cssi/SciSciGPT-SciSciNet huggingface dataset:
Myelo-deception: Luspatercept & TGF-Beta ligand traps in myeloid diseases & anemia

Myelodysplastic syndromes (MDS) encompass a clinically heterogenous group of diseases defined by a clonal bone marrow failure state. Patients with lower-risk MDS primarily suffer from the consequences of anemia, with a subset having increased risks of bleeding and infection. There are few good therapeutic options for this patient population, as patients are dependent on cytokine support to improve hematopoiesis. Our review will discuss luspatercept, a transforming growth factor (TGF)-Beta ligand trap, the first new Food & Drug Administration (FDA)-approved treatment in MDS in over a decade. We will explore the different TGF-Beta ligand traps that have been developed for a number of diseases, with a focus on myeloid malignancies.
Effect of free trade agreements on pharmaceutical market competition: The case of the 2009 US-Peru free trade agreement and its implementation as national drug policy

Abstract Free Trade Agreements (FTA) are controversial for threatening essential aspects of health, especially access to affordable medicines. The US-Peru FTA required changes in the Peruvian pharmaceutical legislation that resulted in the implementation of the National Drug Policy (NDP) of 2009. The NDP included more robust technical requirements for registration, a Peruvian Good Manufacturing Practices certificate, a longer timeline for drug registration, and an increase in registration fees. This study evaluated the impact of the FTA on the number of registrations and competition in the Peruvian pharmaceutical market. Data for the period January 2005 to April 2014 were provided by the Peruvian drug regulatory authority (Direccion General de Medicamentos, Insumos y Drogas, DIGEMID). A total of 31,114 pharmaceutical products with unique registration numbers were evaluated. Brand drug new registrations decreased from 1789 in 2005 to 455 in 2013, and the number of generic registrations decreased from 621 in 2005 to 114 in 2013. Brand re-registrations also decreased from 714 in 2005 to 58 in 2013. There were 228 brand products awaiting registration in 2009 and 1,908 in 2013. The proportion of products awaiting registration was three times greater for brand than for generic products in 2009–2013. Registration of brand and generic medicines significantly declined after the implementation of the US-Peru FTA in 2009. The decline in the number of registrations was associated with more robust technical requirements, a longer DIGEMID registration timeline, and an increase in registration fees. The stronger registration requirements are expected to increase the quality of the drugs marketed in the country, but also less competition and a reduction in domestic registrations.
How a Terminal Tag Can Display Epistemic Stance and Constrain Responses: The Case of Oder Nicht in German

This conversation analytic study explores German turn-final oder nich(t), as in Soll ich jetzt weiterlesen oder nicht (“should I continue reading or not”). These oder nicht-appended questions raise...
Guest Editorial Special Issue on Control of Very-Large-Scale Robotic (VLSR) Networks

Future applications of autonomous systems promise to involve increasingly large numbers of collaborative robots individually equipped with onboard sensors, actuators, and wireless communications. By sharing and coordinating information, plans, and decisions, these very-large-scale robotic (VLSR) networks can dramatically improve their performance and operate over long periods of time with little or no human intervention. Controlling many collaborative agents to this day presents significant technical challenges. Besides requiring satisfactory communications, the amount of computation associated with most coordinated control algorithms increases with the number of agents. It is well-known, for example, that the optimal control of N collaborative agents for path planning and obstacle avoidance is a PSPACE-hard problem. Also, while necessary for performing basic tasks such as localization and mapping, many sensing and estimation approaches suffer from the curse of dimensionality, and their performance may degrade as uncertainties from disparate sources propagate through the network.
High Parental Education Protects Against Changes in Adolescent Stress and Mood Early in the COVID-19 Pandemic.

Abstract Purpose The COVID-19 pandemic has brought dramatic changes to the daily lives of U.S. adolescents, including isolation from friends and extended family, transition to remote learning, potential illness and death of loved ones, and economic distress. This study’s purpose is to measure changes in adolescents’ perceived stress and mood early in the pandemic. Methods The present study drew from a racially and ethnically diverse sample of high school student participants in an ongoing intervention study in the Midwestern U.S., 128 of whom provided reports of their daily stress and mood both before (December 2017 to March 2020) and during (March–July 2020) the COVID-19 pandemic. We expected to see increases in perceived stress, declines in positive mood states, and increases in negative mood states, with larger impacts on individuals from households with lower parental education levels. Results Multilevel models revealed increases in perceived stress primarily for adolescents from low/moderate education families during the pandemic. Impacts on mood states also diverged by education: adolescents from low/moderate education households reported feeling more ashamed, caring, and excited than before the pandemic, changes that were not shared by their peers from high education households. Although changes in mood that arose with the onset of the pandemic became less pronounced over time, increased levels of home- and health-related stress stayed high for low/moderate education adolescents. Conclusions During the COVID-19 period, we observed disparate impacts on adolescents according to household education level, with more dramatic and negative changes in the emotional well-being of adolescents from low/moderate education households.
Bostock, Backlash, and Beyond the Pale: Religious Retrenchment and the Future of LGBTQ Antidiscrimination Advocacy in the Wake of Title VII Protection

