cssi/SciSciGPT-SciSciNet huggingface dataset:
Clinical evaluation of compounds targeting PD-1/PD-L1 pathway for cancer immunotherapy

Significant enthusiasm currently exists for new immunotherapeutic strategies: blocking the interaction between programmed death-1 receptor on T-cells and programmed death-ligand 1 on tumor cells to boost immune system stimulation to fight cancer. Immunomodulation with the antiprogrammed death-1/programmed death-ligand 1 monoclonal antibodies has shown to mediate tumor shrinkage and extend overall survival from several pivotal phase I/II studies in melanoma, renal cell carcinoma, and non-small cell lung cancer. This has prompted multiple large ongoing phase III trials with the expectation for fast-track FDA approvals to satisfy unmet medical needs. Compounds targeting the programmed death-1 pathway that are in clinical trials fall into two major categories, namely antiprogrammed death-1 antibodies: Nivolumab, MK-3475, and pidilizumab; and antiprogrammed death-ligand 1 antibodies: MPDL3280A, BMS-936559, MEDI4736, and MSB0010718C. We reviewed the clinical efficacy and safety of each compound based upon major registered clinical trials and published clinical data. Overall, response rate of more than 20% is consistently seen across all these trials, with maximal response of approximately 50% achieved by certain single antiprogrammed death-1 agents or when used in combination with cytotoxic T-lymphocyte antigen-4 blockade. The responses seen are early, durable, and have continued after treatment discontinuation. Immune-related adverse events are the most common side effects seen in these clinical trials. Overall, the skin and gastrointestinal tract are the most common organ systems affected by these compounds while hepatic, endocrine, and neurologic events are less frequent. These side effects are low grade, manageable, and typically resolve within a relatively short time frame with a predictable resolution pattern given proper management. We therefore propose detailed guidelines for management of major immune-related adverse events that are anticipated with antiprogrammed death-1/programmed death-ligand 1 therapies based on general experience with other monoclonal antibodies and the established management algorithms for immune-related adverse events for cytotoxic T-lymphocyte antigen-4 blockade with ipilimumab. We anticipate that the antiprogrammed death-1 strategy will become a viable and crucial clinical strategy for cancer therapy.
CLASSIFICATION OF STELLAR SPECTRA WITH LOCAL LINEAR EMBEDDING

We investigate the use of dimensionality reduction techniques for the classification of stellar spectra selected from the Sloan Digital Sky Survey. Using local linear embedding (LLE), a technique that preserves the local (and possibly nonlinear) structure within high-dimensional data sets, we show that the majority of stellar spectra can be represented as a one-dimensional sequence within a three-dimensional space. The position along this sequence is highly correlated with spectral temperature. Deviations from this 'stellar locus' are indicative of spectra with strong emission lines (including misclassified galaxies) or broad absorption lines (e.g., carbon stars). Based on this analysis, we propose a hierarchical classification scheme using LLE that progressively identifies and classifies stellar spectra in a manner that requires no feature extraction and that can reproduce the classic MK classifications to an accuracy of one type.
Essential role of thyroid hormones in maturation of olfactory receptor neurons: an immunocytochemical study of number and cytoarchitecture of OMP-positive cells in developing rats.

Abstract Neurogenesis and proliferation of olfactory receptor neurons (ORNs) in the olfactory epithelium (OE) are reduced in postnatal hypothyroid rats and upregulated following restoration of thyroid function, leading to compensatory growth and restitution of these deficits [Paternostro M. A. and Meisami E. (1993). Dev. Brain Res. 76 , 151–161; Paternostro M. A. and Meisami E. (1994). Dev. Brain Res. 83 , 151–162]. To investigate thyroid hormonal role on maturation of ORNs, serial sections of the septal OE from normal newborn, 25- and 90-day-old rats were immunostained for olfactory marker protein (OMP), a marker for mature ORNs, and compared with the same from age-matched hypothyroid rats and those allowed to recover from thyroid deficiency at the time of weaning (day 25). The parameters studied were the localization and distribution of the OMP(+) cells within the OE and their density and total number. Hypothyroidism was induced by adding the reversible goitrogen propylthiouracil (PTU) to the rats' drinking water (1 g/l) from birth to days 25 or 90. Recovery from hypothyroidism was induced by withdrawal of PTU at day 25. The OMP(+) cells occupied a distinct, broad band in the normal rat OE, while in hypothyroid animal, this band was narrow and restricted to OE's apical zones. Recovery resulted in broadening of the OMP(+) cell band and normalized distribution of OMP(+) cells as evident in the 90-day-old recovery animals. In normal control rats, density of OMP(+) cells increased by 2.5- and 1.3-fold during the suckling and post-weaning period (days 25–90), while total numbers of these cells increased by 12- and 3-fold, respectively, during the same age periods. Hypothyroidism decreased the growth in density by 25 and 30%, while total number of OMP(+) neurons were reduced by 40 and 70% in the 25- and 90-day-old animals, respectively. Withdrawal of PTU resulted in marked restoration of these deficits so that, at 90 days, the total number of OMP(+) cells were only 20% less than 90-day-old controls. These results indicate that thyroid hormones are essential for maturation of single ORNs and accretion of new mature ORNs in the OE of suckling and post-weaning rat. Also, the process of maturation and the final number of mature ORNs show remarkable recovery from hypothyroid-induced growth retardation.
Micro- and macrogeographic allozyme variation in Littorina fabalis; do sheltered and exposed forms hybridize?

