cssi/SciSciGPT-SciSciNet huggingface dataset:
SpCas9-NG self-targets the sgRNA sequence in plant genome editing

Streptococcus pyogenes Cas9 (SpCas9)-NG recognizes NGN protospacer adjacent motifs and expands the scope of genome-editing tools. In this study, we found that SpCas9-NG not only targeted the genome but also efficiently self-targeted the single-guide RNA sequence in transfer DNA in transgenic plants, potentially increasing off-target risk by generating new single-guide RNAs. We further showed that the self-target effect of SpCas9-NG could be greatly alleviated by using a modified single-guide RNA scaffold starting with a GCCCC sequence.
Rapid evolutionary changes in gene expression in response to climate fluctuations.

There is now abundant evidence of rapid evolution in natural populations, but the genetic mechanisms of these changes remain unclear. One possible route to rapid evolution is through changes in the expression of genes that influence traits under selection. We examined contemporary evolutionary gene expression changes in plant populations responding to environmental fluctuations. We compared genome‐wide gene expression, using RNA‐seq, in two populations of Brassica rapa collected over four time points between 1997 and 2014, during which precipitation in southern California fluctuated dramatically and phenotypic and genotypic changes occurred. By combining transcriptome profiling with the resurrection approach, we directly examined evolutionary changes in gene expression over time. For both populations, we found a substantial number of differentially expressed genes between generations, indicating rapid evolution in the expression of many genes. Using existing gene annotations, we found that many changes occurred in genes involved in regulating stress responses and flowering time. These appeared related to the fluctuations in precipitation and were potentially adaptive. However, the evolutionary changes in gene expression differed across generations within and between populations, indicating largely independent evolutionary trajectories across populations and over time. Our study provides strong evidence for rapid evolution in gene expression, and indicates that changes in gene expression can be one mechanism of rapid evolutionary responses to selection episodes. This study also illustrates that combining resurrection studies with transcriptomics is a powerful approach for investigating evolutionary changes at the gene regulatory level, and will provide new insights into the genetic basis of contemporary evolution.
Why Risk Managers

Banks rely on risk managers to prevent their employees from making high risk low value investments. Why can't the CEOs directly incentivize their employees to choose the most profitable investment? I show that having a separate risk manager is more profitable for banks and is also socially efficient. This is because there is conflict between proving incentive to choose the most profitable investment and providing incentives to exert effort on those investments. Hence, if the tasks are split between a risk manager who approves the investments and a loan officer (or trader) who exerts effort, then both optimal investment choice and optimal effort can be achieved. I further examine some reasons for risk management failure wherein a CEO may ignore the risk manager when the latter is risk averse and suggests safe investments. As is usually the case before a financial crisis, my model predicts that the CEO is more likely to ignore the risk manager when the risky investments are yielding higher profits.
Skydio Autonomy Engine: Enabling The Next Generation Of Autonomous Flight

Drones hold the promise of massive positive impact Existing use cases are easier and more reliable New use cases that were previously impossible are enabled
Improving Process Discovery Results by Filtering Out Outliers from Event Logs with Hidden Markov Models

Process Mining is a technique for extracting process models from event logs. Event logs contain abundant explicit information related to events, such as the timestamp and the actions that trigger the event. Much of the existing process mining research has focused on discovering the process models behind these event logs. However, Process Mining relies on the assumption that these event logs contain accurate representations of an ideal set of processes. These ideal sets of processes imply that the information contained within the log represents what is really happening in a given environment. However, many of these event logs might contain noisy, infrequent, missing, or false process information that are generally classified as outliers. Extending beyond process discovery, there are many research efforts towards cleaning the event logs to deal with these outliers. In this paper, we present an approach that uses hidden Markov models to filter out outliers from event logs prior to applying any process discovery algorithms. Our proposed filtering approach can detect outlier behavior, and consequently, help process discovery algorithms return models that better reflect the real processes within an organization. Furthermore, we show that this filtering method outperforms two commonly used filtering approaches, namely the Matrix Filter approach and the Anomaly Free Automation approach for both artificial event logs and real-life event logs.
The Russian Uniform State Examination in Mathematics: The Latest Version

This paper aims to tell how the Russian national examination in mathematics (the Uniform State Examination or USE) has been conducted most recently. The author must say at once that the history of the system of secondary school graduation examinations or even the history of the USE will be covered only to the small degree that is necessary for understanding the current situation (more information can be found in Karp & Zvavich, 2011; Karp, 2007; Karp, 2003; these papers also served as a resource for writing the introductory sections of this paper). The goal of this paper looks modest, particularly given that the format of the USE obviously is subject to change; the USE, however, is so important for the Russian mathematics education, and the current situation is so typical of the challenges that are confronted in conducting assessment on the national level, that this situation deserves to be analyzed in considerable detail.
Effect of Coherin™ on intraocular pressure, pupil size and heart rate in the glaucomatous Beagle: a pilot study

Objective To evaluate effects of Coherin™ on intraocular pressure (IOP), pupil size (PS), and heart rate (HR) in glaucomatous Beagles in single-dose studies in a pilot study. Materials and methods Intraocular pressure, PS, and HR were measured in eight glaucomatous Beagles. One randomly chosen eye received single 50 μL doses of differing concentrations of Coherin™ (treated eye) or vehicle (placebo-treated eye), and the fellow eye served as the untreated control. After the first measurements, a single dose of either Coherin™ or sterile water vehicle was instilled in the drug and placebo eyes, respectively. Results The mean ± SEM diurnal changes in IOP after 0.005%, 0.01%, 0.2%, 0.284%, 1%, 2%, and 4% topical Coherin™ once daily were 7.6 ± 3.2 mmHg, 15.5 ± 5.3 mmHg, 11.2 ± 4.4 mmHg, 11.8 ± 4.4 mmHg, 19.1 ± 3.8 mmHg, 5.0 ± 1.8 mmHg, and 8.8 ± 2.8 mmHg, respectively. The declines in IOP were significantly different (P < 0.05) from the untreated control eyes with the 0.2% and 0.284% Coherin™-treated eyes and suggestive for 1% Coherin™ concentrations. No signs of irritation, significant PS, and HR changes were detected in the Coherin™-treated eyes. Conclusion Of seven different concentrations, 2% and 0.248% Coherin™ produced significant declines in IOP in the glaucomatous beagle in single-dose studies when compared to both untreated control and placebo-treated eyes. One percent Coherin™ solution produced significant IOP decreases compared with the placebo-treated eye but not the untreated control eyes. No local ocular irritation, PS and HR changes were observed in Coherin™-treated eyes. This pilot study suggests that topical Coherin™ has potential as an ocular hypotensive agent.
Informing decision makers and identifying niche opportunities for windpower: Use of multiattribute trade off analysis to evaluate non-dispatchable resources

The operational and flexibility characteristics of renewable energy technologies are often overlooked in traditional head to head technology comparisons. This impedes their adoption since identification of environmental and risk mitigation advantages requires evaluation of such non-dispatchable technologies in a systemwide context. Use of multiattribute resource planning tools in a trade off analysis framework identifies the complementary emissions reduction and fuel diversification characteristics of renewables. Data visualization using trade off analysis communicates electric resource interactions and the risks of following various strategies to diverse stakeholder audiences, promoting acceptance. This paper provides an overview of the multiattribute trade off approach and applies it to resource strategies incorporating windpower in the New England regional power system. Examples focus on the interaction of wind resources with demand-side management and supply-side options under fuel cost uncertainty.
Probability and Dynamics

The notion of complexity as an object of scientific interest is relatively new. Prior to the 20 th century, the main concern was that of simplicity, with the implication that there existed an opposite pole of complexity. Thus there existed the insinuation that scientific epistemological perception was defined as a delicate balancing act. In some sense, this idea is anomalous to the whole modern scientific enterprise as developed from the 16 th century onward. Although the dictum has proved its usefulness as a support for many scientific theories, the last century witnessed a gradual concern for simplicity's complement. Classical dynamics describes processes in which the future can be derived from the past, and past can be traced from future by time inversion. For the treatment of the material, insight is emphasized rather than mathematical rigor with few exceptions. The implications of such a formulation are rarely considered because it usually works well. An important distinction in the discussions is the fact that mathematical and experimental (real) models do not necessarily coincide. This chapter provides a different perspective in the study of nonlinear dynamics with additional attention to biological and social systems.
Synergistic and tunable human gene activation by combinations of synthetic transcription factors

Mammalian genes are regulated by the cooperative and synergistic actions of many transcription factors. In this study we recapitulate this complex regulation in human cells by targeting endogenous gene promoters, including regions of closed chromatin upstream of silenced genes, with combinations of engineered transcription activator–like effectors (TALEs). These combinations of TALE transcription factors induced substantial gene activation and allowed tuning of gene expression levels that will broadly enable synthetic biology, gene therapy and biotechnology.
Actions of cycloheximide on the submaxillary glands in normal and castrate mice.

Abstract Multiple injections of cycloheximide (daily × 5) to normal and castrate mice led to reduce levels of ribonucleic acid (RNA) in the submaxillary glands, when these levels are expressed as micrograms per organ. The antagonistic action of this agent was more evident when testicular androgens were removed. Cycloheximide effectively antagonized the stimulatory actions of testosterone on mouse submaxillary gland RNA. Although cycloheximide reduced salivary gland weights and protein contents, the most consistent alteration was observed in RNA levels.
Distribution and Properties of Visceral Nociceptive Neurons in Rabbit Cingulate Cortex

