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Analysis of long-term data (1987–2019) was carried out on the morphology and autecology of the benthic colonial large-cell species Striatella unipunctata (Lyngbye) C. A. Agardh, 1832 in the microphytobenthos of the Black Sea and Sea of Japan, including water areas of specially protected natural areas of Russia. The species is widely found on natural and artificial substrates in the Black Sea year-round, and in the Sea of Japan, at a water temperature down to −1.5 °C. St. unipunctata quantitative data were determined by direct cell counting in the Goryaev camera under light microscopes (LMs) Biolam L-212, Axioskop 40, and Olympus BX41. Species morphology, phytogeography, and ecology are described. The cell size range of populations is presented: for the Black Sea, valves 25–148 µm long, 8–22 µm wide, frustules 36.3–50.4 µm wide, 18–24 fibulae in 10 µm, and 7–8 girdle bands in 10 µm; for the Sea of Japan, valves 85–125 µm long, 12–21 µm wide, 7–8 girdle bands in 10 µm, 20–25 fibulae in 10 µm, frustules 32.0–34.3 µm long, 10–11 µm wide, and 25 fibulae in 10 µm. For the first time, St. unipunctata valves and frustules were studied in vivo under LMs, and frustule ultrastructure, under a scanning electron microscope (SEM). For the first time, quantitative indicators of the species populations from the Black Sea and Sea of Japan were compared. The morphology of the frustule ultrastructure of St. unipunctata was studied under a Hitachi SEM, model SU3500 (Japan), in Leica EM ACE200 gold-palladium-coated samples. In the Kazachya Bay of the Black Sea near the Oceanarium, the absolute maximum abundance was recorded – 41.6·10³ cells·cm−2 with a biomass of 1.73 mg·cm−2 in January (t = +6.9 °C) in the epizoon of the cultured mussel Mytilus galloprovincialis Lamarck, 1819 at a depth of 0.5 m at excessive organic pollution of water. The minimum values were of 0.26·10³ cells·cm−2 and 0.011 mg·cm−2, respectively, in July (t = +23.5 °C) at a depth of 2.5 m. In the Paris Bay (Russky Island) of the Sea of Japan in the water area of the Marine Mammal Research Base of the Primorsky Oceanarium (Vladivostok), the abundance in the asbestos plates periphyton was of 207·10³ cells·cm−2 in the summer. For the first time, unique micrographs of the species in vivo were obtained under a LM, and of purified frustules – under a SEM.

Introduction: Most intraocular pressure (IOP)-lowering eye drops are preserved with benzalkonium chloride (BAK). This can increase side effects and decrease adherence. Particularly, damage to the mucin-producing conjunctival goblet cells may be an issue due to instability of the tear film. We aimed to investigate the effect of IOP-lowering eye drops preserved with BAK on cultured human conjunctival goblet cells. Methods: Eye drops Brimonidine Tartrate Teva (BT) with 0.005% BAK, Dorzolamide Stada (DS) with 0.0075% BAK, Optimol® (OP) with 0.01% BAK, and Latanoprost Teva (LT) with 0.02% BAK were included. Human primary cultured goblet cell survival was evaluated using a lactate dehydrogenase assay on human goblet cells after treatment for 30 min and 6 h with the different anti-glaucoma drug formulations. Results: All eye drops examined, except BT, reduced goblet cell survival. The impact of eye drops on goblet cell viability was correlated with the time of exposure as well as to the concentration of BAK. After 30 min of exposure, cell viability was 93% for BT (0.005% BAK; p = 0.93), 71% for DS (0.0075% BAK; p = 0.067), 70% for OP (0.01% BAK; p = 0.054), and 69% for LT (0.02% BAK; p = 0.022), and exposure for 6 h reduced cell survival to 74% for BT (p = 0.217), 52% for DS (p = 0.011), 34% for OP (p = 0.017), and 31% for LT (p = 0.0007). Conclusion: LT, OP, and DS reduced human goblet cell survival in a time-dependent manner. BT did not affect goblet cell survival. Cell survival was correlated with the BAK concentration in the eye drops making 0.02% BAK-preserved LT most toxic and 0.005% BAK-preserved BT least toxic. Based on the present study, decreasing BAK in eye drops for chronic use seems important to reduce damage to the goblet cells. However, future studies are needed to further explore this finding.

The endothelial adhesion protein E-selectin/CD62E is not required for leukocyte homing, unlike closely related family member P-selectin/CD62P. As transmigration through the endothelium is one of the first steps in generating a local immune response, we hypothesized that E-selectin may play additional roles in the early stages of immune activation. We found contact with E-selectin, but not P-selectin or vascular cell adhesion molecule 1 (CD106), induced phosphorylation of protein kinase B (AKT) and nuclear factor-κB in mouse bone marrow-derived macrophages (BMDMs) in vitro. This occurred within 15 min of E-selectin contact and was dependent on phosphatidylinositol-3 kinase activity. Binding to E-selectin activated downstream proteins including mammalian target of rapamycin, p70 ribosomal protein S6 kinase and eukaryotic translation initiation factor 4E-binding protein 1. Functionally, adhesion to E-selectin induced upregulation of CD86 expression and CCL2 secretion. We next asked whether contact with E-selectin impacts further BMDM stimulation. We found enhanced secretion of both interleukin (IL)-10 and CCL2, but not tumor necrosis factor or IL-6 in response to lipopolysaccharide (LPS) stimulation after adhesion to E-selectin. Importantly, adhesion to E-selectin did not polarize BMDMs to one type of response but enhanced both arginase activity and nitric oxide production following IL-4 or LPS stimulation, respectively. In cultured human monocytes, adhesion to E-selectin similarly induced phosphorylation of AKT. Finally, when E-selectin was blocked in vivo in mice, thioglycollate-elicited macrophages showed reduced CD86 expression, validating our in vitro studies. Our results imply functions for E-selectin beyond homing and suggest that E-selectin plays an early role in priming and amplifying innate immune responses.

