cssi/SciSciGPT-SciSciNet huggingface dataset:
Current and Future Novel Targets of Gene Therapy for Hypertension

Traditional therapeutic approaches for the treatment and control of hypertension are effective in normalizing blood pressure (BP) in less than a third of patients with hypertension. These pharmacological approaches may have reached a plateau in their effectiveness and newer strategies need to be investigated to not only increase the number of patients achieving BP control, but to find ways to cure the disease instead of just manage it. Since completion of the Human Genome Project and the continuous advancement of gene delivery systems, it is now possible to investigate genetic means for the treatment and possible cure for hypertension. In this review, we discuss potential genetic targeting for treatment of hypertension. There are two generalized gene transfer approaches that have been used successfully for hypertension. One is an induction approach where genes that lower blood pressure are overexpressed. A second method is a reduction approach where products of genes that are known to increase blood pressure are decreased. There are a variety of methods that have been utilized to meet these objectives, such as “knockout” and “ knock-in” animal models, and the use of sense and antisense (AS) technology. This review will focus on the sense and antisense applications, and how this technique is becoming more refined and precise through the targeting of specific tissues, the regulation and induction of components of the system, and use of other newer technologies, such as short interfering RNA (siRNA). Our lab has generally focused on the reduction approach, specifically in the genetic manipulation of components of the renin-angiotensin system (RAS). This system not only modulates BP, but has also been implicated in cardiac hypertrophy and morphology and in insulin resistance, which is highly correlated with hypertension. We will also discuss how new genes can be identified and subsequently serve as targets for the treatment of human hypertension.
Evaluation of VTE prophylaxis and the impact of alternate regimens on post-operative bleeding and thrombotic complications following bariatric procedures.

Studies examining utilization and impact of venous thromboembolism (VTE) chemoprophylaxis for patients undergoing bariatric surgery are limited. Determination of the optimal prophylactic regimen to minimize complications is crucial. The Cerner Health Facts database from 2003 to 2013 was queried using ICD-9 codes to identify patients undergoing laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB). VTE chemoprophylaxis regimens were divided into pre-operative alone (PreP), post-operative alone (PostP), both pre-operative and post-operative (PPP), or no prophylaxis (NP). Specific chemoprophylaxis agents were compared. Comparisons in inpatient clinical outcomes were based on univariate analysis and multivariable logistic regression when appropriate. We identified 11,860 patients who underwent LSG and RYGB. 634 (5.35%) had PreP, 4593 (38.73%) had PostP, 2646 (22.31%) had PPP, and 3987 (33.62%) had NP. The overall rates of transfusion, DVT, and PE were 2.48, 0.27, and 0.18%, respectively. Patients without chemoprophylaxis had higher rate of DVT compared to any chemoprophylaxis (0.58 vs 0.11%, p < 0.0001), without any significant difference in PE rate. Patients with pre-operative chemoprophylaxis were more likely to receive transfusion compared to patients with post-operative prophylaxis alone (OR 1.98, 95% CI 1.28–3), without significant difference in having VTE. When examining heparin versus enoxaparin versus mixed regimen in the PostP group, mixed regimen was associated with increased transfusion requirements (p < 0.001). Bariatric surgical VTE chemoprophylaxis utilization is inconsistent. In this study, post-operative VTE chemoprophylaxis was associated with decreased VTE events compared to NP, while minimizing bleeding compared to PreP. Mixed therapy using heparin and enoxaparin was associated with more bleeding.
5.6 – Mass-Independent Isotopic Composition of Terrestrial and Extraterrestrial Materials

Classical isotope effects and measurements have been used for more than 70 years as a tracer of physical and chemical processes. Isotope measurements of stable isotope ratios provide details of a wide range of processes, especially atmospheric. It is now known that the measurement of multi-isotope mass-independent ratios in atmospheric samples has provided insight into sources, transport, and transformation mechanisms of atmospheric species that could not have been otherwise observed. This chapter reviews the basic physical–chemical processes associated with these unusual isotope effects as well as natural sample measurements on Earth (present and past) and Mars. The Earth's earliest atmosphere (billion years) and near past (100 000 years to present) can be followed using mass-independent isotopic measurements. Sulfur and oxygen isotopic composition of sulfate and nitrate aerosols in ice cores and sediments helped reveal the stratospheric chemistry and biogeochemical processes. Present-day greenhouse gas fates and budgets, such as carbon dioxide and nitrous oxide, are also presented. Mass-independent isotopic observations of Martian meteorites have provided new information on its atmosphere–regolith interactions. Isotopic measurements and laboratory studies have also provided insight into the origin and evolution of the solar system.
THE NATIONAL FLOOD INSURANCE PROGRAM: A U.S. APPROACH TO FLOOD LOSS REDUCTION

The National Flood Insurance Program (NFIP) is the United States Government’s primary vehicle for nationwide reduction in damages due to flooding and for financial recovery by the victims of flooding. The purpose of this paper is to describe the components of the NFIP, how they are integrated with one another, and the specific challenges associated with maximizing their effectiveness.
Observations on Structure and Function of the Olivocochlear Projections in Cat