Abstract Earlier studies of Swedish populations of the marine snail Littorina fabalis show that snails from different microhabitats (with a greater and lesser exposure to wave action) have almost diagnostic differences in one allozyme locus (arginine kinase, Ark ), and differ in adult size. Snails with «sheltered» and «exposed» Ark genotypes occur in sympatry in intermediary exposed sites and here adult sizes remain distinct. Approaching the microgeographic differentiation we studied the parts of two populations where the frequency of Ark changes dramatically over zones 50–120 m wide. The aim was to test if the transitional zones are best described as areas of mixing of two genetically separate populations, or if hybridization between the exposed and sheltered groups occurs. Heterozygotes were in deficiency along both clines but were still roughly twice as common as expected from a pure mixing of «sheltered» and «exposed» groups suggesting hybridization. Hybridization was also supported by the observation that snails homozygous for sheltered and exposed alleles mated at random with each other in both populations. On the macrogeographic scale, we found populations from exposed and sheltered sites in France and Wales being fixed for the same exposed and sheltered Ark alleles as found in Sweden. However, variation in three other highly polymorphic loci indicated geographic affinity rather than habitat similarity being the main factor of genetic coherence. These observations support a hypothesis of gene flow between exposed and sheltered populations of L. fabalis . Two Spanish populations were remarkably different with unique alleles at high frequencies in three of four strongly polymorphic loci.
Effects of Discharge of Spent Cooling Water from an Oligotrophic Lake to a Polluted Eutrophic Lake

Water quality and related management issues for a proposed lake source cooling (LSC) facility discharge of water from oligotrophic Lake Ontario to polluted eutrophic Onondaga Lake, NY, are considered in the context of ongoing rehabilitation programs for domestic waste and industrial contamination at Onondaga Lake. The analysis is supported by monitoring data for the lakes, a nearby LSC facility, a domestic wastewater treatment discharge (Metro), and local meteorological conditions. Model simulations are presented to address effects of a LSC discharge on thermal stratification, hypolimnetic dissolved oxygen, and epilimnetic total phosphorus, critical features for cold water fish and eutrophication. Eight LSC discharge scenarios, representing a range of flows, entry depths within the lake, and mixture with Metro effluent, are identified and evaluated. The high salinity of Onondaga Lake would prevent retention of the LSC discharge within the hypolimnion and associated benefits with respect to oxygen resource...
Acute Angle-closure Glaucoma Associated With Intranasal Cocaine Abuse

Purpose We report a case of acute angle-closure glaucoma associated with ipsilateral intranasal cocaine abuse. Methods We examined and treated a 55-yearold white man who developed primary angleclosure glaucoma in the right eye shortly after intranasal cocaine abuse. Results The patient was successfully treated with Nd:YAG laser peripheral iridotomy on the right eye. Conclusion Cocaine causes mydriasis and can induce angle closure in predisposed individuals.
Deep-Flow Variability at Drake Passage

Abstract A rotary empirical orthogonal function analysis of the currents measured in central Drake Passage during DRAKE 79 shows that the deep (2500 m) flow has the same spatial and temporal structure as the flow at 500 m, suggesting that current variability in this region penetrates to the bottom. However, comparison of the time amplitude of the corresponding modes indicates that the variability of the 2500 m flow resulting from north to south shifts in the location of the Polar Front lap that at 500 m by one to three days. This implies that the Polar Front slopes to the east or south (looking up from the bottom). A similar time structure was associated with the flow variations detected at moorings located downstream of a line of seamounts that extend into central Drake Passage. Additionally, the presence of mesoscale features (warm- and cold-core rings and meanders) can block or enhance the deep flow through the narrow channels separating the seamounts in Drake Passage. Such episodic changes in transpor...
The Southern Diaspora and the Urban Dispossessed: Demonstrating the Census Public Use Microdata Samples.

Historians have been slow to make use of the Census Public Use Microdata Samples (PuMs) that have been issued in the past decade. These resources, now available for nearly every census since 1850, are too valuable to be left to demographers and cliometricians. The following is a demonstration of how the Public Use Samples can clarify old debates and open new avenues for social-historical research.
Salvage Radiotherapy for Patients with PSA Relapse Following Radical Prostatectomy: Issues and Challenges

A progressively rising level of serum prostate specific antigen (PSA) after radical prostatectomy (RP) invariably indicates the recurrence of prostate cancer. The optimal management of patients with post-RP PSA relapse has remained uncertain due to a wide variability in the natural course of post-RP PSA relapse and the inability to separate a recurrent disease confined to the prostate bed from that with occult distant metastasis. Management uncertainty is further compounded by the lack of phase III clinical studies demonstrating which therapeutic approach, if any, would prolong life with no significant morbidity. Radiotherapy has been the main therapeutic modality with a curative potential for patients with post-RP PSA relapse. This review article depicts issues and challenges in the management of patients with post-RP PSA relapse, presents the literature data for the efficacy of salvage radiotherapy, either alone or in combination of androgen ablation therapy, and discusses future directions that can optimize treatment strategies.
Chondroitinase ABC promotes selective reactivation of somatosensory cortex in squirrel monkeys after a cervical dorsal column lesion