Interleukin (IL)-22 is a multifunctional cytokine with a very short half-life that activates STAT3 and can elicit strong anti-inflammatory effects in the intestine but can induce inflammation in other sites. Several long-circulating IL-22 fusion proteins have been manufactured to date; however, those were associated with adverse effects in other organs limiting their utility for treating intestinal inflammation. Targeted delivery of IL-22 to the intestine could utilize its anti-inflammatory properties and overcome systemic toxicity. Therefore, this study aimed to synthesise large pore mesoporous silica nanoparticles (LPMSN), load recombinant (r)IL-22 in the LPMSN and test its bioactivity in the STAT3 reporter LS174T, wild type LS174T, Caco-2 intestinal epithelial cells, and healthy human colonic organoids. Our data showed one hundred percent loading capacity (w/w) of the synthesised LPMSN, which prolonged IL-22 induced STAT3 luciferase activities in LS174T and p-STAT3 immunofluorescence in Caco-2 cells. LPMSN also stabilized and increased the permeability of rIL-22 across Caco-2 monolayers. Moreover, LPMSN-IL-22 retained the functionality of the cytokine in human colonic organoids. Taken together, these data demonstrate the protection and effective delivery of IL-22 using bio-nanomaterials (LPMSN) that could enable targeted oral delivery of this IL-22.

Background & Aims Chronic bowel inflammation increases the risk of colon cancer; colitis-associated cancer (CAC). Thiopurine treatments are associated with a reduction in dysplasia and CAC in inflammatory bowel disease (IBD). Abnormal Wnt/β-catenin signalling is characteristic of >90% of colorectal cancers. Immunosuppression by thiopurines is via Rac1 GTPase, which also affects Wnt/β-catenin signalling. Autophagy is implicated in colonic tumors, and topical delivery of the thiopurine thioguanine (TG) is known to alleviate colitis and augment autophagy. This study investigated the effects of TG in a murine model of CAC and potential mechanisms. Methods Colonic dysplasia was induced by exposure to azoxymethane (AOM) and dextran sodium sulfate (DSS) in wild-type (WT) mice and mice harboring intestinal epithelial cell–specific deletion of autophagy related 7 gene (Atg7ΔIEC). TG or vehicle was administered intrarectally, and the effect on tumor burden and β-catenin activity was assessed. The mechanisms of action of TG were investigated in vitro and in vivo. Results TG ameliorated DSS colitis in wild-type but not Atg7ΔIEC mice, demonstrating that anti-inflammatory effects of locally delivered TG are autophagy-dependent. However, TG inhibited CAC in both wild-type and Atg7ΔIEC mice. This was associated with decreased β-catenin activation/nuclear translocation demonstrating that TG’s inhibition of tumorigenesis occurred independently of anti-inflammatory and pro-autophagic actions. These results were confirmed in cell lines, and the dependency on Rac1 GTPase was demonstrated by siRNA knockdown and overexpression of constitutively active Rac1. Conclusions Our findings provide evidence for a new mechanism that could be exploited to improve CAC chemoprophylactic approaches., Graphical abstract

Antitumor and immunotropic effects of κ-, λ-carrageenan from red marine algae Chondrus armatus and their low-molecular weight (LMW) degradation products were explored. Effects on human esophageal cancer cell lines KYSE30 and FLO1 viability and ability to induce production of pro- and anti-inflammatory cytokines by human monocytes was assessed. All polysaccharides demonstrated antimetabolic and cytostatic activity towards cancer lines, with high-molecular weight carrageenans possessing higher antimetabolic and lower cytostatic activity than their LMW degradation products. All carrageenans induced monocytes to produce pro-inflammatory cytokines IL1β, IL6, IL18, and TNFα. However, secretion of anti-inflammatory cytokine IL10 was induced only by LMW λ-carrageenan, which exhibited the highest cytokine production inducing efficacy overall. We demonstrate that LMW carrageenan degradation products not only retain biological activity of their precursors, but also increase their efficacy in type-dependent manner, allowing for their future development for pharmacological practice.

Enhanced osteoclast-mediated bone resorption and diminished formation may promote bone loss. Pleckstrin homology (PH) domain and leucine-rich repeat protein phosphatase 1 (Phlpp1) regulates protein kinase C (PKC) and other proteins in the control of bone mass. Germline Phlpp1 deficiency reduces bone volume, but the mechanisms remain unknown. Here, we found that conditional Phlpp1 deletion in murine osteoclasts increases their numbers, but also enhances bone mass. Despite elevating osteoclasts, Phlpp1 deficiency did not increase serum markers of bone resorption, but elevated serum markers of bone formation. These results suggest that Phlpp1 suppresses osteoclast formation and production of paracrine factors controlling osteoblast activity. Phlpp1 deficiency elevated osteoclast numbers and size in ex vivo osteoclastogenesis assays, accompanied by enhanced expression of proto-oncogene C-Fms (C-Fms) and hyper-responsiveness to macrophage colony-stimulating factor (M-CSF) in bone marrow macrophages. Although Phlpp1 deficiency increased TRAP(+) cell numbers, it suppressed actin-ring formation and bone resorption in these assays. We observed that Phlpp1 deficiency increases activity of PKCζ, a PKC isoform controlling cell polarity, and that addition of a PKCζ pseudosubstrate restores osteoclastogenesis and bone resorption of Phlpp1-deficient osteoclasts. Moreover, Phlpp1 deficiency increased expression of the bone-coupling factor collagen triple helix repeat-containing 1 (Cthrc1). Conditioned growth medium derived from Phlpp1-deficient osteoclasts enhanced mineralization of ex vivo osteoblast cultures, an effect that was abrogated by Cthrc1 knockdown. In summary, Phlpp1 critically regulates osteoclast numbers, and Phlpp1 deficiency enhances bone mass despite higher osteoclast numbers because it apparently disrupts PKCζ activity, cell polarity, and bone resorption and increases secretion of bone-forming Cthrc1.

We develop an effective theory approach to investigate the phase properties of globular proteins. Instead of interactions between individual atoms or localized interaction centers, the approach builds directly on the tertiary structure of a protein. As an example we construct the phase diagram of (apo)myoglobin with temperature (T) and acidity (pH) as the thermodynamical variables. We describe how myoglobin unfolds from the native folded state to a random coil when temperature and acidity increase. We confirm the presence of two molten globule folding intermediates, and we predict an abrupt transition between the two when acidity changes. When temperature further increases we find that the abrupt transition line between the two molten globule states terminates at a tricritical point, where the helical structures fade away. Our results also suggest that the ligand entry and exit is driven by large scale collective motions that destabilize the myoglobin F-helix.

We investigate aspects of topology in protein folding. For this we numerically simulate the temperature driven folding and unfolding of the slipknotted archaeal virus protein AFV3-109. Due to knottiness the (un)folding is a topological process, it engages the entire backbone in a collective fashion. Accordingly we introduce a topological approach to model the process. Our simulations reveal that the (un)folding of AFV3-109 slipknot proceeds through a folding intermediate that has the topology of a trefoil knot. We observe that the final slipknot causes a slight swelling of the folded AFV3-109 structure. We disclose the relative stability of the strands and helices during both the folding and unfolding processes. We confirm results from previous studies that pointed out that it can be very demanding to simulate the formation of knotty self-entanglement, and we explain how the problems are circumvented: The slipknotted AFV3-109 protein is a very slow folder with a topologically demanding pathway, which needs to be properly accounted for in a simulation description. When we either increase the relative stiffness of bending, or when we decrease the speed of ambient cooling, the rate of slipknot formation rapidly increases.

