cssi/SciSciGPT-SciSciNet huggingface dataset:
Intraoperative assessment of isocitrate dehydrogenase mutation status in human gliomas using desorption electrospray ionization-mass spectrometry.

OBJECTIVE The authors describe a rapid intraoperative ambient ionization mass spectrometry (MS) method for determining isocitrate dehydrogenase (IDH) mutation status from glioma tissue biopsies. This method offers new glioma management options and may impact extent of resection goals. Assessment of the IDH mutation is key for accurate glioma diagnosis, particularly for differentiating diffuse glioma from other neoplastic and reactive inflammatory conditions, a challenge for the standard intraoperative diagnostic consultation that relies solely on morphology. METHODS Banked glioma specimens (n = 37) were analyzed by desorption electrospray ionization-MS (DESI-MS) to develop a diagnostic method to detect the known altered oncometabolite in IDH-mutant gliomas, 2-hydroxyglutarate (2HG). The method was used intraoperatively to analyze tissue smears obtained from glioma patients undergoing resection and to rapidly diagnose IDH mutation status (< 5 minutes). Fifty-one tumor core biopsies from 25 patients (14 wild type [WT] and 11 mutant) were examined and data were analyzed using analysis of variance and receiver operating characteristic curve analysis. RESULTS The optimized DESI-MS method discriminated between IDH-WT and IDH-mutant gliomas, with an average sensitivity and specificity of 100%. The average normalized DESI-MS 2HG signal was an order of magnitude higher in IDH-mutant glioma than in IDH-WT glioma. The DESI 2HG signal intensities correlated with independently measured 2HG concentrations (R2 = 0.98). In 1 case, an IDH1 R132H-mutant glioma was misdiagnosed as a demyelinating condition by frozen section histology during the intraoperative consultation, and no resection was performed pending the final pathology report. A second craniotomy and tumor resection was performed after the final pathology provided a diagnosis most consistent with an IDH-mutant glioblastoma. During the second craniotomy, high levels of 2HG in the tumor core biopsies were detected. CONCLUSIONS This study demonstrates the capability to differentiate rapidly between IDH-mutant gliomas and IDH-WT conditions by DESI-MS during tumor resection. DESI-MS analysis of tissue smears is simple and can be easily integrated into the standard intraoperative pathology consultation. This approach may aid in solving differential diagnosis problems associated with low-grade gliomas and could influence intraoperative decisions regarding extent of resection, ultimately improving patient outcome. Research is ongoing to expand the patient cohort, systematically validate the DESI-MS method, and investigate the relationships between 2HG and tumor heterogeneity.
Dexmedetomidine Provides Fewer Respiratory Events Compared With Propofol and Fentanyl During Third Molar Surgery: A Randomized Clinical Trial.

Purpose Propofol and fentanyl can cause airway obstruction and respiratory depression when used together for intravenous sedation. This study investigated whether dexmedetomidine and midazolam would decrease respiratory events requiring intervention during deep sedation compared with propofol, fentanyl, and midazolam. Patients and methods A prospective, randomized, double-blinded, controlled trial was designed to assess 2 intravenous treatment groups during third molar surgery. Patients were randomized into 2 groups. The control group (group P) received 0.8 μg/kg of fentanyl followed by propofol infusion at 125 μg/kg per minute over a 10-minute period with intraoperative boluses of 0.1 μg/kg. The study group (group D) received dexmedetomidine bolus infusion of 1 μg/kg over a 10-minute period followed by maintenance infusion at 0.5 μg/kg per hour. Both groups were given 0.03 mg/kg of midazolam before infusion. Scorers, masked to group, viewed the procedure remotely and evaluated the primary outcome variable of respiratory events requiring intervention. Secondary outcome variables evaluated by the scorers included the Behavioral Pain Scale for non-intubated patients at initial injection, cooperation score at 5 and 15 minutes, and time to ambulation and discharge. Patient satisfaction and hemodynamic stability were measured. The difference between groups regarding the occurrence of respiratory events was tested using the Fisher exact test, and mixed-effects models were used to compare repeated vital signs. Results The sample was composed of 141 patients randomly assigned to either group P (n = 67) or group D (n = 74). No statistically significant differences in the distribution of study variables were found between groups at baseline. A statistically significant difference in respiratory events requiring deliberate intervention existed between group P (25.4%) and group D (2.7%) (P Conclusions Using dexmedetomidine and midazolam for outpatient surgery resulted in fewer respiratory events requiring deliberate intervention compared with propofol, fentanyl, and midazolam. Ambulation and discharge times were not prolonged using dexmedetomidine.
Divergent Amygdala Volume Asymmetries for Male and Female Youth With High Versus Low Callous-Unemotional Traits:

Although callous-unemotional (CU) traits have been associated with amygdala hypoactivity, it is unclear whether such traits are associated with amygdala structure. This study examines the relations...
The Dietitian Role in Non-Celiac Gluten Sensitivity

