cssi/SciSciGPT-SciSciNet huggingface dataset:
Histologic changes in prostate carcinomas treated with leuprolide (luteinizing hormone-releasing hormone effect). Distinction from poor tumor differentiation.

Background. Treatment of patients with prostate carcinoma using drugs with antiandrogenic effects is increasingly common. One of the most popular agents is leuprolide (with or without flutamide), an agonist of luteinizing hormone-releasing hormone (LH-RH). Prostates exposed to antiandrogenic agents develop distinctive pathologic changes. The ability of a group of 18 pathologists to recognize these LH-RH effects on prostate cancers and to distinguish them from poor tumor differentiation was tested using a Delphi technique. Methods. The Delphi method maximizes the opportunity for individual contributions by eliminating opportunities for group dynamics and confrontational interaction. In this study, participants were provided with a set of duplicate transparencies and a list of written definitions of both poor tumor differentiation and LH-RH effect. They were instructed to examine the cases privately using the definitions provided and to distinguish poor tumor differentiation from LH-RH effect. Responses of the participants were shared anonymously, and each was asked to reexamine the cases in light of this knowledge. Results. After a learning experience accomplished by one round of examination and feedback, LH-RH effect could be correctly distinguished from poor tumor differentiation in greater than 90% of cases by 83% of the participants. A small percentage of cases confounded complete consensus, although every case was correctly identified by most participants. Conclusion. The pathologic effects associated with androgen deprivation with leuprolide (plus flutamide) are sufficiently distinctive to be recognized by knowledgeable pathologists. In most cases, the tissue shrinkage representing a favorable response to the drug can be distinguished from solid or infiltrating patterns of poorly differentiated carcinoma. Cancer 1994; 73:1472–7.
Grandfather - granddaughter incest: a trigenerational view

Grandfather-granddaughter incest accounts for about 10% of all reported cases of intrafamilial childhood sexual abuse. In a sample of 10 such cases, all referrals came from mothers of the child victims; six of these mothers had themselves been abused in childhood by the perpetrator. For eight of the 10 perpetrators, multiple child sexual victims were identified in a pattern that suggests facultative pedophilia. Only two of the 18 grandchildren sexually abused by the 10 grandfathers were asymptomatic at the time of report. Grandchild victims from chaotic families showed educational and behavioral symptoms; those from stable families exhibited fears and phobias. Eight of the 18 grandchildren were victimized by multiple perpetrators. The results cast doubt on the assumption that grandparent incest is a benign form of abuse and indicate that there is some justification for the fears expressed by adult incest victims about visitation between their children and the father-perpetrator.
A Positive Psychology Perspective on Post-9/11 Security

Positive psychology is a newly-christened field concerned with what makes life most worth living. At first glance, it would seem to have little to say about the post-9/11 world, but its central concerns�positive emotions, good character, and enabling institutions�are all pertinent to how people rise to the occasion of challenge and threat. What is good in life is not the mere absence of what is bad, and any attempts to create security must go beyond the minimization of danger to address how people can flourish in any and all circumstances. The present article discusses some of the implications of positive psychology for understanding and achieving post-9/11 security and flourishing.
FKBP12.6 Inhibits Resting Ryanodine Receptor Activity but PKA-Dependent Phosphorylation Does Not Alter FKBP12.6-RyR2 Binding in Rat Permeabilized Myocytes

FK506-binding proteins FKBP12.6 and FKBP12 are associated with the cardiac ryanodine receptor (RyR2), and PKA dependent hyperphosphorylation of RyR2 has been proposed to interrupt the FKBP12.6-RyR2 interaction and activate RyR2 opening. However, the physiological function of FKBP12.6/12.0 in cardiac myocytes and the role of PKA-dependent RyR2 phosphorylation are controversial. We used permeabilized rat ventricular myocytes, and fluorescently-labeled FKBP12.6/12.0 to directly measure in situ binding of FKBP12.6/12.0 to RyR2, with simultaneous Ca sparks measurements as an RyR2 functional index. We found that both FKBP12.6 and FKBP12 concentrate at the Z-line, consistent with RyR2 binding. However, only FKBP12.6 inhibits resting RyR2 activity. Assessment of fluorescent FKBP binding at the Z-line of permeabilized myocytes revealed a high affinity of FKBP12.6-RyR2 (Kd = 0.97 ± 0.1 nM) and much lower affinity of FKBP12-RyR2 (Kd = 206 ± 70 nM). Fluorescence recovery after photobleach of FKBP in myocytes confirmed these different affinities and showed that the main difference was in koff. Activation of RyR2 phosphorylation by PKA had no significant affect on either binding kinetics or affinity of FKBP12.6/12-RyR2. Using quantitative immunoblots, we determined the concentration of endogenous FKBP12 in intact myocytes was ∼1 μM, while FKBP12.6 is at most ∼150 nM. Taken together, our data suggest that FKBP12.6 binds to and stabilizes the resting RyR2 but cAMP-dependent RyR2 phosphorylation does not dissociate FKBP12.6 (or FKBP12) from RyR2 in the myocyte environment. More important, this study highlights the importance of in situ binding properties measurement and clarifies some aspects of controversy.
Relationship of fluoride and dietary fats to serum cholesterol in rats.

