Rescaling invariance and anomalous energy transport in a small vertical column of grains.

It is well known that energy dissipation and finite size can deeply affect the dynamics of granular matter, often making usual hydrodynamic approaches problematic. Here we report on the experimental investigation of a small model system, made of ten beads constrained into a 1D geometry by a narrow vertical pipe and shaken at the base by a piston excited by a periodic wave. Recording the beads motion with a high frame rate camera allows to investigate in detail the microscopic dynamics and test hydrodynamic and kinetic models. Varying the energy, we explore different regimes from fully fluidized to the edge of condensation, observing good hydrodynamic behavior down to the edge of fluidization, despite the small system size. Density and temperature fields for different system energies can be collapsed by suitable space and time rescaling, and the expected constitutive equation holds very well when the particle diameter is considered. At the same time, the balance between dissipated and fed energy is not well described by commonly adopted dependence due to the up-down symmetry breaking. Our observations, supported by the measured particle velocity distributions, show a different phenomenological temperature dependence, which yields equation solutions in agreement with experimental results.

Simple and User-Friendly Methodology for Crystal Water Determination by Quantitative Proton NMR Spectroscopy in Deuterium Oxide.

In drug research and development, knowledge of the precise structure of an active ingredient is crucial. However, it is equally important to know the water content of the drug molecule, particularly the number of crystal waters present in its structure. Such knowledge ensures the avoidance of drug dosage and formulation errors since the number of water molecules affects the physicochemical and pharmaceutical properties of the molecule. Several methods have been used for crystal water measurements of organic compounds, of which thermogravimetry and crystallography may be the most common ones. To the best of our knowledge, solution-state NMR spectroscopy has not been used for crystal water determination in deuterium oxide. Quantitative NMR (qNMR) method will be presented in the paper with a comparison of single-crystal X-ray diffraction and thermogravimetric analysis results. The qNMR method for water content measurement is straightforward, reproducible, and accurate, including measurement of 1H NMR spectrum before and after the addition of the analyte compound, and the result can be calculated after integration of the reference compound, analyte, and HDO signals using the given equation. In practical terms, there is no need for weighing the samples under study, which makes it simple and is a clear advantage to the current determination methods. In addition, the crystal structures of two model bisphosphonates used herein are reported: that of monopotassium etidronate dihydrate and monosodium zoledronate trihydrate.

Structural Diversity in Antiosteolytic Bisphosphonates: Deciphering Structure-Activity Trends in Ultra Long Controlled Release Phenomena.

Bisphosphonate (BP)-based treatments have been extensively prescribed for bone-related conditions, particularly for osteoporosis. Their low bioavailability creates the need for prescribed dosage increase to reach therapeutic levels but generates a plethora of undesirable side effects. A viable approach to alleviating these issues is to design and exploit controlled release strategies. Herein, the controlled release profiles of 15 structurally characterized BPs (actual drugs and structural analogs) were thoroughly studied from tablets containing three (cellulose, lactose, and silica) or two (cellulose, and silica) excipients in human stomach-simulated pH conditions. The BPs were of two types, alkyl-BPs and amino-BPs. Alkyl-BPs included four derivatives of etidronate (acid, disodium, tetra-sodium, and monopotassium forms), medronic acid, and three analogs of etidronate, in which the -CH3 group was replaced by the moieties -H, -CH2CH2CH3, and -CH2CH2CH2CH2CH3. Amino-BPs included the commercial drugs pamidronate, alendronate, neridronate, and ibandronate, as well as three analog compounds. Release curves were constructed based on data taken from 1H NMR peak integration and were expressed as "% BP release" vs time. The controlled release profiles (initial release rate, plateau value, etc.) were correlated with certain structural features (number of hydrogen and metal-oxygen bonds), showing that the molecular and crystal lattice features of each BP profoundly influence its release characteristics. It was concluded that for all BPs, in general, the initial rate became lower as the total number of lattice interactions increased. For the alkyl-BPs elongation of the alkyl side chain seems to decelerate the release. Amino-BPs, in general, show slower release than the alkyl-BPs. No adverse effects of alkyl- and amino-BP drugs on NIH3T3 cell viability were noted.

Transition in endocrinology: predictors of drop-out of a heterogeneous population on a long-term follow-up.