Ability of high molecular weight (HMW) κ- and λ-carrageenans of the red marine algae Chondrus armatus and their low molecular weight degradation products (LMWDPs) (0.7-20 and 10-170 kDa respectively) to influence functional properties (motility and phagocytosis) of murine peritoneal macrophages was assessed in this study as an in vitro and a weeklong feeding experiment. We demonstrated that, with an exception of one, all carrageenan samples at 100 μg/ml increased cellular motility and dose-dependently decreased phagocytic activity; LMWDPs of λ-carrageenan suppressed motility and had no effect on phagocytosis. Oral administration of all the carrageenan samples at 100 μg/kg/day for 7 days to mice had no effect on their clinical appearance, body weight, weight of their liver, spleen or thymus or development of noticeable changes to their inner organs. All samples induced a shift of the cell composition of the peritoneal cavity towards macrophages. Consumption of LMWDPs of κ-carrageenan resulted in development of leukopenia, however, no changes to relative WBC count were introduced by either of the samples. All samples decreased murine peritoneal macrophages phagocytic activity, with λ-samples possessing higher efficacy than their κ-counterparts; all LMWDPs stimulated peritoneal macrophages motility, with κ-samples possessing higher efficacy than their λ-counterparts In conclusion, we have shown that κ- and λ-carrageenans of the C. armatus and their LMWDPs suppress phagocytotic activity of peritoneal macrophages under both in vitro and in vivo conditions. This allows them to be viewed as pharmacologically active substances andpropagates the need for their further investigation as such.

Site specific oral delivery of many biopharmaceutical classification system (BCS) class II and IV drugs is challenging due to their poor solubility, low permeability and degradation in the gastrointestinal tract. Whilst colloidal carriers have been used to improve the bioavailability of such drugs, most nanocarriers based drug delivery systems suffer from multiple disadvantages, including low encapsulation efficiency (liposomes, polymeric nanoparticles), complex synthesis methods (silica, silicon-based materials) and poorly understood biodegradability (inorganic nanoparticles). Herein, a novel pH responsive nanocolloids were self-assembled using natural compounds such as bovine β-lactoglobulin (BLG) and succinylated β-lactoglobulin (succ. BLG) cross-linked with epsilon poly l-lysine (BCEP and BCP), and found to possess high loading capacity, high aqueous solubility and site-specific oral delivery of a poorly soluble nutraceutical (curcumin), improving its physicochemical properties and biological activity in-vitro and ex-vivo. Our optimized synthesis formed colloids of around 200 nm which were capable of encapsulating curcumin with ~100% encapsulation efficiency and ~10% w/w drug loading. By forming nanocomplexes of curcumin with BLG and succ. BLG, the aqueous solubility of curcumin was markedly increased by ~160-fold and ~86-fold, respectively. Encapsulation with BLG increased the solubility, whereas succ. BLG prevent release of encapsulated curcumin when subjected to gastric fluids as it is resistant to breakdown on exposure to pepsin at acidic pH. In conditions mimicking the small intestine, Succ. BLG was more soluble resulting in sustained release of the encapsulated drug at pH 7.4. Additionally, crosslinking succ. BLG with E-PLL significantly enhanced curcumin's permeability in an in-vitro Caco-2 cell monolayer model compared to curcumin solution (dissolved in 1% DMSO), or non-crosslinked BLG/succ. and BLG. In a mouse-derived intestinal epithelial 3D organoid culture stimulated with IL-1β, BLG-CUR and crosslinked BCEP nanoparticles reduced the production of inflammatory cytokines and chemokines such as Tnfα and Cxcl10 more than curcumin solution or suspension while these nanoparticles were non-toxic to organoids. Overall this work demonstrates the promise of nutraceutical-based hybrid self-assembled colloidal system to protect hydrophobic drugs from harsh gastrointestinal conditions and improve their solubility, dissolution, permeability and biological activity.

Bone-stimulatory therapeutics include bone morphogenetic proteins (e.g. BMP2), parathyroid hormone, and antibody-based suppression of WNT antagonists. Inhibition of the epigenetic enzyme enhancer of zeste homolog 2 (EZH2) is both bone anabolic and osteoprotective. EZH2 inhibition stimulates key components of bone-stimulatory signaling pathways, including the BMP2 signaling cascade. Because of high costs and adverse effects associated with BMP2 use, here we investigated whether BMP2 dosing can be reduced by co-treatment with EZH2 inhibitors. Co-administration of BMP2 with the EZH2 inhibitor GSK126 enhanced differentiation of murine (MC3T3) osteoblasts, reflected by increased alkaline phosphatase activity, Alizarin Red staining, and expression of bone-related marker genes (e.g. Bglap and Phospho1). Strikingly, co-treatment with BMP2 (10 ng/ml) and GSK126 (5 μm) was synergistic and was as effective as 50 ng/ml BMP2 at inducing MC3T3 osteoblastogenesis. Similarly, the BMP2-GSK126 co-treatment stimulated osteogenic differentiation of human bone marrow-derived mesenchymal stem/stromal cells, reflected by induction of key osteogenic markers (e.g. Osterix/SP7 and IBSP). A combination of BMP2 (300 ng local) and GSK126 (5 μg local and 5 days of 50 mg/kg systemic) yielded more consistent bone healing than single treatments with either compound in a mouse calvarial critical-sized defect model according to results from μCT, histomorphometry, and surgical grading of qualitative X-rays. We conclude that EZH2 inhibition facilitates BMP2-mediated induction of osteogenic differentiation of progenitor cells and maturation of committed osteoblasts. We propose that epigenetic priming, coupled with bone anabolic agents, enhances osteogenesis and could be leveraged in therapeutic strategies to improve bone mass.

