Van der Waals polarity-engineered 3D integration of 2D complementary logic.

Vertical three-dimensional integration of two-dimensional (2D) semiconductors holds great promise, as it offers the possibility to scale up logic layers in the z axis1-3. Indeed, vertical complementary field-effect transistors (CFETs) built with such mixed-dimensional heterostructures4,5, as well as hetero-2D layers with different carrier types6-8, have been demonstrated recently. However, so far, the lack of a controllable doping scheme (especially p-doped WSe2 (refs. 9-17) and MoS2 (refs. 11,18-28)) in 2D semiconductors, preferably in a stable and non-destructive manner, has greatly impeded the bottom-up scaling of complementary logic circuitries. Here we show that, by bringing transition metal dichalcogenides, such as MoS2, atop a van der Waals (vdW) antiferromagnetic insulator chromium oxychloride (CrOCl), the carrier polarity in MoS2 can be readily reconfigured from n- to p-type via strong vdW interfacial coupling. The consequential band alignment yields transistors with room-temperature hole mobilities up to approximately 425 cm2 V-1 s-1, on/off ratios reaching 106 and air-stable performance for over one year. Based on this approach, vertically constructed complementary logic, including inverters with 6 vdW layers, NANDs with 14 vdW layers and SRAMs with 14 vdW layers, are further demonstrated. Our findings of polarity-engineered p- and n-type 2D semiconductor channels with and without vdW intercalation are robust and universal to various materials and thus may throw light on future three-dimensional vertically integrated circuits based on 2D logic gates.

Dynamic expression of Schlafen 11 (SLFN11) in circulating tumour cells as a liquid biomarker in small cell lung cancer.

INTRODUCTION: Small cell lung cancer (SCLC) is an aggressive malignancy with no established biomarkers. Schlafen 11(SLFN11), a DNA/RNA helicase that sensitises cancer cells to DNA-damaging agents, has emerged as a promising predictive biomarker for several drug classes including platinum and PARP inhibitors. Detection of SLFN11 in circulating tumour cells (CTCs) may provide a valuable alternative to tissue sampling. METHODS: SLFN11 expression was evaluated in tumour samples and characterised in circulating tumour cells (CTC) longitudinally to determine its potential role as a biomarker of response. RESULTS: Among 196 SCLC tumours, 51% expressed SLFN11 by IHC. In addition, 20/29 extra-thoracic high-grade neuroendocrine tumours expressed SLFN11 expression. In 64 blood samples from 42 SCLC patients, 83% (53/64) of samples had detectable CTCs, and SLFN11-positive CTCs were detected in 55% (29/53). Patients actively receiving platinum treatment had the lowest number of CTCs and a lower percentage of SLFN11-positive CTCs (p = 0.014). Analysis from patients with longitudinal samples suggest a decrease in CTC number and in SLFN11 expression that correlates with clinical response. CONCLUSIONS: SLFN11 levels can be monitored in CTCs from SCLC patients using non-invasive liquid biopsies. The ability to detect SLFN11 in CTCs from SCLC patients adds a valuable tool for the detection and longitudinal monitoring of this promising biomarker.

Clinical characteristics of axial spondyloarthritis patients in China: results from ChinaSpA, the Chinese Spondyloarthritis Registry.

OBJECTIVES: The objective of this study is to describe the clinical features of patients with axial spondyloarthritis (axial SpA) in the ChinaSpA registry. METHODS: Patients with clinical diagnosis of ankylosing spondylitis (AS) or axial SpA were enrolled into the registry. Patients with a complete set of pelvis radiograph, pelvis MRI and HLA-B27 (Complete Set group, CS group) were further categorised based on classification criteria into AS, radiographic axial SpA (r-axSpA) and non-radiographic axial SpA (nr-axSpA). Early axial SpA was defined as symptom duration of less than three years. Descriptive statistics were used to describe clinical characteristics of enrolled patients. ANOVA analyses were used to compare patients in different groups. RESULTS: A total of 5270 patients were enrolled in the study, and 3223 patients had complete sets of pelvis radiographs, MRIs and HLA-B27 status. Among them, more than 80% patients met both the ASAS criteria for r-axSpA and the modified New York criteria for AS. Among those with early axial SpA, 92% of patients had sacroiliitis on pelvis radiograph, 3.8% had sacroiliitis only on pelvis MRI, and 3.8% were in the clinical arm without any sacroiliitis on imaging studies. Patients in nr-axSpA clinical arm had less diagnosis delay, lower inflammatory markers and ASDAS, compared topatients in the r-axSpA, nr-axSpA MRI arm. CONCLUSIONS: In the ChinaSpA registry, patients in nr-axSpA clinical arm had the shortest diagnostic delay, lower inflammatory markers and ASDAS, but no difference in extra-articular manifestation, compared to patients in the r-axSpA and nr-axSpA MRI arm.

Clinical characteristics of re-hospitalized COVID-19 patients with recurrent positive SARS-CoV-2 RNA: a retrospective study.

At present, it has been noticed that some patients recovered from COVID-19 present a recurrent positive RNA test of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) after being discharged from hospitals. The purpose of the current study was to characterize the clinical features of re-hospitalized patients with recurrent SARS-CoV-2 positive results. From January 12 to April 1 of 2020, our retrospective study was conducted in China. The exposure history, baseline data, laboratory findings, therapeutic schedule, and clinical endpoints of the patients were collected. All the patients were followed until April 10, 2020. Among all COVID-19 patients included in the current study, there were 14 re-hospitalized patients due to recurrent positive tests of SARS-CoV-2 RNA. Fever (11 [78.6%]), cough (10 [71.4%]), and fatigue (7 [50.0%]) were the most common symptoms on the patient's first admission, and less symptoms were found on their second admission. The average duration from the onset of symptoms to admission to hospital was found to be 8.4 days for the first admission and 2.6 days for the second admission (P = 0.002). The average time from the detection of RNA (+) to hospitalization was 1.9 days for the first admission and 2.6 days for the second admission (P = 0.479), and the average time from RNA (+) to RNA (-) was 11.1 days for the first admission and 6.3 days for the second admission (P = 0.030). Moreover, the total time in hospital was 18.6 days for the first admission and 8.0 days for the second admission (P = 0.000). It may be necessary to increase the isolation observation time and RT-PCR tests should be timely performed on multiple samples as soon as possible.

A Pilot Study on Feasibility of Ultrashort Echo Time T2* Cartilage Mapping in the Sacroiliac Joints.

PURPOSE: Assess feasibility of ultrashort echo time (UTE) T2* cartilage mapping in sacroiliac (SI) joints. METHODS: Prospective magnetic resonance imagings with UTE T2* cartilage maps obtained on 20 SI joints in 10 subjects. Each joint was segmented into thirds by 2 radiologists. The UTE T2* maps were analyzed; reliability and differences in UTE T2* values between radiologists were assessed. RESULTS: Mean UTE T2* value was 10.44 ± 0.60 ms. No difference between right/left SI joints (median, 10.52 vs 10.45 ms; P = 0.940), men/women (median, 10.34 vs. 10.57 ms; P = 0.174), or different anatomic regions (median range 10.55-10.69 ms; P = 0.805). Intraclass correlation coefficients were 0.94 to 0.99 (intraobserver) and 0.91 to 0.96 (interobserver). Mean bias ± standard deviation on Bland-Altman was -0.137 ± 0.196 ms (limits of agreement -0.521 and 0.247) without proportional bias (ß = 0.148, P = 0.534). CONCLUSIONS: The UTE T2* cartilage mapping in the SI joints is feasible with high reader reliability.

Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan. A Retrospective Observational Study.

Rationale: The global death toll from coronavirus disease (COVID-19) virus as of May 12, 2020, exceeds 286,000. The risk factors for death were attributed to advanced age and comorbidities but have not been accurately defined.Objectives: To report the clinical features of 85 fatal cases of COVID-19 in two hospitals in Wuhan.Methods: Medical records were collected of 85 fatal cases of COVID-19 between January 9, 2020, and February 15, 2020. Information recorded included medical history, exposure history, comorbidities, symptoms, signs, laboratory findings, computed tomographic scans, and clinical management.Measurements and Main Results: The median age of the patients was 65.8 years, and 72.9% were male. Common symptoms were fever (78 [91.8%]), shortness of breath (50 [58.8%]), fatigue (50 [58.8%]), and dyspnea (60 [70.6%]). Hypertension, diabetes, and coronary heart disease were the most common comorbidities. Notably, 81.2% of patients had very low eosinophil counts on admission. Complications included respiratory failure (80 [94.1%]), shock (69 [81.2%]), acute respiratory distress syndrome (63 [74.1%]), and arrhythmia (51 [60%]), among others. Most patients received antibiotic (77 [90.6%]), antiviral (78 [91.8%]), and glucocorticoid (65 [76.5%]) treatments. A total of 38 (44.7%) and 33 (38.8%) patients received intravenous immunoglobulin and IFN-α2b, respectively.Conclusions: In this depictive study of 85 fatal cases of COVID-19, most cases were males aged over 50 years with noncommunicable chronic diseases. The majority of the patients died of multiple organ failure. Early onset of shortness of breath may be used as an observational symptom for COVID-19 exacerbations. Eosinophilopenia may indicate a poor prognosis. A combination of antimicrobial drugs did not offer considerable benefit to the outcome of this group of patients.

Clinical Characteristics of COVID-19 Patients With Digestive Symptoms in Hubei, China: A Descriptive, Cross-Sectional, Multicenter Study.

OBJECTIVE: Since the outbreak of Coronavirus Disease 2019 (COVID-19) in December 2019, various digestive symptoms have been frequently reported in patients infected with the virus. In this study, we aimed to further investigate the prevalence and outcomes of COVID-19 patients with digestive symptoms. METHODS: In this descriptive, cross-sectional, multicenter study, we enrolled confirmed patients with COVID-19 who presented to 3 hospitals from January 18, 2020, to February 28, 2020. All patients were confirmed by real-time polymerase chain reaction and were analyzed for clinical characteristics, laboratory data, and treatment. Data were followed up until March 18, 2020. RESULTS: In the present study, 204 patients with COVID-19 and full laboratory, imaging, and historical data were analyzed. The average age was 52.9 years (SD ± 16), including 107 men and 97 women. Although most patients presented to the hospital with fever or respiratory symptoms, we found that 103 patients (50.5%) reported a digestive symptom, including lack of appetite (81 [78.6%] cases), diarrhea (35 [34%] cases), vomiting (4 [3.9%] cases), and abdominal pain (2 [1.9%] cases). If lack of appetite is excluded from the analysis (because it is less specific for the gastrointestinal tract), there were 38 total cases (18.6%) where patients presented with a gastrointestinal-specific symptom, including diarrhea, vomiting, or abdominal pain. Patients with digestive symptoms had a significantly longer time from onset to admission than patients without digestive symptoms (9.0 days vs 7.3 days). In 6 cases, there were digestive symptoms, but no respiratory symptoms. As the severity of the disease increased, digestive symptoms became more pronounced. Patients with digestive symptoms had higher mean liver enzyme levels, lower monocyte count, longer prothrombin time, and received more antimicrobial treatment than those without digestive symptoms. DISCUSSION: We found that digestive symptoms are common in patients with COVID-19. Moreover, these patients have a longer time from onset to admission, evidence of longer coagulation, and higher liver enzyme levels. Clinicians should recognize that digestive symptoms, such as diarrhea, are commonly among the presenting features of COVID-19 and that the index of suspicion may need to be raised earlier in at-risk patients presenting with digestive symptoms. However, further large sample studies are needed to confirm these findings.

The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China.