The efferent projections to the inner ear are composed of two fundamentally different fiber types [Warr and Guinan, ’79]: a system of relatively large myelinated fibers whose major peripheral target is the bases of outer hair cells (OHCs) [Kimura and Wersall, ’62] and a system of smaller. unmyelinated fibers which project mainly to the dendrites of afferent fibers in the region under the inner hair cells (OHCs) [Smith, ’61], as schematized in Figure I. In addition, to these “classic” terminals of the olivocochlear bundle (OCB), there are a number of reports in the literature of other vesiculated terminals within the organ of Corti which may also be derived from the OCB [Ginzberg and Morest, ’84; Hashimoto et al., ’90; Bredberg, ’77]. In most previous studies of OC projections, electron microscopic (EM) analysis has been used to distinguish afferent from efferent terminals. Due to the inherent sampling limitations of EM studies, the cochlear distribution of the various vesiculated terminals has never been systematically described.
Accomplished Insect Fliers

The flight characteristics of dragonflies, and to a lesser extent hawk moths, have been summarized. Wing kinematics, aerodynamic force generation and flow-wing interactions are presented. It is clear that these insects generate and use unsteady separated flow structures to support flight. Prominent vortex-wing interactions are routinely documented in conjunction with significant force generation. The wing geometry and kinematics dictate optimal unsteady flow generation as long as the wingbeat frequencies are maintained within prescribed ranges. The dragonfly appears able to readily switch between the use of unsteady flows and the use of more conventional steady state aerodynamics. The latter is used for gliding, a major element of dragonfly territoriality defense as seen in patrolling. The hawk moth appears to use similar unsteady flow strategies but doesn’t exploit gliding. What we believe we have observed is (1) a mechanistic, self-correcting device for creating unsteady flows, (2) a set of devices for using these flows and (3) a set of principles for unsteady flow exploitation by other biological flight systems.
Life Cycle Impact and Benefit Trade-Offs of a Produced Water and Abandoned Mine Drainage Cotreatment Process

A cotreatment process for produced water and abandoned mine drainage (AMD) has been established and demonstrated at the pilot-scale. The present study evaluates the potential of the proposed process to aid in management of two high volume wastewater resources in Pennsylvania. A systems-level approach is established to evaluate the primary trade-offs, including cotreatment process environmental impacts, transportation impacts, and environmental benefits realized from precluding direct AMD release to the environment. Life cycle impact assessment was used to quantify the environmental and human health impacts as well as to identify “hot spots” of the cotreatment process. Electricity use was found to be the dominant contributor to all impact categories. Extending the system boundary to include transportation of the two wastewaters to a to-be-determined cotreatment site revealed the important impact of transportation. An optimization approach was employed (using the region of Southwest Pennsylvania) to evaluat...
Safe-AR: Reducing Risk While Augmenting Reality

Augmented reality (AR) systems excel at offering users real-time, situation-aware information to support users' decision making. With AR, rich visualizations of relevant data can be displayed to users without blocking their view of the real world. For example, an AR-enabled automotive windshield can display a red outline around a pedestrian to alert a driver starting a turn into that cross street. Other critical uses of AR applications that are or will soon be deployed include surgery, emergency response, vehicle maintenance, and pilot training. Many of these applications can enhance operational safety. However, developing risk analysis methods to handle failure modes in the melded virtual and physical realities remains an open problem. This paper proposes a risk analysis method with which to study computer-generated AR visualizations of system and environment states. The analysis framework incorporates three levels at which AR interfaces with the user: perception, comprehension, and decision-making. This method enables broader risk analysis of the entire cyber-physical-human system that an AR application may indirectly control. Preliminary results show that this method yields improved coverage of user-involved failure modes over current approaches. While the focus here is on safety, the method also appears applicable to AR security risks.
Abstract # 3177 Early infant institutionalization leads to a premature accumulation of terminally differentiated CD57 + T cells by adolescence

Early rearing conditions can exert a strong influence on the immune system, affecting regulation and the capacity to respond effectively to pathogens. Most PNI research focuses on inflammatory processes, but the absence of typical parenting can also result in a polarization of T cells. An optimized multicolor immunophenotyping panel was used to enumerate T cell lineages, comparing adolescents who had spent 1–2 years in an orphanage to typically raised teenagers. This presentation will focus primarily on CD4 + CD57 + and CD8 + CD57 + cells, further subdivided into naive, central memory and effector/memory subsets, including cells in the terminally differentiated state. As compared to family-reared American teenagers, the adopted adolescents, especially males, had significantly more TEMRA cells. High frequencies of this cell population are normally associated with aging and immune senescence in older adults, resulting in a lower homeostatic capacity. They also reflect sustained activation and participate in containing latent Herpes viruses. Institutional rearing during infancy was associated with a greater likelihood of being CMV seropositive, which contributed to, but did not entirely account for the persistent effects of early rearing on T cell profiles in male adolescents. Our analysis also found that rearing conditions affected cytokine responses to several T cell and inflammatory stimulants in culture. Following overnight stimulation of whole blood with PHA, LPS, IO/PMA, or anti-CD3/anti-CD28 MoAB, cytokine concentrations were determined by multi-analyte electrochemiluminesence array.
Cross-linked poly(methyl vinyl ether-co-maleic acid)/poly(ethylene glycol)/nanocellulosics foams via directional freezing.

