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Background Hyperkeratosis lenticularis perstans (HLP), also known as Flegel disease, is a rare skin disease presenting with asymptomatic small hyperkeratotic papules. The lesions often appear on the dorsal feet and lower legs, and typically develop after the fourth decade of life. A genetic basis for HLP is suspected; however, so far no gene defect linked to the development of HLP has been identified. Objectives We aimed to identify the genetic cause of HLP. Methods For mutational analysis we studied a cohort of five patients with HLP using next-generation sequencing (NGS). We used DNA ­extracted from fresh skin biopsies alongside ethylenediamine tetraacetic acid (EDTA) blood samples from two patients, and formalin-fixed ­paraffin-embedded skin biopsy material from three patients. In addition, immunofluorescence staining of HLP lesions from four patients was investigated. Results In all samples from the five patients with HLP we identified by NGS rare variants in the SPTLC1 gene. In four patients we detected small deletions/frameshift variants and in one patient a splicing variant, predicted to disturb the splicing process. In blood samples the detected variants were heterozygous with an allele frequency of 49% and 50%, respectively. In skin biopsies the allele frequency was within the range of 46–62%. Immunofluorescence staining revealed reduced SPTLC1 protein levels in skin of patients. Conclusions Our findings suggest that pathogenic variants in the SPTLC1 gene are the underlying genetic cause of HLP. Of note, the identified variants were either frameshift- or splicing variants probably leading to nonsense-mediated mRNA decay and thus reduced SPTLC1 protein levels. We conclude that diminished SPTLC1, the key enzyme in sphingolipid biosynthesis, leads to the development of HLP, which highlights the sphingolipid pathway as a new therapeutic target.

Study design Systematic review and meta-analysis Objectives Postoperative ileus (POI) can negatively impact patient recovery and surgical outcomes after spine surgery. Emerging studies have focused on the risk factors for POI after spine surgery. This study aimed to review the available literature on risk factors associated with POI following elective spine surgery. Methods Electronic databases were searched to identify relevant studies. Meta-analysis was performed using random-effect model. Risk factors for POI were summarized using pooled odds ratio (OR) with 95% confidence intervals (CI). Results Twelve studies were included in the present review. Meta-analysis demonstrated males exhibited a higher risk of POI than females odds ratio (OR, 1.76; 95% CI, 1.54-2.01). Patients with anemia had a higher risk of POI than those without anemia (OR, 1.48; 95% CI, 1.04-2.11). Patients with liver disease (OR, 3.3; 95% CI, 1.2-9.08) had a higher risk of POI. The presence of perioperative fluid and electrolyte imbalances was a predictor of POI (OR, 3.24; 95% CI, 2.62-4.02). Spine surgery involving more than 3 levels had a higher risk of POI compared to that with 1-2 levels (OR, 1.82; 95% CI, 1.03-3.23). Conclusions Male sex and the presence of anemia and liver disease were significant patient factors associated with POI. Perioperative fluid and electrolyte imbalance and multilevel spine surgery significantly increased the risk of POI. In addition, through this comprehensive review, we identified several perioperative risk factors associated with the development of POI after spine surgery.

Surgery or whole-brain radiotherapy (WBRT) for the management of brain metastasis of hepatocellular carcinoma (HCC) is associated with improved survival. However, the efficacy of multi-tyrosine kinase inhibitors (TKIs) and possible bleeding complications have not been studied in these patients. Therefore, this study aimed at investigating TKI safety and efficacy in these patients. We retrospectively reviewed 39 patients who underwent surgery or WBRT for brain metastasis of HCC. Intracranial tumor bleeding rates were compared between patients who did and did not receive TKIs. Survival outcomes were analyzed using the log-rank and Cox regression tests. A total of 22 and 7 patients received sorafenib and lenvatinib, respectively. The intracranial tumor bleeding rates were 61.5% and 70% in patients who did and did not receive TKIs, respectively (p > 0.99). Survival analysis revealed craniotomy (adjusted odds ratio [AOR]: 0.45, p = 0.04), a higher Karnofsky Performance Score (AOR: 0.97, p < 0.01), and TKI use (AOR: 0.26, p < 0.01) were positive prognostic factors for overall survival. TKIs were associated with better survival outcomes in patients who underwent surgery or WBRT for brain metastasis of HCC and did not increase intracranial bleeding. Therefore, TKIs are efficacious and safe for treating brain metastasis of HCC.

