Miracle-dz/UniFAR-FTUs huggingface dataset:
Some data on matching behavior in the pigeon.

In matching behavior, the subject is first presented with a standard stimulus, and then required to select the corresponding stimulus from a set (usually two) of comparison stimuli. There has been increasing contemporary interest in this situation (Blough, 1957, 1959; Ferster, 1960), perhaps because it shares a number of common dimensions with several other important research areas. If the number of standard stimuli is made large, the matching procedure relates closely to the "learning set" problems of Harlow (1959). If time intervals are introduced between the presentation of the standard and comparison stimuli, contact is made with studies of delayed responding. If, after a specified history, the subject is required to match "novel" stimuli, the procedure is relevant to investigations of generalization and concept formation. Finally, if the set of comparison stimuli is suitably chosen, psychophysical functions are generated. Preliminary data are reported here on a procedure which can be easily adapted to the study of all of these problems.
Mechanisms Limiting Distribution of the Threonine-Protein Kinase B-RaFV600E Inhibitor Dabrafenib to the Brain: Implications for the Treatment of Melanoma Brain Metastases

Brain metastases are a common cause of death in stage IV metastatic melanoma. Dabrafenib is a BRAF (gene encoding serine/threonine-protein kinase B-Raf) inhibitor that has been developed to selectively target the valine 600 to glutamic acid substitution (BRAFV600E), which is commonly found in metastatic melanoma. Clinical trials with dabrafenib have shown encouraging results; however, the central nervous system distribution of dabrafenib remains unknown. Thus, the objective of the current study was to evaluate the brain distribution of dabrafenib in mice, and to see whether active efflux by P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) restricts its delivery across the blood-brain barrier (BBB). In vitro accumulation studies conducted in Madin-Darby canine kidney II cells indicate that dabrafenib is an avid substrate for both P-gp and BCRP. Directional flux studies revealed greater transport in the basolateral to apical direction with corrected efflux ratios greater than 2 for both P-gp and Bcrp1 transfected cell lines. In vivo, the ratio of area under the concentration-time curve (AUC)brain to AUCplasma (Kp) of dabrafenib after an i.v. dose (2.5 mg/kg) was 0.023, which increased by 18-fold in Mdr1 a/b−/−Bcrp1−/− mice to 0.42. Dabrafenib plasma exposure was ∼2-fold greater in Mdr1 a/b−/−Bcrp1−/− mice as compared with wild-type with an oral dose (25 mg/kg); however, the brain distribution was increased by ~10-fold with a resulting Kp of 0.25. Further, compared with vemurafenib, another BRAFV600E inhibitor, dabrafenib showed greater brain penetration with a similar dose. In conclusion, the dabrafenib brain distribution is limited in an intact BBB model, and the data presented herein may have clinical implications in the prevention and treatment of melanoma brain metastases.
Do dimensions from the Copenhagen Psychosocial Questionnaire predict vitality and mental health over and above the job strain and effort—reward imbalance models?

Aims: The Copenhagen Psychosocial Questionnaire (COPSOQ) comprises dimensions (emotional demands, demands of hiding emotions, meaning of work, quality of leadership, and predictability) that are not in the job strain or the effort—reward imbalance (ERI) models. The study aim was to investigate whether these dimensions explain changes in vitality and mental health over and above the job strain and ERI models. Methods: A cohort of 3552 employees in 2000 were followed up in 2005 (cohort participation of 51%). Regression analyses were carried out with mental health and vitality as dependent variables. A significance level of 0.01 was applied when comparing regression models. Results: Regarding mental health, both the full COPSOQ—ERI model (p = 0.005) and the full job strain—COPSOQ model (p = 0.01) were significantly better than the ERI and the job strain models. Regarding vitality, none of the full COPSOQ models (i.e. with new COPSOQ dimensions together with job strain or ERI respectively) was significantly better than the ERI (p = 0.03) or the job strain (p = 0.04) models. Emotional demands and low meaning of work predicted poor mental health and low vitality. Conclusions: In relation to mental health, new psychosocial risk factors have the potential to add to the predictive power of the job strain and ERI models. The current practice of including only items from the ERI and job strain models in public health studies should be reconsidered. Theories regarding the status of, for example, emotional demands and meaning of work should be developed and tested.
Somatoform abdominal pain in surgery: is SD worthy of surgical attention? Case reports and literature review

Somatoform disorders (SD) or medically unexplained physical symptoms (MUPS) are a group of disorders that represent a group of symptoms that cannot be explained by an organic or physical pathology. These disorders are widely prevalent, and, if unrecognised, SD may lead medical professionals to embark on tests or procedures which may inflict unnecessary iatrogenic complications. Despite the high prevalence, they are only poorly included in medical training curricula, at both undergraduate and postgraduate levels. In this article, we review the literature and present two cases. The first one presented with a recurrent acute abdomen had an unnecessary CT abdomen. The second case had laparoscopy for acute right-sided abdominal pain which turned out to be normal, and was readmitted again after a short period with acute urine retention which resolved spontaneously following discussion with the patient and family. Both cases were referred for psychiatric assessment and their family doctors were informed.
E2F3 Is a Mediator of DNA Damage-Induced Apoptosis

ABSTRACT The E2F transcription factors have emerged as critical apoptotic effectors. Herein we report that the E2F family member E2F3a can be induced by DNA damage through transcriptional and posttranslational mechanisms. We demonstrate that the posttranslational induction of human E2F3a is dependent on the checkpoint kinases. Moreover, we show that human E2F3a is a substrate for the checkpoint kinases (chk kinases) and that mutation of the chk phosphorylation site eliminates the DNA damage inducibility of the protein. Furthermore, we demonstrate that E2F1 and E2F2 are transcriptionally induced by DNA damage in an E2f3-dependent manner. Finally, using both in vitro and in vivo approaches, we establish that E2f3 is required for DNA damage-induced apoptosis. Thus, our data reveal the novel ability of E2f3 to function as a master regulator of the DNA damage response.
Investigation of nanostructural changes following acute injury using atomic force microscopy in rabbit vocal folds

There continues to be a paucity of data regarding the nanostructural changes of vocal fold (VF) collagen after injury. The aim of this study is to investigate the nanostructural and morphological changes in the rabbit VF lamina propria following acute injury using atomic force microscopy (AFM). Unilateral VF injury was performed on 9 New Zealand breeder rabbits. Sacrifice and laryngeal harvest were performed at three time points: 1 day, 3 days, and 7 days after injury. Histology and immunohistochemistry data were collected to confirm extracellular matrix (ECM) changes in rabbit VF. The progressive changes in thickness and D‐spacing of VF collagen fibrils were investigated over a 7‐day postinjury period using AFM. At post‐injury day 1, a fibrin clot and inflammatory cell infiltration were observed at the injured VF. The inflammatory score at postinjury day 1 was highest in injured VF tissue, with a significant decrease at postinjury day 7. The immunoreactivity of inflammatory proteins (COX‐2, TNF‐α) was observed in VF up to day 7 after injury. AFM investigation showed clustered and disorganized collagen fibrils at the nanoscale resolution at post‐injury day 7. Collagen fibrils in injured VF at postinjury day 7 were significantly thicker than control and postinjury days 1 and 3 (P < 0.001). D‐spacing of collagen at postinjury day 7 was not studied due to loss of distinct edges resulting from immature collagen deposition. AFM investigation of VF could add valuable information to understanding micromechanical changes in VF scar tissue. Microsc. Res. Tech. 78:569–576, 2015. © 2015 Wiley Periodicals, Inc.
Regulation of phenylalanine biosynthesis in Escherichia coli K-12: control of transcription of the pheA operon

Bacteriophage lambda ppheA-lac was used to obtain strains of Escherichia coli K-12 in which pheA and lacZ are each transcribed from a separate pheA promoter. Mutants in which both beta-galactosidase and chorismate mutase P-prephenate dehydratase (the pheA gene product) were derepressed were isolated, and a transacting gene (pheR) was identified. pheR was mapped at min 93 on the E. coli chromosome; pheR mutants acquired the wild-type phenotype when either F117 (which covers the 93-min region) or F116 (which covers min 59 to 65) was introduced into the cell. A rifampin resistance mutation, rpoB366, was found to derepress transcription of the pheA operon. pheR and rpoB366 affected two different systems for the phenylalanine-mediated control of pheA. A mutation in miaA (trpX), a gene known to be involved in attenuation in the tryptophan operon, was also shown to increase transcription of the pheA gene.
Estrogen-plus-progestin use and mammographic density in postmenopausal women: Women's Health Initiative randomized trial.