Human imaging localizes most visceral nociceptive responses to anterior cingulate cortex (ACC), however, imaging in conscious subjects cannot completely control anticipatory and reflexive activity or resolve neuron activity. This study overcame these shortcomings by recording individual neuron responses in 12 anesthetized and paralyzed rabbits to define the visceronociceptive response pattern by region and layer. Balloon distension was applied to the colon at innocuous (15 mmHg) or noxious (60 mmHg) intensities, and innocuous and noxious mechanical, thermal and electrical stimuli were applied to the skin. Simultaneous recording from multiple regions assured differences were not due to anesthesia and neuron responses were resolved by spike sorting using principal components analysis. Of the total 346 neurons, 48% were nociceptive; responding to noxious levels of visceral or cutaneous stimulation, or both. Visceronociceptive neurons were most frequent in ACC (39%) and midcingulate cortex (MCC, 36%) and infrequent in retrosplenial cortex (RSC, 12%). In contrast, cutaneous nociceptive units were higher in MCC (MCC, 43%; ACC, 32%; RSC, 23%). Visceral-specific neurons were proportionately more frequent in ACC (37%), while cutaneous-specific units predominated in RSC (62.5%). Visceral nociceptive response durations were longer than those for cutaneous responses. Postmortem analysis of electrode tracks confirmed regional designations, and laminar analysis found inhibitory responses mainly in superficial layers and excitatory in deep layers. Thus, cingulate visceral nociception extends beyond ACC, this is the first report of nociceptive activity in RSC including nociceptive cutaneous responses, and these regional differences require a new model of cingulate nociceptive processing.
Evaluation of back end of line structures underneath wirebond pads in ultra low-k device

Mechanical integrity of back end of line structures underneath wirebond pads was evaluated using 32 nm ultra low-k device by wire pull testing and 3D finite element analysis. Pad tearout rate at wire pull testing was measured for various Cu line/via structures. One key factor for robust bond pads is effective modulus in ULK levels. In addition, increased via and wiring metal density reduces the risk of pad tearout. For the evaluated structures in this work, a calculated effective modulus in ULK was a better index than metal layout type for assessment of bond pad robustness in cooperation with finite element analysis data. Wirebonding is another key factor affecting pad tearout. In this work, effects of wirebond geometry (i.e. wire size and bond ball size) on pad tearout were focused rather than the effect of parameter itself. With the robust BEOL stack and appropriate wirebonding conditions, module level reliability of 35 μm ultra fine pitch wirebond on ultra low-k chip with circuit underneath bond pads was also demonstrated with a PBGA package.
Development of tungsten coatings for the corrosion protection of alumina-based ceramics

Abstract A method is developed for the application of tungsten coatings to an alumina- yttria ceramic by conventional powder processing techniques. The coatings are shown to be free from interconnected porosity which suggests that they will protect the substrate from corrosion by liquid species. They are also both thermally stable and shock resistant.
Biomimetic assembly of zinc oxide nanorods onto flexible polymers.

We employ principles derived from biomineralization to assemble functional nanoscale inorganic materials onto flexible polymer substrates under low-temperature, benign chemical conditions. Our biomimetic approach involves the selective functionalization of polymer surfaces to create regions of differing surface energy which can promote heterogeneous nucleation in designated regions while suppressing it in others. Specifically, ZnO is grown into ordered microarrays on flexible polycarbonate films and polyester filaments directly out of aqueous solutions. The resulting block, checkerboard, and grid shaped microarrays consist of either ZnO nanorods or microplates with feature sizes down to 4 μm. The approach reported is general, does not require traditional lithography, uses no seed layers or self-assembled monolayers, and can be easily applied to a variety of planar or three-dimensional polymer substrates enabling numerous applications in flexible macroelectronics and smart textiles.
Generalized locus of control and health locus of control of surgical patients.

Sumry.-The relationship of generalized locus of control expectancies and specific health locus of control beliefs was explored in a sample of 24 cholecysteaomy patients prior to surgery. The Internality, Powerful Others, and Chance scales were used to assess generalized locus of control expectancies, and specific health locus of control beliefs were assessed by the Multidimensional Health Locus of Control scales. The results question the theoretical commonality between the two locus of control measures and suggest that the alternate forms of the health locus of control scales are not equivalent Crossvalidation on a larger sample i; required. Rotter (1966) developed the locus of control concept to describe the degree to which an individual believes that desired outcomes are contingent upon his actions and abilities. A person who believes that his own behavior is an important factor in achieving valued goals is described as having an internal locus of control. Conversely, an individual who perceives outside forces
Outcome of de novo hepatitis C virus infection in heart transplant recipients.

The outcome ofde novohepatitis C virus (HCV) infection in heart transplant recipients of HCV-antibody positive organs is not known. The aim of the study was to determine the short-term outcome of de novoHCV infection in recipients of HCV-positive donor organs. HCV-antibody negative recipients of HCV-antibody positive hearts were identified from January 1, 1991 to February 28, 1998. Control patients matched for year of transplantation were also identified. Twenty-eight patients (22 males, mean age of 56 ± 11 SD) received hearts from HCV-antibody–positive donors. The control group was similar to the patients in all clinical and demographic aspects. Twenty-three patients had detectable viremia by reverse-transcription polymerase chain reaction (RT-PCR). Of these 23 patients withde novoHCV infection, 7 (30%) developed HCV-related liver disease. Three patients (13%) had chronic hepatitis and 4 patients (17%) developed severe acute cholestatic hepatitis (ACH). Mycophenolate mofetil (MMF) use (P= .04) and high viral load at onset of acute liver disease (P= .02) were associated with ACH. Overall survival was similar between patients withde novoHCV infection and controls (P= .20). Development of ACH (P= .02) and MMF use (P= .0009) were associated with decreased survival in patients withde novoHCV infection. The present study showed that survival of patients withde novo HCV infection was similar to a matched control group. HCV-related severe ACH is associated with a poor short-term outcome in patients withde novoHCV infection. MMF use may be associated with a higher incidence of HCV-related severe ACH and a poor short-term outcome.
Similarities between LAK cells derived from human thymocytes and peripheral blood lymphocytes: Expression of the NKH-1 and CD3 antigens

Abstract Human thymocytes are devoid of NK cells but develop lymphokine-activated killer (LAK) activity after culture with recombinant interleukin-2 (rIL-2). The most active precursor for this activity appears to be a CD3-negative cell. The purpose of these studies was to compare the phenotype and functional activities of thymocyte and peripheral blood lymphocyte (PBL) LAK cells. Following culture, rIL-2-activated thymocytes resemble PBL-generated LAK and PBL NK cells. For each of these populations, lytic activity is highest in NKH-1-positive cells. Two-color fluorescence of each population also indicates that NKH-1 + cells are highly granular, as measured by staining with the lysosomotropic vital dye quinacrine. PBL, PBL-derived LAK cells, and thymus-derived LAK cells have a portion of cells that express both CD3 and NKH-1. However, approximately 60–80% of NKH-1 + cells lack detectable CD3. This suggests that both CD3 + and CD3 − cells may be capable of LAK activity. Thymic-derived LAK cells respond to interferon in a manner very similar to NK and PBL-derived LAK cells, but lack the NK-associated CD16 antigen. Thus, despite the absence of NK cells in the thymus, it is possible to generate thymocyte LAK activity which bears a strong resemblance to LAK activity derived from peripheral blood lymphocytes.
The Effect of the New England Seamounts on Gulf Stream Meandering as Observed from Satellite IR Imagery

Abstract It is commonly held belief that meandering of the Gulf Stream increases dramatically downstream of the New England Seamount chain. In fact this appears not to be the case. The envelope of Gulf Stream northern edges derived from 30 months of satellite data remains constant from 65° to 58°W. Only the mean of the integrated path length normalized by the mean path length appears to increase downstream of the seamounts, but at very nearly the same rate as upstream of them.
Dual conformations for the HIV-1 gp120 V3 loop in complexes with different neutralizing Fabs

Abstract Background: The third hypervariable (V3) loop of HIV-1 gp120 has been termed the principal neutralizing determinant (PND) of the virus and is involved in many aspects of virus infectivity. The V3 loop is required for viral entry into the cell via membrane fusion and is believed to interact with cell surface chemokine receptors on T cells and macrophages. Sequence changes in V3 can affect chemokine receptor usage, and can, therefore, modulate which types of cells are infected. Antibodies raised against peptides with V3 sequences can neutralize laboratory-adapted strains of the virus and inhibit syncytia formation. Fab fragments of these neutralizing antibodies in complex with V3 loop peptides have been studied by X-ray crystallography to determine the conformation of the V3 loop. Results: We have determined three crystal structures of Fab 58.2, a broadly neutralizing antibody, in complex with one linear and two cyclic peptides the amino acid sequence of which comes from the MN isolate of the gp120 V3 loop. Although the peptide conformations are very similar for the linear and cyclic forms, they differ from that seen for the identical peptide bound to a different broadly neutralizing antibody, Fab 59.1, and for a similar peptide bound to the MN-specific Fab 50.1. The conformational difference in the peptide is localized around residues Gly-Pro-Gly-Arg, which are highly conserved in different HIV-1 isolates and are predicted to adopt a type II β turn. Conclusions: The V3 loop can adopt at least two different conformations for the highly conserved Gly-Pro-Gly-Arg sequence at the tip of the loop. Thus, the HIV-1 V3 loop has some inherent conformational flexibility that may relate to its biological function.
Pharmacological study of a cholinergic mechanism within the rat posterior hypothalamic nucleus which mediates a hypertensive response

In unanesthetized freely moving rats, microinjection of a variety of cholinergic agonists into the posterior hypothalamic nucleus (PHN) consistently produced an elevation in mean arterial pressure (MAP). Experiments were undertaken to pharmacologically characterize this cholinergic mechanism. Microinjection of carbachol (0.1--100 nmol) into the PHN elicited reproducible and dose-related increase in MAP (17--47 mm Hg) and variable changes in heart rate. Similar responses, although longer in onset and duration, were produced by microinjection of the cholinesterase inhibitors, neostigmine, physostigmine and echothiophate. The pressor responses produced by neostigmine and physostigmine, but not by carbachol, were shown to be dependent upon intact stores of acetylcholine in the PHN. Blockade of postsynaptic muscarinic receptors by prior microinjection of atropine abolished the rise in MAP to subsequent injection of cholinergic agonists; however, similar pretreatment with the antinicotinic agent, mecamylamine, was without effect. The peripheral mechanism through which a rise in MAP was produced by cholinergic stimulation of PHN was the sympathetic nervous system since i.v. injection of an alpha-adrenergic blocking agent, phentolamine, attenuated the pressor response to intrahypothalamic injection of carbachol or neostigmine. Adrenal catecholamine release or vasopressin release were not important mechanisms in this regard. From this study we conclude that within the rat PHN there exists a muscarinic, cholinergic mechanism which, upon activation, mediates a rise in MAP through an increase in sympathetic tone.
Volatile compounds produced during acftyeene reduction by detached soybean nodules

Abstract Two previously unidentified volatile compounds formed during acctylene reduction assay of detached soybean nodules were determined to be acctaldehde were determined to be acctaldehyde and acctone. Addition of acctaldehyde vapor to assay systems resulted in accumulation of another volatile previously identified as ethanol Neithera acetaldehvde nor acetone appeared to be implicated in inhibition of C 2 H 2 reduction. The formation of all three volatiles was studied in assay systems having a high module mass to incubation volume ratio at varving concentrations of O 2 At O 2 conncentrations in excess of 40 per cent there was a delay in ethanol formation and a corresponding extension of initial rates of C 2 H 2 reduction Evidence indicated that ethanol was the most likely cause of cessation in C 2 H 2 reduction during prolonged assay of detached nodules.
Noradrenergic modulation of dendrodendritic inhibition in the olfactory bulb

Noradrenaline containing fibres in the central nervous system (CNS) have been characterized in detail by histochemical techniques1–3. A particularly striking feature of this neurotransmitter system is its diffuse pattern of innervation. Although noradrenaline generally inhibits spontaneous activity of neurones4–7, in a number of systems5,8–10 it can actually enhance orthodromic excitatory responses. Enhancement of excitatory transmission through sensory relay neurones is consistent with the view that noradrenergic systems are intimately involved in such behaviours as arousal and attention11. However, the basis for this enhancement is unclear. Two proposed hypotheses are a facilitation of excitatory transmitter action5 and a disinhibitory action in which noradrenaline inhibits inhibitory inter-neurones8. The olfactory bulb is ideally suited for studying the cellular action of noradrenaline because the neuronal circuitry is relatively simple. Using intracellular recording techniques we have now found that noradrenaline attenuates the inhibitory feedback onto relay neurones, thus facilitating their firing, while glutamate and aspartate augment the inhibitory feedback.
Magnetic Resonance Elastography Methodology for the Evaluation of Tissue Engineered Construct Growth

Traditional mechanical testing often results in the destruction of the sample, and in the case of long term tissue engineered construct studies, the use of destructive assessment is not acceptable. A proposed alternative is the use of an imaging process called magnetic resonance elastography. Elastography is a nondestructive method for determining the engineered outcome by measuring local mechanical property values (i.e., complex shear modulus), which are essential markers for identifying the structure and functionality of a tissue. As a noninvasive means for evaluation, the monitoring of engineered constructs with imaging modalities such as magnetic resonance imaging (MRI) has seen increasing interest in the past decade. For example, the magnetic resonance (MR) techniques of diffusion and relaxometry have been able to characterize the changes in chemical and physical properties during engineered tissue development. The method proposed in the following protocol uses microscopic magnetic resonance elastography (μMRE) as a noninvasive MR based technique for measuring the mechanical properties of small soft tissues. MRE is achieved by coupling a sonic mechanical actuator with the tissue of interest and recording the shear wave propagation with an MR scanner. Recently, μMRE has been applied in tissue engineering to acquire essential growth information that is traditionally measured using destructive mechanical macroscopic techniques. In the following procedure, elastography is achieved through the imaging of engineered constructs with a modified Hahn spin-echo sequence coupled with a mechanical actuator. As shown in Figure 1, the modified sequence synchronizes image acquisition with the transmission of external shear waves; subsequently, the motion is sensitized through the use of oscillating bipolar pairs. Following collection of images with positive and negative motion sensitization, complex division of the data produce a shear wave image. Then, the image is assessed using an inversion algorithm to generate a shear stiffness map. The resulting measurements at each voxel have been shown to strongly correlate (R(2)>0.9914) with data collected using dynamic mechanical analysis. In this study, elastography is integrated into the tissue development process for monitoring human mesenchymal stem cell (hMSC) differentiation into adipogenic and osteogenic constructs as shown in Figure 2.
Periodic Nanomechanical Stimulation in a Biokinetics Model Identifying Anabolic and Catabolic Pathways Associated With Cartilage Matrix Homeostasis

Enhancing the available nanotechnology to describe physicochemical interactions during biokinetic regulation will strongly support cellular and molecular engineering efforts. In a recent mathematical model developed to extend the applicability of a statically loaded, single-cell biomechanical analysis, a biokinetic regulatory threshold was presented (Saha and Kohles, 2010, “A Distinct Catabolic to Anabolic Threshold Due to Single-Cell Static Nanomechanical Stimulation in a Cartilage Biokinetics Model,” J. Nanotechnol. Eng. Med., 1(3), p. 031005). Results described multiscale mechanobiology in terms of catabolic to anabolic pathways. In the present study, we expand the mathematical model to continue exploring the nanoscale biomolecular response within a controlled microenvironment. Here, we introduce a dynamic mechanical stimulus for regulating cartilage molecule synthesis. Model iterations indicate the identification of a biomathematical mechanism balancing the harmony between catabolic and anabolic states. Relative load limits were defined to distinguish between “healthy” and “injurious” biomolecule accumulations. The presented mathematical framework provides a specific algorithm from which to explore biokinetic regulation.
Carotenoid stability during production and storage of tomato juice made from tomatoes with diverse pigment profiles measured by infrared spectroscopy.

Chemical changes in carotenoids and lipids were studied during production and storage of canned tomato juice using ATR infrared spectroscopy and HPLC. Samples from 10 groups of tomatoes with different carotenoid profiles were analyzed fresh, after hot-break and screening, after canning, and at five different time points during 1 year of storage. An apparent increase of carotenoids was observed after hot-break due to improved extraction efficiency. This increase was accompanied by some degree of lipid oxidation and carotenoid isomerization. Canning produced the most intense changes in the lipid profile with breakdown of triglycerides (∼1743 cm−1), formation of fatty acids (∼1712 cm−1), and degradation and isomerization of trans-carotenoids (∼960 and ∼3006 cm−1). Isomerization was corroborated by the relative increase of HPLC areas corresponding to carotenoid cis isomers. Canning reduced trans-lycopene, trans-δ-carotene, trans-β-carotene, and trans-lutein by 30, 34, 43, and 67%, respectively. HPLC data indi...
Inhibition of prostate cancer growth by estramustine and etoposide

Background. Metastatic prostate cancer that is refractory to hormone therapy remains an incurable disease without effective therapy. The authors used the nuclear matrix, the RNA-protein network of the nucleus that plays an important role in DNA replication and gene expression, as a target for cancer chemotherapy. In preclinical models, estramustine and etoposide appeared to interact to inhibit the growth of the hormone-refractory prostate cancer cells. Methods. These agents were tested in a Phase II clinical trial of patients with metastatic hormone-refractory prostate cancer. Estramustine,15 mg/kg/day, and etoposide, 50 mg/M 2 /day, were administered orally in divided doses for 21 days every 28 days. Therapy continued until evidence of disease progression. Results. Fifty-two patients were enrolled in this trial and had a minimum of 40 weeks follow-up. In 20 patients with measurable soft tissue disease, 3 patients demonstrated a complete response (15%) and 6 patients had a partial response (30%) for more than 2 months. Of 32 patients with disease limited to bone, 8 (25%) demonstrated improvement and 12 (38%) demonstrated stability in their bone scans. Overall, 13 men (25%) demonstrated a decrease of at least 75%, and 28 men (54%) demonstrated at least a 50% decrease in their pretreatment prostate specific antigen levels. Conclusions. The combination of estramustine and etoposide may be an active oral regimen in hormone-refractory prostate cancer. Cancer 1995 ;75 :1920-6.
Evolution and Function of Leukocyte RNase A Ribonucleases of the Avian Species, Gallus gallus

In this study, we explore the evolution and function of two closely related RNase A ribonucleases from the chicken, Gallus gallus. Separated by ∼10 kb on chromosome 6, the coding sequences of RNases A-1 and A-2 are diverging under positive selection pressure (dN > dS) but remain similar to one another (81% amino acid identity) and to the mammalian angiogenins. Immunoreactive RNases A-1 and A-2 (both ∼16 kDa) were detected in peripheral blood granulocytes and bone marrow. Recombinant proteins are ribonucleolytically active (kcat = 2.6 and 0.056 s-1, respectively), and surprisingly, both interact with human placental ribonuclease inhibitor. RNase A-2, the more cationic (pI 11.0), is both angiogenic and bactericidal; RNase A-1 (pI 10.2) has neither activity. We demonstrated via point mutation of the catalytic His110 that ablation of ribonuclease activity has no impact on the bactericidal activity of RNase A-2. We determined that the divergent domains II (amino acids 71-76) and III (amino acids 89-104) of RNase A-2 are both important for bactericidal activity. Furthermore, we demonstrated that these cationic domains can function as independent bactericidal peptides without the tertiary structure imposed by the RNase A backbone. These results suggest that ribonucleolytic activity may not be a crucial constraint limiting the ongoing evolution of this gene family and that the ribonuclease backbone may be merely serving as a scaffold to support the evolution of novel, nonribonucleolytic proteins.
Detecting chlorophyll, Secchi disk depth and surface temperature in a sub-alpine lake using Landsat imagery

