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A chemiluminescence assay using a handheld luminometer to measure the activity of alkaline phosphatase was developed that can detect 0.002% or more of unpasteurized milk in various milk products. Evaluation of the assay followed an National Conference on Interstate Milk Shipments (NCIMS)–approved protocol in which aliquots of pasteurized milk products were spiked with raw milk at various levels. Milk products evaluated included skim white milk, 1 and 2% fat content white milk, whole white milk, strawberry-flavored 1% fat content milk, chocolate-flavored 1% fat content milk, half-and-half, and heavy cream. Split samples were prepared, and alkaline phosphatase activities were determined in triplicate on 4 days by three NCIMS-accredited laboratories by the chemiluminescent method and NCIMS-approved reference methods. Equivalence of the chemiluminescent method to the approved reference methods was demonstrated for all eight products evaluated over a range of raw milk concentration from 0 to 0.5%, using criteria established by NCIMS, in which mean results obtained by the three laboratories by the chemiluminescent method were within 1 standard deviation of the mean results obtained by the NCIMS-approved reference methods at each alkaline phosphatase concentration. Procedures for measurement of microbial and reactivated alkaline phosphatase were also established for the method. [ABSTRACT FROM AUTHOR]

This paper analyzes the financial feasibility and the investment attractiveness of a wind farm that uses a Lidar unit for proactive turbine controls. A thorough technical analysis is performed for evaluating the effectiveness of the Lidar for proactive blade pitch control. It is observed that using a Lidar for individual blade pitch control results in a significant reduction of the blade root damage equivalent loads. Furthermore, a pro-forma cashflow based economic tool is developed for modeling, comparing, and analyzing wind energy projects. This tool utilizes capital budgeting tools such as net present value, internal rate of return, equivalent annual annuity and payback period for analyzing investment attractiveness. Moreover, this paper utilizes wind conditions, costs and expenses, financing schemes, incentives, and operational strategies for analyzing wind projects with or without Lidars. The component fatigue load reduction achieved using Lidar based control can either be used to increase the useful life of the farm or to up-rate (repower) the turbine for the same operational life. This work analyzes the financial impacts of each of the aforementioned scenarios for a range of wind conditions. Also, the financial impact of PTC availability on a Lidar-assisted wind project has been analyzed in this research. [ABSTRACT FROM AUTHOR]

The mechanical response of a wire strand is inherently complex because the helical wires undergo evolving stress and contact conditions as the strand is loaded. Further complications are added to the strand behavior if one or more of the wires break due to strand degradation over time. Although a detailed investigation on strand behavior is critically important for predicting the capacity of a broken strand as well as developing new monitoring approaches for wire break detection, there is little study available in the literature on wire breakage in a stressed strand. This paper provides an extensive investigation on stressing and post-breakage dynamic behavior of a prestressing strand. A finite element model is generally useful to study the global strand response, along with many localized phenomena that have strong influence on its performance, but are difficult to capture either experimentally or through closed-form analytical models. Investigations on certain behaviors, such as wire breaks, however, require a relatively large or even a full-scale model to adequately develop contact and frictional conditions. Moreover, such a sizeable model can account for any deviation points and may avoid edge effects. Consequently, several finite element parameters, such as the load ramp profile and duration, effects of damping and interwire friction, become critical for an accurate and efficient model. This paper first presents the use of a parametrized model to study strand behavior and evaluates the effects of these modeling parameters on strand response; load distribution and redistribution among the wires at the onset of interwire motion are also considered. The model is then used to simulate wire breakage in a prestressing strand, so that various aspects of post-breakage response can be examined. Numerical results show that a linear load ramp or stressing too quickly may lead to an inaccurate axial tension developed in the strand, whereas the inclusion of nominal mass-based damping has been found effective in achieving a quasi-static solution at a reasonable computational cost. In addition, the wire break simulation results indicate that breakage of an outer wire results in greater prestress loss than breakage of the center wire, which might have important implications for non-destructive wire breakage detection. [ABSTRACT FROM AUTHOR]

