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Due to increasing integrated circuit design complexity, engineering change orders (ECOs) have become a necessary technique to resolve late-found functional errors and/or performance deficiencies. To fix timing violations, gate sizing and buffer insertion are commonly used in postmask ECO. These techniques, however, may not be powerful enough, especially when spare cells are inserted to balance between functional and timing repair capabilities. We propose a postmask ECO technique, called TRECO, to remedy timing violations based on technology remapping, which also supports functional ECO. Unlike conventional technology mapping, TRECO performs technology mapping with respect to a limited set of spare cells and confronts dynamic changes of wiring cost incurred by selection of different spare cells. With a precomputed lookup table of representative circuit templates, TRECO iteratively performs technology remapping to restructure timing critical subcircuits until no timing violation can be further removed. Experimental results on five industrial designs show the effectiveness of TRECO in ECO timing optimization and in timing-aware functional ECO. [ABSTRACT FROM AUTHOR]

Functional dependency is concerned with rewriting a Boolean function f as a function h over a set of base functions {g1; . . . ; gn}, i.e., f = h(g1; . . . ; gn). It plays an important role in many aspects of electronic design automation (EDA). Prior approaches to the exploration of functional dependency are based on binary decision diagrams (BDDs), which may not be easily scalable to large designs. This paper formulates both single-output and multiple-output functional dependencies as satisfiability (SAT) solving and exploits extensively the capability of a modern SAT solver. Thereby, functional dependency can be detected effectively through incremental SAT solving, and the dependency function h, if it exists, is obtained through Craig interpolation. The proposed method enables 1) scalable detection of functional dependency, 2) fast enumeration of dependency function under a large set of candidate base functions, and 3) potential application to large-scale logic synthesis and formal verification. Experimental results show that the proposed method is far superior to prior work and scales well in dealing with the largest ISCAS and ITC benchmark circuits with up to 200K gates. [ABSTRACT FROM AUTHOR]

Objective: To investigate the influence of single-port laparoscopic percutaneous extraperitoneal closure (LPEC) on the orientation of the vas deferens and the volume and perfusion of the testis in pediatric patients undergoing inguinal hernia repair., Methods: A total of 92 consecutively enrolled boys diagnosed with unilateral inguinal hernia underwent single-port LPEC between June 2013 and June 2014. The orientation of the vas deferens and the testicular volume and perfusion of the patients were ultrasonographically assessed preoperatively and at 1 and 6 months after surgery., Results: All the surgical procedures were performed successfully without conversion or serious perioperative complications. Ultrasonography showed no angulation or distortion of the vas deferens on the surgical side during a six-month follow-up period. Similarly, no obvious changes were observed in the testicular volume or perfusion., Conclusions: Single-port LPEC is safe and effective in the treatment of pediatric inguinal hernia and does not affect the orientation of the vas deferens or testicular volume and perfusion.

Background & Aims: Accurate evaluation of liver fibrosis is crucial for predicting progression of chronic hepatitis B virus (HBV) infection. We assessed the utility of a novel fibrosis glycobiomarker Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA + -M2BP) for evaluating liver fibrosis and disease progression in patients with chronic HBV infection., Methods: We enrolled 774 patients with chronic HBV infection, with or without fibrosis, diagnosed by liver biopsy/FibroScan. Patients who underwent liver biopsy (n = 297) were divided into training (n = 221) and validation (n = 76) groups. Serum WFA + -M2BP values were measured and compared with FIB-4 index, aspartate aminotransferase (AST)-to-platelet ratio (APRI) and AST-to-alanine aminotransferase ratio (AAR) using receiver-operating characteristic (ROC) analysis., Results: Serum WFA + -M2BP levels increased significantly with fibrosis progression (P < 0.0001). Area under the ROC curve of WFA + -M2BP for diagnosing significant fibrosis was higher than that of FIB-4 (P = 0.198), APRI (P = 0.017) and AAR (P < 0.001), with sensitivity and specificity in the training set of 60.5% and 79.8% and validation set of 59.5% and 82.1%, respectively. Serum WFA + -M2BP levels were significantly correlated with FibroScan values (P < 0.0001) and improved the accuracy of FibroScan in assessing significant fibrosis. Changes in WFA + -M2BP levels were parallel with those in FibroScan values during nucleot(s)ide analogues therapy in patients with chronic HBV infection., Conclusions: WFA + -M2BP is an accurate serum indicator for assessing early stages of liver fibrosis and may monitor regression of fibrosis during the treatment of chronic HBV infection. WFA + -M2BP provides a simple and reliable alternative or complementary method to liver biopsy and FibroScan., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Implementing application-specific computation and control tasks within a biochemical system has been an important pursuit in synthetic biology. Most synthetic designs to date have focused on realizing systems of fixed functions using specifically engineered components, thus lacking flexibility to adapt to uncertain and dynamically-changing environments. To remedy this limitation, an analog and modularized approach to realize reconfigurable neuromorphic computation with biochemical reactions is presented. We propose a biochemical neural network consisting of neuronal modules and interconnects that are both reconfigurable through external or internal control over the concentrations of certain molecular species. Case studies on classification and machine learning applications using the DNA strain displacement technology demonstrate the effectiveness of our design in both reconfiguration and autonomous adaptation.

