Sensing and avoiding sick conspecifics requires Gαi2+ vomeronasal neurons.

BACKGROUND: Rodents utilize chemical cues to recognize and avoid other conspecifics infected with pathogens. Infection with pathogens and acute inflammation alter the repertoire and signature of olfactory stimuli emitted by a sick individual. These cues are recognized by healthy conspecifics via the vomeronasal or accessory olfactory system, triggering an innate form of avoidance behavior. However, the molecular identity of the sensory neurons and the higher neural circuits involved in the detection of sick conspecifics remain poorly understood. RESULTS: We employed mice that are in an acute state of inflammation induced by systemic administration of lipopolysaccharide (LPS). Through conditional knockout of the G-protein Gαi2 and deletion of other key sensory transduction molecules (Trpc2 and a cluster of 16 vomeronasal type 1 receptors), in combination with behavioral testing, subcellular Ca2+ imaging, and pS6 and c-Fos neuronal activity mapping in freely behaving mice, we show that the Gαi2+ vomeronasal subsystem is required for the detection and avoidance of LPS-treated mice. The active components underlying this avoidance are contained in urine whereas feces extract and two selected bile acids, although detected in a Gαi2-dependent manner, failed to evoke avoidance behavior. Our analyses of dendritic Ca2+ responses in vomeronasal sensory neurons provide insight into the discrimination capabilities of these neurons for urine fractions from LPS-treated mice, and how this discrimination depends on Gαi2. We observed Gαi2-dependent stimulation of multiple brain areas including medial amygdala, ventromedial hypothalamus, and periaqueductal grey. We also identified the lateral habenula, a brain region implicated in negative reward prediction in aversive learning, as a previously unknown target involved in these tasks. CONCLUSIONS: Our physiological and behavioral analyses indicate that the sensing and avoidance of LPS-treated sick conspecifics depend on the Gαi2 vomeronasal subsystem. Our observations point to a central role of brain circuits downstream of the olfactory periphery and in the lateral habenula in the detection and avoidance of sick conspecifics, providing new insights into the neural substrates and circuit logic of the sensing of inflammation in mice.

Insights Into the Mechanochemical Glass Formation of Zeolitic Imidazolate Frameworks.

Metal-organic framework (MOF) glasses, known for their potential in gas separation, optics, and solid-state electrolytes, benefit from the processability of their (supercooled) liquid state. Traditionally, MOF glasses are produced by heating MOF crystals to their melting point and then cooling the liquid MOF to room temperature under an inert atmosphere. While effective, this melt-quenching technique requires high energy due to the high temperatures involved. It also limits the scope of new material development by restricting the compositional range to only those combinations of metal ions and linkers that are highly thermally stable. An alternative, mechanical milling at room temperature, has demonstrated its capability to transform MOF crystals into amorphous phases. However, the specific conditions under which these amorphous phases exhibit glass-like behavior remain uncharted. In this study, we explore the mechanochemical amorphization and vitrification of a variety of zeolitic imidazolate frameworks (ZIFs) with diverse linkers and different metal ions (Zn2+, Co2+ and Cu2+) at room temperature. Our findings demonstrate that ZIFs capable of melting can be successfully converted into glasses through ball-milling. Remarkably, some non-meltable ZIFs can also be vitrified using the ball-milling technique, as highlighted by the preparation of the first Cu2+-based ZIF glass.

Central role of G protein Gαi2 and Gαi2+ vomeronasal neurons in balancing territorial and infant-directed aggression of male mice.

