Miracle-dz/UniFAR-FTUs huggingface dataset:
Site-directed Mutagenesis in the B-Neuropilin-2 Domain Selectively Enhances Its Affinity to VEGF165, but Not to Semaphorin 3F*

Neuropilins (NRPs) are 130-kDa receptors that bind and respond to the class 3 semaphorin family of axon guidance molecules (SEMAs) and to members of the vascular endothelial growth factor (VEGF) family of angiogenic factors. Two NRPs have been reported so far, NRP1 and NRP2. Unlike NRP1, little is known about NRP2 interactions with its ligands, VEGF165 and SEMA3F. Cell binding studies reveal that VEGF165 and SEMA3F bind NRP2 with similar affinities, 5.2 and 3.9 nm, respectively, and are competitive NRP2 ligands. Immunoprecipitation studies show that the B (b1b2) extracellular domain of NRP2 is sufficient for VEGF165 binding, whereas SEMA3F requires both the A (a1a2) and B domains. To identify residues of B-NRP2 involved in VEGF165 binding, point mutations were introduced by site-directed mutagenesis. VEGF165 is a basic protein. Reduction of the electronegative potential of B-NRP2 by exchanging acidic residues for uncharged alanine (B-NRP2 E284A,E291A) in the 280–290 b1-NRP2 loop resulted in a 2-fold reduction in VEGF165 affinity. Conversely, enhancing the electronegative potential (B-NRP2 R287E,N290D and R287E,N290S) significantly increased VEGF165 affinity for B-NRP2 by 8- and 6.6-fold, respectively. The mutagenesis did not affect SEMA3F/B-NRP2 interactions. These results demonstrate that it is possible to alter VEGF165 affinity for NRP2 without affecting SEMA3F affinity. They also identify NRP2 residues involved in VEGF165 binding and suggest that modifications of B-NRP2 could lead to potentially high affinity selective inhibitors of VEGF165/NRP2 interactions.
Classification Deficits in Alzheimer's Disease with Special Reference to Living and Nonliving Things

The present study was conducted to assess the hypothesis that visual similarity between exemplars within a semantic category may affect differentially the recognition process of living and nonliving things, according to task demands, in patients with semantic memory disorders. Thirty-nine Alzheimer's patients and 39 normal elderly subjects were presented with a task in which they had to classify pictures and words, depicting either living or nonliving things, at two levels of classification: subordinate (e.g., mammals versus birds or tools versus vehicles) and attribute (e.g., wild versus domestic animals or fast versus slow vehicles). Contrary to previous results (Montañes, Goldblum, & Boller, 1995) in a naming task, but as expected, living things were better classified than nonliving ones by both controls and patients. As expected, classifications at the subordinate level also gave rise to better performance than classifications at the attribute level. Although (and somewhat unexpectedly) no advantage of picture over word classification emerged, some effects consistent with the hypothesis that visual similarity affects picture classification emerged, in particular within a subgroup of patients with predominant verbal deficits and the most severe semantic memory disorders. This subgroup obtained a better score on classification of pictures than of words depicting living items (that share many visual features) when classification is at the subordinate level (for which visual similarity is a reliable clue to classification), but met with major difficulties when classifying those pictures at the attribute level (for which shared visual features are not reliable clues to classification). These results emphasize the fact that some "normal" effects specific to items in living and nonliving categories have to be considered among the factors causing selective category-specific deficits in patients, as well as their relevance in achieving tasks which require either differentiation between competing exemplars in the same semantic category (naming) or detection of resemblance between those exemplars (categorization).
Theoretical perspectives and applications of group learning in PBL

