Nano-scale charge trapping memory based on two-dimensional conjugated microporous polymer.

There is a growing interest in new semiconductor nanostructures for future high-density high-performance flexible electronic devices. Two-dimensional conjugated microporous polymers (2D-CMPs) are promising candidates because of their inherent optoelectronic properties. Here, we are reporting a novel donor-acceptor type 2D-CMP based on Pyrene and Isoindigo (PI) for a potential nano-scale charge-trapping memory application. We exfoliated the PI polymer into ~ 2.5 nm thick nanoparticles (NPs) and fabricated a Metal-Insulator-Semiconductor (MIS) device with PI-NPs embedded in the insulator. Conductive AFM (cAFM) is used to examine the confinement mechanism as well as the local charge injection process, where ultrathin high-κ alumina supplied the energy barrier for confining the charge carrier transport. We have achieved a reproducible on-and-off state and a wide memory window (ΔV) of 1.5 V at a relatively small reading current. The device displays a low operation voltage (V < 1 V), with good retention (104 s), and endurance (103 cycles). Furthermore, a theoretical analysis is developed to affirm the measured charge carriers' transport and entrapment mechanisms through and within the fabricated MIS structures. The PI-NPs act as a nanoscale floating gate in the MIS-based memory with deep trapping sites for the charged carriers. Moreover, our results demonstrate that the synthesized 2D-CMP can be promising for future low-power high-density memory applications.

A Rational Design of Isoindigo-Based Conjugated Microporous n-Type Semiconductors for High Electron Mobility and Conductivity.

The development of n-type organic semiconductors has evolved significantly slower in comparison to that of p-type organic semiconductors mainly due to the lack of electron-deficient building blocks with stability and processability. However, to realize a variety of organic optoelectronic devices, high-performance n-type polymer semiconductors are essential. Herein, conjugated microporous polymers (CMPs) comprising isoindigo acceptor units linked to benzene or pyrene donor units (BI and PI) showing n-type semiconducting behavior are reported. In addition, considering the challenges of deposition of a continuous and homogeneous thin film of CMPs for accurate Hall measurements, a plasma-assisted fabrication technique is developed to yield uniform thin films. The fully conjugated 2D networks in PI- and BI-CMP films display high electron mobility of 6.6 and 3.5 cm2 V-1 s-1 , respectively. The higher carrier concentration in PI results in high conductivity (5.3 mS cm-1 ). Both experimental and computational studies are adequately combined to investigate structure-property relations for this intriguing class of materials in the context of organic electronics.

Mentoring in Times of Crisis and Beyond.

During the global crisis triggered by the COVID-19 pandemic, university programs, meetings, and conferences have moved to virtual settings, with consequent erosion of mentorship opportunities for students and early-career professionals. This calls for mentorship platforms that are adapted to the new landscape in order to bring about a positive change. Our Viewpoint Article shares the perspective of the Transformative Education program and Mentorship Talks initiative at the American University of Beirut in Lebanon, with the aim of providing insights that could stimulate other mentorship platforms.

Metallated Isoindigo-Porphyrin Covalent Organic Framework Photocatalyst with a Narrow Band Gap for Efficient CO2 Conversion.

Photocatalytic CO2 reduction into formate (HCOO-) has been widely studied with semiconductor and molecule-based systems, but it is rarely investigated with covalent organic frameworks (COFs). Herein, we report a novel donor-acceptor COF named Co-PI-COF composed of isoindigo and metallated porphyrin subunits that exhibits high catalytic efficiency (∼50 µmol formate g-1 h-1) at low-power visible-light irradiation and in the absence of rare metal cocatalysts. Density functional theory calculations and experimental diffuse-reflectance measurements are used to explain the origin of catalytic efficiency and the particularly low band gap (0.56 eV) in this material. The mechanism of photocatalysis is also studied experimentally and is found to involve electron transfer from the sacrificial agent to the excited Co-PI-COF. The observed high-efficiency conversion could be ascribed to the enhanced CO2 adsorption on the coordinatively unsaturated cobalt centers, the narrow band gap, and the efficient transfer of the charge originating from the postsynthetic metallation. It is anticipated that this study will pave the way toward the design of new simple and efficient catalysts for photocatalytic CO2 reduction into useful products.

