Miracle-dz/UniFAR-FTUs huggingface dataset:
Fabrication of low-cost micropatterned polydimethyl-siloxane scaffolds to organise cells in a variety of two-dimensioanl biomimetic arrangements for lab-on-chip culture platforms

We present the rapid-prototyping of type I collagen micropatterns on poly-dimethylsiloxane substrates for the biomimetic confinement of cells using the combination of a surface oxidation treatment and 3-aminopropyl triethoxysilane silanisation followed by glutaraldehyde crosslinking. The aim of surface treatment is to stabilise microcontact printing transfer of this natural extracellular matrix protein that usually wears out easily from poly-dimethylsiloxane, which is not suitable for biomimetic cell culture platforms and lab-on-chip applications. A low-cost CD-DVD laser was used to etch biomimetic micropatterns into acrylic sheets that were in turn replicated to poly-dimethylsiloxane slabs with the desired features. These stamps were finally inked with type I collagen for microcontact printing transfer on the culture substrates in a simple manner. Human hepatoma cells (HepG2) and rat primary hepatocytes, which do not adhere to bare poly-dimethylsiloxane, were successfully seeded and showed optimal adhesion and survival on simple protein micropatterns with a hepatic cord geometry in order to validate our technique. HepG2 cells also proliferated on the stamps. Soft and stiff poly-dimethylsiloxane layers were also tested to demonstrate that our cost-effective process is compatible with biomimetic organ-on-chip technology integrating tunable stiffness with a potential application to drug testing probes development where such cells are commonly used.
Relation between social functioning and neurocognitive test results using the Optional Thinking Test in schizophrenia

Abstract The current study investigated the relationship between clinical evaluations of social functioning and neurocognitive test results, including various fluency tests for assessing divergent thinking, in patients with schizophrenia. The Optional Thinking Test (OTT) was used to measure the ability of individuals to conceive of alternatives. This test assesses alternative thinking, or the capacity to generate solutions to problems. The current study examined 36 schizophrenia patients and 25 normal subjects using the Mini‐Mental State Examination (MMSE), the Rey Auditory Verbal Learning Test (RAVLT), the Letter Cancellation Test (LCT), the Letter and Category Fluency Tests, and the OTT for neurocognitive assessment, as well as the Positive and Negative Syndrome Scale (PANSS), the Global Assessment of Functioning (GAF), the Social Functioning Scale (SFS), and the Life Assessment Scale for the Mentally Ill – Interpersonal Relations (LASMI‐I) for clinical measures. The schizophrenia patients had significantly poorer performances on the MMSE, RAVLT, LCT (time), fluency tests, and OTT than the controls. In the OTT, the proportions of classified strategies were indistinguishable between the schizophrenia patients and the controls. Alternative thinking, as measured by the OTT, was correlated with verbal fluency and attention but was not correlated with the social functioning scores (GAF, SFS, LASMI‐I), whereas the Means‐Ends Problem‐Solving was correlated with the GAF in schizophrenia. Patients with schizophrenia could conceive of the same categories of alternatives as healthy people, but could not conceive as many alternatives.
Significance of monitoring plasma levels of amitriptyline, and its hydroxylated and desmethylated metabolites in prediction of the clinical outcome of depressive state

Abstract The clinical significance of monitoring the plasma levels of amitriptyline and its metabolites in prediction of the clinical outcome of depressive episode was investigated in 49 inpatients. Discriminant analysis of drug concentrations (at two weeks after initiation of drug treatment) and clinical outcome revealed that increasing the plasma levels of amitriptyline, cis‐isomers of hydroxylated metabolites (Z‐10‐hydroxyamitriptyline and Z‐10‐hydroxynortriptyline) predicted a better clinical outcome, while increasing of plasma levels of nortriptyline and trans‐isomers of hydroxylated metabolites (E‐10‐hydroxyamitriptyline and E‐10‐hydroxynortriptyline) were shown to predict a poor clinical outcome in the depressive episode of the subjects, and that clinical outcome of approximately 73% of the subjects could be correctly predicted.
Differentiation of High Lipid Content From Low Lipid Content Adrenal Lesions Using Single-Source Rapid Kilovolt (Peak)-Switching Dual-Energy Multidetector CT

