cssi/SciSciGPT-SciSciNet huggingface dataset:
Why is the New York Times writing so much about Alzheimer's disease therapies?

Can we go back to proving that drugs work in preventing, postponing, and ameliorating familial Alzheimer's disease (ad)? Ad is so devastating that there is a great public interest in the drug discovery process as evinced by the sheer number of articles in the serious popular press. The presently available, yet poorly performing, drugs have been approved despite their multiple peripheral side effects. The research on disease-modifying agents for the treatment of ad is largely focused on reducing amyloid plaques. However, it is now clear that companies and researchers alike are losing hope in finding an efficacious therapy rapidly that works in ad patients who are already cognitively impaired, and that people who staked their scientific and professional career on finding a cure for ad based on the amyloid hypothesis are shaken by the series of failed clinical trials within a short period of time. It is emerging that we may start to treat ad far too late to be able to make any significant slowing of the disease or postponing the onset of the symptoms of the disease. The history of drug development for other diseases should encourage us to focus on patients in whom we can identify the genetic markers associated with familial ad. Then when we have an efficacious and very safe drug, we will be able to establish its efficacy on, most importantly, cognition, but also at the level of plaques. This will provide the pharmacological evidence needed to show that it is worth fighting amyloidosis because it saves memory. We have a successful and lucrative history of preventive medicine on a large scale, all we need now is the foresight and will to switch strategy and no longer look for a magic bullet to fix ad, but to discover drugs that will delay and prevent the onset of ad, drugs that may be safely taken by symptom-free patients who are vulnerable and susceptible to ad. The initial population that might be preventatively treated against ad would indeed be those with genetic predisposition. While prevention trials are long and expensive as emphasized by the industry, the market for a safe and effective drug would be extended to the large number of patients susceptible to sporadic ad. Since the highest risk factor for sporadic ad is age, this would be an extraordinarily large market.
Scalability of the Bayesian optimization algorithm

To solve a wide range of different problems, the research in black-box optimization faces several important challenges. One of the most important challenges is the design of methods capable of automatic discovery and exploitation of problem regularities to ensure efficient and reliable search for the optimum. This paper discusses the Bayesian optimization algorithm (BOA), which uses Bayesian networks to model promising solutions and sample new candidate solutions. Using Bayesian networks in combination with population-based genetic and evolutionary search allows BOA to discover and exploit regularities in the form of a problem decomposition. The paper analyzes the applicability of the methods for learning Bayesian networks in the context of genetic and evolutionary search and concludes that the combination of the two approaches yields robust, efficient, and accurate search.
Spectral diffusion of molecular electronic transitions in amorphous solids: Weak and strong two-level-system phonon coupling.

The two-level-system (TLS) model of glasses is used with nonphenomenological TLS distribution functions [R. Jankowiak et al., J. Phys. Chem. 90, 3896 (1986)] to account for the time-dependent spectral-diffusion data for cresyl violet and zinc porphin in ethanol glasses at low temperatures [K. A. Littau and M. D. Fayer, Chem. Phys. Lett. 176, 551 (1991); H. C. Meijers and D. A. Wiersma, Phys. Rev. Lett. 68, 381 (1992)]. The two distributions of faster and slower TLS relaxation rates required to fit the data are characterized for both weak and strong TLS-phonon coupling. Comparison of the values obtained for the TLS parameters with those determined earlier for specific heat, thermal conductivity, pure dephasing, and spontaneous filling of nonphotochemical holes establishes that the faster and slower distributions are associated with intrinsic and extrinsic TLS. The pronounced effects of strong coupling on the TLS relaxation-rate distributions are discussed.
Subclinical Effects of Cigarette Smoking: A Five-Year Follow-Up of Physiologic Comparisons of Healthy Middle-aged Smokers and Nonsmokers

Measurements of ventilatory function, lung elastic recoil, diffusing capacity, and distribution of ventilation were obtained on healthy middle-aged cigarette smokers and nonsmokers on two occasions five years apart in order to assess the effects of smoking and the change which may occur over this five-year interval. Subjects were drawn from a randomly selected sample of the population of Tucson, AZ. Exactly the same protocol, methods, and equipment were employed in both studies. Although very few of these healthy subjects had abnormal function, there were significant differences in most indices of function between smokers and nonsmokers. However, we could discern no difference between smokers and nonsmokers in change in function over five years. It appears that, in smokers who remain free of serious respiratory trouble, there are subtle changes which accumulate over the years and which are too gradual to detect over a five-year interval.
Proton transfer reaction studies of multiply charged proteins in a high mass-to-charge ratio quadrupole mass spectrometer.