After large but incomplete lesions of ascending dorsal column afferents in the cervical spinal cord, the hand representation in the contralateral primary somatosensory cortex (area 3b) of monkeys is largely or completely unresponsive to touch on the hand. However, after weeks of spontaneous recovery, considerable reactivation of the hand territory in area 3b can occur. Because the reactivation process likely depends on the sprouting of remaining axons from the hand in the cuneate nucleus of the lower brainstem, we sought to influence cortical reactivation by treating the cuneate nucleus with an enzyme, chondroitinase ABC, that digests perineuronal nets, promoting axon sprouting. Dorsal column lesions were placed at a spinal cord level (C5/C6) that allowed a portion of ascending afferents from digit 1 to survive in squirrel monkeys. After 11–12 wk of recovery, the contralateral forelimb cortex was reactivated by stimulating digit 1 more extensively in treated monkeys than in control monkeys. The results are consistent with the proposal that the treatment enhances the sprouting of digit 1 afferents in the cuneate nucleus and that this sprouting allowed these preserved inputs to activate cortex more effectively.
Cyberwar: A New ‘Absolute Weapon’? The Proliferation of Cyberwarfare Capabilities and Interstate War

Abstract This article examines the implications of the proliferation of cyberwarfare capabilities for the character and frequency of war. Consideration of strategic logic, perceptions, and bargaining dynamics finds that the size of the effect of the proliferation of cyberwarfare capabilities on the frequency of war will probably be relatively small. This effect will not be constant across all situations; in some cases the advent of cyberwarfare capabilities may decrease the likelihood of war. On the other hand, the use of computer network attack as a brute force weapon will probably become increasingly frequent.
Labor productivity differences between foreign and domestic firms in Mexico

Abstract This paper examines labor productivity differences between foreign and domestic firms in Mexican manufacturing industries. Controlling for differences in capital intensity, labor quality, scale, and concentration, we find that foreign affiliates are significantly more productive than are their Mexican counterparts. This suggests that multinational corporations have other advantages that are specific to that type of ownership.
Research studies in patterns of scientific communication: II. The role of the national meeting in scientific and technical communication☆

Abstract We describe the results of a comprehensive study of scientific/technical communication associated with eleven national meetings which were sponsored by nine physical-, social- and engineering-science disciplines. Three groups of meeting participants were studied: authors (persons who presented papers) attendants (sample of persons who were present at these paper-presentations), and requestors (sample of persons who requested copies of these papers). The results showed that the national meeting is the first public announcement of a large portion of current research findings in any discipline and much of the information-exchange behavior encountered at the meeting is intrinsically exploratory. The meeting presentation itself usually constitutes an interim report since most material presented there ultimately finds its way into the journal literature. Some discussion is presented of the relationship of the information-exchange activities to characteristics of meeting participants.
Bone loss in adults receiving alternate day glucocorticoid therapy

Bone mineral content was measured by photon absorption densitometry in 25 patients with rheumatic diseases receiving glucocorticoids on an alternate day treatment schedule, and in 25 age-, sex-, and race-matched patients receiving daily steroid therapy. Mean values for cortical (diaphyseal) mass, trabecular (metaphyseal) mass, and the cortical/trabecular mass ratios were not different in the two groups. Steroid-induced osteopenia, defined as an elevated ratio of cortical to trabecular mass, occurred in both therapeutic regimens (8 of 25 on alternate day; 11 of 25 on daily). Therefore, bone loss was demonstrable in individuals on alternate day regimens. Serum levels of calcium, ionized calcium, alkaline phosphatase, and parathyroid hormone were similar in the two groups.
Ionospheric signatures of a plasmaspheric plume over Europe

[1] Previously, ionospheric signatures of plasmaspheric plumes were reported only at the North American longitude sector. This led to the hypothesis that the geomagnetic field configuration at those longitudes played a vital role in the observation of plasmaspheric plume signatures only over the American continent. Combining ground-based GPS total electron content (TEC), EISCAT incoherent scattering radar (ISR), and DMSP F15 ion drift meter observations we have observed greatly elevated density over the European continent during storm recovery phase on 12 September 2005. The TEC seen over Europe has a tongue of enhanced ionization extending to higher latitudes, which is identical to the plasmaspheric plume signatures that have been often observed over North America. Therefore, our observations clearly demonstrate that ionospheric signatures of plasmaspheric plumes are not limited to the North American sector and suggest that they may be observed at any longitude as long as a dense array of instruments are available to identify these signatures. Citation: Yizengaw, E., M. B. Moldwin, and D. A. Galvan (2006), Ionospheric signatures of a plasmaspheric plume over Europe, Geophys. Res. Lett., 33, L17103, doi:10.1029/2006GL026597.
An algorithm to compute circumscription

