Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase of atmospheric secondary organic material affects its reactivity

The interconversion of atmospheric organic particles among solid, semisolid, and liquid phases is of keen current scientific interest, especially for particles of secondary organic material (SOM). Herein, the influence of phase on ammonia uptake and subsequent particle-phase reactions was investigated for aerosol particles of adipic acid and α-pinene ozonolysis SOM. The nitrogen content of the particles was monitored by online mass spectrometry for increasing ammonia exposure. Solid and semisolid adipic acid particles were inert to the ammonia uptake for low RH (< 5%). For the solid particles, ammonia exposure at high relative humidity (RH; > 94%) induced a first-order deliquescence phase transition into aqueous particles. Solid particles exposed to supersaturated (RH > 100%) conditions and cycled back to high RH (> 94%), thereby becoming acidic metastable particles, underwent a gradual second-order transition upon ammonia exposure to form aqueous, partially neutralized particles. For α-pinene SOM, ammonia exposure at low RH increased the particle-phase ammonium content by a small amount. Mass spectrometric observations suggest a mechanism of neutralization and co-condensation of acidic gas-phase species, consistent with a highly viscous semisolid upon which adsorption occurs. At high RH the ammonium content increased greatly, indicative of rapid diffusion and absorption in a liquid environment. The mass spectra indicated the production of organonitrogen compounds, possibly by particle-phase reactive chemistry. The present results demonstrate that phase can be a key regulator of the reactivity of atmospheric SOM particles.
Introduction of a cyclophosphamide-based treatment strategy and the risk of ESRD in patients with idiopathic membranous nephropathy: a nationwide survey in the Netherlands.

BACKGROUND The efficacy of immunosuppressive therapy in preventing ESRD in patients with idiopathic membranous nephropathy (iMN) is debated. From 1991 onwards, we have advocated a restrictive treatment strategy in our university hospital and regional referring hospitals. We advised the use of immunosuppressive therapy, consisting of a combination of steroids and oral cyclophosphamide for 12 months, in patients with iMN at high risk for ESRD. METHODS Primary renal diagnosis of all patients who start renal replacement therapy in the Netherlands is registered in the RENINE database. We studied the incidence of ESRD due to iMN in the Netherlands in the period 1991-2005. We mailed a questionnaire to all nephrology centres that entered a patient with ESRD and iMN in the RENINE database after 2000. RESULTS The introduction of the cyclophosphamide-based treatment strategy in the Nijmegen region resulted in a significant 70% reduction in the incidence of ESRD in patients with iMN as compared to an unchanged incidence in other parts of the Netherlands. The response rate to the questionnaire was 65%. There were 45 patients (34 M, 11 F) with a mean age of 49 +/- 17 years at diagnosis and a median serum creatinine of 138 micromol/l (range 60-1798). Overall, only 22 patients (49%) had been treated with immunosuppressive therapy, consisting of prednisone monotherapy in 7. CONCLUSIONS Our data suggest that the introduction of a cyclophosphamide-based restrictive treatment policy has reduced the risk of ESRD in iMN. The questionnaires reflect the differences in opinion on the optimal treatment of high-risk patients with iMN.
Children and sun protection

Sun protection is a central measure to avoid the development of skin cancer and premature aging of the skin. In this context skin protection of children is of particular relevance since children spend a lot of time outdoors and they cannot provide themselves with sun protection measures as adults can. In addition to this sunburn reactions in childhood are particularly important in the development of melanoma skin cancer. This special situation of children with regards to sun protection has not only become aware to dermatologists but also to politicians, which is why a recent recommendation of the European Union explicitly points out the necessity of stringent sun protection of children. This review summarizes the current knowledge about sun protection of children. Underlying mechanisms of skin carcinogenesis in children, available sun protection measures as well as practical advice on daily sun protection of children are discussed.
Self-boosting vaccines and their implications for herd immunity

Advances in vaccine technology over the past two centuries have facilitated far-reaching impact in the control of many infections, and today’s emerging vaccines could likewise open new opportunities in the control of several diseases. Here we consider the potential, population-level effects of a particular class of emerging vaccines that use specific viral vectors to establish long-term, intermittent antigen presentation within a vaccinated host: in essence, “self-boosting” vaccines. In particular, we use mathematical models to explore the potential role of such vaccines in situations where current immunization raises only relatively short-lived protection. Vaccination programs in such cases are generally limited in their ability to raise lasting herd immunity. Moreover, in certain cases mass vaccination can have the counterproductive effect of allowing an increase in severe disease, through reducing opportunities for immunity to be boosted through natural exposure to infection. Such dynamics have been proposed, for example, in relation to pertussis and varicella-zoster virus. In this context we show how self-boosting vaccines could open qualitatively new opportunities, for example by broadening the effective duration of herd immunity that can be achieved with currently used immunogens. At intermediate rates of self-boosting, these vaccines also alleviate the potential counterproductive effects of mass vaccination, through compensating for losses in natural boosting. Importantly, however, we also show how sufficiently high boosting rates may introduce a new regime of unintended consequences, wherein the unvaccinated bear an increased disease burden. Finally, we discuss important caveats and data needs arising from this work.
The Process of Clinical Supervision

A multidisciplinary research team studied the process of marriage and family therapy clinical supervision in an accredited doctoral training program. Direct observation of the supervision process and interviews with supervisors and supervisees served as sources of data. Supervision was characterized by three persistent themes: imparting knowledge, self-understanding, and shift hierarchies. The unexpected and powerful second order change effects on the clinical program as a result of this study are discussed, along with implications of the research.
Designed guanidinium-rich amphipathic oligocarbonate molecular transporters complex, deliver and release siRNA in cells

The polyanionic nature of oligonucleotides and their enzymatic degradation present challenges for the use of siRNA in research and therapy; among the most notable of these is clinically relevant delivery into cells. To address this problem, we designed and synthesized the first members of a new class of guanidinium-rich amphipathic oligocarbonates that noncovalently complex, deliver, and release siRNA in cells, resulting in robust knockdown of target protein synthesis in vitro as determined using a dual-reporter system. The organocatalytic oligomerization used to synthesize these co-oligomers is step-economical and broadly tunable, affording an exceptionally quick strategy to explore chemical space for optimal siRNA delivery in varied applications. The speed and versatility of this approach and the biodegradability of the designed agents make this an attractive strategy for biological tool development, imaging, diagnostics, and therapeutic applications.
Mesangial C4d deposition: a new prognostic factor in IgA nephropathy.

BACKGROUND It has been shown that patients with IgA nephropathy can be divided into two groups on the basis of the pattern of complement activation. Activation of the lectin pathway of complement is associated with more severe renal disease. Glomerular deposition of C4d is a marker of activation of the lectin pathway of complement. The aim of our study was to determine whether C4d staining at the time of the renal biopsy could identify patients with a different long-term prognosis in IgA nephropathy. METHODS This retrospective cohort study included all patients with IgA nephropathy who underwent renal biopsy at our centre from January 1992 to December 2006. We evaluated baseline age, sex, presence of macroscopic haematuria, hypertension, serum creatinine and glomerular filtration rate (GFR), urine protein, mesangial C4d staining, glomerulosclerosis, interstitial fibrosis and extracapillary proliferation. Kaplan-Meier survival and Cox proportional hazards analyses were performed, with end-stage renal disease (ESRD) being defined as onset of dialysis or transplantation. RESULTS Nineteen patients (32.2%) were C4d positive and 40 patients (67.8%) C4d negative. Age, hypertension, absence of macroscopic haematuria, serum creatinine levels, GFR, glomerular sclerosis, interstitial fibrosis and C4d-positive staining were all univariately associated with evolution to ESRD. Renal survival at 10 years was 43.9% in C4d-positive patients versus 90.9% in C4d-negative patients (log-rank, P = 0.0005). CONCLUSION Negative mesangial C4d staining in glomeruli in patients with IgA nephropathy helps to identify patients with a good long-term prognostic for whom aggressive treatments are not justified.
Potential mechanisms of adverse outcomes in trials of anemia correction with erythropoietin in chronic kidney disease.