SummarySerum cholesterol level was determined in 5 series of rats receiving either different fats in their diets or different fats plus fluoride to determine whether the use of fluoride is associated with an increased serum cholesterol level. After administration of 2 mg of fluoride daily throughout a 10-week period there was no significant change in serum cholesterol level of rats regardless of their dietary fat source or the presence of fluoride. Comparison of body weight gains of the various groups fails to suggest that any of the fats used resulted in increased fluoride toxicity.
Medulloblastoma development: tumor biology informs treatment decisions

Medulloblastoma is the most common malignant pediatric brain tumor. Current treatments including surgery, craniospinal radiation and high-dose chemotherapy have led to improvement in survival. However, the risk for recurrence as well as significant long-term neurocognitive and endocrine sequelae associated with current treatment modalities underscore the urgent need for novel tumor-specific, normal brain-sparing therapies. It has also provided the impetus for research focused on providing a better understanding of medulloblastoma biology. The expectation is that such studies will lead to the identification of new therapeutic targets and eventually to an increase in personalized treatment approaches.
In-line Fraunhofer holography at a few far fields.

The process of in-line Fraunhofer holography of particles is studied by an analysis of the four terms in the reconstructed field. Specific results are discussed for objects with circular cross section. The image shape and contrast are described in detail. The study is particularly useful when the recording is performed at a few far fields. It has been found that the recording at a higher far field is better due to a higher image-to-background irradiance ratio at the edges of the reconstructed image.
The effect of capital structure on a firm's liquidation decision☆

Abstract A firm's liquidation can impose costs on its customers, workers, and suppliers. An agency relationship between these individuals and the firm exists in that the liquidation decision controlled by the firm (as the agent) affects other individuals (the customers, workers, and suppliers as principals). The analysis in this paper suggests that capital structure can control the incentive/conflict problem of this relationship by serving as a pre-positioning or bonding mechanism. Appropriate selection of capital structure assures that incentives are aligned so that the firm implements the ex-ante value-maximizing liquidation policy.
DNA synthesis in human lymphocytes: Intermediates in DNA synthesis, in vitro and in vivo

Two in vitro systems, one using a whole cell lysate, and the other a suspension of washed nuclei prepared from a human lymphocyte line, are characterized with respect to their requirements for the synthesis of DNA and to the nature of the synthetic product. Ribonucleoside triphosphates have a stimulatory effect on DNA synthesis that cannot be accounted for by their effect in maintaining deoxyribonucleosidetriphosphate levels. The rate of synthesis in the lysate is approximately 10% of the in vivo rate and is linear for 20 to 40 minutes; in those nuclei that are active, a maximum of 1% of the cellular DNA is newly synthesized. A class of fragments, with a mean chain length of 120 nucleotides, can be distinguished on polyacrylamide gels and is the earliest labeled intermediate in the whole cell lysate. These short fragments grow to several hundred nucleotides and then attach to high molecular weight DNA. The in vitro synthetic product consists of continuous strands several million daltons in size. The in vitro fork movement rate, and probably also the individual chain growth rate, are approximately 10% of the corresponding in vivo rates. Washed nuclei make 120-nucleotide intermediates similar to those of the lysate; nuclei, however, do not synthesize high molecular weight DNA, the largest product being around 10 S. If cytoplasmic extract is added back to nuclei some of the ability to synthesize large DNA is restored. In intact exponentially growing cells labeled with radioactive thymidine, a similar 120-nucleotide DNA fragment has been identified.
Predictable tissue shrinkage during frozen section histopathologic processing for Mohs micrographic surgery.

Background. When confronted with a histologic specimen that is appreciably smaller than the same tissue specimen immediately after acquisition, the Mohs surgeon is faced with two possibilities, namely that the tissue has either shrunken during laboratory processing or that the histologic specimen is incomplete due to the introduction of technical errors during embedding, cutting, or staining of the skin specimen. Because the entire objective of Mohs micrographic surgery is to precisely examine the entire surgical margin of skin specimens, the surgeon must be able to determine that any size discrepancies introduced during laboratory processing are not related to incomplete surgical specimens. Although there are anecdotal suggestions that skin, like other human tissues, undergoes some degree of shrinkage during routine frozen section processing, the exact nature and magnitude of this phenomenon has not been previously investigated. Objective. To quantify the degree of tissue shrinkage in Mohs micrographic surgical specimens processed with routine frozen sections and subsequent hematoxylin and eosin staining. Methods. A total of 117 Mohs surgery patients (135 cutaneous tumors) were prospectively enrolled. The dimensions of initial stage surgical specimens were determined after removal from the patient, after freezing in a mounting medium, after placement on a glass microscopic slide, and after hematoxylin and eosin staining. Statistical analyses were performed in order to determine the significance of any discrepancies in specimen sizes introduced during laboratory processing. Results. Skin specimens processed by frozen section techniques during Mohs micrographic surgery undergo statistically significant alterations in length. On average the measurements of specimens at the conclusion of histologic processing were 11.6% shorter than the measurements of the same specimens obtained immediately after surgical excision. Tissue specimens obtained from the trunk or extremities showed a greater degree of tissue shrinkage (16.3%) than specimens obtained from the head and neck (10.2%). Conclusions. Our results support anecdotal suggestions that skin specimens do indeed shrink during frozen section processing. By realizing that frozen section specimens can be expected to show some slight degree of shrinkage, the Mohs surgeon can appreciate situations that might allow greater confidence that a smaller specimen is nonetheless representative of the entire lateral and deep surgical margins.
Incorporating Speculative Execution in Exact Control-Dependent Scheduling