Abstract McCarthy's theory of circumscription appears to be the most powerful among various formalizations of nonmonotonic reasoning designed to handle incomplete and negative information in knowledge representation systems. In this paper we describe a query answering algorithm for circumscriptive theories. The Closed-World Assumption (CWA) and its generalizations, the Generalized Closed-World Assumption (GCWA) and the Extended Closed-World Assumption (ECWA), can be considered as special forms of circumscription. Consequently, our algorithm also applies to answering queries in theories using the Closed-World Assumption and its generalizations. Similarly, since prioritized circumscription is equivalent to a conjunction of (parallel) circumscriptions, our algorithm can be used to answer queries in theories circumscribed by prioritized circumscription.
Number fields with solvable Galois groups and small Galois root discriminants

We apply class field theory to compute complete tables of number fields with Galois root discriminant less than 8πeγ . This includes all solvable Galois groups which appear in degree less than 10, groups of order less than 24, and all dihedral groups Dp where p is prime. Many people have studied questions of constructing complete lists of number fields subject to conditions on degree and possibly Galois group, with a goal of determining complete lists of such fields with discriminant less than a fixed bound. This study can be phrased in those terms, with the principle distinction being that our discriminant bounds apply to Galois fields, rather than to particular stem fields. For a finite group G and bound B > 0, let K(G,B) be the set of number fields in C which are Galois over Q and which have root discriminant ≤ B. It is a classical theorem that each set K(G,B) is finite. The first author and Roberts [JR07a] considered these sets with B = Ω = 8πe ≈ 44.7632, a constant introduced by Serre [Ser86]. They conjecture that there are only finitely many such fields in the union of the K(G,Ω), with G running through all finite groups. They determine all sets K(A,Ω) where A is an abelian group, and most sets K(G,Ω) for groups G which appear as Galois groups of irreducible polynomials of degree at most 6. Here we extend those results using class field theory. We complete their study of Galois groups which appear in degree 6, all solvable extensions in degrees 7–9, as well as for all groups G with |G| ≤ 23. Finally, we determine the sets K(D`,Ω) where ` is an odd prime. The primary theoretical difficulty in carrying out these computations is to deduce bounds which effectively screen out conductors for our extensions. Section 1 sets notation and describes some of the methods used before Section 2 addresses this question, and describes our overall process. Section 3 summarizes the results of our computations. 1. Notation and Conventions 1.1. Groups. We let Cn denote the cyclic group of order n, and Dn the dihedral group of order 2n. Direct products are indicated by juxtaposition, so G1 ×G2 will be denoted by simply G1G2, and G1 × G1 will be written G1. Many groups will be semidirect products, and N : H will denote a semidirect product with normal subgroup N and complimentary subgroup H. We will write G1 : G2 : G3 to mean (G1 : G2) : G3. If H ≤ Sn, then the wreath product is denoted G oH ∼= G : H. An extension of G1 by G2 will be denoted by G1.G2. 2010 Mathematics Subject Classification. Primary 11R21; Secondary 11R37.
Molecular Constants and Chemical Theories

A few selected topics from four papers by Samuel on the theory of valence are critically examined. The conclusions are drawn that Samuel's bond‐moments for molecules containing ``pentacovalent nitrogen'' are not as satisfactory as claimed, and provide no evidence in favor of the existence of pentacovalent nitrogen; that Samuel's eigenfunctions for structures with pentacovalent nitrogen are identical with the ones set up in the now conventional manner for structures without pentacovalent nitrogen but with semipolar double bonds instead; that the existence of antibonding orbitals seems to be theoretically necessary; and that several of Samuel's further conclusions are either based upon the use of words in unfamiliar senses, or else are erroneous.
Full-Length Metallic Double J Stents: A Review of Resonance® Stents

Ureteral stricture, regardless of etiology, remains difficult to treat. Mainstays of therapy include polymeric double J stents and percutaneous nephrostomy tubes, each with respective complications. Multiple retrospective studies have now been published using the Resonance metallic double J stent, which is the focus of this review. A literature search was completed utilizing Pub Med. Key words included metallic stent, Resonance stents, and ureteral stricture. All identified papers were included. The stent is generally well tolerated, with infections, hematuria, and voiding symptoms requiring removal in 0% –14% of patients. Stents remained in place for mean of 4 to 9.4 months with the exception of a single study evaluating ureteroenteric strictures, where average duration was 21 days. In most studies a subset of patients kept the stent in situ for >12 months, indicating that for some, the Resonance stent is a viable option, though predicting which patients will do well remains difficult.
On the Asymptotic Properties of a Kernel-Type Quantile Estimator from Censored Samples.