Abstract Aligned micro- and nanoporous materials have gained tremendous interest since they provide great potential in organic electronics, absorbents, biomedicine and tissue engineering. Herein, cellulose nanofibrils (CNFs) and cellulose nanocrystals (CNCs) cross-linked with poly(methyl vinyl ether-co-maleic acid) (PMVEMA) and poly(ethylene glycol) (PEG) foams were prepared by both the directional and un-directional freezing techniques. Aligned three-dimensional porous structures were observed for the directional frozen foams after lyophilization via scanning electron microscope (SEM). As a result, these highly organized structures exhibited enhanced mechanical performance properties. Particularly, for the 25% CNF foams, the compression modulus increased 60% compared with the un-directional frozen samples. These nanocellulosics-based foams could absorb up to 10-fold water of their initial weight with excellent water stability when immersed in water for more than 48 h. Overall, this study describes a novel process combining cross-linking and directional freezing which successfully fabricates naturally derived foams with anisotropic structure.
Enhanced resistance to the poplar fungal pathogen, Septoria musiva, in hybrid poplar clones transformed with genes encoding antimicrobial peptides

Plasmids, pCA1 and pCWEA1, carrying antimicrobial peptide gene(s), Ac-AMP1.2 and ESF12, were used to transform hybrid poplar clones Ogy and NM6. Peptide Ac-AMP1.2 is an analog of Ac-AMP1 which is one of the smallest chitin-binding proteins. Synthetic peptide ESF12 mimics the amphipathic α-helix found in magainins. Transgene mRNA was detected in the transformed plants. When evaluated for resistance to hybrid poplar pathogen Septoria musiva with an in vitro leaf disk assay, the transformed Ogy plants showed significantly increased pathogen resistance as compared to the untransformed Ogy.
Abstract 171: User Beware: Understanding the Adjusted Estimates of Propensity Score Methods

Background: Propensity score methods are used in observational studies to compensate for the lack of random allocation by balancing measured baseline characteristics between treated and untreated p...
Relating Nonuniform Deformations to Fracture in Uniaxially Loaded Non-Woven Fiber Networks

The porous, cellulosic fiber networks in commercial paper are generally regarded as continuum materials when the sheet is large compared to the size of fiber agglomerates (flocs). In this manuscript we reveal that even when the average macroscopic tensile response of copy paper specimens is well described by orthotropic anisotropy, the local deformation characteristics inside a specimen and among different specimens are not uniform as predicted by continuum theories. Using a non-contact, high resolution full-field strain measurements, we present specimen orientation specific strain maps and deformation fields. The characteristic length scales of strain hot spots are obtained using thresholding and lineal path correlation and are compared to the characteristic size of flocs. We quantify the spatial distribution and extent of nonaffine (non-continuum) deformations during tensile loading of a commercial paper, and show how they are critical features of deformation and tearing mechanisms in paper.
Human Factors and Usability for Health Information Technology: Old and New Challenges.

Objectives: Despite national mandates, incentives, and other programs, the design of health information technology (IT) remains problematic and usability problems continue to be reported. This paper reviews recent literature on human factors and usability of health IT, with a specific focus on research aimed at applying human factors methods and principles to improve the actual design of health IT, its use, and associated patient and clinician outcomes. Methods: We reviewed recent literature on human factors and usability problems of health IT and research on human-centered design of health IT for clinicians and patients. Results: Studies continue to show usability problems of health IT experienced by multiple groups of health care professionals (e.g., physicians and nurses) as well as patients. Recent research shows that usability is influenced by both designers (e.g., IT vendors) and implementers in health care organizations, and that the application of human-centered design practices needs to be further improved and extended. We welcome emerging research on the design of health IT for teams as team-based care is increasingly implemented throughout health care. Conclusions: Progress in the application of human factors methods and principles to the design of health IT is occurring, with important information provided on their actual impact on care processes and patient outcomes. Future research should examine the work of health IT designers and implementers, which would help to develop strategies for further embedding human factors engineering in IT design processes.
Human embryoid bodies as a 3D tissue model of the extracellular matrix and α-dystroglycanopathies.

The basal lamina is a specialized sheet of dense extracellular matrix (ECM), linked to the plasma membrane of specific cell types in their tissue context, that serves as a structural scaffold for organ genesis and maintenance. Disruption of the basal lamina and its functions is central to many disease processes, including cancer metastasis, kidney disease, eye disease, muscular dystrophies, and specific types of brain malformation. The latter three pathologies occur in the α-dystroglycanopathies, which are caused by dysfunction of the ECM receptor α-dystroglycan. However, opportunities to study the basal lamina in various human disease tissues are restricted due to its limited accessibility. Here, we report the generation of embryoid bodies from human induced pluripotent stem cells to model the basal lamina. Embryoid bodies cultured via this protocol mimic pre-gastrulation embryonic development, consisting of an epithelial core surrounded by a basal lamina and a peripheral layer of ECM-secreting endoderm. In α-dystroglycanopathy patient embryoid bodies, electron and fluorescence microscopy reveal ultrastructural basal lamina defects and reduced ECM accumulation. By starting from patient-derived cells, these results establish a method for the in vitro synthesis of patient-specific basal lamina and recapitulate disease-relevant ECM defects seen in the α-dystroglycanopathies. Finally, we apply this system to evaluate an experimental ribitol supplement therapy on genetically diverse α-dystroglycanopathy patient samples.
Disease associated mutations in mitochondrial precursor tRNAs affect binding, m1R9 methylation and tRNA processing by mtRNase P