Abstract An essential part of problem-based learning (PBL) is group learning. Thus, an in depth understanding of the theoretical underpinnings of group learning in PBL allows educators to bridge theory and practice more effectively thus providing ideas and tools to enhance PBL practices and research. The theory-driven applications examined in this article establish grounds for future research in PBL. The purpose of this article is to describe and examine two theoretical perspectives of group learning in PBL and their potential applications to improve educational practice. They include: (1) social interdependence theory and the meaning of positive interdependence, (2) socio cognitive theory of networked expertise and the concept of knowledge creation in innovative knowledge communities (IKC). Potential applications include the following: development of instructional material to foster positive interdependency using concept maps; formal and structured use of peer feedback throughout PBL courses to promote individual and group accountability; creation and sharing of new knowledge about different topics within and across IKC; and use of rotating students with hybrid abilities across PBL groups to foster distributed cognition.
At-the-Market Offerings

We study at-the-market (ATM) equity offerings, which are direct share issuances sold in the secondary market that forgo underwriters and “dribble-out” shares over time rather than raising them all at once. Enabled in 2008, their use has increased dramatically, and in 2016, their incidence and total proceeds were, respectively, 63% and 26% of those for seasoned equity offerings (SEOs). Determinants of firms’ choice between ATMs and SEOs are consistent with the costly certification hypothesis of Chemmanur and Fulghieri (1994). We also find that 65% of ATM proceeds are used to stockpile cash compared to 84% of SEO proceeds.
Long‐Term Non–End‐Stage Renal Disease Risks After Living Kidney Donation

Despite generally positive outcomes and high rates of satisfaction, living kidney donors are at risk for both medical and psychosocial problems. In this review, the authors summarize non–end‐stage renal disease (ESRD) risks for donors and describe limitations to the data. We review the evidence of medical risks (e.g. increased cardiovascular disease and mortality, preeclampsia) and psychosocial risks (e.g. mood disturbance, financial burden). We then discuss the evidence of differential risks among subsets and the impact of postdonation events (e.g. development of diabetes). Collectively, available evidence indicates the following. (1) Recognizing the importance of non‐ESRD risks has been overshadowed by analyses of the reported risk of ESRD. This imbalance should be remedied. (2) There is little quantification of the true contribution of donation to medical and psychosocial outcomes. (3) Most studies, to date, have been retrospective, with limited sample sizes and diversity and with less‐than‐ideal controls for comparison of outcomes. (4) Many postdonation events (diabetes and hypertension) can now be reasonably predicted, and their association with adverse outcomes can be quantified. (5) Mechanisms and systems need to be implemented to evaluate and care for donors who develop medical and/or psychosocial problems. (6) Costs to donors are a significant burden, and making donation financially neutral should be a priority.
The use of chaperones in general practice: Is this just a ‘Western’ concept?

Background The literature about medical chaperones in primary care is limited to a handful of English-speaking countries. It remains largely unknown to what extent chaperones are offered (and used) outside the published literature. Objective The current study aimed to explore the attitudes and experiences of a group of general practitioners (GPs; family doctors) attending an international primary care conference regarding their use of medical chaperones. Methods Ninety international GPs completed a validated questionnaire, providing information on their current practice, availability and preferred choice of chaperone. Participants expressed their opinion on the importance of, and facilitators and barriers for chaperone use. Results Although most participants had knowledge of the term ‘medical chaperone’ (75%), those with a qualification from Europe (other than the UK) were less likely to offer a chaperone. Two-thirds of all participants would consider offering a chaperone and were more likely to work in the public sector (p = .04; Cramér’s V = 0.27). A practice nurse was most commonly used as chaperone. Chaperone users ranked the ‘medico-legal protection of doctors’, ‘doctors’ professional practice’ and ‘protection of patients’ as the most important factors for using a chaperone. Non-users reported ‘personal choice of the doctor’, ‘confidentiality’ and ‘impact on the doctor–patient relationship’ as the main areas influencing their decision not to use a chaperone. Conclusion International doctors hold different views about the use (or not) of chaperones within their clinical practice and its effect on the doctor–patient consultation. Further research is needed to tease out the reasons for this.
Role of specific immunoglobulin E in diagnosis of acute toxoplasma infection and toxoplasmosis