Proton transfer reactions of multiply charged ions at high mass-to-charge ratios were explored with a low frequency quadrupole mass spectrometer. This instrument enabled a qualitative comparison of proton transfer reaction rates at low charge states for ions generated by electrospray ionization (ESI) from different solution conformations and for disulfide-linked versus disulfide-reduced protein ions. Proton transfer reactions that efficiently reduced the number of charges for ESI-generated ions to approximately the number of arginines in the polypeptide sequence were observed. No significant differences in gas-phase reaction rates were noted between different solution conformers. Differences in reaction rates between “native” and disulfide-reduced proteins were much smaller than those observed below m/z 2000 with lower proton affinity reagents or by using lower reagent concentrations. These smaller differences in reaction rates are thought to reflect the reduced electrostatic contributions from widely spaced charge sites and thus, the reduced sensitivi ty to an ion’s three-dimensional structure or U compactness.
Rotational analysis of the O−O band of the first singletπ *-n system ofcis glyoxal-d1

A rotational analysis of the O−O band of the first singlet (π *-n) system ofcis glyoxal-d1 has been carried out and the following principal constants obtained:A′=0.8085(1),B′=0.19515(4),C′=0.15713(6),A″=0.7958(1),B″=0.20279(4),C″=0.16197(6),ν 00 = 20517.99 cm−1. These data have been combined with the rotational constants ofCurrie andRamsay [1] forcis glyoxal and the following molecular parameters derived: excited state −r(CH)=1.120±0.010 A (assumed), r(CO)=1.250±0.015 A, r(CC)=1.44±0.03 A, ∠HCC=113.5±1.5°, ∠OCC=127.1±0.8° ground state −r(CH)=1.115±0.010 A and r(CO)=1.210±0.005 A assumed, r(CC)=1.505±0.015 A, ∠HCC=115.5±1.5°, ∠OCC=123.8±0.4°.
The Intelligible, the Sensible, and Fictivist Thought: Angela Carter's Window on the Wolves

Abstract The phenomenological and Derridean opposition between the ‘intelligible’ and the ‘sensible’ reflects a distinction between ‘theory’ (featuring systematicity, noncontradiction, and procedural recoverability) and a ‘fictivist thought’ – the processual intellectual work of creative writers. The first of these is marked by an impulse towards logical closure (and is coded to the practice of academic theorists) while the second is marked by an impulse to resist or repudiate such closure, a working ambivalence that marks (some) fictive texts. There is a formal contradiction, however, in building an intelligible discourse on the subject of the unintelligible. Angela Carter's sequence of texts (radio play, short stories, screenplay) reworking Red Riding Hood works through this contradiction intertextually to throw light on the use of ambivalence as an intellectual strategy entailing both a structuration (a reflection on ambivalence) and destructuration (the ambivalent refusal to reify ambivalence). She ac...
Isolation and Component Structure in Spaces of Composition Operators

We establish a condition that guarantees isolation in the space of composition operators acting between H p (B N ) and H q (B N ), for 0 < p ≤ ∞, 0 < q < ∞, and N ≥ 1. This result will allow us, in certain cases where 0 < q < p ≤ ∞, completely to characterize the component structure of this space of operators.
Preclinical Studies for Induced Pluripotent Stem Cell-based Therapeutics

Induced pluripotent stem cells (iPSCs) and their differentiated derivatives can potentially be applied to cell-based therapy for human diseases. The properties of iPSCs are being studied intensively both to understand the basic biology of pluripotency and cellular differentiation and to solve problems associated with therapeutic applications. Examples of specific preclinical applications summarized briefly in this minireview include the use of iPSCs to treat diseases of the liver, nervous system, eye, and heart and metabolic conditions such as diabetes. Early stage studies illustrate the potential of iPSC-derived cells and have identified several challenges that must be addressed before moving to clinical trials. These include rigorous quality control and efficient production of required cell populations, improvement of cell survival and engraftment, and development of technologies to monitor transplanted cell behavior for extended periods of time. Problems related to immune rejection, genetic instability, and tumorigenicity must be solved. Testing the efficacy of iPSC-based therapies requires further improvement of animal models precisely recapitulating human disease conditions.
Microwave assisted solution combustion synthesis of strontium phosphate (SrP) whiskers

Abstract A rapid microwave assisted solution combustion process is used to synthesize SrCaP and SrP whiskers. It is observed that SrP whiskers composed of Sr 2 P 2 O 7 and Sr 5 (PO 4 ) 3 Cl can be efficiently synthesized. However, co-existence of Ca 2+ and Sr 2+ ions in the reaction can inhibit one-dimensional crystal growth. The introduction of Cl − ions to the reacting system is the key to induce the crystal formation towards to one-dimensional structure. The as-synthesized SrP whiskers were characterized and evaluated for potential biomedical applications.
Relapse situations and self-efficacy: An integrative model☆☆☆

Researchers studying relapse for an addictive behavior have employed two different conceptual models. Researchers concerned with typologies of relapse situations have developed a variety of discrete classes of high risk situations. Researchers who have employed a Self-efficacy approach have typically assessed different situations but scored the measure as a single general construct. Using structural modeling, this paper evaluates five alternative measurement models, representing alternative conceptualizations. A hierarchical model which integrates the previously competing models provided the best fit to the data and serves to explain a large body of previous findings. The model includes three first order constructs (Positive/Social; Negative/Affective; and Habit/Addictive) and one general second-order factor. The results were replicated across two different response formats and two different subject samples.
MEN1 tumor‐suppressor protein localizes to telomeres during meiosis