This paper describes a symbolic formulation that allows incorporation of speculative operation execution (preexecution) in an exact control-dependent scheduling of arbitrary forward branching control/data paths. The technique provides a closed form solution set in which all satisfying schedules are encapsulated in a compressed OBDD-based representation. To extract parallelism implicit in the input specification Boolean 'guard' functions are used to identify paths where operations have to be scheduled and the execution order of the conditionals is dynamically resolved. An efficient and systematic iterative construction method is presented along with benchmark results.
A single-specification principle for functional-to-timing simulator interface design

Microarchitectural simulators are often partitioned into separate, but interacting, functional and timing simulators. These simulators interact through some interface whose level of detail depends upon the needs of the timing simulator. The level of detail supported by the interface profoundly affects the speed of the functional simulator, therefore, it is desirable to provide only the detail that is actually required. However, as the microarchitectural design space is explored, these needs may change, requiring corresponding time-consuming and error-prone changes to the interface. Thus simulator developers are tempted to include extra detail in the interface "just in case" it is needed later, trading off simulator speed for development time. We show that this tradeoff is unnecessary if a single-specification design principle is practiced: write the simulator once with an extremely detailed interface and then derive less-detailed interfaces from this detailed simulator. We further show that the use of an Architectural Description Language (ADL) with constructs for interface specification makes it possible to synthesize simulators with less-detailed interfaces from a highly-detailed specification with only a few lines of code and minimal effort. The speed of the resulting low-detail simulators is up to 14.4 times the speed of high-detail simulators.
Preparation and in vitro evaluation of solid dispersions of halofantrine.

Abstract The low aqueous solubility of halofantrine (HF) and its low bioavailability from commercially available tablets (Halfan®) suggested the formulation of solid dispersions (SDs) of HF to reduce its particle size and improve its wettability and aqueous solubility. Preformulation studies involved the development of a high performance liquid chromatography (HPLC) method for the analysis of HF. In addition, solubility studies were conducted on HF in aqueous solutions containing different concentrations of various carriers. Formulation studies included the preparation of SDs and physical mixtures (PMs) of HF with different carriers and their physicochemical characterization using differential scanning calorimetry (DSC), Fourier-Transform infra-red (FT-IR) spectroscopy and dissolution studies. A 3-month stability study at elevated temperatures was conducted on representative SDs of HF with selected carriers.
Use of Magneto-Optic Kerr Effect Measurements to Study Strain and Misfit Accommodation in Thin Films of Ni/Cu (100)

We have detected magnetic transitions in Ni/Cu (100) films as a function of Ni thickness through in situ measurements of the magneto-optic Kerr effect (MOKE). Crystalline quality was monitored using in situ RHEED and Auger electron spectroscopy. Films were deposited by molecular beam epitaxy on silicon wafers and cleaved sodium chloride with varying epitaxial Ni layer thicknesses between 10 and 200 A. High-resolution TEM images of these films indicate decreasing misfit dislocation spacing and decreasing strain as measured by moire fringe analysis with increasing Ni thickness. These observations have been correlated with changes in magnetic anisotropy as measured by MOKE. MOKE, therefore, may provide a tool for in situ monitoring of the kinetics of misfit accommodation in magnetic thin films.
Adjusting step length for rough terrain locomotion

The task of controlling step length in the context of a dynamic biped robot that actively balances itself as it runs is discussed. Three methods for controlling step length, each of which adjusts a different parameter of the running cycle, are discussed. The adjusted parameters are forward running speed, running height, and duration of ground contact. All three control methods are successful in manipulating step length in laboratory experiments, but the method that adjusted forward speed provided the widest range of step lengths with accurate control of step length. The three methods for controlling step length manipulated the dynamics of the system so the feet could be placed on the available footholds without disturbing the system's balance. An alternative approach which ignores balance for a single step, placing the foot directly on the desired foothold, and recovering balance later is described. >
Temporal and vertical variability in photosynthesis in the North Pacific Subtropical Gyre

