks binding of all known ligands to LRP. Furthermore, treatment with FVIIa plus TFPI caused monocyte TF to colocalize with α-adaptin, a component of clathrin-coated pits. Thus, in addition to reversibly inhibiting TF/FVIIa catalytic activity, TFPI also mediates the permanent down-regulation of cell-surface TF in monocytic cells via LRP-dependent internalization and degradation. This represents an unusual mechanism for receptor internalization, requiring ligand-dependent bridging of one cell-surface receptor (TF) to a second cell-surface receptor (LRP), the latter being capable of clathrin-mediated internalization.
Ultrabrief (0.3 ms) or Brief (0.5 ms) Pulses for Right Unilateral Electroconvulsive Therapy: Is There a Difference in Seizure Thresholds?

Objectives To compare the minimum charge to elicit a seizure using 2 different pulse widths, the brief pulse (0.5 milliseconds [ms]) and the ultrabrief pulse (0.3 ms). Methods We compared retrospectively the last 30 patients in our ECT unit whose seizure thresholds were titrated using a pulse width of 0.5 ms to the last 30 patients whose seizure thresholds were titrated using a pulse width of 0.3 ms. The former were regular clinical patients, and the latter were participating in a clinical trial on the use of ultrabrief pulse treatment. All titrations were performed with right unilateral electrode positioning. Most patients continued to use psychotropic medications. Results Initial seizure threshold (as measured in millicoulombs [mC]) for the brief pulse group (0.5 ms) was 16 (n = 1); 32 (n = 21), and 64 (n = 8); whereas for the ultrabrief pulse group (0.3 ms), it was 9.2 (n = 3), 38.4 (n = 21), 19.2 (n = 3), 76.8 (n = 2), and 307.2 (n = 1). Excluding the outlier, there was no statistical difference between mean seizure thresholds. Conclusions If we exclude the outlier from the ultrabrief group (seizure threshold [ST], 307 mC), we can observe that most of the patients in both groups had an ST between 30 and 40 mC. No patient in the brief pulse group showed a lower ST than 16 mC, probably because this was the first step of titration for this group. The data suggest that the difference between 0.3 and 0.5 ms may not be big, although randomized prospective studies with a more precise and similar steps used for titration are needed. Clinical efficacy was not compared in the present study.
Relations of thyroid function to body weight: cross-sectional and longitudinal observations in a community-based sample.

BACKGROUND Overt hypothyroidism and hyperthyroidism may be associated with weight gain and loss. We assessed whether variations in thyroid function within the reference (physiologic) range are associated with body weight. METHODS Framingham Offspring Study participants (n=2407) who attended 2 consecutive routine examinations, were not receiving thyroid hormone therapy, and had baseline serum thyrotropin (TSH) concentrations of 0.5 to 5.0 mIU/L and follow-up concentrations of 0.5 to 10.0 mIU/L were included in this study. Baseline TSH concentrations were related to body weight and body weight change during 3.5 years of follow-up. RESULTS At baseline, adjusted mean weight increased progressively from 64.5 to 70.2 kg in the lowest to highest TSH concentration quartiles in women (P< .001 for trend), and from 82.8 (lowest quartile) to 85.6 kg (highest quartile) in men (P= .007 for trend). During 3.5 years of follow-up, mean (SD) body weight increased by 1.5 (5.6) kg in women and 1.0 (5.0) kg in men. Baseline TSH concentrations were not associated with weight change during follow-up. However, an increase in TSH concentration at follow-up was positively associated with weight gain in women (0.5-2.3 kg across increasing quartiles of TSH concentration change; P< .001 for trend) and men (0.4-1.3 kg across quartiles of TSH concentration change; P= .007 for trend). CONCLUSIONS Thyroid function (as assessed by serum TSH concentration) within the reference range is associated with body weight in both sexes. Our findings raise the possibility that modest increases in serum TSH concentrations within the reference range may be associated with weight gain.
Validation of the Doubly Labeled Water Method in Bald Eagles (Haliaeetus leucocephalus) and a Comparison of Two Equations for the Calculation of Energy Expenditure

We validated the doubly labeled water (DLW) technique for measurement of energy expenditure in bald eagles (Haliaeetus leucocephalus) in captivity by simultaneously measuring metabolizable energy intake in a feeding trial. We calculated CO₂ production using two equations, one typically used by animal ecologists (the "one-pool" equation) and the other typically used by human nutritionists (the "two-pool" equation). Metabolizable energy intake, as determined by feeding trials, for two adult eagles eating rats averaged 1,160 ± 89 kJ d⁻¹ and for four nestlings eating fish averaged 2,124 ± 40 kJ d⁻¹. Energy expenditure measured from DLW turnover using the one-pool equation averaged 2.2% ± 7.1% higher than metabolizable energy intake measured by feeding trials (not significantly different, P > 0.50), but when the two-pool equation was used, energy expenditure measured with DLW averaged 17.7% ± 6.7% lower than metabolizable energy intake measured by feeding trials (significantly different, 0.025 < P < 0.05). Thus, the use of the DLW technique with CO₂ production calculated by the one-pool equation was validated for bald eagles.
Postnatal development of different classes of cat retinal ganglion cells