T lymphocyte infiltration with immunotherapy potentially suppresses most devastating brain tumors. However, local immune privilege and tumor heterogeneity usually limit the penetration of immune cells and therapeutic agents into brain tumors, leading to tumor recurrence after treatment. Here, a rabies virus glycoprotein (RVG)-camouflaged gold yarnball (RVG@GY) that can boost the targeting efficiency at a brain tumor

Unilateral sphenoid dysplasia is a rare but distinctive manifestation of neurofibromatosis type 1, causing pulsatile exophthalmos, decreased vision, and facial deformity. Surgical intervention is required to prevent visual deterioration. However, the reconstruction of a complex cranial base defect while fulfilling cosmetic needs is challenging. The asymmetric anatomy impedes identification and preservation of vital structures, and the use of bone grafts is often unsustainable due to resorption. Here we demonstrate a multimodal technique combining mirror-image-based virtual surgical planning, stereolithography, and neuronavigation to achieve skull base reconstruction and restore facial symmetry in an neurofibromatosis type 1 patient with sphenoid dysplasia. Preoperative surgical planning involved mirror-image simulation based on the unaffected contralateral counterpart and a stereolithographic skull-base model fabricated to design a patient-specific titanium mesh. Surgical reconstruction via the transcranial approach under intraoperative neuronavigation was performed. Immediate resolution of pulsatile proptosis was observed postoperatively. With the help of virtual surgical planning, stereolithography, and neuronavigation, precise and sustainable reconstruction with patient-specific implants can be tailored for a complex skull base defect.

Climate change has gradually become a great challenge for heritage conservation. This study demonstrated that a hierarchal strategy corresponding to the scale of climate or weather date can be an alternative approach to making heritage conservation more efficient and sustainable. Therefore, the passive environmental control strategies at neighborhood and block scales are developed to effectively connect climate actions, normally at global or city scales, and the traditional preservation methods at building scale. The research results reflect the same conclusion as previous studies in that wind is the key factor affecting degradation mechanisms on heritage assets. Moreover, the adoption of weather data is a critical factor that influences the accuracy of computational fluid dynamics (CFD) simulation results of the detailed regional wind performance, which is supportive for strategy development. According to the simulation results, the study site, Huatzai village, with neighborhood-scale strategy can gain an improvement in overall wind impact. The velocity reduction is more than 70% in the windward areas. The block-scale strategy with the reuse of existing structures can bring 90% velocity reduction for the wake areas and the high-risk zones with strong turbulence.

Compared to the full-bridge diode rectifier, this paper presents a Parallel-SSHI piezoelectric energy harvesting system to improve the efficiency in a 0.35-um CMOS process. The implemented interface based on the Parallel-SSHI technique can harvest from periodic and shock excitations. The device is capable of cold startup and provides a stable output voltage for powering an application.

A high-frequency magnetic field (MF) generates an electric current by charging conductors that enable the induction of various biological processes, including changes in cell fate and programming. In this study, we show that electromagnetized carbon porous nanocookies (NCs) under MF treatment facilitate magnetoelectric conversion for growth factor release and cell stimulation to induce neuron cell differentiation and proliferation in vitro and in vivo. Integrating four-dimensional printing technology, the NCs are exposed on the surface, which enhances the cell adhesion and allows direct manipulation of electromagnetic stimulation of the cells. Remarkably, large amounts of growth factor encapsulated in NC@conduit resulted in excellent permeability and on-demand release, improving the in vivo layers of myelin sheaths and directing the axon orientation at 1 month postimplantation. This study offers proof of principle for MF-guided in vivo neuron regeneration as a potentially viable tissue regeneration approach for neuronal diseases. Researchers in Taiwan have developed a printable biomaterial that has potential for neuron regeneration and treating neural diseases. Four-dimensional printed materials are objects created using 3D printing technology but whose properties can be altered in time, by electrical pulses for example. A team led by San-Yuan Chen from National Chiao Tung University and Shang-Hsiu Hu from National Tsing Hua University, both in Hsinchu, made biomedical four-dimensional printed material by combining stretchable and biocompatible graphene oxide nanosheets with so-called nanocookies: porous carbon with silica embedded into its surface. The pores in the carbon act as a scaffold on which neurons can grow, and an electric current induced in the silica by a high-frequency magnetic field stimulated this growth. The team observed this stimulation in both cell cultures and rat models. 4D Printing Conduits: Electromagnitized carbon porous nanoccookies (NCs) under MF facilitate magneto-electrical conversion for growth factor release and cell simulation. Integrating four-dimensional (4D) printed technology, exposed NCs are able to enhances the cell adhesion and manifest directly electromagnetic stimulation to cells.

