Protein structure prediction based on fragment assembly and parameter optimization.
We propose a novel method for ab-initio prediction of protein tertiary structures based on the fragment assembly and global optimization. Fifteen residue long fragment libraries are constructed using the secondary structure prediction method PREDICT, and fragments in these libraries are assembled to generate full-length chains of a query protein. Tertiary structures of 50 to 100 conformations are obtained by minimizing an energy function for proteins, using the conformational space annealing method that enables one to sample diverse low-lying local minima of the energy. Then in order to enhance the performance of the prediction method, we optimize the linear parameters of the energy function, so that the native-like conformations become energetically more favorable than the non-native ones for proteins with known structures. We test the feasibility of the parameter optimization procedure by applying it to the training set consisting of three proteins: the 10-55 residue fragment of staphylococcal protein A (PDB ID 1bdd), a designed protein betanova, and 1fsd.

title: Measures for the assessment of fuzzy predictions of protein secondary structure.
abstract: Many of the recent secondary structure prediction methods incorporate the idea of fuzzy set theory, where instead of assigning a definite secondary structure to a query residue, probability for the residue being in each of the conformational states is estimated. Moreover, continuous assignment of conformational states to the experimentally observed protein structures can be performed in order to reflect inherent flexibility. Although various measures have been developed for evaluating performances of secondary structure prediction methods, they depend only on the most probable secondary structures. They do not assess the accuracy of the probabilities produced by fuzzy prediction methods, and they cannot incorporate information contained in continuous assignments of conformational states to observed structures. Three important measures for evaluating performance of a secondary structure prediction algorithm, Q score, Segment OVerlap (SOV) measure, and the k-state correlation coefficient (Corr), are deformed into fuzzy measures F score, Fuzzy OVerlap (FOV) measure, and the fuzzy correlation coefficient (Forr), so that the new measures not only assess probabilistic outputs of fuzzy prediction methods, but also incorporate information from continuous assignments of secondary structure. As an example of application, prediction results of four fuzzy secondary structure prediction methods, PSIPRED, PROFking, SABLE, and PREDICT, are assessed using the new fuzzy measures.

title: A rapid screening method for the detection of viable spores in powder using bioluminescence.
abstract: A rapid diagnosis of a biological threat in a powder sample is important for fi rst responders who have to make decisions on-site. The present culture-based method does not provide timely results, which is a critical barrier for a quick response when a suspicious powder sample is found. The ATP bioluminescence method, combined with a heat shock, was investigated to determine the presence of spores in powder. The results show that only spore-containing powder samples provided a dramatic increase in the bioluminescence signal after the heat shock, which induces germination of the spores. Various conditions were tested to fi nd the most effective and rapid germination procedure. Elevated temperatures (37 degrees C and 50 degrees C) were more effective in germination than room temperature. At 50 degrees C, a double-strength germinant was more effective in germination than the regular strength. The 37 degrees C/15 min procedure induced the germination of spores most effectively, while a 50 degrees C/2 min procedure provided reasonably high signals, so it could make the entire procedure even faster (< 5 min). The detection limit of the bioluminescence method is < 100 spores.

title: Surgical management of pediatric adhesive bowel obstruction.
abstract: The objective of this study was to analyze a population-based database for recent trends in surgical management of pediatric adhesive bowel obstruction and compare open versus laparoscopic lysis of adhesions (LOA).



Pediatric adhesive bowel obstruction cases were identified in the Kids' Inpatients Database from 1997, 2000, 2003, 2006, and 2009. Data analysis included patients' demographics, hospital variables, length of stay (LOS), and total hospital charges (THC). Complications analysis included postoperative shock, hemorrhage, hematoma, seroma, wound complications, infection, fistula, and pulmonary complications.



In total, 20,679 pediatric adhesive bowel obstruction cases were identified during the study period. These were characterized by a median age of 11 years old, with 59.0% of the population female. Overall treatment included 88.6% open and 11.4% laparoscopic LOA. A more than twofold increase in utilization of laparoscopy was observed from 7.2% in 1997 to 17.2% in 2009 (P<.001). Complication rates were lower for laparoscopic LOA versus open (5.6% versus 10.4%; odds ratio 0.512; 95% confidence interval 0.394-0.667; P<.001), especially accidental puncture or laceration rate (2.2% versus 3.9%; odds ratio 0.566; 95% confidence interval 0.375-0.854; P=.006). Conversion to open LOA occurred in 1.9%. Laparoscopy was associated with a shorter median LOS (6 versus 8 days; P<.001) and a lower mean THC ($38,241.11 versus $48,552.51; P<.001) compared with open LOA. Multivariate regression analysis did not find hospital bed size, location, teaching status, and regions to be statistically significant predictors for utilization of laparoscopy.