The chapter presents the management of a young adult female with longstanding history of abdominal pain, bloating, diarrhea, and fatigue, all of which improved with dietary restrictions following a diagnosis of non-celiac gluten sensitivity (NCGS). The dietitian assesses the response to low-FODMAP elimination diet after 4 weeks, followed by the rechallenge phase with individualized diet for asymptomatic food categories. The patient was instructed on how to liberalize her diet to reduce or avoid trigger foods found during the rechallenge phase. The chapter addresses dietary interventions to differentiate between NCGS and fructan intolerance.
The Role of Intuition and Perception in Decision Making under Time Constraint in Tournament Chess and Probability: J M Keynes and Herbert Simon

Keynes’s father, J N Keynes ,was a ranked and rated chess master in tournament chess who played first board in OTB (Over-The- Board) matches for Cambridge University in the late 1870’s and early 1880’s.J M Keynes undoubtedly learned how to play chess from his father. However, what he also learned was the important role that intuition and perception play in the OTB chess competition, but not in correspondence (postal) chess. The nearly three hundred year old claim, originally made by J.Bentham , which is still the foundation for all classical ,neoclassical, new classical, and new neoclassical theories, is that decision makers are able to calculate an optimal numerical outcome and an optimal ,numerical probability, on which to base their future decisions (moves) in the game of life (chess) under no time constraint. Thus, the decision problem specified by Bentham is, by analogy, the type of situation faced in Correspondence or postal chess. This is also what F P Ramsey’s subjective approach to probability entails-There is no time constraint on the decision maker. Ramsey would have been a horrible (under 800 USCF) OTB chess player since he would lose all his games on time as his clock fell. However, Ramsey’s approach would have made him a very formidable postal or correspondence chess player, where one has no effective time constraint and a player can search for the best, optimal move whereas OTB players are looking for a good (Simon’s satisfactory outcome) move based on their intuitive perception of their study of similar positions from chess theory and competitive experience, given the unclear and ambiguous positions that appear often in middle game situations on the chessboard. Both Keynes and Simon understood that, in most situations on the chess (OTB) board, as well in the game of life, the operational time constraint makes it impossible to calculate a best or optimal outcome or probability over the board or in real life economic, political, and social decision problems or situations. However, it is possible to discover what is called a good or interesting move, which Simon characterized as a satisfying approach, as opposed to maximizing. I know of no tournament chess player in my lifetime of any rating, excluding those who have become academic economists and have turned their backs on the qualities they know were required to become a good chess player, so as to be in step with the Benthamite Utilitarian economist claim that all decision makers can calculate optimal or best decisions in the future, who believes that they can generally calculate precisely over the board.
Pain modulatory network is influenced by sex and age in a healthy state and during osteoarthritis progression in rats.

Old age and female sex are risk factors for the development of osteoarthritis (OA) and chronic pain. We investigated the effects of sex and age on pain modulatory networks in a healthy state and during OA progression. We used functional MRI to determine the effects of sex and age on periaqueductal gray functional connectivity (PAG FC) in a healthy state (pre-OA) and during the early and late phases of monosodium iodoacetate (MIA)-induced OA in male and female Fischer 344 rats (young, 3-6 mo / old, 20-24 mo). For functional MRI, rats were scanned using a Bruker 7T MRI (TR = 1500 ms, in plane resolution = 400 μm, slice thickness 1 mm, acquisition time: 15 minutes) and under isoflurane anesthesia ≤ 1.5%. We then examined how sex and age affect longitudinal changes in PAG FC in OA. In a healthy state, females exhibited more widespread PAG FC than males, and this effect was exaggerated with aging. Young males had moderate PAG FC changes during the early phase but recruited additional brain regions, including the rostral anterior cingulate cortex (ACC), during the late phase. Young females exhibited widespread PAG FC in the early phase, which includes connections to insula, caudal ACC, and nucleus accumbens (NAc). Older groups had strong PAG FC with fewer regions in the early phase, but they recruited additional brain regions, including NAc, in the late phase. Overall, our findings show that PAG FC is modulated by sex and age in a healthy state. A widespread PAG network in the early phase of OA pain may contribute to the transition from acute to chronic OA pain and the increased risk of developing chronic pain for females. Enhanced PAG FC with the reward system may represent a potential mechanism underlying chronic OA pain in elderly patients. NIH-NIA grant AG053783 (JYR) and NIH-NIDCR grant DE0027808 (JYR).
Position and orientation of vaginal pessaries in situ on magnetic resonance imaging.