BACKGROUND Increased mammographic density reduces the sensitivity of screening mammography, is associated with increased breast cancer risk, and may be hormone related. We assessed the effect of estrogen-plus-progestin therapy on mammographic density. METHODS In a racially and ethnically diverse ancillary study of the Women's Health Initiative, we examined data from 413 postmenopausal women who had been randomly assigned to receive daily combined conjugated equine estrogens (0.625 mg) plus medroxyprogesterone acetate (i.e., progestin; 2.5 mg) (n = 202) or daily placebo (n = 211). We assessed the effect of estrogen plus progestin on measured mammographic percent density and abnormal findings over a 1-year and 2-year period. All tests of statistical significance were two-sided and were based on F tests or t tests from mixed-effects models. RESULTS Mean mammographic percent density increased by 6.0% at year 1, compared with baseline, in the estrogen-plus-progestin group but decreased by 0.9% in the placebo group (difference = 6.9%, 95% confidence interval [CI] = 5.3% to 8.5%; P < .001). The mean changes in mammographic density persisted but were attenuated slightly after 2 years, with an absolute increase of 4.9% in the estrogen-plus-progestin group and a decrease of 0.8% in the placebo group (difference = 5.7%, 95% CI = 4.3% to 7.3%; P < .001). These effects were consistent across racial/ethnic groups but were higher among women aged 70-79 years in the estrogen-plus-progestin group (mean increase at year 1 = 11.6%) than in the placebo group (mean decrease at year 1 = 0.1%) (difference of the means = 11.7%, 95% CI = 8.2% to 15.4%; P < .001, comparing across age groups). At year 1, women who were adherent to treatment in the estrogen-plus-progestin group had a mean increase in density of 7.7% (95% CI = 5.9% to 9.5%), and women in the placebo group had a mean decrease in density of 1.1% (95% CI = 0.3% to 1.9%). Use of estrogen plus progestin was associated with an increased risk of having an abnormal mammogram at year 1 (relative risk = 3.9, 95% CI = 1.5 to 10.2; P = .003), compared with placebo, that was not explained by an increase in density. CONCLUSIONS Use of up to 2 years of estrogen plus progestin was associated with increases in mammographic density.
Recovery of dielectric strength after DC interruption in vacuum

In order to investigate the influence of the electrode separation, arc time and frequency of the reverse current on the breaking capacity of vacuum breakers in a DC interrupting process, the dielectric recovery strength was measured after the interruption of a breaker. A high speed actuator mixed with a permanent magnetic actuator and a repulsion actuator was designed. And a circuit which can produce a high voltage pulse was set up to measure the dielectric recovery strength after the extinction of arcs. By the method of forced current-zero, experiments were carried out to interrupt a small DC current in a synthetic test circuit. Then the dielectric recovery strength under conditions of different electrode separations, different arc time and different frequencies of the reverse current was measured with the method of monopole discharge. The experimental results indicated that there existed a critical electrode separation in the DC interrupting process. Within this electrode separation, the dielectric recovery strength can be enhanced by increasing the electrode separation and decreasing the arc time. In addition, decreasing the frequency of the reverse current can also improve the dielectric recovery strength.
Pressure-Induced Structural Transformations of ZnO Nanowires Probed by X-ray Diffraction

ZnO nanowires were investigated at high pressures of up to 27 GPa in situ in a diamond anvil cell using synchrotron X-ray diffraction. Upon compression, a wurtzite-to-rocksalt phase transformation was observed, but both the onset and the completion pressures of this transformation were enhanced compared with all previously studied morphologies of ZnO, including nanocrystals and their bulk counterparts. Upon decompression, the rocksalt phase was found to sustain at near ambient pressure and could be recovered in a significant amount. Moreover, the pressure–volume equations of state for both the wurtzite and the rocksalt phases indicate that their bulk moduli are significantly higher than those of bulk ZnO and nanocrystals. The SEM images of the ZnO nanowires both before and after the compression suggest the pressure-induced morphology modifications, corroborating the understanding of other structure and property evolutions with pressure. Finally, possible pressure-induced phase transition mechanisms were e.
CrossTalk proposal: Weighing the evidence for Class A GPCR dimers, the evidence favours dimers

