Charge Storage and Reliability Characteristics of Nonvolatile Memory Capacitors with HfO2/Al2O3-Based Charge Trapping Layers

Flash memories are the preferred choice for data storage in portable gadgets. The charge trapping nonvolatile flash memories are the main contender to replace standard floating gate technology. In this work, we investigate metal/blocking oxide/high-k charge trapping layer/tunnel oxide/Si (MOHOS) structures from the viewpoint of their application as memory cells in charge trapping flash memories. Two different stacks, HfO₂/Al₂O₃ nanolaminates and Al-doped HfO₂, are used as the charge trapping layer, and SiO₂ (of different thickness) or Al₂O₃ is used as the tunneling oxide. The charge trapping and memory windows, and retention and endurance characteristics are studied to assess the charge storage ability of memory cells. The influence of post-deposition oxygen annealing on the memory characteristics is also studied. The results reveal that these characteristics are most strongly affected by post-deposition oxygen annealing and the type and thickness of tunneling oxide. The stacks before annealing and the 3.5 nm SiO₂ tunneling oxide have favorable charge trapping and retention properties, but their endurance is compromised because of the high electric field vulnerability. Rapid thermal annealing (RTA) in O₂ significantly increases the electron trapping (hence, the memory window) in the stacks; however, it deteriorates their retention properties, most likely due to the interfacial reaction between the tunneling oxide and the charge trapping layer. The O₂ annealing also enhances the high electric field susceptibility of the stacks, which results in better endurance. The results strongly imply that the origin of electron and hole traps is different—the hole traps are most likely related to HfO₂, while electron traps are related to Al₂O₃. These findings could serve as a useful guide for further optimization of MOHOS structures as memory cells in NVM.     

Novel Mutations in the DYNC1H1 Tail Domain Refine the Genetic and Clinical Spectrum of Dyneinopathies

The heavy chain 1 of cytoplasmic dynein (DYNC1H1) is responsible for movement of the motor complex along microtubules and recruitment of dynein components. Mutations in DYNC1H1 are associated with spinal muscular atrophy (SMA), hereditary motor and sensory neuropathy (HMSN), cortical malformations, or a combination of these. Combining linkage analysis and whole‐exome sequencing, we identified a novel dominant defect in the DYNC1H1 tail domain (c.1792C>T, p.Arg598Cys) causing axonal HMSN. Mutation analysis of the tail region in 355 patients identified a de novo mutation (c.791G>T, p.Arg264Leu) in an isolated SMA patient. Her phenotype was more severe than previously described, characterized by multiple congenital contractures and delayed motor milestones, without brain malformations. The mutations in DYNC1H1 increase the interaction with its adaptor BICD2. This relates to previous studies on BICD2 mutations causing a highly similar phenotype. Our findings broaden the genetic heterogeneity and refine the clinical spectrum of DYNC1H1, and have implications for molecular diagnostics of motor neuron diseases.     

Post-traumatic onset of secondary progression of gynecomastia

Gynecomastia is a benign enlargement of the male breast which can be a source of significant anxiety and embarrassment for the patients. A great variety of etiologic factors have been investigated and discussed. However, only few studies in the literature have accentuated on the possible role of the chronic tissue trauma for the de novo development of gynecomastia. Nevertheless, the exact mechanism of its onset in such cases remains unclear. The authors report on a case of posttraumatic unilateral progression of preexisting stable gynecomastia. The possible role of a single episode of acute trauma as a trigger mechanism for the new onset of the breast enlargement is discussed.Level of Evidence: Level V, risk/prognostic study.     

Age-related changes of the dentate nuclei in normal adults as revealed by 3D fast low angle shot (FLASH) echo sequence magnetic resonance imaging