We hypothesize that there are differences in the position and orientation of ring and Gellhorn pessaries in situ on magnetic resonance imaging (MRI). This was a retrospective cohort study comparing MRI findings in 25 women with pessaries in situ at the time of imaging. Scanner coordinates for anatomic and pessary landmarks were obtained and transformed to 3D Pelvic Inclination Correction System coordinates using MATLAB software. The normal vector to the pessary disc was computed and compared to the positive y-axis in the sagittal and coronal planes to determine XY and YZ disc angles, respectively. Comparisons between groups were made using Wilcoxon rank, Fisher’s exact, and Brown-Forsythe tests. Twenty-one women with ring pessaries and four women with Gellhorn pessaries met inclusion criteria for the study. Women with ring pessaries were younger (68.4 vs. 80.7 years, p = 0.003) but had similar BMI, vaginal parity, history of hysterectomy, and anatomic characteristics. Ring pessaries had a smaller diameter (59.5 vs. 79.3 mm, p = 0.004) and were positioned further posterior with respect to the inferior pubic point (midpoint X position 42.6 vs. 29.5 mm, p = 0.004). There were significant differences in the magnitude and variance of the XY disc angle (57.0 ± 14.0 vs. -1.2 ± 2.8 degrees, p = 0.002 for magnitude, p = 0.012 for variance) but not the YZ disc angle (3.3 ± 30.6 vs. 1.5 ± 7.7 degrees, p > 0.05 for both) between groups. We found differences in the position and orientation between ring and Gellhorn pessaries in situ using an anatomic 3D reference system. These findings provide insight into the mechanism of action of vaginal pessaries.
Soft Issues in the Software Industry (a)

This case is part of the Giving Voice to Values (GVV) curriculum. To see other material in the GVV curriculum, please visit http://store.darden.virginia.edu/giving-voice-to-values.Rahul had to make an important decision that could affect the career of several people, including his boss. Excerpt UVA-OB-1172 Giving Voice to Values Rev. Dec. 28, 2016 Soft Issues in the Software Industry (A), On the evening of 30 September 2008, Rahul sat in his cubicle at XYZ's Gurgaon office, with his head in his hands. Over the next few hours, he had to make an important decision that could affect the career of several people, including his boss. Just 36 hours ago, his client's main database, which included a record of all transactions on the client's online supply-chain portal, had been critically affected when more than 10 million transactions were deleted. On discovering this, Rahul's team had worked continuously and tirelessly to rectify the mistake with minimum data losses. The whole team had sighed with relief after the problem had been resolved. . . .
Photodynamic Therapy for Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of human cancers. Clinical trials of various chemotherapy, radiotherapy, targeted agents and combination strategies have generally failed to provide meaningful improvement in survival for patients with unresectable disease. Photodynamic therapy (PDT) is a photochemistry-based approach that enables selective cell killing using tumor-localizing agents activated by visible or near-infrared light. In recent years, clinical studies have demonstrated the technical feasibility of PDT for patients with locally advanced PDAC while a growing body of preclinical literature has shown that PDT can overcome drug resistance and target problematic and aggressive disease. Emerging evidence also suggests the ability of PDT to target PDAC stroma, which is known to act as both a barrier to drug delivery and a tumor-promoting signaling partner. Here, we review the literature which indicates an emergent role of PDT in clinical management of PDAC, including the potential for combination with other targeted agents and RNA medicine.
Experimental warming and its legacy effects on root dynamics following two hurricane disturbances in a wet tropical forest

Tropical forests are expected to experience unprecedented warming and increases in hurricane disturbances in the coming decades; yet, our understanding of how these productive systems, especially their belowground component, will respond to the combined effects of varied environmental changes remains empirically limited. Here we evaluated the responses of root dynamics (production, mortality, and biomass) to soil and understory warming (+4°C) and after two consecutive tropical hurricanes in our in situ warming experiment in a tropical forest of Puerto Rico: Tropical Responses to Altered Climate Experiment (TRACE). We collected minirhizotron images from three warmed plots and three control plots of 12 m2 . Following Hurricanes Irma and Maria in September 2017, the infrared heater warming treatment was suspended for repairs, which allowed us to explore potential legacy effects of prior warming on forest recovery. We found that warming significantly reduced root production and root biomass over time. Following hurricane disturbance, both root biomass and production increased substantially across all plots; the root biomass increased 2.8-fold in controls but only 1.6-fold in previously warmed plots. This pattern held true for both herbaceous and woody roots, suggesting that the consistent antecedent warming conditions reduced root capacity to recover following hurricane disturbance. Root production and mortality were both related to soil ammonium nitrogen and microbial biomass nitrogen before and after the hurricanes. This experiment has provided an unprecedented look at the complex interactive effects of disturbance and climate change on the root component of a tropical forested ecosystem. A decrease in root production in a warmer world and slower root recovery after a major hurricane disturbance, as observed here, are likely to have longer-term consequences for tropical forest responses to future global change.
Neonatal infratentorial subdural hematoma contributing to obstructive hydrocephalus in the setting of therapeutic cooling: A case report.