The 2019-nCoV is officially called SARS-CoV-2 and the disease is named COVID-19. This viral epidemic in China has led to the deaths of over 1800 people, mostly elderly or those with an underlying chronic disease or immunosuppressed state. This is the third serious Coronavirus outbreak in less than 20 years, following SARS in 2002-2003 and MERS in 2012. While human strains of Coronavirus are associated with about 15% of cases of the common cold, the SARS-CoV-2 may present with varying degrees of severity, from flu-like symptoms to death. It is currently believed that this deadly Coronavirus strain originated from wild animals at the Huanan market in Wuhan, a city in Hubei province. Bats, snakes and pangolins have been cited as potential carriers based on the sequence homology of CoV isolated from these animals and the viral nucleic acids of the virus isolated from SARS-CoV-2 infected patients. Extreme quarantine measures, including sealing off large cities, closing borders and confining people to their homes, were instituted in January 2020 to prevent spread of the virus, but by that time much of the damage had been done, as human-human transmission became evident. While these quarantine measures are necessary and have prevented a historical disaster along the lines of the Spanish flu, earlier recognition and earlier implementation of quarantine measures may have been even more effective. Lessons learned from SARS resulted in faster determination of the nucleic acid sequence and a more robust quarantine strategy. However, it is clear that finding an effective antiviral and developing a vaccine are still significant challenges. The costs of the epidemic are not limited to medical aspects, as the virus has led to significant sociological, psychological and economic effects globally. Unfortunately, emergence of SARS-CoV-2 has led to numerous reports of Asians being subjected to racist behavior and hate crimes across the world.

Unilateral curved versus bipedicular vertebroplasty in the treatment of osteoporotic vertebral compression fractures.

BACKGROUND: Vertebral compression fracture is one of the most common complications of osteoporosis. In this study an unilateral curved vertebroplasty device was developed, and the safety, effectiveness, and surgical parameters of curved vertebroplasty (CVP) in the treatment of painful osteoporotic vertebral compression fractures was investigated and compared with traditional bipedicular vertebroplasty (BVP). METHODS: We investigated 104 vertebral augmentation procedures performed over 36 months. CVP and BVP procedures were compared for baseline clinical variables, pain relief (Visual Analog Scale, VAS), disability improvement (Oswestry Disability Index, ODI), operation time, number of fluoroscopic images, volume of cement per level, and cement leakage rate for each level treated. Complications and refracture incidence were also recorded in the two groups. RESULTS: The VAS and ODI in both group had no significant difference preoperative (P > 0.05), and a significant postoperative improvement in the VAS scores and ODI was found in both group (P < 0.001). However, the CVP group had significantly lower operation time, number of fluoroscopic images, and cement leakage rate per level than the BVP group (P < 0.05); however, the volumes of cement per level were similar in the two groups (P > 0.05). Neither group had any serious complications. Five and two patients in the BVP group developed refractures at non-adjacent and adjacent levels, respectively, with one patient developing refractures twice; however, none of the patients in the CVP group developed refractures at any level. CONCLUSIONS: Our findings revealed that both CVP and BVP were safe and effective treatments for osteoporotic vertebral compression fractures, and CVP entails a shorter operation time, less exposure to fluoroscopy, and lower rate of cement leakage.

Epidemiology of axial spondyloarthritis: an update.

PURPOSE OF REVIEW: To provide an update of the prevalence and incidence of axial spondyloarthritis in the general population and in patients with spondyloarthritis-related conditions, environmental risk factors for ankylosing spondylitis, progression from nonradiographic axial spondyloarthritis to ankylosing spondylitis, mortality, and risks for cardiovascular events in patients with ankylosing spondylitis. RECENT FINDINGS: Increasingly, administrative healthcare data have been used to study disease frequency and outcomes. The prevalence of ankylosing spondylitis ranged from 9 to 30 per 10 000 persons, which are lower than previous estimates. Data on whether childhood infections influence the risk of ankylosing spondylitis were equivocal, while having been breast-fed may be protective. Progression of patients with nonradiographic axial spondyloarthritis to ankylosing spondylitis is slow, with estimates of 5.1% in 5 years and 19% in 10 years. Risk of mortality is slightly increased in ankylosing spondylitis. Risks for cardiovascular events in ankylosing spondylitis were either not different from, or only slightly higher than in controls. No studies have examined these outcomes in the broader group of patients with axial spondyloarthritis. SUMMARY: Expanded use of administrative and registry data has facilitated studies of the epidemiology of ankylosing spondylitis, but lack of specific diagnostic codes limits use of these resources for studying axial spondyloarthritis in general.