Hdac3 is a lysine deacetylase that removes acetyl groups from histones and additional proteins. Although Hdac3 functions within mesenchymal lineage skeletal cells are defined, little is known about Hdac3 activities in bone-resorbing osteoclasts. In this study we conditionally deleted Hdac3 within Ctsk-expressing cells and examined the effects on bone modeling and osteoclast differentiation in mice. Hdac3 deficiency reduced femur and tibia periosteal circumference and increased cortical periosteal osteoclast number. Trabecular bone was likewise reduced and was accompanied by increased osteoclast number per trabecular bone surface. We previously showed that Hdac3 deacetylates the p65 subunit of the NF-κB transcriptional complex to decrease DNA-binding and transcriptional activity. Hdac3-deficient osteoclasts demonstrate increased K310 NF-κB acetylation and NF-κB transcriptional activity. Hdac3-deficient osteoclast lineage cells were hyper-responsive to RANKL and showed elevated ex vivo osteoclast number and size and enhanced bone resorption in pit formation assays. Osteoclast-directed Hdac3 deficiency decreased cortical and trabecular bone mass parameters, suggesting that Hdac3 regulates coupling of bone resorption and bone formation. We surveyed a panel of osteoclast-derived coupling factors and found that Hdac3 suppression diminished sphingosine-1-phosphate production. Osteoclast-derived sphingosine-1-phosphate acts in paracrine to promote bone mineralization. Mineralization of WT bone marrow stromal cells cultured with conditioned medium from Hdac3-deficient osteoclasts was markedly reduced. Expression of alkaline phosphatase, type 1a1 collagen, and osteocalcin was also suppressed, but no change in Runx2 expression was observed. Our results demonstrate that Hdac3 controls bone modeling by suppressing osteoclast lineage cell responsiveness to RANKL and coupling to bone formation.

Marine algae are abundant and inexhaustive sources of the bioactive compounds with the various benefits for human health. Among these substances an attention is given to the sulfated polysaccharides presented as the complexes of polymer macromolecules with excellent biological features including antioxidant, anti-inflammatory anticoagulant, antiviral, and immunomodulatory activities. In addition to the aforementioned properties there is a growing number of research results suggesting the bioactive sulfated polysaccharides such as carrageenan, fucoidan, laminarin, and others exert anticancer and antimetastatic properties. The present review contains the main results of experimental studies of the carrageenan anticancer activity including systemic and intracellular mechanisms of the antiproliferative influence. Relationships between structure, physico-chemical properties of carrageenan and their antitumor effects are described. There are data on the toxicology and pharmacokinetics of carrageenans as well as other aspects of their pharmacotherapeutic and pharmacoprophylactic influence that allow considering them as the potential anticancer agents.

Hexavalent chromium raises high concern because of its wide industrial applications and reported toxicity. Long-term (135 days) oral exposure of Wistar rats to chromium in the form of K2Cr2O7 (exposed group~20 mg/kg/day) led to a decrease in thymus mass and thymocytes' number and caused structural and functional changes in the lymph nodes and spleen, namely lymphoreticular hyperplasia and plasmocytic macrophage transformation. Programmed cell death was increased in both thymocytes and splenocytes and decreased in lymphocytes in the T-zones of spleen and lymph nodes. Moreover, Cr (VI) administration decreased myeloid cells' and neutrophils' number, while it increased lymphoid and erythroid cells' number in bone marrow. Cr (VI) immune system effects seem to be related to oxidative stress induction, as depicted by the increased levels of diene conjugates and malondialdehyde in the spleen and liver and by the decreased activity of catalase and superoxide dismutase in rats’ erythrocytes. In addition, exposure to Cr (VI) decreased copper, nickel and iron concentrations in blood and liver, while Cr levels in blood, spleen and liver were increased, as expected. The observed changes in the series of immunological parameters studied contribute to the development of new approaches for the prevention of low level Cr exposure toxicity. This is peer-reviewed version of the following article: Karaulov, A. V.; Renieri, E. A.; Smolyagin, A. I.; Mikhaylova, I. V.; Stadnikov, A. A.; Begun, D. N.; Tsarouhas, K.; Buha Djordjevic, A.; Hartung, T.; Tsatsakis, A. Long-Term Effects of Chromium on Morphological and Immunological Parameters of Wistar Rats. Food Chem. Toxicol. 2019, 133, 110748. [https://doi.org/10.1016/j.fct.2019.110748]

Excess fat within bone marrow is associated with lower bone density. Metabolic stressors such as chronic caloric restriction (CR) can exacerbate marrow adiposity, and increased glucocorticoid signaling and adrenergic signaling are implicated in this phenotype. The current study tested the role of glucocorticoid signaling in CR-induced stress by conditionally deleting the glucocorticoid receptor (Nr3c1; hereafter abbreviated as GR) in bone marrow osteoprogenitors (Osx1-Cre) of mice subjected to CR and ad libitum diets. Conditional knockout of the GR (GR-CKO) reduced cortical and trabecular bone mass as compared to WT mice under both ad libitum feeding and CR conditions. No interaction was detected between genotype and diet, suggesting that the GR is not required for CR-induced skeletal changes. The lower bone mass in GR-CKO mice, and the further decrease in bone by CR, resulted from suppressed bone formation. Interestingly, treatment with the β-adrenergic receptor antagonist propranolol mildly but selectively improved metrics of cortical bone mass in GR-CKO mice during CR, suggesting interaction between adrenergic and glucocorticoid signaling pathways that affects cortical bone. GR-CKO mice dramatically increased marrow fat under both ad libitum and CR-fed conditions, and surprisingly propranolol treatment was unable to rescue CR-induced marrow fat in either WT or GR-CKO mice. Additionally, serum corticosterone levels were selectively elevated in GR-CKO mice with CR, suggesting the possibility of bone–hypothalamus–pituitary–adrenal crosstalk during metabolic stress. This work highlights the complexities of glucocorticoid and β-adrenergic signaling in stress-induced changes in bone mass, and the importance of GR function in suppressing marrow adipogenesis while maintaining healthy bone mass.

Oral glucocorticoids are backbones for the acute management of inflammatory bowel disease (IBD). However, the clinical effectiveness of conventional oral dosage forms of glucocorticoids is hindered by their low delivery efficiency and systemic side effects. To overcome this problem, a smart drug delivery system with high loading capacity and colonic release by coating functionalized mesoporous silica nanoparticles (MSNs) with a pH‐responsive polymer Eudragit S100 is proposed. In vitro dissolution tests show that Eudragit‐coated MSNs can limit the burst release of loaded prednisolone and budesonide in the gastric environment with more than 60% of the drugs released only at colonic pH (i.e., pH ≥ 7). In vivo therapeutic efficacy of budesonide‐loaded nanoparticles is tested in a murine model of dextran sodium sulfate‐induced colitis. An oral budesonide dose of 0.2 mg kg−1 nanoparticles with Eudragit coating improves the disease activity index compared to other groups. Interestingly, both coated and uncoated nanoparticles show pathological improvements demonstrated by similar levels of histological colitis score. However, coated nanoparticles significantly decrease mRNA expression of the cytokines (Il‐1β, Il‐17, and Il‐10) particularly in proximal colon, indicating colonic delivery. Overall, this study demonstrates the effectiveness of a simple method to fabricate targeted nanomedicine for the treatment of IBD.