Neonatal infratentorial subdural hematoma contributing to obstructive hydrocephalus in the setting of therapeutic cooling: A case report
Multiple Coil Pulsed Magnetic Resonance Method for Measuring Cold SSC Dipole Magnet Field Quality

The operating principles and system architecture for a method to measure the magnetic field multipole expansion coefficients are described in the context of the needs of SSC dipole magnets. The operation of an 8-coil prototype system is discussed. Several of the most important technological issues that influence the design are identified and the basis of their resolution is explained. The new features of a 32-coil system presently under construction are described, along with estimates of its requirements for measurement time and data storage capacity.
The geodesic flow generates a fast dynamo: an elementary proof

C. CHICONE AND Y. LATUSHKIN(Communicated by Je rey B. Rauch)Abstract. We give elementary and explicit arguments to show that the geo-desic ﬂow on the unit tangent bundle of a two dimensional Riemannian mani-fold with constant negative curvature provides an example of a \fast" dynamofor the magnetic kinematic dynamo equation.
A Systolic (VLSI) Array for Processing Simple Relational Queries

This paper discusses die use of systolic arrays (a conceptual and design tool for VLSI systems [11]) to produce VLSI capable of processing simple relational database queries, which are by far the most frequently executed queries in practical large database systems. We will be concerned with the exploitation of VLSI technology to process “simple” relational queries very rapidly; the design of an array for this task is described below. The systolic properties of the array design arc considered, and are shown to have analogs in the domain of databases by using the systolic properties to prove certain consistency and scheduling complexity properties of all transactions executed by the array (hereinafter called the simple query array, or SQA). The SQA is intended for use as an integral part of a systolic database machine [13], which would handle very large databases and is expected to have a high performance gain over conventional database systems. The machine should also compare quite favorably with other database machine designs (for example [1,4,16,17,19]), especially when used for databases with frequent simple queries, i.e. those databases used by most commercial applications!
Many-trillionfold amplification of single RNA virus particles fails to overcome the Muller's ratchet effect.

Abstract We showed earlier that transfers of large populations of RNA viruses lead to fitness gains and that repeated genetic bottleneck transfers result in fitness losses due to Muller's ratchet. In the present study, we examined the effects of genetic bottleneck passages intervening between population passages, a process akin to some natural viral transmissions, using vesicular stomatitis virus as a model. Our findings show that the pronounced fitness increases that occur during two successive population passages cannot overcome the fitness decreases caused by a single intervening genetic bottleneck passage. The implications for natural transmissions of RNA viruses are discussed.
Physical layer design issues unique to cognitive radio systems

Cognitive radio systems offer the opportunity to improve spectrum utilization by detecting unoccupied spectrum bands and adapting the transmission to those bands while avoiding the interference to primary users. This novel approach to spectrum access introduces unique functions at the physical layer: reliable detection of primary users and adaptive transmission over a wide bandwidth. In this paper, we address design issues involved in an implementation of these functions that could limit their performance or even make them infeasible. The critical design problem at the receiver is to achieve stringent requirements on radio sensitivity and perform signal processing to detect weak signals received by a wideband RF front-end with limited dynamic range. At the transmitter, wideband modulation schemes require adaptation to different frequency bands and power levels without creating interference to active primary users. We introduce algorithms and techniques whose implementation could meet these challenging requirements
Leiomyosarcoma metastatic to the oral region: Report of three cases

Leiomyosarcoma, a malignant lesion of smooth muscle origin, is rare in the oral region. Metastatic leiomyosarcoma may originate from several potential primary sites, and the lung is the most common target tissue for metastatic deposits. This article describes three cases of leiomyosarcoma that were metastatic to the oral cavity and discusses the clinical and histopathologic differential diagnosis.
Measuring orbital angular momentum of light with a single, stationary lens

We demonstrate that average orbital angular momentum (OAM) can be measured with a simplified twist parameter measurement technique. This technique uses a stationary apparatus composed of only a cylindrical lens and a CCD.
Heat transfer in oscillating flows with sudden change in cross section

Oscillating fluid flow (zero mean) with heat transfer, between two parallel plates with a sudden change in cross section, was examined computationally. The flow was assumed to be laminar and incompressible with inflow velocity uniform over the channel cross section but varying sinusoidally with time. Over 30 different cases were examined; these cases cover wide ranges of Re sub max (187.5 to 30000), Va (1 to 350), expansion ratio (1:2, 1:4, 1:8, and 1:12) and A sub r (0.68 to 4). Three different geometric cases were considered (asymmetric expansion and/or contraction, symmetric expansion/contraction, and symmetric blunt body). The heat transfer cases were based on constant wall temperature at higher (heating) or lower (cooling) value than the inflow fluid temperature. As a result of the oscillating flow, the fluid undergoes sudden expansion in one half of the cycle and sudden contraction in the other half. One heating case is examined in detail, and conclusions are drawn from all the cases (documented in detail elsewhere). Instantaneous friction factors and heat transfer coefficients, for some ranges of Re sub max and Va, deviated substantially from those predicted with steady state correlations.
Rapid prototyping of microchannels with surface patterns for fabrication of polymer fibers

Microfluidic technology has provided innovative solutions to numerous problems, but the cost of designing and fabricating microfluidic channels is impeding its expansion. In this work, Shrinky-Dink thermoplastic sheets are used to create multilayered complex templates for microfluidic channels. We used inkjet and laserjet printers to raise a predetermined microchannel geometry by depositing several layers of ink for each feature consecutively. We achieved feature heights over 100 μm, which were measured and compared with surface profilometry. Templates closest to the target geometry were then used to create microfluidic devices from soft-lithography with the molds as a template. These microfluidic devices were in turn used to fabricate polymer microfibers using the microfluidic focusing approach to demonstrate the potential that this process has for microfluidic applications. Finally, an economic analysis was conducted to compare the price of common microfluidic template manufacturing methods. We showed that multilayer microchannels can be created significantly quicker and cheaper than current methods for design prototyping and point-of-care applications in the biomedical area.
When the War Ends: A Population-Based Survey on Attitudes about Peace, Justice, and Social Reconstruction in Northern Uganda