Binding experiments provided initial evidence that GPCRs were multimeric, with allostery explaining cooperativity measured between different equivalents of ligand (De Lean et al. 1980). However, this was overshadowed by the discovery that G proteins allosterically modulated receptors, focusing attention on receptor–G protein interactions. Ligand binding studies explicitly suggest that oligomeric receptors explain such cooperativity (Chidiac et al. 1997; Ma et al. 2007). Conceivably, a ‘shared’ G protein between two GPCR monomers might be the agent through which such cooperativity is manifested (Chabre et al. 2009). However, allostery between ligand binding sites in receptor homodimers
Doppler‐defined pulmonary hypertension and the risk of death in children with sickle cell disease followed for a mean of three years

Pulmonary hypertension (PH) is associated with increased mortality in adults with sickle cell disease (SCD), but its prognostic significance in children is unknown. Eighty‐eight children with SCD were followed after echocardiographic screening for PH. After a mean follow‐up of 3 years, all 18 subjects with PH were alive. In our children, as in adults with SCD, PH was associated with increased haemolysis. In contrast, our subjects with PH did not have overt systemic disease observed in adults. PH may be a manifestation of progressive organ damage from chronic haemolysis and systemic vasculopathy that ultimately leads to early death in adulthood.
Correlation between hyporesponsiveness to Toll‐like receptor ligands and liver dysfunction in patients with chronic hepatitis C virus infection

Summary. Hepatitis C virus (HCV)‐associated antigens, such as the core and nonstructural antigens, activate host innate immune systems via Toll‐like receptors (TLRs). We previously showed that chronic exposure to the core antigen induces hyporesponsiveness to TLR ligands in antigen‐presenting cells via activation of TLR2 and that stimulation with TLR ligands results in impaired IL‐6 production by peripheral blood monocytes from HCV‐infected patients. In the present study, peripheral blood mononuclear cells (PBMCs) isolated from patients with chronic HCV or hepatitis B virus (HBV) infection were stimulated with TLR ligands to determine the production of IL‐6 and IL‐8 and to identify the clinical parameters associated with hyporesponsiveness to TLR ligands in patients with chronic HCV infection. The results showed that pro‐inflammatory cytokine responses to TLR ligands were suppressed in PBMCs isolated from HCV‐infected, but not HBV‐infected, patients. The reduced cytokine responses to TLR ligands seen in HCV‐infected patients correlated with platelet counts and serum prothrombin time levels. In contrast, there was no correlation between TLR‐induced cytokine responses and serum levels of core antigen. Thus, hyporesponsiveness to TLR ligands in HCV‐infected patients is correlated with liver dysfunction. In conclusion, both host factors and viral factors may be involved in the generation of hyporesponsiveness to TLR ligands in patients with chronic HCV infection.
The appearance of the UmuD'C protein complex in Escherichia coli switches repair from homologous recombination to SOS mutagenesis

The process of SOS mutagenesis in Escherichia coli requires (i) the replisome enzymes, (ii) RecA protein, and (iii) the formation of the UmuD'C protein complex which appears to help the replisome to resume DNA synthesis across a lesion. We found that the UmuD'C complex is an antagonist of RecA‐mediated recombination. Homologous recombination in an Hfr x F‐ cross decreased as a function of the UmuD'C cell concentration; this effect was challenged by increasing RecA concentration. Recombination of a u.v. ‐damaged F‐lac with the lac gene of an F‐ recipient was reduced by increasing the UmuD'C concentration while lac mutagenesis increased, showing an inverse relationship between recombination and SOS mutagenesis. We explain our data with the following model. The kinetics of appearance of the UmuD'C complex after DNA damage is slow, reaching a maximum after an hour. Within that period, excision and recombinational repair have had time to occur. When the UmuD'C concentration relative to the number of residual RecA filaments, not resolved by recombinational repair, becomes high enough, UmuD'C proteins provide a processive factor for the replisome to help replication bypass and repel the standing RecA filament. Thus, at a high enough concentration, the UmuD'C complex will switch repair from recombination to SOS mutagenesis.
Radiographic Bone Changes Around Immediately Placed Immediately Restored Dental Implants In Periodontally Compromised Sites