Columnar Mesomorphism of Board-Shaped Perylene, Diketopyrrolopyrrole, Isoindigo, Indigo, and Quinoxalino-Phenanthrophenazine Dyes.

The properties of organic dyes depend as much on their intermolecular interactions as on their molecular structure. While it is generally predictable what supramolecular structure would be ideal for a specific application, the generation of specific supramolecular structures by molecular design and suitable processing methods remains to be a challenge. A versatile approach to different supramolecular structures has been the application of mesomorphism in conjunction with alignment techniques and self-assembly at interfaces. Reviewed here is the columnar mesomorphism of board-shaped dyes perylene, indigo, isoindigo, diketopyrrolopyrrole, and quinoxalinophenanthrophenazine. They generate a larger number of different supramolecular structures than conventional disc-shaped (discotic) mesogens because of their non-circular shape and directional intermolecular interactions. The mesomorphism of all but the perylene derivatives is systematically and comprehensively covered for the first time.

Post-mTBI Pain Interference in a U.S. Military Population: A Chronic Effects of Neurotrauma Consortium Study.

INTRODUCTION: Chronic pain is a significant problem for service members and veterans with mild traumatic brain injury (mTBI). While the root cause of pain is not clearly understood, comorbidities may contribute to how their pain disrupts their functional status, a construct termed "pain interference." The purpose of this study is to examine the associations between mTBI, other comorbidities, and pain interference. MATERIALS AND METHODS: The sample comprised participants with mTBI(s) from The Chronic Effects of Neurotrauma Consortium multicenter observational study. Potential concussive events were identified using a modified Ohio State University traumatic brain injury (TBI) Identification interview and then further with a structured interview. Pain interference was measured with the TBI quality-of-life pain interference score, which was categorized into insignificant, moderate, and high pain interference. Comorbidities of interest included anxiety, depression, post-traumatic stress disorder, insomnia, and arthritis. Multivariable relationships were analyzed using logistic regression. RESULTS: The analysis sample included 346 participants with mTBI(s). In adjusted analysis, those with high pain interference were more likely to have history of ≥ 3 TBIs (odds ratio (OR) 3.1, 95% confidence interval [CI] 1.4, 6.9) and to have clinical levels of post-traumatic stress disorder (OR 5.4, 95% CI 1.9, 15.7), depression (OR 2.5, 95% CI, 1.0, 6.1), anxiety (OR 4.9, 95% CI, 2.0, 11.7), and sleep disturbances (OR 6.1, 95% CI 2.0, 19.0) versus those with insignificant pain interference. CONCLUSION: These results identify clinical features of veterans and service members with mTBI(s) who are at highest risk for pain-related disability. These findings also demonstrate the need to consider mental health and sleep problems in their pain evaluation and treatment approach.

Elliptical metallic rings-shaped fractal metamaterial absorber in the visible regime.

Achieving the broadband response of metamaterial absorbers has been quite challenging due to the inherent bandwidth limitations. Herein, the investigation was made of a unique kind of visible light metamaterial absorber comprising elliptical rings-shaped fractal metasurface using tungsten metal. It was found that the proposed absorber exhibits average absorption of over 90% in the visible wavelength span of 400-750 nm. The features of perfect absorption could be observed because of the localized surface plasmon resonance that causes impedance matching. Moreover, in the context of optoelectronic applications, the absorber yields absorbance up to ~ 70% even with the incidence obliquity in the range of 0°-60° for transverse electric polarization. The theory of multiple reflections was employed to further verify the performance of the absorber. The obtained theoretical results were found to be in close agreement with the simulation results. In order to optimize the results, the performance was analyzed in terms of the figure of merit and operating bandwidth. Significant amount of absorption in the entire visible span, wide-angle stability, and utilization of low-cost metal make the proposed absorber suitable in varieties of photonics applications, in particular photovoltaics, thermal emitters and sensors.

Perception, attitude, practice and barriers towards medical research among undergraduate students.