Multiple endocrine neoplasia type 1 is an autosomal dominant cancer predisposition syndrome caused by mutations in the tumor-suppressor gene MEN1. The gene encodes a nuclear protein, menin, with no recognized functional motifs. Menin has been shown negatively to regulate transcriptional activation mediated by JunD, although the significance of this interaction in normal cell physiology and how the absence of menin leads to tumorigenesis are unknown. Menin is highly expressed in testes. We used immunocytochemistry to explore its role in meiosis and found that it localizes exclusively at telomeres. JunD was not found at telomeres in meiotic cells. In view of elevated telomerase activity or abnormal telomere structure in virtually all malignancies, regulation of telomere function would be an appealing role for a tumor suppressor. However, menin does not specifically associate with telomeres in somatic cells, as indicated by lack of co-localization with the known telomeric protein TRF2. Cells overexpressing menin had normal telomerase activity, and tumors with homozygous MEN1 mutations showed no aberrations in telomere length, indicating that menin does not directly regulate telomerase activity. The role of menin at meiotic telomeres appears to be independent of JunD and may not have a counterpart in somatic cells. These results suggest that menin may play different roles in different tissues through interactions with different proteins. © 2002 Wiley-Liss, Inc.
Autonomous cross-country navigation: an integrated perception and planning system

The development of a software system for obstacle avoidance that controls a vehicle smoothly, continuously, and safely across natural terrain en route to a goal is discussed. The work, carried out as part of the Strategic Computing Initiative of the US Defense Advanced Research Projects Agency (DARPA), was performed on the Autonomous Land Vehicle at Martin Marietta's Denver facilities. The planning software uses digital maps to plan a preferred route, and then, as the vehicle traverses that route, sensors are used to obtain scene descriptions. Techniques necessary to detect and avoid obstacles in cross-country terrain, with minimum delay between sensing and acting, are used. The system architecture, the cross-country perception system, the planning system for obstacle avoidance, the simulation environment, and the experiments are described. Work to develop a fine-grained control architecture, internalized plans, multisensor perception, and color image segmentation is discussed. >
Binding of Calcium Ions by the Aorta

PREVIOUS work1 has shown that the aorta has an inherent ability to bind calcium ions in vitro. This binding in turn had a marked influence on the stability of emulsions, causing precipitation. The distribution and solubility characteristics of the primary substance suggested that collagen was responsible for the calcium binding, although other possibilities were recognized. Because of the importance attributed to binding of calcium ions by the aorta in plaque formation1, further work is reported here to add to the information concerning the identity of the binding agent(s). This was accomplished by noting the effect of various enzymes and extractive procedures on the aortic binding of calcium chloride labelled with calcium-45 which could be followed autoradiographically.
Cutaneous metastasis from adenoid cystic carcinoma of the parotid gland.

Background. Cutaneous metastasis from adenoid cystic carcinoma of the salivary gland is very rare. Objective. To present an unusual case of cutaneous metastasis from adenoid cystic carcinoma of the right parotid gland. Methods. A 63-year-old woman with multiple subcutaneous nodules on the abdomen and a gradually enlarged mass over the right parotid area was examined. A skin biopsy was taken from one of the abdominal nodules. Result. Skin biopsy demonstrated the characteristic histopathologic features of metastatic adenoid cystic carcinoma. A subsequent computerized tomography of the head and neck revealed a huge soft tissue mass involving the right parotid gland. Computerized tomography of the chest revealed extensive nodular pleural thickening, and pleural biopsy also showed typical histopathologic features of metastatic adenoid cystic carcinoma. All of these results are consistent with the diagnosis of an adenoid cystic carcinoma of the right parotid gland with disseminated metastases. Conclusion. We report a rare case of cutaneous metastasis from adenoid cystic carcinoma of the right parotid gland. The presentation of cutaneous metastasis is often nonspecific and may mimic benign lesions. Subcutaneous nodules that are rapidly developing or eruptive, are rapidly growing and have stony hardness in nature, have pain or tenderness, and have nonhealing ulceration remind us of the possibility of cutaneous metastases. Dermatologists and dermatologic surgeons should keep the diagnosis of cutaneous metastasis in mind and always perform skin biopsy when encountering these lesions.
Kidney development in cadherin-6 mutants: delayed mesenchyme-to-epithelial conversion and loss of nephrons.

During nephrogenesis, dynamic changes in the expression of cell adhesion molecules are evident as epithelial structures differentiate from the induced mesenchyme. The cadherins are thought to play an important role in the metanephric mesenchyme, when cells aggregate to form the renal vesicle, a polarized epithelial structure which eventually fuses with the ureteric bud to generate a continuous nascent nephron. We have generated and analyzed mice with a targeted mutation in the gene encoding cadherin-6 (Cad-6), a type II cadherin expressed during early stages of nephrogenesis. These mice are viable and fertile, and they complete both early and late aspects of nephrogenesis. However, upon closer examination in vitro and in vivo, a fraction of the induced metanephric mesenchyme in Cad-6 mutant kidneys fails to form a fully polarized epithelium on schedule. Moreover, a significant number of the renal vesicles in Cad-6 mutant kidneys apparently fail to fuse to the ureteric bud. These alterations in epithelialization and fusion apparently lead to a loss of nephrons in the adult. These studies support the idea that cadherins play an essential role in the formation of epithelial structures and underscore the importance of timing in orchestrating the morphogenesis of complex epithelial tissues.
Game Theoretical Pattern Recognition: Application to Imperfect Noncooperative Learning and to Multiclass Classification