The Supreme Court’s landmark decision in Bostock v. Clayton County is undoubtedly an influential ruling affecting future LGBTQ rights projects. However, the Court’s ability to produce social and political change through legally formalistic decisions relating to highly contentious social issues is routinely undercut by public backlash. In the context of LGBTQ legal advocacy, social and political backlash against the Court’s ruling is perpetuated further when the Court negligently ignores the lived experiences of LGBTQ litigants arguing before the bench. Despite the recent history of pro-LGBTQ Supreme Court decisions, sexual minorities are still constrained to the margins of society and viewed as less than—or sometimes not even considered at all. As such, this Article provides strong evidence that courts eliminating symbolic manifestations of oppression through antidiscrimination law cannot be seen as a permanent pronouncement of society’s commitment to ending subordination of sexual minorities. This is especially true, as was the case in Bostock, when the Court fails to clarify the intersection of religious liberty and federal antidiscrimination law. As a result of the Bostock Court neglecting the lived experiences of LGBTQ employees, this Article suggests that Bostock served as a catalyst to a period of religious retrenchment of LGBTQ rights. In forming a countervailing force to religious retrenchment for future LGBTQ rights projects, this Article sets forth and applies a three-prong theoretical framework to nullify the threats of religious retrenchment on substantive equality.
Cyclic Polarization Measurements—Experimental Procedure and Evaluation of Test Data

ASTM Subcommittee G01.11 on Electrochemical Measurements in Corrosion Testing has conducted round-robin testing on the reproducibility of cyclic potentiodynamic polarization measurements for determining susceptibility to localized corrosion. This work was used in the development of a practice that provides a standard experimental procedure for conducting these tests. This paper presents the experimental procedure and results of the round-robin tests with statistical analysis of the data. The reproducibility of the measurements and sources of error are discussed.
An analysis of risk factors for pancreatic fistula after robotic pancreaticoduodenectomy: outcomes from a consecutive series of standardized pancreatic reconstructions.

Proponents of the robotic platform site its potential advantages in complex reconstructions such as the pancreaticojejunal anastomosis; however, the incidence and risk factors for postoperative pancreatic fistula (POPF) after robotic pancreaticoduodenectomy (RPD) have not been characterized. To identify independent risk factors for POPF after RPD. A prospectively maintained database of patients that underwent RPD (2008–2013) with a standardized pancreaticojejunostomy was analyzed. Univariate and multivariate analyses (UVA/MVA) were used to identify independent predictors for POPF. The POPF prognostic scores developed by Braga and Callery for open pancreaticoduodenectomy were then applied with logistic regression analysis on this RPD cohort. One hundred and fifty consecutive RPDs were analyzed. POPF occurred in 26 (17.3 %); 13 (8.6 %) of which were ISGPF category B and C. On UVA, patients with POPF had larger body mass index (BMI), smaller pancreatic duct diameter, smaller tumor size, longer OR time, larger estimated blood loss (EBL) and RBC transfusion (all p < 0.05). Higher EBL, duct size <4 mm, larger BMI and small tumor size remained the best independent risk factors for POPF on MVA. Increased Callery (OR 1.46, 95 % CI, p = 0.001) and Braga (OR 1.2, 95 % CI, p = 0.005) scores predicted an increased risk of POPF in this RPD cohort. Larger BMI, higher EBL, smaller tumor size and smaller duct diameter are the main predictors of POPF in RPD.
Loss of the N-terminal methyltransferase NRMT1 increases sensitivity to DNA damage and promotes mammary oncogenesis.

// Lindsay A. Bonsignore 1 , Jill Sergesketter Butler 1 , Carolyn M. Klinge 1 , Christine E. Schaner Tooley 1 1 Department of Biochemistry & Molecular Genetics, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY, USA Correspondence to: Christine E. Schaner Tooley, email: // Keywords : DNA damage, DNA repair, breast cancer, N-terminal methylation, NRMT1 Received : November 13, 2014 Accepted : February 27, 2015 Published : March 26, 2015 Abstract Though discovered over four decades ago, the function of N-terminal methylation has mostly remained a mystery. Our discovery of the first mammalian N-terminal methyltransferase, NRMT1, has led to the discovery of many new functions for N-terminal methylation, including regulation of DNA/protein interactions, accurate mitotic division, and nucleotide excision repair (NER). Here we test whether NRMT1 is also important for DNA double-strand break (DSB) repair, and given its previously known roles in cell cycle regulation and the DNA damage response, assay if NRMT1 is acting as a tumor suppressor. We find that NRMT1 knockdown significantly enhances the sensitivity of breast cancer cell lines to both etoposide treatment and γ-irradiation, as well as, increases proliferation rate, invasive potential, anchorage-independent growth, xenograft tumor size, and tamoxifen sensitivity. Interestingly, this positions NRMT1 as a tumor suppressor protein involved in multiple DNA repair pathways, and indicates, similar to BRCA1 and BRCA2, its loss may result in tumors with enhanced sensitivity to diverse DNA damaging chemotherapeutics.
Organoboranes : XXIV. Facile substitution and exchange reactions of 9-borabicyclo[3.3.1]nonane (9-BBN) and its B-substituted derivatives. Simple convenient preparations of B-halo derivatives☆

Abstract The exchange and substitution reactions of 9-borabicyclo[3.3.1]nonane (9-BBN) and its B -substituted derivatives with various reagents have been studied. The reaction of 9-BBN with halogens and hydrogen halides provides a simple route to B -halo-9-BBN's ( B -X-9-BBN, X = Cl, Br, I). These B -X-9BBN's can also be prepared by the facile redistribution reaction between the respective boron trihalides and 9-BBN or B -OMe-9-BBN. The alcoholysis of 9-BBN or B -X-9-BBN affords B -alkoxy-9-BBN in high yield. The exchange reaction between B -alkoxy-9-BBN and borane-methyl sulfide affords 9-BBN in quantitative yield. This study reports the simple procedures for the interconversion of a variety of B -substituted 9-BBN's.
The Evolution of Floral Form: Insights from an Alpine Wildflower, Polemonium viscosum (Polemoniaceae)

The morphological diversity of flowers has long fascinated evolutionary biologists. In his treatise on the origin of species, Darwin (1859) described a close correspondence between corolla length in clover and tongue length of its bumblebee pollinators to illustrate the concept of coevolution. Similarly, the elaborate structural mimicry of euglossine female bees by flowers of neotropical orchids and the unique inflorescence structure (synconia) of wasp-pollinated figs provide some of the most compelling evidence for evolutionary specialization in flowering plants (Feinsinger, 1983). Major phylogenetic shifts in floral morphology are presumed to reflect historical shifts in the availability or diversity of animal pollinators (Grant and Grant, 1965; Crepet, 1983). Modern comparative studies that map pollination syndromes onto statistically robust phylogenies afford promising tests of hypotheses on the adaptive radiation of flower form at a macroevolutionary scale (Donoghue, 1989; Systma, et al. 1991; Armbruster 1993 see also Chapter 9). However, to truly understand the process of floral evolution as it proceeds, we must turn our attention to the natural populations that comprise the arena for pollinator-mediated selection and gene flow. Recent advances in the analysis of heredity in morphometric traits and selection on them offer us a powerful set of tools with which to attempt this task (Lande and Arnold, 1983; Arnold and Wade, 1984; Mitchell-Olds and Shaw, 1987; Shaw, 1987).
Diffuse Intramural Esophageal Diverticulosis

Diffuse intramural esophageal diverticulosis is a rare disease. The results of clinical, radiographic, endoscopic, motility, and biopsy studies in a patient followed for more than 2 years are presented.
A hypothesis about how to achieve anticoagulation without bleeding

The hypothesis is set forth that a prothrombotic state is frequently caused by epinephrine-activated platelets initiating the intrinsic coagulation cascade by binding factor XII, a pathway which is enhanced by stasis. This pathway explains spontaneous non-injury related thrombosis in atrial fibrillation on the arterial side of the circulation and deep vein thrombosis/pulmonary embolism on the venous side of the circulation. Pharmacological interventions directed against targets in this pathway, for example factor XII, the putative factor XII receptor on activated platelets, and the α2-adrenoceptor on platelets, would be expected to provide effective anticoagulation for most clinical indications for anticoagulation without incurring the bleeding risk associated with pharmacological blockade of the extrinsic pathway, which is the limiting factor for conventional anticoagulants. Thrombotic stroke is another possible indication for such a treatment.
Safe Conversion From Tacrolimus to Belatacept in High Immunologic Risk Kidney Transplant Recipients With Allograft Dysfunction

There is no literature on the use of belatacept for sensitized patients or regrafts in kidney transplantation. We present our initial experience in high immunologic risk kidney transplant recipients who were converted from tacrolimus to belatacept for presumed acute calcineurin inhibitor (CNI) toxicity and/or interstitial fibrosis/tubular atrophy. Six (mean age = 40 years) patients were switched from tacrolimus to belatacept at a median of 4 months posttransplant. Renal function improved significantly from a peak mean estimated glomerular filtration rate (eGFR) of 23.8 ± 12.9 mL/min/1.73 m(2) prior to the switch to an eGFR of 42 ± 12.5 mL/min/1.73 m(2) (p = 0.03) at a mean follow-up of 16.5 months postconversion. No new rejection episodes were diagnosed despite a prior history of rejection in 2/6 (33%) patients. Surveillance biopsies performed in 5/6 patients did not show subclinical rejection. No development of donor-specific antibodies (DSA) was noted. In this preliminary investigation, we report improved kidney function without a concurrent increase in risk of rejection and DSA in six sensitized patients converted from tacrolimus to belatacept. Improvement in renal function was noted even in patients with chronic allograft fibrosis without evidence of acute CNI toxicity. Further studies with protocol biopsies are needed to ensure safety and wider applicability of this approach.
Promoting the Positive Development of Latino Youth in an Alternative School Setting: A Culturally Relevant Trauma-informed Intervention

Edited byJacquelyn H. Flaskerud, PhD, RN, FAANUniversity of California—Los Angeles, School of Nursing, Los Angeles, California, USADespite years of prevention and intervention research, Latino male...
Effects of alum treatment on water quality and sediment in the Minneapolis Chain of Lakes, Minnesota, USA