Aggression is controlled by the olfactory system in many animal species. In male mice, territorial and infant-directed aggression are tightly regulated by the vomeronasal organ (VNO), but how diverse subsets of sensory neurons convey pheromonal information to limbic centers is not yet known. Here, we employ genetic strategies to show that mouse vomeronasal sensory neurons expressing the G protein subunit Gαi2 regulate male-male and infant-directed aggression through distinct circuit mechanisms. Conditional ablation of Gαi2 enhances male-male aggression and increases neural activity in the medial amygdala (MeA), bed nucleus of the stria terminalis, and lateral septum. By contrast, conditional Gαi2 ablation causes reduced infant-directed aggression and decreased activity in MeA neurons during male-infant interactions. Strikingly, these mice also display enhanced parental behavior and elevated neural activity in the medial preoptic area, whereas sexual behavior remains normal. These results identify Gαi2 as the primary G protein α-subunit mediating the detection of volatile chemosignals in the apical layer of the VNO, and they show that Gαi2+ VSNs and the brain circuits activated by these neurons play a central role in orchestrating and balancing territorial and infant-directed aggression of male mice through bidirectional activation and inhibition of different targets in the limbic system.

Psychometric evaluation of the Persian version of the Lymphedema Life Impact Scale (LLIS, version 1) in breast cancer patients.

BACKGROUND: Despite the high prevalence of lymphedema in Iranian breast cancer patients, there is no valid instrument for measuring quality of life in this population. The aim of this study was to assess reliability and validity of the Persian version of Lymphedema Life Impact Scale (LLIS) in breast cancer patients. METHODS: Forward-backward procedure was applied to translate The LLIS from English into Persian. The LLIS is an 18-item measure of physical, psychosocial, and functional impairments caused by lymphedema. Experts and patients assessed content and face validity, respectively. Discriminant validity was evaluated by comparing breast cancer patients with and without lymphedema. Convergent validity was assessed by comparing LLIS score with SF-36 (functional component) and the EORTC-QLQ-C30 (functional component). The construct validity also was evaluated using confirmatory and exploratory factor analyses. Internal consistency was evaluated by Cronbach's alpha coefficient. Stability was assessed by test-retest analysis over a one-week interval in 13 patients. RESULTS: In all 446 breast cancer patients were entered into the study. The content and face validity of Persian version of LLIS were acceptable and minor corrections were applied in final version. The questionnaire differentiated well in patients' with and without lymphedema and not lending support to its discriminant validity. Confirmatory factor analysis showed a good fit for the data. Cronbach's alpha coefficient in physical, psychosocial and functional subscales were 0.873, 0.854 and 0.884 respectively. Intra-class correlation coefficient of total score of the LLIS was 0.96. CONCLUSIONS: The findings of this study suggest a first indication that reliability and validity of the Persian version of LLIS in patients with breast cancer induced lymphedema was good. Application of this instrument for identifying problems of patients with upper extremity lymphedema may be helpful in designing interventions to improve quality of life.

Trpm5 expression in the olfactory epithelium.

The Ca2+-activated monovalent cation channel Trpm5 is a key element in chemotransduction of taste receptor cells of the tongue, but the extent to which Trpm5 channels are expressed in olfactory sensory neurons (OSNs) of the main olfactory epithelium (MOE) of adult mice as part of a specific pheromonal detection system is debated. Here, we used a novel Trpm5-IRES-Cre knockin strain to drive Cre recombinase expression, employed previously validated Trpm5 antibodies, performed in situ hybridization experiments to localize Trpm5 RNA, and searched extensively for Trpm5 splice variants in genetically-labeled, Trpm5-expressing MOE cells. In contrast to previous reports, we find no evidence for the existence in adult mouse OSNs of the classical Trpm5 channel known from taste cells. We show that Trpm5-expressing adult OSNs express a novel Trpm5 splice variant, Trpm5-9, that is unlikely to form a functional cation channel by itself. We also demonstrate that Trpm5 is transiently expressed in a subpopulation of mature OSNs in the embryonic olfactory epithelium, indicating that Trpm5 channels could play a specific role in utero during a narrow developmental time window. Ca2+ imaging with GCaMP3 under the control of the Trpm5-IRES-Cre allele using a newly developed MOE wholemount preparation of the adult olfactory epithelium reveals that Trpm5-GCaMP3 OSNs comprise a heterogeneous group of sensory neurons many of which can detect general odorants. Together, these studies are essential for understanding the role of transient receptor potential channels in mammalian olfaction.