Abstract: Sinorhizobium meliloti salt tolerance is important in establishing a nitrogen fixing symbiosis with alfalfa under high osmolarity. In order to resist osmotic stress, rhizobia accumulate a number of osmolytes including a potent osmoprotectant, glycine-betaine (GB). S. meliloti is able to synthesize GB from choline via a pathway encoded by the chromosomal betICBA operon. The last enzyme in the biochemical pathway, BetB, encodes a betaine aldehyde dehydrogenase, which converts betaine aldehyde to GB. Deletion of betB in S. meliloti strain Rm2011 leads to loss of detectable BADH activity. A second betB-related gene, betB2, is present on the S. meliloti pSymA megaplasmid and deletion of this gene has no effect on the observed level of BADH. However, an Rm2011 deletion mutant with only 144 aa from the N-terminal domain of BetB2 has lost the ability to tolerate high osmolarity, no longer accumulates GB under osmotic stress, has high levels of NAD-BADH, and has gained the ability to utilize GB for growth. These results suggest that truncated BetB2-144 stimulates GB catabolism, preventing it from being used as an osmoprotectant. [Copyright &y& Elsevier]

Abstract: Four representative Illinois Department of Transportation (IDOT) highway sign support trusses were evaluated analytically and in the field to assess their design load capacity and fatigue resistance when subjected to wind loading. The three overhead span bridge and one cantilever welded aluminum truss structures were instrumented for static and dynamic field testing with strain gages and accelerometers to collect structural behavior data when subjected to manual excitation, wind loading, and truck gust excitation. Companion analytical models were developed and calibrated to represent the structures in the field, after which these were then used to assess the response of the trusses at full design wind loads. Current IDOT and AASHTO highway sign support structure design loading and resistance approaches with respect to both strength and fatigue have been critically assessed in light of the analyses and field test results, with recommendations made for improving future designs. [Copyright &y& Elsevier]

Abstract: A fundamental issue inherent to education policy is whether teacher qualifications such as certification status, degree level, preparation, and experience predict student achievement. While existing research provides some direction regarding the potential importance of these qualifications for productivity in secondary schools, less is known about their importance for productivity in elementary schools. This study draws on data from the Early Childhood Longitudinal Study (ECLS) to analyze the relationship between elementary school teacher qualifications and first-grade achievement in reading and mathematics. While we find no effects for certification status, we report positive effects for teachers’ degree type and experience on reading achievement. We also discover potential contextual effects of teachers’ qualifications on student achievement, with first-graders demonstrating higher levels of reading and mathematics achievement in schools where teachers report higher levels of coursework emphasis in these subject areas. We discuss the implications of these findings for policy and future research. [Copyright &y& Elsevier]

Abstract: Objective:: To evaluate the efficacy of HBOC-201 for resuscitation of hemorrhagic shock in a swine model incorporating soft tissue injury and delayed evacuation. Methods:: A muscle crush injury and 40% estimated blood volume controlled hemorrhage was completed in 24 Yucatan mini-pigs. Pigs were untreated or resuscitated with HBOC-201 or 6% hetastarch (HEX) at 20min. Invasive hemodynamics and clinical variables were monitored for 4h (pre-hospital phase) and subsequent fluid infusions were administered for severe hypotension or tachycardia. Animals were recovered from anesthesia and monitored non-invasively to 72h (hospital phase). Results:: 100% (8/8) of HBOC-201-, 88% (7/8) of HEX-, and 63% (5/8) of non-resuscitated pigs, survived to 72h (p =0.27). Mean arterial pressure, mean pulmonary arterial pressure and systemic vascular resistance index were higher in HBOC-201 pigs. By 90min, cardiac index was restored to baseline in the HBOC-201 group and was 1.4-fold greater than baseline in the HEX group. HBOC-201 pigs had lower fluid requirements than HEX pigs (18.8±1.8 and 29.9±1.1ml/kg, p <0.001) in the pre-hospital phase and required fewer blood transfusions (1.3±1.3 and 9.4±0.6ml/kg, respectively, p <0.001) in the hospital phase. Urine output and blood creatinine were comparable in HBOC-201 and HEX pigs. Tissue oxygenation levels were highest in the HBOC-201 group. Conclusions:: As HBOC-201 restored hemodynamics and tissue oxygenation and decreased fluid requirements, in comparison with HEX, HBOC-201 was at least as efficacious and possibly a superior resuscitative fluid in a military-relevant delayed evacuation hemorrhagic shock swine model. [Copyright &y& Elsevier]