This paper studies in theory, and gives a solution to, the following concerns which may eventually be simultaneous: 1) obtain alternative classification decisions, ranked by some decreasing order of class membership probabilities; 2) imperfect teacher at the learning stage, or effects of labeling errors due to unsupervised learning by clustering; 3) noncooperative teacher, manipulating the a priori class probabilities; 4) unknown a priori class probabilities. These requirements are taken into account by considering a game between the recognition system and the teacher, in a game theoretical framework. Both players will ultimately select ``mixed strategies,'' which are probability distributions over the set of N alternative pattern classes, determined for each feature vector to be classified. This solution concept is interpreted in terms of the requirements 1)-4); numerical algorithms, as well as numerical examples are given with their solutions.
Microgravity, bacteria, and the influence of motility

Abstract Space microbiology studies date back to the 1960s, with most investigations reporting that increased bacterial populations occur in flight compared to ground controls. Several exceptions to these findings, however, have created controversy and complicated explanations of how, or whether, microgravity affects microorganisms. Upon closer examination of the literature, we identified a trend relating cell motility to experimental outcome. Related studies conducted in microgravity analog devices, such as the clinostat or rotating wall vessel bioreactor, further corroborate this trend. We review the literature regarding bacterial growth experiments conducted in space (and using microgravity analogs) and analyze the influence of bacterial motility.
Measuring providers' verbal and nonverbal emotion recognition ability: reliability and validity of the Patient Emotion Cue Test (PECT).

Abstract Objective To describe the development and validation of the Patient Emotion Cue Test (PECT) as a tool to measure providers’ emotion cue recognition ability. Methods The PECT consists of 47 video clips depicting emotion cues that systematically vary in intensity of both verbal and nonverbal contents. The PECT assesses the provider's ability to detect and identify patients’ emotion cues accurately. A multi-stage development process produced the PECT. Reliability and validity were assessed in three studies. Results Scores on the PECT are normally distributed with significantly above chance responding. Across three studies, the PECT demonstrates convergent validity through significant correlations with standardized tests representing multiple channels of emotion recognition, including the face, body, and voice. The PECT shows adequate inter-item and split-half reliability. Conclusion The PECT is an easily administered, reliable, and valid test of emotion cue recognition. Practice implications The PECT can be used in future research on providers’ emotion recognition ability, for evaluating self-assessment of ability, and as a teaching tool in medical schools.
Dentate hilar mossy cells and somatostatin-containing neurons are immunoreactive for the α8 integrin subunit: characterization in normal and kainic acid-treated rats

Integrins are heterodimeric cell surface receptors composed of different alpha and beta subunits that mediate cell-cell and cell-extracellular matrix interactions. They have been implicated in the regulation of neuronal migration, differentiation, process outgrowth, and plasticity. The alpha8 integrin subunit associates exclusively with the beta1 subunit to form a receptor (alpha8beta1) for fibronectin, vitronectin, tenascin, and osteopontin. In a previous study, we demonstrated that hippocampal dentate hilar neurons are immunoreactive for alpha8. The present study identifies the major types of alpha8-immunoreactive hilar neurons and characterizes the effects of kainic acid-induced seizures on alpha8-immunoreactivity in these cells. Examination of the hilus in normal rats revealed alpha8-immunoreactivity in the somatodendritic compartments of large hilar neurons identified as mossy cells, including a subset of dendritic thorny excrescences that were contacted by large mossy fiber terminals. alpha8-immunoreactivity also was found in approximately 71% of somatostatin-containing hilar cells. Kainic acid-induced seizures dramatically and rapidly altered the levels and distribution of alpha8-immunoreactivity in hilar neurons. After 1.5 h of seizures, alpha8-immunoreactivity in their dendrites was reduced greatly. One day after kainic acid treatment, labeling was diminished throughout the somatodendritic compartments of most hilar cells. This decrease appeared to be transient, since alpha8 labeling returned to normal levels in surviving hilar neurons within 2 weeks of treatment. In addition, many alpha8-immunoreactive hilar neurons, particularly in caudal dentate regions, were lost 3-5 weeks after kainic acid treatment. Our findings suggest that alpha8beta1 may mediate adhesive interactions of the dendritic processes of mossy cells and somatostatin-containing hilar neurons with other cellular elements or with extracellular matrix components. They also suggest that alpha8 may be susceptible to activity-dependent proteolysis that could modulate its function in the somatodendritic compartment of these cells.
Transmission-Line Analogies of Plane Electromagnetic-Wave Reflections

The similarity between the equations for unguided plane electromagnetic-wave propagation and those of propagation along conventional transmission lines is illustrated here. It is shown that the conventional transmission-line equations expressed in terms of receiving-end voltage and current may be used to express the field-intensity components of uniform plane waves in any medium. Normal-incidence reflection of plane waves at surfaces of discontinuity are shown to be analogous to transmission-line reflections at impedance discontinuities. The transmission-line equations are then modified to apply to oblique incidence reflection. The relationships developed here assist in visualizing as well as solving plane-wave propagation and reflection problems using the conventional transmission-line equations. It also makes possible the use of transmission-line charts for the solution of wave-reflection problems.
Characterization and properties of preβ-HDL particles formed by ABCA1-mediated cellular lipid efflux to apoA-I