BACKGROUND: Early exposure to medical research, specifically at the undergraduate level, contributes in building a solid medical education for students. In 2014, the Medical Research Volunteer Program (MRVP) was established at the American University of Beirut (AUB). This program provides undergraduate students with the opportunity to be involved in ongoing medical research projects, on a voluntary basis. Little is known about undergraduates' outlook on medical research and the challenges they face. The aim of this study was to assess, among AUB undergraduate students, the perception, attitude, practice and barriers towards medical research, as well as to identify factors affecting them, such as background characteristics and research involvement. METHODS: A cross sectional study was carried out at AUB, where undergraduate students enrolled in specific chosen classes were surveyed in spring 2019 via paper based questionnaires. Close-ended questions assessed students' attitude, perception, practice and barriers towards medical research using a 5-point likert scale. Moreover, demographic characteristics and research involvement information were collected. RESULTS: Five hundred and twenty three students were surveyed. About half of the students were premedical students (51.5%), and only 43.6% of them were aware of the medical research program at their university. The average attitude, perception, practice and barriers scores were found to be 3.58, 4.35, 3.58 and 2.60, respectively (on a scale from 1 to 5). Students found the lack of mentoring and guidance to be the main barrier in conducting medical research. CONCLUSION: Our findings reveal that students express interest towards medical research and recognize its importance. A medical research program at the undergraduate level is indispensable in guiding students in their future career endeavors. Therefore, research programs should be constantly monitored to assure a research-oriented environment within institutions.

Percutaneous coronary intervention for left main stem disease: Impact of diabetes mellitus on mortality.

OBJECTIVES: We assessed the impact of diabetes mellitus (DM) on mortality after percutaneous coronary intervention (PCI) for left main stem (LMS) disease. Second, we compared mortality outcomes between non-insulin treated (NITDM) and insulin treated diabetes (ITDM) in different clinical settings. BACKGROUND: There is a paucity of "real world" outcomes data in diabetic patients undergoing LMS PCI. METHODS: We undertook a retrospective analysis of consecutive patients undergoing unprotected LMS PCI at 2 high volume tertiary centers. Diabetic status and clinical setting for PCI were recorded. The primary outcome measure was all-cause 30-day and long-term mortality (up to 36 months) post index PCI. RESULTS: Between 2003 and 2017, 2,675 patients undergoing index LMS PCI were analyzed. Of those, 77.1% were non-DM, 15.8% NITDM, and 7.1% ITDM. Overall, DM status was not associated with higher 30-day mortality (OR 1.39, 95% CI 0.89-2.16, p = .15). During a median follow-up of 36 months, there was a borderline statistical association of DM with long-term mortality in all PCI settings (HR 1.31, 95% CI 1.00-1.71, p = .05). Compared to non-DM, ITDM but not NITDM was associated with short- and long-term mortality in all clinical presentations. CONCLUSIONS: Overall, DM did not impact on 30-day mortality and had only a borderline statistical association with long-term mortality. It did not have an influence on mortality in non-emergency LMS PCI. The impact of DM on mortality outcomes following LMS PCI was only significant in the insulin treated patients.

Autophagic and endo-lysosomal dysfunction in neurodegenerative disease.

Due to their post-mitotic state, metabolic demands and often large polarised morphology, the function and survival of neurons is dependent on an efficient cellular waste clearance system both for generation of materials for metabolic processes and removal of toxic components. It is not surprising therefore that deficits in protein clearance can tip the balance between neuronal health and death. Here we discuss how autophagy and lysosome-mediated degradation pathways are disrupted in several neurological disorders. Both genetic and cell biological evidence show the diversity and complexity of vesicular clearance dysregulation in cells, and together may ultimately suggest a unified mechanism for neuronal demise in degenerative conditions. Causative and risk-associated mutations in Alzheimer's disease, Frontotemporal Dementia, Amyotrophic Lateral Sclerosis, Parkinson's disease, Huntington's disease and others have given the field a unique mechanistic insight into protein clearance processes in neurons. Through their broad implication in neurodegenerative diseases, molecules involved in these genetic pathways, in particular those involved in autophagy, are emerging as appealing therapeutic targets for intervention in neurodegeneration.

Alzheimer's Disease Associated Genes Ankyrin and Tau Cause Shortened Lifespan and Memory Loss in Drosophila.