Some bio-physical parameters, such as chlorophyll a concentration, Secchi disk depth and water surface temperature were mapped in the sub-alpine Lake Iseo (Italy) using Landsat Thematic Mapper (TM) data acquired on the 7 March 1997. In order to adequately investigate the water-leaving radiance, TM data were atmospherically corrected using a partially image-based method, and the atmospheric transmittance was measured in synchrony with the satellite passage. An empirical approach of relating atmospherically corrected TM spectral reflectance values to in situ measurements, collected during the satellite data acquisition, was used. The models developed were used to map the chlorophyll concentration and Secchi disk depth throughout the lake. Both models gave high determination coefficients (R2 = 0.99 for chlorophyll and R2 = 0.85 for the Secchi disk) and the spatial distribution of chlorophyll concentration and Secchi disk depth was mapped with contour intervals of 1 mg/m3 and 1 m, respectively. A scene-independent procedure was used to derive the surface temperature of the lake from the TM data with a root mean square error of 0.3 degrees C.
IRT Item Bias Detection Procedures: Issues of Model Misspecification, Robustness, and Parameter Linking

This article examines the consequences of employ ing IRT item bias detection procedures with multidi mensional IRT item data. Parameter linking methods used in previous studies of item bias were investigated in a simulation that minimized the need for such link ing. The results illustrate shortcomings of two linking methods that have been employed in IRT item bias de tection studies. The effectiveness of these methods de pended on several factors, including the number of biased items in a fixed-length test, whether bias was against only one group or more than one group, and the correlation between the two latent abilities. The findings indicated that some current IRT-based statisti cal procedures for detecting item bias were not gener ally effective at differentiating biased from unbiased items. Index terms: item bias, item response theory, multidimensional IRT data, parameter linking, reverse bias, statistical artifacts.
Biosynthesis of radioactive sugars using cantaloupe leaves.

Abstract Cantaloupe leaves having a high initial starch content were employed for the preparation of C 14 -labeled glucose by photosynthesis. The leaves were used without the customary carbohydrate-depletion procedure. The starch was extracted with perchloric acid. The labeled glucose obtained by the hydrolysis of the starch must be carefully crystallized in order to eliminate radioactive impurities.
Biomolecular realizations of a parallel architecture for solving combinatorial problems

A coherent approach to the problem of carrying out computations in aqueous solution is provided. The conceptual level of the presentation provides for many different molecular realizations to be explored in the future. Several possibilities are suggested. Our initial implementations have provided wet lab prototype computations for two of the classicalNP complete graph theoretic problems: the maximum independent set problem and the minimum dominating set problem. A wet lab prototype computation is in progress for the determination of the satisfiability of sets of disjunctive clauses.
Control-Oriented Design Using Surrogate-Based Optimization and Existence Conditions for Robust Performance

M ISSION capability of a vehicle is ultimately evaluated by closed-loop performance. Such capability depends on a synergistic integration of aerodynamics, structures, propulsion, and control, which results in flight dynamics that are optimal for the mission. Unfortunately, most systems such as aircraft are traditionally designed using a sequential series of open-loop optimizations that cannot account for, or optimize, any synergistic integrations. A formulation for design that inherently considers control must therefore be developed to enable optimal closed-loop performance. The issue of cost function is actually quite critical to the inclusion of control synthesis for design optimization. Every discipline has metrics that are unique to their objectives, so a single cost that encompasses all these metrics can be challenging to formulate. One approach that considers vibration control uses norms, both for vibration level and effort, as a cost in a linear-quadratic framework [1]. A mixed-norm approach is formulated that considers both H2 andH1 in summation to represent independent metrics of the design [2]. A positive-real condition across frequency is also introduced as a cost that has time-domain interpretations for design [3]. Several formulations formulate cost functions and solution methodologies for designs that include linear matrix inequalities (LMIs) associated with H1-norm synthesis. One generates a nonconvex formulation and uses iterations to solve the associated optimization [4]. Another approximates functions associated with perturbed state-spacematrices as LMIs to be solved using an iterative approach [5]. A two-step procedure is used for an optimization coupled with an LMI solver for the controller [6] as an multidisciplinary optimization approach. Another approach considers an iterative sequential control design and a coupled redesign with each iteration involving the solution of an LMI [7]. This Note introduces a control-oriented approach for design that avoids the common difficulties of simultaneous structure-control design, which is known to be nonconvex [8–11]. The approach actually considers an existence question that notes if a controller exists for a given structure that achieves a desired level of performance. The approach does not design both the structure and control to optimize a closed-loop norm; rather, it designs a structure for which a controller exists that optimizes a closed-loop norm. Formulations using control synthesis to minimize an H1-norm metric and anH2-norm are derived using their appropriate existence conditions. As important, a solution methodology is used based on surrogate modeling to avoid the iterations and expensive computations associated with techniques doing design with LMI expressions. The surrogate-based optimization is shown to be efficient and effective and exploring a design space to optimize the closed-loop metric.
Dioxin-inducible transactivation in a chromosomal setting. Analysis of the acidic domain of the Ah receptor.