In situ fast-repetition-rate fluorometric (FRRF) surveys were conducted in the North Pacific Subtropical Gyre (NPSG) at Station ALOHA (Sta. ALOHA, 22u459N, 158u009W), from September 2002 to December 2004, to assess temporal and vertical photosynthetic variability in relation to environmental conditions. The nighttime potential photosynthetic efficiency of the photoautotrophic microbial assemblage (given as the ratio of variable to maximal fluorescence, FV :F M) was low in the mixed layer and increased with depth. High FV :F M values were observed at and below the deep chlorophyll maximum layer (DCML); some values approached the theoretical maximum for prokaryotes grown under nutrient-replete conditions in the laboratory (0.60). In contrast, the absorption cross section of photosystem II (sPSII) was high at the surface and decreased with depth; minima (1,000 A ˚ 2 quanta21) occurred around the DCML. These vertical patterns suggest photosynthetic stress conditions in surface photoautotrophic populations. No significant seasonal cycles were found for FV :F M, but surface sPSII values peaked in winter and decreased during summer, suggesting that seasonal variations in light availability may influence the observed sPSII variability. A significant correlation was found among surface FV :F M, sPSII, and the distance from the mixed-layer depth (MLD) to the top of the nutricline. Neither nutrient nor light variations were significantly related to FV :F M and sPSII in the DCML. Within this layer, FV :F M variability was positively and negatively related to concentrations of chlorophyll b and zeaxanthin, respectively. Our results suggest that, at Sta. ALOHA, surface photosynthesis takes place under chronic nutrient limitation, while higher photosynthetic efficiency in the lower euphotic zone appears to be sensitive to community-structure changes.
Design and characterization of ESD solutions with EMC robustness for automotive applications

Abstract Electrostatic discharge (ESD) protection design and characterization with consideration of harmful electromagnetic compatibility (EMC) events for automotive interface networks are presented. The EMC events discussed in this paper include: electrostatic discharge (ESD), electrical fast transient (EFT), surge and automotive environment transients. Key electrical parameters defined in those standards are extracted and compared. To provide efficient protection against these EMC requirements, two major automotive process technologies namely, full-dielectric isolation or silicon on insulator (SOI) and junction isolation (JI), are compared with respect to the leakage current, latch-up immunity, design complexity, EMC handling capability and cost. Protection solutions for EMC-compliance issues are reviewed at both the off-chip and on-chip levels. Trade-offs among several off- and on-chip protection devices with varying degrees of area efficiency and robustness are analyzed.
Metallized ultrathin nanocrystalline Si membranes as biochemical SPR sensors

Metal-coated ultrathin nanocrystalline Si membranes provides a novel substrate for biochemical sensing. FDTD simulations show SPR formation. The SPR peak is polarization dependent. Sensing experiments are performed with IPA and methanol.
Pharmacologic treatments for heroin and cocaine dependence

Given the difficulty of achieving sustained recovery, pharmacotherapy of opioid and cocaine addiction is more effective when combined with behavioral and psychosocial approaches. Effective pharmacotherapies for opioid dependence and withdrawal include methadone, L-alpha acetylmethadol (LAAM), naltrexone, buprenorphine, and clonidine. Treatment of cocaine addiction includes anti-craving agents, dopamine agonists or blocking agents, antidepressants, and treatment of co-morbid psychiatric disorders, but all with mixed results. In this paper, we discuss the use of medication in the context of general principles of opioid and cocaine addiction treatment. Both established medications and promising directions in pharmacotherapy will be addressed.
A higher dimensional theory of contact resistance

Electrical contact is an important issue for wafer evaluation of manufactured integrated circuits. It has also repeatedly surfaced in our ongoing studies of high power microwave sources, wire-array Z pinches, field emitters, and metal- insulator-vacuum junctions. Because of the surface roughness on a microscopic scale, true contact between two pieces of metal occurs only on the asperities of the two contacting surfaces. Current flows only through these asperities, which occupy a small fraction of the area of the nominal contacting surfaces. This gives rise to contact resistance. We have recently developed an analytic theory of the contact resistance of an asperity that has a finite axial length (h) connecting two metal blocks. We construct a scaling law for arbitrary aspect ratios of the asperity, with the h = 0 limit reducing to the classical "a-spot theory" of Holm and Timsit. While asperities of finite length may be a small step closer to reality, this higher-dimensional treatment could link the contact resistance to the geometrical deformations in response to an applied pressure, and eventually to the hardness of the material. Potential applications and extensions of the theory, such as the RF contact resistance, will be presented.
Prevalence of Cocaine Use and Its Impact on Asthma Exacerbation in an Urban Population