A wideband image-rejection sub-harmonic in-phase/quadrature (IQ) mixer is designed and implemented on standard $0.18-\mu\mathrm{m}$ CMOS technology. To maintain high image-rejection ratio over a wide bandwidth, a local oscillator (LO) broadband 45° power splitter combined with a doubly balanced sub-harmonic Gilbert-cell mixer has been selected. The image rejection ratio is better than −30 dB from 22 to 40 GHz. The measured conversion gain of the receiver lies within −25 to −8 dB.

The human skin is involved in protecting the inner body from constant exposure to outer environmental stimuli. There is an evident need to screen for toxicity and the efficacy of drugs and cosmetics applied to the skin. To date, animal studies are still the standard method for substance testing, although they are currently controversially discussed Therefore, the multi-organ chip is an attractive alternative to replace animal testing. The two-organ chip is designed to hold 96-well cell culture inserts (CCIs). Small-sized skin equivalents are needed for this. In this study, full-thickness skin equivalents (ftSEs) were generated successfully inside 96-well CCIs. These skin equivalents developed with in vivo-like histological architecture, with normal differentiation marker expressions and proliferation rates. The 96-well CCI-based ftSEs were successfully integrated into the two-organ chip. The permeation of fluorescein sodium salt through the ftSEs was monitored during the culture. The results show a decreasing value for the permeation over time, which seems a promising method to track the development of the ftSEs. Additionally, the permeation was implemented in a computational fluid dynamics simulation, as a tool to predict results in long-term experiments. The advantage of these ftSEs is the reduced need for cells and substances, which makes them more suitable for high throughput assays. The human skin is involved in protecting the inner body from constant exposure to outer environmental stimuli. There is an evident need to screen for toxicity and the efficacy of drugs and cosmetics applied to the skin. To date, animal studies are still the standard method for substance testing, although they are currently controversially discussed Therefore, the multi-organ chip is an attractive alternative to replace animal testing. The two-organ chip is designed to hold 96-well cell culture inserts (CCIs). Small-sized skin equivalents are needed for this. In this study, full-thickness skin equivalents (ftSEs) were generated successfully inside 96-well CCIs. These skin equivalents developed with in vivo-like histological architecture, with normal differentiation marker expressions and proliferation rates. The 96-well CCI-based ftSEs were successfully integrated into the two-organ chip. The permeation of fluorescein sodium salt through the ftSEs was monitored during the culture. The results show a decreasing value for the permeation over time, which seems a promising method to track the development of the ftSEs. Additionally, the permeation was implemented in a computational fluid dynamics simulation, as a tool to predict results in long-term experiments. The advantage of these ftSEs is the reduced need for cells and substances, which makes them more suitable for high throughput assays.

In vitro cultivated skin models have become increasingly relevant for pharmaceutical and cosmetic applications, and are also used in drug development as well as substance testing. These models are mostly cultivated in membrane-insert systems, their permeability toward different substances being an essential factor. Typically, applied methods for determination of these parameters usually require large sample sizes (e.g., Franz diffusion cell) or laborious equipment (e.g., fluorescence recovery after photobleaching (FRAP)). This study presents a method for determining permeability coefficients directly in membrane-insert systems with diameter sizes of 4.26 mm and 12.2 mm (cultivation area). The method was validated with agarose and collagen gels as well as a collagen cell model representing skin models. The permeation processes of substances with different molecular sizes and permeation through different cell models (consisting of collagen gel, fibroblast, and HaCaT) were accurately described. Moreover, to support the above experimental method, a simulation was established. The simulation fits the experimental data well for substances with small molecular size, up to 14 x 10-10 m Stokes radius (4,000 MW), and is therefore a promising tool to describe the system. Furthermore, the simulation can considerably reduce experimental efforts and is robust enough to be extended or adapted to more complex setups.