Purpose This study aimed to determine if a single-source rapid kilovolt (peak)-switching dual-energy (RSDE) multidetector computed tomography (CT) can differentiate high lipid content (HLC) from low lipid content (LLC) incidental adrenal lesions. Methods A retrospective intrapatient study of 40 consecutive adults with known hepatic or pancreatic pathology who underwent multiphasic abdominal RSDE for nonadrenal-related clinical indications and had adrenal lesions was done. Arterial phase was acquired with RSDE, conventional unenhanced (CU) images with standard MDCT. RSDE measurements included lesion attenuation in Hounsfield units on simulated monochromatic 140-keV images and density (in milligrams per milliliter) on material decomposition images, using water-iodine and fat-iodine basis pairs. Each variable was correlated with CU Hounsfield units (Pearson coefficient). RSDE lesion values were compared with analysis of variance and Tukey HSD test. Receiver operating characteristic (ROC) analysis was performed to identify RSDE thresholds comparable to 10 HU on unenhanced MDCT. Results Twenty-nine HLC and 18 LLC lesions were evaluated in 40 subjects (21 men; mean age, 66.5 years). RSDE variables correlated with CU Hounsfield units, r = 0.90–0.92, P < 0.001. Myelolipomas, HLC, and LLC lesions were different by analysis of variance, P < 0.001 for all dual-energy variables. Excluding myelolipomas from ROC curve analysis, ROC areas for Hounsfield unit 140-keV images, fat(-iodine), and water(-iodine) were 0.929 (0.039), 0.917 (0.046), and 0.912 (0.048), respectively (P < 0.001); using a specificity of 94.4%, 64% of adenomatous lesions had 140 keV values of less than 9.5 HU, 59% had fat(-iodine) values of less than 987 mg/mL, and 50% had water(-iodine) values of less than 994 mg/mL. Conclusions There is a strong correlation between RSDE measures and accepted MDCT attenuation values for HLC and LLC adrenal lesions. In some patients undergoing postcontrast RSDE who are found to have incidental adrenal nodules, further unenhanced CT or adrenal-protocol CT or magnetic resonance imaging may not be necessary.
MEDIEVAL ROTATING COLUMN-INDICATORS: AN UNRECORDED SECOND EXAMPLE IN A THIRTEENTH CENTURY BIBLE (CAMBRIDGE, CORPUS CHRISTI COLLEGE MS 49)

ing column-indicators remaining in British libraries; four out of six of these are in Cambridge. It also records the existence of a second rotating column-indicator, hitherto unnoticed, in a thirteenth-century Bible in the Parker Library. Rotating column-indicators are attached to cords which can be placed anywhere in the book. They slide up and down the cord so that the line can be indicated by the position of the indicator. However, only the two indicators in CCCC 49 actually have 'linea written on them between the column numbers. The column-indicator is made of
Early vocalization of preterm infants with extremely low birth weight (ELBW), part I: from birth to expansion stage

The vocalization of preterm infants with extremely low birth weight (ELBW) up to the expansion stage was systematically described and compared with those of healthy full-term infants. The sample consisted of 18 preterm ELBW infants and the control group of 11 full-term infants. The follow-up was performed intensively using video-recordings. The vocalization of the preterm and full-term infants was analyzed quantitatively according to the categorical stages created by Oller. A descriptive analysis of all the vocalizations produced by the infants was performed. The preterm infants entered the primitive articulation stage later than the full-term infants and failed to produce more skills during that stage. According to this sample, there was no difference in entering the expansion stage, but the preterm infants failed to produce more skills than the full-term infants. The number of vocalization acts varied differently by age between the groups.
Induction of Cyclin D2 in Rat Granulosa Cells Requires FSH-dependent Relief from FOXO1 Repression Coupled with Positive Signals from Smad*