Abstract The effects of aluminum sulfate (alum) treatment on water quality in 4 lakes of the Minneapolis Chain of Lakes (MN, USA) were examined. Lakes Harriet and Calhoun (treated in 2001) and Cedar Lake and Lake of the Isles (treated in 1996) all showed initial water quality improvement based on surface water total phosphorus (TP), chlorophyll a (Chl-a), and Secchi disk depth. Three lakes (Harriet, Calhoun, and Cedar) were at or below historical estimates of growing season average TP after treatment and showed continued improvement in surface water quality through 2005. Lake of the Isles, which received the lowest alum dose, returned to pretreatment conditions after 6 years. Estimates of sediment phosphorus (P) release rates, however, indicated that alum treatment still limited internal P release in all 4 lakes. Although the alum application to Lake Harriet was a littoral-only treatment, water quality improved in this lake as well. The aluminum hydroxide floc drifted to the deeper part of the lake, reduc...
Increase in quinine tolerance with incremental training

When hungry rats were given quinine-adulterated food pellets, it was found that the quinine tolerance level could be raised if quinine concentration was increased gradully and that, with more minute increments, the tolerance could be further increased.
Enzymatic reduction of 11-cis-retinal bound to cellular retinal-binding protein.

Abstract Cellular retinal-binding protein from bovine retina purifies with bound 11- cis -retinal and 11- cis -retinol as endogenous ligands. Inasmuch as these retinoids are interconvertible by a dehydrogenase reaction the accessibility of the aldehyde function of bound 11- cis -retinal to chemical and enzymatic reducing agents was determined. An 11- cis -retinol dehydrogenase from retinal pigment epithelial microsomes, first described by Lion, F., Rotmans, J.P., Daemen, F.J.M. and Bonting, S.L. (Biochim. Biophys. Acta 384, 283–292, 1975) was found to reduce complexed 11- cis -retinal at pH 5.5 and 37°C rapidaly and nearly quantitatively. The product of the reduction, 11- cis -retinol, remained complexed with the binding protein following the reaction. Reduction proceeded 3-times more rapidly with NADH than with NADPH. No change in geometrical isomeric configuration occurred during the reaction. The dehydrogenase from retinal pigment epithelium oxidized 11- cis -retinol complexed with cellular retinal-binding protein at pH 8.5 in the presence of NAD. In spite of the ready enzymatic reduction of 11- cis -retinal complexed with cellular retinal-binding protein, the aldehyde function was inaccessible to several chemical reducing agents. Incubation of the complex with NaBH 4 at pH 7.5 and NaCNBH 3 or borane dimethylamine at pH 5.5 did not result in reduction of 11- cis -retinal unless the complex had been exposed to white light, a treatment known to produce all- rans -retinal which has little affinity for the binding protein. Liver alcohol dehydrogenase produced only 10% reduction of 11- cis -retinal complexed with cellular retinal-binding protein in 15 min at 37°C when added in amounts which produced about 60% reduction of the uncomplexed retinoid. The results suggest that the interaction between the 11- cis -retinol dehydrogenase and the 11- cis -retinal complexed to cellular retinal-binding protein is a specific one of that the binding protein may function as a substrate carrier for a dehydrogenase.
Is peacekeeping a new form of imperialism

Phyllis Bennis, Calling the Shots: How Washington Dominates Today's U.N., New York: Olive Branch Press, 1996. Pp.272. US$17.95. ISBN 1–56656–206–6.
Small size for gestational age and the risk for infant mortality in the subsequent pregnancy

Abstract Purpose To examine the association between small for gestational age (SGA) in the first pregnancy and risk for infant mortality in the second pregnancy. Methods This is a population-based, retrospective cohort study in which we used the Missouri maternally linked cohort dataset for 1978–2005. Analyses were restricted to women who had two singleton pregnancies during the study period. The exposure was SGA in the first pregnancy, whereas the primary outcome was infant mortality in the second pregnancy. Kaplan-Meier Estimate and Cox proportional hazard regression were conducted. Results Infant mortality was significantly greater among mothers with previous SGA ( P Conclusions Women with previous SGA bear increased risks for subsequent infant mortality, which was greater among black mothers. Hence, SGA plays an important role in the black−white disparity in infant mortality. Women's previous childbearing experiences could serve as important criterion in determining appropriate interconception strategies to improve infant health and survival.
Specification and verification of security requirements in a programming model for decentralized CSCW systems

We present, in this paper, a role-based model for programming distributed CSCW systems. This model supports specification of dynamic security and coordination requirements in such systems. We also present here a model-checking methodology for verifying the security properties of a design expressed in this model. The verification methodology presented here is used to ensure correctness and consistency of a design specification. It is also used to ensure that sensitive security requirements cannot be violated when policy enforcement functions are distributed among the participants. Several aspect-specific verification models are developed to check security properties, such as task-flow constraints, information flow, confidentiality, and assignment of administrative privileges.
Latitudinal variation in freezing tolerance of Melampus bidentatus (Say) (Gastropoda:Pulmonata)