The contribution of ABCA1-mediated efflux of cellular phospholipid (PL) and cholesterol to human apolipoprotein A-I (apoA-I) to the formation of preβ1-HDL (or lipid-poor apoA-I) is not well defined. To explore this issue, we characterized the nascent HDL particles formed when lipid-free apoA-I was incubated with fibroblasts in which expression of the ABCA1 was upregulated. After a 2 h incubation, the extracellular medium contained small apoA-I/PL particles (preβ1-HDL; diameter = 7.5 ± 0.4 nm). The preβ1-HDL (or lipid-poor apoA-I) particles contained a single apoA-I molecule and three to four PL molecules and one to two cholesterol molecules. An apoA-I variant lacking the C-terminal α-helix did not form such particles when incubated with the cell, indicating that this helix is critical for the formation of lipid-poor apoA-I particles. These preβ1-HDL particles were as effective as lipid-free apoA-I molecules in mediating both the efflux of cellular lipids via ABCA1 and the formation of larger, discoidal HDL particles. In conclusion, preβ1-HDL is both a product and a substrate in the ABCA1-mediated reaction to efflux cellular PL and cholesterol to apoA-I. A monomeric apoA-I molecule associated with three to four PL molecules (i.e., lipid-poor apoA-I) has similar properties to the lipid-free apoA-I molecule.
Clinical comparison of freeze-dried and fresh frozen patellar tendon allografts for anterior cruciate ligament reconstruction of the knee

The aim of this study was to evaluate the clinical outcome of freeze-dried compared to fresh frozen al lograft tissue used as a substitute for a ruptured ACL of the knee. In addition, the incidence of any graft rejection phenomena was recorded. Forty-one patients with ACL deficient knees underwent reconstructive sur gery using a patellar bone-tendon-bone allograft that had been freeze-dried (Group 1, N = 14) or fresh frozen (Group 2, N = 27). All patients underwent the same implant technique and rehabilitation program. Followup ranged from 24 to 36 months. The evaluation consisted of subjective, objective, and instrumented laxity testing (KT-1000, MEDmetric, San Diego, CA; and Genucom, FARO Medical Technologies, Inc., Montreal, Canada). There were 31 males and 10 females.Eleven (79%) patients in Group 1 thought their knee was "normal" or "improved," and 25 (93%) in Group 2 thought the same. In addition, 10 (71%) patients in Group 1 denied any "giving way," compared to 26 (96%) in Group 2. The mean Lysholm...
Integration and recovery processes contribute to the temporal selectivity of neurons in the midbrain of the northern leopard frog, Rana pipiens.

This study examined the mechanisms underlying amplitude modulation selectivity in the anuran auditory midbrain. Single units were recorded extracellularly in the torus semicircularis of the northern leopard frog, Rana pipiens. Two physiologically distinct classes of neurons were identified, based on their response latencies and their selectivities to pulse repetition rates. Cells in one group had short response latencies (median=31 ms) and responded best to pulse repetition rates below 40 Hz. Tuning to low amplitude modulation rates was largely determined by recovery processes and phasic response properties. Cells in the second group had much longer latencies (median=81 ms) and were generally selective for pulse repetition rates greater than 40–50 Hz. Sensitivity to higher amplitude modulation rates resulted from integration processes; these units only responded when a threshold number of pulses were presented at a minimum pulse density (amplitude modulation rate). At amplitude modulation rates above their best rate, their responses decreased, apparently due to inadequate recovery time between pulses.
The radius of the essential spectrum

Abstract In this paper we define an operator measure s on L(X) into R+ ∪ {0} satisfying suitable conditions. Then letting I = s−1(0), we consider the quotient algebra L(X) I , instead of Calkin algebra and define α1(T) = {λ∈ C Π2(λ−T) is not invertible in L(X) I where Π 2 : L(X) → L(X) I is the natural homomorphism, and r 1 (T) = sup {¦λ¦:λ ϵ σ 1 (T)} . After proving the fact that σ1(T) is equal to the essential spectrum of T and replacing standard measure of noncompactness with suitably defined s-measures we obtain that the radius re(T) of the essential spectrum is equal to lim n (s(T n )) 1 n . We also construct examples of such operator measures.
Intravascular Optical Coherence Tomography Detection of Atherosclerosis and Inflammation in Murine Aorta

Objective— The goal of this study was to evaluate the feasibility of imaging the aorta of apolipoprotein E–deficient (ApoE –/– ) mice for the detection of atherosclerosis and macrophages using optical coherence tomography (OCT) compared with histology. Methods and Results— Atherosclerosis was induced by high-fat diet in 7-week-old ApoE –/– mice for 10 (n=7) and 22 (n=7) weeks. Nine-week-old ApoE –/– mice (n=7) fed a standard chow diet were used as controls. OCT images of a 10-mm descending aorta in situ were performed in 4 mice for each, and plaque and macrophages were determined at 0.5-mm intervals. Automated detection and quantification of macrophages were performed independently using a customized algorithm. Coregistered histological cross-sections were stained with hematoxylin-eosin, Mac-3, and von Kossa. Three mice in each group had en face OCT imaging to detect macrophages, which were compared with lipid-positive area with Sudan IV. OCT images were successfully acquired in all mice. OCT and histology were able to discriminate macrophages and plaque among the 3 groups and showed excellent correlation for (1) visual detection of plaque ( r =0.98) and macrophages ( r =0.93), (2) automated detection and quantification of macrophages by OCT versus Mac-3-positive area ( r =0.92), and (3) en face OCT detection of macrophages versus Sudan IV–positive area ( r =0.92). Conclusion— Murine intra-aortic OCT is feasible and shows excellent correlation with histology for detection of atherosclerotic plaque and macrophages.
Evidence that the Effects of Methadone and Marihuana on Male Reproductive Organs are Mediated at Different Sites in Rats