Loss-of-function mutations in sodium channel Nav1.7 cause anosmia.

Loss of function of the gene SCN9A, encoding the voltage-gated sodium channel Na(v)1.7, causes a congenital inability to experience pain in humans. Here we show that Na(v)1.7 is not only necessary for pain sensation but is also an essential requirement for odour perception in both mice and humans. We examined human patients with loss-of-function mutations in SCN9A and show that they are unable to sense odours. To establish the essential role of Na(v)1.7 in odour perception, we generated conditional null mice in which Na(v)1.7 was removed from all olfactory sensory neurons. In the absence of Na(v)1.7, these neurons still produce odour-evoked action potentials but fail to initiate synaptic signalling from their axon terminals at the first synapse in the olfactory system. The mutant mice no longer display vital, odour-guided behaviours such as innate odour recognition and avoidance, short-term odour learning, and maternal pup retrieval. Our study creates a mouse model of congenital general anosmia and provides new strategies to explore the genetic basis of the human sense of smell.

Self-care status, symptom burden, and reported infections in individuals with lower-extremity primary lymphedema.

PURPOSE: The purposes of this study were (a) to evaluate self-care, symptom burden, and reported infections among individuals with lower-extremity primary lymphedema; (b) to examine the differences in self-care, symptom burden, and reported infections between individuals with unilateral and those with bilateral lower-extremity primary lymphedema; and (c) to examine the associations among self-care status, symptom burden, and reported infections in individuals with lower-extremity primary lymphedema. DESIGN: A secondary data analysis was used. Data were collected from a cross-sectional survey study supported by the National Lymphedema Network from March 2006 through January 2010. The surveys were available both online and in hard copy in order to increase accessibility. METHODS: Descriptive statistics were conducted and associations between variables were assessed using Mann-Whitney tests and chi-square tests of independence. Multiple logistic regression was used to test for associations while controlling for potentially confounding variables. FINDINGS: A total of 803 participants reported having lower-extremity primary lymphedema. The majority of the participants were female (82.9%), White (74.2%), and from the United States (90.7%). Approximately two thirds of the respondents conducted some home daily lymphedema self-care. Over half of the respondents reported experiencing symptom burden and 44.8% reported at least one episode of infection. Compared to individuals with unilateral lower-extremity primary lymphedema, individuals with bilateral lower-extremity lymphedema were more likely to conduct skin care (p = .004), use alternative medications (p = .005), more frequently reported symptoms (p < .05), and more likely to report at least one episode of infection (p = .002). Respondents who reported use of compression garments also were less likely to have self-reported pain (p = .002), poor range of motion (p = .026), and numbness (p = .001). Participants who reported exercising also were less likely to have self-reported pain (p = .003). Participants who reported at least one episode of infection also reported experiencing more symptoms (p < .001). CONCLUSIONS: Individuals with lower-extremity primary lymphedema experienced substantial symptom burden and infection episodes. Significant associations were identified among self-care, symptom burden, and reported infections. CLINICAL RELEVANCE: The findings support the need for clinicians to educate patients with lower-extremity primary lymphedema regarding the importance of self-care, symptom management, and infection control. It is critically important for clinicians to evaluate symptom burden and reduce infections in individuals with lower-extremity primary lymphedema.

Factors Associated with Reported Infection and Lymphedema Symptoms among Individuals with Extremity Lymphedema.

PURPOSE: This study aimed to examine factors associated with reported infection and symptoms among individuals with extremity lymphedema. DESIGN: A cross-sectional study was used. METHODS: Data were collected from a survey supported by the National Lymphedema Network from March 2006 through January 2010. A total of 1837 participants reported having extremity lymphedema. Logistic regression analyses were used. FINDINGS: Factors associated with reported infection among individuals with extremity lymphedema included male gender, decreased annual household income, decreased self-care, self-report of heaviness, and lower extremity as opposed to upper extremity. Factors associated with symptoms included infection, decreased self-care, lower knowledge level of self-care, decreased annual household income, and presence of secondary lower extremity lymphedema. CONCLUSIONS/CLINICAL RELEVANCE: Select factors of income, self-care status, and site of lymphedema were associated with increased occurrence of infection and symptoms among individuals with extremity lymphedema. Longitudinal studies are needed to identify risk factors contributing to infections and symptoms in individuals with lymphedema.