In this paper, a partial parity cache and data cache management method is presented for reducing the parity updating cost of a solid-state disk (SSD) based redundant array of inexpensive disk (RAID) system, thereby which the input/output (I/O) performance of the RAID system can be improved. SSDs have many advantages compared to hard disk drives. However, it is not advisable to directly add SSDs into a RAID system because doing so will decrease the performance and the life-time of the SSDs. In the RAID-5 system, parity generation includes read and write operations to the SSDs. Whenever there is a new write request to the RAID, the related parity must be updated and written to the SSDs. Such frequent parity updates result in poor RAID performance and shortens the life-time of the SSDs. This paper combines the prior methods and the proposed efficient buffer management method with a data cache. The proposed method reduces the number of read and write operations for generating parities in the RAID system. Experimental results show that the I/O performance of the RAID-5 system can be improved by 76% by using the proposed method.

The resistance switching behavior in sputtered Ti/ZrO2/Pt sandwiched structure was investigated for nonvolatile memory application. Multiple current-voltage measurements reveal highly uniform distribution of the conduction current and switching voltage. This bipolar resistive switching driven by bias of proper magnitude and polarity is interpreted by filament model. The reset threshold increases with the compliance setting imposed on the turn-on transition, while the switching currents in high and low resistance states are not varied for different top-electrode areas. Both characteristics are ascribed to the electro-chemical reactions of field-induced reduction-oxidation processes.

Background The Multi-Organ-Chip (MOC) is a new micro size bioreactor. It offers two tissue cultivation segments (e.g. skin model, liver cells), which are connected by a dynamic micro pump system. [1,2] One future application of this system is the dermal application of substances for drug testing in vitro. In this study a method to simulate and validate the permeation of fluorescein sodium salt through a barrier in the MOC was established. Fluorescein sodium salt has a molecular weight of 376.28 g/mol which is in the range of steroid hormones like testosterone (288.4 g/mol), aldesterone (360.4 g/mol), hydrocortisone (362.5.4 g/ mol) and corticosterone (346 g/mol) [3]. Furthermore, first permeation experiments through four cell-collagen models, as reference for skin models, were carried out.

Purpose: To investigate dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) of advanced nonsmall-cell lung cancer (NSCLC) patients treated with the antiangiogenic agent bevacizumab combined with gemcitabine and cisplatin as first-line treatment. Materials and Methods: All patients were enrolled for MRI and computed tomography (CT) before and after the first three courses of bevacizumab combination chemotherapy. Pharmacokinetic parameters (Ktrans, kep, ve, vp) derived from DCE MRI were computed for the main mass. Parametric histogram analysis was obtained to evaluate changes of the internal tumor composition and for correlation with tumor response measured on CT. Results: After three cycles of treatment, 11 patients showed decreased tumor size and a decreased value of all MR-derived pharmacokinetic parameters. Among these parameters, there was a significant decrease of mean and standard deviation of the Ktrans histogram as well as a decrease of mean of the kep histogram (P < 0.05). Tumors with larger mean values of rate constant kep (P < 0.0001) and smaller standard deviation of volume of extravascular extracellular space fraction ve (P < 0.0001) on histograms before chemotherapy were considered predictors for treatment response. Conclusion: DCE MRI enables a functional analysis of the treatment response of NSCLC. MRI parametric histogram has the potential to predict early treatment response of combined bevacizumab, gemcitabine, and cisplatin. J. Magn. Reson. Imaging 2012;36:387–396. ©2012 Wiley Periodicals, Inc.