Twenty-one years of war, destruction, and the displacement of over 1.5 million people have turned northern Ugandan into a humanitarian disaster. One of the war’s principal perpetrators has been the Lord’s Resistance Army (LRA). A significant shift in the war occurred in late 2005 when the LRA withdrew its forces to the southern Sudan and then crossed the Nile, assembling in Garamba National Park in the Democratic Republic of Congo. In the summer of 2006, peace talks between the Government of Uganda and the LRA commenced in Juba, and a first Cessation of Hostilities Agreement was signed on 26 August 2006. With the withdrawal of the LRA to the Congo, security in northern Uganda has improved considerably. Some displacement-camp residents have moved to new settlement sites closer to their villages. Yet others fear leaving the relative safety of the camps until a final peace agreement has been signed and the LRA fighters have been demobilized. This is a delicate stage of the conflict, and a deeper understanding of the needs and desires of affected populations will be crucial to a long-term resolution.This report presents the findings of a population-based study conducted by the Human Rights Center, University of California Berkeley, Payson Center for International Development, Tulane University, and the International Center for Transitional Justice. The research was based on a cross-sectional survey of 2,875 individuals, supplemented by in-depth qualitative interviews, in eight districts of northern Uganda most affected by the conflict from April to June 2007. The study capture attitudes about peace, justice, and social reconstruction while peace talks were taking place between the Ugandan government and the LRA in Juba, south Sudan.
Influence of hormones on glycogen and glucose metabolism in embryonic chick intestine

Previous studies on the development of embryonic intestine in vitro have revealed a stimulation of epithelial differentiation by the hormones hydrocortisone (HC) and thyroxine (T4). To determine whether these hormones also influence epithelial metabolism, duodena from 14-day-old chicken embryos were cultured for 72 h in the absence of hormones (controls) or in the presence of 1 nM T4 or 1 microM HC. In control cultures, glycogen accumulated within the duodenal epithelium to the level found at 17 days in vivo. T4 reduced glycogen accumulation to 34% of control values, whereas HC increased epithelial glycogen content by 45%. These hormonal effects were due, in part, to modulation of glycogen degradation. In T4 cultures, glucose oxidation activities within the epithelial layer and submucosal tissue were 300 and 140% of control values, respectively, and glucose utilization (removal from the culture medium) was increased. HC significantly decreased both glucose oxidation activity within the submucosal tissue and glucose utilization. These results are consistent with the hypothesis that HC regulates the early phase of epithelial differentiation that is characterized by low metabolic rate and accumulation of energy stores, whereas T4 elicits the prehatching phase of differentiation that is correlated with an increase in metabolic rate and utilization of stored products.
Regional Blood—Brain Glucose Transfer and Glucose Utilization in Chronically Hyperglycemic, Diabetic Rats following Acute Glycemic Normalization

Regional rates of brain glucose utilization (rCMRglc) and glucose influx (rJin), along with regional brain tissue glucose concentrations, were measured in chronically hyperglycemic diabetic (CHD) rats following acute glycemic normalization. These results were compared to those obtained in nondiabetic normoglycemic controls. The diabetic rats were evaluated at 6–8 weeks following i.p. streptozotocin injection. All rats were N2O (70%) sedated, paralyzed, and artificially ventilated for study. Acutely normoglycemic (plasma glucose = 7.9 µmol/ml) CHD rats, compared to control (plasma glucose = 8.5 µmol/ml), demonstrated significantly higher (p < 0.05) rCMRglc and rJin values in 8 of the 11 regions analyzed. Tissue/plasma glucose concentration ratios were significantly greater than control in 9 of 11 regions. Prior to acute glycemic normalization, rCMRglc values in CHD rats were either unchanged or moderately lower than control. These findings indicate that no blood–brain barrier glucose transport repression i...
Effects of continuous inhalation of dichloromethane in the mouse: morphologic and functional observations.

Abstract Continuous inhalation of 5000 ppm CH 2 Cl 2 caused balloon degeneration, transient severe fatty change and partial inhibition of leucine incorporation into liver proteins of 20–32 g female mice of the ICR stain. The earliest lesion was identified at 12 hr of exposure and consisted of dissociation of polyribosomes and swelling of hepatocyte rough endoplasmic reticulum (so-called “balloon” degeneration). Balloon degeneration peaked in severity at 2 days of exposure and then partially reversed. Liver fatty change was also partially reversible. There was a 12-fold increase in liver triglycerides with 3 days of exposure, but at 1 wk of continuous exposure liver triglycerides were two to three times control values. Necrosis was observed in a few isolated hepatocytes. The reversibility of the liver changes suggests that partial tolerance develops in hepatocytes with continuous exposure to 5000 ppm dichloromethane. Liver lesions produced in the mouse liver by dichloromethane bear some resemblance to the lesions of carbon tetrachloride hepatotoxicity but appear to be less severe.
Critical determinants in PLGA/PLA nanoparticle-mediated gene expression.