Toxoplasma immunoglobulin E (IgE) antibodies were evaluated in an immunosorbent agglutination assay (ISAGA) and an enzyme-linked immunosorbent assay (ELISA) to determine their usefulness in the diagnosis of acute infection with Toxoplasma gondii. IgE antibodies were not detected in serum specimens from otherwise seronegative individuals, individuals with chronic toxoplasma infection, or infants without congenital toxoplasmosis. In contrast, they were detected in pregnant women who seroconverted during gestation (100% by ELISA, 63% by ISAGA), patients with toxoplasmic lymphadenopathy (96% by ELISA, 88% by ISAGA), infants with signs of congenital toxoplasmosis which prompted serologic testing in the postnatal period (92% by ELISA, 67% by ISAGA), children and adults with toxoplasmic chorioretinitis (36% by ELISA, 18% by ISAGA), and adult patients with AIDS and toxoplasmic encephalitis (33% by ELISA, 25% by ISAGA). In many of the serum specimens, the titer of IgE antibodies detected by the ISAGA were close to or at the positive cutoff value. The duration of detectable IgE antibodies in patients with acute infections varied considerably among individuals but showed a trend toward a briefer duration by the ISAGA than by the ELISA. These results reveal that recrudescence of IgE antibodies in patients with reactivated chronic infection (toxoplasmic chorioretinitis and toxoplasmic encephalitis) may be useful diagnostically and that demonstration of toxoplasma IgE antibodies is a useful adjunct to currently available serologic tests for the diagnosis of acute toxoplasma infection and toxoplasmosis.
A case of cluster headache treated with rotigotine: Clinical and neurophysiological correlates

Background Chronic cluster headache (CCH) is characterized by recurrent bouts of facial pain lasting up to 180 minutes in the absence of a long remission period. Case We report the case of a 43-year-old male patient with treatment-resistant CCH, who improved with administration of transdermal rotigotine. We also evaluated the nociceptive blink reflex habituation that was reduced before the treatment (as is usual in CH patients) and normalized by transdermal rotigotine. Conclusions We suggest that rotigotine could represent a further therapeutic option in the treatment of drug-resistant CCH.
Maternal panic disorder: infant temperament, neurophysiology, and parenting behaviors.

OBJECTIVE To determine whether 4- and 14-month-old infants of mothers with panic disorder (PD) would be more likely to show differences in temperament, neurophysiology (salivary cortisol and sleep), and relationships with their mothers than controls. METHOD Two cohorts were recruited: 4-month-old infants with PD mothers (n = 25) and 4-month-old controls (n = 24), and 14-month-old infants with PD mothers (n = 27) and 14-month-old controls (n = 18). Mothers completed diagnostic interviews and questionnaires concerning infant temperament, sleep, and parenting. Infant salivary cortisol samples and standard observational procedures to measure infant temperament, sleep, attachment, and parenting were also used. RESULTS Infants with PD mothers did not show more high reactivity, behavioral inhibition, or ambivalent/resistant attachment but did demonstrate different neurophysiology (higher salivary cortisol and more disturbed sleep) than controls. PD mothers also displayed less sensitivity toward their infants and reported parenting behaviors concerning infant sleep and discipline that have been associated with child problems. CONCLUSIONS While infants with PD mothers did not show early behavioral differences from controls, they did display neurophysiological divergences consistent with higher arousal/arousability. Such neurophysiological divergences (elevated salivary cortisol and disturbed sleep) might be important early indicators of risk. Helping PD mothers parent their more highly aroused/arousable infants could reduce the development of psychopathology.
The German Mittelstand: Antithesis to the Silicon Valley entrepreneurship model?

Whilst internationally, the Mittelstand in Germany is admired and many countries try to emulate it, the current debate in Germany praises the Silicon Valley model of entrepreneurship, contrasting the Mittelstand as low-growth, low-tech and non-innovative - in short: as a hindrance to Germany's economic future. We therefore ask whether the Mittelstand actually is the antithesis to the Silicon Valley entrepreneurship model. We show that Mittelstand is more than a small and medium enterprise size, identifying its distinctive features (identity of ownership and management, sense of belonging). In this regard, we also discuss the influence of historical paths and current institutional settings on the Mittelstand model. Asking to what extent the Mittelstand is distinctive, we address its diverse contributions to economy and society. We suggest that the Mittelstand is an excellent example of everyday entrepreneurship and a vibrant segment of economy which is also competitive, innovative, and growth orientated; albeit in different ways compared to Silicon Valley entrepreneurship. In concluding, we outline ideas for future research and implications for policymakers. In our view, future research and policies should stand back from dichotomies such as "Mittelstand versus Silicon Valley entrepreneurship" and acknowledge the diversity and heterogeneity of entrepreneurship.
Inverse regulatory coordination of motility and curli-mediated adhesion in Escherichia coli.