Mitochondrial diseases linked to mutations in mitochondrial (mt)tRNA sequences are abundant. However, the contributions of these tRNA mutations to the development of diseases is mostly unknown. Mutations may affect interactions with (mt)tRNA maturation enzymes or protein synthesis machinery leading to mitochondrial dysfunction. In human mitochondria, the first step of tRNA processing is the removal of the 59end of precursor tRNAs (pre-tRNA) catalyzed by the three-component enzyme, mtRNase P. Additionally, one sub-component of mtRNase P, mitochondrial RNase P protein 1 (MRPP1) catalyzes methylation of the R9 base in pre-tRNAs. Despite the central role of 59 end processing in mitochondrial tRNA maturation, the link between mtRNase P and diseases is mostly unexplored. Here we investigate how 11 different human disease-linked mutations in (mt)pre-tRNAs affect the activities of mtRNase P. We find that several mutations weaken the pre-tRNA binding affinity, while the majority of mutations decrease 59 end processing and methylation activity catalyzed by mtRNase P. Furthermore, all of the investigated mutations in (mt)pre-tRNALeu(UUR) alter the tRNA fold which contributes to the partial loss of function of mtRNase P. Overall, these results reveal an etiological link between early steps of (mt)tRNA-substrate processing and mitochondrial disease.
Alignment of a PhD program in nursing with the AACN report on the research-focused doctorate in nursing: A descriptive analysis.

Abstract Those involved in preparing the next generation of nurse scientists face numerous challenges, including but not limited to: relatively older age at completion of doctoral studies, insufficient funding for full-time PhD students in nursing, inadequate funding for nursing research, and the limited number of well-funded mentors in nursing doctoral programs. These issues have limited the number of students enrolled in PhD nursing programs and graduates to supply the research faculty of the future and generate nursing science. This phenomenon persists despite numerous calls to increase the number of PhD doctoral students and graduates and expedite the PhD process without compromising educational integrity. This article describes the BSN-to-PhD Pathway and the Accelerated (3 year) Pathway to the nursing PhD at an established research doctoral program that required a shift in the approach to student recruitment, curriculum development, and timely progression. Implications for practice and research are discussed.
Accurate BGA Package Solder Joint Modeling for High Speed SerDes Interfaces

The solder joint of the ball grid array (BGA) package becomes a performance bottleneck as the serializer/deserializer (SerDes) speeds increase beyond 112 Gbps. This paper presents a comprehensive methodology to correctly model the volume and shape variations of solder joints for both nominal and worst-case electrical models. It is found that it is indispensable to accurately predict the performance of vertical transitions from package to board beyond 30 GHz. Construction of a worst-case solder joint model is also critical to ensure adequate electrical performance for a high-volume manufacturing solution.
Testing the efficacy of existing USDA Rhizobium germplasm collection accessions as inoculants for guar

Abstract Legume inoculants are products that introduce legume-specific rhizobia bacteria to the soil and promote the process of biological nitrogen fixation. Guar (Cyamopsis tetragonoloba L. Taub.), also known as clusterbean, is a legume produced in semi-arid regions around the world, primarily for industrial uses of guar gum, but there is only one known commercial inoculant products for the crop, which is not available worldwide. The USDA-ARS National Rhizobium Germplasm Collection has four Rhizobium strains listed as compatible with guar: USDA 3089, USDA 3385, USDA 3386, and USDA 3595. The objective of this research was to test the efficacy of four peat-based, seed-applied inoculants derived from these strains, as well as a mixture of all four strains, compared with un-inoculated plants in controlled greenhouse conditions. Among the tested strains, USDA 3089 and USDA 3386 had the greatest positive impacts, as they increased nodule weight, total assimilated nitrogen, biomass production, and protein production per plant relative to the un-inoculated control. USDA 3385 and the Mix likewise increased nodule weight. No inoculant affected other measured aboveground plant morphological and productivity parameters or nodule number. These Rhizobium strains, particularly USDA 3089 and 3386, were identified as beneficial and recommended for further testing in the field in development of an effective inoculant for guar.
Sustainable Newborn Care: Helping Babies Breathe and Essential Newborn Care

Globally, adverse birth outcomes remain a problem especially in low-middle-income countries. Neonatal deaths account for nearly half of all under-5 mortality. The majority of neonatal deaths are from preventable causes. Increasing knowledge of the neonate, along with advances in care and technology, has led to progressively improved neonatal outcomes. However, more expensive care does not necessarily result in better neonatal outcomes. There are evidence-based, low-cost, low-technology interventions proven to impact and significantly reduce neonatal morbidity and mortality. This chapter focuses on sustainable, cost-effective solutions for neonatal resuscitation and essential newborn care, specifically developed for low resource settings to reduce morbidity and mortality. It describes the origin of Helping Babies Breathe, a revolutionary and successful newborn resuscitation program, and how this has expanded into the Helping Babies Survive program with the addition of Essential Care for Every Baby, Essential Care for Small Babies and quality improvement. It will also discuss the benefits of Kangaroo Mother Care as part of essential newborn care. We argue that, with available evidence-based interventions and international commitment and collaboration, the future success of sustainable neonatal care is feasible.
Is hiking worth it? A contingent valuation case study of Multnomah Falls, Oregon