PURPOSE: To evaluate: (1) clinical and epidemiological characteristics of outpatients transitioned from Pediatrics Endocrine (PED) to Adult Endocrine Department (AED) in a tertiary center; (2) transition process features, and predictors of drop-out. METHODS: Demographic, clinical, and transition features of 170 consecutive patients with pediatric onset of chronic endocrine or metabolic disease (excluded type 1 diabetes) who transitioned from PED to AED (2007-2020) were retrospective evaluated. RESULTS: The age at transition was 18.4 ± 4 years (F:M = 1.2: 1), and mean follow-up 2.8 years. The population was heterogeneous; the most (69.4%) was affected by one, 24.1% by two or more endocrine diseases, 6.5% were followed as part of a cancer survivor's surveillance protocol. The comorbidity burden was high (37, 20.6, and 11.2% of patients had 2, 3, 4, or more diseases). The number of visits was associated with the number of endocrine diseases and the type of them. Adherent subjects had a higher number of comorbidities. Thyroid disorders and more than one comorbidity predicted the adherence to follow-up. Having performed one visit only was predictive of drop-out, regardless of the pathology at diagnosis. CONCLUSION: This is the first study that analyzed a specific transition plan for chronic endocrine diseases on long-term follow-up. The proposed "one-size-fits-all model" is inadequate in responding to the needs of patients. A structured transition plan is an emerging cornerstone.

Synthesis of the biologically important dideuterium-labelled adenosine triphosphate analogue ApppI(d 2).

The chemical synthesis of the dideuterium-labelled ATP analogue 1-adenosin-5'-yl-3-(3-methylbut-3-en-1,1-d 2-1-ol) triphosphoric acid diester (ApppI(d 2)) is described. ApppI has been reported to be an important mevalonate pathway metabolite, induced by nitrogen-containing bisphosphonates used for the treatment of several diseases related to the calcium metabolism, of which osteoporosis is the most well-known. The availability of ApppI(d 2) opens possibilities to quantitative measurements of ApppI in biological samples by mass spectrometry. The synthesized target compound ApppI(d 2) was purified by high-performance counter current chromatography and characterized by 1H, 13C, and 31P NMR spectroscopy as well as high-resolution mass spectrometry.

Real-Time On-Site Multielement Analysis of Environmental Waters with a Portable X-ray Fluorescence (pXRF) System.

Strict regulations are in place to control the effluents of mining sites and other industries. Heavy metal contamination of aquatic systems caused by leakages is difficult to mitigate as it takes time to detect and localize the leak. Dynamic sampling would drastically reduce the time to locate leakages and allow faster actions to reduce the impact on the environment. The present study introduces a novel portable multielement water analysis system to simultaneously measure Mn, Ni, Cu, Zn, Pb, and U in water samples from natural sources within 15 min from the sampling. The metals are preconcentrated from a 10 mL water sample into a nanoporous filter based on bisphosphonate-modified thermally carbonized porous silicon. The metals can be conveniently analyzed from the filter with a portable XRF analyzer in field conditions. The system was empirically calibrated for a lake water matrix with neutral pH and low alkaline metal concentration. A strong correlation between the XRF intensities and the ICP-MS results was obtained in a concentration range from 50 to 10 000 µg/L. With a DPO-2000C XRF analyzer, the detection limits were 103, 86, 92, 35, 44, and 43 µg/L for Mn, Ni, Cu, Zn, Pb, and U, respectively. The corresponding values with X-MET8000 Expert Geo were 137, 46, 62, 38, 29, and 54. The system was successfully validated with simulated multielement lake water samples and piloted in field conditions. The system provides an efficient way to monitor metals in environmental waters in cases where quick on-site results are needed.

Crystal structure of ADAMTS13 CUB domains reveals their role in global latency.

ADAMTS13 is a plasma metalloprotease that is essential for the regulation of von Willebrand factor (VWF) function, mediator of platelet recruitment to sites of blood vessel damage. ADAMTS13 function is dynamically regulated by structural changes induced by VWF binding that convert it from a latent to active conformation. ADAMTS13 global latency is manifest by the interaction of its C-terminal CUB1-2 domains with its central Spacer domain. We resolved the crystal structure of the ADAMTS13 CUB1-2 domains revealing a previously unreported configuration for the tandem CUB domains. Docking simulations between the CUB1-2 domains with the Spacer domain in combination with enzyme kinetic functional characterization of ADAMTS13 CUB domain mutants enabled the mapping of the CUB1-2 domain site that binds the Spacer domain. Together, these data reveal the molecular basis of the ADAMTS13 Spacer-CUB interaction and the control of ADAMTS13 global latency.

Breakdown of Scaling and Friction Weakening in Intermittent Granular Flow.