BackgroundHip replacement and hip resurfacing are common surgical procedures with an estimated risk of revision of 4% over 10 year period. Approximately 58% of hip replacements will last 25 years. Some implants have higher revision rates and early identification of poorly performing hip replacement implant brands and cup/head brand combinations is vital.AimsDevelopment of a dynamic monitoring method for the revision rates of hip implants.MethodsData on the outcomes following the hip replacement surgery between 2004 and 2012 was obtained from the National Joint Register (NJR) in the UK. A novel dynamic algorithm based on the CUmulative SUM (CUSUM) methodology with adjustment for casemix and random frailty for an operating unit was developed and implemented to monitor the revision rates over time. The Benjamini-Hochberg FDR method was used to adjust for multiple testing of numerous hip replacement implant brands and cup/ head combinations at each time point.ResultsThree poorly performing cup brands and two cup/ head brand combinations have been detected. Wright Medical UK Ltd Conserve Plus Resurfacing Cup (cup o), DePuy ASR Resurfacing Cup (cup e), and Endo Plus (UK) Limited EP-Fit Plus Polyethylene cup (cup g) showed stable multiple alarms over the period of a year or longer. An addition of a random frailty term did not change the list of underperforming components. The model with added random effect was more conservative, showing less and more delayed alarms.ConclusionsOur new algorithm is an efficient method for early detection of poorly performing components in hip replacement surgery. It can also be used for similar tasks of dynamic quality monitoring in healthcare.

Quantum dot/SiOx film structures synthesized using a new hydrogen fluoride technology of silicon nanoparticles in a porous silicon oxide matrix have been studied in detail. A physical mechanism of influence of chemical treatment in HF vapors in air on structural and light emitting properties of nanosized silicon film porous systems has been proposed. We show that passivation of broken bonds on the surface of Si nanoinclusions as a result of treatment with the participation of oxygen, fluorine and hydrogen atoms reduces the non-emitting recombination channel. A model has been suggested accounting for the shift of the photoluminescence spectrum towards the blue region as a result of treatment due to a decrease in the sizes of the Si quantum dots during the oxidation of their surface layer.

International audience; The gut microbiota is increasingly implicated in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC) although the identity of the bacteria that underpin these diseases has remained elusive. The pathobiont Bacteroides vulgatus has been associated with both diseases although relatively little is known about how its growth and functional activity might drive the host inflammatory response. We identified an ATP Binding Cassette (ABC) export system and lipoprotein in B. vulgatus ATCC 8482 and B. vulgatus PC510 that displayed significant sequence similarity to an NF-kappa B immunomodulatory regulon previously identified on a CD-derived metagenomic fosmid clone. Interestingly, the ABC export system was specifically enriched in CD subjects suggesting that it may be important for colonization and persistence in the CD gut environment. Both B. vulgatus ATCC 8482 and PC510 activated NF-kappa B in a strain and growth phase specific manner in a HT-29/kb-seap-25 enterocyte like cell line. B. vulgatus ATCC 8482 also activated NF-kappa B in a Caco-2-NF-kappa Bluc enterocyte like and an LS174T-NF-kappa Bluc goblet cell like cell lines, and induced NF-kappa B-p65 subunit nuclear translocation and IL-6, IL-8, CXCL-10 and MCP-1 gene expression. Despite this, NF-kappa B activation was not coincident with maximal expression of the ABC exporter or lipoprotein in B. vulgatus PC510 suggesting that the regulon may be necessary but not sufficient for the immunomodulatory effects.

Photoelectric Properties of Heterostructures with Oxide Films Containing Si(Ge) Quantum Dots Formed by Pulsed Laser Deposition A. V. Sachenko1, D. V. Korbutyak1, Yu. V. Kryuchenko1 ∗, E. B. Kaganovich1, E. G. Manoilov1, E. V. Begun1, O. M. Sreseli2, and I. I. Geru3 1V Lashkarev Institute of Semiconductor Physics, National Academy of Sciences of Ukraine, Kyiv 03028, Ukraine 2Ioffe Physical-Technical Institute of the Russian Academy of Sciences, St.-Petersburg 199034, Russia 3Institute of Chemistry of the Academy of Sciences of Moldova, Chisinau, MD-2028, Moldova

The Women and Jails Project involved a jail in-reach brief screening and feedback intervention for women experiencing problems with alcohol or other substances. The screening and brief intervention (SBI) protocol involved the application of an evidence-informed screening interview (the Alcohol Use Disorder Identification Test-Including Drugs, or AUDIT-12) and the provision of personalized feedback on each woman's screening results, delivered in a brief motivational interview format. Comparisons of interview data while incarcerated and 2 months postrelease indicated significantly greater improvement in alcohol and other substance use screening results (lower AUDIT-12 scores) among women randomly assigned to intervention versus treatment as usual groups. This greater improvement could not be attributed to greater treatment engagement because that difference was not significant. The authors discuss practice and future research implications of the jail in-reach intervention and providing resource information ...

It is shown that preparations containing thiram inhibit reproduction of fast-growing strains of bacteria and lead to the death of slow-growing ones. Pesticides Cruiser, Chinufur, Maxim, and Fundazol have a weak inhibiting effect on them and abundant formation of bacterial mass is restored on the 10th day. Treatment of seeds with these preparations is compatible with bacterization, which increases soybean yield.

Production and hydrochemical characteristics of ice, under-ice water, and sediments in the Razdol’naya River estuary (Sea of Japan) were studied during the ice cover periods of the years 2007 and 2008. In 2007, snow cover was absent until mid-February and PAR levels under ice were sufficient for the development of phytoplankton. The chlorophyll a content in ice, under-ice water, and surface sediments was high, while nutrient levels were decreased. After a snowfall, the chlorophyll content in ice and under-ice water decreased sharply. In winter 2008, snow cover was formed immediately after freeze-up; therefore, PAR levels in the ice and under-ice water were significantly reduced. The chlorophyll content was lower, but nutrient levels were higher than in 2007. In both winter seasons, the greatest portion of chlorophyll (up to 85%) was contained in surface sediments. Diatoms were dominant in ice and under-ice water. In the absence of snow, primary production at the end of ice cover period may reach 1 g cal/(m2 day). With snow cover present, this index was markedly reduced.