Block scheduling involves the reallocation of instructional time into longer class sessions to encourage more active teaching strategies, reduce fragmentation inherent in single-period schedules, and improve student performance. To the degree that such policies reallocate existing resources to realize higher levels of desired educational outcomes, the goal of productivity can be served. Despite widespread experimentation with various forms of block scheduling, there is conflicting evidence on the impact of these innovations on student achievement, and little evidence of their effect on classroom practice. This study explores these relationships. More specifically, the study draws on data from the National Education Longitudinal Study: 1988 to estimate the impact of block-scheduled mathematics courses on tenth-grade student achievement and teachers'' use of class time. Findings suggest that while block scheduling is positively associated with teachers'' use of multiple instructional methods and more individualized instruction, this scheduling reform has a negative impact on students'' tenth-grade mathematics scores, controlling for other factors. Implications for educational productivity are discussed. [Copyright &y& Elsevier]

Biosynthesis of riboflavin (RF), the precursor of the redox cofactors FMN and FAD, was thought to be well understood in bacteria, with all the pathway enzymes presumed to be known and essential. Our previous research has challenged this view by showing that, in the bacterium Sinorhizobium meliloti, deletion of the ribBA gene encoding the enzyme that catalyzes the initial steps on the RF biosynthesis pathway only causes a reduction in flavin secretion rather than RF auxotrophy. This finding led us to hypothesize that RibBA participates in the biosynthesis of flavins destined for secretion, whereas S. meliloti has another enzyme that performs this function for internal cellular metabolism. Here, we identify and biochemically characterize a novel formamidase (SMc02977) involved in the production of RF for intracellular functions in S. meliloti. This catalyst, which we named Sm-BrbF, releases formate from the early RF precursor 2-amino-5-formylamino-6- ribosylamino-4(3H)-pyrimidinone 5'-phosphate to yield 2,5-diamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate. We show that homologs of this enzyme are present in many bacteria, are highly abundant in the Rhizobiales order, and that sequence homologs from Brucella abortus and Liberobacter solanacearum complement the RF auxotrophy of the Sm1021ΔSMc02977 mutant. Furthermore, we show that the B. abortus enzyme (Bab2_0247, Ba-BrbF) is also an 2-amino-5-formylamino-6-ribosylamino-4(3H)-pyrimidinone 5'-phosphate formamidase, and that the bab2_0247 mutant is a RF auxotroph exhibiting a lower level of intracellular infection than the wildtype strain. Finally, we show that Sm-BrbF and Ba-BrbF directly interact with other RF biosynthesis pathway enzymes. Together, our results provide novel insight into the intricacies of RF biosynthesis in bacteria. [ABSTRACT FROM AUTHOR]

DNA- based vaccines have demonstrated the potential as a safe and effective modality. PlaCCine, a DNA-based vaccine approach described subsequently relies on a synthetic DNA delivery system and is independent of virus or device. The synthetic functionalized polymer combined with DNA demonstrated stability over 12 months at 4C and for one month at 25C. Transfection efficiency compared to naked DNA increased by 5–15-fold in murine skeletal muscle. Studies of DNA vaccines expressing spike proteins from variants D614G (pVAC15), Delta (pVAC16), or a D614G + Delta combination (pVAC17) were conducted. Mice immunized intramuscular injection (IM) with pVAC15, pVAC16 or pVAC17 formulated with functionalized polymer and adjuvant resulted in induction of spike-specific humoral and cellular responses. Antibody responses were observed after one immunization. And endpoint IgG titers increased to greater than 1x 105 two weeks after the second injection. Neutralizing antibodies as determined by a pseudovirus competition assay were observed following vaccination with pVAC15, pVAC16 or pVAC17. Spike specific T cell immune responses were also observed following vaccination and flow cytometry analysis demonstrated the cellular immune responses included both CD4 and CD8 spike specific T cells. The immune responses in vaccinated mice were maintained for up to 14 months after vaccination. In an immunization and challenge study of K18 hACE2 transgenic mice pVAC15, pVAC16 and pVAC17 induced immune responses lead to decreased lung viral loads by greater than 90 % along with improved clinical score. These findings suggest that PlaCCine DNA vaccines are effective and stable and further development against emerging SARS-CoV-2 variants is warranted. [ABSTRACT FROM AUTHOR]