Abstract : In reliability and medical studies, it is often of interest to estimate various quantiles of the unknown lifetime distribution. In particular, the median lifetime and extreme quantiles are of interest to the experimenter in such studies. In many life testing and medical follow-up experiments, however, arbritrarily right-censored data arise, and it is important to be able to estimate the quantiles of interest based on the censored data. For such data, some kernel-type quantile estimators are considered in this paper which give smoother estimates than the usual product-limit quantile function. Keywords: Random right-censorship; Kernel estimation; Product-limit quantile function; Asymptotic normality; and Mean-square convergence.
Endoglin-Mediated Suppression of Prostate Cancer Invasion Is Regulated by Activin and Bone Morphogenetic Protein Type II Receptors

Mortality from prostate cancer (PCa) is due to the formation of metastatic disease. Understanding how that process is regulated is therefore critical. We previously demonstrated that endoglin, a type III transforming growth factor β (TGFβ) superfamily receptor, suppresses human PCa cell invasion and metastasis. Endoglin-mediated suppression of invasion was also shown by us to be dependent upon the type I TGFβ receptor, activin receptor-like kinase 2 (ALK2), and the downstream effector, Smad1. In this study we demonstrate for the first time that two type II TGFβ receptors are required for endoglin-mediated suppression of invasion: activin A receptor type IIA (ActRIIA) and bone morphogenetic protein receptor type II (BMPRII). Downstream signaling through these receptors is predominantly mediated by Smad1. ActRIIA stimulates Smad1 activation in a kinase-dependent manner, and this is required for suppression of invasion. In contrast BMPRII regulates Smad1 in a biphasic manner, promoting Smad1 signaling through its kinase domain but suppressing it through its cytoplasmic tail. BMPRII’s Smad1-regulatory effects are dependent upon its expression level. Further, its ability to suppress invasion is independent of either kinase function or tail domain. We demonstrate that ActRIIA and BMPRII physically interact, and that each also interacts with endoglin. The current findings demonstrate that both BMPRII and ActRIIA are necessary for endoglin-mediated suppression of human PCa cell invasion, that they have differential effects on Smad1 signaling, that they make separate contributions to regulation of invasion, and that they functionally and physically interact.
The induction of the TNFalpha death domain signaling pathway in Alzheimer's disease brain.

The tumor necrosis factor-α death domain pathway contributes to cellular degeneration in a variety of conditions. This study investigates the hypothesis that this death domain pathway is progressively induced in the brain during the progression of Alzheimer's disease (AD). AD cases had increased levels of proapoptotic markers including tumor necrosis factor-α (TNFα), TNF receptor type 1 (TNF-R1), TNF receptor–associated death domain (TRADD), and caspase-3, 2- to 10-fold higher (P < .01) than age-matched controls and 1 to 3 times higher than transitional cases. In striking contrast, potentially neuroprotective TNF receptor type 2 (TNF-R2), and Fas-associated death domain-like interleukin-1β–converting enzyme (FLICE) inhibitor protein (FLIP) were decreased in AD as compared with age-matched control cases (P < .01). Overall, there was an elevation in proapoptotic elements, including a 5-fold increase in TNF-R1 and a 12-fold decrease in FLIP in AD brains. These changes may translate to increased degenerative potential because the downstream effector caspase-3 and product of the TNF pathway was also increased in parallel with enhanced TNF proapoptotic conditions. Our findings suggest that the TNF death receptor pathway and caspases are activated in the early stages of neuronal degeneration in AD.
Determination of S-methylmethionine ion in plant materials by automated amino acid analysis

Abstract By altering the pH of the 4.26 buffer employed in the Spackman, Stein, and Moore automated system for amino acids analysis, S -methylmethionine ion was separated from other amio acids of some plant extracts. The content of this substance in several vegetables is reported.
A Model for Agro-Economic Analysis of Soil pH Mapping

Core soil sampling followed by laboratory analysis is the traditional method used to map soil pH prior to variable rate application (VRA) of lime on cropland. A recently developed automated soil sampling system capable of measuring soil pH on-the-go has significantly increased sampling resolution. However, adoption of such systems must be justified economically. This paper presents a method for assessing the economic benefit from automated mapping of soil pH prior to variable rate lime application. In this work, geostatistical, agronomic, and economic methods were used to generate a comprehensive numerical model for quantitative assessment of the net return over cost of liming for different lime management strategies. The strategies included: automated pH mapping, manual grid soil sampling, and whole field sampling used in combination with either variable or fixed rate liming. The model was demonstrated using a simulated field with known average pH and semivariogram model. The analysis showed the largest benefit ($6.13ha−1year−1) from using VRA with automated soil pH mapping versus VRA based on 1ha (2.5acres) manual grid point sampling for the selected simulated field conditions. A sensitivity analysis demonstrated that for a wide range of field conditions and crop prices, VRA plus automated mapping promises higher relative benefits than VRA based on either manual grid point or grid cell sampling.
Hypoxia and the lung: beyond hypoxic vasoconstriction.

