On the origin of enhanced sensitivity in nanoscale FET-based biosensors.

Electrostatic counter ion screening is a phenomenon that is detrimental to the sensitivity of charge detection in electrolytic environments, such as in field-effect transistor-based biosensors. Using simple analytical arguments, we show that electrostatic screening is weaker in the vicinity of concave curved surfaces, and stronger in the vicinity of convex surfaces. We use this insight to show, using numerical simulations, that the enhanced sensitivity observed in nanoscale biosensors is due to binding of biomolecules in concave corners where screening is reduced. We show that the traditional argument, that increased surface area-to-volume ratio for nanoscale sensors is responsible for their increased sensitivity, is incorrect.

Carbon-ionogel supercapacitors for integrated microelectronics.

To exceed the performance limits of dielectric capacitors in microelectronic circuit applications, we design and demonstrate on-chip coplanar electric double-layer capacitors (EDLCs), or supercapacitors, employing carbon-coated gold electrodes with ionogel electrolyte. The formation of carbon-coated microelectrodes is accomplished by solution processing and results in a ten-fold increase in EDLC capacitance compared to bare gold electrodes without carbon. At frequencies up to 10 Hz, an areal capacitance of 2.1 pF µm(-2) is achieved for coplanar carbon-ionogel EDLCs with 10 µm electrode gaps and 0.14 mm(2) electrode area. Our smallest devices, comprised of 5 µm electrode gaps and 80 µm(2) of active electrode area, reach areal capacitance values of ∼0.3 pF µm(-2) at frequencies up to 1 kHz, even without carbon. To our knowledge, these are the highest reported values to date for on-chip EDLCs with sub-mm(2) areas. A physical EDLC model is developed through the use of computer-aided simulations for design exploration and optimization of coplanar EDLCs. Through modeling and comparison with experimental data, we highlight the importance of reducing the electrode gap and electrolyte resistance to achieve maximum performance from on-chip EDLCs.

Antiphospholipid antibodies and cerebellar ataxia: a clinical analysis and literature review.

BACKGROUND: Although it has been established that antiphospholipid antibodies (APAbs) bind to and modulate the signaling of cerebellar neurons in vitro, the clinical correlation between increased APAbs and cerebellar ataxia has rarely been investigated. METHODS: We reviewed 10 patients presenting with cerebellar ataxia with increased blood APAbs from our database along with 3 APAb-associated cerebellar ataxia patients in the literature. RESULTS: Of these 10 patients, 4 exhibited a subacute onset of progressive ataxia, and there were no significant structural changes in their brains that appeared to be responsible for the symptoms. Another 6 showed a chronic course of ataxia, and shared similar morphological changes that included symmetrical lesions in bilateral hemispheres, periventricular lucency and central and temporal atrophy of varying severity; the cerebellum was spared. The predominant APAbs for subacute and chronic ataxia were the anti-beta2-glycoprotein I antibody and anticardiolipin antibody, respectively. Cancer was found in 1 patient with subacute ataxia and in 4 with chronic ataxia. The removal of the cancer, the plasmapheresis and immunosuppressive therapy successfully abolished the ataxia and increased APAb levels in all 5 patients. CONCLUSIONS: The relation between APAbs and nonvascular neurological disorders, such as cerebellar ataxia, should be further studied. APAbs may mediate neurological deficits via different mechanisms such as structural damage or functional neurotoxicity. Clinically, the examination of blood APAb levels is recommended for patients with cerebellar ataxia without a determined cause, and the further survey of systemic cancers in the case of APAb positivity is also recommended. Finally, plasmapheresis is a reasonable and effective treatment for APAb-associated cerebellar ataxia.

Periodic drop thumb, hypokalemia and adrenal adenoma.

OBJECTIVE: To report an unusual involvement of focal distal muscles but not proximal muscles in a patient with hypokalemic periodic paralysis (hypoPP). CLINICAL PRESENTATION AND INTERVENTION: A middle-aged woman presented with episodic weakness of the bilateral thumbs lasting for 2 years. Hypokalemia and a left adrenal mass were subsequently found. Her weakness subsided after surgical removal of the adrenal mass, which was pathologically proven to be an adrenal adenoma. CONCLUSION: The findings for this patient should alert physicians to consider focal distal motor paresis due to hypoPP. A preexisting occult trauma may predispose to paralysis at an atypical location in secondary hypoPP.