Altered synaptic transmission at olfactory and vomeronasal nerve terminals in mice lacking N-type calcium channel Cav2.2.

We investigated the role of voltage-activated calcium (Cav) channels for synaptic transmission at mouse olfactory and vomeronasal nerve terminals at the first synapse of the main and accessory olfactory pathways, respectively. We provided evidence for a central role of the N-type Cav channel subunit Cav2.2 in presynaptic transmitter release at these synapses. Striking Cav2.2 immunoreactivity was localised to the glomerular neuropil of the main olfactory bulb (MOB) and accessory olfactory bulb (AOB), and co-localised with presynaptic molecules such as bassoon. Voltage-clamp recordings of sensory nerve-evoked, excitatory postsynaptic currents (EPSCs) in mitral/tufted (M/T) and superficial tufted cells of the MOB and mitral cells of the AOB, in combination with established subtype-specific Cav channel toxins, indicated a predominant role of N-type channels in transmitter release at these synapses, whereas L-type, P/Q-type, and R-type channels had either no or only relatively minor contributions. In Cacna1b mutant mice lacking the Cav2.2 (α1B) subunit of N-type channels, olfactory nerve-evoked M/T cell EPSCs were not reduced but became blocker-resistant, thus indicating a major reorganisation and compensation of Cav channel subunits as a result of the Cav2.2 deletion at this synapse. Cav2.2-deficient mice also revealed that Cav2.2 was critically required for paired-pulse depression of olfactory nerve-evoked EPSCs in M/T cells of the MOB, and they demonstrated an essential requirement for Cav2.2 in vomeronasal nerve-evoked EPSCs of AOB mitral cells. Thus, Cacna1b loss-of-function mutations are unlikely to cause general anosmia but Cacna1b emerges as a strong candidate in the search for mutations causing altered olfactory perception, such as changes in general olfactory sensitivity and altered social responses to chemostimuli.

Presynaptic GABAB receptors inhibit vomeronasal nerve transmission to accessory olfactory bulb mitral cells.

Vomeronasal sensory neurons (VSNs) recognize pheromonal and kairomonal semiochemicals in the lumen of the vomeronasal organ. VSNs send their axons along the vomeronasal nerve (VN) into multiple glomeruli of the accessory olfactory bulb (AOB) and form glutamatergic synapses with apical dendrites of mitral cells, the projection neurons of the AOB. Juxtaglomerular interneurons release the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Besides ionotropic GABA receptors, the metabotropic GABAB receptor has been shown to modulate synaptic transmission in the main olfactory system. Here we show that GABAB receptors are expressed in the AOB and are primarily located at VN terminals. Electrical stimulation of the VN provokes calcium elevations in VSN nerve terminals, and activation of GABAB receptors by the agonist baclofen abolishes calcium influx in AOB slice preparations. Patch clamp recordings reveal that synaptic transmission from the VN to mitral cells can be completely suppressed by activation of GABAB receptors. A potent GABAB receptor antagonist, CGP 52432, reversed the baclofen-induced effects. These results indicate that modulation of VSNs via activation of GABAB receptors affects calcium influx and glutamate release at presynaptic terminals and likely balances synaptic transmission at the first synapse of the accessory olfactory system.

Rasch validation and refinement of the Lymphedema Life Impact Scale version 2 in an Italian cohort with secondary lymphedema.