Objective: To evaluate the influence of insertion mutations occurring in the hydrophobic region, between amino acids 114 and 115, of the hepatitis B surface antigen (HBsAg) on viral antigenicity and replication., Methods: Hepatitis B virus (HBV) DNA was obtained from patients with HBsAg-positive chronic hepatitis B (CHB) infection and subjected to sequence analysis and comparison to GenBank reference sequences for HBV genotype B (AB073826) and genotype C (AF286594). Insertion mutations detected in the HBsAg region were used to make recombinant expression plasmids via site-directed mutagenesis. After transfecting the recombinant HBsAg into Huh7 cells, the mutants' effects on viral antigenicity and replication were evaluated by chemiluminescence microparticle immunoassay (CMIA) and Southern blot hybridization, respectively. The viral antigenicity of each mutant was predicted by bioinformatic analysis, using the Jameson-Wolf method to predict the antigenic index, the Hopp-Woods method to predict hydrophilicity, the Emini method to predict the probability of a region lying of the protein's surface, and the Karplus-Schulz method to predict the flexibility of the protein backbone., Results: Two CHB patients harbored HBV with insertion mutations in HBsAg: one with two (NT) and one with three (NTT) inserted amino acids between 114 and 115. The NTT recombinant HBsAg mutant showed no impact on viral replication and reacted weakly with anti-HBs in CMIA (P = 0.02). The antigen indices for the insertion of NTT were 1.00, -0.16, and 0.18, and insertion of the three amino acids affected the index values of five proximal amino acid sites (with an average increase of 0.13). The hydrophilic indices for the insertion of NTT were 0.2, -0.4, and -0.4, with no significant effect on the proximal amino acids. The insertion of the three amino acids changed both the surface probability (range: -0.55 to 2.97; affecting eight proximal amino acids) and the flexibility (range: -0.01 to 1.1; affecting five proximal amino acids)., Conclusion: The NTT three amino acids insertion in the HBsAg open reading frame, between 114 and 115 of the wild-type sequence, detected in a CHB patient may play a role in HBV immune escape without influencing the viral replicative capacity.

The objective of this study was to find potential biomarkers for predicting sustained virologic responses to interferon-alpha (IFN-alpha) treatment in chronic hepatitis B (CHB) patients. A total of 101 CHB patients were treated with pegylated IFN-alpha2a for 48 weeks and followed up for 24 weeks, including 34 IFN responders (IFN-Rs) and 67 IFN nonresponders (IFN-NRs). After peripheral blood mononuclear cells (PBMCs) and Epstein-Barr virus-transferred B (EBV-B) cell lines were treated with different concentrations of IFN-alpha in vitro, activated IFN-stimulated gene factor3 (ISGF3) and IFN-gamma-activation factor (GAF) were measured by EMSA, and MxA, OAS1, and PKR mRNA were measured by real-time PCR. Polymorphisms in the MxA promoter were genotyped to find the possible association. IFN-alpha-activated ISGF3 and GAF levels were similar between IFN-NRs and IFN-Rs. However, MxA mRNA induction in IFN-Rs was higher than that in IFN-NRs, and such discrepancy increased when highly concentrated IFN was used to stimulate. The OAS1 and PKR mRNA induction have a similar pattern between IFN-Rs and IFN-NRs. In addition, frequency of the MxA-88G/T genotype was significantly different between IFN-Rs and IFN-NRs, and this polymorphism was also functional because MxA mRNA induction in patients with GG genotype was lower than those with GT genotype. Regression analysis showed that MxA mRNA induction after 10,000 IU/mL IFN stimulation could serve as an independent factor for predicting IFN-alpha, with an area under curve (AUC) of 0.838, a positive predictive value of 68% for IFN-Rs, and a negative predictive value of 89% for IFN-NRs. MxA mRNA induced by IFN-alpha might predict sustained virologic responses to IFN-alpha treatment in CHB patients.