ASGPR‐Mediated Uptake of Multivalent Glycoconjugates for Drug Delivery in Hepatocytes

Liver cells are an essential target for drug delivery in many diseases. The hepatocytes express the asialoglycoprotein receptor (ASGPR), which promotes specific uptake by means of N‐acetylgalactosamine (GalNAc) recognition. In this work, we designed two different chemical architectures to treat Wilson's disease by intracellular copper chelation. Two glycoconjugates functionalized with three or four GalNAc units each were shown to enter hepatic cells and chelate copper. Here, we studied two series of compounds derived from these glycoconjugates to find key parameters for the targeting of human hepatocytes. Efficient cellular uptake was demonstrated by flow cytometry using HepG2 human heptic cells that express the human oligomeric ASGPR. Dissociation constants in the nanomolar range showed efficient multivalent interactions with the receptor. Both architectures were therefore concluded to be able to compete with endogeneous asialoglycoproteins and serve as good vehicles for drug delivery in hepatocytes.     

Urodynamic picture in high spinal cord ischemia, induced by addictive use of cocaine. Report of a case

Since in vitro experiments had excluded interactions between Fe-gluconate (Fe-gluc) and magnesium-L-aspartate hydrochloride (MAH) in aqueous solutions the present in vivo studies seemed to be justified. Animal studies: Rats were kept on magnesium-(Mg)- and iron-(Fe)- sufficient and deficient diets. The intragastral administration of Fe-gluc significantly increased plasma Fe after 3 h, either given alone, or in combination with MAH (inducing hypermagnesemia). Same results were obtained when fortified diets were offered to Fe/Mg-deficient animals. Human studies: The combination of Fe-gluc (2 x 50 mg Fe per day, per os) plus MAH (2 x 7.5 mmol Mg per day, p.o.) was well tolerated by healthy volunteers. Single dose experiments revealed that Fe-gluc alone and in combination with MAH increased plasma Fe levels during 3 h to the same extent. Two groups of pregnant women with moderately reduced hemoglobin levels either received Fe-gluc (out-patients) or its combination with MAH (at least temporarily hospitalised because of preterm labor). Treatments were well tolerated. Hemoglobin levels did not further decrease, as expected without Fe supplements, during the course of pregnancy, thus indicating the therapeutic availability of the electrolytes in both study groups. Progesterone-induced constipation is frequently observed during pregnancy; hence stool softening reported by 50% of the women receiving Fe-gluc plus MAH (versus 33% in the Fe-gluc group) can be regarded as desirable effect. It is concluded that MAH does not interfere with the enteral absorption of Fe-gluc when both electrolytes are orally administered together. Taking both electrolytes together instead of 2 to 3 h apart from each other, as actually recommended, means a less complicated dosage regimen and probably improves compliance.     

Parallel query processing with zigzag trees

In this article, we describe our approach to the compile-time optimization and parallelization of queries for execution in DBS3 or EDS. DBS3 is a shared-memory parallel database system, while the EDS system has a distributed-memory architecture. Because DBS3 implements a parallel dataflow execution model, this approach applies to both architectures. Using randomized search strategies enables the exploration of a search space large enough to include zigzag trees, which are intermediate between left-deep and right-deep trees. Zigzag trees are shown to provide better response time than right-deep trees in case of limited memory. Performance measurements obtained using the DBS3 prototype show the advantages of zigzag trees under various conditions.     

Comparison of hindquarter metabolite uptakes in Belgian Blue double-muscled bulls at maintenance or during fattening

Metabolism of muscle growth in the hindquarter was investigated by the arterio-venous difference (AVD) technique in Belgian Blue double-muscled type bulls at maintenance or at fattening. The bulls were fitted with an aortic ultrasonic blood flow probe and with catheters in the aorta and vena cava. They were offered a diet allowing for maintenance (MP) during a period of 15 d, at the end of which measurements were made over 3 d. Bulls were then given a fattening diet (FP) and the measurements were repeated. Arterial blood flow was approximately 1 L/min greater when the bulls were standing than when lying. Blood flow was 2 L/min higher during FP than during MP. The AVD and uptake of glucose were maximal at 1400 and 1600. Uptake of alpha-amino nitrogen decreased immediately after a meal. The increase in glucose from MP to FP fitted very well with the calculated energy needs for muscle growth. The AVD and uptake of alpha-amino nitrogen, total amino acids, and total nonessential amino acids were negative during MP and positive and significantly higher during FP. There was also a significant increase in AVD and uptake of essential and branched-chain amino acids when the bulls were changed from MP to FP. When changing from maintenance to fattening, the incremental glucose and amino acid hindquarter uptake provided energy and supply for muscle protein accretion, respectively. The level of alanine transamination was also sharply reduced.     

A Technical Word- and Term-Translation Aid Using Noisy Parallel Corpora across Language Groups

Technical-term translation represents one of the most difficult tasks for human translators since (1) most translators are not familiar with terms and domain-specific terminology and (2) such terms are not adequately covered by printed dictionaries. This paper describes an algorithm for translating technical words and terms from noisy parallel corpora across language groups. Given any word which is part of a technical term in the source language, the algorithm produces a ranked candidate match for it in the target language. Potential translations for the term are compiled from the matched words and are also ranked. We show how this ranked list helps translators in technical-term translation. Most algorithms for lexical and term translation focus on Indo-European language pairs, and most use a sentence-aligned clean parallel corpus without insertion, deletion or OCR noise. Our algorithm is language- and character-set-independent, and is robust to noise in the corpus. We show how our algorithm requires minimum preprocessing and is able to obtain technical-word translations without sentence-boundary identification or sentence alignment, from the English–Japanese awk manual corpus with noise arising from text insertions or deletions and on the English–Chinese HKUST bilingual corpus. We obtain a precision of 55.35% from the awk corpus for word translation including rare words, counting only the best candidate and direct translations. Translation precision of the best-candidate translation is 89.93% from the HKUST corpus. Potential term translations produced by the program help bilingual speakers to get a 47% improvement in translating technical terms.     

Gestion de réseau: État de la normalisation

The need for multi-media communication is currently rapidly increasing. This leads to a sharp increase in the number of public and private networks, and they must inter-operate in spite of their being heterogeneous. Mastering those networks is a complex but crucial task. This can only be achieved via good management. Thus, users have been impulsing a heavy thrust in the field of network management and especially its standardization. This paper focusses on the current status of network management standards in the main international bodies, highlighting the main points. It also describes some of France Telecom’s experiments concerning the implementation of the standards.     

Increasing Reliability in Cable-Free Radio LANs Low Level Forwarding in HIPERLAN

Radio LANs are emerging in the computing world. They are supported by distinct configurations: on the one hand radio LANs with base stations and a wired backbone, on the other hand radio LANs implementing Intra-forwarding. Adding a new node in a radio LAN with Intra-forwarding, increases the reliability, while this reliability decreases with ad hoc or hub configurations. This advantage of Intra-forwarding is quantified. Intra-forwarding, as defined in the HIPERLAN standard, is based on a hop-by-hop policy and link check procedures. It is shown how point-to-point packets and broadcast packets are forwarded. The three basic components of Intra-forwarding needed to build and update the Intra-forwarding database are described. The originality of this approach is the use of multipoint relays which enable better scalability. The correctness of the Intra-forwarding protocol is proved and its cost is evaluated.