Publications

EPR-based, quality-related process parameters: a nationwide assessment

The aim of the study was to determine whether or not primary care EPR-based data can be used to measure specific process parameters that can then, in turn, be used to assess the quality of care provided to chronic patients. We analysed data from a large research network that collects data from all Belgian GP practices through both manual and automatic extraction procedures. We built a number of quality-related process parameters and observed the concordance of our results with two external databases: a nationwide reimbursement database and a regional EPR-based network. We found that only the automatic data extraction method was suitable for building process parameters. The current research network may lead to an underestimation of the quality of care processes. We suggested ways to improve this network.

Antiviral Activity Spectrum and Target of Action of Different Classes of Nucleoside Analogues

Abstract Depending on the target enzyme with which they interact, nucleoside analogues exhibit marked differences in their antiviral activity spectrum. The activity spectrum of those nucleoside analogues that interact with cellular enzymes involved in the biosynthesis of the RNA and DNA precursor nucleotides encompasses virtually all RNA and DNA viruses. In contrast, the activity spectrum of those nucleoside analogues that are targeted at a specific viral enzyme will be limited to those specific virus types whose enzyme(s) they interact with. For a given compound, the antiviral activity spectrum can often be predicted from identification of the target enzyme, and, vice versa, the mode of action can be deduced from the activity spectrum.1 This concordance between antiviral activity spectrum and mode (target) of antiviral action will be scrutinized for the following categories of nucleoside analogues: AKAR analogues (i.e. ribavirin) that are targeted at IMP dehydrogenase; carbocyclic adenosine analogues (i.e. neplanocin A) that are targeted at AdoHcy hydrolase; OMP decarboxylase inhibitors such as pyrazofurin; CTP synthetase inhibitors such as cyclopentenylcytosine; acyclic guanosine analogues (i.e. acyclovir, ganciclovir) which act as viral DNA chain terminators following initial phosphorylation by the virus-encoded thymidine kinase (TK) or protein kinase; thymidine analogues (ie. BVDU) whose antiviral action (at the viral DNA polymerase level) also depends on a preferential phosphorylation by the viral TK; acyclic nucleoside phosphonates which can be divided into different subcategories depending on whether their activity spectrum includes all major DNA viruses (herpes, adeno, pox, papova and hepadna, or herpes-, hepadna-, and retroviruses, or only hepadna- and retroviruses); 2′,3′-dideoxynucleoside analogues which, following phosphorylation to the 5′-triphosphate form by cellular enzymes, act as chain terminators of the retro- and hepadnaviral reverse transcriptase; and certain nucleoside derivatives (i.e. HEPT, TSAO) which act as highly specific inhibitors of the reverse transcriptase of human immunodeficiency virus type 1 (HIV-1) (Table 1).

ChemInform Abstract: 5′‐O‐Alkyl‐5‐fluorouridines: Synthesis and Biological Activity.

Abstract The preparation of the title compounds (XII) and (XVIII) is reported.

New Anti-HIV Agents in Preclinical or Clinical Development

Virtually all the compounds that are currently used (or have been the subject of advanced clinical trials) for the treatment of HIV infections, belong to one of the following classes: (i) nucleoside reverse transcriptase inhibitors (NRTIs): i.e., zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir, emtricitabine and nucleotide reverse transcriptase inhibitors (NtRTIs) (i.e., tenofovir disoproxil fumarate); (ii) non-nucleoside reverse transcriptase inhibitors (NNRTIs): i.e., nevirapine, delavirdine, efavirenz, emivirine; and (iii) protease inhibitors (PIs): i.e., saquinavir, ritonavir, indinavir, nelfinavir, amprenavir and lopinavir. In addition to the reverse transcriptase and protease reaction, various other events in the HIV replicative cycle can be considered as potential targets for chemotherapeutic intervention: (i) viral adsorption, through binding to the viral envelope glycoprotein gp120 (polysulfates, polysulfonates, polycarboxylates, polyoxometalates, polynucleotides, and negatively charged albumins); (ii) viral entry, through blockade of the viral coreceptors CXCR4 (i.e., bicyclam (AMD3100) derivatives) and CCR5 (i.e., TAK-779 derivatives); (iii) virus-cell fusion, through binding to the viral envelope glycoprotein gp41 (T-20, T-1249); (iv) viral assembly and disassembly, through NCp7 zinc finger-targeted agents (2,2′-dithiobisbenzamides (DIBAs), azadicarbonamide (ADA)); (v) proviral DNA integration, through integrase inhibitors such as 4-aryl-2,4-dioxobutanoic acid derivatives; (vi) viral mRNA transcription, through inhibitors of the transcription (transactivation) process (flavopiridol, fluoroquinolones). Also, various new NRTIs, NNRTIs and PIs have been developed that possess, respectively: (i) improved metabolic characteristics (i.e., phosphoramidate and cyclosaligenyl pronucleotides by-passing the first phosphorylation step of the NRTIs), (ii) increased activity (“second” generation NNRTIs (i.e., TMC-125, DPC-083)) against those HIV strains that are resistant to the “first” generation NNRTIs, or (iii), as in the case of PIs, a different, modified peptidic (i.e., azapeptidic (atazanavir)) or non-peptidic scaffold (i.e., cyclic urea (mozenavir), 4-hydroxy-2-pyrone (tipranavir)). Non-peptidic PIs may be expected to inhibit HIV mutant strains that have become resistant to peptidomimetic PIs.

Syntheses and anti‐HIV Activities of (.+‐.)‐Norcarbovir and (.+‐.)‐Norabacavir.

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Using X-ray computed tomography to improve the porosity level of polyamide-12 laser sintered parts

Porosity is a key parameter determining the functional application limits of polymeric parts produced by laser sintering (LS). In this paper, X-ray computed tomography (CT) is used to investigate the influence of the LS scanning parameters (laser power, hatch spacing, and scan speed) and part or feature size on the distribution and size of pores within polyamide-12 (PA12) laser sintered parts. CT model slices are created parallel to the original LS manufacturing layers in order to determine the porosity distribution and variation within each layer as well as along subsequent layers. Mapping the porosity distribution within these slices onto the laser scanning trajectory moreover allows investigating the influence of LS scanning parameters. Correlation of these porosity data with results from mechanical testing allows identifying optimal LS scanning parameters.

Synthesis and Antiviral and Cytostatic Evaluations of the New C-5 Substituted Pyrimidine and Furo[2,3-<i>d</i>]pyrimidine 4‘,5‘-Didehydro-<scp>l</scp>-ascorbic Acid Derivatives

The novel C-5 alkynyl substituted pyrimidine (1-11) and furo[2,3-d]pyrimidine derivatives (12-22) of l-ascorbic acid were synthesized by coupling of 5-iodouracil-4',5'-didehydro-5',6'-dideoxy-l-ascorbic acid with terminal alkynes by using Sonogashira cross-coupling reaction conditions. The new compounds were evaluated for their cytostatic and antiviral activities. Among all evaluated compounds, the octynyl-substituted uracil derivative of l-ascorbic acid (3) exhibited the most pronounced cytostatic activities against all examined tumor cell lines (IC50 = 2-12 microM). Pyrimidine derivatives of l-ascorbic acid containing p-substituted phenylacetylene groups (8-11) displayed also a rather pronounced (IC50 = 3-37 microM) inhibitory effect toward all tumor cell lines. From the bicyclic series of compounds, 6-butylfuro[2,3-d]pyrimidine derivative (12) and 6-p-bromophenylfuro[2,3-d]pyrimidine derivative (19) showed the highest cytostatic activity (IC50 = 4.5-20 microM), particularly against malignant leukemia (L1210) and T-lymphocyte (Molt4/C8 and CEM) cells. Compounds 3 and 9 showed specific albeit moderate activity against cytomegalovirus (CMV, Davis strain, EC50 = 1.8 and 3.8 microM, respectively, for compounds 3 and 9) at a approximately 5-fold lower concentration than that required to show cytotoxicity.

A computer aided process planning system for electrical discharge machining

No abstract is provided for this article.

Synthesis and Antiviral Evaluation of Some 3′‐Fluoro Bicyclic Nucleoside Analogues.

Abstract For Abstract see ChemInform Abstract in Full Text.

Additive manufacturing in aerospace

No abstract is provided for this article.

Selective Laser Melting process optimization of Ti–Mo–TiC metal matrix composites

Selective Laser Melting (SLM) was used to process a powder mixture of CP Ti, 6.5 wt% Mo and 3.5 wt% Mo2C. The process parameters were optimized to obtain full-density, crack free parts. After the in situ decomposition of Mo2C in favor of the formation of TiC, the material consisted of a homogeneous dispersion of submicrometer sized TiC platelets in a β-(Ti,Mo) matrix exhibiting a high hardness up to 550 HV and compressive yield stress of 1164 ± 37 MPa. The microstructure and mechanical properties could be tailored by variation of the process parameters within the high-density processing window, as well as through post-process heat treatments.

Polyadenylic·polyxanthylic·polyuridylic acid triple helix

Poly(xanthylic acid) [X)n] abolished the ability of (A)n-(U)n to induce interferon in "superinduced" (actinomycin D and cycloheximide) primary rabbit kidney cells. Under the same conditions, (X)n had a relatively minor effect on the interferon inducing capacity of (I)n-(C)n. Evidence based on mixing curves, melting profiles, pancreatic ribonuclease resistance and sucrose gradient ultracentrifugation pointed to the conclusion that the following three reactions occur depending on stoichiometry: (1) 2(A)n-(U)n + (X)n leads to (A)n-2(U)n + (A)n-(X)n; (2) (A)n-(U)n + (X)n leads to (A)n-(U)n-(X)n; (3) (A)n-(U)n + 2(X)n + (X)n-(U)n. The second reaction represents the formation of a new triple helix which can also be formed according to the following reactions: (X)n-(U)n + (A)n leads to (A)n-(X)n-(U)n; (A)n-(X)n + (U)n leads to (A)n-(X)n-(U)n.

CMM hardware error simulation for uncertainty evaluation

No abstract is provided for this article.

Inhibition of tubulin polymerization by select alkenyldiarylmethanes

Observation of Ramsey fringes with optical CPT pulses

International audience

Chronic herpetic infection in an immunocompromised patient: Report of a case

Wire EDM Machining of Si3N4, ZrO2 and Al2O3-based Ceramics

Advanced engineering ceramics are more and more employed in modern industries because of their excellent mechanical properties such as high hardness, high compressive strength, chemical and abrasive resistance.This paper investigates the Wire EDM of ShN 4 -based, ZrOz-based, and Ah03-based ceramics, provided that the ceramics have sufficiently high electrical conductivity.First, this paper investigates the cutting rate, the surface quality and surface integrity of Si3N4-TiN, Zr0 2 -TiN and Ah03-SiCw-TiC by Wire EDM.Furthermore, it is pointed out that besides typical material removal mechanisms like melting and evaporation, other mechanisms such as decomposition and oxidation have been identified.The latter mechanism results in a remarkable increase of the cutting rate, but a poorer surface quality.

CCDC 863846: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.