Previous investigators have documented the postnatal development of alpha and beta type ganglion cells in cat retinae (Ramoa et al. [1987] Science 237:522–525; Ramoa et al. [1988] J. Neurosci. 8:4239–4261; Dann et al. [1987] Neurosci. Lett. 80:21–26; Dann et al. [1988] J. Neurosci. 8(5):1485–1499). The development of the remaining cells (about 50%), which constitute a heterogeneous group and are referred to here collectively as gamma cells (Boycott and Wässle, '74), has not been studied in detail. The purpose of this study was to compare the postnatal development of alpha, beta, and gamma cells in kitten and adult retinae using horseradish peroxidase histochemistry and the fluorescent dye Dil. In the kitten, alpha, beta, and gamma cells are recognizable. We find, as have others, that kitten alpha and beta cell bodies and dendritic fields are significantly smaller than in the adult. However, kitten gamma cells are nearly adult sized. In fact, at birth the cell bodies of beta cells throughout the retina are significantly smaller than those of gamma cells. During the first 12 weeks of life, alpha and beta cell bodies increase in size from 90% to 680% depending upon eccentricity. Gamma cells hardly increase in size at all. Also, the normal adult center‐to‐peripheral cell size gradient for alpha and beta cells is not seen in the neonate. Gamma cells show no such gradient in the neonate or adult. Our results suggest that the morphological development of alpha and beta cells occurs later than that of gamma cells and may explain some of the differences in the effects of visual deprivation and surgical manipulation upon the parallel Y‐, X‐, and W‐cell pathways. © 1994 Wiley‐Liss, Inc.
Prevalence of incontinence in patients after stroke during rehabilitation: a multi-centre study.

OBJECTIVE To report the prevalence and degree of isolated urinary and faecal incontinence and double incontinence (i.e. both urinary and faecal incontinence) in patients after stroke during post-acute rehabilitation and the factors related to incontinence. DESIGN A multi-centre prospective study. METHODS Data were extracted from the Thai Stroke Rehabilitation Registry. A total of 185 patients admitted within 4 weeks post-stroke were recruited. Based on the Barthel Index of Activities of Daily Living, the prevalence and degree of isolated urinary incontinence or faecal incontinence, and double incontinence were reported. Multivariate analysis was performed to identify any factors related to incontinence. RESULTS The admission prevalence for isolated urinary incontinence was 12.4%, for isolated faecal incontinence 7.6% and for double incontinence 33%. At discharge, the prevalence had decreased, to 8.1% for isolated urinary incontinence, 4.9 % for isolated faecal incontinence and 15.1% for double incontinence. Cognitive (adjusted odds ratio (OR) 3.63; 95% confidence interval (CI) 1.71-7.70) and leg muscle functions impairments (adjusted OR 2.79; 95% CI 1.29-6.07) were significantly related to urinary incontinence; whereas, age (adjusted OR 1.98; 95% CI 1.07-3.67) was related to faecal incontinence at admission. CONCLUSION Double incontinence was more prevalent than isolated incontinence in patients after stroke during post-acute rehabilitation. The decrease in prevalence at discharge reflected a recovery of bladder and bowel control. Age, cognitive and leg motor function impairments were related to incontinence.
SIRT1 attenuates high glucose-induced insulin resistance via reducing mitochondrial dysfunction in skeletal muscle cells

Insulin resistance is often characterized as the most critical factor contributing to the development of type 2 diabetes mellitus (T2DM). Sustained high glucose is an important extracellular environment that induces insulin resistance. Acquired insulin resistance is associated with reduced insulin-stimulated mitochondrial activity as a result of increased mitochondrial dysfunction. Silent information regulator 1 (SIRT1) is one member of the SIRT2 (Sir2)-like family of proteins involved in glucose homeostasis and insulin secretion in mammals. Although SIRT1 has a therapeutic effect on metabolic deterioration in insulin resistance, it is still not clear how SIRT1 is involved in the development of insulin resistance. Here, we demonstrate that pcDNA3.1 vector-mediated overexpression of SIRT1 attenuates insulin resistance in the high glucose-induced insulin-resistant skeleton muscle cells. These beneficial effects were associated with ameliorated mitochondrial dysfunction. Further studies have demonstrated that SIRT1 restores mitochondrial complex I activity leading to decreased oxidative stress and mitochondrial dysfunction. Furthermore, SIRT1 significantly elevated the level of another SIRT which is named SIRT3, and SIRT3 siRNA-suppressed SIRT1-induced mitochondria complex activity increments. Taken together, these results showed that SIRT1 improves insulin sensitivity via the amelioration of mitochondrial dysfunction, and this is achieved through the SIRT1–SIRT3–mitochondrial complex I pathway.
Association between preadmission oral antibiotic therapy and cerebrospinal fluid findings and sequelae caused by Haemophilus influenzae type b meningitis