This study investigated the sites of action of methadone, ���tetrahydrocannabinol (�‘-THC) and cannabinol (CBN) in male reproductive organs using hypophysectomized (hypox), castrated (CD) and sham operated (SO) rats. Treatments were given as follows: the SO rats received either methadone, A9-THC, or CBN; the hypox received hCG plus the drugs; the CD rats received A#{176}THC or CBN plus testosterone (T) or dihydrotestosterone (DHT). Blood plasma T and DUT levels were quantitated in the SO and hypox rats and weights of ventral prostates (VP) and seminal vesicles (SV) were recorded in all groups. In addition, the effect of CBN on the 5-alpha reductase in the VP was determined. The results of the study show that methadone, �‘-THC, or CBN treatment significantly decreased (P<0.01) T and DHT levels and the weights of VP and SV in the SO rats. In the hypox group treated with hCG plus �‘-THC, the stimulatory effect of hCG on VP and SV weights was significantly (P<0.01) blocked, but T and DHT levels were unaffected. Methadone treatment had no effect on either VP and SV weights or T and DI-IT levels in the hypox rats. The effect of CBN on the hypox rats was similar to that of �‘-THC in all respects except that in CBN treatment plasma DHT levels were significantly decreased (P<0.01). In vitro and in vivo treatment demonstrated that CBN did not appear to have any effect on 5-alpha reductase in the VP. In the CD rats, �‘-THC and CBN blocked the stimulatory effect of T and DHT on VP and SV weights. It is concluded that methadone affects the male accessory sex organs indirectly by influencing the hypothalamic hypophyseal axis whereas �9-THC and CBN effects appear to be both direct at the tissue level and indirect at the hypothalamic-hypophyseal site.
Genetic Evidence for the Physiological Significance of the d-Tagatose 6-Phosphate Pathway of Lactose and d-Galactose Degradation in Staphylococcus aureus

Mutants of Staphylococcus aureus were isolated which were unable to utilize d-galactose or lactose, but which were able to utilize all other carbohydrates tested. Growth of the mutants on a peptone-containing medium was inhibited by d-galactose. Of those mutants selected for further study, one (tagI2) was missing d-galactose 6-phosphate isomerase, one (tagK3) was missing d-tagatose 6-phosphate kinase, and one (tagA4) was missing d-tagatose 1, 6-diphosphate aldolase. Each of these mutants accumulated the substrate of the missing enzyme intracellularly. Spontaneous revertants of each of the mutants simultaneously regained their ability to utilize d-galactose and lactose, lost their sensitivity to d-galactose, regained the missing enzymatic activities, and no longer accumulated intermediates of the d-tagatose 6-phosphate pathway. These data support our previous contention that the physiologically significant route for the metabolism of d-galactose and the d-galactosyl moiety of lactose in S. aureus is the d-tagatose 6-phosphate pathway. Furthermore, a mutant constitutive for all three enzymes of this pathway was isolated, indicating that the products of the tagI, tagK, and tagA genes are under common genetic control. This conclusion was supported by the demonstration that d-galactose 6-phosphate isomerase, d-tagatose 6-phosphate kinase, and d-tagatose 1, 6-diphosphate aldolase are coordinately induced in the parental strain.
Analyzing Soviet Images of the United States A Psychological Theory and Empirical Study

Interpretations of Soviet foreign policy often rest on assumptions about Soviet perceptions of the United States. This article presents a method for inferring Soviet perceptions. The effort builds ...
Normal Cells, but Not Cancer Cells, Survive Severe Plk1 Depletion

We previously reported the phenotype of depletion of polo-like kinase 1 (Plk1) using RNA interference (RNAi) and showed that p53 is stabilized in Plk1-depleted cancer cells. In this study, we further analyzed the Plk1 depletion-induced phenotype in both cancer cells and primary cells. The vector-based RNAi approach was used to evaluate the role of the p53 pathway in Plk1 depletion-induced apoptosis in cancer cells with different p53 backgrounds. Although DNA damage and cell death can occur independently of p53, p53-deficient cancer cells were much more sensitive to Plk1 depletion than cancer cells with functional p53. Next, the lentivirus-based RNAi approach was used to generate a series of Plk1 hypomorphs. In HeLa cells, two weak hypomorphs showed only slight G2/M arrest, a medium hypomorph arrested with 4N DNA content, followed later by apoptosis, and a strong Plk1 hypomorph underwent serious mitotic catastrophe. In well-synchronized HeLa cells, a medium level of Plk1 depletion caused a 2-h delay of mitotic progression, and a high degree of Plk1 depletion significantly delayed mitotic entry and completely blocked cells at mitosis. In striking contrast, normal hTERT-RPE1 and MCF10A cells were much less sensitive to Plk1 depletion than HeLa cells; no apparent cell proliferation defect or cell cycle arrest was observed after Plk1 depletion in these cells. Therefore, these data further support suggestions that Plk1 may be a feasible cancer therapy target.
Direct Measurements of the Outer Membrane Stage of Ferric Enterobactin Transport POSTUPTAKE BINDING