Purpose. The aim of the study was to determine the critical determinants in nanoparticle-mediated gene transfection. It was hypothesized that different formulation parameters could affect the nanoparticle characteristics and hence its gene transfection.
Functional analysis of the propeptide of subtilisin E as an intramolecular chaperone for protein folding. Refolding and inhibitory abilities of propeptide mutants

The amino-terminal propeptide, consisting of 77 amino acid residues, is known to be required as an intramolecular chaperone to guide the folding of mature subtilisin E, a serine protease, into active mature enzyme. Many mutations within the pro-sequence have been shown to abolish the production of active subtilisin E (Kobayashi, T., and Inouye, M. (1992) J. Mol. Biol. 226, 931-933). Here we report characterization, refolding, and inhibitory abilities of six single amino acid substitution mutations (Ile-67-->Val, Ile-48-->Thr, Gly-44-->Asp, Lys-36-->Glu, Ala-30-->Thr, and Pro-15-->Leu) and a nonsense mutation (N59-mer) at the codon for Lys-18. These mutant propeptides were expressed in Escherichia coli using a T7 expression system and were purified to homogeneity. Surprisingly, Lys-36-->Glu, Ala-30-->Thr and Pro-15-->Leu were found to still function as a chaperone for in vitro refolding of denatured subtilisin BPN' with 60, 80, and 54% efficiency compared to the wild-type propeptide, respectively. The Ki values against subtilisin BPN' were 1.6 x 10(-9) M, and 2.1 x 10(-9) M, respectively. The Ki values against subtilisin BPN' were 1.6 x 10(-9) M, and 2.1 x 10(-9) M, respectively, almost identical to the Ki value exhibited by the wild-type propeptide (1.4 x 10(-9) M). In contrast, Ile-67-->Val and Gly-44-->Asp were able to refold denatured subtilisin BPN' with only 18 and13% efficiencies and had Ki values of 10 and 11 x 10(-9) M, respectively. The Ile-48-->Thr mutant propeptide was unable to refold denatured subtilisin BPN' and gave a 100-fold higher Ki (118 x 10(-9) M) than the wild-type propeptide. The N59-mer propeptide extending from Leu-19 to Met-78 was unable to function as a chaperone. Like the wild-type propeptide, none of the mutant propeptides had secondary structures as judged by their circular dichroism spectra. The present results demonstrate that the ability of the propeptide as a chaperone to refold the denatured protein is well correlated with its ability as a competitive inhibitor for the active enzyme. This supports the notion that the secondary and tertiary structures of the propeptide are identical or highly homologous between the renatured propeptide-subtilisin complex and the inhibitory complex formed between the propeptide and the active enzyme.
Duration of red blood cell storage and outcomes following orthotopic liver transplantation

Liver transplantation may be complicated by massive intraoperative bleeding, and red blood cell (RBC) transfusions may be required. The storage duration or age of transfused RBCs has been shown to affect the morbidity and mortality of critically ill, trauma, and cardiac surgery patients. Here we investigate the effect of RBC age on the outcomes of liver transplant patients. Five hundred thirty-one patients underwent orthotopic liver transplantation between January 1, 2000 and August 15, 2010. The patient demographics, the Model for End-Stage Liver Disease–sodium (MELD-Na) score, and the number and age of RBC units were evaluated with univariate and multivariate models of outcomes, which included mortality rates 2 years after transplantation, postoperative infections, and organ rejection. In a univariate analysis, the number of RBC units (but not the RBC age) was associated with increased 2-year mortality, an increased risk of infection, and a decreased risk of organ rejection. Only the number of RBC units was associated with increased 2-year mortality in a multivariate Cox regression model. The mortality risk was decreased by two-thirds for patients who received <10 U of RBCs versus those who received ≥10 U (hazard ratio = 0.33, 95% confidence interval = 0.16-0.69, P = 0.003). The number of transfused RBC units was not associated with the risk of infection or organ rejection in a multivariate logistic regression model. In conclusion, the RBC age is not associated with infection, organ rejection, or death in liver transplant patients. Patients who receive more blood have an increased risk of death. In a multivariate model, the MELD-Na score was not associated with increased mortality, and this is consistent with previous studies demonstrating that the MELD-Na score is a poor predictor of long-term survival after transplantation. Liver Transpl 18:475–481, 2012. © 2012 AASLD.
Analytical Chemistry of Nonlinear Systems

Analytical methods for characterizing complex, nonlinear chemical systems are reviewed. Emphasis is on those aspects of systems which make their characterization more difficult than just measuring concentrations or simple reaction rates. Examples include phase transitions, oscillating chemical reactions, laser fluctuations, and electrochemical oscillations. Data reduction algorithms specific to such systems are described.
Conformational Preferences of cis-1,3-Cyclopentanedicarboxylic Acid and Its Salts by 1H NMR Spectroscopy: Energetics of Intramolecular Hydrogen Bonds in DMSO