Abstract The limiting factor hypothesis was examined in relation to the latitudinal distribution of the marsh snail Melampus bidentatus (Say). Populations from Massachusetts and Delaware were more resistant to freezing than were the animals from South Carolina. Patterns of cold acclimation also differed among the populations. Mass mortality in local populations of Melampus from South Carolina was observed during the severe winter of 1976–1977 but not during the winter of 1977–1978. Transfer experiments showed that snails from South Carolina could not resist the winter in Massachusetts and had reduced survival compared to native animals in Delaware. Delaware animals survived in Massachusetts but were compromised in their reproductive potential. It is suggested that M. bidentatus is represented by at least two physiological races and the southern populations are limited in their range expansion at least in part by low temperature.
Spectacle as spectralization, untimely timelessness: Marcelino pan y vino and mid-1950s' Francoism

This article asserts an intrinsic link between the spectacle and the specter. More precisely, I argue that the spectacularization of some dead bodies spectralizes others and that the spectacle's pursuit of a sense of timelessness necessarily brings about its own shadowy untimeliness. The beloved classic Spanish film Marcelino pan y vino (Ladislao Vajda, 1955), when examined against the backdrop of the Franco regime's official ideology of the mid-1950s, shows how these connections play out in a specific context. The film, based on a popular short story by the militant Falangist Jose Maria Sanchez Silva, clearly attempts to promote National-Catholicism and the timelessness of the imagined Espana eterna characterized by essentialized traditional values exalted at the time by the regime. As we will see, the spectacle of the title character's glorified death in the film resonates with the contemporaneous enshrinement of the “caidos por Dios y Espana,” that is, the deceased from the winning side of the war. How...
Influence of sampling on the reproducibility of ovarian follicle counts in mouse toxicity studies

Different ovarian follicle counting procedures were investigated to reduce labor while retaining statistical power. Intact ovaries of untreated CD-1 mice (20/group) from National Toxicology Program Reproductive Assessment by Continuous Breeding (RACB) studies were serially sectioned at 6 microm. Mean numbers of small and growing follicles were used to assess sampling efficiency. In 10 mice per group, comparisons were made between 10% nonrandom samples from every 10th section starting at either the first or sixth section having follicles (approximately 40 sections per ovary). These 10% counts were compared with 5% (20 sections) and 20% (80 sections) nonrandom samples and with 1% (4 sections), 5%, or 10% random samples from the same 10 animals. For two studies, a 10% nonrandom sample was analyzed from 20 mice per group. Follicle counts for each group were comparable regardless of the sampling paradigm. Four to 10 animals provided 90% confidence that a 20% difference in mean counts would be detected. The 1% sample had a larger error term and, thus, slightly reduced statistical power. These data suggest that follicle counts from 1% or 5% random samples may provide a suitable screen for ovarian toxicity.
Identification and purification of a phenothiazine binding fragment from bovine brain calmodulin

Calmodulin is a small, acidic, intracellular calciumbinding protein which has been shown to influence the activity of a number of enzymic and structural systems in a calcium dependent manner (review [ 11). The protein, which is apparently ubiquitous in eukaryotes, has been implicated as one of the principal intracellular targets for the calcium released intracellularly following various external stimuli. Of the various probes used to study the role of calmodulin one of the more useful has been the class of antipsychotic drugs the phenothiazines which are able to bind to calmodulin in the presence of calcium, and block its modulating activity [2]. The specificity of the interaction of the various phenothiazines with calmodulin and the pharmacological significance of the interaction have been the subject of debate [3-S]. eluting from the column at -0.3-0.35 M NaCl in_ 20 mM Tris-HCl, 15 mM 2-mercaptoethanol, 1 mM EDTA (pH 7.8) was adjusted to a total concentration of 2 mM CaCla by addition of 1 /Sooth vol. 1 M CaClz to give -1 mM free Ca’+ion. The pool was then applied directly to a column (2.5 X 2dcm) of fluphenazineSepharose (prepared as in [7]) equilibrated in 50 mM imidazole, 200 mM NaCl, 1 mM CaCl,, 15 mM 2-mercaptoethanol (pH 7.2). Unbound material was washed from the column with 500 ml of this buffer, and the calmodulin then eluted with 300 ml of the same buffer but containing 5 mM EGTA in place of CaC12. Fractions (9 ml) were collected and the eluate monitored for calmodulin by alkaline urea slab-gel electrophoresis of samples from every tube. The calmodulin containing eluate was pooled, dialyzed against 2 changes of 50 vol. each of 2 mM Tris-HCl 15 mM 2mercaptoethanol (pH 7.8) and lyophilized. Here we have attempted to identify sites of interaction of phenothiazines on calmodulin using affinity chromatography of cyanogen bromide fragments of the molecule on fluphenazine-Sepharose.
Is airway remodeling clinically relevant in asthma

The social and economic impact of asthma is substantial worldwide. Although current therapies targeting both airway inflammation and airway hyperreactivity effectively relieve and prevent symptoms in the majority of patients, some patients experience persistent symptoms and a progressive decline in lung function, described as irreversible or refractory asthma. Indeed, there are many unanswered questions about the role of airway remodeling in asthma. This review addresses several topics of controversy, including whether all patients with asthma demonstrate airway remodeling; the contribution of distinct airway resident cells to the development of remodeling; the role of biomarkers or noninvasive measurements in predicting airway remodeling; and the effectiveness of current therapies on airway remodeling and disease progression.
Kink-Bands in germanium

