Experimental study of single-electron phenomena in silicon nanocrystal memories.

In this paper we present experimental evidence for single-electron phenomena in solid-state memories based on silicon nanocrystals as storage elements. The stepwise evolution of the channel current of a written memory cell biased in the subthreshold regime is monitored by means of a purposely designed low noise acquisition system with a bandwidth of 1 kHz. Each channel current step-up is ascribed to a single-electron emission from the silicon nanocrystal to the silicon substrate and each current step-down is ascribed to a single-electron capture from the silicon substrate into the silicon nanocrystal. The effect of the measurement system bandwidth on the detection of single-electron events is discussed and a procedure for extracting the threshold voltage shift associated to these events is proposed. It is shown that single-electron charging and discharging events in a memory cell with an area of 4.5 x 10(-10) cm2 can cause threshold voltage shift at room-temperature of the order of several millivolts. Qualitative explanation for the observed threshold voltage shift distribution is given.

Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide.

BACKGROUND: Two reports from China have suggested that arsenic trioxide can induce complete remissions in patients with acute promyelocytic leukemia (APL). We evaluated this drug in patients with APL in an attempt to elucidate its mechanism of action. METHODS: Twelve patients with APL who had relapsed after extensive prior therapy were treated with arsenic trioxide at doses ranging from 0.06 to 0.2 mg per kilogram of body weight per day until visible leukemic cells were eliminated from the bone marrow. Bone marrow mononuclear cells were serially monitored by flow cytometry for immunophenotype, fluorescence in situ hybridization, reverse-transcription-polymerase-chain-reaction (RT-PCR) assay for PML-RAR-alpha fusion transcripts, and Western blot analysis for expression of the apoptosis-associated proteins caspases 1, 2, and 3. RESULTS: Of the 12 patients studied, 11 achieved complete remission after treatment that lasted from 12 to 39 days (range of cumulative doses, 160 to 495 mg). Adverse effects were relatively mild and included rash, lightheadedness, fatigue, and musculoskeletal pain. Cells that expressed both CD11b and CD33 (antigens characteristic of mature and immature cells, respectively), and which were found by fluorescence in situ hybridization to carry the t(15;17) translocation, increased progressively in number during treatment and persisted in the early phase of complete remission. Eight of 11 patients who initially tested positive for the PML-RAR-alpha fusion transcript by the RT-PCR assay later tested negative; 3 other patients, who persistently tested positive, relapsed early. Arsenic trioxide induced the expression of the proenzymes of caspase 2 and caspase 3 and activation of both caspase 1 and caspase 3. CONCLUSIONS: Low doses of arsenic trioxide can induce complete remissions in patients with APL who have relapsed. The clinical response is associated with incomplete cytodifferentiation and the induction of apoptosis with caspase activation in leukemic cells.

A hardware implementation of a biological neural system for target localization.

The optical axes in an array of photoreceptors in the eyes of mantis shrimps have a particular skewing pattern that provides the animal with a monocular distance evaluation. A hardware (HW) device for target recognition was built based on the mathematical model of the biological visual system. The pattern of inputs was simulated by an array of glass fibers connected to phototransistors. In the biological system inputs are picked up by an integrating nerve fiber, in the HW model by an RC network with compartmental threshold devices. The network state is read by a host PC through an array of threshold comparators. The output consists of pulse patterns that can be generated either by a simulation program or in the HW itself. The system can be used as a selective distance/motion detector and can be employed in several applications involving target detection or obstacle avoidance.

Using coherent pulse width and edge modulations in artificial neural systems.

This paper describes an existing silicon implementation of an artificial neural system based on coherent pulse width and edge modulation techniques. A chip set with different neural functions has been conceived, manufactured and tested. Neural circuits have been optimized for lowest computation energy and highest reconfigurability. The main device is a 32 x 32 synaptic array consuming 10 mW of power at 140 MCPS. Synapsis size is about 7.200 microns 2 using a standard 1.5 microns CMOS technology. The problem of interfacing robotic sensors and actuators is addressed: voltage, current and resistance-based sensors are considered for the measurement of physical quantities such as temperature, pressure, strain, etc. Low resolution imaging sensors for robotic vision are also considered.

Development of a questionnaire for detecting potential adverse drug reactions.

OBJECTIVE: To develop a comprehensive list of symptoms categorized by body system as part of a questionnaire for detecting potential adverse drug reactions. DATA SOURCES: A preliminary list of symptoms in lay terminology was extracted from the "Side Effects" section of all drug monographs contained in the United States Pharmacopeia Dispensing Information (USP DI) computerized database (Volume II, Advice for the Patient) using natural language processing software. The list was sorted alphabetically and duplicate terms were eliminated. Symptoms were then categorized by body system or anatomic region. A preferred term for each symptom was selected when multiple synonyms and related words were listed. Finally, all of the symptom terms were incorporated into a thesaurus from which the questionnaire was derived. RESULTS: The questionnaire will be used as part of a computer-assisted interview, developed to solicit information from patients regarding their medication regimens and to systematically query them regarding the presence of salient symptoms or complaints. The computer system will eventually interface with the USP DI database to identify drugs from a patient's regimen that may be associated with adverse symptoms. The symptom thesaurus will provide the link to the USP DI database. Preliminary experience with the questionnaire in a limited number of patients has been encouraging. CONCLUSIONS: The questionnaire can assist clinicians in identifying drug-related symptoms including unreported adverse clinical effects of newly marketed or investigational therapeutic agents. When the questionnaire is computerized and linked to a comprehensive database, it can be more widely used to alert healthcare providers of potential adverse drug reactions that may otherwise go undetected.

Evaluation of two over-the-counter natural thyroid hormone preparations in human volunteers.

OBJECTIVE: To determine the pharmacologic activity of over-the-counter (OTC) thyroid preparations. DESIGN: In vitro analysis and a prospective, crossover study in vivo. SETTING: Tertiary care center. PARTICIPANTS: Two healthy adult volunteers. INTERVENTION: Three OTC preparations (Thyrotrophin PMG [bovine thyroid PMG extract], Thyro Forte [thyroid lymphogland concentrate with synergistic complex], and Thyro Complex [thyroid lyophilized gland concentrate with synergistic complex]) were analyzed in vitro. Volunteers were administered two times the manufacturer's maximum recommended daily dose of either Thyrotrophin PMG or Thyro Forte for one week, washed out for four to five weeks, and crossed over to receive the opposite tablet preparation for an additional week. MAIN OUTCOME MEASURES: The triiodothyronine (T3) and thyroxine (T4) contents of OTC preparations were measured by HPLC. Vital signs, serum total and free T4, total T3, thyroid stimulating hormone, thyroxine binding globulin, thyroglobulin, and general chemistry tests (including glucose and cholesterol) were monitored before, during, and between administration of the products. RESULTS: HPLC analysis of the three OTC preparations showed no T4 but did show possible T3 in two of these products. We found no definite clinical or laboratory evidence of thyroid hormone excess with either product. CONCLUSIONS: Healthcare professionals should advise against the use of these scientifically unsound and relatively expensive OTC thyroid preparations, of which the therapeutic efficacy is unknown.

Transdermally administered fentanyl for pain management.

The physicochemical properties, pharmacology, pharmacokinetics, serum concentrations and clinical effects, adverse effects and contraindications, and dosage of transdermally administered fentanyl are described, and clinical studies evaluating the use of a transdermal fentanyl system in the treatment of postoperative pain and chronic cancer-associated pain are reviewed. After application of a transdermal system, fentanyl is absorbed into the skin beneath the patch, where a depot forms in the upper skin layers. Plasma fentanyl concentrations are barely detectable for about two hours after patch placement. Eight to 12 hours after patch placement, concentrations approximate those achieved with equivalent i.v. doses of fentanyl. Some studies comparing transdermally administered fentanyl with placebo in postoperative patients showed that the patients who received fentanyl required fewer supplementary analgesics and reported less pain than the patients who received placebo. However, the overall efficacy and safety of the transdermal fentanyl system for the treatment of postoperative pain have not been adequately evaluated. Studies of cancer patients showed that transdermally administered fentanyl appears to be effective in the management of chronic, cancer-related pain. Dermatological reactions to the fentanyl patch are generally transient and mild. Other adverse effects are those that are commonly associated with narcotic analgesics. The 25-micrograms/hr patch should be used for initial treatment in patients not previously treated with narcotics. The dosage may be gradually increased until effective analgesia is obtained. Although experience with the product is limited, transdermally administered fentanyl appears to be effective for the long-term management of cancer-related pain.

Pulse-stream VLSI neural networks mixing analog and digital techniques.

The pulse-stream technique, which represents neural states as sequences of pulses, is reviewed. Several general issues are raised, and generic methods appraised, for pulsed encoding, arithmetic, and intercommunication schemes. Two contrasting synapse designs are presented and compared. The first is based on a fully analog computational form in which the only digital component is the signaling mechanism itself-asynchronous, pulse-rate encoded digital voltage pulses. In this circuit, multiplication occurs in the voltage/current domain. The second design uses more conventional digital memory for weight storage, with synapse circuits based on pulse stretching. Integrated circuits implementing up to 15000 analog, fully programmable synaptic connections are described. A demonstrator project is described in which a small robot localization network is implemented using asynchronous, analog, pulse-stream devices.

[Pseudoachondrodysplasia (pseudoachondroplastic spondyloepiphyseal dysplasia). Description of 2 non-familial cases]. / Pseudoacondroplasia (displasia spondiloepifisaria pseudoacondroplastica). Descrizione di due casi non famigliari.

Two non familial cases of pseudoachondroplasia are reported. The patients, observed at 4 years and 6 months and 5 years respectively, show short-limb dwarfism with disproportionated long trunk and with normal head and face. Flattening of vertebral bodies with biconvex deformity and short tubular bones with irregular epiphyses and metaphyses are the major radiographic features. In these patients to state the type of genetic transmission is very arduous, as the genetic heterogeneity of the pseudoachondroplasia.