Nanoparticles of N-Vinylpyrrolidone Amphiphilic Copolymers and Pheophorbide a as Promising Photosensitizers for Photodynamic Therapy: Design, Properties and In Vitro Phototoxic Activity.

A series of nanoparticles (NPs) with a hydrodynamic radius from 20 to 100 nm in PBS was developed over the solubilization of hydrophobic dye methyl pheophorbide a (chlorin e6 derivative) by amphiphilic copolymers of N-vinylpyrrolidone with (di)methacrylates. Photophysical properties and biological activity of the NPs aqueous solution were studied. It was found that the dye encapsulated in the copolymers is in an aggregated state. However, its aggregation degree decreases sharply, and singlet oxygen quantum yield and the fluorescence signal increase upon the interaction of these NPs with model biological membranes-liposomes or components of a tissue homogenate. The phototoxic effect of NPs in HeLa cells exceeds by 1.5-2 times that of the reference dye chlorin e6 trisodium salt-one of the most effective photosensitizers used in clinical practice. It could be explained by the effective release of the hydrophobic photosensitizer from the NPs into biological structures. The demonstrated approach can be used not only for the encapsulation of hydrophobic photosensitizers for PDT but also for other drugs, and N-vinylpyrrolidone amphiphilic copolymers show promising potential as a modern platform for the design of targeted delivery vehicles.

Pathogen population structure can explain hospital outbreaks.

Hospitalized patients are at risk for increased length of stay, illness, or death due to hospital acquired infections. The majority of hospital transmission models describe dynamics on the level of the host rather than on the level of the pathogens themselves. Accordingly, epidemiologists often cannot complete transmission chains without direct evidence of either host-host contact or a large reservoir population. Here, we propose an ecology-based model to explain the transmission of pathogens in hospitals. The model is based upon metapopulation biology, which describes a group of interacting localized populations and island biogeography, which provides a basis for how pathogens may be moving between locales. Computational simulation trials are used to assess the applicability of the model. Results indicate that pathogens survive for extended periods without the need for large reservoirs by living in localized ephemeral populations while continuously transmitting pathogens to new seed populations. Computational simulations show small populations spending significant portions of time at sizes too small to be detected by most surveillance protocols and that the number and type of these ephemeral populations enable the overall pathogen population to be sustained. By modeling hospital pathogens as a metapopulation, many observations characteristic of hospital acquired infection outbreaks for which there has previously been no sufficient biological explanation, including how and why empirically successful interventions work, can now be accounted for using population dynamic hypotheses. Epidemiological links between temporally isolated outbreaks are explained via pathogen population dynamics and potential outbreak intervention targets are identified.

[Necrotizing ulcerative diseases in military population].

Necrotizing ulcerative diseases were prevalent in military personnel throughout history. Nowadays, its prevalence declined substantially in industrialized countries. Studies among immunocompromised patients suggest it is still a reason for concern among this population. We present two cases diagnosed and treated at our department. It seems that necrotizing ulcerative diseases are still a relevant entity in the Israeli Defense forces therefore it is of great importance to conduct proper diagnosis, treatment and follow up of the patients.

Chain Dynamics, Relaxation Times, and Conductivities of Bithiophene--Acene Copolymers Measured Using High Frequency Saturation Transfer EPR.

We present a study to probe the formation of localized aromatic sextets and their effects on the charge transport properties in polymers with acene cores. Bithiophene-acene copolymers containing benzene, naphthalene, or anthracene as acene cores were synthesized using Yamamoto polymerization. Drop-casted polymer films were chemically doped and analyzed using high frequency saturation transfer EPR (HF ST-EPR), a method which has proven useful in the study of conducting polymers. The spin-spin and spin-lattice relaxation times were determined for these polymers at low temperatures (4 to 20 K) and used to obtain inter- and intrachain spin diffusion rates and conductivities. Similar interchain spin diffusion rates were seen across all polymer systems; however, anthracene containing polymer poly(hexylTTATT) was found to have the largest intrachain spin diffusion rate. The poly(hexylTTATT) intrachain spin diffusion rate may be artificially high if the anthracene ring restricts the diffusion of spin to the hexylated quaterthiophene segment in poly(hexylTTATT) whereas the spins diffuse through the acene cores in the benzene and naphthalene derivatives. Alternatively, as both the spin diffusion rates and conductivities vary unpredictably with temperature, it is possible that the π-electron localization previously seen in the anthracene core could be relieved at lower temperatures.

Selection on stability across ecological scales.

Much of the focus in evolutionary biology has been on the adaptive differentiation among organisms. It is equally important to understand the processes that result in similarities of structure among systems. Here, we discuss examples of similarities occurring at different ecological scales, from predator-prey relations (attack rates and handling times) through communities (food-web structures) to ecosystem properties. Selection among systemic configurations or patterns that differ in their intrinsic stability should lead generally to increased representation of relatively stable structures. Such nonadaptive, but selective processes that shape ecological communities offer an enticing mechanism for generating widely observed similarities, and have sparked new interest in stability properties. This nonadaptive systemic selection operates not in opposition to, but in parallel with, adaptive evolution.

Direct, catalytic monofluorination of sp³ C-H bonds: a radical-based mechanism with ionic selectivity.

Recently, our group unveiled a system in which an unusual interplay between copper(I) and Selectfluor effects mild, catalytic sp(3) C-H fluorination. Herein, we report a detailed reaction mechanism based on exhaustive EPR, (19)F NMR, UV-vis, electrochemical, kinetic, synthetic, and computational studies that, to our surprise, was revealed to be a radical chain mechanism in which copper acts as an initiator. Furthermore, we offer an explanation for the notable but curious preference for monofluorination by ascribing an ionic character to the transition state.

The Evolution of Compact Binary Star Systems.

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Mergings of compact-star binaries are expected to be the most important sources for forthcoming gravitational-wave (GW) astronomy. In the first part of the review, we discuss observational manifestations of close binaries with NS and/or BH components and their merger rate, crucial points in the formation and evolution of compact stars in binary systems, including the treatment of the natal kicks, which NSs and BHs acquire during the core collapse of massive stars and the common envelope phase of binary evolution, which are most relevant to the merging rates of NS-NS, NS-BH and BH-BH binaries. The second part of the review is devoted mainly to the formation and evolution of binary WDs and their observational manifestations, including their role as progenitors of cosmologically-important thermonuclear SN Ia. We also consider AM CVn-stars, which are thought to be the best verification binary GW sources for future low-frequency GW space interferometers.

Charge delocalization through benzene, naphthalene, and anthracene bridges in π-conjugated oligomers: an experimental and quantum chemical study.

To understand the influence of orthogonal conjugation pathways fused directly to π-conjugated polymer backbones, we synthesized and studied three series of thiophene-based model compounds containing benzene, naphthalene, and anthracene peri-substituted central cores as representative acenes. These models were functionalized with methyl groups at the reactive thiophene positions in order to generate and observe oxidized species without complications from follow-up polymerization. The neutral monomers and their oxidized charged counterparts were subjected to cyclic voltammetry, spectroelectrochemistry, and EPR spectroscopy as appropriate, and these results were further corroborated with thorough density functional theory studies. This joint experimental and theoretical analysis allowed us to determine that benzene-based conjugated linkers led to more delocalized charge carriers on account of the quinoidal character maintained within the benzene core. In contrast, anthracene-based linkers displayed very localized carriers due to torsional strain between the adjacent aryl groups and to the local evolution of formal aromatic sextets on the benzo-fused rings orthogonal to the backbone in the quinoidal state. In some cases, the electronics of the thiophene-based substituent dominated the electronic properties of the oxidized species regardless of the nature of the central acene linker. These results highlight the dramatic influence that orthogonal conjugation pathways can exert on the electronic properties of π-conjugated materials.

The May threshold and life-history allometry.