Ovarian follicles undergo exponential growth in response to follicle-stimulating hormone (FSH), largely as a result of the proliferation of granulosa cells (GCs). In vitro under serum-free conditions, rat GCs differentiate in response to FSH but do not proliferate unless activin is also present. In the presence of FSH plus activin, GCs exhibit enhanced expression of cyclin D2 as well as inhibin-α, aromatase, steroidogenic factor-1 (SF-1), cholesterol side chain (SCC), and epiregulin. In this report we sought to identify the signaling pathways by which FSH and activin promote GC proliferation and differentiation. Our results show that these responses are associated with prolonged Akt phosphorylation relative to time-matched controls and are dependent on phosphatidylinositol 3-kinase (PI 3-kinase) and Smad2/3 signaling, based on the ability of the PI 3-kinase inhibitor LY294002 or infection with adenoviral dominant negative Smad3 (DN-Smad3) mutant to attenuate induction of cyclin D2, inhibin-α, aromatase, SCC, SF-1, and epiregulin. The DN-Smad3 mutant also abolished prolonged Akt phosphorylation stimulated by FSH plus activin 24 h post-treatment. Infection with the adenoviral constitutively active forkhead box-containing protein, O subfamily (FOXO)1 mutant suppressed induction of cyclin D2, aromatase, inhibin-α, SF-1, and epiregulin. Transient transfections of GCs with constitutively active FOXO1 mutant also suppressed cyclin D2, inhibin-α, and epiregulin promoter-reporter activities. Chromatin immunoprecipitation results demonstrate in vivo the association of FOXO1 with the cyclin D2 promoter in untreated GCs and release of FOXO1 from the cyclin D2 promoter upon addition of FSH plus activin. These results suggest that proliferation and differentiation of GCs in response to FSH plus activin requires both removal of FOXO1-dependent repression and positive signaling from Smad2/3.
Disodium 4,4′-oxydibenzoate

The crystal structure of the title compound, 2Na+·C14H8O5 2−, consists of alternating layers of sodium cations and 4,4′-oxydibenzoate anions; the layers are perpendicular to the a axis, with the distance between the layers of cations (or anions) being half this axial length. The Na atoms are disordered over three sites [occupancies 0.775 (4), 0.781 (6) 0.444 (6)].
Measuring the extent and effectiveness of protected areas as an indicator for meeting global biodiversity targets

There are now over 100 000 protected areas worldwide, covering over 12% of the Earth's land surface. These areas represent one of the most significant human resource use allocations on the planet. The importance of protected areas is reflected in their widely accepted role as an indicator for global targets and environmental assessments. However, measuring the number and extent of protected areas only provides a unidimensional indicator of political commitment to biodiversity conservation. Data on the geographic location and spatial extent of protected areas will not provide information on a key determinant for meeting global biodiversity targets: ‘effectiveness’ in conserving biodiversity. Although tools are being devised to assess management effectiveness, there is no globally accepted metric. Nevertheless, the numerical, spatial and geographic attributes of protected areas can be further enhanced by investigation of the biodiversity coverage of these protected areas, using species, habitats or biogeographic classifications. This paper reviews the current global extent of protected areas in terms of geopolitical and habitat coverage, and considers their value as a global indicator of conservation action or response. The paper discusses the role of the World Database on Protected Areas and collection and quality control issues, and identifies areas for improvement, including how conservation effectiveness indicators may be included in the database to improve the value of protected areas data as an indicator for meeting global biodiversity targets.
A study of the combined effects of the EHD3 and FREM3 genes in patients with major depressive disorder

Major depressive disorder (MDD) is a common chronic mental disease with diverse clinical presentation. Although the genome‐wide association study (GWAS) has remarkably facilitated the understanding of genetic mechanisms of MDD at a deep molecular level, the combined effect of these disease‐underlying genes still needs further investigation. A total of 1,062 unrelated patients with MDD and 992 unrelated healthy subjects were recruited from a Chinese Han population to test 16 MDD‐associated genes identified by GWAS. A tag SNP‐based linkage‐disequilibrium map was then constructed over the loci that showed MDD association in the study sample. Of the 16 genes tested, EHD3 and FREM3 were associated with MDD in the Chinese population. The conditional test showed disease association for the rs619002(EHD3)‐rs1112714(FREM3) combination (P = 0.0059) and for the rs644926(EHD3)‐rs13130123(FREM3) combination (P = 0.007), of which a reduced risk was found for the rs619002(G)‐rs1112714(T) combination (OR = 0, P = 4.02 × 10−6) and for the rs644926(A)‐rs11938298(G) combination (OR = 0.12, 95% CI = 0.035–0.39, P = 3.85 × 10−6). Quantitative trait analysis revealed that rs13130123 in the FREM3 locus was strongly associated with the insomnia early symptom in patients carrying the rs619002(G) allele (P = 0.001) and those carrying the rs644926(A) allele (P = 0.00077). The combined effect of the EHD3 and FREM3 genes may play an important role in developing MDD. © 2012 Wiley Periodicals, Inc.
The glycine 90 to aspartate alteration in the Aβ subunit of PP2A (PPP2R1B) associates with breast cancer and causes a deficit in protein function