Objectives To assess the prevalence of cocaine use, and its impact on severity of presentation, among adults presenting to the emergency department (ED) with asthma. A secondary aim was to assess the use of various asthma treatment modalities, with reference to the 1997 National Asthma Education and Prevention Program (NAEPP) guidelines. Methods All adults aged 18 to 55 years who presented to the ED of this institution with an asthma attack, were approached about participating in the study, which required giving informed consent, answering a facilitated questionnaire, and giving a urine sample for drug screening. Results Patients were enrolled during a 7-month period. A total of 163 patients were approached to enter the study; 116 patients consented to participate in the study, with 103 submitting complete urine samples. Thirty-seven patients refused to participate, and 10 were excluded. Sixty-eight percent of the patients were women, with a mean age of 33 years. African-Americans made up 89% of the total group. Thirty-five percent were cigarette smokers. Urine cocaine tests were positive in 13 of 103 (13%); 6 of 103 (5.8%) were positive for opiates. In the cocaine-positive group, 5 of 13 patients (38%) were admitted to the hospital, including two patients requiring intubation and mechanical ventilation. Of the total group, 23 of 103 patients (22%) were admitted, and 5 of those 23 admitted patients (22%) were cocaine-positive. Length of stay was significantly longer (5 vs 2.5 days, p Conclusions The prevalence of cocaine use may be much higher than the 13% shown in this study, because of patients' refusal to participate in the study. Second, the severity of exacerbation appears to be worse in the cocaine-positive group. Finally, the majority of patients presenting did not use ICS in accordance with the NAEPP guidelines.
DARPP-32: Regulator of the Efficacy of Dopaminergic Neurotransmission

Dopaminergic neurons exert a major modulatory effect on the forebrain. Dopamine and adenosine 3',5'-monophosphate-regulated phosphoprotein (32 kilodaltons) (DARPP-32), which is enriched in all neurons that receive a dopaminergic input, is converted in response to dopamine into a potent protein phosphatase inhibitor. Mice generated to contain a targeted disruption of the DARPP-32 gene showed profound deficits in their molecular, electrophysiological, and behavioral responses to dopamine, drugs of abuse, and antipsychotic medication. The results show that DARPP-32 plays a central role in regulating the efficacy of dopaminergic neurotransmission.
An anylytical inversion of the 180° Exponential Radon Transform with a numerical kernel

This work presents an inversion algorithm for the exponential Radon transform (ERT) over 180deg range of view angles. The algorithm can be applied to two-dimensional parallel beam geometry in single photon emission computed tomography. First the differentiation of the ERT over pi is backprojected. A convolutional relation between this backprojected differentiation and the original image is then established. In order to invert the convolution relation, the least-squares method is utilized to obtain a numerically generated filtering kernel, which readily restores the original image. The advantages of the proposed algorithm are, first, it only requires half the view angles of the conventional inversion algorithm, second, it deals with truncation in ERT data in certain situations, and third, the numerically generated filtering kernel can be pre-calculated and stored for later applications. The algorithm is an analytical approach except for the pre-calculated inverse kernel.
Potential pitfalls in MALDI-TOF MS analysis of abiotically synthesized RNA oligonucleotides.

Demonstration of the abiotic polymerization of ribonucleotides under conditions consistent with conditions that may have existed on the prebiotic Earth is an important goal in “RNA world” research. Recent reports of abiotic RNA polymerization with and without catalysis rely on techniques such as HPLC, gel electrophoresis, and MALDI-TOF MS to analyze the reaction products. It is essential to understand the limitations of these techniques in order to accurately interpret the results of these analyses. In particular, techniques that rely on mass for peak identification may not be able to distinguish between a single, linear RNA oligomer and stable aggregates of smaller linear and/or cyclic RNA molecules. In the case of MALDI-TOF MS, additional complications may arise from formation of salt adducts and MALDI matrix complexes. This is especially true for abiotic RNA polymerization reactions because the concentration of longer RNA chains can be quite low and RNA, as a polyelectrolyte, is highly susceptible to adduct formation and aggregation. Here we focus on MALDI-TOF MS analysis of abiotic polymerization products of imidazole-activated AMP in the presence and absence of montmorillonite clay as a catalyst. A low molecular weight oligonucleotide standard designed for use in MALDI-TOF MS and a 3′-5′ polyadenosine monophosphate reference standard were also run for comparison and calibration. Clay-catalyzed reaction products of activated GMP and UMP were also examined. The results illustrate the ambiguities associated with assignment of m/z values in MALDI mass spectra and the need for accurate calibration of mass spectra and careful sample preparation to minimize the formation of adducts and other complications arising from the MALDI process.
Nanometer-resolution measurement and modeling of lateral variations of the effective work function at the bilayer Pt / Al / SiO 2 interface

A ballistic electron emission microscopy (BEEM) comparison of the dependence on gate voltage of the average energy barrier of a metal bilayer $\text{Pt}/\text{Al}/{\text{SiO}}_{2}/\text{Si}$ sample and a $\text{Pt}/{\text{SiO}}_{2}/\text{Si}$ sample suggests that the metal/oxide interface of the $\text{Pt}/\text{Al}/{\text{SiO}}_{2}/\text{Si}$ sample is laterally inhomogeneous at nm length scales. However, BEEM images of the bilayer sample do not show significantly larger lateral variations than observed on a (uniform) $\text{Pt}/{\text{SiO}}_{2}/\text{Si}$ sample, indicating that any inhomogeneous ``patches'' of lower-energy barrier height have size smaller than the lateral resolution of BEEM, estimated for these samples to be $\ensuremath{\sim}10\text{ }\text{nm}$. Finite element electrostatic simulations of an assumed inhomogeneous interface with nm size patches of different effective work function can fit the experimental data of the bilayer sample much better than an assumed homogenous interface, indicating that the bilayer film is laterally inhomogeneous at the nm scale.
Towards an Understanding of Neuropsychiatric Manifestations in Fragile X Premutation Carriers.