Zoster sine herpete, vertebral artery stenosis, and ischemic stroke.

Although a previous or recent history of varicella-zoster virus (VZV) infection is known to increase the risk of stroke in both children and adults, the influence of zoster sine herpetic remains unclear. We report an immunocompetent man with common cold symptoms and conjunctivitis, followed by an acute onset of bulbar weakness and hemihypesthesia without preceding skin rash. Acute medullary infarction and left vertebral artery stenosis were detected. VZV infection was finally identified. Zoster sine herpetic interferes with accurate diagnosis of infectious stroke, and vertebral artery involvement is unusual in ischemic stroke in this situation. An unexplained course of ischemic stroke event should be suspected in patients with VZV cerebrovasculopathy, especially in those without conventional stroke risk factors and those exhibiting concomitant infectious complications.

Nummular headache after trans-sphenoidal surgery: a referred pain-based headache syndrome.

Nummular headache (NH) is a newly categorized primary headache characterized by a consistent location, shape and size of painful area in each attack. The etiopathogenesis is entirely unknown. Currently, the peripheral theory of epicranial neuralgia is accepted more widely than the central theory but it cannot fully explain the clinical picture. We report a patient who suffered from a relapsing and remitting course of NH at the high parietal area and vertex shortly after resection for pituitary prolactinoma via a trans-sphenoidal approach. There was no focal trophic change or paresthesia but a mild allodynia in the painful area. The patient did not exhibit trigeminal sensory disorder or cranial trauma thoroughly. The pain responded well to gabapentin. Therefore, physicians should be aware of postoperative NH, which is amenable to treatment. The findings in our patient support a dual mechanism of NH and suggest that central NH is a form of referred pain.

The antemortem neurobehavior in fatal paramethoxymethamphetamine usage.

Paramethoxymethamphetamine (PMMA) is an emerging and prevalent psychoactive drug with a structure analogous to amphetamine and related psychostimulants. However, the neurobehavioral effect is only studied in experimental animals and is barely mentioned in human. The authors report the antemortem neurobehavioral manifestations in 8 patients with PMMA use. There were 2 different antemortem presentations. The first group of patients showed delirium, hypertalkativity, and incoherence speech and then turned into convulsion and death. They did not exhibit the typical hyperdopaminergic movement disorder. The second group of patients gradually fell asleep and then suffered respiratory or cardiovascular collapse. The heart blood PMMA level was higher in the second group than in the first group of patients. Forensic autopsy showed variable findings, ranging from no remarkable change to significant pathological damage similar to serotonin syndrome in both groups of patients. PMMA seems to enhance serotoninergism than dopaminergism, and exerts a concentration-related dual effect on human.

Ischemic stroke after low-voltage electric injury in a diabetic and coagulopathic woman.

Electric injury is a common physical injury in daily life. Because of the low resistance of vascular tissue, vascular injury and thrombosis are frequently found in cases of high-voltage electric injury but are rarely reported in low-voltage conditions. We present the case of a diabetic woman who suffered symptomatic brainstem stroke after a short duration of 60 Hz/110 V alternate current electric contact with a home washer socket. A stroke risk factor survey did not reveal remarkable cardiac or vascular abnormality, except increased glycohemoglobin levels and decreased protein C activity. In contrast to a direct and adequate energy transfer in high-voltage electric injury, a pre-existing vasculohemostatic deficit, such as coagulopathy, has been proposed to provide a predisposition to thrombosis in low-voltage electric injury. Nevertheless, the findings in this patient remind the possibility of physical triggering factor for stroke occurrence in our environment as new technology and product generates rapidly enough for understanding their safety and biologic effect.

Awareness of meaning and quest for meaning: The mechanisms between future orientation and prosociality among youth during pandemic.

Introduction: The positive relationship between future orientation and prosocial tendency has been consistently reported. However, the possible mechanism has not been examined yet. Previous research revealed the positive relationship between future orientation and meaning in life, as well as between meaning in life and prosocial tendency. Hence, it is hypothesized that the two components of meaning in life (presence of meaning and search for meaning) possibly mediate the relationship between future orientation and prosocial tendency. Methods: During the first half of 2020, 430 Hong Kong youths aged 15-35 (male: 30.5%; female: 69.5%) were recruited to participate an online cross-sectional survey. The survey included three scales: (1) The Scale for Measuring Adult's Prosocialness, (2) Consideration of Future Consequence Scale, and (3) Meaning in Life Questionnaire. Results: The key findings showed that: (1) females had higher level of prosocial tendency than males, and (2) significant partial mediating effects of both presence of meaning and search for meaning on the relationship between future orientation and prosocial tendency. Nevertheless, the multi-group mediation model did not show significant gender difference. Discussion: These findings implied that future-oriented and meaning-focused interventions could possibly enhance youth's sense of meaning in everyday life and foster their meaning searching tendency, which further strengthen the positive effect of their future orientation on prosocial tendency, even during life adversities.

A stacked memory device on logic 3D technology for ultra-high-density data storage.

We have demonstrated, for the first time, a novel three-dimensional (3D) memory chip architecture of stacked-memory-devices-on-logic (SMOL) achieving up to 95% of cell-area efficiency by directly building up memory devices on top of front-end CMOS devices. In order to realize the SMOL, a unique 3D Flash memory device and vertical integration structure have been successfully developed. The SMOL architecture has great potential to achieve tera-bit level memory density by stacking memory devices vertically and maximizing cell-area efficiency. Furthermore, various emerging devices could replace the 3D memory device to develop new 3D chip architectures.

Spontaneous Cleavages of a Heterologous Protein, the CenA Endoglucanase of Cellulomonas fimi, in Escherichia coli.

CenA is an endoglucanase secreted by the Gram-positive cellulolytic bacterium, Cellulomonas fimi, to the environment as a glycosylated protein. The role of glycosylation in CenA is unclear. However, it seems not crucial for functional activity and secretion since the unglycosylated counterpart, recombinant CenA (rCenA), is both bioactive and secretable in Escherichia coli. Using a systematic screening approach, we have demonstrated that rCenA is subjected to spontaneous cleavages (SC) in both the cytoplasm and culture medium of E. coli, under the influence of different environmental factors. The cleavages were found to occur in both the cellulose-binding (CellBD) and catalytic domains, with a notably higher occurring rate detected in the former than the latter. In CellBD, the cleavages were shown to occur close to potential N-linked glycosylation sites, suggesting that these sites might serve as 'attributive tags' for differentiating rCenA from endogenous proteins and the points of initiation of SC. It is hypothesized that glycosylation plays a crucial role in protecting CenA from SC when interacting with cellulose in the environment. Subsequent to hydrolysis, SC would ensure the dissociation of CenA from the enzyme-substrate complex. Thus, our findings may help elucidate the mechanisms of protein turnover and enzymatic cellulolysis.

Nanoparticles suppress fluid instabilities in the thermal drawing of ultralong nanowires.

Ultra-long metal nanowires and their facile fabrication have been long sought after as they promise to offer substantial improvements of performance in numerous applications. However, ultra-long metal ultrafine/nanowires are beyond the capability of current manufacturing techniques, which impose limitations on their size and aspect ratio. Here we show that the limitations imposed by fluid instabilities with thermally drawn nanowires can be alleviated by adding tungsten carbide nanoparticles to the metal core to arrive at wire lengths more than 30 cm with diameters as low as 170 nm. The nanoparticles support thermal drawing in two ways, by increasing the viscosity of the metal and lowering the interfacial energy between the boron silicate and zinc phase. This mechanism of suppressing fluid instability by nanoparticles not only enables a scalable production of ultralong metal nanowires, but also serves for widespread applications in other fluid-related fields.

On Modeling Diversity in Electrical Cellular Response: Data-Driven Approach.

Electrical properties of biological cells and tissues possess valuable information that enabled numerous applications in biomedical engineering. The common foundation behind them is a numerical model that can predict electrical response of a single cell or a network of cells. We analyzed the past empirical observations to propose the first statistical model that accurately mimics biological diversity among animal cells, yeast cells, and bacteria. Based on membrane elasticity and cell migration mechanisms, we introduce a more realistic three-dimensional geometry generation procedure that captures membrane protrusions and retractions in adherent cells. Together, they form a model of diverse electrical response across multiple cell types. We experimentally verified the model with electrical impedance spectroscopy of a single human cervical carcinoma (HeLa) cell on a microelectrode array. The work is of particular relevance to medical diagnostic and therapeutic applications that involve exposure to electric and magnetic fields.

Feasibility of Tracking Multiple Single-Cell Properties with Impedance Spectroscopy.

Electric cell-substrate impedance sensing (ECIS) has been instrumental in tracking collective behavior of confluent cell layers for decades. Toward probing cellular heterogeneity in a population, the single-cell version of ECIS has also been explored, yet its intrinsic capability and limitation remain unclear. In this work, we argue for the fundamental feasibility of impedance spectroscopy to track changes of multiple cellular properties using a noninvasive single-cell approach. While changing individual properties is experimentally prohibitive, we take a simulation approach instead and mimic the corresponding changes using a 3D computational model. From the resultant impedance spectra, we identify the spectroscopic signature characteristic to each property considered herein. Since multiple properties change concurrently in practice, the respective signatures often overlap spectroscopically and become hidden. We further attempt to deconvolve such spectra and reveal the underlying property changes. This work provides the theoretical foundation to inspire experimental validation and adoption of ECIS for multiproperty single-cell measurements.

Cloning and characterization of the yjeA gene, encoding a novel deoxyribonuclease, from Bacillus subtilis.

The yjeA gene, encoding a secreted protein, YjeA, of Bacillus subtilis, was cloned and characterized. A derivative of YjeA, the recombinant YjeA-H, which contained a C-terminal His(6)-tag, was purified from Escherichia coli for functional studies. YjeA-H was shown to be an endonuclease, which hydrolyses both single-stranded and double-stranded DNA, but not RNA. Covalently closed circular pBR322 DNA incubated with YjeA-H was shown by gel electrophoresis to be first nicked to an open circular form, and then to a linearized structure on a background of DNA smear, and finally to small species of linear molecules that accumulated gradually. When (32)P-labelled pBR322 DNA was used as substrate, YjeA-H was shown to progressively nick both DNA strands in a random fashion, creating intermediates of various structures, as well as DNA smears comprising linear molecules of different sizes. The final products were found to consist essentially of degraded species of DNA. The detection of a putative signal peptide at the N-terminus of YjeA, together with the purification of YjeA-H from the culture supernatants of E. coli yjeA-H clones, and the identification of YjeA in the culture medium of Bacillus subtilis, supports the conclusion that YjeA is a secretory protein of Bacillus subtilis.

Cheiro-pedal syndrome: A revisit of etiology, localization and outcome.

OBJECTIVE: Cheiro-pedal syndrome (CPS) is an incomplete sensory disorder confined to hand and foot and is generally considered a benign entity. However, knowledge comes from case report or case series only. The aim of this study is to clarify the etiology, localization and outcome of CPS. PATIENT AND METHOD: A total of 21 CPS patients from our database and another 9 patients from literature were reviewed. CPS was classified into 4 types, namely unilateral and ipsilateral (Type I), bilateral (Type II), incomplete bilateral (Type III), and crossed (Type IV). RESULTS: They were 20 men and 10 women; including 20 Type I patients, 9 Type II patients, 1 Type III patients, and 0 Type IV patient. Vascular disorders, non-vascular cervical disorder and polyneuropathy were the responsible causes in 18 patients, 7 patients, and 2 patients, respectively. Etiology was unknown in another 3 patients. Lesions were located at brain parenchyma in 16 patients, and cervical cord above C5 level in 9 patients. Disable motoroparesis occurred between 4days to 2 months in two-third of deteriorated patients. In three patients, their lesions were detected only on recurrence or exacerbation of CPS 4 months to 2 years later. Recovery, residual deficit and deterioration ensued in 44%, 28% and 28% patients, respectively. A 33.3% of brain involvement patients and 100.0% of spinal involvement patients terminated to residual deficit or deterioration. The sensitivity and specificity of prediction for deterioration was 77.8% and 100%, respectively, by type II or III CPS. CONCLUSION: CPS is actually not a benign neurological disorder but a sensory alarm sign. A thorough examination of brain parenchyma and cervical spinal cord is urgent for identifying any treatable or preventable pathological lesions to reduce harmful consequence, especially in case of type II or III CPS.

Self-Locking Optoelectronic Tweezers for Single-Cell and Microparticle Manipulation across a Large Area in High Conductivity Media.