Many materials are produced, processed and stored as grains, while granularity of matter can be crucial in triggering potentially catastrophic geological events like landslides, avalanches and earthquakes. The response of grain assemblies to shear stress is therefore of utmost relevance to both human and natural environment. At low shear rate a granular system flows intermittently by distinct avalanches. In such state the avalanche velocity in time is expected to follow a symmetrical and universal average behavior, whose dependence on the slip size reduces to a scale factor. Analyzing data from long lasting experiments, we observe a breakdown of this scaling: While in short slips velocity shows indeed a self-similar and symmetric profile, it does not in long slips. The investigation of frictional response in these different regimes evidences that this breakdown can be traced back to the onset of a friction weakening, which is of dynamical origin and can amplify instabilities exactly in this critical state, the most frequent state for natural hazards.

(E)-Di-iodination of Alkynes Using Dried Dowex H+/NaI Approach.

We investigated the usefulness of the dried Dowex H+/NaI approach for the selective di-iodination of alkynes. The Dowex H+/NaI approach selectively produces only (E)-di-iodinated products; it is very straightforward and nontoxic. The utilization of 2-propanol as a solvent in the reactions can be considered as a "green" approach and the method maybe extended to radio-iodination. The method allows access to highly important building blocks. An initial example of the di-iodination and esterification in the same one-pot reaction is also presented.

Green and Efficient Esterification Method Using Dried Dowex H+/NaI Approach.

The usefulness of dried Dowex H+ cation-exchange resin with or without sodium iodide (NaI) as a catalyst system for different kinds of esterifications using carboxylic acids and alcohols as starting materials has been systematically investigated. The Dowex H+/NaI approach is very effective, generally high yielding, energy-efficient, and nontoxic, and the Dowex H+ resin is reusable. Since the whole procedure from start to product isolation is also very simple, these features make the method environmentally friendly. The method is regioselective, and its potential for separation of valuable carboxylic acids like resin acids from mixtures containing other kinds of carboxylic acids has been demonstrated. Examples for green and straightforward esterification of highly important natural amino acids are also presented.

A Holistic Approach to Assessment of Population Exposure to Radiation: Challenges and Initiatives of a Regulatory Authority.

A regulatory authority for radiation safety should continuously evaluate and improve the national safety framework, in line with current requirements and standards. In this context, the Greek Atomic Energy Commission initiated a series of concerted actions. The radiation dose to the population due to public and medical exposures was assessed. The assessment of dose due to public exposure was based on measurements of radon concentrations in dwellings, radionuclide concentrations in environmental samples, and air dose rates; the assessment of dose due to medical exposure was based on dose measurements for typical examinations or procedures and data on their frequency. The mean effective dose to a member of the population was found to be 4.5 mSv (1.8 mSv and 2.7 mSv from medical and public exposures, respectively). Regarding occupational exposure, aircrew dose assessment, eye lens monitoring, and the national dose registry were significantly improved. With respect to artificial tanning (sun beds), the ultraviolet radiation produced was assessed and the practices followed were observed. Results demonstrated exceedance of the 0.3 W m erythema effective irradiance limit set in European Union standards by 63.5% of the sun beds measured, along with general noncompliance with standards. An overarching activity was the upgrade of the Greek Atomic Energy Commission information system in order to collect and disseminate radiation data electronically, launch a networking strategy for interaction with stakeholders, and facilitate the process of regulatory control. In response to the above findings, regulatory actions have been initiated.

A strategic framework for the development and enhancement of safety culture in the artificial tanning sector in Greece.

Herein, a strategic framework for the development and enhancement of safety culture in the artificial tanning sector in Greece is presented. This framework has been designed and promoted by the competent national regulatory authority, which is the Greek Atomic Energy Commission (EEAE). The aim is to ensure a common understanding regarding ultraviolet radiation (UVR) and artificial tanning among artificial tanning professionals, stakeholders and the general public. The strategic framework is founded on the recommendations of international organizations, EU requirements and the relevant technical standards. It comprises three autonomous but interconnected components: (A) a sunbed operators' e-training course and certification process; (B) a code of practice addressed individually to business owners, sunbed operators and sunbed users; (C) communication strategies aiming to raise awareness regarding UVR and artificial tanning among all interested parties. The artificial tanning safety culture framework presented here is the policy option undertaken by the EEAE and is embedded in the upcoming legislation and regulations for the provision of artificial tanning services in Greece. EEAE considers that the structure of the artificial tanning safety culture strategic framework will serve as a guide for the development and promotion of relevant strategic safety culture frameworks for the provision of aesthetic/wellness services utilising other non-ionising radiation sources, which do not currently exist.

Uniaxial and biaxial structures in the elastic Maier-Saupe model.

We perform statistical mechanics calculations to analyze the global phase diagram of a fully connected version of a Maier-Saupe-Zwanzig lattice model with the inclusion of couplings to an elastic strain field. We point out the presence of uniaxial and biaxial nematic structures, depending on temperature T and on the applied stress σ. Under uniaxial extensive tension, applied stress favors uniaxial orientation, and we obtain a first-order boundary along which there is a coexistence of two uniaxial paranematic phases, and which ends at a simple critical point. Under uniaxial compressive tension, stress favors biaxial orientation; for small values of the coupling parameters, the first-order boundary ends at a tricritical point, beyond which there is a continuous transition between a paranematic and a biaxially ordered structure. For some representative choices of the model parameters, we obtain a number of analytic results, including the location of critical and tricritical points and the line of stability of the biaxial phase.

Semi-preparative high-performance countercurrent chromatography method for the purification of chemically synthesized ATP analogue, ApppI.

An efficient high-performance countercurrent chromatography (HPCCC) based method has been developed for the purification of chemically synthesized 1-adenosin-5'-yl 3-(3-methylbut-3-enyl)triphosphoric acid diester (ApppI). ApppI is an adenosine triphosphate (ATP) analogue with biological significance due to its varied actions in the body. ApppI was synthesized and purified as its tetrabutylammonium (TBA) salt and converted successfully into its more practical sodium salt form after purification. The amount of TBA hydroxide (2.0, 2.5 and 3.0 eq) used in the synthesis of ApppI was shown to exert an effect on the purification process with HPCCC and on the overall yield (8%, 16% and 22%, respectively). 1-Adenosin-5'-yl 3-(3-methylbut-3-enyl)diphosphoric acid diester (AppI) was also isolated as a side product.

Synthesis of a Biologically Important Adenosine Triphosphate Analogue, ApppD.

The chemical synthesis of a adenosine triphosphate analogue, 1-adenosin-5'-yl 3-(3-methylbut-2-enyl) triphosphoric acid diester (ApppD), is described. ApppD is known to be an active metabolite of the mevalonate pathway in the human body like its structural isomer isopentenyl ester of ATP (ApppI). Very recently, ApppI has been found to possess novel function(s); now it will also be possible to examine the effects of ApppD more precisely because it can be synthesized in reasonable amounts. 1-Adenosin-5'-yl 3-(3-methylbut-2-enyl) diphosphoric acid diester (AppD; a adenosine diphosphate analogue) was also isolated from the synthesis mixture. Both ApppD and AppD were characterized by 1H, 13C, 31P NMR and mass spectrometry methods.

Correction to "Synthesis of a Biologically Important Adenosine Triphosphate Analogue, ApppD".

[This corrects the article DOI: 10.1021/acsomega.7b00531.].

Synthesis of medronic acid monoesters and their purification by high-performance countercurrent chromatography or by hydroxyapatite.

We achieved the synthesis of important medronic acid monoalkyl esters via the dealkylation of mixed trimethyl monoalkyl esters of medronic acid. Two methods were developed for the purification of medronic acid monoesters: 1) small scale (10-20 mg) purification by using hydroxyapatite and 2) large scale (tested up to 140 mg) purification by high-performance countercurrent chromatography (HPCCC).

Increasing 'ease of sliding' also increases friction: when is a lubricant effective?

We investigate experimentally the effective Coulomb friction exerted by a granular medium on a shearing plate, varying the medium depth. The plate is driven by a spring connected to a motor turning at a constant speed and, depending on the system configuration, performs continuous sliding or stick and slip in different proportions. We introduce an order parameter which discriminates between the different regimes expressing the fraction of time spent in slipping. At low driving speed, starting from zero layers of interstitial granular material, the average friction coefficient decreases when a few layers are added, while the order parameter stays close to zero. By further increasing the granular depth, the friction undergoes a sudden increase but the order parameter does not change notably. At an intermediate driving speed, however, both the friction and the order parameter undergo a sudden increase, which for the order parameter amounts to several orders of magnitude, indicating that the plate is more braked but nevertheless keeps sliding more easily. For medium-high driving speeds, full sliding is obtained for only one layer of interstitial matter, where friction has a minimum, and is maintained for all increasing depths while friction increases. These observations show that the ease of slipping is not determined by friction alone, rather by the highly complex interplay between driving velocity, friction, and the depth of the medium.