Appropriate ventilation in a classroom is helpful for enhancing air exchange rate and student concentration. This study focuses on the effects of fenestration in a four-story school building by performing numerical simulation of a building when considering indoor and outdoor environments simultaneously. The wind profile function embedded in PHOENICS code was set as the inlet boundary condition in a suburban environment. Sixteen fenestration combinations were compared in a classroom containing thirty seats. This study evaluates mean age of air (AGE) and airflow pattern of a classroom on different floors. Considering both wind profile and fenestration effects, the airflow on higher floors is channeled toward the area near ceiling in a room and causes older mean age of air in the breathing zone. The results in this study serve as a useful guide for enhancing natural ventilation in a typical school building., {"references":["V. Straaten, Thermal Performance of buildings, Amsterdam: Elsevier,\n1967.","W.H Chiang, C.J. Wu, K.Y. Weng, and L.D. Yang, \"The effects of fa├ºade\ndesign on cross-ventilation for Taiwanese classroom,\" ASHRAE\nTransactions, vol.111, pp.333-339, Jun. 2005.","E. Prianto and P. Depecker, \"Optimization of architectural design\nelements in tropical humid region with thermal comfort approach,\"\nEnergy and Buildings, vol.35, no.3, pp.273-280, Mar. 2003.","S. S. Ayad, \"Computational study of natural ventilation,\" Wind\nengineering and industrial aerodynamics, vol.82, no.1-3, pp.49-68, Aug.\n1999.","C.C. Hsu and T.K. Huang, The plane of module size for dwelling house\nand school building, Taiwan: Architecture and Building Research\nInstitute, Ministry of the Interior, 1991.","C.Y. Liou, The appropriate size of building materialÔÇö the cases of\nalumina door and window, and brick on building fa├ºade, Master thesis of\nNational Cheng-Kung University, 1991.","W.I. Li, the study of the influence on students as teacher-s personality,\nMater thesis of National Cheng-Chi University, 1998.","M. Santamouris and D. Asimakopoulos, Passive cooling of building, UK:\nJames & James, 1996.","S. Kato, S. Murakami, T. Takahashi, and T. Gyobu, \"Chained analysis of\nwind tunnel test and CFD on cross ventilation of large-scale market\nbuilding,\" Wind Engineering and Industrial Aerodynamics, vol.67-68,\npp.573-587, Apr.-Jun. 1997.\n[10] G.C. Graca, Q. Chen, L.R. Glicksman, and L.K. Norford, \"Simulation of\nwind-driven ventilation cooling systems for an apartment building in\nBeijing and Shanghai,\" Energy and Buildings, vol.34, no.1, pp.1-11, Jan.\n2002.\n[11] Z. Zhai, S.D. Hamilton, J. Huang, C. Allocca, N. Kobayashi, and Q. Chen,\n\"Integration of indoor and outdoor airflow study for natural ventilation\ndesign using CFD,\" in Conf. Proceedings of the 21st AIVC Annual Conf.\non Innovations in Ventilation Technology, Netherlands, 2000.\n[12] J. Seifert, Y. Li, J. Axley, and M. Rösler, \"Calculation of wind-driven\ncross ventilation in buildings with large openings,\" Wind Engineering and\nIndustrial Aerodynamics, vol.94, no.12, pp.925-947, Dec. 2006.\n[13] J. Franke, A. Hellsten, H. Schl├╝nzen, and B. Carissimo, \"Best practice\nguideline for the CFD simulation of flows in the urban environment.\"\nCOST Action 732: Quality assurance and improvement of microscale\nmeteorological models, 2007.\n[14] T. Karimipanah, H.B. Awbi, M. Standberg, and C. Blomqvist,\n\"Investigation of air quality, comfort parameters and effectiveness for two\nfloor-level air supply systems in classrooms,\" Building and Environment,\nvol.42, no.2, pp.547-655, Feb. 2007.\n[15] H.B. Awbi, \"Chapter7-ventilation,\" Renewable and Sustainable Energy\nReviews, vol.2, pp.157-188, 1998.\n[16] ASHRAE, ASHRAE Handbook Fundamentals, 2005, chapter 27:\nventilation and infiltration.\n[17] \"Air change rates for typical rooms and buildings\" in\nhttp://www.engineeringtoolbox.com/air-change-rate-room-d_867.html.\n[18] ASHRAE, ASHRAE Standard 62-1989: Ventilation for acceptable indoor\nair quality, Atlanta, GA, 1989.\n[19] V. Chanteloup and P.S. Mirade, \"Computational fluid dynamics modeling\nof mean age of air distribution in forced-ventilation food plants.\" Journal\nof Food Engineering, vol.90, no.1, pp.90-103, Jan. 2009.\n[20] X. Li, D. Li, X. Yang, and J. Yang, \"Total air age: an extension of the air\nage concept,\" Building and Environment, vol.38, no.11, pp.1263-1269,\nNov. 2003."]}