Abstract. The aim of the present study was to investigate age-related changes in iron-deposition in dentate nuclei using iron-induced susceptibility effects in magnetic resonance imaging. MR images from 74 healthy subjects (age range 20–68 years) were obtained using a three-dimensional (3D) T1-weighted fast low angle shot (FLASH) echo sequence. Signal intensities of the dentate nuclei and cerebellar white matter were bilaterally measured independently by three blinded investigators. The signal intensities of dentate nuclei were intraindividually normalised to the corresponding signal intensities of the cerebellar white matter of corresponding slices. Mean normalised signal intensities were correlated with age and compared between different age decades and gender. Intraclass correlation coefficients were high (dentate nuclei: 0.98, cerebellar white matter: 0.75) indicating sufficient interrater reliabilities for the determination of signal intensities. Bland-Altman analysis confirmed this finding. The normalised mean signal intensity of the dentate nuclei correlated inversely with age (r = –0.462, p < 0.0001). Comparison of age decades revealed that significant decreases took place between the third and fourth decade and to a lesser degree between the fourth and fifth decade. Moreover, variability of normalised mean signal intensities of the dentate nuclei increased significantly with age (r = 0.964, p = 0.008). There were no differences of the normalised mean signal intensities between genders. The present study revealed an agedependent decrease of signal intensities in dentate nuclei most likely reflecting an age-dependent increase in dentate iron concentration. These age-dependent changes have to be taken into account in interpretation of disease related MR changes of cerebellar nuclei in patients with degenerative or acquired cerebellar ataxia.     

Effect of MG132 on proteasome activity and prooxidant/antioxidant status of rat liver subjected to ischemia/reperfusion injury.

Aim: Previous studies have shown that proteasome inhibitors exerted protective effects against ischemia/reperfusion injury (IRI) of brain, heart, kidney and intestine. The aim of the present study was to investigate: (i) whether the proteasome inhibitor MG132 protects rat liver against IRI; and (ii) whether MG132 modulates prooxidant/antioxidant status of rat liver subjected to warm IRI. Methods: The left lateral and medial lobes (approximately 70% of the total liver volume) of livers of male Wistar rats were subjected to 30-min ischemia followed by 60-min reperfusion. Lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels were measured in the plasma. Proteasome chymotryptic-like (ChT-L) activity, levels of thiobarbituric acid-reactive substances (TBARS), protein carbonyls (PC) and glutathione (GSH), as well as superoxidase dismutase (SOD), catalase (CAT), glutathionine peroxidase and glutathionine reductase activities were measured in liver fractions. Results: Thirty-min ischemia followed by 60-min reperfusion increased liver TBARS and PC, CAT and SOD activities, but decreased GSH level. Ischemia/reperfusion-induced oxidative stress was exacerbated in mitochondria, indicating that these organelles are the preferential target of IRI. Plasma LDH and AST levels were decreased by MG132 during both ischemia and reperfusion, while ALT values were decreased only after 30 min of reperfusion. MG132 did not significantly affect liver TBARS and GSH levels, but it increased PC and decreased ChT-L activity; the activities of CAT and SOD were also decreased. Conclusions: MG132 exerts a protective effect during the early phase of reperfusion and it modulates prooxidant/antioxidant status of rat liver subjected to warm IRI.     

Irritable Bowel Syndrome Patients’ Ideal Expectations and Recent Experiences with Healthcare Providers: A National Survey

The purpose of this paper is to identify patients’ ideal expectations from their healthcare providers. The IBS-Patient Education Questionnaire was developed using focus groups, and was administered to a national sample of IBS patients. Frequencies of item endorsements were obtained. Subgroup analysis was done comparing the responses for patients’ ideal expectations of their healthcare providers vs. their experiences with their last provider. Among the 1,242 patients who completed the survey, the mean age was 39.3 years, educational attainment 15 years, 85% female, IBS duration 6.9 years, 1,028 (83%) had seen a physician for IBS in the past, and 92.6% have used the Internet to obtain health information. Among the subjects who have seen a physician for IBS, the most desired qualities of providers were to give comprehensive information (96%), to refer to a source for additional information (95.8%), to answer questions (95.9%), to listen (94.4%), to provide information about IBS studies and medications (94%), and to provide support (88.6%) and hope (82.1%). Importantly, patients’ prior experiences with their last healthcare provider differed from their ideal expectations: “provide information” (38.3%); answer questions during the visit (68%), “to listen” (63.8%), and support (47.1%). Patients’ ideal expectations from healthcare providers (what patients ideally would like to experience) relate to obtaining information and relationship needs of receiving support and hope. Notably, their prior experiences with recent healthcare providers (what patients perceived actually occurred) were different from their ideal expectations. A better understanding of different types of expectations is necessary in order to construct an effective therapeutic relationship, which is critical for the management of IBS. Practice implications: Practice guidelines for IBS should emphasize a better understanding of a patient’s expectations and the therapeutic value of patient–provider communication.