During the transition from post-exponential to stationary phase, Escherichia coli changes from the motile-planktonic to the adhesive-sedentary "lifestyle. " We demonstrate this transition to be controlled by mutual inhibition of the FlhDC/motility and sigma(S)/adhesion control cascades at two distinct hierarchical levels. At the top level, motility gene expression and the general stress response are inversely coordinated by sigma(70)/sigma(FliA)/sigma(S) competition for core RNA polymerase and the FlhDC-controlled FliZ protein acting as a sigma(S) inhibitor. At a lower level, the signaling molecule bis-(3'-5')-cyclic-diguanosine monophosphate (c-di-GMP) reduces flagellar activity and stimulates transcription of csgD, which encodes an essential activator of adhesive curli fimbriae expression. This c-di-GMP is antagonistically controlled by sigma(S)-regulated GGDEF proteins (mainly YegE) and YhjH, an EAL protein and c-di-GMP phosphodiesterase under FlhDC/FliA control. The switch from motility-based foraging to the general stress response and curli expression requires sigma(S)-modulated down-regulation of expression of the flagellar regulatory cascade as well as proteolysis of the flagellar master regulator FlhDC. Control of YhjH by FlhDC and of YegE by sigma(S) produces a fine-tuned checkpoint system that "unlocks" curli expression only after down-regulation of flagellar gene expression. In summary, these data reveal the logic and sequence of molecular events underlying the motile-to-adhesive "lifestyle" switch in E. coli.
Evidence that Spt3 functionally interacts with Mot1, TFIIA, and TATA-binding protein to confer promoter-specific transcriptional control in Saccharomyces cerevisiae

Spt3 of Saccharomyces cerevisiae is a factor required for normal transcription from particular RNA polymerase II-dependent promoters. Previous genetic and biochemical analyses have shown that Spt3 interacts with the yeast TATA-binding protein (TBP). To identify other factors that might interact with Spt3, we have screened for mutations that, in combination with an spt3 null mutation, lead to inviability. In this way, we have identified a mutation in MOT1, which encodes an ATP-dependent inhibitor of TBP binding to TATA boxes: Previous analyses suggested that Mot1 causes repression in vivo. However, our analysis of mot1 mutants shows that, similar to spt3 mutants, they have decreased levels of transcription from certain genes, suggesting that Mot1 may function as an activator in vivo. In addition, mot1 mutants have other phenotypes in common with spt3 delta mutants, including suppression of the insertion mutation his4-912 delta. Motivated by these Spt3-Mot1 genetic interactions, we tested for genetic interactions between Spt3 and the general transcription factor TFIIA. TFIIA has been shown previously to be functionally related to Mot1. We found that overexpression of TFIIA partially suppresses an spt3 delta mutation, that toa1 mutants have Spt-phenotypes, and that spt3 delta toa1 double mutants are inviable. We believe that, taken together, these data suggest that Spt3, Mot1, and TFIIA cooperate to regulate TBP-DNA interactions, perhaps at the level of TATA box selection in vivo.
Chronic Peritoneal Inflammation by Cyanate in Rats

Objective During peritoneal dialysis, the peritoneum is exposed to waste products, including urea. Urea forms cyanate spontaneously at body temperature and pH, and cyanate carbamylates amino acids, peptides, and proteins. Cyanate may contribute to peritoneal injury with morphological changes in the peritoneum. To test this hypothesis, we injected cyanate into rats. Methods Experiments were performed in two groups of 7 rats each. In the cyanate group, each rat received 1 mL of 1.5 μmol/L potassium cyanate dissolved in 40 mmol/L sodium bicarbonate solution intraperitoneally each experiment day. In the control group, each rat received 1 mL of 1.5 μmol/L potassium bicarbonate instead of potassium cyanate. The rats in both groups were anesthetized and killed at the 85th day after the first injection. After formalin fixation, tissue samples from abdominal walls and livers were sliced, embedded in a standard manner, and stained with hematoxylin and eosin. Results Parietal peritoneum from rats in the cyanate group showed a mild increase in the number of fibroblasts, with collagen deposits, infiltration by mononuclear cells, vascular congestion, round-shaped transformation of mesothelial cells, widening of submesothelial spaces, and abundant denudation of mesothelial cells. The visceral peritoneum from rats in the cyanate group showed collagen deposits with fibroblastic proliferation. Conclusions Cyanate can induce chronic inflammation in the peritoneum, and exposure of the peritoneum to cyanate may contribute to peritoneal injury in patients being treated with peritoneal dialysis.
A History of New Zealand

This vivid history of New Zealand, by the late Professor Keith Sinclair of the University of Auckland's history department, has long been regarded as a classic, one of the most authoritative studies of this country's history. This updated version has been brought up-to-date by Raewyn Dalziel, Professor of History at the University of Auckland (and Sinclair's widow). It brings the story up to the end of the 1990s and the election of the Labour Government in the second MMP General Election.
Severe Left Ventricular Systolic Dysfunction May Reverse with Renal Transplantation: Uremic Cardiomyopathy and Cardiorenal Syndrome

Chronic heart failure (CHF) and chronic kidney disease (CKD) are serious medical conditions with significant morbidity and mortality. Emerging evidence indicates that the function of these two organ systems are affected by each other in a complex interplay. Most patients with CKD suffer frequently from cardiac abnormalities including left ventricular hypertrophy (LVH), left ventricular dilatation (LVD), left ventricular (LV) diastolic and/or systolic dysfunction. Although previously thought that LV systolic dysfunction was an absolute contraindication to renal transplantation, several observational studies have shown this not to be true and that transplantation can lead to significant improvement in LV systolic function. Furthermore, correction of the uremic state by renal transplantation leads to improvement of LVD and possibly regression of LVH. In fact, the reduction of LVH postkidney transplantation was shown to be dependent on adequate renal function and hypertension control. Diabetes mellitus does not seem to be a confounding factor in the improvement of uremic cardiomyopathy with renal transplantation.
Chronic widespread pain prevalence in the general population: A systematic review

Chronic widespread pain (CWP) is a significant burden in communities. Understanding the impact of population‐dependent (e.g., age, gender) and contextual‐dependent (e.g. survey method, region, inequality level) factors have on CWP prevalence may provide a foundation for population‐based strategies to address CWP. Therefore, the purpose of this study was to estimate the global prevalence of CWP and evaluate the population and contextual factors associated with CWP. A systematic review of CWP prevalence studies (1990–2017) in the general population was undertaken. Meta‐analyses were conducted to determine CWP prevalence, and study population data and contextual factors were evaluated using a meta‐regression. Thirty‐nine manuscripts met the inclusion criteria. Study CWP prevalence ranged from 1.4% to 24.0%, with CWP prevalence in men ranging from 0.8% to 15.3% and 1.7% to 22.1% in women. Estimated overall CWP prevalence was 9.6% (8.0–11.2%). Meta‐regression analyses showed gender, United Nations country development status, and human development index (HDI) influenced CWP prevalence, while survey method, region, methodological and reporting quality, and inequality showed no significant effect on the CWP estimate. Globally CWP affects one in ten individuals within the general population, with women more likely to experience CWP than men. HDI was noted to be the socioeconomic factor related to CWP prevalence, with those in more developed countries having a lower CWP prevalence than those in less developed countries. Most CWP estimates were from developed countries, and CWP estimates from countries with a lower socioeconomic position is needed to further refine the global estimate of CWP.