One of Robert May's classic results was finding that population dynamics become chaotic when the average lifetime rate of reproduction exceeds a certain value. Populations whose reproductive rates exceed this May threshold probably become extinct. The May threshold in each case depends upon the shape of the density-dependence curve, which differs among models of population growth. However, species of different sizes and generation times that share a roughly similar density-dependence curve will also share a similar May threshold. Here, we argue that this fact predicts a striking allometric regularity among animal taxa: lifetime reproductive rate should be roughly independent of body size. Such independence has been observed in diverse taxa, but has usually been ascribed to a fortuitous combination of physiologically based life-history allometries. We suggest, instead, that the ecological elimination of unstable populations within groups that share a value of the May threshold is a likely cause of this allometry.

Analogical thinking in ecology: looking beyond disciplinary boundaries.

We consider several ways in which a good understanding of modern techniques and principles in physics can elucidate ecology, and we focus on analogical reasoning between these two branches of science. Analogical reasoning requires an understanding of both sciences and an appreciation of the similarities and points of contact between the two. In the current ecological literature on the relationship between ecology and physics, there has been some misunderstanding about the nature of modern physics and its methods. Physics is seen as being much cleaner and tidier than ecology. When compared to this idealized, fictional version of physics, ecology looks very different, and the prospect of ecology and physics learning from one another is questionable. We argue that physics, once properly understood, is more like ecology than ecologists have thus far appreciated. Physicists and ecologists can and do learn from each other, and, in this paper, we outline how analogical reasoning can facilitate such exchanges.

Maternal effects mechanism of population cycling: a formidable competitor to the traditional predator-prey view.

In the language of mathematics, one needs minimally two interacting variables (two dimensions) to describe repeatable periodic behaviour, and in the language of density dependence, one needs delayed, not immediate, density dependence to produce cyclicity. Neither language specifies the causal mechanism. There are two major potential mechanisms: exogenous mechanisms involving species interactions as in predator-prey or host-parasite, and endogenous mechanisms such as maternal effects where population growth results from the cross-generational transmission of individual quality. The species interactions view stemming from a major observation of Elton and a simultaneous independent theory by Lotka and Volterra is currently dominant. Most ecologists, when faced with cyclic phenomena, automatically look for an interacting species one step below or above in a food chain in order to find an explanation. Maternal effects hypothesis, verbally suggested in the 1950s, had only found its theoretical implementation in the 1990 s. In a relatively short time, the degree of acceptance of this view grew to the level of a 'minority opinion' as evidenced by the widely used textbook of Begon et al. This short review attempts to describe the arguments for and against this internal two-dimensional approach.

Generation of oxynitrenes and confirmation of their triplet ground states.

New sulfoximine- and phenanthrene-based photochemical precursors to oxynitrenes have been developed. These precursors have been used to examine the chemistry and spectroscopy of oxynitrenes. The first EPR spectra of oxynitrenes are reported and are consistent with their triplet ground states. Additional support for the triplet ground state of oxynitrenes is provided by trapping and reactivity studies, nanosecond time-resolved IR investigations, and computational studies.

DNA oxidation in anionic reverse micelles: ruthenium-mediated damage at Guanine in single- and double-stranded DNA.

One-electron guanine oxidation in DNA has been investigated in anionic reverse micelles (RMs). A photochemical method for generating Ru3+ from the ruthenium polypyridyl complex tris(2-2'-bipyridine)ruthenium(II) chloride ([Ru(bpy)3]Cl2) is combined with high-resolution polyacrylamide gel electrophoresis (PAGE) to quantify piperidine-labile guanine oxidation products. As characterized by emission spectroscopy of Ru(bpy)3(2+), the addition of DNA to RMs containing Ru(bpy)3(2+) does not perturb the environment of Ru(bpy)3(2+). The steady-state quenching efficiency of Ru(bpy)3(2+) with K3[Fe(CN)6] in buffer solution is approximately 2-fold higher than that observed in RMs. Consistent with the difference in quenching efficiency in the two media, a 1.5-fold higher yield of piperidine-labile damage products as monitored by PAGE is observed for duplex oligonucleotide in buffer vs RMs. In contrast, a 13-fold difference in the yield of PAGE-detected G oxidation products is observed when single-stranded DNA is the substrate. Circular dichroism spectra showed that single-stranded DNA undergoes a structural change in anionic RMs. This structural change is potentially due to cation-mediated adsorption of the DNA phosphates on the anionic headgroups of the RMs, leading to protection of the guanine from oxidatively generated damage.