Optoelectronic tweezers (OET) has advanced within the past decade to become a promising tool for cell and microparticle manipulation. Its incompatibility with high conductivity media and limited throughput remain two major technical challenges. Here a novel manipulation concept and corresponding platform called Self-Locking Optoelectronic Tweezers (SLOT) are proposed and demonstrated to tackle these challenges concurrently. The SLOT platform comprises a periodic array of optically tunable phototransistor traps above which randomly dispersed single cells and microparticles are self-aligned to and retained without light illumination. Light beam illumination on a phototransistor turns off the trap and releases the trapped cell, which is then transported downstream via a background flow. The cell trapping and releasing functions in SLOT are decoupled, which is a unique feature that enables SLOT's stepper-mode function to overcome the small field-of-view issue that all prior OET technologies encountered in manipulation with single-cell resolution across a large area. Massively parallel trapping of more than 100,000 microparticles has been demonstrated in high conductivity media. Even larger scale trapping and manipulation can be achieved by linearly scaling up the number of phototransistors and device area. Cells after manipulation on the SLOT platform maintain high cell viability and normal multi-day divisibility.

Semiconductor Electronic Label-Free Assay for Predictive Toxicology.

While animal experimentations have spearheaded numerous breakthroughs in biomedicine, they also have spawned many logistical concerns in providing toxicity screening for copious new materials. Their prioritization is premised on performing cellular-level screening in vitro. Among the screening assays, secretomic assay with high sensitivity, analytical throughput, and simplicity is of prime importance. Here, we build on the over 3-decade-long progress on transistor biosensing and develop the holistic assay platform and procedure called semiconductor electronic label-free assay (SELFA). We demonstrate that SELFA, which incorporates an amplifying nanowire field-effect transistor biosensor, is able to offer superior sensitivity, similar selectivity, and shorter turnaround time compared to standard enzyme-linked immunosorbent assay (ELISA). We deploy SELFA secretomics to predict the inflammatory potential of eleven engineered nanomaterials in vitro, and validate the results with confocal microscopy in vitro and confirmatory animal experiment in vivo. This work provides a foundation for high-sensitivity label-free assay utility in predictive toxicology.

Point-of-Care Technologies for the Advancement of Precision Medicine in Heart, Lung, Blood, and Sleep Disorders.

The commercialization of new point of care technologies holds great potential in facilitating and advancing precision medicine in heart, lung, blood, and sleep (HLBS) disorders. The delivery of individually tailored health care to a patient depends on how well that patient's health condition can be interrogated and monitored. Point of care technologies may enable access to rapid and cost-effective interrogation of a patient's health condition in near real time. Currently, physiological data are largely limited to single-time-point collection at the hospital or clinic, whereas critical information on some conditions must be collected in the home, when symptoms occur, or at regular intervals over time. A variety of HLBS disorders are highly dependent on transient variables, such as patient activity level, environment, time of day, and so on. Consequently, the National Heart Lung and Blood Institute sponsored a request for applications to support the development and commercialization of novel point-of-care technologies through small businesses (RFA-HL-14-011 and RFA-HL-14-017). Three of the supported research projects are described to highlight particular point-of-care needs for HLBS disorders and the breadth of emerging technologies. While significant obstacles remain to the commercialization of such technologies, these advancements will be required to achieve precision medicine.

[Exploring the changes of the lived experience among siblings of children with cancer].

Few nursing studies in the past two decades have focused on siblings of children with cancer. Taking care of a hospitalized child with cancer, parents might neglect other children at home. Nursing providers need more information related to siblings and their psychosocial adaptation when one of their children is diagnosed with cancer and undergoing a variety of treatment protocols. The purpose of this study was to explore the changes in the experiences of preschool and school age siblings of children with cancer. A phenomenological study was conducted at a teaching hospital in southern Taiwan. Three children aged between five and nine years old who were siblings of a hospitalized cancer patient were approached in 2003-2004. Their families were also interviewed. Data included in-depth, formal and informal interviews, process recordings, drawings by the children, and a diary of reflections kept by the first author. Interviews lasted between 30 and 90 minutes. The qualitative data analysis method devised by Miles and Huberman (1994) was used. The findings indicated that there were three different changes in experience: Changes in psychological status, i.e., increase in worry about life, anxiety about the disease, and negative self-concepts; Changes in family interaction, i.e., relationship with mother, relationship with father, relationship with other siblings; Changes in social relationship, i.e., hunger for companions, changing recreation. Siblings do experience changes in their lives and may experience mal-adaptation. Nursing providers need to be aware of these changes and identify the health needs among caregivers and siblings of children with cancer. The findings of this study may be helpful to clinical nurses seeking to understand the needs of siblings of children with cancer.