Identity of Leu-19 (CD56) leukocyte differentiation antigen and neural cell adhesion molecule.

Neural cell adhesion molecule (N-CAM) is a membrane glycoprotein expressed on neural and muscle tissues that is involved in homotypic adhesive interactions. We have demonstrated that N-CAM also is expressed on hematopoietic cells, and is recognized by the anti-Leu-19 mAb. Leu-19 is preferentially expressed on NK cells and T lymphocytes that mediate MHC-unrestricted cytotoxicity, but is also present on some myeloid leukemia cell lines. On NK cells, T cells, the KG1a.5 hematopoietic cell line, and a neuroblastoma cell line, Leu-19 is a approximately 140-kD polypeptide with N-linked carbohydrates and abundant sialic acid residues. Sequential immunoprecipitation and peptide mapping demonstrated that the Leu-19 and N-CAM molecules expressed on leukocyte and neuroblastoma cell lines are similar structures. These findings suggest that the Leu-19 antigen on leukocytes may be involved in cell adhesion, analogous to the function on N-CAM on neural cells

Radiographic results of osteotome-driven maxillary sinus floor elevation without grafting materials after 17.5 years radiographic evaluation of minimally-invasive sinus grafting

BACKGROUND There is growing evidence that minimally invasive sinus augmentation works without the use of filler materials. This study assessed the bone integration and sinus projection of single-unit implants in the maxilla, which were placed approximately 18 years ago using a modified filler-free osteotome technique. METHODS Sixteen of the 24 treated patients of a former publication (treatment was performed between 2001 and 2004) were reassessed after a mean implant loading period of 17.5 years. The treated posterior areas were evaluated using cone-beam computed tomography (CBCT), and as a primary outcome parameter, sinus projection was determined in sectional views at the mesial, distal, buccal, and oral sites. Additionally, the percentage of alveolar bone contact was determined with respect to the implant length. Conventional radiographs were used to determine marginal bone levels. Additionally, plaque, bleeding on probing, and probing pocket depth were measured. The reconstructions were checked for chipping and other technical complications such as loss of retention, screw loosening, and screw fracture. RESULTS The mean age of the included patients was 72.8 ± 8.5 years. Two implants were lost. Therefore, fourteen implants were available for CBCT evaluation. The highest sinus projection of 2.1 ± 1.7 mm was observed in the distal aspect, while it was 1.1 ± 1.5, 0.9 ± 1.2, and 0.9 ± 1.1 mm at the mesial, buccal, and oral sites, respectively. The maximal sinus projection in one case was 6.7 mm. The percentage calculation of osseous implant integration (in mm ± standard deviations) with respect to the selected implant length at the mesial, distal, buccal, and oral sites showed values ranging from, 87.9 ± 16.0, 78.4 ± 20.3, 91.0 ± 12.5, and 90.5 ± 11.1%, respectively. Five implants displayed probing pocket depths of more than 4 mm with bleeding; all implants had less than 1 mm of bone loss in the observation period, that is, implants had mucositis. Six of 14 crowns showed small chippings within the ceramic veneering. One case of screw loosening was reported in medical history. DISCUSSION This study showed that implant placement in non-augmented sinuses resulted in good clinical results. The sinus projection, even if persistent and present, leads to no functional impairments. Given adequate maintenance, marginal bone levels remain constant and peri‑implant health can be observed. Moreover, these results represent only a small cohort; and therefore, should be interpreted with caution. However, in view of the existing literature, these highly promising results are in line with other findings. CLINICAL SIGNIFICANCE To the best of our knowledge, this dataset is the report with the longest follow-up. Overall, implants placed in the sinus without fillers represent a valuable alternative for tooth replacement in a minimally interventional manner