The conformational populations of cis-1,3- cyclopentanedicarboxylic acid (1) and its mono- and dianion were established in DMSO solution by comparing the vicinal proton−proton coupling constants (^3JHH) obtained in solution to their theoretical counterparts. Geometries used for ^3JHH theoretical estimation (using Karplus-type equations) were obtained from optimized structures at the B3LYP/6-31G-(2d,2p) level. The diacid (1) adopted many conformations, whereas the ionized species (1A mono- and 1B dianion) assumed single conformations. A downfield chemical shift of 19.45 ppm (Δδ_H = 7.43 ppm) observed at −60 °C was indicative of intramolecular hydrogen bonding in 1A, which was later corroborated by determining the ratio of the first (K_1) to the second (K_2) ionization constants. K_1/K_2 in DMSO (1.3 × 10^7) was significantly larger than the value in water (2 × 10). In addition, K_1/K_E = 200 (where K_E is the acidity constant of the monomethylester of 1) was greater than the intramolecular hydrogen bonding threshold value of 2. The calculated intramolecular hydrogen bond strength of 1A was ∼3.1 kcal mol^(−1), which is ∼2.7 kcal mol^(−1) more stable than the values for cis- 1,3-cyclohexanedicarboxylic acid (2A). Thus, the relative energies of intramolecular hydrogen bonding in the monoanions 1A and 2A suggests that 1,3-diaxial conformers are more favored for cyclopentane than for cyclohexane rings.
Are cohort mortality rates autocorrelated

In this paper the author examines the proposition that heterogeneity in individual frailty leads to autocorrelation in cohort mortality rates. A simple model is used to construct analytic expressions for the covariance of cohort mortality rates at different ages under a number of alternative assumptions about the stochastic process generating shocks in mortality. The model then is used to construct a procedure that uses correlations in cohort mortality rates to estimate the extent of heterogeneity in a population without relying on strong assumptions about the distribution of frailty or the shape of the underlying hazard. The procedure then is used to show that cohort mortality data from France are consistent with a generalized random-effects model in which frailty is gamma-distributed. nt]mis|Initial stages of this work were carried out at the University of California, Berkeley and were supported by a Population Council Graduate Fellowship. Additional support was provided by a grant from the University of Pennsylvania Research Foundation. I am indebted to Kenneth Wachter for suggesting that a formal analysis of this question might prove interesting and to John Wilmoth for making the French data available. I am grateful to Kenneth Wachter, Ronald Lee, John Wilmoth, George Alter, and Samuel Preston for their comments and suggestions. Any remaining errors are of course my own responsibility.
Simple unified form for the major no-hidden-variables theorems.

Two examples are given that substantially simplify the no-hidden-variables theorem of Kochen and Specker, greatly reducing the number of observables considered and requiring no intricate geometric argument. While one of the examples also obeys a more powerful version of Bell's theorem, the other does not. The examples provide a new perspective on both of these fundamental theorems and on the relation between them.
The Little Village Project: A Community Approach to the Gang Problem

Based on substantial preliminary evidence, a four-year Gang Violence Reduction Project has demonstrated its effectiveness in terms of process and outcome. An innovative approach in the prevention and control of a serious gang violence problem was based on key interrelated strategies of community mobilization, social intervention, suppression, opportunities provision, organizational development, and targeting. A team of community youth workers, tactical police officers, adult probation officers, and representatives of a neighborhood organization operated under the aegis of the Chicago Police Department. Of special interest was the interrelated practice roles of police tactical officers and community youth workers, many of whom were former gang members.
Determination of Markers in Digesta and Feces by Direct Current Plasma Emission Spectroscopy

A method is described for the preparation of bovine ruminal contents, duodenal digesta, and feces for analysis of Co, Cr, La, Sm, Eu, and Yb by direct current plasma emission spectroscopy. Ground, dried sample was refluxed in concentrated nitric acid until 2 to 3 ml of acid remained. The ash was redissolved in 6N HCl. Lithium hydroxide was added to suppress ionization, and the samples were diluted with distilled water for analysis. Element recovery, expressed as the ratio of element recovered from digesta samples augmented prior to ashing compared with those augmented after sample digestion, ranged from 71.5 to 100.5% and was affected by digesta type. Addition of 1000 ppm of Li to the sample matrix improved recovery of Co and La from 93.4 and 83.3% to 97.8 and 98.3%, respectively. Lithium did not affect recovery of the other elements. Type of digesta matrix affected emission intensity. Addition of 1000 ppm of Li to the sample matrices enhanced signal output in the digesta matrices by 25 to 30% for each element. Lithium tended to minimize differences in signal output caused by the organic matrix but did not eliminate them. Increasing Li concentration from 1000 to 4000 ppm did not increase signal output or completely buffer out the higher emission intensity associated with the organic matrix. Sensitivity of analysis of Co, Cr, and rare earth elements was comparable with or better than sensitivities reported with neutron activation analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Mathematical determination of emissivity and surface temperature of aluminum alloys using multispectral radiation thermometry