Abstract Multnomah Falls, a 620-ft-tall waterfall in the Columbia River Gorge, is the most visited natural site in Oregon. Its economic value is unclear, however, as the Falls are free to access. Due to a wildfire in 2017, the site was partially closed for over a year. Costly repair work was carried out along the single trail that allows visitors to hike to the top of the waterfall. In this study, we first determined the overall economic value of this iconic site. Secondly, we broke down the economic value by the different trail segments at Multnomah Falls. Using the contingent valuation method, we estimated willingness-to-pay (WTP) for the Falls (n = 1190) and counted visitors using infrared sensors along the trail and parking lot count data from June to September 2019 to obtain economic benefits across the population. We found that visitors who travelled to the top of the Falls experienced greater WTP than ones who only travelled to the bottom, with mean WTP ranging from $8.24 - $9.66 per trip. The total annual benefit provided by Multnomah Falls is estimated to be at least $11.23 m, which considerably exceeds the cost of repairing the trails after the fire (approximately $3 m).
John Skelton's "Phyllyp Sparowe" as satire: a revaluation

This reassessment of Phyllyp Sparowe argues that the poem, contrary to previous scholarly consensus, is a satire reflecting the debates between the humanists and conservative Catholics on the issue of liturgical reform. It attacks the extreme position of those denouncing religious ritual and espousing the study of the classics as an alternative to prayer. The counterpoint between the liturgical framework of the poem and Jane's wandering thoughts serves as a commentary on the inefficacy of both affective devotions and classical studies as a substitute means of achieving spirituality. Skelton agrees that affective devotion inspired religious hysteria on the one hand and sacrilege on the other. The parodies of popular carols and hymns he employs in his description of Jane Scrope show that the language of fine amour should be returned to its rightful place secular art forms. That Jane ultimately finds solace in the traditional liturgy illustrates Skelton's conservative Catholic stance.
Amaurosis Fugax in Ocular Vascular Occlusive Disorders

Amaurosis fugax is a transient brief blindness, dimming, fogging, or blurring of vision, lasting from a few seconds to minutes or even hours, depending upon the etiology. It has also been called transient visual obscuration or blackout. It occurs in many ocular vascular occlusive disorders, i.e., central retinal artery occlusion, branch retinal arteriole occlusion, central retinal vein occlusion alone, central retinal vein occlusion with cilioretinal artery occlusion, hemicentral retinal vein occlusion, branch retinal vein occlusion, ocular ischemic syndrome, and both non-arteritic and arteritic anterior ischemic optic neuropathy. There are a few reports about amaurosis fugax in giant cell arteritis [1–7]. Amaurosis fugax may be the presenting symptom and, if so, always requires urgent evaluation. No comprehensive study on amaurosis fugax in ocular vascular occlusive disorders had been published and no detailed discussion of its pathogeneses in those disorders. Therefore, I conducted a comprehensive, systematic study in a large cohort of patients dealing with prevalence of amaurosis fugax in central retinal artery occlusion, branch retinal arteriole occlusion, central retinal vein occlusion alone, central retinal vein occlusion with cilioretinal artery occlusion, hemicentral retinal vein occlusion, branch retinal vein occlusion, ocular ischemic syndrome, both non-arteritic and arteritic anterior ischemic optic neuropathy, and giant cell arteritis [8]. Various features of all these diseases are discussed in previous chapters. In this chapter, I shall discuss only the amaurosis fugax features in them. The findings of my study are discussed in detail elsewhere [8] and following are the main features.
Studies on the metabolism of 1, 2-propanediol-1-phosphate.

Hanzlik et al. (1) observed the glycogenic action of propylene glycol in rats, and Lindberg (2) has isolated its phosphorylated ester from sea urchin eggs. The latter worker has subsequently demonstrat’ed the presence of 1 ,%propanediol phosphate (PDP) in other t’issues (3). Rudney (4, 5) has suggested that PDP might be an intermediate in the conversion of acetone to “formate” and Cz fragment, while Sakami and Lafaye (6) have suggested that PDP is an intermediate in Ohe metabolism of acetone and a precursor of a 3-carbon compound of the glycolytic cycle. Reports from this laboratory have suggested an alternative pathway of 3-carbon compounds of the glycolytic cycle (7, 8). It appeared to us that PDP might be an intermediate in the alternative pathway suggested by experiments in which slices of heart ventricle anabolizing lactic acid were not inhibited by a concentrat’ion of fluoride sufficient to inhibit enolase. Further, it occurred to us, in view of the recent observations of Harting (9), t,hat PDP might react in the same enzyme systems that normally oxidize cY-glycerophosphate, provided the primary alcohol group is not essential for cr-glycerophosphate dehydrogenase activity. The work reported here demonstrates the oxidation of PDP by a-glycerophosphate dehydrogenase and the removal of the end-product of this oxidation by a further oxidation by addition of a heart muscle extract (10). It has been found that a crystalline preparation of n-glyceraldehyde-3phosphate dehydrogenase will replace the heart’ muscle extract. The data suggest a new series of reactions by which the carbon of PDP might be diverted into pyruvic acid of the glycolytic cycle.
Why Bother With Syntax

When economists represent and reason about knowledge, they typically do so at a semantic (or set-theoretic) level. In this paper, it is argued that there are also benefits in using a syntactic representation.
Adoption of high yielding rice varieties in Bangladesh: An econometric analysis

Abstract In this paper we build two logistic type econometric models to explain HYRV diffusion rate in Bangladesh. Long-run potentials (ceiling), diffusion rates, and the effects of other economic variables on the adoption path are determined simultaneously within the model. Results from our final model indicate that the diffusion rate is not constant over time. Furthermore, rate and level of adoption are found to be influenced by flood damage, jute-rice price ratio and HYRV—local rice variety price ratio. An important outcome of our analysis is that the ceiling adoption level for Bangladesh has nearly been reached. Unless new HYRVs are developed with wider adaptability, especially for drought and flood prone areas, little scope exists for production increases through HYRV acreage expansion. This conclusion has significant policy implications for agricultural planners and development agents in Bangladesh.
Teduglutide-Stimulated Intestinal Adaptation Is Complemented and Synergistically Enhanced by Partial Enteral Nutrition in a Neonatal Piglet Model of Short Bowel Syndrome.

Background: Teduglutide, a glucagon-like peptide-2 (GLP-2) analogue, is available for long-term use by parenteral nutrition (PN)–dependent adults to promote intestinal adaptation but is not approved for use in pediatric patients. The objective of this study was to assess teduglutide-stimulated induced intestinal adaptation, potential synergies with partial enteral nutrition (PEN), and distinct temporal markers of adaptation in a neonatal piglet model of short bowel syndrome (SBS). Materials and Methods: Neonatal piglets (48 hours old; n = 72) underwent an 80% jejunoileal resection and were randomized to 1 of 4 treatment groups, in a 2 × 2 factorial design, with PN or PEN (80% standard PN/20% standard enteral nutrition) and teduglutide (0.1 mg/kg/d) or control. Piglets received nutrient infusions for 4 hours, 48 hours, or 7 days. Results: Teduglutide improved (P < .05) mucosal surface area (villus height: duodenum, jejunum, ileum; crypt depth: ileum, colon; proliferation: duodenum, jejunum, ileum; colon; a...
The causes of Haldane's rule.

How do new species form? A clue comes from the ubiquitous Haldane9s rule, which predicts that when offspring of a mating between different animal species display sterility or inviability in one sex only, the afflicted sex has sex chromosomes of different types. In his Perspective, Turelli explains how new results presented in this issue by Presgraves and Orr explain how both of the major hypotheses explaining Haldane9s rule are correct.
The complexity of some regex crossword problems

In a typical regular expression (regex) crossword puzzle, you are given two nonempty lists $R_1,\ldots,R_m$ and $C_1,\ldots,C_n$ of regular expressions over some alphabet, and your goal is to fill in an $m\times n$ grid with letters from that alphabet so that the string formed by the $i$th row is in $L(R_i)$, and the string formed by the $j$th column is in $L(C_j)$, for all $1\le i\le m$ and $1\le j\le n$. Such a grid is a solution to the puzzle. It is known that determining whether a solution exists is NP-complete. We consider a number of restrictions and variants to this problem where all the $R_i$ are equal to some regular expression $R$, and all the $C_j$ are equal to some regular expression $C$. We call the solution to such a puzzle an $(R,C)$-crossword. Our main results are the following: 1. There exists a fixed regular expression $C$ over the alphabet $\{0,1\}$ such that the following problem is NP-complete: "Given a regular expression $R$ over $\{0,1\}$ and positive integers $m$ and $n$ given in unary, does an $m\times n$ $(R,C)$-crossword exist?" This improves the result mentioned above. 2. The following problem is NP-hard: "Given a regular expression $E$ over $\{0,1\}$ and positive integers $m$ and $n$ given in unary, does an $m\times n$ $(E,E)$-crossword exist?" 3. There exists a fixed regular expression $C$ over $\{0,1\}$ such that the following problem is undecidable (equivalent to the Halting Problem): "Given a regular expression $R$ over $\{0,1\}$, does an $(R,C)$-crossword exist (of any size)?" 4. The following problem is undecidable (equivalent to the Halting Problem): "Given a regular expression $E$ over $\{0,1\}$, does an $(E,E)$-crossword exist (of any size)?"
Tracing Teams, Texts, and Topics: Applying Social Network Analysis to Understand Archaeological Knowledge Production at Çatalhöyük