Abstract Coarse kink-bands were observed in single crystals of germanium extended above 700°C. The formation and appearance of these bands are discussed. Their crystallographic geometry was found by X-ray analysis to be similar to that reported for face-centered cubic metals. The occurrence of kinkbands appears orientation-dependent, and is associated with heterogeneities in the flow process. Kink-bands were not observed in crystals in which extensive slip occurred on several systems. Analysis of Laue spots revealed polygonization in crystals exhibiting extensive kinking at 850°C.
Kinetic characteristics of the four-electron bridging carbonyl

Abstract The structure of Mn 2 (CO) 5 (dpm) 2 (dpm = Ph 2 PCH 2 PPh 2 ) is discussed and by NMR spectroscopy it is shown to have a four-electron bridging carbonyl group.
810. Comparison of Anti-HIV Activity from Various Lentiviral Vectors Carrying Anti-HIV shRNA In Vitro

Eight pHIV-7-GFP lentiviral vectors encoded anti-HIV-1 small hairpin RNA (shRNA) were constructed. Three target sites in the HIV genome were selected to construct the shRNAs. The first site (SI) resides in a region of rev that overlaps with the adjacent tat gene, while the second (SII) and third sites (SIII) are selected in conserved regions that reside exclusively in rev or tat. The expression and functionality were compared using snRNA Pol III U6 versus Pol II U1 promoters in the following constructs:
Characteristics of exudative age-related macular degeneration determined in vivo with confocal and indirect infrared imaging.

Purpose: To evaluate the current and future interventions in age-related macular degeneration (AMD), it is essential to delineate the early clinical features associated with later visual loss. The authors describe the retinal pigment epithelium (RPE)/Bruch membrane region in ten patients with advanced exudative AMD using current angiographic techniques and a noninvasive method: infrared (IR) imaging with the scanning laser ophthalmoscope. Methods: Ten patients with exudative AMD, evidenced by choroidal neovascularization (CNV), fibrovascular scar formation, pigment epithelial detachment, or serous subretinal fluid, were examined using IR imaging, fluorescein angiography, indocyanine green angiography, and stereoscopic viewing of fundus slides. The authors determined the number and size of drusen and subretinal deposits and the topographic character of the RPE/Bruch membrane area and of CNV. Results: In all patients, IR imaging yielded the greatest number of drusen and subretinal deposits. Sheets of subretinal material, but few lesions consistent with soft drusen, were seen. Infrared imaging provided topographic information of evolving CNV. Choroidal neovascularization appeared as a complex with a dark central core, an enveloping reflective structure which created a halo-like appearance in the plane of focus, and outer retinal/subretinal striae. Conclusions: Infrared imaging provides a noninvasive, in vivo method to image early changes in the RPE/Bruch membrane. It offers advantages over current imaging techniques by minimizing light scatter through cloudy media and enhancing the ability to image through small pupils, retinal hyperpigmentation, blood, heavy exudativn, or subretinal fluid. It provides additional information regarding early CNV, and the character of drusen and subretinal deposits.
Direct versus indirect determination of suspended sediment associated metals in a mining-influenced watershed

The differentiation between the concentration of metals associated with suspended sediments and those in the dissolved phase is often of importance in aquatic ecosystems, for such reasons as toxicity evaluation, total maximum daily load calculations, and a better understanding of metal transport. Often, published water quality data include only concentrations of total and dissolved metals, with particulate concentrations assumed equal to the difference between the two. The validity of this assumption for mining-influenced waters is addressed in this paper by comparing data determined from the subtraction of total (acid-soluble) and dissolved (operationally defined as less than 0.45-μm) metal concentrations (difference method) with data obtained from acid-digestion of the particles retained on the filters used for filtering the dissolved fraction (digestion method). Greater than fifty water samples containing suspended sediment were collected from each of three sites in the Clear Creek Watershed in Colorado during a two and one-half year study on the fate and transport of metals in the watershed. Volumes of water filtered ranged from 50 to 250 ml, representative of typical volumes used for the determination of dissolved metal concentrations. The particulate-associated concentrations of Al, Cu, Fe, Mn, and Zn determined from the difference method compared well with the concentrations determined by the digestion method. Statistical analyses indicated that there is not a statistically significant difference between the two methods at the 95% confidence level, with p-values of 0.65, 0.88, 0.39, 0.67, and 0.75, for Al, Cu, Fe, Mn, and Zn, respectively, over the three sites.
Developmental regulation of expression of the α1 and α2 subunits mRNAs of the voltage-dependent calcium channel in a differentiating myogenic cell line

The voltage-dependent calcium channel (VDCC) in skeletal muscle probably plays a key role in transducing membrane charge movement to the calcium release channel. We report here that the expression of VDCC α1 and α2 mRNAs is developmentally regulated in differentiating C2Cl2 myogenic cells. The α1 mRNA is not detectable in the myoblast form of C2Cl2 cells while its expression is induced 20-fold in differentiated myotubes. In contrast, the α2 mRNA is weakly expressed in myoblasts but is also induced upon myogenic differentiation.
Transcriptional Response of the Murine Mammary Gland to Acute Progesterone Exposure