Alzheimer's disease (AD) is the most common form of dementia and is characterized by intracellular neurofibrillary tangles of hyperphosphorylated Tau, including the 0N4R isoform and accumulation of extracellular amyloid beta (Aß) plaques. However, less than 5% of AD cases are familial, with many additional risk factors contributing to AD including aging, lifestyle, the environment and epigenetics. Recent epigenome-wide association studies (EWAS) of AD have identified a number of loci that are differentially methylated in the AD cortex. Indeed, hypermethylation and reduced expression of the Ankyrin 1 (ANK1) gene in AD has been reported in the cortex in numerous different post-mortem brain cohorts. Little is known about the normal function of ANK1 in the healthy brain, nor the role it may play in AD. We have generated Drosophila models to allow us to functionally characterize Drosophila Ank2, the ortholog of human ANK1 and to determine its interaction with human Tau and Aß. We show expression of human Tau 0N4R or the oligomerizing Aß 42 amino acid peptide caused shortened lifespan, degeneration, disrupted movement, memory loss, and decreased excitability of memory neurons with co-expression tending to make the pathology worse. We find that Drosophila with reduced neuronal Ank2 expression have shortened lifespan, reduced locomotion, reduced memory and reduced neuronal excitability similar to flies overexpressing either human Tau 0N4R or Aß42. Therefore, we show that the mis-expression of Ank2 can drive disease relevant processes and phenocopy some features of AD. Therefore, we propose targeting human ANK1 may have therapeutic potential. This represents the first study to characterize an AD-relevant gene nominated from EWAS.

Self-Assembly of Board-Shaped Diketopyrrolopyrrole and Isoindigo Mesogens into Columnar π-π Stacks.

Diketopyrrolopyrrole and isoindigo are commercially important dyes that have recently found broad application as electron acceptor and light-absorbing groups in organic semiconductors. Their self-assembly into specific supramolecular structures to control optoelectronic properties has been hampered by limited options for substitution and their high propensity for crystallization. Reported here is a molecular design that directs self-assembly into previously elusive columnar mesophases of π-π stacking cores. Although attachment of bis(trisoctyloxyphenyl)-1,3,5-triazine groups to both ends of diketopyrrolopyrrole-thiophene and isoindigo cores generated mesomorphic dyes of similar overall shapes and dimensions, distinct differences in their mesomorphism and optoelectronic properties were observed.

Prevalence and Predictors of Home Use of Glucometers in Diabetic Patients.

BACKGROUND: Self-monitoring of blood glucose (SMBG) is a critical component of diabetes care. However, it has been shown that use of glucometers in developing countries such as Pakistan is limited. The aim of this study was to determine the frequency of glucometer usage in the urban diabetic population of Karachi and to identify variables that influenced the likelihood of practice of SMBG. METHODS: A cross-sectional study was conducted among 567 adult diabetic patients selected at random from the out-patient departments of multiple healthcare institutions in Karachi categorized into two settings; Government and Private. Non-diabetics, patients having gestational diabetes, diabetes insipidus and Cushing's syndrome and terminally ill patients were excluded. Pearson Chi-square and Mann-Whitney U test were applied as the primary statistical method. RESULTS: Prevalence of home glucometer usage was 59% (n= 331). High socioeconomic status (p < 0.001), receiving care from private institutions (p < 0.001), higher education (p < 0.001), a family history of diabetes (p =0.001), awareness regarding diabetes (p < 0.001), having diabetes for > five years (p <0.001), and managing diabetes via pharmacological interventions (p <0.001) (versus diet and exercise) were significant positive predictors of glucometer usage. CONCLUSIONS: Our study demonstrates the increasing trend in use of SMBG. Lack of awareness and cost of glucometers were reported to be the main reasons for not practicing SMBG. Given these factors are easily modifiable, government subsidized initiatives and awareness programs can result in a successful public health strategy to promote SMBG.

Rate of active Helicobacter pylori infection among symptomatic patients of Pakistan.

Only few epidemiological studies have examined the rate of active H. pylori infection in the symptomatic population in Pakistan. This retrospective study presents the laboratory data collected during the past 13 years (2002 to 2015) from 2315 symptomatic patients referred to the BreathMAT Lab, Nuclear Medicine, Oncology and Radiotherapy Institute, Islamabad for the diagnosis of active H. pylori infection using the 13C Urea Breath Test. Rate of infection and its association with gender and age were evaluated. The overall rate of active H. pylori infection was 49.5% and there was no association of this rate of infection with gender. An increase in rate of infection was observed with increasing age with significant difference (p < 0.05). The patients that tested negative for this infection might be having symptoms due to stress and indiscriminate use of non-steroidal antiinflammatory drugs (NSAIDs) in this community. The fact that half of the symptomatic patients were negative needs to be highlighted and further suggests that symptomatic patients should be tested by the 13C UBT before prescribing antibiotic treatment for H. pylori eradication. In addition, there is a need to educate this community about the harmful and side effects of self medication and overuse of NSAIDs.