Background: The aim of this study is to evaluate radiographic success of immediately restored dental implants placed immediately after extraction of periodontally compromised anterior teeth. Methods: In this prospective clinical trial human study, ten patients were selected from outpatient clinic of the Department of Oral Medicine, Periodontology, Oral Diagnosis, and Radiology, Faculty of Dentistry, Tanta University. Teeth were extracted as a result of sever periodontal destruction, followed by immediate implant placement and immediate implant restoration. Implant survival, bone level was evaluated for each patient at 6, 9 and 12-month follow-up period. Subtraction radiography was performed to compare the baseline image from 12 months follow up period image. Results: The survival rates of the immediately placed implants in the present study were 100%. Results showed significant reduction of the bone defect depth at 6, 9 and 12 months when compared to immediate post-operative record. Also massive increase of the mean bone density scores at 12 months when compared to immediate post operative record. Conclusion: Based on the results of this clinical trial, placement of implants immediately in fresh extraction sockets affected by periodontal disease followed by immediate restoration may be a valid operative technique that leads to predictable results if adequate preoperative and postoperative care is taken.
Copper Toxicity Syndrome

It was noted in a general practice that when Hair Mineral analysis was performed a significant number showed increased copper levels. Very little reference to this problem could be gleaned from the medical literature. In time it was noted that similar symptoms were described in a number of individuals with raised hair copper. These were symptoms of the affective disorders — with individuals showing degrees of anxiety, depression and sleep disorders as well as other problems. Serum and urine assessment for raised copper rarely showed abnormal levels. Chelation therapy using DPenicillamine would on occasion elicit a prompt reduction of symptoms. Twenty four hour urine output of copper during chelation therapy was generally proportional to the level of copper in hair analysis. Since significantly raised hair copper levels are rare in most other geographical areas, it is postulated that there are high levels of copper in domestic water supplies of the area (Vancouver, B.C.).
Characterization of Flavonoids and Phenolic Acids in Myrcia bella Cambess. Using FIA-ESI-IT-MSn and HPLC-PAD-ESI-IT-MS Combined with NMR

The leaves of Myrcia DC. ex Guill species are used in traditional medicine and are also exploited commercially as herbal drugs for the treatment of diabetes mellitus. The present work aimed to assess the qualitative and quantitative profiles of M. bella hydroalcoholic extract, due to these uses, since the existing legislation in Brazil determines that a standard method must be developed in order to be used for quality control of raw plant materials. The current study identified eleven known flavonoid-O-glycosides and six acylated flavonoid derivatives of myricetin and quercetin, together with two kaempferol glycosides and phenolic acids such as caffeic acid, ethil galate, gallic acid and quinic acid. In total, 24 constituents were characterized, by means of extensive preparative chromatographic analyses, along with MS and NMR techniques. An HPLC-PAD-ESI-IT-MS and FIA-ESI-IT-MSn method were developed for rapid identification of acylated flavonoids, flavonoid-O-glycosides derivatives of myricetin and quercetin and phenolic acids in the hydroalcoholic M. bella leaves extract. The FIA-ESI-IT-MS techinique is a powerful tool for direct and rapid identification of the constituents after isolation and NMR characterization. Thus, it could be used as an initial method for identification of authentic samples concerning quality control of Myrcia spp extracts.
Knowledge Centers in Professional Services Firms: Design and Empirical Evidence

Complementing knowledge management (KM) initiatives, specialized service units can support intra-organizational knowledge transfer by conducting research, offering edited contents, or participating in internal networks. This research concentrates specifically on the knowledge center (KC) model, thus following Hertlein et al., whose blueprint is evaluated and further developed by building on a multiple case study. In this design science research process, five KCs from the branch of professional services firms are studied, with particular emphasis on the process dimension. This allows new insights to be gained into the characteristics of KCs. Not only is the KC model largely confirmed, but new details are also added. Furthermore, directions for further research – specifically on the KC’s integration into KM initiatives– are provided.