Our mechanistic understanding of progesterone’s involvement in murine mammary morphogenesis and tumorigenesis is dependent on defining effector pathways responsible for transducing the progesterone signal into a morphogenetic response. Toward this goal, microarray methods were applied to the murine mammary gland to identify novel downstream gene targets of progesterone. Consistent with a tissue undergoing epithelial expansion, mining of the progesterone-responsive transcriptome revealed the up-regulation of functional gene classes involved in epithelial proliferation and survival. Reassuringly, signaling pathways previously reported to be responsive to progesterone were also identified. Mining this informational resource for rapidly induced genes, we identified “inhibitor of differentiation 4” (Id4) as a new molecular target acutely induced by progesterone exposure. Mammary Id4 is transiently induced during early pregnancy and colocalizes with progesterone receptor (PR) expression, suggesting that Id4 mediates the early events of PR-dependent mammary morphogenesis. Chromatin immunoprecipitation assay detecting direct recruitment of ligand occupied PR to the Id4 promoter supports this proposal. Given that Id4 is a member of the Id family of transcriptional regulators that have been linked to the maintenance of proliferative status and tumorigenesis, the establishment of a mechanistic link between PR signaling and Id4 promises to furnish a wider conceptual framework with which to advance our understanding of normal and abnormal mammary epithelial responses to progestins. In sum, the progesterone-responsive transcriptome described herein not only reinforces the importance of progesterone in mammary epithelial expansion but also represents an invaluable information resource with which to identify novel signaling paradigms for mammary PR action.
Engineering pathways to biofuels in photoautotrophic microorganisms.

>Recent advances in the metabolic manipulation of photosynthetic microorganisms for the production of biofuels have enabled the production of a suite of targeted products. Particularly salient for the production of next-generation biofuels is leveraging recently discovered enzymes that enable the synthesis of alkanes, fatty alcohols and novel terpenoids. Titers must now be improved to realize a viable biofuels industry leveraging these organisms. Many of the achievements attained in the engineering of nonphotosynthetic organisms such as yeast and Escherichia coli are likely transferable to photosynthetic microorganisms. Combining these metabolic engineering templates with the rapidly expanding palette of novel biofuel relavent enzymes has the potential to produce a consolidated bioprocessing catalyst for the conversion of sunlight and CO2 directly to commodity chemicals, without the need for secondary organisms
The limits of coercion

(2000). The limits of coercion. Bulletin of the Atomic Scientists: Vol. 56, Government Secrecy, pp. 18-20.
A Formal Restatement of Durkheim's “Division of Labor” Theory*:

Despite frequent references in the sociological literature to Durkheim's theory about the division of labor, sociologists have made few attempts to test it. The paucity of attempts and the very debatable outcomes thereof are due largely to Durkheim's use of the traditional discursive mode of theory construction. A discursively stated theory's logical structure is likely to be obscure, and for that reason alone tests of it are difficult and controversial. Rather than perpetuate the exegetical tradition in sociological treatments of the subject, this paper restates Durkheim's theory in accordance with a particular formal mode. That restatement identifies the theory's shortcomings and problems. But the eight premises imply only one testable theorem, and the theorem's predictive accuracy appears minimal unless “population concentration” is substituted for “density” in the first axiom. Nonetheless, the restatement clearly shows how extension of the theory (additional postulates) could further its testability.
Performance of Monolingual and Bilingual Speakers of English and Spanish on the Synthetic Sentence Identification Test

Differences in the performance of adults with normal hearing were evaluated on the English and Spanish versions of the Synthetic Sentence Identification (SSI) test in the ipsilateral competing message (ICM) format. Previous work has shown that bilingual subjects perform significantly better on the Spanish version of the SSI at a –30 dB message-to-competition ratio (MCR). The previous investigators attributed this difference in performance to the existence of a greater number of pauses in the competing message of the Spanish version compared to the English version. In the present study, seven bilingual speakers and ten monolingual speakers each of English and Spanish completed two conditions—the standard competing message (SC) and the competing message mixed with speech noise (SC+N)—in order to reduce or eliminate the effect of pauses on performance. Bilingual subjects’ scores in each language were not significantly different from monolingual subjects’ scores. Scores from bilinguals were significantly bett...
Long-term follow-up after palliative operation for univentricular heart

Abstract Data are presented from 84 patients (45 males, 39 females), aged 6 days to 25 years (mean 10 years), with univentricular heart who underwent a palliative surgical procedure. The mean follow-up period was 5 years (range 1 month to 25 years). Of the 84 patients, 33 died and 51 are alive. The survivors were 1.5 to 41 years (mean 15). Systemic pulmonary artery shunts alone were performed in 43 patients, pulmonary artery banding in 15, and a combination of procedures in 26. Five years after diagnosis, 70% of patients with type A and 54% with type C uni-ventricular heart were alive, with no statistical difference in survival between the patient groups. Because of the high attrition rate in these patients despite palliation, further attempts to perfect corrective surgery appear justified.
A Construct Validity Study of the Myers-Briggs Type Indicator:

