Impact ionization-induced bistability in CMOS transistors at cryogenic temperatures for capacitorless memory applications.

Cryogenic operation of complementary metal oxide semiconductor (CMOS) silicon transistors is crucial for quantum information science, but it brings deviations from standard transistor operation. Here, we report on sharp current jumps and stable hysteretic loops in the drain current as a function of gate voltage V G for both n- and p-type commercial-foundry 180-nm-process CMOS transistors when operated at voltages exceeding 1.3 V at cryogenic temperatures. The physical mechanism responsible for the device bistability is impact ionization charging of the transistor body, which leads to effective back-gating of the inversion channel. This mechanism is verified by independent measurements of the body potential. The hysteretic loops, which have a >107 ratio of high to low drain current states at the same V G, can be used for a compact capacitorless single-transistor memory at cryogenic temperatures with long retention times.

Spread of cochlear excitation during stimulation with pulsed infrared radiation: inferior colliculus measurements.

Infrared neural stimulation (INS) has received considerable attention over the last few years. It provides an alternative method to artificially stimulate neurons without electrical current or the introduction of exogenous chromophores. One of the primary benefits of INS could be the improved spatial selectivity when compared with electrical stimulation. In the present study, we have evaluated the spatial selectivity of INS in the acutely damaged cochlea of guinea pigs and compared it to stimulation with acoustic tone pips in normal-hearing animals. The radiation was delivered via a 200 µm diameter optical fiber, which was inserted through a cochleostomy into the scala tympani of the basal cochlear turn. The stimulated section along the cochlear spiral ganglion was estimated from the neural responses recorded from the central nucleus of the inferior colliculus (ICC). ICC responses were recorded in response to cochlear INS using a multichannel penetrating electrode array. Spatial tuning curves (STCs) were constructed from the responses. For INS, approximately 55% of the activation profiles showed a single maximum, ∼22% had two maxima and ∼13% had multiple maxima. The remaining 10% of the profiles occurred at the limits of the electrode array and could not be classified. The majority of ICC STCs indicated that the spread of activation evoked by optical stimuli is comparable to that produced by acoustic tone pips.

Establishment of technical prerequisites for cell irradiation experiments with laser-accelerated electrons.

PURPOSE: In recent years, laser-based acceleration of charged particles has rapidly progressed and medical applications, e.g., in radiotherapy, might become feasible in the coming decade. Requirements are monoenergetic particle beams with long-term stable and reproducible properties as well as sufficient particle intensities and a controlled delivery of prescribed doses at the treatment site. Although conventional and laser-based particle accelerators will administer the same dose to the patient, their different time structures could result in different radiobiological properties. Therefore, the biological response to the ultrashort pulse durations and the resulting high peak dose rates of these particle beams have to be investigated. The technical prerequisites, i.e., a suitable cell irradiation setup and the precise dosimetric characterization of a laser-based particle accelerator, have to be realized in order to prepare systematic cell irradiation experiments. METHODS: The Jena titanium:sapphire laser system (JETI) was customized in preparation for cell irradiation experiments with laser-accelerated electrons. The delivered electron beam was optimized with regard to its spectrum, diameter, dose rate, and dose homogeneity. A custom-designed beam and dose monitoring system, consisting of a Roos ionization chamber, a Faraday cup, and EBT-1 dosimetry films, enables real-time monitoring of irradiation experiments and precise determination of the dose delivered to the cells. Finally, as proof-of-principle experiment cell samples were irradiated using this setup. RESULTS: Laser-accelerated electron beams, appropriate for in vitro radiobiological experiments, were generated with a laser shot frequency of 2.5 Hz and a pulse length of 80 fs. After laser acceleration in the helium gas jet, the electrons were filtered by a magnet, released from the vacuum target chamber, and propagated in air for a distance of 220 mm. Within this distance a lead collimator (aperture of 35 mm) was introduced, leading, along with the optimized setup, to a beam diameter of 35 mm, sufficient for the irradiation of common cell culture vessels. The corresponding maximum dose inhomogeneity over the beam spot was less than 10% for all irradiated samples. At cell position, the electrons posses a mean kinetic energy of 13.6 MeV, a bunch length of about 5 ps (FWHM), and a mean pulse dose of 1.6 mGy/bunch. Cross correlations show clear linear dependencies for the online recorded accumulated bunch charges, pulse doses, and pulse numbers on absolute doses determined with EBT-1 films. Hence, the established monitoring system is suitable for beam control and a dedicated dose delivery. Additionally, reasonable day-to-day stable and reproducible properties of the electron beam were achieved. CONCLUSIONS: Basic technical prerequisites for future cell irradiation experiments with ultrashort pulsed laser-accelerated electrons were established at the JETI laser system. The implemented online control system is suitable to compensate beam intensity fluctuations and the achieved accuracy of dose delivery to the cells is sufficient for radiobiological cell experiments. Hence, systematic in vitro cell irradiation experiments can be performed, being the first step toward clinical application of laser-accelerated particles. Further steps, including the transfer of the established methods to experiments on higher biological systems or to other laser-based particle accelerators, will be prepared.

Use of the pinna reflex as a test of hearing in mutant mice.

Although it is a gross measure, the pinna reflex test is easily administered and is, therefore, incorporated as a general screening tool in mutagenesis programs. Our recent application of this approach indicated that mutant mice lacking one of the small Maf proteins, in this case MafG, failed to exhibit a pinna reflex. In contrast, littermate controls, with the same mixed 129/CD1 background, and including both wild type and heterozygous mutant animals, passed the test. Because previous studies indicate that mafG is expressed in both cochlear and vestibular parts of the mouse inner ear, the source of this 'presumed deafness' was further assessed by making round window recordings to determine compound action potential thresholds. Auditory brainstem responses were also acquired to assess function along portions of the central auditory pathway. In all cases, responses in homozygous mutants (-/-) were comparable to those obtained from littermate controls, either wild type (+/+) or heterozygous mutants (+/-). Gross anatomy of the organ of Corti was also found to be similar in all three groups of mice. Hence, the lack of a pinna reflex must relate to nonauditory causes.

Anti- and pro-oxidative properties of PADMA 28, a Tibetan herbal formulation.

There is growing public interest in traditional medicine. PADMA 28, a multicompound herbal preparation derived from Tibetan medicine, has proven efficacy in some clinical trials and tests at the cellular level. We report here on studies of PADMA 28 at the molecular level. Extracts of PADMA 28 contain both reducing and metal ion-chelating substances. In this way, PADMA 28 acts as a powerful antioxidant or prooxidant, depending on its concentration and the reaction under study.

Prevalence of resistance to clarithromycin and its clinical impact on the efficacy of Helicobacter pylori eradication.

BACKGROUND: Triple therapy with a proton-pump inhibitor (PPI) in combination with metronidazole and clarithromycin is the method of choice for eradication of Helicobacter pylori. Failures have been primarily blamed on the development of resistance to clarithromycin. The present study investigated the prevalence and clinical significance of resistance to clarithromycin and metronidazole in determining therapeutic success of both triple therapy as a primary eradication method and high-dose dual therapy in non-responders. METHODS: On the basis of prior therapy, H. pylori-positive patients were assigned to one of two groups in the present prospective study. Group A (n = 93) included patients who had not undergone any prior eradication treatment, whereas group B (n = 15) consisted of patients who had received clarithromycin but in whom eradication had been unsuccessful. All patients underwent endoscopy with biopsy for bacterial culture and resistance studies. Patients in group A were treated with a 7-day regimen of pantoprazole (40 mg twice daily), metronidazole (500 mg twice daily), and clarithromycin (250 mg twice daily), whereas those in group B received omeprazole (40 mg three times a day) and amoxycillin (1000 mg three times a day ) for 14 days. Success of the eradication treatment was ascertained by means of the 13C urea breath test. RESULTS: In group A resistance to clarithromycin and metronidazole was identified in 3 patients (4.9%) and in 14 patients (22.9%), respectively. Eradication proved successful in 78 of 84 patients (92.6%) followed up. Two of the 3 patients with primary clarithromycin resistance and 1 of the 14 patients with metronidazole resistance did not respond to treatment. In group B isolated or combined resistance to clarithromycin was found in seven patients, whereas another four showed isolated resistance to metronidazole. Eradication proved successful in 10 of 13 controlled patients (76.9%) followed up, and only 2 patients reported severe side effects. CONCLUSION: Determination of antibiotic resistance before initiating therapy is not necessary, since primary resistance to clarithromycin is rare. The Italian triple therapy remains a highly effective primary therapeutic method. Further, routine determination of resistance in non-responders also seems to be superfluous because high-dose dual therapy is an effective and well-tolerated second-line therapy regardless of the patients' resistance status.

Perioperative management in thoracic surgery.

The quality of perioperative treatment for patients undergoing thoracic surgery is of the utmost importance for postoperative morbidity and mortality. Hence, it was the purpose of this study to examine various aspects of our own procedure. The clinical course following 812 successive thoracotomies in 792 patients over a period of 3 years was documented and analysed. The overall complication rate was found to be 19.7%, with a mortality of 3.8% over a 30-day period. Secretostasis, atelectasis and pneumonia were the most common complications. Owing to the predeposition of autologous blood, the percentage of patients requiring allogeneic blood transfusion was reduced from 27% to 9%. There was no evidence suggesting an increase in the complication rate or a longer stay in hospital. Perioperative antibiotic prophylaxis has reduced postoperative wound infection significantly. Similar reductions in the FEV1 are recorded following thoracic surgery, irrespective of the amount of lung tissue resected. This observation indicates that the remaining lung tissue is severely compromised throughout the postoperative period and that the surgical trauma alone is a major factor influencing postoperative pulmonary function for at least 2 weeks.

rhEPO treatment of postpartum anemia.

Postpartum hemorrhage is a continuing problem occurring in 5-10% of all deliveries. Due to recent problems with blood transfusion, heterologous blood is nowadays restricted to life-threatening indications. As a consequence the clinician is faced with many patients suffering from overt symptoms of anemia. We therefore investigated the effect of recombinant human erythropoietin (rhEPO) in combination with adequate iron supplementation as an alternative for blood transfusion in postpartum anemia. In a pilot study we could show that rhEPO can enhance the effect of endogenous erythropoietin on erythropoiesis. These data could be confirmed in a larger randomized trial. In another study we could show that rhEPO given s.c. is as effective as i.v. Measurement of the iron stores, however, demonstrated low values at the end of pregnancy indicating that iron is a limiting factor for erythropoiesis in postpartum anemia. In a next study i.v. iron combined with rhEPO showed a greater increase in Hb compared to i.v. iron alone. The chosen dose of i.v. iron, however, was too small as shown by the low ferritin levels. We concluded from these previous studies that rhEPO enhances endogenous erythropoiesis, but so far the effect was only slight (ca 1 g/dl within 14 days); all treated patients developed overt iron deficiency in terms of low ferritin levels despite oral and i.v. iron supplementation; no major side-effects were seen. A further study in healthy non pregnant volunteers demonstrated an effect on erythropoiesis lasting for 3-4 days after a single dose of 300 U/kg rhEPO.(ABSTRACT TRUNCATED AT 250 WORDS)

Recombinant human erythropoietin and parenteral iron in the treatment of pregnancy anemia: a pilot study.

Our aim was to correct severe iron deficiency anemia during pregnancy by using a combination therapy of recombinant human erythropoietin and parenteral iron. Eleven anemic pregnant women were treated once weekly until a hemoglobin value of 11.0 g/dl was reached. Red blood cell production was monitored by reticulocyte flow cytometry and hemoglobin increase. Iron status was assessed by serum ferritin values and transferrin saturation values. 8/11 patients showed an immediate response, noted by a continuous increase of reticulocytes, high fluorescent reticulocyte ratio and hemoglobin levels. Three patients who had lower serum ferritin values, low transferrin saturation and a lower reticulocyte count before treatment showed little response. The combination of rhEPO and parenteral iron is effective in stimulating erythropoiesis and in treating certain pregnancy anemias. This therapy could be an alternative for patients refusing blood transfusions or who are resistant to iron alone. Poor response to the treatment can be due to insufficient iron supplementation during therapy with rhEPO or due to factors that inhibit erythropoiesis during pregnancy, such as undetected infections.

Anti-Ata causing mild hemolytic disease of the newborn.

We report here a case of moderately severe hemolytic disease of the newborn (HDN) due to anti-Ata. The gravida 5 proposita was group A rr and previously was found to have anti-Ata and -D. At the 35-week mark of this pregnancy, her anti-Ata demonstrated a titer of 256, score 79. Fluid obtained by amniocentesis at 36 weeks showed an optical density at 450 nm of 0.08 (midzone). The baby was delivered at 38 weeks by cesarean section. The cord cells were group A rr with a 3+ direct antiglobulin test. The dichloromethane eluate of the infant's cells demonstrated anti-Ata specificity only. At birth, the infant's total bilirubin (TB) was 2.1 mg per dl and the hematocrit level (Hct) was 33.8 percent. Within 8 hours, the TB had risen to 3.8 mg per dl. Phototherapy was initiated at 7-1/2 hours and maintained for 40 hours. The infant's TB rose to a maximum level of 10.5 mg per dl 24 hours after phototherapy was discontinued. At discharge 4 days postpartum, the infant's TB had dropped to 9.2 mg per dl, and the Hct value was 38 percent. On a visit 7 days postpartum, the infant's TB level had fallen to 6.5 mg per dl and the hct value was 38 percent. Transfusions were not necessary.

Mechanism of alloxan-induced calcium release from rat liver mitochondria.

The objective of the present work was to investigate the mechanism of alloxan-induced Ca2+ release from rat liver mitochondria. Transport of Ca2+, oxidation and hydrolysis of mitochondrial pyridine nucleotides, changes in the mitochondrial membrane potential, and oxygen consumption by mitochondria were investigated. Alloxan does not inhibit the uptake of Ca2+ but stimulates the release of Ca2+ from liver mitochondria, which is accompanied by oxidation and hydrolysis of pyridine nucleotides. Oxidation of mitochondrial pyridine nucleotides by alloxan is not mediated by glutathione peroxidase and glutathione reductase and may occur largely nonenzymatically. Measurements of the mitochondrial membrane potential in combination with inhibitors of Ca2+ reuptake indicate that Ca2+ release takes place from intact liver mitochondria via a distinct pathway. Limited redox cycling of alloxan by mitochondria is indicated by measurements of the membrane potential and O2 consumption in the presence of cyanide. It is concluded that alloxan can cause Ca2+ release from intact rat liver mitochondria. Redox cycling of alloxan is not significantly involved in the Ca2+ release mechanism. Oxidation and hydrolysis of pyridine nucleotides, possibly in conjunction with oxidation of critical sulfhydryl groups, seem to be key events in the alloxan-induced Ca2+ release. Disturbance of cellular Ca2+ homeostasis may partly explain alloxan toxicity.

Growth hormone 3.6-h pulsatile secretion and feeding times have similar periods in rats.

In rats, lengths of cycles of growth hormone secretion and of cycles of feeding are 3,6-4.0 h. The two may be controlled by the same timing mechanism.

Hydroperoxides can modulate the redox state of pyridine nucleotides and the calcium balance in rat liver mitochondria.

When rats are fed a selenium-deficient diet, the glutathione peroxidase activity in liver mitochondria decreases within 5 weeks to 0-6% of that of control animals fed on a diet supplemented with 0.5 ppm of selenium as sodium selenite. Analysis of the temperature dependence of energy-linked Ca(2+) uptake by means of Arrhenius plots reveals two breaks (at around 11 degrees C and 24 degrees C) in mitochondria isolated from selenium-supplemented animals, whereas in selenium-deficient rats the break at 11 degrees C is absent. Ca(2+)-loaded mitochondria of selenium-supplemented rats-i.e., with active glutathione peroxidase in the matrix-lose Ca(2+) rapidly, with a concomitant oxidation of endogenous NAD(P)H, when exposed to t-butyl hydroperoxide or H(2)O(2). In contrast, in selenium deficiency, t-butyl hydroperoxide and H(2)O(2) induce neither a release of Ca(2+) nor an oxidation of NAD(P)H. The peroxide-induced oxidation of NAD(P)H is reversible in the presence of succinate when no Ca(2+) has been taken up. When Ca(2+) has previously been accumulated, however, the oxidation of NAD(P)H is irreversible. Enzymatic analysis of mitochondrial pyridine nucleotides reveals that the peroxide-induced oxidation of NAD(P)H in Ca(2+)-loaded mitochondria leads to a loss of NAD(+) and NADP(+). It is proposed that the redox state of mitochondrial pyridine nucleotides can be or is in part controlled by glutathione peroxidase and glutathione reductase and is a factor in the balance of Ca(2+) between mitochondria and medium.

"Dark-active" rat transformed into "light-active" rat by destruction of 24-hr clock: function of 24-hr clock and synchronizers.

In alternating 12-hr periods of light and dark the rat is active mainly in the dark. Its activity in the dark (beginning at 1800) depends exclusively on release of activity by the 24-hr clock. In the light (beginning at 0600) the 24-hr clock inhibits activity; the normal rat becomes totally inactive in the light except for activity resulting from external stimulation. After section of the connections between the optic chiasma and the hypothalamus, some rats become totally and permanently inactive in the dark. This sectioning destroys the 24-hr clock. After destruction of the clock removes inhibition of activity in the light period, the rat becomes active promptly at start of the light period--i.e., becomes a "light-active" animal. In the normal rat, activity becomes synchronized to start of the dark (by the electric clock at 1800), regardless of the amounts of activity. Destruction of the 24-hr clock eliminates the synchronizer at 1800. However, almost at once, activity, eating, and drinking are kept together by a second synchronizer, start of the light (by the electric clock at 0600). This may explain the ability of the rat to survive after destruction of the 24-hr clock.