We analyzed the transactivation function of the acidic segment of the Ah receptor (amino acids 515–583) by reconstituting AhR-defective mouse hepatoma cells with mutants. Our data reveal that both hydrophobic and acidic residues are important for transactivation and that these residues are clustered in two regions of the acidic segment of AhR. Both regions are crucial for function, because disruption of either one substantially impairs transactivation of the chromosomal CYP1A1target gene. Neither region contains an amino acid motif that resembles those reported for other acidic activation domains. Furthermore, proline substitutions in both regions do not impair transactivation in vivo, a finding that implies that α-helix formation is not required for function.
Structural Health Monitoring of Rotordynamic Systems by Wavelet Analysis

This work describes a foundation of sophisticated diagnostic techniques for the detection of shaft cracks in rotordynamic systems, considering the dynamical behavior of a rotating cracked shaft under the application of external loads. The response is modeled as a modified Jeffcott rotor, while the crack is assumed to induce a time-varying stiffness in the model. The focus of this work is the development of external loading strategies to create damage sensitive measures of vibration response and then analyze that using advanced technologies such as wavelet analysis. This will enable the detection of the crack depth, as represented by the magnitude of the damage-induced time-varying stiffness, from vibration measurements. This entails developing external forcing functions for which features of the vibration response are sensitive to the presence of the damage. The development of such inputs is based on a multiple-scales analysis of the full equations of motion, including the time-varying stiffness. From this, a resonance (called combination resonance) is identified between the operating speed of the shaft, the fundamental frequency of the shaft, and the frequency of the external forcing. When the system is operated at this resonant condition, the translational vibrations of the shaft contain a spectral component near the fundamental shaft frequency that is proportional to the amplitude of the time-varying stiffness. The resonance bandwidth, obtained from this analysis, enables us to build a framework for the development of damage detection techniques for rotating machinery. Continuous Wavelet Transform (CWT) is applied to the vibration response of a rotordynamic system that utilizes harmonic forcing satisfying combination resonance. The variation of wavelet coefficients with respect to the variation of different system parameters is examined. Attention is focused on how the resonant bandwidth affects the variation of wavelet coefficients as crack grows.Copyright © 2006 by ASME
Odontogenic keratocyst: to decompress or not to decompress? A comparative study of decompression and enucleation versus resection/peripheral ostectomy.

Purpose We discuss the outcome of 2 well-established and widely accepted methods used for the treatment of odontogenic keratocyst (OKC), enucleation with peripheral ostectomy or resection and decompression followed by enucleation and peripheral ostectomy. Patients and Methods A retrospective chart review of all cases of OKC treated in the University of Maryland’s Department of Oral and Maxillofacial Surgery between 1994 and 2004 was undertaken. A total of 31 patients with OKCs was identified. Three of these patients diagnosed with basal cell nevus syndrome and multiple OKCs and 6 patients who did not have adequate follow-up were excluded from this study; thus, 22 patients were evaluated. Of these 22 patients, 11 were treated with resection or enucleation with peripheral ostectomy (group I) and 11 were treated with decompression followed by enucleation when indicated (group II). Results A total of 22 patients with biopsy-proven OKC ranging in age from 18 to 90 years were separated into 2 treatment arms. Group I comprised 6 females and 5 males, age 18 to 71 years, with 6 OKCs located in the mandible and 5 in the maxilla. Group II comprised 6 females and 5 males, age 24 to 90 years, with 10 OKCs in the mandible and 1 in the maxilla. The choice of treatment approach was based on the size of the cyst, recurrence status, and radiographic evidence of cortical perforation. The last follow-up revealed no recurrences in group I and 2 recurrences in group II. Both patients with recurrence in group II had undergone enucleation of the same lesion in the past, and both cysts recurred within 2 years after initial treatment. Conclusions Our study results concur with the literature regarding recurrence rates of OKC. The aggressive nature of some OKCs necessitates equally aggressive treatment, whereas long-term follow up even for nonsyndromic patients with single lesions is of paramount importance. Age of the patient and the site and histological characteristics of the treated lesions were not significantly associated with the incidence of recurrence.
PERCUTANEOUS NEPHROSTOLITHOTOMY: PREDICTORS OF LENGTH OF STAY

ABSTRACTPurpose: Percutaneous nephrostolithotomy (PNL) is commonly used to treat patients with complex renal calculi. A goal at our medical center is to discharge patients home less than 24 hours after PNL. We performed a study to determine factors that caused patients to be hospitalized longer than this period.Material and Methods: The available hospital records and office charts of 133 consecutive patients undergoing initial PNL at our institution between January 1, 1999 and December 31, 2000 were reviewed. All PNL procedures were performed by one of us using a (DGA) 1-stage technique. Mean patient age was 52 years (range 25 to 84). Of the subjects 85 were male and 48 were female.Results: A total of 91 patients (68%) were discharged home less than 24 hours after surgery. The overall stone-free rate was 91%. Mean length of stay in the entire group was 1.97 days. Mean length of stay in those hospitalized longer than 24 hours was 4.12 days. Mean operative time, including time to obtain access, was 188.6 mi...