This study assessed the construct validity of the Myers-Briggs Type Indicator, MBTI (Myers, 1976). The rationale was that friends or relatives can make judgments about an individual which will be associated with his/her predominant personality type. Forty-eight subjects rated themselves on two seven-point Likert scales designed to assess behavioral styles. These inventories (designated, "Behavioral Style Inventories") were designed for this study based on the operational definitions of type outlined by Myers in the manual to the MBTI. One inventory assessed perceptions held by subjects of themselves (Form S); the other was a measure of perceptions of their ideal selves (Form I). Forty-five of the subjects were also independently rated by their spouses who used a similar form of the inventory (Form M). All subjects then took the MBTI. Scores were converted to type categories and compared by using the coefficient of agreement for nominal data, Kappa. Self-typing on Form S of the Behavioral Styles Inventory ...
The impact of lithification on the diversity, size distribution, and recovery dynamics of marine invertebrate assemblages

Lithified marine sediments are not equitably distributed through time, raising the possibility that lithification masks biological signals when data from unlithified and lithified sediments are compared or combined. Using mollusk-dominated assemblages from the early Cenozoic of the Gulf Coastal Plain, we find that lithification conceals small taxa, decreases taxonomic resolution, and exacerbates the undersampling of rare taxa. Lithified assemblages appear less diverse and have less even abundance distributions than coeval unlithified samples. These limitations cannot be overcome by standardization procedures, nor are they likely to be circumvented by collecting larger samples. The effects of this bias, however, can be mitigated by restricting analyses to a single lithification state or to specific size classes. Since lithification selectively obscures small taxa, the magnitude of this bias will be most severe when organisms are particularly small, such as in the aftermath of mass extinctions. In the study area, lithification artificially protracts the recovery period following the Cretaceous-Paleogene mass extinction by ~7 m.y.
Current Concepts of Integrated Coronary Physiology in the Catheterization Laboratory

Over the last 15 years, the use of invasive coronary physiology in the catheterization laboratory has demonstrated favorable outcomes for decision making in patients with intermediate single-vessel stenoses, complex bifurcation and ostial branch stenoses, multivessel coronary artery disease, and left main stenoses. A recent large multicenter study (FAME [FFR versus Angiography for Multivessel Evaluation]) found that a physiologically-guided approach was superior to the standard angiographically-guided approach for percutaneous revascularization in patients with multivessel coronary artery disease. This review addresses selected pertinent concepts and studies supporting the integration of coronary physiology in the catheterization laboratory for optimal patient outcomes.
Alkali dimers on the surface of liquid helium

A recent paper by Ancilottoet al. (Zeitschrift fur Physik B, in press), presented calculations of adsorption energies and the geometry of a surface dimple for alkali atoms bound to the surfaces of quantum liquids (4He,3He, H2). Here we present a study of the adsorption of two alkali dimers (Li2, Na2) on the surface of liquid helium. The calculations employ a model of an abrupt interface formulated by Ancilotto et al. as well as one using a diffuse interface. Our conclusion its that the dimers are bound to the surface more strongly than their respective monomers. In the case of dimers there is an additional degree of freedom-the orientation of the molecular axis relative to the surface. We study the influence of molecular anisotropy on adsorption by comparing the cases of “erect” and “spinning flat” orientations and conclude that the latter is energetically favored.
Clay-mineral suites, sources, and inferred dispersal routes: Southern California continental shelf.

Clay mineralogy is useful in determining the distribution, sources, and dispersal routes of fine-grained sediments. In addition, clay minerals, especially smectite, may control the degree to which contaminants are adsorbed by the sediment. We analyzed 250 shelf sediment samples, 24 river-suspended-sediment samples, and 12 river-bed samples for clay-mineral contents in the Southern California Borderland from Point Conception to the Mexico border. In addition, six samples were analyzed from the Palos Verdes Headland in order to characterize the clay minerals contributed to the offshore from that point source. The <2 microm-size fraction was isolated, Mg-saturated, and glycolated before analysis by X-ray diffraction. Semi-quantitative percentages of smectite, illite, and kaolinite plus chlorite were calculated using peak areas and standard weighting factors. Most fine-grained sediment is supplied to the shelf by rivers during major winter storms, especially during El Nino years. The largest sediment fluxes to the region are from the Santa Ynez and Santa Clara Rivers, which drain the Transverse Ranges. The mean clay-mineral suite for the entire shelf sediment data set (26% smectite, 50% illite, 24% kaolinite+chlorite) is closely comparable to that for the mean of all the rivers (31% smectite, 49% illite, 20% kaolinite+chlorite), indicating that the main source of shelf fine-grained sediments is the adjacent rivers. However, regional variations do exist and the shelf is divided into four provinces with characteristic clay-mineral suites. The means of the clay-mineral suites of the two southernmost provinces are within analytical error of the mineral suites of adjacent rivers. The next province to the north includes Santa Monica Bay and has a suite of clay minerals derived from mixing of fine-grained sediments from several sources, both from the north and south. The northernmost province clay-mineral suite matches moderately well that of the adjacent rivers, but does indicate some mixing from sources in adjacent provinces.