Social network analysis (SNA) is an analytical technique rapidly gaining popularity within archaeology for its applicability to a wide variety of issues relating to past communities. Using the 20-year project at Catalhoyuk, Turkey, as a case study, I demonstrate how SNA can be helpfully used to understand knowledge production in archaeology. Balancing network visualization and computation with contextual knowledge, combining SNA with topic modeling, and concentrating on social structures all work to provide a diachronic view of how information flows between disparate research teams at Catalhoyuk as well as the social structures and specific individuals promoting this flow. SNA has the undeniable potential to provide new perspectives on how dispersed datasets are assembled to produce archaeological knowledge, illustrating the value of retaining focus on the social conditions of scientific practice even as significant insights are being derived from instead investigating objects and ontology.
Immuno-PET of Murine T Cell Reconstitution Postadoptive Stem Cell Transplantation Using Anti-CD4 and Anti-CD8 Cys-Diabodies

The proliferation and trafficking of T lymphocytes in immune responses are crucial events in determining inflammatory responses. To study whole-body T lymphocyte dynamics noninvasively in vivo, we generated anti-CD4 and -CD8 cys-diabodies (cDbs) derived from the parental antibody hybridomas GK1.5 and 2.43, respectively, for 89Zr-immunoPET detection of helper and cytotoxic T cell populations. Methods: Anti-CD4 and -CD8 cDbs were engineered, produced via mammalian expression, purified using immobilized metal affinity chromatography, and characterized for T cell binding. The cDbs were site-specifically conjugated to maleimide-desferrioxamine for 89Zr radiolabeling and subsequent small-animal PET/CT acquisition and ex vivo biodistribution in both wild-type mice and am odel of hematopoietic stem cell (HSC) transplantation. Results: Immuno-PET and biodistribution studies demonstrate targeting and visualization of CD4 and CD8 T cell populations in vivo in the spleen and lymph nodes of wild-type mice, with specificity confirmed through in vivo blocking and depletion studies. Subsequently, a murine model of HSC transplantation demonstrated successful in vivo detection of T cell repopulation at 2, 4, and 8 wk after HSC transplantation using the 89 Zr-radiolabeled anti-CD4 and -CD8 cDbs. Conclusion: These newly developed anti-CD4 and -CD8 immuno-PET reagents represent a powerful resource to monitor T cell expansion, localization, and novel engraftment protocols. Future potential applications of T cell–targeted immuno-PET include monitoring immune cell subsets in response to immunotherapy, autoimmunity, and lymphoproliferative disorders, contributing overall to preclinical immune cell monitoring.
Physicians and the Difficult Patient

Despite almost universal client contact with physicians, social workers have paid little attention to the nature of the physician-patient relationship and its impact on the quality of health care received by their clients. A central concern is the quality of care received by individuals defined by their physicians as "difficult" patients. This article examines physicians' emotional reactions to patients and reviews recent medical literature regarding the role of those reactions in the labeling of the difficult patient. The labeling of a patient as difficult is conceptualized as a relationship problem between physician and patient. Implications for social worker efforts to humanize this relationship are explored, and strategies for increasing social worker collaboration with physicians are presented.
Role of adenosine A2 receptors in brain stimulation reward under baseline conditions and during cocaine withdrawal in rats.

The present experiments tested the hypothesis that adenosine A2 receptors are involved in central reward function. Adenosine receptor agonists or antagonists were administered to animals that had been trained to self-stimulate in a rate-free brain stimulation reward (BSR) task that provides current thresholds as a measure of reward. The adenosine A2A receptor-selective agonists 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamido adenosine hydrochloride (CGS 21680) (0.1–1.0 mg/kg) and 2-[(2-aminoethylamino)carbonylethyl phenylethylamino]-5′-N-ethylcarboxamido adenosine (APEC) (0.003–0.03 mg/kg) elevated reward thresholds without increasing response latencies, a measure of performance. Specifically, CGS 21680 had no effect on response latency, whereas APEC shortened latencies. Bilateral infusion of CGS 21680 (3, 10, and 30 ng/side), directly into the nucleus accumbens, elevated thresholds but shortened latencies. The highly selective A2A antagonist 8-(3-chlorostyryl)caffeine (0.01–10.0 mg/kg) and the A2-preferring antagonist 3,7-dimethyl-1-propargylxanthine (DMPX) (0.3–10.0 mg/kg) did not alter thresholds or latencies, but DMPX (1.0, 10.0 mg/kg) blocked the threshold-elevating effect of APEC (0.03 mg/kg). In another study, repeated administration of cocaine (eight cocaine injections of 15 mg/kg, i.p., administered over 9 hr) produced elevations in thresholds at 4, 8, and 12 hr after cocaine. DMPX (3 and 10 mg/kg), administered before both the 8 and 12 hr post-cocaine self-stimulation tests, reversed the threshold elevation produced by cocaine withdrawal. These results indicate that stimulating adenosine A2A receptors diminishes BSR without producing performance deficits, whereas blocking adenosine receptors reverses the reward impairment produced by cocaine withdrawal or by an A2A agonist. These findings indicate that adenosine, via A2A receptors, may inhibit central reward processes, particularly during the neuroadaptations associated with chronic drug-induced neuronal activation.
Glutathione S-transferase isoenzymes in rat brain neurons and glia