PURPOSE: To produce and validate an Italian version of the Lymphedema Life Impact Scale version 2 (LLISv2-It), a tool measuring the impact of lymphedema on health-related quality of life, and investigate its main psychometric characteristics. METHODS: After translation and cross-cultural adaptation of the LLISv2, we administered it to 156 subjects with secondary lymphedema (upper or lower limb), together with (depending on the limb involved) either the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH) or the Lower Extremity Functional Scale (LEFS). We analyzed the performance of LLISv2-It using Classical Test Theory and Rasch methods. RESULTS: Cronbach alpha was 0.89. Item fit statistics indicated that item #12 was underfitting (Infit MnSQ = 1.56; Outfit MnSq = 1.75). Test-retest reliability of the 17-item version (without item #18, not scored, according to the original authors) and of a 16-item version (without #12 and #18-a unidimensional item set) were both excellent (ICC2.1 = 0.93; 95%). The minimum detectable change was 8.9 points. The correlation of LLISv2-It with DASH and LEFS was r = 0.81 and -0.57, respectively. CONCLUSIONS: The Italian version of the LLISv2 is reliable and valid. To make the tool more psychometrically sound, we recommend to not calculate items #12 and #18 in the total score.IMPLICATIONS FOR REHABILITATIONThe Lymphedema Life Impact Scale (LLISv2) is particularly useful as a validated condition-specific health-related quality of life measure for patients with chronic edema/lymphedema. We have validated its Italian version (LLISv2-It).We also examined the psychometric properties of the LLISv2 in individuals with secondary lymphedema of either upper or lower limb, using both classical test theory and Rasch techniques, to provide insights for further refinement of the questionnaire.Based on our results, we recommend not to count item #12 in the total score (besides #18, as already suggested by the original authors). Moreover, we determined that the minimum detectable change of the LLISv2 was 9 points. This information is helpful in clinical practice to understand if the change in score is not due to chance (measurement error).Although further research is warranted, the present validation study of the LLISv2 increases the confidence in the metric quality and clinical utility of the scale to assess lymphedema-specific health-related quality of life in individuals with secondary lymphedema of either upper or lower limb.

Quantification of gas-accessible microporosity in metal-organic framework glasses.

Metal-organic framework (MOF) glasses are a new class of glass materials with immense potential for applications ranging from gas separation to optics and solid electrolytes. Due to the inherent difficulty to determine the atomistic structure of amorphous glasses, the intrinsic structural porosity of MOF glasses is only poorly understood. Here, we investigate the porosity features (pore size and pore limiting diameter) of a series of prototypical MOF glass formers from the family of zeolitic imidazolate frameworks (ZIFs) and their corresponding glasses. CO2 sorption at 195 K allows quantifying the microporosity of these materials in their crystalline and glassy states, also providing excess to the micropore volume and the apparent density of the ZIF glasses. Additional hydrocarbon sorption data together with X-ray total scattering experiments prove that the porosity features of the ZIF glasses depend on the types of organic linkers. This allows formulating design principles for a targeted tuning of the intrinsic microporosity of MOF glasses. These principles are counterintuitive and contrary to those established for crystalline MOFs but show similarities to strategies previously developed for porous polymers.

Temperature-induced self-assembly of triple-responsive triblock copolymers in aqueous solutions.

A series of triple-thermoresponsive triblock copolymers from poly(N-n-propylacrylamide) (PNPAM, A), poly(methoxydiethylene glycol acrylate) (PMDEGA, B), and poly(N-ethylacrylamide) (PNEAM, C) was synthesized by sequential reversible addition-fragmentation chain transfer polymerizations. Polymers of differing block sequences, ABC, BAC, and ACB, with increasing phase transition temperatures in the order A < B < C were prepared. Their aggregation behavior in dilute aqueous solution was investigated using dynamic light scattering, turbidimetry, and NMR spectroscopy. The self-organization of such polymers was found to dependent strongly on the block sequence. While polymers with a terminal low-LCST (lower critical solution temperature) block undergo aggregation above the first phase transition temperature at 20-25 °C, triblock copolymers with the low-LCST block in the middle show aggregation only above the second phase transition. The collapse of the middle block is not sufficient to induce aggregation but produces instead stable, unimolecular micelles with a collapsed middle block, as supported by NMR and fluorescence probe data. Continued heating of all copolymers led to two additional thermal transitions at 40-55 and 70-80 °C, which could be correlated to the phase transitions of the B and C blocks, respectively. All polymers show a high tendency for cluster formation, once aggregation is induced. The carrier abilities of the triple responsive triblock copolymers for hydrophobic agents were probed with the solvatochromic fluorescence dye Nile Red. With passing through the first thermal transition, the block copolymers are capable of solubilizing Nile Red. In the case of block copolymers with sequences ABC or ACB, which bear the low-LCST block at one terminus, notable amounts of dye are solubilized already at this stage. In contrast, the hydrophobic probe is much less efficiently incorporated by the BAC triblock copolymer, which forms unimolecular micelles. Only after the collapse of the B block, when reaching the second phase transition at about 45 °C, does aggregation occur and solubilization becomes efficient. In the case of ABC and ACB polymers, the hydrophobic probe seems to partition between the originally collapsed A chains and the additional hydrophobic chains formed after the collapse of the less hydrophobic B block.