The composition of photoluminescent films containing low-dimensional silicon and germanium is studied. Si, Ge, and Al oxide films containing Si and Ge quantum dots are produced by pulsed laser ablation. The infrared transmittance spectra in the range of wave numbers from 650 to 1400 cm−1 and the time-resolved photoluminescence spectra in the energy range from 1.4 to 3.2 eV at room temperature are recorded. Correlations between the conditions of formation of the films, their photoluminescence properties, and the stretching vibrations of Si-O-Si, Ge-O-Ge, and Al-O bonds are established.

Time-resolved studies of photoluminescence in the energy range 1.4–3.2 eV are carried out for GeOx films (x ≤ 2) containing Ge nanoclusters. The relaxation times vary in the range from 50 ns to 20 μs. The films are produced by single-stage pulsed laser ablation and deposited from the direct and reverse fluxes of particles of the erosion spray in oxygen and argon atmosphere. The dependences of the photoluminescence properties of the films on the conditions of deposition and on doping with gold are studied. The photoluminescence bands, with peaks at the energies 1.42–2.1 eV, are narrow, slow, and close to each other in energy, whereas the other bands, with peaks near 2.5 eV and in the range 2.7–2.9 eV, are broad, faster, and only slightly overlapping in energy. The results are interpreted in the context of the model of photoluminescence in Ge quantum dots, whose dimensions are controlled by the conditions of their formation.

To understand how novel functions arise, we must identify common patterns and mechanisms shaping the evolution of new genes. Here, we take advantage of data from three Drosophila genes, jingwei , Adh-Finnegan , and Adh-Twain , to find evolutionary patterns and mechanisms governing the evolution of new genes. All three of these genes are independently derived from Adh , which enabled us to use the extensive literature on Adh in Drosophila to guide our analyses. We discovered a fundamental similarity in the temporal, spatial, and types of amino acid changes that occurred. All three genes underwent rapid adaptive amino acid evolution shortly after they were formed, followed by later quiescence and functional constraint. These genes also show striking parallels in which amino acids change in the Adh region. We showed that these early changes tend to occur at amino acid residues that seldom, if ever, evolve in Drosophila Adh . Changes at these slowly evolving sites are usually associated with loss of function or hypomorphic mutations in Drosophila melanogaster . Our data indicate that shifting away from ancestral functions may be a critical step early in the evolution of chimeric fusion genes. We suggest that the patterns we observed are both general and predictive.

The cross sections of (n, x) nuclear reactions on Y, La, Ta, Pb and Bi were measured at the neutron energy 14.5 MeV by activation method with γ-ray spectra studies. The excitation functions in the range En=13.5÷14.6 MeV were investigated for reactions on Pb and Ta. The experimental results are compared both with the experimental data of other authors and with evaluated data from JENDL-3.2. The theoretical calculations for most of measured cross sections were performed with the use of STAPRE-H95 code.

Maintenance of bone mass and geometry is influenced by mechanical stimuli. Paradigms suggest that osteocytes embedded within the mineralized matrix and osteoblasts on the bone surfaces are the primary responders to physical forces. However, other cells within the bone marrow cavity, such as megakaryocytes (MKs), are also subject to mechanical forces. Recent studies have highlighted the potent effects of MKs on osteoblast proliferation as well as bone formation in vivo. We hypothesize that MKs are capable of responding to physical forces and that the interactions between these cells and osteoblasts can be influenced by mechanical stimulation. In this study, we demonstrate that two MK cell lines respond to fluid shear stress in culture. Furthermore, using laser capture microdissection, we isolated MKs from histologic sections of murine tibiae that were exposed to compressive loads in vivo. C-fos, a transcription factor shown to be upregulated in response to load in various tissue types, was increased in MKs from loaded relative to non-loaded limbs at a level comparable to that of osteocytes from the same limbs. We also developed a co-culture system to address whether mechanical stimulation of MKs in culture would impact osteoblast proliferation and differentiation. The presence of MKs in co-culture, but not conditioned media, had dramatic effects on proliferation of preosteoblast MC3T3-E1 cells in culture. Our data suggests a minimal decrease in proliferation as well as an increase in mineralization capacity of osteoblasts co-cultured with MKs exposed to shear compared to co-cultures with unstimulated MKs.

A complex of two proteins, Xrcc4 and DNA ligase IV, plays a fundamental role in DNA non-homologous end joining (NHEJ), a cellular function required for double-strand break repair and V(D)J recombination. Here we report the crystal structure of human Xrcc4 bound to a polypeptide that corresponds to the DNA ligase IV sequence linking its two BRCA1 C-terminal (BRCT) domains. In the complex, a single ligase chain binds asymmetrically to an Xrcc4 dimer. The helical tails of Xrcc4 undergo a substantial conformational change relative to the uncomplexed protein, forming a coiled coil that unwinds upon ligase binding, leading to a flat interaction surface. A buried network of charged hydrogen bonds surrounded by extensive hydrophobic contacts explains the observed tightness of the interaction. The strong conservation of residues at the interface between the two proteins provides evidence that the observed mode of interaction has been maintained in NHEJ throughout evolution.

Background: Adrenaline is localized to specific regions of the central nervous system (CNS), but its role therein is unclear because of a lack of suitable pharmacologic agents. Ideally, a chemical is required that crosses the blood-brain barrier, potently inhibits the adrenaline-synthesizing enzyme PNMT, and does not affect other catecholamine processes. Currently available PNMT inhibitors do not meet these criteria. We aim to produce potent, selective, and CNS-active PNMT inhibitors by structure-based design methods. The first step is the structure determination of PNMT. Results: We have solved the crystal structure of human PNMT complexed with a cofactor product and a submicromolar inhibitor at a resolution of 2.4 A. The structure reveals a highly decorated methyltransferase fold, with an active site protected from solvent by an extensive cover formed from several discrete structural motifs. The structure of PNMT shows that the inhibitor interacts with the enzyme in a different mode from the (modeled) substrate noradrenaline. Specifically, the position and orientation of the amines is not equivalent. Conclusions: An unexpected finding is that the structure of PNMT provides independent evidence of both backward evolution and fold recruitment in the evolution of a complex enzyme from a simple fold. The proposed evolutionary pathway implies that adrenaline, the product of PNMT catalysis, is a relative newcomer in the catecholamine family. The PNMT structure reported here enables the design of potent and selective inhibitors with which to characterize the role of adrenaline in the CNS. Such chemical probes could potentially be useful as novel therapeutics.