Mutations of the PPP2R1B gene, which encodes the Aβ scaffolding subunit of serine/threonine protein phosphatase 2A (PP2A), have been identified in several types of cancer including lung and breast carcinoma. One of these mutations results in an alteration of glycine 90 to aspartic acid (G90D), which has been found in both tumor and genomic DNA, raising the possibility that it is associated with an increased risk for cancer. A novel microarray‐based technology was used to screen for this single‐nucleotide polymorphism in 387 cancer patients and 329 control individuals. These data were used for case–control and family‐based comparisons in order to study the association of this polymorphism with susceptibility to lung carcinoma, breast carcinoma, and acute lymphoblastic leukemia. The frequency of the G90D polymorphism in breast cancer patients was significantly higher in cases (3%) than in controls (0.3%). The wild‐type Aβ subunit interacted with the B56γ (PPP2R5C), PR72 (PPP2R3A), and PR48 subunits of PP2A but did not interact with the B55α (PPP2R2A), B56α (PPP2R5A), or B56β (PPP2R5B) regulatory subunits in an in vitro binding assay. The G90D alteration inhibited the interaction of Aβ with the B56γ subunit but had no effect on binding to the PR72 subunit. These results provide evidence that the G90D alteration of the Aβ subunit of PP2A is associated with a low frequency of breast carcinoma and that the role of this alteration in transformation is likely to involve decreased interaction with the B56γ regulatory subunit. © 2005 Wiley‐Liss, Inc.
Cardiac symptoms before sudden cardiac death caused by hypertrophic cardiomyopathy: a nationwide study among the young in Denmark.

AIMS Hypertrophic cardiomyopathy (HCM) is a frequent cause of sudden cardiac death (SCD) among the young (SCDY). The aim of this study was to characterize symptoms before SCDY due to HCM. METHODS AND RESULTS Through review of all death certificates, we identified all SCDs in Danes aged 1-35 years in 2000-2009. Nationwide we included all deaths (n = 8756) and identified 431 autopsied SCDYs. All available records from hospitals and general practitioners were retrieved. To compare symptoms, we included a control groups consisting of traffic accident victims (n = 74). In the 10-year study period, 431 autopsied SCDY cases were reviewed and 38 cases (9%) were included, of which 22 (58%) had morphologic findings diagnostic of HCM and 16 (42%) had findings suggestive, but not diagnostic, of HCM ('possible HCM'). Cardiac symptoms >1 h prior to death were reported in 21 (55%) of cases, and 16 (42%) sought medical attention. One (1%) control had cardiac symptoms before death. Consequently, a significantly higher proportion of cases had cardiac symptoms before death and cases more often sought medical attention than controls (P < 0.001). CONCLUSION In conclusion, this nationwide study demonstrates a high frequency of cardiac symptoms prior to death in SCDY cases who died of HCM, as 55% had cardiac symptoms and nearly half of the cases sought medical attention.
Technical note: an algebraic method for calculating fecal output from a pulse dose of an external marker.

Fecal output estimates derived from a one-compartment, Gamma-2, age-dependent model were compared with estimates derived algebraically by computing the area under the marker excretion curve for lambs given a pulse dose of ytterbium-labeled forage. Lambs were fed one of four diets (as-fed basis): 100% alfalfa hay, 100% prairie hay, 50:50 alfalfa:sorghum grain, and 50:50 prairie hay:sorghum grain. For the one-compartment model, fecal output was calculated as the dose of Yb (micrograms) divided by the initial concentration in the compartment (micrograms of Yb/gram of DM) multiplied by the age-dependent rate constant (hours-1). For the algebraic method, fecal output was calculated as the dose of Yb divided by the area under the marker excretion curve ([micrograms of Yb/gram of fecal DM].hours), both with the full complement of fecal samples and with fecal samples collected at 12-h intervals. Fecal output estimated by the three methods did not differ (P > .15) from measured fecal output (total collection). Marker retention time calculated from the one-compartment, age-dependent model was numerically greater (P > .10) than retention time calculated algebraically (sum of concentration x time divided by sum of concentrations weighted for collection interval) for lambs fed all four diets. These results suggest that the area under the marker excretion curve generated from a pulse dose of Yb-labeled forage will provide estimates of fecal output that do not differ from those calculated from a one-compartment, age-dependent model.
Interval training program optimization in highly trained endurance cyclists.