When Gram-negative bacteria acquire iron, the metal crosses both the outer membrane (OM) and the inner membrane, but existing radioisotopic uptake assays only measure its passage through the latter bilayer, as the accumulation of the radionuclide in the cytoplasm. We devised a methodology that exclusively observes OM transport and used it to study the uptake of ferric enterobactin (FeEnt) by Escherichia coli FepA. This technique, called postuptake binding, revealed previously unknown aspects of TonB-dependent transport reactions. The experiments showed, for the first time, that despite the discrepancy in cell envelope concentrations of FepA and TonB (∼35:1), all FepA proteins were active and equivalent in FeEnt uptake, with a maximum turnover number of ∼5/min. FepA-mediated transport of FeEnt progressed through three distinct phases with successively decreasing rates, and from its temperature dependence, the activation energy of the OM stage was 33–35 kcal/mol. The accumulation of FeEnt in the periplasm required the binding protein and inner membrane permease components of its overall transport system; postuptake binding assays on strains devoid of FepB, FepD, or FepG did not show uptake of FeEnt through the OM. However, fluorescence labeling data implied that FepA was active in the ΔfepB strain, suggesting that FeEnt entered the periplasm but then leaked out. Further experiments confirmed this futile cycle; cells without FepB transported FeEnt across the OM, but it immediately escaped through TolC.
Purposes of the Christian University

What is the task of the Christian university and the task of Christian educators? Given that the church of Jesus Christ is losing its influence in the Western world Christians have becomealiens in the present culture. Somehow,the world culture especiallythe youth culture - has moved beyond the Christianstory and searchedfor the meaning of life elsewhere. Christian universities must make use of Christian principlesin the pedagogicand curricularprocess. In 2012, Hanover Research published its findings on the current status of religious educations entitled: TheologicalEducationfor the 21st Century - Trends,Issues, and the Way Forwardand challenged theological education providers in the United States to adapt to 'a multitude of changes in cultural norms, educational models, international tensions, business practices, and religious presence.'2 According to the Association for Theological Schools (ATS), these changes include the following: • Weakening denominational affiliation and structures and a resulting ambiguity within non-denominational Christian identity and practice; • Increasing religious plurality and ethnic diversity within North America; • A shifting centre of Christianity to the Global South; • Increasing student and labour market demand for alternative ministerial credentialing programs, as well as theological education to prepare students for bi-vocational and lay-ministry pathways; • Technological advancement and the rise of distance learning delivery methods.3
Evolution of Genomic Content in the Stepwise Emergence of Escherichia coli O157:H7

Genome comparisons have demonstrated that dramatic genetic change often underlies the emergence of new bacterial pathogens. Evolutionary analysis of Escherichia coli O157:H7, a pathogen that has emerged as a worldwide public health threat in the past two decades, has posited that this toxin-producing pathogen evolved in a series of steps from O55:H7, a recent ancestor of a nontoxigenic pathogenic clone associated with infantile diarrhea. We used comparative genomic hybridization with 50-mer oligonucleotide microarrays containing probes from both pathogenic and nonpathogenic genomes to infer when genes were acquired and lost. Many ancillary virulence genes identified in the O157 genome were already present in an O55:H7-like progenitor, with 27 of 33 genomic islands of >5 kb and specific for O157:H7 (O islands) that were acquired intact before the split from this immediate ancestor. Most (85%) of variably absent or present genes are part of prophages or phage-like elements. Divergence in gene content among these closely related strains was ∼140 times greater than divergence at the nucleotide sequence level. A >100-kb region around the O-antigen gene cluster contained highly divergent sequences and also appears to be duplicated in its entirety in one lineage, suggesting that the whole region was cotransferred in the antigenic shift from O55 to O157. The β-glucuronidase-positive O157 variants, although phylogenetically closest to the Sakai strain, were divergent for multiple adherence factors. These observations suggest that, in addition to gains and losses of phage elements, O157:H7 genomes are rapidly diverging and radiating into new niches as the pathogen disseminates.
Bowel Evisceration Through the Bladder Neck in a Paraplegic Female Secondary to Urethral Coitus