Evaluation of Ophthalmic Artery Branch Retrograde Intervention in the Treatment of Central Retinal Artery Occlusion (CRAO).

BACKGROUND Central retinal artery occlusion (CRAO) is the occlusion of the central retinal artery resulting in retinal infarction and acute vision loss. Digital subtraction angiography (DSA)-guided superselective ophthalmic artery or selective carotid thrombolysis remains the preferred treatment method for CRAO. This study aimed to evaluate the safety and clinical efficacy of the novel ophthalmic artery branch retrograde thrombolytic intervention for CRAO. MATERIAL AND METHODS Fifty patients with monocular CRAO were enrolled, including 28 males and 22 females (mean age: 55.7±2.3 years). The patients were randomly divided into two groups for thrombolysis with urokinase (400,000 U) and papaverine (30 mg) by either ophthalmic artery branch retrograde intervention (group A, n=26) or superselective ophthalmic artery/selective carotid intervention (group B, n=24). There was no significant difference in age (P=0.58), gender ratio (P=0.49), and time to onset (P=1.00) between the two groups. The adverse reactions and clinical efficacy were evaluated by postoperative DSA, fundus fluorescein angiography (FFA), and visual acuity tests. RESULTS No serious complications, abnormal eye movement, or vitreous hemorrhage occurred in either group. DSA showed that group A had an effective rate (92.30%) comparable to that of group B (100%, χ²=2.08, P=0.25). FFA suggested that both groups had similar treatment efficacy (χ²=3.09, P=0.21). Visual acuity tests also confirmed a similar efficacy of the two intervention approaches (χ²=0.25, P=0.88). CONCLUSIONS The developed novel ophthalmic artery branch retrograde intervention is highly effective and safe for CRAO, and may be a superior method compared with the conventional approach.

Comparative efficacy of non-steroidal anti-inflammatory drugs in ankylosing spondylitis: a Bayesian network meta-analysis of clinical trials.

OBJECTIVE: To compare the efficacy of 20 non-steroidal anti-inflammatory drugs (NSAIDs) in the short-term treatment of ankylosing spondylitis (AS). METHODS: We performed a systematic literature review of randomised controlled trials of NSAIDs in patients with active AS. We included trials that reported efficacy at 2-12 weeks. Efficacy outcomes were the change in pain score and change in the duration of morning stiffness. We also examined the number of adverse events. We used Bayesian network meta-analysis to compare effects directly and indirectly between drugs. RESULTS: We included 26 trials (66 treatment arms) of 20 NSAIDs with 3410 participants in the network meta-analysis. Fifty-eight per cent of trials had fewer than 50 participants. All 20 NSAIDs reduced pain more than placebo (standardised mean difference ranging from -0.65 to -2.2), with 15 NSAIDs significantly better than placebo. Etoricoxib was superior to celecoxib, ketoprofen and tenoxicam in pain reduction, but no other interdrug comparisons were significant. There were no significant differences among NSAIDs in decreases in the duration of morning stiffness or the likelihood of adverse events. Adverse events were uncommon in these short-term studies. In 16 trials that used NSAIDs at full doses, etoricoxib was superior to all but two other NSAIDs in pain reduction. CONCLUSIONS: Etoricoxib was more effective in reducing pain in AS than some other NSAIDs, but there was otherwise insufficient evidence to conclude that any particular NSAID was more effective in the treatment of AS. Comparisons were limited by small studies.