Analyzing the Essential Attributes of Nationally Issued COVID-19 Contact Tracing Apps: Open-Source Intelligence Approach and Content Analysis.

BACKGROUND: Contact tracing apps are potentially useful tools for supporting national COVID-19 containment strategies. Various national apps with different technical design features have been commissioned and issued by governments worldwide. OBJECTIVE: Our goal was to develop and propose an item set that was suitable for describing and monitoring nationally issued COVID-19 contact tracing apps. This item set could provide a framework for describing the key technical features of such apps and monitoring their use based on widely available information. METHODS: We used an open-source intelligence approach (OSINT) to access a multitude of publicly available sources and collect data and information regarding the development and use of contact tracing apps in different countries over several months (from June 2020 to January 2021). The collected documents were then iteratively analyzed via content analysis methods. During this process, an initial set of subject areas were refined into categories for evaluation (ie, coherent topics), which were then examined for individual features. These features were paraphrased as items in the form of questions and applied to information materials from a sample of countries (ie, Brazil, China, Finland, France, Germany, Italy, Singapore, South Korea, Spain, and the United Kingdom [England and Wales]). This sample was purposefully selected; our intention was to include the apps of different countries from around the world and to propose a valid item set that can be relatively easily applied by using an OSINT approach. RESULTS: Our OSINT approach and subsequent analysis of the collected documents resulted in the definition of the following five main categories and associated subcategories: (1) background information (open-source code, public information, and collaborators); (2) purpose and workflow (secondary data use and warning process design); (3) technical information (protocol, tracing technology, exposure notification system, and interoperability); (4) privacy protection (the entity of trust and anonymity); and (5) availability and use (release date and the number of downloads). Based on this structure, a set of items that constituted the evaluation framework were specified. The application of these items to the 10 selected countries revealed differences, especially with regard to the centralization of the entity of trust and the overall transparency of the apps' technical makeup. CONCLUSIONS: We provide a set of criteria for monitoring and evaluating COVID-19 tracing apps that can be easily applied to publicly issued information. The application of these criteria might help governments to identify design features that promote the successful, widespread adoption of COVID-19 tracing apps among target populations and across national boundaries.

A central mechanism of analgesia in mice and humans lacking the sodium channel NaV1.7.

Deletion of SCN9A encoding the voltage-gated sodium channel NaV1.7 in humans leads to profound pain insensitivity and anosmia. Conditional deletion of NaV1.7 in sensory neurons of mice also abolishes pain, suggesting that the locus of analgesia is the nociceptor. Here we demonstrate, using in vivo calcium imaging and extracellular recording, that NaV1.7 knockout mice have essentially normal nociceptor activity. However, synaptic transmission from nociceptor central terminals in the spinal cord is greatly reduced by an opioid-dependent mechanism. Analgesia is also reversed substantially by central but not peripheral application of opioid antagonists. In contrast, the lack of neurotransmitter release from olfactory sensory neurons is opioid independent. Male and female humans with NaV1.7-null mutations show naloxone-reversible analgesia. Thus, inhibition of neurotransmitter release is the principal mechanism of anosmia and analgesia in mouse and human Nav1.7-null mutants.