PURPOSE The purpose of this study was to examine the influence of three different high-intensity interval training (HIT) regimens on endurance performance in highly trained endurance athletes. METHODS Before, and after 2 and 4 wk of training, 38 cyclists and triathletes (mean +/- SD; age = 25 +/- 6 yr; mass = 75 +/- 7 kg; VO(2peak) = 64.5 +/- 5.2 mL x kg(-1) min(-1)) performed: 1) a progressive cycle test to measure peak oxygen consumption (VO(2peak)) and peak aerobic power output (PPO), 2) a time to exhaustion test (T(max)) at their VO(2peak) power output (P(max)), as well as 3) a 40-km time-trial (TT(40)). Subjects were matched and assigned to one of four training groups (G(2), N = 8, 8 x 60% T(max) at P(max), 1:2 work:recovery ratio; G(2), N = 9, 8 x 60% T(max) at P(max), recovery at 65% HR(max); G(3), N = 10, 12 x 30 s at 175% PPO, 4.5-min recovery; G(CON), N = 11). In addition to G(1), G(2), and G(3) performing HIT twice per week, all athletes maintained their regular low-intensity training throughout the experimental period. RESULTS All HIT groups improved TT(40) performance (+4.4 to +5.8%) and PPO (+3.0 to +6.2%) significantly more than G(CON) (-0.9 to +1.1%; P < 0.05). Furthermore, G(1) (+5.4%) and G(2) (+8.1%) improved their VO(2peak) significantly more than G(CON) (+1.0%; P < 0.05). CONCLUSION The present study has shown that when HIT incorporates P(max) as the interval intensity and 60% of T(max) as the interval duration, already highly trained cyclists can significantly improve their 40-km time trial performance. Moreover, the present data confirm prior research, in that repeated supramaximal HIT can significantly improve 40-km time trial performance.
A Pulmonary Formulation of l-Dopa Enhances Its Effectiveness in a Rat Model of Parkinson's Disease

The efficacy of oral l-dopa becomes problematic with the progression of Parkinson's disease, due in large part to a lost ability to accommodate l-dopa's inherently poor pharmacokinetics. Pulmonary delivery represents a novel approach to reducing this problem. l-dopa was formulated into inhalable (Alkermes AIR) particles, and its pharmacokinetics and pharmacodynamics compared with those of an oral formulation. Pulmonary administration of l-dopa (2 mg) to rats resulted in a rapid elevation of plasma levels (Cmax = 4.8 ± 1.10 μg/ml at 2 min), whereas oral administration of l-dopa produced a much delayed and lower Cmax (1.8 ± 0.40 μg/ml at 30 min). In a rat model of Parkinson's disease (unilateral 6-hydroxydopamine lesion), the pulmonary formulation of l-dopa (0.5-2.0 mg) yielded more rapid and robust elevations in striatal l-dopa, dopamine, and dihydroxyphenylacetic acid levels, as well as 2.5 to 3.7 times as many c-fos-expressing striatal neurons. Moreover, motor function was significantly improved by 10 min after administration, with peak improvements occurring within 15 to 30 min. In contrast, considerably higher doses (6.8-10 mg) of orally administered l-dopa took over three times longer to produce similar effects. These results suggest that an inhalable formulation of l-dopa has superior pharmacokinetic properties and may provide patients with a more effective form of rescue therapy as well as being a reliable adjuvant or replacement for first-line oral therapy.
CNS control of a critical period for peripheral induction of central neurons in the leech

Most midbody ganglia in the central nervous system (CNS) of the leech Hirudo medicinalis contain about 400 neurons. However, those in the fifth and sixth midbody segments (ganglia M5 and M6) are specialized for reproductive functions, and each contain several hundred additional small neurons. These neurons arise late in embryogenesis as a result of an innervation-dependent inductive interaction between the male genitalia and M5 and M6 and are therefore known as peripherally induced central (PIC) neurons. The results of a series of ablation and transplantation experiments show that the PIC neurons are induced during a 1 to 2 day period about midway in embryogenesis (E15). The male genitalia are not necessary for induction before or after this period, and their presence for only one day may be sufficient for the induction to take place. Heterochronic transplantation of male genitalia shows that the critical period of interaction is independent of the age of the inducing tissues. Since the inductive signal is available from E10 to postembryonic stages, both the beginning and the end of the inductive period are determined by the CNS, not the periphery.