Syndesmophyte growth in ankylosing spondylitis.

PURPOSE OF REVIEW: Syndesmophytes are characteristic components of the spine disorder of ankylosing spondylitis. Understanding their growth may reveal insights to pathogenesis and potential treatment. We review recent studies on rates of development of syndesmophytes, patient characteristics associated with more rapid syndesmophyte growth, local vertebral abnormalities that precede syndesmophytes, systemic biomarkers of syndesmophytes, and studies of medications. RECENT FINDINGS: New syndesmophytes develop in one-third of patients over 2 years. Consistent clinical predictors are male sex, elevated serum C-reactive protein levels, and preexisting syndesmophytes. Concomitant vertebral inflammation and fat dysplasia on MRI predict future syndesmophytes at the same vertebral location, but most syndesmophytes do not have recognized antecedents. Associations with serum levels of Wingless pathway proteins are inconsistent, as are the results of observational studies of tumor necrosis factor-alpha inhibitors. SUMMARY: Although there is better understanding of the frequency of syndesmophyte development, the pathogenesis of syndesmophytes remains unclear.

The Understanding and Compact Modeling of Reliability in Modern Metal-Oxide-Semiconductor Field-Effect Transistors: From Single-Mode to Mixed-Mode Mechanisms.

With the technological scaling of metal-oxide-semiconductor field-effect transistors (MOSFETs) and the scarcity of circuit design margins, the characteristics of device reliability have garnered widespread attention. Traditional single-mode reliability mechanisms and modeling are less sufficient to meet the demands of resilient circuit designs. Mixed-mode reliability mechanisms and modeling have become a focal point of future designs for reliability. This paper reviews the mechanisms and compact aging models of mixed-mode reliability. The mechanism and modeling method of mixed-mode reliability are discussed, including hot carrier degradation (HCD) with self-heating effect, mixed-mode aging of HCD and Bias Temperature Instability (BTI), off-state degradation (OSD), on-state time-dependent dielectric breakdown (TDDB), and metal electromigration (EM). The impact of alternating HCD-BTI stress conditions is also discussed. The results indicate that single-mode reliability analysis is insufficient for predicting the lifetime of advanced technology and circuits and provides guidance for future mixed-mode reliability analysis and modeling.

Intermittent hypoxic pretreatment exacerbates house dust mite-induced asthma airway inflammation.

BACKGROUND: Asthma is widely recognized as an inflammatory disorder. In the context of this inflammatory microenvironment, the involvement of hypoxia and its impact on related pathways have drawn considerable attention. However, the exact role of hypoxia, a prevalent environmental factor, in the development and progression of asthma remains poorly understood. METHODS: Mice were treated with house dust mite (HDM) extracts for 23 days to induce asthma. Mice were divided into room air (RA) group and intermittent hypoxic (IH) group by exposing to different conditions and IH preconditioning (IHP) were underwent to the above groups before the hypoxic regimen. Airway inflammation in mice was evaluated by airway hyperresponsiveness, excessive mucus secretion, and recruitment of inflammatory cells. Immunohistochemistry was employed to quantify the expression levels of NF-κB. Subsequently, the dose of allergen was modified to investigate whether the impact of hypoxia on asthma is affected by different doses of allergens. RESULT: Compared to the RA and IH groups, HDM-treated mice in the IHP group exhibited aggravated inflammatory cell infiltration and airway hyperresponsiveness (p＜.05). Moreover, there was an increased release of inflammatory mediators and higher expression levels of NF-κB (p＜.05). Importantly, the impact ia on asthma was found to be influenced by high dose of allergen (p＜.05). CONCLUSION: IHP treatment potentially exacerbates HDM-induced airway inflammation in asthma, with the involvement of NF-κB, particularly under high-dose allergen stimulation.

Comparison of inebilizumab or rituximab in addition to glucocorticoid therapy for neuromyelitis optica spectrum disorders.