Ca2+ -calmodulin feedback mediates sensory adaptation and inhibits pheromone-sensitive ion channels in the vomeronasal organ.

The mammalian vomeronasal organ (VNO) mediates the regulation of social behaviors by complex chemical signals. These cues trigger transient elevations of intracellular Ca(2+) in vomeronasal sensory neurons (VSNs), but the functional role of such Ca(2+) elevations is unknown. We show that stimulus-induced Ca(2+) entry plays an essential role as a negative feedback regulator of VSN sensitivity. Electrophysiological VSN responses undergo effective sensory adaptation that requires the influx of Ca(2+) and is mediated by calmodulin (CaM). Removal of the Ca(2+)-CaM feedback eliminates this form of adaptation. A key target of this feedback module is the pheromone-sensitive TRPC2-dependent cation channel of VSNs, as its activation is strongly inhibited by Ca(2+)-CaM. Our results reveal a previously unrecognized CaM-signaling pathway that endows the VSNs with a mechanism for adjusting gain and sensitivity of chemosensory signaling in the VNO.

Universal polymer analysis by (1)H NMR using complementary trimethylsilyl end groups.

New degenerative chain transfer agents, namely 4-(trimethylsilyl)benzyl 4'-(trimethylsilyl)butane-dithioate, 4-(trimethylsilyl)benzyl 3'-(trimethylsilyl)propyl trithiocarbonate and their 3-(trimethylsilyl)benzyl isomers, that are two-fold labeled with complementary trimethylsilyl (TMS) markers, were designed and shown to be powerful tools for universal polymer analysis by conventional (1)H NMR spectroscopy. Their use in controlled free radical polymerization, here the reversible addition-fragmentation chain transfer (RAFT) method, resulted in polymers with low polydispersities up to high molar masses, as well as with defined complementary TMS end groups. Thus, routine (1)H NMR spectra allowed facile determination of the molar masses of polymers of various chemical structures up to at least 10(5) g/mol, and simultaneously provided crucial information about the content of end groups that is typically >95% when polymerizations are correctly performed. Polymerizations were carried out in various solvents for two standard monomers, namely n-butyl acrylate and styrene, as well as for two specialty monomers, so-called inimers, namely 2-(2-chloropropionyloxy)ethyl acrylate and 2-(2-chloropropionyloxy)ethyl acrylamide. The complementary end group markers revealed marked differences in the suitability of commonly used solvents for RAFT polymerization. The results demonstrate-beyond good polymerization control-that the new RAFT agents are universal, powerful tools for facile polymer analysis by routine (1)H NMR spectroscopy, of their absolute molar masses as well as of the content of end groups. This is crucial information, e.g., for the synthesis of high-quality telechelics and, in particular, of block copolymers, which is difficult to obtain by other methods. Preliminary screening experiments indicate that similar uses can be envisaged for analogous ATRP systems.

Glycinergic input of widefield, displaced amacrine cells of the mouse retina.

Glycine receptors (GlyRs) of displaced amacrine cells of the mouse retina were analysed using whole cell recordings and immunocytochemical staining with subunit-specific antibodies. During the recordings the cells were filled with a fluorescent tracer and 11 different morphological types could be identified. The studies were performed in wild-type mice and in mutant mice deficient in the GlyRalpha1 (Glra1(spd-ot), 'oscillator' mouse), the GlyRalpha2 (Glra2(-/-)) and the GlyRalpha3 subunit (Glra3(-/-)). Based on their responses to the application of exogenous glycine in the retinas of wild-type and mutant mice, the cells were grouped into three major classes: group I cells (comprising the morphological types MA-S5, MA-S1, MA-S1/S5, A17, PA-S1, PA-S5 and WA-S1), group II cells (comprising the morphological types PA-S4, WA-S3 and WA-multi) and ON-starburst cells. For further analysis, spontaneous inhibitory postsynaptic currents (sIPSCs) were measured both in wild-type and mutant mouse retinas. Glycinergic sIPSCs and glycine induced currents of group I cells remained unaltered across wild-type and the three mutant mice (mean decay time constant of sIPSCs, tau approximately 25 ms). Group II cells showed glycinergic sIPSCs and glycine induced currents in wild-type, Glra1(spd-ot) and Glra3(-/-) mice (tau approximately 25 ms); however, glycinergic currents were absent in group II cells of Glra2(-/-) mice. Glycine induced currents and sIPSCs recorded from ON-starburst amacrine cells did not differ significantly between wild-type and the mutant mouse retinas (tau approximately 50-70 ms). We propose that GlyRs of group II cells are dominated by the alpha2 subunit; GlyRs of ON-starburst amacrine cells appear to be dominated by the alpha4 subunit.