The glutathione S-transferases (GSTs) constitute a family of cytosolic isoenzymes and a structurally unrelated microsomal enzyme that is involved in the detoxication of electrophilic xenobiotics. These enzymes also participate in the intracellular binding and transport of a broad range of lipophilic compounds including bilirubin, and hormones such as the glucocorticoids and thyroid hormones. The present investigation demonstrates that GSTs are present in neurons of the brainstem, forebrain, and cerebellum. An isoenzyme-specific distribution of GSTs was found in cytoplasm, nuclei, and nucleoli. The regional and cellular distribution of cytosolic GSTs in the brain was studied by immunohistochemistry, spectrophotometric enzyme assay, and reverse-phase HPLC. Polyclonal antibody against microsomal GST was strongly reactive with Purkinje cells throughout the cerebellar cortex, and with neurons in the brainstem and hippocampus. Nuclei of Purkinje cells and of neurons in the brainstem, hippocampus, and cerebral cortex were immunopositive for alpha-class GST 1-1 (YaYa), whereas alpha-class GST 2-2 (YcYc) antibody was consistently immunoreactive with the nucleolus, but not with the nucleus or soma. All alpha-class GST antibodies studied were reactive, to various degrees, with astrocytes and choroid plexus; however, ependymal cells of the subventricular zones were immunonegative. alpha-class GST 8-8 (YkYk) immunoreactivity was specifically localized to endothelial cells and/or astrocytic end feet associated with blood vessels. Reverse-phase HPLC indicated that there were also substantial regional differences in the pattern of alpha-, mu-, and pi-class GST subunit expression. For example, the thalamus/hypothalamus had the highest GST activity and greatest concentration of total GST protein and mu-class GST subunit 6 (Yb3), whereas the brainstem had the greatest concentration of pi-class GST subunit (Yp). This regional variation in GST expression may be reflective of regional differences in cell populations. In cerebellar cortex, the concentration of mu-class GST subunit 4 (Yb2) was greatest in the flocculus and lowest in the vermis. This is of clinical interest because the pattern of expression of mu-class GST subunit 4 (Yb2) in the cerebellum coincides with the known regional susceptibility of this structure to degeneration after exposure to toxic or metabolic insults. The vermis is most susceptible to these insults, whereas the lateral lobes and flocculus are most resistant.(ABSTRACT TRUNCATED AT 400 WORDS)
Stereochemistry of the succinic dehydrogenase system.

IN continuation of work1–3 on the stereochemistry of Krebs-cycle reactions, the stereochemistry of the succinic dehydrogenase reaction has been investigated with substrates that constrain the enzyme system to demonstrate its stereospecificity. These substrates are L-chlorosuccinic acid, newly found by us, and the L-enantiomorph of methylsuccinic acid; the racemic modification of the latter having been previously demonstrated4,5 to decolorize methylene blue in the crude heart preparations.
The rapid evaluation of volume integrals of potential theory on general regions

Abstract We present a new method for the rapid, high order accurate evaluation of certain volume integrals in potential theory on general irregular regions. The kernels of the integrals are either a fundamental solution, or a linear combination of the derivatives of a fundamental solution of a second-order linear elliptic differential equation. Instead of using a standard quadrature formula or the exact evaluation of any integral, the methods rely on rapid methods of solving the differential equation which the kernel is the solution of. Therefore, the number of operations needed to evaluate the volume integral is essentially equal to the number of operations needed to solve the differential equation on a rectangular region with a regular grid, and the method requires no evaluation of the kernel.
Characterization of a Multicopper Oxidase Gene from Staphylococcus aureus

A multicopper oxidase gene from Staphylococcus aureus was cloned and overexpressed. Purified recombinant multicopper oxidase oxidized the substrate 3,3′-dimethoxybenzidine in the presence of copper. Disruption of mco showed copper sensitivity and H2O2 resistance, suggesting roles for mco in copper homeostasis and oxidative stress response. Northern blot analysis showed copper-induced mco transcription.
A pathsearch damped Newton method for computing general equilibria

Computable general equilibrium models and other types of variational inequalities play a key role in computational economics. This paper describes the design and implementation of a pathsearch damped Newton method for solving such problems. Our algorithm improves on the typical Newton method (which generates and solves a sequence of LCPs) in both speed and robustness. The underlying complementarity problem is reformulated as a normal map so that standard algorithmic enhancements of Newton's method for solving nonlinear equations can be easily applied. The solver is implemented as a GAMS subsystem, using an interface library developed for this purpose. Computational results obtained from a number of test problems arising in economics are given.
Determining Structure-Mechanics Relationships of Viscoelastic Microtubule Networks through Microscale Manipulation

The microtubule cytoskeleton is essential in maintaining the shape, strength and organization of cells and its misregulation has been implicated in neurological disorders and cancers. To better understand the structure-mechanics relationships in microtubule networks, we measure the time- and force-dependent viscoelastic responses of entangled and crosslinked microtubule networks to precise microscale manipulation. We use magnetic tweezers devices to apply calibrated step stresses and measure the resultant strain as a function of time. To understand the molecular origins of network behavior, we use a newly-developed portable magnetic tweezers device to observe network morphology using a confocal microscope while simultaneously applying point-like stresses to embedded magnetic particles. Our results are important to understanding the role of the cytoskeleton in regulating cargo transport in vivo, as well as the basic physics of non-affine deformations in rigid rod polymer networks.