This article extends the influence and effects of hypoxia on the lung beyond vasoconstriction and regional blood flow control. Clearly, hypoxia, via the transcription factor hypoxia-inducible factor (HIF)-1α, induces a large number of genes encoding proteins, which control cellular metabolism and growth and also participate in inflammation. Hypoxia, likely via vascular endothelial growth factor (VEGF), recruits bone marrow precursor cells to the lung and affects the behavior of immune cells. How hypoxia shapes immune responses through VEGF and its receptors on mast cells, eosinophils, and dendritic cells and through lung endothelial cell/lymphocyte interactions will be a productive area for future research.
H Bounded Fault Detection Filter

A key issue in practical fault detection e lter applications is sensitivity to system disturbances and sensor noise. In this paper, a stabilizing fault detection e lter gain is found that bounds the H1 norm of the transfer matrix from system disturbances and sensor noise to the residual. For multidimensional faults, a residual direction is identie ed that enhances the fault signal-to-noise ratio while maintaining the H1 norm bound. By retaining the faultdetection e lterstructure,thepracticalapplicability oftheproposed approach isthesameasforfaultdetection e lter designs found by conventional eigenvector assignment. In contrast to an unknown input observer approach wherein noise is explicitly decoupled from the fault signal, a noise bounding approach does not impose additional geometric constraints on the e lter structure. This allows a given e lter to isolate more faults, an important feature because in practical applications low-order e lter dynamics are common. Further, the possibility of ill-conditioned e lter eigenvectors, occasionally imposed by geometric constraints, may be reduced.
Management of Recurrent HPV-Related Oropharyngeal Cancer

There is a rise in the incidence and prevalence of HPV-associated oropharyngeal squamous cell carcinoma in the population worldwide. In general, evidence of HPV is associated with a better prognosis and higher disease-free survival as compared to the HPV-negative oropharyngeal cancer population. However, even among these patients, there is a subset of patients who fail initial therapy and demonstrate evidence of either persistent or recurrent disease. This review will discuss the current literature regarding patient management after the initial treatment including surveillance and the use of imaging. Additionally, it will discuss the available literature regarding the management of recurrent oropharyngeal squamous cell carcinoma, specifically highlighting the literature relevant to patients with HPV-positive disease. The review will highlight the currently available literature regarding disease-free survival, overall survival, and other outcomes with different salvage modalities such as surgery, re-irradiation with or without chemotherapy, and stereotactic whole-body radiotherapy.
A Botanical Perspective on the Identity of Soma (Nelumbo Nucifera Gaertn.) Based on Scriptural and Iconographic Records

Abstract An examination of the mythic and artistic records of India and Southeast Asia indicates that the famous psychotropic of the ancient Aryans was the eastern lotus, Nelumbo nucifera. Vedic epithets, metaphors, and myths that describe the physical and behavioral characteristics of the ‘soma’ plant as a sun, serpent, golden eagle, arrow, lightning bolt, cloud, phallic pillar, womb, chariot, and immortal navel, relate individually or as a whole to the eastern lotus. Since most Hindu and Buddhist gods and goddesses trace their origins from the Vedas and have always shared close symbolic associations with Nelumbo, there is reason to believe the divine status of this symbolic plant derives from India's prehistoric past.
Silencing of UCHL1 by CpG Promoter Hyper-methylation is Associated with Metastatic Gastroenteropancreatic Well-Differentiated Neuroendocrine (Carcinoid) Tumors

Well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare tumors with varying metastatic potential. The underlying molecular basis for metastasis by GEP-NETs remains undefined. Quantitative PCR and immunohistochemistry (IHC) staining for ubiquitin carboxyl-terminal esterase L1 (UCHL1) gene and protein expression was performed on a group of localized and metastatic well-differentiated GEP-NET samples acquired from a prospectively maintained tissue bank. The ability of extent of UCHL1 IHC staining to differentiate localized and metastatic tumors was compared with Ki-67 index. Among 46 total samples, UCHL1 expression at both the gene and protein level was significantly greater among localized GEP-NETs compared with metastatic tumors and metastases (p < 0.001). Hypermethylation of the UCHL1 promoter was commonly observed among metastatic primary tumors and metastases (those with the lowest UCHL1 expression) but not among localized tumors (p < 0.001). Poor staining (<50 %) for UCHL1 was observed in 27 % of localized tumors compared with 87 % of metastatic tumors (p = 0.001). The presence of <50 % staining for UCHL1 was 88 % sensitive and 73 % specific for identifying metastatic disease. In contrast, there was no association between Ki-67 index and metastatic disease. In multivariable analysis, only UCHL1 staining <50 % [odds ratio (OR) 24.5, p = 0.035] and vascular invasion (OR 38.4, p = 0.03) were independent risk factors for metastatic disease at the time of initial surgery. Loss of UCHL1 expression by CpG promoter hypermethylation is associated with metastatic GEP-NETs. Extent of UCHL1 staining should be explored as a potentially clinically useful adjunct to Ki-67 index in evaluating GEP-NETs for aggressive features.
Temporal regulation of the Dictyostelium glycogen phosphorylase 2 gene

The product of the glycogen phosphorylase-2 gene in Dictyostelium functions to provide the glucose units that are used to construct the structural components of the terminal stage of development. In this report, we link a 1233 bp upstream gp2 fragment to a luciferase reporter gene in order to study the sequences that are involved in the temporal expression of the gene. Various deletions of the promoter-luciferase fusion were then transformed into Dictyostelium cells. All deletion constructs, from -1216 to -486 nucleotides from the translational start codon, showed the same temporal pattern of expression as the authentic gp2 gene, as well as similar luciferase activities. Removal of an additional 37 nucleotides resulted in nearly 100-fold decrease in activity, yet retained the normal temporal expression of luciferase. Analysis of DNA binding proteins with the gel shift assay revealed a stage-dependent pattern of proteins that bound to the gp2 promoter. A similar pattern of temporal expression of the binding proteins was observed with either the full-length probe or with oligonucleotide probes that contained sequences that were identified as putative regulatory sites. Likewise, the full-length and oligonucleotide probes demonstrated identical binding patterns during several steps of purification of the DNA binding proteins. SDS-PAGE and Southwestern blot analysis of a DNA-affinity purified fraction, identified a 23 kDa peptide as the binding protein.
Mechanisms controlling soil respiration (CO2 and CH4) in southern peatlands

Abstract Production of soil gases is important in nutrient and carbon cycling, particularly in peatlands due to their large atmospheric emissions of several greenhouse gases. We examined factors controlling aerobic and anaerobic soil respiration in three contrasting types of freshwater North Carolina peatland communities (short pocosins, tall pocosins and gum swamps) which occur along a natural soil nutrient availability gradient. Short pocosins occur in the ombrotrophic center of the bog complexes and are extremely nutrient-deficient; tall pocosins are slightly less nutrient-deficient; and gum swamps are relatively nutrient-rich. Short pocosin had the lowest soil CO 2 production rates under both aerobic and anaerobic conditions in laboratory experiments, while rates in tall pocosin were similar to or somewhat less than in the gum swamp. Methanogenesis rates were extremely low in laboratory experiments, and indicate that CH 4 production is not a significant pathway of carbon flow in these peatlands. Methane production is also low in relation to other peatlands. Amendment experiments indicate that the poor substrate quality of the highly decomposed, humified peat limits both CO 2 and CH 4 production rates, even though the peat is 95% organic matter. Low soil nutrient concentrations and low pH do not directly limit soil respiration in these peatlands, although there is a positive feedback of nutrients with organic matter inputs and litter quality, causing greater soil respiration in nutrient-rich sites. In situ CO 2 emissions similarly differed between the communities, with highest rates in the gum swamp and lowest rates in the pocosins. Emissions were highly seasonal with soil temperature explaining the majority of the temporal variability. Maximum potential CH 4 emission estimates derived from laboratory temperature relationships and in situ soil temperature data indicate that pocosins make an insignificant contribution to the global atmospheric CH 4 flux. The continued existence of peatlands in warm climates may to a large extent depend on the low substrate quality of their soil organic matter, which maintains low decomposition rates under both aerobic and anaerobic conditions.
Compatible families of elliptic type

In axiomatizing their study of Frobenius distributions [5], Lang and Trotter introduce the notion of an adelic Galois representation of elliptic type, and they ask in passing whether every such representation arises from an elliptic curve (see pp. 5 and 19 of [5]). Formulated in the language of `-adic representations [7], their question is as follows. Put G = Gal(Q/Q), let p denote a prime, and write σp for any Frobenius element at a prime ideal of Q over p. Let {ρ`} be a two-dimensional strictly compatible family of integral `-adic representations ofG with exceptional set S, and for p / ∈ S put a(p) = tr ρ`(σp) with any ` 6= p. Also, let ω` : G→ Z` denote the `-adic cyclotomic character. Although ρ` is a priori a map into GL(2,Q`), after a conjugation in GL(2,Q`) we may regard it as a map G→ GL(2,Z`).
Utilization and productivity of the Duke physician's associate

Abstract The objectives of this study were as follows: (1) Formulate a theoretical model of the typical medical practice as a system for producing medical care, with particular attention to the role of middle-level health workers such as graduates of Duke University's Physician's Associate Program. (2) Develop a methodology for collecting data necessary to estimate the relevant parameters in the model, and to describe current patterns of utilization of Duke PA's. (3) Draw substantive conclusions, insofar as the model and data collection methodology permit, about the actual and potential productivity of Duke PA's. As of October 1971 Duke University had graduated 68 PA's from its Physician's Associate Program. Of these, 34 are employed as assistants in family practice or general medicine in a variety of private and institutional settings. Data were collected on eleven of these 34 PA's. No attempt was made to study the other 34 graduates engaged in clinical specialties, administration, or other functions. Neither was any attempt made to collect data on or draw inferences about the utilization and productivity of graduates of any other program such as the MEDEX Program. §
Toward a Conceptual Framework for Understanding Community Belonging and Well-Being: Insights from a Queer-Mixed Perspective

Although previous research indicates a positive relationship between community belonging and well-being, little is known about how this relationship is experienced within diverse communities. In this study, interviews were conducted with 12 queer-mixed-identified individuals. Proposed is a conceptual framework for understanding how and why experiences of community belonging contribute to and detract from well-being. Specifically, the dimensions being close, being read, being seen, and being heard are explored through participants’ intersectional and often-contradictory narratives. This study may enhance scholarship regarding lived experiences of community; research and practice related to multiracial, queer, and trans* experiences; and community efforts to promote well-being.
Feasibility of quantitative texture analysis of cardiac magnetic resonance imagery: preliminary results