Synthesis of diacetylene-containing peptide building blocks and amphiphiles, their self-assembly and topochemical polymerization in organic solvents.

A series of functional iodoacetylenes was prepared and converted into the corresponding diacetylene-substituted amino acids and peptides via Pd/Cu-promoted sp-sp carbon cross-coupling reactions. The unsymmetrically substituted diacetylenes can be incorporated into oligopeptides without a change in the oligopeptide strand's directionality. Thus, a series of oligopeptide-based, amphiphilic diacetylene model compounds was synthesized, and their self-organization as well as their UV-induced topochemical polymerizability was investigated in comparison to related polymer-substituted macromonomers. Solution-phase IR spectroscopy, gelation experiments, and UV spectroscopy helped to confirm that a minimum of five N-H...O=C hydrogen-bonding sites was required in order to obtain reliable aggregation into stable beta-sheet-type secondary structures in organic solvents. Furthermore, the non-equidistant spacing of these hydrogen-bonding sites was proven to invariably lead to beta-sheets with a parallel beta-strand orientation, and the characteristic IR-spectroscopic signatures of the latter in organic solution was identified. Scanning force micrographs of the organogels revealed that compounds with six hydrogen-bonding sites gave rise to high aspect ratio nanoscopic fibrils with helical superstructures but, in contrast to the related macromonomers, did not lead to uniform supramolecular polymers. The UV-induced topochemical polymerization within the beta-sheet aggregates was successful, proving parallel beta-strand orientation and highlighting the effect of the number and pattern of N-H...O=C hydrogen-bonding sites as well as the hydrophobic residue in the molecular structure on the formation of higher structures and reactivity.

Diffusion Dynamics of Radiology IT - Systems in German Hospitals - A Bayesian Bass Model.

Radiology has a reputation for having a high affinity to innovation - particularly with regard to information technologies. Designed for supporting the peculiarities of radiological diagnostic workflows, Radiology Information Systems (RIS) and Picture Archiving and Communication Systems (PACS) developed into widely used information systems in hospitals and form the basis for advancing the field towards automated image diagnostics. RIS and PACS can thus serve as meaningful indicators of how quickly IT innovations diffuse in secondary care settings - an issue that requires increased attention in research and health policy in the light of increasingly fast innovation cycles. We therefore conducted a retrospective longitudinal observational study to research the diffusion dynamics of RIS and PACS in German hospitals between 2005 and 2017. Based upon data points collected within the "IT Report Healthcare" and building on Rogers' Diffusion of Innovation (DOI) theory, we applied a novel methodological technique by fitting Bayesian Bass Diffusion Models on past adoption rates. The Bass models showed acceptable goodness of fit to the data and the results indicated similar growth rates of RIS and PACS implementations and suggest that market saturation is almost reached. Adoption rates of PACS showed a slightly higher coefficient of imitation (q = 0.25) compared to RIS (q = 0.11). However, the diffusion process expands over approximately two decades for both systems which points at the need for further research into how innovation diffusion can be accelerated effectively. Furthermore, the Bayesian approach to Bass modelling showed to have several advantages over the classical frequentists approaches and should encourage adoption and diffusion research to adapt similar techniques.