ABSTRACT: Fragile X-associated disorders are a group of disorders caused by expansion of noncoding CGG repeat elements in the fragile X (FMR1) gene. One of these disorders, fragile X syndrome, is the most common heritable cause of intellectual disability, and is caused by large CGG repeat expansions (>200) resulting in silencing of the FMR1 gene. An increasingly recognized number of neuropsychiatric fragile X-associated disorders have recently been identified that are caused by ‘premutation’ range expansions (55–200). These disorders are characterized by a spectrum of neuropsychiatric manifestations ranging from an increased risk of neurodevelopmental, mood and anxiety disorders to neurodegenerative phenotypes, such as the fragile X-associated tremor ataxia syndrome. This article reviews the advances in the clinical understanding of neuropsychiatric disorders in premutation carriers across the lifespan and offers guidance for the detection of such disorders by practicing psychiatrists and neurologists.
Organophosphorus compounds as active site-directed inhibitors of elastase

Abstract Four ethyl p -nitrophenyl alkylphosphonates were studied for the inhibition of elastase. A pH-dependence study using the assay substrate BOC-Ala-ONp or the phosphonate inhibitors showed the participation of an ionizing group with an apparent pKa of 6.9 and a decrease of reaction or inhibition at higher pH. Out of the four compounds investigated ethyl p -nitrophenyl pentylphosphonate was found to be the best inhibitor of elastase as judged from the value of k 2 K I . This value, which is the measure of inhibitory capacity, is the highest reported so far for the inhibition of elastase.
Interferometric method of measuring the spectral slit width of spectrometers.

The spectral slit width of a monochromator is defined as the half-intensity band width of frequencies passed by the exit slit. This paper discusses its measurement using methods similar to those used to measure the frequency transmission of electrical networks. A Fabry-Perot interferometer, used as a sinusoidal signal generator, produces interference fringes constantly spaced in wave numbers at a known amplitude input to the monochromator. It can be shown that the attenuation of the fringe pattern as the spacing is changed is a function of the exit-slit output-intensity distribution function. From this information the spectral slit width in any spectral region can be measured and the exit-slit function indicated.The sensitivity of measurement is limited by the fringe amplitude obtainable from the interferometer, which is a function of the reflectivity of the interferometer plates and their adjustment. Rays passing through the interferometer at other than normal incidence tend also to damp the fringe pattern.
Potential Importance of Leucine in Treatment of Obesity and the Metabolic Syndrome

Diets with total protein intake >1.5 g.kg(-1).d(-1) and carbohydrate intake <150 g/d are effective for treatment of obesity, type 2 diabetes, and the Metabolic Syndrome. These diets improve body composition and enhance glycemic control. During weight loss, protein-rich diets reduce loss of lean tissue and increase loss of body fat. Specific mechanisms to explain each of these clinical outcomes remain to be fully elucidated. We propose that keys to understanding the relationship between dietary protein and carbohydrates are the relationships between the branched-chain amino acid leucine and insulin and glucose metabolism. Leucine is known to interact with the insulin signaling pathway to stimulate downstream signal control of protein synthesis, resulting in maintenance of muscle protein during periods of restricted energy intake. Leucine also appears to modulate insulin signaling and glucose use by skeletal muscle. Whereas total protein is important in providing substrates for gluconeogenesis, leucine appears to regulate oxidative use of glucose by skeletal muscle through stimulation of glucose recycling via the glucose-alanine cycle. These mechanisms produce protein sparing and provide a stable glucose environment with low insulin responses during energy-restricted periods.
Intra-Flit Skew Reduction for Asynchronous Bypass Channel in NoCs

Various novel NoC designs attempt to improve network throughput and latency by leveraging upon asynchronous bypass and specialized clock routing. The performance of such architectures is limited by the skewing of signal transitions on the bit-lines of link due to cross talk noise. This work proposes a two-step technique: TransSync-RecSync, to eliminate packet errors resulting from inter-bit-line transition skew. TransSync preemptively adds delay to bits in a flit before they are transmitted to overcome skewing of transitions on link while RecSync de-skews the bits at the receiving end by delaying all the transitions by the same amount as the maximum skew on the bus. The approach adds minimally to router complexity and involves no wire overhead. The proposed scheme when employed to augment a NoC design with asynchronous bypass channel was found to improve the average network latency by 38%.
Texture-Based Remote-Sensing Image Segmentation

Typically, high-resolution remote sensing (HRRS) images contain a high level noise as well as possess different texture scales. As a result, existing image segmentation approaches are not suitable to HRRS imagery. In this paper, we have presented an unsupervised texture-based segmentation algorithm suitable for HRRS images, by extending the local binary pattern texture features and the lossless wavelet transform. Our experimental results using USGS 1 ft orthoimagery show a significant improvement over the previously proposed LBP approach
Pion Interferometry at RHIC: Probing a Thermalized Quark-Gluon Plasma?