Ovarian Cancer is the most lethal gynecologic malignancy and the fifth most common malignancy affecting women. Advanced disease is often characterized by the widespread dissemination into the peritoneal cavity. We have previously shown that repeated intraperitoneal delivery of an interleukin-12 (IL-12) plasmid formulated into nanocomplexes with a novel polymeric delivery system (PPC) has shown efficacy in treating a variety of disseminated peritoneal malignancies in mice, including disseminated epithelial ovarian cancer. As part of a pre-clinical development plan the safety and toxicity of four weekly IP doses of murine IL-12 formulated with PPC was evaluated in mice. For this GLP study 168 mice (males and females) were used. The weekly administrations were given at three dose levels of 10, 50 and 250 μg (total DNA/ mouse) and correspond to ∼1.5, 7.5 and 38 mg/m2 respectively. These doses represent significant multiples of the starting dose currently being used in Phase I clinical testing. Specifically the low, medium and high doses are approximately 2.5, 12.5 and 60 fold higher than the starting dose in humans based on a 25 g mouse and a 70 kg human. Regular clinical observations were made during the dosing phase of the study. One week and one month following the final dose the animals were euthanized and samples obtained for histopathology and clinical pathology analysis. There were no apparent treatment related effects on mortality, clinical signs, body weight, food consumption and gross necropsy findings. A dose dependent increase in spleen weight was observed. Additionally, test article related microscopic findings consisting of granulmatous to pyogranulamtous inflammatory reaction were seen in multiple organs and tissues of the peritoneal cavity. These effects were considered mild to moderate and were resolved by one month after the last treatment. Based on the observation of some inflammation in the animals at the 250 μg dose the no-observed adverse effect level (NOAEL) was considered to be the 50 μg dose level. In summary, IP delivery of mIL12/PPC was well tolerated. The effects associated with delivery were inflammatory in nature and not considered adverse but expected physiologic/pharmacologic responses associated with interleukin-12 immunotherapy. The results of this safety/toxicity study have supported the current clinical testing of IP delivered hIL-12/PPC for treating recurrent ovarian cancer.Molecular Therapy (2006) 13, S109–S109; doi: 10.1016/j.ymthe.2006.08.341 [ABSTRACT FROM AUTHOR]

We have designed a series of versatile lipopolyamines which are amenable to chemical modification for in vivo delivery of small interfering RNA (siRNA). This report focuses on one such lipopolyamine (Staramine), its functionalized derivatives and the lipid nanocomplexes it forms with siRNA. Intravenous (i.v.) administration of Staramine/siRNA nanocomplexes modified with methoxypolyethylene glycol (mPEG) provides safe and effective delivery of siRNA and significant target gene knockdown in the lungs of normal mice, with much lower knockdown in liver, spleen, and kidney. Although siRNA delivered via Staramine is initially distributed across all these organs, the observed clearance rate from the lung tissue is considerably slower than in other tissues resulting in prolonged siRNA accumulation on the timescale of RNA interference (RNAi)-mediated transcript depletion. Complete blood count (CBC) analysis, serum chemistry analysis, and histopathology results are all consistent with minimal toxicity. An in vivo screen of mPEG modified Staramine nanocomplexes-containing siRNAs targeting lung cell-specific marker proteins reveal exclusive transfection of endothelial cells. Safe and effective delivery of siRNA to the lung with chemically versatile lipopolyamine systems provides opportunities for investigation of pulmonary cell function in vivo as well as potential treatments of pulmonary disease with RNAi-based therapeutics. [ABSTRACT FROM AUTHOR]

Abstract: This paper examines the relationship between area-level social capital and non-specific psychological distress. It demonstrates that not controlling for non-time-varying omitted variables can seriously bias research findings. We use data from three cross-sections of the US National Health Interview Survey (1999, 2000, and 2001): 37,172 observations nested within 58 Metropolitan Statistical Areas. We also add data from the Area Resource File and County Business Patterns. We use a validated measure of social capital, the Petris Social Capital Index (PSCI), which measures structural social capital. We estimate a two-level multilevel linear model with a random intercept. Non-specific psychological distress is measured using a valid and reliable indicator, the K6. Individual-level variables include sex, age, race/ethnicity, marital status, education, family income, smoking status, exercise status, and number of visits to a health professional. Area-level covariates include the PSCI, the unemployment rate, psychiatrists per 1000 population, non-psychiatric physicians per 1000 population, and area-level indicators to account for non-time-varying area-level omitted variable bias. Time dummies are also included. We find that lagged area-level social capital is negatively related to non-specific psychological distress among individuals whose family income is less than the median. These associations are much larger when we control for non-time-varying area-level omitted variables. [Copyright &y& Elsevier]