NF-κB and IκB proteins have central roles in regulation of inflammation and innate immunity in mammals. Homologues of these proteins also play an important role in regulation of the Drosophila immune response. Here we present a molecular population genetic analysis of Relish, a Drosophila NF-κB/IκB protein, in Drosophila simulans and D. melanogaster. We find strong evidence for adaptive protein evolution in D. simulans, but not in D. melanogaster. The adaptive evolution appears to be restricted to the IκB domain. A possible explanation for these results is that Relish is a site of evolutionary conflict between flies and their microbial pathogens.

Raman spectra have been used to identify and characterize aqueous hydroxouranyl(VI) complexes from 0.0038 to 0.647M at pH from 0.24 to 14.96 adjusted witheither HCF3SO3 and/or (CH3)4NOH under ambient conditions. In acidic media(0.24 ≤ pH ≤ 5.63), the existence of four species UO2+ 2,(UO2)2(OH)3+,(UO2)2(OH)2+ 2, and (UO2)3(OH)+ 5 was confirmed. At high uranium concentrations(ΣU ≥ 0.1M) and in strongly acidic solutions (pH ≤ 1.94), one additional weakband was observed at 883±1 cm−1. This band was assumed torepresent thespecies UO2+ 2 with a reduced hydration number.In neutral and basic solutions(5.63 ≤ pH ≤ 14.96), five complexes were postulated: (UO2)3(OH)− 7,(UO2)3(OH)2− 8,(UO2)3(OH)4− 10,(UO2)3(OH)5− 11, andUO2(OH)2− 4, based on theassigned symmetrical stretching frequencies of the UO2 group in each complex.(UO2)3(OH)− 7 is the dominant species over mostof the pH range (4.53–12.78).The stability ranges of the other trinuclear species are:(UO2)3(OH)2− 8 (10.97 ≤pH ≤ 13.83), (UO2)3(OH)4− 10 (10.97 ≤ pH ≤ 13.85) and (UO2)3(OH)5− 11(12.53 ≤pH ≤ 14.10), which were identified for the first time. Finally, the monomericuranate anion OU2(OH)2− 4 dominates in highly basic solution (12.48 ≤ pH ≤14.96). The linear correlation between the symmetrical vibrational frequency v 1of the linear O = U = O entity and the average number $$\overline n$$ of hydroxide ligandscoordinated to each uranium atom in a given species has been reaffirmed andexpanded: $$v_1 ({\text{cm}}^{{\text{ - 1}}} ) = - 22X\overline n + 870$$ The v 1 correlation was also used to predict the vibration frequencies of theundetected monomers UO2(OH)+, UO2(OH)o 2,UO2(OH)− 3 at 848±2, 826±2, and804±2 cm±1, respectively. Characteristic band areas for eachuranyl hydrolyzedspecies were determined by Raman spectra decomposition and their hydrolysisquotients log Q, were calculated. Structures of the four triuranylspecies are proposed.

High-resolution crystal structures are described for seven macrocycles complexed with HIV-1 protease (HIVPR). The macrocycles possess two amides and an aromatic group within 15-17 membered rings designed to replace N- or C-terminal tripeptides from peptidic inhibitors of HIVPR. Appended to each macrocycle is a transition state isostere and either an acyclic peptide, nonpeptide, or another macrocycle. These cyclic analogues are potent inhibitors of HIVPR, and the crystal structures show them to be structural mimics of acyclic peptides, binding in the active site of HIVPR via the same interactions. Each macrocycle is restrained to adopt a P-strand conformation which is preorganized for protease binding. An unusual feature of the binding of C-terminal macrocyclic inhibitors is the interaction between a positively charged secondary amine and a catalytic aspartate of HIVPR. A bicyclic inhibitor binds similarly through its secondary amine that lies between its component N-terminal and C-terminal macrocycles. In contrast, the corresponding tertiary amine of the N-terminal macrocycles does not interact with the catalytic aspartates. The amine-aspartate interaction induces a 1.5 Angstrom N-terminal translation of the inhibitors in the active site and is accompanied by weakened interactions with a water molecule that bridges the ligand to the enzyme, as well as static disorder in enzyme flap residues. This flexibility may facilitate peptide cleavage and product dissociation during catalysis. Proteases [Aba(67,95)]HIVPR and [Lys(7),Ile(33),Aba(67,95)]- HIVPR used in this work were shown to have very similar crystal structures.

Investigation of the Raman spectra of the molten MgCl2-KCl system by the use of factor analysis indicates that the melt is a two-component system involving equilibrium between MgCl and Mg2Cl. The pure Raman spectra corresponding to these two species are recovered from the broad features via a self-modeling method.

Basic fibroblast grown factor (bFGF) is a potent mitogen for mesenchymal cells, including fibroblasts cultured from prostate, and has been postulated to play a role in the development of benign prostatic hyperplasia (BPH). If this is the case, it might be expected that bFGF levels would be elevated in the adenomas of BPH and in the periurethral region of the prostate where BPH is believed to arise. This study was undertaken to test this hypothesis. The concentration of bFGF was evaluated in 31 prostates, 13 normal glands and 18 with BPH. A method for quantitating bFGF by radioimmunoassay was developed that enabled growth factor levels to be correlated to the geographic region of the prostate and the histopathology of the specimen. A 2- to 3-fold higher concentration of bFGF (ng./g. of tissue) was noted in the benign hyperplastic prostates when compared with the adult normal glands. Pubertal specimens demonstrated low growth factor levels comparable to those observed in the normal adult group. Two prepubertal prostates analyzed had high levels similar to those measured in the hyperplastic glands. While the levels of bFGF in the normal adult prostates were highest in the periurethral region, statistical analysis failed to demonstrate a significant difference. Similarly, quantitative morphometric evaluation failed to demonstrate any significant differences in bFGF concentration related to the proportion of stromal, epithelial, or lumenal elements in the tissue sections.