We calculate the Gaussian radius parameters of the pion-emitting source in high-energy heavy-ion collisions, assuming a first-order phase transition from a thermalized quark-gluon plasma (QGP) to a gas of hadrons. Such a model leads to a very long-lived dissipative hadronic rescattering phase which dominates the properties of the two-pion correlation functions. The radii are found to depend only weakly on the thermalization time ${\ensuremath{\tau}}_{i}$, the critical temperature ${T}_{c}$ (and thus the latent heat), and the specific entropy of the QGP. The model calculations suggest a rapid increase of ${R}_{\mathrm{out}}/{R}_{\mathrm{side}}$ as a function of ${K}_{T}$ if a thermalized QGP were formed.
The gaptooth scheme, patch dynamics and equation-free controller design for distributed complex/multiscale processes

We present an equation-free multiscale computational framework for the design of "coarse" controllers for spatially distributed processes described by microscopic/mesoscopic evolution rules. In particular, we exploit the smoothness in space of the process observables to estimate the unknown coarse system dynamics. This is accomplished through appropriately initialized and linked ensembles of microscopic simulations realizing only a small portion of the macroscopic spatial domain (the so-called gaptooth and patch-dynamics schemes, (I.G. Kevrekidis, et al., 2003). We illustrate this framework by designing discrete-time, coarse linear controllers for a Lattice-Boltzmann (LB) scheme modelling a reaction-diffusion process (a kinetic-theory based realization of the FitzHugh-Nagumo equation in one spatial dimension).
A composite approach towards a complete model of the myosin rod

Sarcomeric myosins have the remarkable ability to form regular bipolar thick filaments that, together with actin thin filaments, constitute the fundamental contractile unit of skeletal and cardiac muscle. This has been established for over 50 years and yet a molecular model for the thick filament has not been attained. In part this is due to the lack of a detailed molecular model for the coiled-coil that constitutes the myosin rod. The ability to self-assemble resides in the C-terminal section of myosin known as light meromyosin (LMM) which exhibits strong salt-dependent aggregation that has inhibited structural studies. Here we evaluate the feasibility of generating a complete model for the myosin rod by combining overlapping structures of five sections of coiled-coil covering 164 amino acid residues which constitute 20% of LMM. Each section contains ∼ 7-9 heptads of myosin. The problem of aggregation was overcome by incorporating the globular folding domains, Gp7 and Xrcc4 which enhance crystallization. The effect of these domains on the stability and conformation of the myosin rod was examined through biophysical studies and overlapping structures. In addition, a computational approach was developed to combine the sections into a contiguous model. The structures were aligned, trimmed to form a contiguous model, and simulated for >700 ns to remove the discontinuities and achieve an equilibrated conformation that represents the native state. This experimental and computational strategy lays the foundation for building a model for the entire myosin rod.
Remote Sensing and the Rancher: Linking Rancher Perception and Remote Sensing

In recent years, steps have been taken to implement a new crop insurance program for rangeland and pasture. Unlike traditionally insured row and cereal crops, which have directly measurable yields, there is no such simple, ideal yield standard for rangeland and pasture because of uncertainties regarding how to generally and objectively quantify annual production. With remotely sensed imagery acquired by the Advanced Very High Resolution Radiometer transformed to the Normalized Difference Vegetation Index (NDVI), we derived a proxy relative yield measurement for rangeland and pasture vegetation. This proxy measurement could potentially solve a critical component of the yield quantification problem facing implementation of a rangeland insurance program. In order to evaluate this proxy measurement and how ranchers might accept it, we surveyed a group of Kansas and Oklahoma ranchers to determine how their perception of rangeland productivity compared to NDVI-based proxy measurements of rangeland productivity in the surveyed rancher's county for the growing seasons of 1999–2003. At the scale of the ranch, correlation analysis showed that perception was not highly correlated with the satellite indices. Higher correlations were observed when perception data were aggregated and compared to rangeland indices at the county and study area levels, with performance comparable to using precipitation information. The year with the strongest correlation was the worst drought year of the 5, a desirable outcome in the context of an insurance program. Results from this case study provide some support for using remote sensing data in a national rangeland and pasture insurance program. Such a program would be an important new risk mitigation tool for ranchers.
Theory of Electron Emission and Transport Properties of Diamond

Electron field emission from diamond films was calculated using a model consisting of the projection of the energy-band surfaces in the , and emission directions. It is found that the tunneling from bulk conduction and valance bands is negligible in p-type diamond, while emission from n-type doped diamond, surface states located near the conduction band edge, and hypothesized defect bands in the energy gap all have sufficient transmission probabilities to produce the low power-high current observed in experiments. To understand the mechanism for supplying electrons to these tunneling states, we analyze charge transport in diamond with internal fields. In particular, a Monte Carlo simulation was performed for electrons in the conduction band as a function of field and film thickness. The results predict hot electron behavior at lower fields with a transition to ballistic-like behavior for high fields (≥ 10 V/µm) and thin samples (≤0.1 µm). It is suggested that if a viable electron injection mechanism into the conduction band of a diamond-metal or diamond-semiconductor interface could be found for those faces of diamond exhibiting NEA, then a copious cold cathode electron emitter with field tunable energies is feasible.
CONTEMPORARY PATTERNS OF MIGRATION IN THE CENTRAL ANDES