Summary: Objectives: To test our hypothesis that the hemoglobin based oxygen carrier HBOC-201 would have similar or superior efficacy to 6% hetastarch (HEX) as a pre-hospital ‘bridging’ fluid for hemorrhagic shock when delay to definitive medical care is prolonged to 24h. Methods: Twenty-four pigs were anesthetized, instrumented, given a soft tissue injury, and bled 55% estimated blood volume. Pigs were randomized to receive HBOC-201, HEX, or no resuscitation fluids (NON). At 4h post-injury, surgical sites were repaired and pigs were recovered from anesthesia. Animals were non-invasively monitored, administered blood for anemia or saline for hypotension at 24 and 48h, and monitored for 72h. Results: Survival to 72h was 87.5% (7/8) in HBOC-201 and HEX pigs compared to 25% (2/8) in NON pigs (p =0.01). Increased mean arterial pressure was observed in the HBOC-201 group (p <0.0001). Cardiac index was highest in HEX pigs (overall p <0.001, HBOC-201 versus HEX p =0.002). Transcutaneous tissue oxygenation was higher with HBOC-201 (overall p =0.04, HBOC-201 versus HEX p <0.01). HBOC-201 and HEX pigs had comparable heart rates, pulmonary pressures, pre-hospital fluid requirements, venous O2 saturation, base deficit, and lactic acid. Hemoglobin was decreased with HEX (overall p <0.0001, HBOC-201 versus HEX p <0.0002). At 24h, 14.3% (1/7) HBOC-201 pigs required blood transfusions versus 100% HEX (7/7) and NON (2/2) pigs (p >0.001). Conclusions: HBOC-201 restored hemodynamics, maintained tissue oxygenation, and decreased blood transfusions in comparison to HEX in severe controlled HS with 24h delay to simulated hospital care. These results support the potential use of HBOC-201 as a bridging resuscitation fluid for HS. [Copyright &y& Elsevier]

Abstract: Introduction: Unavailability of blood (and oxygen delivery) for pre-hospital resuscitation in haemorrhagic shock patients are major problems, supporting the importance for novel resuscitation strategies. In a combined polytrauma model of uncontrolled haemorrhage and traumatic brain injury (TBI) in swine, we investigated if pre-hospital administration of the haemoglobin based oxygen carrier HBOC-201 will improve tissue oxygenation and physiologic parameters compared to Lactated Ringer''s (LR) solution. Materials and methods: Anaesthetised Yorkshire swine underwent fluid-percussion TBI and Grade III liver laceration. During a 30-min pre-hospital phase, the animals were resuscitated with a single infusion of HBOC-201, LR solution, or nothing (NON). Upon hospital arrival, the animals were given blood or normal saline as needed. Surviving animals were euthanised 6h post-injury. Cerebral blood flow was measured by microsphere injection, and pathology was assessed by gross observation and immunohistochemical analysis. Results: Mean TBI force (2.4±0.1atm) (means±standard error of the mean) and blood loss (22.5±1.7mL/kg) were similar between groups. Survival at the 6h endpoint was similar in all groups (∼50%). Cerebral perfusion pressure (CPP) and brain tissue oxygen tension were significantly greater in HBOC-201 as compared with LR animals (p <0.005). Mean arterial pressure (MAP) and mean pulmonary artery pressure (MPAP) were not significantly different amongst groups. Blood transfusion requirements were delayed in HBOC-201 animals. Animals treated with HBOC-201 or LR showed no immunohistopathological differences in glial fibrillary acidic protein (GFAP) and microtubule-associated protein 2 (MAP-2). Severity of subarachnoid and intraparenchymal haemorrhages were similar for HBOC and LR groups. Conclusion: In this polytrauma swine model of uncontrolled haemorrhage and TBI with a 30-min delay to hospital arrival, pre-hospital resuscitation with one bolus of HBOC-201 indicated short term benefits in systemic and cerebrovascular physiological parameters. True clinical benefits of this strategy need to be confirmed on TBI and haemorrhagic shock patients. [Copyright &y& Elsevier]

An abstract of the article "A Novel Functionalized Polymeric Formulation for use in Delivering Therapeutic Genes for the Treatment of Solid Tumors," by Jason Fewell, Majed Matar, Jennifer Rice, Gregory Slobodkin, Bruce Hovanes and Khursheed Anwer is presented.