We present experimental results and theoretical simulations of the adsorption behavior of the metal-organic precursor Co2(CO)8 on SiO2 surfaces after application of two different pre-treatment steps, namely by air plasma cleaning or a focused electron beam pre-irradiation. We observe a spontaneous dissociation of the precursor molecules as well as auto-deposition of cobalt on the pre-treated SiO2 surfaces. We also find that the differences in metal content and relative stability of these deposits depend on the pre-treatment conditions of the substrate. Transport measurements of these deposits are also presented. We are led to assume that the degree of passivation of the SiO2 surface by hydroxyl groups is an important controlling factor in the dissociation process. Our calculations of various slab settings using dispersion corrected density functional theory support this assumption. We observe physisorption of the precursor molecule on a fully hydroxylated SiO2 surface (untreated surface) and chemisorption on a partially hydroxylated SiO2 surface (pre-treated surface) with a spontaneous dissociation of the precursor molecule. In view of these calculations, we discuss the origin of this dissociation and the subsequent autocatalysis., Comment: 22 pages, 8 Figures, In Press Article, Beilstein Journal of Nanotechnology, 2012

The wetted surfaces of the high‐temperature, high‐pressure Raman cell (400 °C and 1 kbar) were constructed of inert materials (i.e., sapphire or quartz and platinum with gold seals) and designed to allow spectroscopic measurements to be made with small volumes (

The Surface-Enhanced Raman spectra of three important polycyclic aromatic dyes used in the food and cosmetic industries. Erythrosine, Eosine, and Phloxine, are recorded for the first time. The ability of the Surface-Enhanced Raman scattering techniques to detect these dyes at trace level is demonstrated. Such techniques minimize the fluorescence background in these highly fluorescing dyes, bringing out the Surface-Enhanced Raman Spectra features. The Normal Raman Spectra of erythrosine and phtalazine were also recorded and compared with their Surface-Enhanced Raman Spectra to illustrate the fluorescence suppression in Surface Enhanced Raman Spectra. The vibrational spectra features of the three dyes are discussed in terms of their molecular structure and the vibrations of the aromatic rings.

The Raman spectra of the aqueous dioxouranium(VI) ion have been measured as a function of ligand and uranyl concentrations at various constant pH values. The ligands investigated were F[sup [minus]], Cl[sup [minus]], Br[sup [minus]], SO[sub 4][sup 2[minus]], HSO[sub 4][sup [minus]], NO[sub 3][sup [minus]], ClO[sub 4][sup [minus]], CH[sub 3]CO[sub 2][sup [minus]], and C[sub 2]O[sub 4][sup 2[minus]]. A linear correlation between the frequency of the O=U=O symmetrical stretching vibration ([nu][sub 1], cm[sup [minus]1]) and the average number [bar n] of ligand coordinated equatorially to the central uranium atom in the given species has been established for the above-mentioned ligands according to the following equation: [nu][sub 1] (cm[sup [minus]1]) = -A[bar n] + 870, where A is a characteristic coefficient (cm[sup [minus]1]) representing the shift in the [nu][sub 1] band for the addition of each ligand to the uranyl(VI) center relative to 870 cm[sup [minus]1] for UO[sub 2][sup 2+](aq). Except for the case of ClO[sub 4][sup [minus]] (A = -15 cm[sup [minus]1]), the values of A are positive and vary in the range 0-15. The preceding equation was derived earlier for OH[sup [minus]] anions with A = 21.5 [+-] 1.0 cm[sup [minus]1]. Results obtained elsewhere for CO[sub 3][sup 2[minus]] also fit this equationmore » with A = 19.0 [+-] 1.0 cm[sup [minus]1]. This linear correlation provides a convenient, nondestructive method of identifying the possible stoichiometry of uranyl(VI) complexes in solution and a means for estimating their stability fields with respect to ligand concentration and pH.« less

Surface-enhanced Raman scattering (SERS) spectra of Thiram (C 6 H 12 N 2 S 4 ) and Ferbam (C 9 H 18 N 3 S 6 Fe); and normal Raman scattering (NRS) spectra of Thiram and Metam-Sodium (C 2 H 4 NNaS 2 ) were investigated. The SERS spectra of the two compounds and NRS spectrum of Metam-Sodium were recorded for the first time. The SERS signals useful for trace analysis of these fungicides are identified. The spectral features of these compounds are discussed and compared with the previous data. The importance of SERS analyses to ensure the environmentally safe use of such compounds is discussed

A novel all-silica fiberoptic probe is described. Instead of cementing individual optical fibers together, the fibers are fused together within a silica tube. This all-silica probe has been used for obtaining Raman spectra of various molten salt systems at temperatures up to 720 °C. It has also been used for Raman spectral studies of samples at ambient temperatures.

The reported Raman spectra of the tetragonal [lead chlorofluoride-type structure, D-P4/nmm (ITC No. 129)] lanthanide oxychlorides are inconsistent. Nuclear site symmetry analysis predicts six Raman bands. Five peaks are consistently observed, whereas the sixth remains controversial. Also, two different sets of irreducible representations are reported: which include the three acoustic modes, A2u{Tz} and Eu{Tx, Ty}. The present analysis of the polarized Raman spectra from PrOCI and NdOCI single crystals clearly showed that the correct irreducible representation contains the B2g symmetry. The symmetries of three Raman-active bands are well determined, a fourth band displays two polarizations and a fifth band has no clear polarization and is assigned Eg by default. The EuOCl Raman spectrum exhibits a weak electronic Raman band which originates in electron-phonon coupling as a result of the closeness between the vibrational and electronic eigenvalues. The low-energy band (LaOCl, 67 cm−1; EuOCI, 70 cm−1; and GdOCl, 65 cm−1) and the high-energy band (525 cm−1 for LaOCl) reported by others for selected lanthanide oxychlorides were not observed in the present work.

A study of the Raman spectra of the soluble magnesium species in melts such as NaCl-KCl-CaCl{sub 2} (41-41-18 mole %) has been carried out. Over the range of 0 to 25 mole % MgCl{sub 2} in NaCl-KCl-CaCl{sub 2} at 700{degree}C, the intensity of the MgCl{sub 4}{sup 2}{double prime} Raman band near 250 cm{sup {minus}1} was found to vary linearly with Mg(II) concentration. A new normalization procedure has been developed to generate these results. An all silica fiberoptic probe has also been developed to carry out these measurements. Details of these studies will be discussed. 6 refs.

The development of standard suspension test methods for disinfectants and antiseptics for adoption in Europe is described. Evaluation of a range of disinfectant agents and products currently used in the UK under conditions as proposed for these tests indicates that the majority of products diluted in water of standard hardness showed satisfactory activity producing a 4·5–5 log reduction in viable count within 5 min against Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecium, Proteus mirabilis and Candida albicans in the absence and presence of 1% albumin. All the products, when diluted with distilled water, produced greater than 5 log reduction in 60 min.

Several new methods for the synthesis of TiPO4 are described. Crystalline phosphate compounds containing boron and titanium in a single III or mixed (III, IV) oxidation states have been synthesized and identified by X-ray diffraction. An additional family of phosphate compounds containing only Ti(III, IV) has also been synthesized and identified. All the compounds exhibit attractive colors, e.g., bright green, blue, purple, and black, and are stable at room temperature in air and in boiling water.