Preparation, Modification, and Evaluation of Cruentaren A and Analogues

An expeditious total synthesis of the highly cytotoxic F-ATPase inhibitor cruentaren A (1) is described based on a ring-closing alkyne metathesis (RCAM) reaction for the formation of the macrocylic ring. Other key transformations comprise a C-acylation of the benzyl lithium reagent derived from orsellinic acid ester 9 with Weinreb amide 7, a CBS reduction of the resulting ketone 10, and a Soderquist propargylation of aldehyde 21 with allenylborane (S)-27 to set the C-15 chiral center of the required alcohol fragment 25. The RCAM precursor 33 was assembled by acylation of 25 with acid fluoride 32, since more conventional methods for ester bond formation were unproductive. Moreover, the choice of the protecting groups, in particular for the secondary alcohol at C-9, which is prone to engage in translactonization, turned out to be critical; a relatively stable TBDPS ether had to be chosen for this site, which was removed in the final step of the synthesis with aqueous HF since other fluoride sources met with failure. The successful synthetic route was then expanded beyond the natural product, bringing a series of analogues into reach that feature incremental but deep-seated structural modifications. Three of these fully synthetic compounds turned out to be as or even more cytotoxic than cruentaren A itself against L-929 mouse fibroblast cells, reaching IC50 values as low as 0.7 ng mL−1

Making things happen : a model of proactive motivation

Being proactive is about making things happen, anticipating and preventing problems, and seizing opportunities. It involves self-initiated efforts to bring about change in the work environment and/or oneself to achieve a different future. The authors develop existing perspectives on this topic by identifying proactivity as a goal-driven process involving both the setting of a proactive goal (proactive goal generation) and striving to achieve that proactive goal (proactive goal striving). The authors identify a range of proactive goals that individuals can pursue in organizations. These vary on two dimensions: the future they aim to bring about (achieving a better personal fit within one’s work environment, improving the organization’s internal functioning, or enhancing the organization’s strategic fit with its environment) and whether the self or situation is being changed. The authors then identify “can do,” “reason to,” and “energized to” motivational states that prompt proactive goal generation and sustain goal striving. Can do motivation arises from perceptions of self-efficacy, control, and (low) cost. Reason to motivation relates to why someone is proactive, including reasons flowing from intrinsic, integrated, and identified motivation. Energized to motivation refers to activated positive affective states that prompt proactive goal processes. The authors suggest more distal antecedents, including individual differences (e.g., personality, values, knowledge and ability) as well as contextual variations in leadership, work design, and interpersonal climate, that influence the proactive motivational states and thereby boost or inhibit proactive goal processes. Finally, the authors summarize priorities for future researc