Medical Research Volunteer Program (MRVP): innovative program promoting undergraduate research in the medical field.

BACKGROUND: Most educational institutions lack a structured system that provides undergraduate students with research exposure in the medical field. The objective of this paper is to describe the structure of the Medical Research Volunteer Program (MRVP) which was established at the American University of Beirut, Lebanon, as well as to assess the success of the program. METHODS: The MRVP is a program that targets undergraduate students interested in becoming involved in the medical research field early on in their academic career. It provides students with an active experience and the opportunity to learn from and support physicians, clinical researchers, basic science researchers and other health professionals. Through this program, students are assigned to researchers and become part of a research team where they observe and aid on a volunteer basis. This paper presents the MRVP's four major pillars: the students, the faculty members, the MRVP committee, and the online portal. Moreover, details of the MRVP process are provided. The success of the program was assessed by carrying out analyses using information gathered from the MRVP participants (both students and faculty). Satisfaction with the program was assessed using a set of questions rated on a Likert scale, ranging from 1 (lowest satisfaction) to 5 (highest satisfaction). RESULTS: A total of 211 students applied to the program with a total of 164 matches being completed. Since the beginning of the program, three students have each co-authored a publication in peer-reviewed journals with their respective faculty members. The majority of the students rated the program positively. Of the total number of students who completed the program period, 35.1 % rated the effectiveness of the program with a 5, 54.8 % rated 4, and 8.6 % rated 3. A small number of students gave lower ratings of 2 and 1 (1.1 % and 0.4 %, respectively). CONCLUSION: The MRVP is a program that provides undergraduate students with the opportunity to learn about research firsthand as they volunteer and aid in different research projects. This program also provides faculty members with the help to conduct their research projects and opportunity to influence future generations. It was shown that so far the MRVP has been successful in reaching its goals, for both students and faculty.

VPS35 pathogenic mutations confer no dominant toxicity but partial loss of function in Drosophila and genetically interact with parkin.

Mutations in VPS35 (PARK17) cause autosomal dominant, late onset Parkinson's disease (PD). VPS35 forms a core component of the retromer complex that mediates the retrieval of membrane proteins from endosomes back to either the Golgi or plasma membrane. While aberrant endosomal protein sorting has been linked to several neurodegenerative diseases, the mechanisms by which VPS35 mutations and retromer function contribute to PD pathogenesis are not clear. To address this, we generated transgenic Drosophila that express variant forms of human VPS35 found in PD cases and the corresponding variants of the Drosophila ortholog. We did not find evidence of dominant toxicity from any variant form including the pathogenic D620N mutation, even with aging. However, assessing the ability of Vps35 variants to rescue multiple vps35-mutant phenotypes, we found that the D620N mutation confers a partial loss of function. Recently, VPS35 has been linked to the formation of mitochondria-derived vesicles, which mediate the degradation of mitochondrial proteins and contribute to mitochondrial quality control. This process is also promoted by two other PD-lined genes parkin (PARK2) and PINK1 (PARK6). We demonstrate here that vps35 genetically interacts with parkin but interestingly not with pink1. Strikingly, Vps35 overexpression is able to rescue several parkin-mutant phenotypes. Together these findings provide in vivo evidence that the D620N mutation likely confers pathogenicity through a partial loss of function mechanism and that this may be linked to other known pathogenic mechanisms such as mitochondrial dysfunction.

Drosophila adult olfactory shock learning.

Drosophila have been used in classical conditioning experiments for over 40 years, thus greatly facilitating our understanding of memory, including the elucidation of the molecular mechanisms involved in cognitive diseases. Learning and memory can be assayed in larvae to study the effect of neurodevelopmental genes and in flies to measure the contribution of adult plasticity genes. Furthermore, the short lifespan of Drosophila facilitates the analysis of genes mediating age-related memory impairment. The availability of many inducible promoters that subdivide the Drosophila nervous system makes it possible to determine when and where a gene of interest is required for normal memory as well as relay of different aspects of the reinforcement signal. Studying memory in adult Drosophila allows for a detailed analysis of the behavior and circuitry involved and a measurement of long-term memory. The length of the adult stage accommodates longer-term genetic, behavioral, dietary and pharmacological manipulations of memory, in addition to determining the effect of aging and neurodegenerative disease on memory. Classical conditioning is induced by the simultaneous presentation of a neutral odor cue (conditioned stimulus, CS(+)) and a reinforcement stimulus, e.g., an electric shock or sucrose, (unconditioned stimulus, US), that become associated with one another by the animal. A second conditioned stimulus (CS(-)) is subsequently presented without the US. During the testing phase, Drosophila are simultaneously presented with CS+ and CS- odors. After the Drosophila are provided time to choose between the odors, the distribution of the animals is recorded. This procedure allows associative aversive or appetitive conditioning to be reliably measured without a bias introduced by the innate preference for either of the conditioned stimuli. Various control experiments are also performed to test whether all genotypes respond normally to odor and reinforcement alone.

CASK and CaMKII function in Drosophila memory.

Calcium (Ca(2+)) and Calmodulin (CaM)-dependent serine/threonine kinase II (CaMKII) plays a central role in synaptic plasticity and memory due to its ability to phosphorylate itself and regulate its own kinase activity. Autophosphorylation at threonine 287 (T287) switches CaMKII to a Ca(2+) independent and constitutively active state replicated by overexpression of a phosphomimetic CaMKII-T287D transgene or blocked by expression of a T287A transgene. A second pair of sites, T306 T307 in the CaM binding region once autophosphorylated, prevents CaM binding and inactivates the kinase during synaptic plasticity and memory, and can be blocked by a TT306/7AA transgene. Recently the synaptic scaffolding molecule called CASK (Ca(2+)/CaM-associated serine kinase) has been shown to control both sets of CaMKII autophosphorylation events during neuronal growth, Ca(2+) signaling and memory in Drosophila. Deletion of either full length CASK or just its CaMK-like and L27 domains removed middle-term memory (MTM) and long-term memory (LTM), with CASK function in the α'/ß' mushroom body neurons being required for memory. In a similar manner directly changing the levels of CaMKII autophosphorylation (T287D, T287A, or TT306/7AA) in the α'/ß' neurons also removed MTM and LTM. In the CASK null mutant expression of either the Drosophila or human CASK transgene in the α'/ß' neurons was found to completely rescue memory, confirming that CASK signaling in α'/ß' neurons is necessary and sufficient for Drosophila memory formation and that the neuronal function of CASK is conserved between Drosophila and human. Expression of human CASK in Drosophila also rescued the effect of CASK deletion on the activity state of CaMKII, suggesting that human CASK may also regulate CaMKII autophosphorylation. Mutations in human CASK have recently been shown to result in intellectual disability and neurological defects suggesting a role in plasticity and learning possibly via regulation of CaMKII autophosphorylation.

KCNQ channels regulate age-related memory impairment.

In humans KCNQ2/3 heteromeric channels form an M-current that acts as a brake on neuronal excitability, with mutations causing a form of epilepsy. The M-current has been shown to be a key regulator of neuronal plasticity underlying associative memory and ethanol response in mammals. Previous work has shown that many of the molecules and plasticity mechanisms underlying changes in alcohol behaviour and addiction are shared with those of memory. We show that the single KCNQ channel in Drosophila (dKCNQ) when mutated show decrements in associative short- and long-term memory, with KCNQ function in the mushroom body α/ßneurons being required for short-term memory. Ethanol disrupts memory in wildtype flies, but not in a KCNQ null mutant background suggesting KCNQ maybe a direct target of ethanol, the blockade of which interferes with the plasticity machinery required for memory formation. We show that as in humans, Drosophila display age-related memory impairment with the KCNQ mutant memory defect mimicking the effect of age on memory. Expression of KCNQ normally decreases in aging brains and KCNQ overexpression in the mushroom body neurons of KCNQ mutants restores age-related memory impairment. Therefore KCNQ is a central plasticity molecule that regulates age dependent memory impairment.