Texture analysis has proven useful in the evaluation of many forms of digital imagery. Our group has shown that texture analysis of echocardiograms may be useful for characterization of myocardial ischemia, contusion, and cardiomyopathies. Recent work in tissue characterization of the brain has used texture analysis of magnetic resonance images to discriminate normal brian tissue from edema and tumor. Magnetic resonance images of the heart have been noted to exhibit visually apparent abnormalities in region image intensity in disease. Based upon these qualitative visual observations, our previous work in cardiac ultrasound texture analysis and the recent application of texture analysis to magnetic resonance brain images, we hypothesized that texture analysis would be useful in evaluating myocardial tissue characteristics from cardiac magnetic resonance images. As a first step towards the goal of cardiac tissue classification, we evaluated the ability of texture analysis to discriminate the left ventricular myocardium from other tissues using magnetic resonance images.
Women Police Officers and the Use of Coercion

Abstract Despite numerous advances in the last thirty years, women police officers continue to face acceptance issues in a male-dominated occupation. Qualitative accounts of policewomen have noted that many of the integration barriers stem from traditional assumptions about police work, much of which revolves around the cultural mandate to display one's coercive authority over citizens. Female officers are often perceived as unwilling (or lacking in ability) to use coercion when encountering citizens. Unfortunately, little empirical evidence is available to support this claim, as gender studies that specifically examine the use of coercion have tended to focus on excessive force. Using data collected as part of a systematic social observation study in Indianapolis, Indiana, and St. Petersburg, Florida, this research examines both verbal and physical coercion that policewomen use in day-to-day encounters with citizens. The results of this study challenge one of the most fundamental stereotypes levied again...
Plasmid transfer for enhancing degradation capabilities.

Abstract The kinetics of plasmid conjugation for the TOL and RP4 plasmids depend strongly on the donor cells' specific growth rate and substrate concentration, both of which determine the cells' energy availability. Although transfer rates can be large when energy availability is high, normal biological processes have low energy availability. Therefore, we propose and evaluate preliminarily a simple scheme to create a small zone of high energy availability.
Enzyme-replacement therapy from birth delays the development of behavior and learning problems in mucopolysaccharidosis type IIIA mice

Mucopolysaccharidosis type IIIA (MPS IIIA; Sanfilippo syndrome) is a lysosomal storage disorder characterized by severe CNS degeneration, resulting in behavioral abnormalities and loss of learned abilities. Early treatment is vital to prevent long-term clinical pathology in lysosomal storage disorders. We have used naturally occurring MPS IIIA mice to assess the effects of long-term enzyme-replacement therapy initiated either at birth or at 6 wk of age. MPS IIIA and normal control mice received weekly i.v. injections of 1 mg/kg recombinant human sulfamidase until 20 wk of age. Sulfamidase is able to enter the brain until the blood-brain barrier completely closes at 10-14 d of age. MPS IIIA mice that were treated from birth demonstrated normal weight, behavioral characteristics, and ability to learn. MPS IIIA mice that were treated from birth performed significantly better in the Morris water maze than MPS IIIA mice that were treated from 6 wk of age or left untreated. A reduction in storage vacuoles in cells of the CNS in MPS IIIA mice that were treated from birth is consistent with the improvements observed. These data suggest that enzyme that enters the brain in the first few weeks of life, before the blood-brain barrier matures, is able to delay the development of behavior and learning difficulties in MPS IIIA mice.
Bone mineral density and its change in pre-and perimenopausal white women: the Michigan Bone Health Study.

There is a need to better understand potential bone mineral density (BMD) loss during the menopausal transition since this period may include the initiation of interventions. The study purpose was to determine if there was BMD loss at the femoral neck, lumbar spine, or total body bone sites in a population-based study of women approaching or transitioning the midlife. The 583 enrollees were 25–45 years of age at the first of four annual measurements from 1992 through 1996. Bone mineral content and bone width were measured using dual-energy X-ray absorptiometry. Considering all enrollees collectively, there was a significant 3-year decline (1%) in BMD at the femoral neck over the 3-year period (p = 0.0076). There was no significant annual change in the lumbar spine (p = 0.11), and a significant annual increase in the total body BMD (p = 0.0003). Within subgroups and cross-sectionally, BMD values of the femoral neck were 5% lower in women classified as perimenopausal compared with premenopausal enrollees; BMD was 3% and 1% lower at the lumbar spine and total body sites, respectively. Longitudinally, among perimenopausal women, a double oophorectomy was associated with BMD loss in the spine (p = 0.0003), even though 75–85% of these women had a hormone replacement prescription at some time during the study period. In summary, the site with evidence of loss was the femoral neck, specifically among perimenopausal women. There was little evidence of substantial total body or lumbar spine BMD loss in premenopausal women with ovaries who maintained follicle-stimulating hormone levels < 20 mIU/l in the early follicular period. Double oophorectomy, even with hormone replacement, was associated with bone loss.