Advanced chronic kidney disease (CKD, stages 3–5) is almost invariably associated with anemia that is primarily caused by depressed production of erythropoietin (EPO), oxidative stress and inflammation [1,2]. This can be compounded by iron deficiency that is caused by loss of blood from repetitive laboratory tests, residual blood remaining in the hemodialysis circuits, fistula puncture site bleeding and uremic platelet dysfunction. In addition, when present, hemolytic disorders, bone marrow suppression, nutritional deficiencies, drug toxicities and hereditary diseases exacerbate the CKD-associated anemia. The EPO-deficiency and iron-deficiency components of anemia are routinely corrected with the use of recombinant human EPO and iron preparations. However, presence of severe oxidative stress and inflammation hampers efficacy of EPO and iron in promoting erythropoiesis. In this context, severe persistent anemia despite high doses of EPO and iron is commonly due to oxidative stress and inflammation that may actually be intensified by intravenous iron and EPO administration [3–5]. Observational studies have revealed a strong association between severity of anemia and risk of morbidity and mortality from cardiovascular disease and other causes in CKD patients [6–10]. These findings have been widely interpreted as evidence for the causal role of anemia in the pathogenesis of adverse outcomes in this population. Contrary to expectations, randomized clinical trials of anemia correction revealed either no effect or increased morbidity and mortality in patients assigned to normal hemoglobin (Hb) targets [11–13]. In fact, meta-
How nature can exploit nonspecific catalytic and carbohydrate binding modules to create enzymatic specificity

Noncatalytic carbohydrate binding modules (CBMs) are components of glycoside hydrolases that attack generally inaccessible substrates. CBMs mediate a two- to fivefold elevation in the activity of endo-acting enzymes, likely through increasing the concentration of the appended enzymes in the vicinity of the substrate. The function of CBMs appended to exo-acting glycoside hydrolases is unclear because their typical endo-binding mode would not fulfill a targeting role. Here we show that the Bacillus subtilis exo-acting β-fructosidase SacC, which specifically hydrolyses levan, contains the founding member of CBM family 66 (CBM66). The SacC-derived CBM66 (BsCBM66) targets the terminal fructosides of the major fructans found in nature. The crystal structure of BsCBM66 in complex with ligands reveals extensive interactions with the terminal fructose moiety (Fru-3) of levantriose but only limited hydrophobic contacts with Fru-2, explaining why the CBM displays broad specificity. Removal of BsCBM66 from SacC results in a ∼100-fold reduction in activity against levan. The truncated enzyme functions as a nonspecific β-fructosidase displaying similar activity against β-2,1– and β-2,6–linked fructans and their respective fructooligosaccharides. Conversely, appending BsCBM66 to BT3082, a nonspecific β-fructosidase from Bacteroides thetaiotaomicron, confers exolevanase activity on the enzyme. We propose that BsCBM66 confers specificity for levan, a branched fructan, through an “avidity” mechanism in which the CBM and the catalytic module target the termini of different branches of the same polysaccharide molecule. This report identifies a unique mechanism by which CBMs modulate enzyme function, and shows how specificity can be tailored by integrating nonspecific catalytic and binding modules into a single enzyme.
Psoriasis and extra domain A fibronectin loops

We have previously postulated that as well as T‐helper (Th) 1 and Th17 cells, the transforming growth factor (TGF)‐β/fibronectin (FN)/α5β1 pathway is central to psoriasis pathogenesis. EDA+ FN refers to an alternatively spliced isoform of FN with an additional domain known as extra domain A. EDA+ FN has two important properties pertinent to psoriasis lesions: it stimulates keratinocyte hyperproliferation, and, through stimulation of Toll‐like receptor (TLR) 4, stimulates production of proinflammatory cytokines. EDA+ FN production induced by TGF‐β stimulation can be maintained in psoriasis lesions via two main feedback loops. Firstly, EDA+ FN stimulates proliferation of keratinocytes, which, in an autocrine fashion, will release more EDA+ FN. Secondly, EDA+ FN stimulates TLR4 expressed by antigen‐presenting cells resulting in the production of proinflammatory cytokines such as tumour necrosis factor‐α, interleukin (IL)‐1, IL‐6 and IL‐12. The resultant promotion of cutaneous inflammation results in the recruitment of Th1 cells, which also produce EDA+ FN. We propose that these ‘FN loops’ contribute to the maintenance and progression of psoriatic lesions. Finally, although the association between psoriasis and heart/thrombotic disease remains unclear one plausible link may be the promotion of atherosclerosis and thrombotic heart disease by EDA+ FN.
How do nephrologists in haemodialysis units consider the symptom of itch? Results of a survey in Germany.