The association between the administration of oral antibiotics and cerebrospinal fluid (CSF) findings and sequelae was investigated in 281 children with Haemophilus influenzae type b meningitis from two prospective studies. Ninety-four (33%) children were pretreated; 59% of pretreated children received ampicillin or amoxicillin. Compared with untreated children, in pretreated children significant decreases were noted in the percentage of poly-morphonuclear leukocytes in the CSF (P < 0.03), CSF protein concentration (P < 0.001) and percentage with a positive CSF Gram stain or culture (P < 0.05). When adjusted for duration of illness prior to admission, only the CSF protein concentration remained different (P < 0.01). Children who were pretreated were more likely (P < 0.05) to have paresis at one or more follow-up visits and sensorineural hearing loss (P < 0.05), but these differences were diminished when adjusted for duration of illness before admission. The duration of illness prior to admission was significantly (P < 0.0001) longer for pretreated (median, 3.0 days) than for untreated children (median, 1.0 day). The incidence of deafness did not correlate with duration of illness before admission by multiple logistic regression analysis (P = 0.132), but deafness was significantly (P < 0.02; relative risk, 5.9) more common when all children who were ill for more than 1 day prior to admission were compared to those children who were ill for 1 day or less. Oral antibiotics prior to admission (1) do not alter the CSF findings in most patients such that a diagnosis of H. influenzae type b meningitis cannot be established and (2) are associated with an increased likelihood of some neurologic sequelae, in part related to a longer duration of illness noted in pretreated patients before definitive therapy when compared to untreated patients.
Power Blurring: Fast Static and Transient Thermal Analysis Method for Packaged Integrated Circuits and Power Devices

High-temperature and temperature nonuniformity in high-performance integrated circuits (ICs) can significantly degrade chip performance and reliability. Thus, accurate temperature information is a critical factor in chip design and verification. Conventional volume grid-based techniques, such as finite-difference and finite-element methods (FEMs), are computationally expensive. In an effort to reduce the computation time, we have developed a new method, called power blurring (PB), for calculating temperature distributions using a matrix convolution technique in analogy with image blurring. The PB method considers the finite size and boundaries of the chip as well as 3-D heat spreading in the heat sink. PB is applicable to both static and transient thermal simulations. Comparative studies with a commercial FEM tool show that the PB method is accurate within 2%, with orders of magnitude speedup compared with FEM methods. PB can be applied to very fine power maps with a grid size as small as 10 μm for a fully packaged IC or submicrometer heat sources in power electronic transistor arrays. In comparison with architecture-level thermal simulators, such as HotSpot, PB provides much more accurate temperature profiles with reduced computation time.
Metabolic correlates of oxygen debt predict posttrauma early acute respiratory distress syndrome and the related cytokine response.

BACKGROUND The purpose of this study was to quantify the relationship between negative base excess (base deficit) and lactate as correlates of oxygen debt and the probability of the early acute respiratory distress syndrome (ARDS) response and with regard to the mediator and metabolic response characteristic of this disease. METHODS Eighty patients with multiple trauma were studied (514 samples) during their intensive care unit courses (Injury Severity Score 27.6+/-8.8, 36% deaths). Simultaneous samples of arterial base excess and lactate as correlates of oxygen debt, and enzyme-linked immunosorbent assay-measured mixed venous cytokines were obtained daily. At each sample period, the patient was categorized as having ARDS or non-ARDS. RESULTS Twenty-nine patients (36%; 19 deaths) developed ARDS over the period studied: 17 in postinjury days 1 to 4 (EARLY ARDS) and 12 in postinjury days 5 or later (LATE ARDS). Patients subsequently developing ARDS had evidence of ischemic acidosis on or within the first 24 hours after hospital admission (lower base excess -7.1 mmol/L and higher lactate 5.2 mmol/L in ARDS versus base excess -3.8 mmol/L and lactate 3.6 mmol/L in non-ARDS; p < 0.05). Patients with EARLY ARDS showed even lower (p < 0.05) initial 24 hour mean base excess and higher lactate (base excess -9.1 mmol/L and lactate 6.4 mmol/L) compared with LATE ARDS (base excess -4.3 mmol/L and lactate 3.3 mmol/L). In EARLY ARDS, this degree of ischemic acidosis was followed by a greater mean IL-6 response in the postinjury days 1 to 4 (323 pg/mL) compared with the LATE ARDS response (141 pg/mL) (p < 0.05) or compared with the non-ARDS IL-6 response (67 pg/mL; p < 0.001). In addition, in EARLY ARDS, mean IL-8 levels in postinjury days 1 to 4 (264 pg/mL) were higher than in LATE ARDS (168 pg/mL) (p < 0.05) and the mean IL-1 response in postinjury days 1 to 4 of EARLY ARDS (65 pg/mL) was greater than non-ARDS (32 pg/mL) (p < 0.05). Derivation of probability curves suggests a critical threshold of base excess -6.6 mmol/L or greater for an increased risk of EARLY ARDS. CONCLUSION These data suggest that the maximum posttrauma oxygen debt (quantified by the ischemia correlates of negative base excess and lactate) is a critical primary determinant of the later fulminant autoinflammatory EARLY ARDS response mediated by the host's endogenous cytokine mediators.