"That a high degree of population mobility characterizes demographic phenomena in most Latin American countries has become a routine statement. That such movements exercise a pervasive influence on the economic, political and demographic structures of both receiving and sending areas is similarly commonplace. Paradoxically, however, the exact dimensions of these movements in recent periods are still largely unknown in many countries while discussions of the manner of their impact on the various aforementioned structures border on the speculative" (Martine, 1975). Widespread migration and population redistribution in Central Andean regions during the recent decades has provoked serious concern over the social, environmental, and biological consequences (UNESCO, 1975). Lima, Peru, illustrates some of these concerns. Migrants to the city of Lima have increased that city's population from 600,000 in 1940 to 4 million in 1970, severely straining, and occasionally overwhelming, the capacity to provide essential services to the hundreds of thousands moving to the city and to the new towns or pueblos jovenes springing up in the outlying desert where water and other resources are in short supply. Many problems plague these crowded settlements: infant malnutrition and unemployment are among the most frequent (Graham and Adrianzen, 1972; ONEC, 1972). The size and extent of the city, the demands for space, water, and food, and also the economic, political, and social characteristics of the inhabitants change. Migration today is indeed a process with widespread ramifications. Short-term population movement and flow of resources, both large-scale and small, among ecozones at varying altitudes was a pattern of population-environment interaction that had been characteristic of Andean peoples for centuries before the European conquest; this is the vertical model of Andean economy discussed by Murra (1972). The arrival of Europeans in the sixteenth century caused a catastrophic disruption to the Andean
Quantitative characterization of planarian wild-type behavior as a platform for screening locomotion phenotypes.

SUMMARY Changes in animal behavior resulting from genetic or chemical intervention are frequently used for phenotype characterizations. The majority of these studies are qualitative in nature, especially in systems that go beyond the classical model organisms. Here, we introduce a quantitative method to characterize behavior in the freshwater planarian Schmidtea mediterranea . Wild-type locomotion in confinement was quantified using a wide set of parameters, and the influences of intrinsic intra-worm versus inter-worm variability on our measurements was studied. We also examined the effect of substrate, confinement geometry and the interactions with the boundary on planarian behavior. The method is based on a simple experimental setup, using automated center-of-mass tracking and image analysis, making it an easily implemented alternative to current methods for screening planarian locomotion phenotypes. As a proof of principle, two drug-induced behavioral phenotypes were generated to show the capacity of this method.
Quantification of Drag from Flat Suspension Line for Parachutes and the Influence of Flow Induced Vibrations

To increase the accuracy of autonomous parachute systems, the drag resulting from a common suspension line was quantified. 1000 pound flat Dacron parachute suspension lines were studied to assess its single line drag contributions and how flow induced vibrations affected the line’s profile drag. Current parachute models either neglect the drag caused by suspension lines or use circular cylinder geometry, leading to incomplete predictions of aerodynamic parameters and thus less-than-optimal performance. To quantify drag, the Jones technique, a modified momentum deficit wake profile technique, was validated against published data on a static 2:1 ellipse and then applied to both static and vibrating suspension lines. In experimental testing, the suspension lines were analyzed at three flow velocities and three tensions which closely simulated flight conditions. While the majority of testing involved the streamlined orientation, the effect of flow incidence angle was also investigated. The line has proved to be quite varied in response to fluid-structure interactions and resulting drag coefficients. When static, the line has coefficients of drag values of approximately 0.3 with uncertainty values of 0.02-0.07 at 0° angle of incidence. Drag coefficients increased to general values of 1.2±0.05 and 1.5±0.09 for 45° and 90°, respectively. The higher drag contributions for a majority of incidence angles make flat braided line suboptimal for higher glide slope parachute systems. Oscillation frequencies proved congruous with previously measured values and predictions, and the torsional vibrations had amplitudes with possibly some sensitivity to flow speed. Drag coefficients for vibrating lines, which only occurred for 0° angle of incidence, fell between 0.30 and 0.45 on the average.
To Alter or Abolish

For most Americans, at least, the most famous part of the Declaration of Independence is its claim that "all men are created equal," and endowed with "certain unalienable rights." But around the world, the Declaration's assertion of the right of "the People" to alter or to abolish government -- and to declare independence -- has been far more influential. During the Civil War, the South relied precisely on this right as its justification for secession. As a result, Americans have tended to downplay these aspects of the Declaration. But in other parts of the world, the Declaration continues to inspire countless movements for revolution, self-determination, and secession.There are any number of books and essays that call upon us to take the Declaration's language seriously -- which usually means taking seriously its inspiring passages about human equality and inalienable human rights. This essay asks what it would mean to take seriously the other parts of the Declaration, and in particular, its assertion of the right of a self-defined "People" to alter or abolish government. Doing so turns out to create an enormous number of theoretical and practical problems, which have played out both in domestic and international politics from the Declaration's day to our own.