AIM: To investigate the short-term efficacy and safety of inebilizumab for neuromyelitis optica spectrum disorders (NMOSD). METHODS: A total of 33 patients with NMOSD treated with inebilizumab (Group INB, n=15) or rituximab (Group RTX, n=18) in addition to high-dose glucocorticoids were included. Both groups underwent hormone shock therapy during the acute phase. Subsequently, Group INB received inebilizumab injections during the remission phase, while Group RTX received rituximab injections. A comparison of aquaporins 4 (AQP4) titer values, peripheral blood B lymphocyte counts, and visual function recovery was conducted before and 8wk after treatment. Additionally, adverse reactions and patient tolerability were analyzed after using inebilizumab treatment regimes. RESULTS: Following inebilizumab treatment, there was a significantly improvement in the visual acuity of NMOSD patients (P<0.05), accompanied by a notable decrease in AQP4 titer values and B lymphocyte ratio (P<0.05). Moreover, inebilizumab treatment showed a partial effect in preventing optic nerve atrophy (P<0.05). However, there were no significant differences in other therapeutic effects compared to rituximab, which has previously demonstrated substantial therapeutic efficacy (P>0.05). Furthermore, inebilizumab exhibited higher safety levels than that of rituximab injections. CONCLUSION: The combination of inebilizumab and high-dose glucocorticoids proves to be effective. In comparison to rituximab injections, inebilizumab displays better tolerance and safety. Moreover, it demonstrates a partial effect in preventing optic nerve atrophy. Thus, it stands as an effective method to reduce the disability rates and improve the daily living ability of patients with NMOSD.

Multidimensional analysis of cortical interneuron synaptic features reveals underlying synaptic heterogeneity.

Cortical interneurons represent a diverse set of neuronal subtypes characterized in part by their striking degree of synaptic specificity. However, little is known about the extent of synaptic diversity because of the lack of unbiased methods to extract synaptic features among interneuron subtypes. Here, we develop an approach to aggregate image features from fluorescent confocal images of interneuron synapses and their post-synaptic targets, in order to characterize the heterogeneity of synapses at fine scale. We started by training a model that recognizes pre- and post-synaptic compartments and then determines the target of each genetically-identified interneuron synapse in vitro and in vivo. Our model extracts hundreds of spatial and intensity features from each analyzed synapse, constructing a multidimensional data set, consisting of millions of synapses, which allowed us to perform an unsupervised analysis on this dataset, uncovering novel synaptic subgroups. The subgroups were spatially distributed in a highly structured manner that revealed the local underlying topology of the postsynaptic environment. Dendrite-targeting subgroups were clustered onto subdomains of the dendrite along the proximal to distal axis. Soma-targeting subgroups were enriched onto different postsynaptic cell types. We also find that the two main subclasses of interneurons, basket cells and somatostatin interneurons, utilize distinct strategies to enact inhibitory coverage. Thus, our analysis of multidimensional synaptic features establishes a conceptual framework for studying interneuron synaptic diversity.

A Coupling Mechanism between Flicker Noise and Hot Carrier Degradations in FinFETs.

A coupling mechanism between flicker noise and hot carrier degradation (HCD) is revealed in this work. Predicting the flicker noise properties of fresh and aged devices is becoming essential for circuit designs, requiring an understanding of the fundamental noise behaviors. While certain models for fresh devices have been proposed, those for aged devices have not been reported yet because of the lack of a clear mechanism. The flicker noise of aged FinFETs is characterized based on the measure-stress-measure (MSM) method and analyzed from the device physics. It is found that both the mean and deviations of the noise power spectral density increase compared with the fresh counterparts. A coupling mechanism is proposed to explain the trap time constants, leading to the trap characterizations in their energy profiles. The amplitude and number of contributing traps are also changing and are dependent on the mode of HCD and determined by the position of the induced traps. A microscopic picture is developed from the perspective of trap coupling, reproducing well the measured noise of advanced nanoscale FinFETs. The finding is important for accurate flicker noise calculations and aging-aware circuit designs.