ABSTRACT Introduction Urethral coitus is rarely reported in the literature. The majority of reported cases have been secondary to vaginal agenesis or hymenal anomalies. Aim We report a case of urethral coitus in a paraplegic patient with a patulous urethra resulting from chronic indwelling catheter use, with the unfortunate presentation of bladder rupture and evisceration per urethra. To our knowledge, this is the only report of urethral coitus due to sequelae from an indwelling catheter, as well as the only report of the subsequent complication of bowel evisceration per urethra. Results After initial temporization at an outside facility, we were able to perform primary cystorrhaphy. There was no need for bowel resection. The patient has chosen to defer her decision on permanent reconstruction. Conclusions Urethral coitus is rare and the subsequent ramifications can be devastating, particularly in neurologically impaired patients. This unusual case speaks to the importance of properly caring for the neurogenic bladder. Brown ET, Koski ME, and LaCour SM. Bowel evisceration through the bladder neck in a paraplegic female secondary to urethral coitus. J Sex Med 2012;9:1226–1228.
Ray and wave chaos in asymmetric resonant optical cavities

OPTICAL resonators are essential components of lasers and other optical devices. A resonator is characterized by a set of modes, each with a resonant frequency ω and resonance width δω= 1/τ, where τ is the lifetime of a photon in the mode. Cylindrical or spherical dielectric resonators have extremely long-lived resonances1 due to 'whispering gallery' modes in which light circulates around the perimeter trapped by total internal reflection. These resonators emit light isotropically. Recently a new category of asymmetric resonant cavities has been proposed in which substantial deformation of the cavity from cylindrical or spherical symmetry leads to partially chaotic ray dynamics. This has been predicted2–4 to give rise to a universal, frequency-independent broadening of the whispering-gallery resonances, and to highly anisotropic emission. Here we present solutions of the wave equation for asymmetric resonant cavities which confirm these predictions but also reveal interesting frequency-dependent effects characteristic of quantum chaos. For small deformations the lifetime is controlled by evanescent leakage, the optical analogue of quantum tunnelling5; here the lifetime is significantly shortened by a process known as 'chaos-assisted tunnelling'6,7. In contrast, for large deformations (˜10%) some resonances are found to have longer lifetimes than predicted by the ray chaos model due to the phenomenon of 'dynamical localization'8.
Frequency-Hopping Code Design for MIMO Radar Estimation Using Sparse Modeling

We consider the problem of multiple-target estimation using a colocated multiple-input multiple-output (MIMO) radar system. We employ sparse modeling to estimate the unknown target parameters (delay, Doppler) using a MIMO radar system that transmits frequency-hopping waveforms. We formulate the measurement model using a block sparse representation. We adaptively design the transmit waveform parameters (frequencies, amplitudes) to improve the estimation performance. Firstly, we derive analytical expressions for the correlations between the different blocks of columns of the sensing matrix. Using these expressions, we compute the block coherence measure of the dictionary. We use this measure to optimally design the sensing matrix by selecting the hopping frequencies for all the transmitters. Secondly, we adaptively design the amplitudes of the transmitted waveforms during each hopping interval to improve the estimation performance. To perform this amplitude design, we initialize it by transmitting constant-modulus waveforms of the selected frequencies to estimate the radar cross section (RCS) values of all the targets. Next, we make use of these RCS estimates to optimally select the waveform amplitudes. We demonstrate the performance improvement due to the optimal design of waveform parameters using numerical simulations. Further, we employ compressive sensing to conduct accurate estimation from far fewer samples than the Nyquist rate.
An Assessment of the Quality of Automated Program Operator Repair

Automated program repair (APR) techniques fix faults by repeatedly modifying suspicious code until a program passes a set of test cases. Although generating a repair is the goal of APR, a repair can have negative consequences. The quality of a repair is reduced when the repair introduces new faults and/or degrades maintainability by adding irrelevant but functionally benign code. We used two APR approaches to repair faulty binary operators: (1) find a repair in existing code by applying a genetic algorithm to replace suspicious code with other existing code as done by GenProg, and (2) mutate suspicious operators within a genetic algorithm. Mutating operators was clearly more effective in repairing faulty operators than using existing code for a repair. We also evaluated the approaches in terms of two potential negative effects: (1) the introduction of new faults and (2) a reduction of program maintainability. We found that repair processes that use tests that satisfy branch coverage reduce the number of new faults. In contrast, repair processes using tests that satisfy statement coverage and randomly generated tests introduce numerous new faults. We also demonstrate that a mutation based repair process produces repairs that should be more maintainable compared to those produced using existing code.
The Technical Possibilities for a Regenerated Silk

The molecular properties of silk fibroin are such as to make the regeneration of silk worthy of serious consideration. Not only is the molecular weight such as to indicate at least 500 units in the polymer, but, also, the component residues are among the simplest amino acids, without bulky side groups. Thus, the interchain attraction is the highest of several representative polymers. The mechanical problems of silk regeneration are not easily overcome, however. Many solvents degrade the fibroin appreciably, and, so far as is known, aqueous solutions of concentration com parable to that found in the silkworm have not been made. The structural simplicity which gives rise to good polymer properties is also conducive to instability of aqueous solutions. While important in an over-all appraisal of silk regeneration, the economic problems are not discussed in this paper.
A continuous approximation to the generalized Schur decomposition

Abstract We consider the problem of approximating the generalized Schur decomposition of a matrix pencil A − λ B by a family of differentiable orthogonal transformations. It is shown that when B is nonsingular this approach is feasible and can be fully expressed as an autonomous differential system. When B is singular, we show that the location of zero diagonal entries of B affects the feasibility of such an approach, and hence we conclude that at least the QZ algorithm cannot be extended continuously.