A relatively simple emissivity model has recently been shown to effectively capture the parameteric effects of wavelength, temperature, alloy and surface roughness on the emissivity of aluminum surfaces. In the present study, a mathematical method is developed for determining both the empirical constant in the emissivity model and the surface temperature based on spectral radiance measurements. This study proves the relationship between reflectance ratio and optical roughness is by no means universal, and the complex effects of wavelength, temperature, alloy and surface roughness are more accurately captured with the aid of a multispectral emissivity model.
Inhibition of neurite polarity by tau antisense oligonucleotides in primary cerebellar neurons

Neurons in culture can have fundamentally distinct morphologies which permit their cytological identification and the recognition of their neurites as axons or dendrites. Microtubules may have a role in determining morphology by the selective stabilization of spatially distinct microtubule subsets. The plasticity of a neurite correlates inversely with the stability of its component microtubules: microtubules in growth cones are very dynamic, and in initial neurites there is continuous incorporation of labelled subunits, whereas in mature neurites, microtubules are highly stabilized. The binding of microtubule-associated proteins to the microtubules very probably contributes to this stability. Cerebellar neurons in dissociated culture initially extend exploratory neurites and, after a relatively constant interval, become polarized. Polarity becomes evident when a single neurite exceeds the others in length. These stable neurites cease to undergo the retractions and extensions characteristic of initial neurites and assume many features of axons and dendrites. We have now studied the role of the neuronal microtubule-associate protein tau in neurite polarization by selectively inhibiting tau expression by the addition of antisense oligonucleotides to the culture media. Although the extension of initial exploratory neurites occurred normally, neurite asymmetry was inhibited by the failure to elaborate an axon.
Buckling and postbuckling of composite ship panels stiffened with preform frames

Abstract The U.S. shipbuilding industry recently has started incorporating composite materials in the construction of both military and commercial ships due to the advantages of composite construction. These advantages include the reduction in total life costs, corrosion resistance, high strength- and stiffness-to-weight ratios, and improved stealth for military applications. One disadvantage is the higher costs of composites compared to steel and other conventional materials. Therefore, new higher quality materials with lower costs and new fabrication methods need to be developed before composite materials will be fully accepted for the construction of large ships. A new composite preform framing technology shows promise in the reduction of fabrication costs for large ship construction. There already has been significant cost savings using this framing technology in the construction of small recreational boats and large yachts. This framing technology involves casting a dry glass fiber-reinforced plastic (GRP) fabric into shape in a closed mold with a foam core. One unresolved issue using this framing technology is the orientation of the fiber for the frames. This paper summarizes experimental results of the testing of composite panels stiffened with preform frames under in-plane uniaxial compressive loads. Biaxial (0,90), quadaxial (0,90,+45,−45), and triaxial (+45,−45,0) laminates were used in the frames.
Unbiased discovery of in vivo imaging probes through in vitro profiling of nanoparticle libraries

In vivo imaging reveals how proteins and cells function as part of complex regulatory networks in intact organisms, and thereby contributes to a systems-level understanding of biological processes. However, the development of novel in vivo imaging probes remains challenging. Most probes are directed against a limited number of pre-specified protein targets; cell-based screens for imaging probes have shown promise, but raise concerns over whether in vitro surrogate cell models recapitulate in vivophenotypes. Here, we rapidly profile the in vitro binding of nanoparticle imaging probes in multiple samples of defined target vs. background cell types, using primary cell isolates. This approach selects for nanoparticles that show desired targeting effects across all tested members of a class of cells, and decreases the likelihood that an idiosyncratic cell line will unduly skew screening results. To adjust for multiple hypothesis testing, we use permutation methods to identify nanoparticles that best differentiate between the target and background cell classes. (This approach is conceptually analogous to one used for high-dimensionality datasets of genome-wide gene expression, e.g. to identify gene expression signatures that discriminate subclasses of cancer.) We apply this approach to the identification of nanoparticle imaging probes that bind endothelial cells, and validate our in vitro findings in human arterial samples, and by in vivo intravital microscopy in mice. Overall, this work presents a generalizable approach to the unbiased discovery of in vivo imaging probes, and may guide the further development of novel endothelial imaging probes.
2007 Special Issue: The apical dendrite theory of consciousness

The neural basis of consciousness is theorized here to be the elevated activity of the apical dendrite within a thalamocortical circuit. Both the anatomical and functional properties of these two brain structures are examined within the general context of the cortical minicolumn, which is regarded as the functional unit of the cerebral cortex. Two main circuits of the minicolumn are described: the axis circuit, which sustains activity for extended durations and produces our sensory impressions, and the shell circuit, which performs input-output processing and produces identifications, categorizations, and ideas. The apical dendrite operates within the axis circuit to stabilize neural activity, which enables conscious impressions to be steady and to be sustained over long periods of time. In an attempt to understand how the conscious aspect of subjective impressions may be related to apical dendrite activity, we examine the characteristics of the electric and magnetic fields during the movement of charges along the apical dendrite. The physical correlate of consciousness is regarded here as the relatively intense electromagnetic field that is located along the inside and the outside close to the surface of the active apical dendrite.