BACKGROUND Despite advances in dialysis treatment of end-stage renal disease, pruritus remains a widespread and distressing concomitant of chronic renal failure. The prevalence of uraemic pruritus (UP) across countries ranges from 10 to 77%. Data from the DOPPS study showed that moderate to severe UP occurs in >40% of patients on haemodialysis. We aimed to provide data on how common and how serious a problem pruritus is as perceived by nephrologists in daily haemodialysis practice. Method. A national cross-sectional survey in 1420 nephrologists assessed information on the number of dialysed patients, gender distribution, perceived prevalence of UP, time-related aspects of UP, characteristics of UP and its association with dialysis and therapy of UP. RESULTS Most respondents reported UP to be prevalent in 1-30% of their patients, and 30% reported an association between UP and dialysis. Seventy-five percent reported an undulating pattern. Nearly half the sample suggested a relationship between quality of dialysis and UP. No substantial differences in recognition and management of UP as a function of organizational affiliation were detected. CONCLUSIONS The prevalence of UP may be underestimated by nephrologists. Large variation in the reported prevalence of UP and the undulating pattern of UP after dialysis may impede the recognition of UP.
Staufen2 functions in Staufen1-mediated mRNA decay by binding to itself and its paralog and promoting UPF1 helicase but not ATPase activity

Staufen (STAU)1-mediated mRNA decay (SMD) is a posttranscriptional regulatory mechanism in mammals that degrades mRNAs harboring a STAU1-binding site (SBS) in their 3′-untranslated regions (3′ UTRs). We show that SMD involves not only STAU1 but also its paralog STAU2. STAU2, like STAU1, is a double-stranded RNA-binding protein that interacts directly with the ATP-dependent RNA helicase up-frameshift 1 (UPF1) to reduce the half-life of SMD targets that form an SBS by either intramolecular or intermolecular base-pairing. Compared with STAU1, STAU2 binds ∼10-fold more UPF1 and ∼two- to fivefold more of those SBS-containing mRNAs that were tested, and it comparably promotes UPF1 helicase activity, which is critical for SMD. STAU1- or STAU2-mediated augmentation of UPF1 helicase activity is not accompanied by enhanced ATP hydrolysis but does depend on ATP binding and a basal level of UPF1 ATPase activity. Studies of STAU2 demonstrate it changes the conformation of RNA-bound UPF1. These findings, and evidence for STAU1−STAU1, STAU2−STAU2, and STAU1−STAU2 formation in vitro and in cells, are consistent with results from tethering assays: the decrease in mRNA abundance brought about by tethering siRNA-resistant STAU2 or STAU1 to an mRNA 3′ UTR is inhibited by downregulating the abundance of cellular STAU2, STAU1, or UPF1. It follows that the efficiency of SMD in different cell types reflects the cumulative abundance of STAU1 and STAU2. We propose that STAU paralogs contribute to SMD by “greasing the wheels” of RNA-bound UPF1 so as to enhance its unwinding capacity per molecule of ATP hydrolyzed.
Rotation‐Misfit‐Free Heteroepitaxial Stacking and Stitching Growth of Hexagonal Transition‐Metal Dichalcogenide Monolayers by Nucleation Kinetics Controls

2D vertical stacking and lateral stitching growth of monolayer (ML) hexagonal transition-metal dichalcogenides are reported. The 2D heteroepitaxial manipulation of MoS2 and WS2 MLs is achieved by control of the 2D nucleation kinetics during the sequential vapor-phase growth. It enables the creation of hexagon-on-hexagon unit-cell stacking and hexagon-by-hexagon stitching without interlayer rotation misfits.
Reprogramming of adult rod photoreceptors prevents retinal degeneration

A prime goal of regenerative medicine is to direct cell fates in a therapeutically useful manner. Retinitis pigmentosa is one of the most common degenerative diseases of the eye and is associated with early rod photoreceptor death followed by secondary cone degeneration. We hypothesized that converting adult rods into cones, via knockdown of the rod photoreceptor determinant Nrl, could make the cells resistant to the effects of mutations in rod-specific genes, thereby preventing secondary cone loss. To test this idea, we engineered a tamoxifen-inducible allele of Nrl to acutely inactivate the gene in adult rods. This manipulation resulted in reprogramming of rods into cells with a variety of cone-like molecular, histologic, and functional properties. Moreover, reprogramming of adult rods achieved cellular and functional rescue of retinal degeneration in a mouse model of retinitis pigmentosa. These findings suggest that elimination of Nrl in adult rods may represent a unique therapy for retinal degeneration.
Hydrophilic Hierarchical Nitrogen‐Doped Carbon Nanocages for Ultrahigh Supercapacitive Performance