The Evolution of Compact Binary Star Systems.

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars - compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.

Rules of thumb for judging ecological theories.

An impressive fit to historical data suggests to biologists that a given ecological model is highly valid. Models often achieve this fit at the expense of exaggerated complexity that is not justified by empirical evidence. Because overfitted theories complement the traditional assumption that ecology is 'messy', they generally remain unquestioned. Using predation theory as an example, we suggest that a fit-driven appraisal of model value is commonly misdirected; although fit to historical data can be important, the simplicity and generality of a theory--and thus its ecological value--are of comparable importance. In particular, we argue that theories whose complexity greatly exceeds the complexity of the problem that they address should be rejected. We suggest heuristics for distinguishing between valuable ecological theories and their overfitted brethren.

Measurement error affects risk estimates for recruitment to the Hudson River stock of striped bass.

We examined the consequences of ignoring the distinction between measurement error and natural variability in an assessment of risk to the Hudson River stock of striped bass posed by entrainment at the Bowline Point, Indian Point, and Roseton power plants. Risk was defined as the probability that recruitment of age-1+ striped bass would decline by 80% or more, relative to the equilibrium value, at least once during the time periods examined (1, 5, 10, and 15 years). Measurement error, estimated using two abundance indices from independent beach seine surveys conducted on the Hudson River, accounted for 50% of the variability in one index and 56% of the variability in the other. If a measurement error of 50% was ignored and all of the variability in abundance was attributed to natural causes, the risk that recruitment of age-1+ striped bass would decline by 80% or more after 15 years was 0.308 at the current level of entrainment mortality (11%). However, the risk decreased almost tenfold (0.032) if a measurement error of 50% was considered. The change in risk attributable to decreasing the entrainment mortality rate from 11 to 0% was very small (0.009) and similar in magnitude to the change in risk associated with an action proposed in Amendment #5 to the Interstate Fishery Management Plan for Atlantic striped bass (0.006)--an increase in the instantaneous fishing mortality rate from 0.33 to 0.4. The proposed increase in fishing mortality was not considered an adverse environmental impact, which suggests that potentially costly efforts to reduce entrainment mortality on the Hudson River stock of striped bass are not warranted.

Collagenous gastritis associated with lymphocytic gastritis and celiac disease.

Collagenous gastritis is a rare disorder, with only 8 cases reported in the literature, 2 in children and 6 in adults. We report an additional case of collagenous gastritis in a 42-year-old man with celiac disease. A thickened (>10 microm) subepithelial collagen band with entrapped capillaries, fibroblasts, and inflammatory cells was seen in the stomach, associated with lymphocytic gastritis. The duodenal mucosa showed severe villous atrophy but no subepithelial collagen deposition. No evidence of lymphocytic or collagenous colitis was found in the colon. The patient became symptom-free on a gluten exclusion diet and showed partial improvement of histopathologic findings after 3 months. Collagenous gastritis is a rare disease, but a wider recognition of its histopathologic features and clinical associations may bring more cases to light and provide additional clues in determining its etiology and pathogenesis.

The unpredictability of seal after post space preparation: a fluid transport study.

A root canal filling remaining after post space preparation is commonly expected to provide adequate seal. Coronal leakage of 30 endodontically treated teeth was measured before post space preparation using a fluid transport assay. In 10 of these teeth post space was prepared, using a two-step procedure, first to a remaining filling of 6 mm and then to 3 mm, with the leakage studied after each step. In 10 teeth the removal was done in one step to a remaining length of 3 mm. The other 10 teeth, with intact root canal fillings, served as controls and were tested twice for leakage. A significant difference was found between the sealing ability of intact fillings and that of partially removed ones (p < 0.05). The difference between the sealing ability of 3 and 6 mm remaining length group was not statistically significant. The lack of statistical differences between the 6 mm and 3 mm fillings was due to a great variability which existed among the 3 mm remaining fillings. These results suggest that 3 to 6 mm fillings provided a seal inferior to that of intact root canal fillings. Reduction of the fillings to 3 mm resulted in an unpredictable seal.