Laparoscopic LOA is a safe option for pediatric adhesive bowel obstruction with lower complication rates and a reduced economic burden. Despite the increase in utilization of laparoscopy in recent years, only a minority of patients underwent laparoscopic LOA. Further studies are needed to identify and characterize the subgroup of patients who benefit from laparoscopic LOA.

title: Conditional deletion of the focal adhesion kinase FAK alters remodeling of the blood-brain barrier in glioma.
abstract: Gliomas generally infiltrate the surrounding normal brain parenchyma, a process associated with increased vascular permeability (VP) and dysregulation of the blood-brain barrier (BBB). However, the molecular mechanisms underlying glioma-induced VP in the brain remain poorly understood. Using a conditional, endothelium-specific deletion of the focal adhesion kinase (FAK) in the mouse (FAK CKO), we show that FAK is critical for destabilization of the tumor endothelium in tumor-bearing mice, with mutant mice exhibiting a relatively normalized vasculature compared with wild-type mice (FAK WT). Tumor vessels in the FAK CKO mice displayed reduced VP compared with FAK WT mice, resulting in reduced tumor growth. Additionally, FAK CKO mice displayed partial restoration of cell-cell junction proteins in the tumor vessels and astrocyte-endothelium interactions in tumors, revealing an additional role of astrocytes in mediating tumor-induced VP. Together, these results provide genetic evidence that FAK is a mediator of tumor-induced VP in the brain. Our findings may help understand how therapeutics might be used to regulate specific cell-type interactions to restore BBB structure/function in cancer and perhaps other pathologic conditions.

title: Improving contrast to noise ratio of resonance frequency contrast images (phase images) using balanced steady-state free precession
abstract: Recent MRI studies have exploited subtle magnetic susceptibility differences between brain tissues to improve anatomical contrast and resolution. These susceptibility differences lead to resonance frequency shifts which can be visualized by reconstructing the signal phase in conventional gradient echo (GRE) acquisition techniques. In this work, a method is proposed to improve the contrast to noise ratio per unit time (CNR efficiency) of anatomical MRI based on resonance frequency contrast. The method, based on the balanced steady-state free precession (bSSFP) MRI acquisition technique, was evaluated in its ability to generate contrast between gray and white matter in human brain at 3T and 7T. The results show substantially improved CNR efficiency of bSSFP phase images (2.85±0.21 times at 3 T and 1.71±0.11 times at 7 T) compared to the GRE data in a limited spatial area. This limited spatial coverage is attributed to the sensitivity of bSSFP to macroscopic B(0) inhomogeneities. With this CNR improvement, high resolution bSSFP phase images (resolution=0.3×0.3×2 mm(3), acquisition time=10min) acquired at 3T had sufficient CNR to allow the visualization of cortical laminar structures in invivo human primary visual cortex. Practical application of the proposed method may require improvement of B(0) homogeneity and stability by additional preparatory scans and/or compensation schemes such as respiration and drift compensation. Without these additions, the CNR benefits of the method may be limited to studies at low field or limited regions of interest.

title: Hydrotropic Solubilization of Paclitaxel: Analysis of Chemical Structures for Hydrotropic Property
abstract: AbstractPurpose. To identify hydrotropic agents that can increase aqueous paclitaxel (PTX) solubility and to study the chemical structures necessary for hydrotropic properties so that polymeric hydrotropic agents can be synthesized.
Methods. More than 60 candidate hydrotropic agents (or hydro- tropes) were tested for their ability to increase the aqueous PTX solubility. A number of nicotinamide analogues were synthesized based on the observation that nicotinamide showed a favorable hydrotropic property. The identified hydrotropes for PTX were used to examine the structure-activity relationship. N,N-Diethylnicotinamide (NNDENA) was found to be the most effective hydrotropic agent for PTX. The aqueous PTX solubility was 39 mg/ml and 512 mg/ml at NNDENA concentrations of 3.5 M and 5.95 M, respectively. These values are 5-6 orders of magnitude greater than the intrinsic solubility of 0.30 ± 0.02 μg/ml. N-Picolylnicotinamide, N-allylnicotinamide, and sodium salicylate were also excellent hydrotropes for PTX. Solubility data showed that an effective hydrotropic agent should be highly water soluble while maintaining a hydrophobic segment.
 The present study identified several hydrotropic agents effective for increasing aqueous solubility of PTX and analyzed the structural requirements for this hydrotropic property. This information can be used to find other hydrotropic compounds and to synthesize polymeric hydrotropes that are effective for PTX and other poorly water-soluble drugs.