The synergism of large surface area, multiscale porous structure, and good conductivity endows hierarchical carbon nanocages with high-level supercapacitive performances. Further nitrogen doping greatly improves the hydrophilicity, which boosts the supercapacitive performances to an ultrahigh specific capacitance of up to 313 F g(-1) at 1 A g(-1).
Initial Poor Graft Dysfunction and Primary Graft Non-Function After Orthotopic Liver Transplantation

Orthotopic liver transplantation (OLT) has become the effective treatment for end-stage liver diseases. Since the 1980s, the successful rate of liver transplantation has increased with the improvement of operative methods and the use of University of Wisconsin (UW) solution. Nevertheless, liver procurement and implantation are inevitably associated with allograft damage. Lack of donor liver hinders OLT and leads to an increase in the number of deaths on the waiting list and as a consequence the transplant community has greatly expanded the use of non-ideal donors to improve the rate of transplant (Delmonico et al., 2005). Donor pool expansion strategies such as the use of living donors, cadaveric split livers, and “extended criteria donors” (ECD)/marginal donors are being pursued. These may predispose recipients to graft dysfunction and increase long-term risk and survival in recipients. Primary graft non-function (PGNF) is the most severe type of graft damage after OLT, followed by initial poor graft function (IPGF) (Chui et al., 2000). Emergency hepatic retransplantation is necessary because of the extreme high mortality of PGNF. Evaluation of IPGF is determined by a high level of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST). IPGF directly influences the survival in the hepatic graft. Ultimately, some grafts recover completely while others need to be retransplanted (Pokorny et al., 2000). IPGF and PGNF are associated with many factors, such as status of donor, quality of hepatic graft, long-term warm ischemia, cold ischemia, primary liver disease, status of liver function of recipients and operative techniques (Brokelman et al., 1999). For evaluation of the donor hepatic allograft with regard to pre-existing diseases, in particular macrovesicular steatosis and post-transplant evaluation of hepatic graft function, liver biopsy is the most challenging and valuable clinical practice. Recently, some progress has been made in the prevention and treatment of early hepatic graft dysfunction. The present review provides broad discussion in the relevant sections.
Toward 3D Printing of Pure Metals by Laser‐Induced Forward Transfer

3D printing of common metals is highly challenging because metals are generally solid at room conditions. Copper and gold pillars are manufactured with a resolution below 5 μm and a height up to 2 mm, using laser-induced forward transfer to create and eject liquid metal droplets. The solidified drop's shape is crucial for 3D printing and is discussed as a function of the laser energy.
Recruitment of oriens-lacunosum-moleculare interneurons during hippocampal ripples

Sharp wave-associated ∼200-Hz ripple oscillations in the hippocampus have been implicated in the consolidation of memories. However, knowledge on mechanisms underlying ripples is still scarce, in particular with respect to synaptic involvement of specific cell types. Here, we used cell-attached and whole-cell recordings in vitro to study activity of pyramidal cells and oriens-lacunosum-moleculare (O-LM) interneurons during ripples. O-LM cells received ripple-associated synaptic input that arrived delayed (3.3 ± 0.3 ms) with respect to the maximum amplitude of field ripples and was locked to the ascending phase of field oscillations (mean phase: 209 ± 6°). In line, O-LM cells episodically discharged late during ripples (∼6.5 ms after the ripple maximum), and firing was phase-locked to field oscillations (mean phase: 219 ± 9°). Our data unveil recruitment of O-LM neurons during ripples, suggesting a previously uncharacterized role of this cell type during sharp wave-associated activity.
Ultrathin Printable Graphene Supercapacitors with AC Line‐Filtering Performance

Ultrathin printable graphene supercapacitors are demonstrated, based on solution-processed electrochemically exfoliated graphene hybrid films on an ultrathin poly(ethylene terephthalate) substrate, exhibiting an unprecedented volumetric capacitance of 348 F cm(-3) , an ultrahigh scan rate of 2000 V s(-1) , and AC line-filtering performance.