The complete digital workflow in fixed prosthodontics: a systematic review

Background The continuous development in dental processing ensures new opportunities in the field of fixed prosthodontics in a complete virtual environment without any physical model situations. The aim was to compare fully digitalized workflows to conventional and/or mixed analog-digital workflows for the treatment with tooth-borne or implant-supported fixed reconstructions. Methods A PICO strategy was executed using an electronic (MEDLINE, EMBASE, Google Scholar) plus manual search up to 2016–09-16 focusing on RCTs investigating complete digital workflows in fixed prosthodontics with regard to economics or esthetics or patient-centered outcomes with or without follow-up or survival/success rate analysis as well as complication assessment of at least 1 year under function. The search strategy was assembled from MeSH-Terms and unspecific free-text words: {((“Dental Prosthesis” [MeSH]) OR (“Crowns” [MeSH]) OR (“Dental Prosthesis, Implant-Supported” [MeSH])) OR ((crown) OR (fixed dental prosthesis) OR (fixed reconstruction) OR (dental bridge) OR (implant crown) OR (implant prosthesis) OR (implant restoration) OR (implant reconstruction))} AND {(“Computer-Aided Design” [MeSH]) OR ((digital workflow) OR (digital technology) OR (computerized dentistry) OR (intraoral scan) OR (digital impression) OR (scanbody) OR (virtual design) OR (digital design) OR (cad/cam) OR (rapid prototyping) OR (monolithic) OR (full-contour))} AND {(“Dental Technology” [MeSH) OR ((conventional workflow) OR (lost-wax-technique) OR (porcelain-fused-to-metal) OR (PFM) OR (implant impression) OR (hand-layering) OR (veneering) OR (framework))} AND {((“Study, Feasibility” [MeSH]) OR (“Survival” [MeSH]) OR (“Success” [MeSH]) OR (“Economics” [MeSH]) OR (“Costs, Cost Analysis” [MeSH]) OR (“Esthetics, Dental” [MeSH]) OR (“Patient Satisfaction” [MeSH])) OR ((feasibility) OR (efficiency) OR (patient-centered outcome))}. Assessment of risk of bias in selected studies was done at a ‘trial level’ including random sequence generation, allocation concealment, blinding, completeness of outcome data, selective reporting, and other bias using the Cochrane Collaboration tool. A judgment of risk of bias was assigned if one or more key domains had a high or unclear risk of bias. An official registration of the systematic review was not performed. Results The systematic search identified 67 titles, 32 abstracts thereof were screened, and subsequently, three full-texts included for data extraction. Analysed RCTs were heterogeneous without follow-up. One study demonstrated that fully digitally produced dental crowns revealed the feasibility of the process itself; however, the marginal precision was lower for lithium disilicate (LS2) restorations (113.8 μm) compared to conventional metal-ceramic (92.4 μm) and zirconium dioxide (ZrO2) crowns (68.5 μm) (p < 0.05). Another study showed that leucite-reinforced glass ceramic crowns were esthetically favoured by the patients (8/2 crowns) and clinicians (7/3 crowns) (p < 0.05). The third study investigated implant crowns. The complete digital workflow was more than twofold faster (75.3 min) in comparison to the mixed analog-digital workflow (156.6 min) (p < 0.05). No RCTs could be found investigating multi-unit fixed dental prostheses (FDP). Conclusions The number of RCTs testing complete digital workflows in fixed prosthodontics is low. Scientifically proven recommendations for clinical routine cannot be given at this time. Research with high-quality trials seems to be slower than the industrial progress of available digital applications. Future research with well-designed RCTs including follow-up observation is compellingly necessary in the field of complete digital processing

Nanocarbon-Based photovoltaics

Carbon materials are excellent candidates for photovoltaic solar cells: they are Earth-abundant, possess high optical absorption, and superior thermal and photostability. Here we report on solar cells with active layers made solely of carbon nanomaterials that present the same advantages of conjugated polymer-based solar cells - namely solution processable, potentially flexible, and chemically tunable - but with significantly increased photostability and the possibility to revert photodegradation. The device active layer composition is optimized using ab-initio density functional theory calculations to predict type-II band alignment and Schottky barrier formation. The best device fabricated is composed of PC70BM fullerene, semiconducting single-walled carbon nanotubes and reduced graphene oxide. It achieves a power conversion efficiency of 1.3% - a record for solar cells based on carbon as the active material - and shows significantly improved lifetime than a polymer-based device. We calculate efficiency limits of up to 13% for the devices fabricated in this work, comparable to those predicted for polymer solar cells. There is great promise for improving carbon-based solar cells considering the novelty of this type of device, the superior photostability, and the availability of a large number of carbon materials with yet untapped potential for photovoltaics. Our results indicate a new strategy for efficient carbon-based, solution-processable, thin film, photostable solar cells

Aerosol delivery to ventilated newborn infants: historical challenges and new directions

There are several aerosolized drugs which have been used in the treatment of neonatal respiratory illnesses, such as bronchodilators, diuretics, and surfactants. Preclinical in vitro and in vivo studies identified a number of variables that affect aerosol efficiency, including particle size, aerosol flows, nebulizer choice, and placement. Nevertheless, an optimized aerosol drug delivery system for mechanically ventilated infants still does not exist. Increasing interest in this form of drug delivery requires more controlled and focused research of drug/device combinations appropriate for the neonatal population. In the present article, we review the research that has been conducted thus far and discuss the next steps in developing the optimal aerosol delivery system for use in mechanically ventilated neonates

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes