Computing Specificity

This note reports on an effort to implement a version of Poole\u27s rule for specificity. Relatively, efficient implementation relies on correcting and improving a pruning lemma of Simari-Loui [92]. This in turn requires revision of Poole\u27s specificity concept. The resulting system is a usable knowledge representation system with first-order-language and defeasible reasoning. Sample input and output are included in an appendix. It is a good candidate for multiple inheritance applications; it is useful for planning, but limited by the underlying search for plans

Identification of plant-derived alkaloids with therapeutic potential for myotonic dystrophy type I

Myotonic dystrophy type I (DM1) is a disabling neuromuscular disease with no causal treatment available. This disease is caused by expanded CTG trinucleotide repeats in the 3 UTR of the dystrophia myotonica protein kinase gene. On the RNA level, expanded (CUG)n repeats form hairpin structures that sequester splicing factors such as muscleblind-like 1 (MBNL1). Lack of availableMBNL1leads to misregulated alternative splicing of many target pre-mRNAs, leading to the multisystemic symptoms in DM1. Many studies aiming to identify small molecules that target the (CUG)n-MBNL1 complex focused on synthetic molecules. In an effort to identify new small molecules that liberate sequesteredMBNL1from (CUG)n RNA, we focused specifically on small molecules of natural origin. Natural products remain an important source for drugs and play a significant role in providing novel leads and pharmacophores for medicinal chemistry. In a new DM1 mechanism-based biochemical assay, we screened a collection of isolated natural compounds and a library of over 2100 extracts from plants and fungal strains. HPLC-based activity profiling in combination with spectroscopic methods were used to identify the active principles in the extracts. The bioactivity of the identified compounds was investigated in a human cell model and in a mouse model of DM1.We identified several alkaloids, including the -carboline harmine and the isoquinoline berberine, that ameliorated certain aspects of theDM1pathology in these models. Alkaloids as a compound class may have potential for drug discovery in other RNA-mediated diseases

The whole is greater than the sum of the parts: Recognising missed opportunities for an optimal response to the rapidly maturing TB-HIV co-epidemic in South Africa

<p>Abstract</p> <p>Background</p> <p>Despite widely acknowledged WHO guidelines for the integration of TB and HIV services, heavily burdened countries have been slow to implement these and thus significant missed opportunities have arisen.</p> <p>Discussion</p> <p>The individual-centred, rights-based paradigm of the SA National AIDS Policy, remains dissonant with the compelling public-health approach of TB control. The existence of independent and disconnected TB and HIV services results in a wastage of scarce health resources, an increased burden on patients' time and finances, and ignores evidence of patients' preference for an integrated service. The current situation translates into a web of unacceptable, ongoing missed opportunities such as failure to maximize collaborative disease surveillance, VCT, adherence support, infection control, and positive prevention. TB services present a readily identifiable cohort for HIV provider-initiated testing. Integrating HAART and DOTS will promote efficient usage of health workers' time and a more navigable experience for patients, ultimately ensuring increased TB treatment completion rates and MDR-TB prevention. As direct observation evolves into a more supportive, empowering experience for patients, adherence to both TB drugs and HAART will be bolstered. Little attention has been paid to the transmission of TB within HIV services. Low cost infection control interventions include: triaging patients, scheduling new and follow-up patients separately; well-ventilated, sheltered waiting rooms; and the use of personal respirators by patients and staff. A more patient-centred approach to TB care may be able to recruit the active participation of TB patients in positive prevention efforts, including maximizing personal infection control, limiting exposure of social contacts to TB during the intensive phase of treatment, advocating isoniazid prophylaxis within the home and patient-centred education efforts to reduce overall transmission. Several model programmes demonstrated synergy, in which the impact of the "whole" or integrated response was greater than the sum of the non-integrated parts.</p> <p>Summary</p> <p>The full potential of an integrated TB-HIV service has not been fully harvested. Missed opportunities discount existing efforts in both programmes, will perpetuate the burden of disease, and prevent major gains in future interventions. This paper outlines simple, readily-implementable strategies to narrow the gap and reclaim existing missed opportunities.</p

Synthesis and X-ray characterization of the organotriboroxinate salts [Me3NCH2CH2OH][Ph4B3O3] and [NEt3H][Ph3B3O3(OH)], and the X-ray structure of the triarylboroxine, (4-MeOC6H4)(3)B3O3

The synthesis and characterization of the organotriboroxinate salts [Me3NCH2CH2OH][B3O4Ph4] (1) and [NEt3H][B3O3Ph3(OH)] (3) are reported. Compound 3 contains the first example of a hybrid inorganic/organic triboroxinate anion. Compounds I and 3 have been structurally characterized by single-crystal X-ray diffraction studies, which reveal H-bond ion-pair interactions between anions and cations in both 1 and 3, and additional anion-anion H-bond interactions in 3. Compound 3 exists as a dimer in the solid-state. A single crystal X-ray diffraction study of the triarylboroxine, (4-MeOC6H4)(3)B3O3, is also reported

Entwicklung integriert-optischer Gassensoren Abschlussbericht

Based on integrated optical transducers, new types of gas sensors were developed. The transducers used are different types of interferometer, grid couplers and adsorption sections. Gas-sensitive coatings were developed and were intensively examined regarding sensitivity, cross-sensitivity and long-term stability. Sensors for CO_2, NH_3 and solvent vapours can be produced in this way. (orig)Auf der Basis integriert-optischer Transducer wurden neuartige Gassensoren entwickelt. Die verwendeten Transducer sind verschiedene Interferometertypen, Gitterkoppler und Absorptionsstrecken. Gassensitive Beschichtungen wurden entwickelt und hinsichtlich Empfindlichkeit, Querempfindlichkeiten und Langzeitstabilitaet intensiv untersucht. Sensoren fuer CO_2, NH_3 und Loesemitteldaempfe sind auf diesem Wege realisierbar. (orig.)Available from TIB Hannover: F94B0324 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman