cssi/SciSciGPT-SciSciNet huggingface dataset:
Activated heme synthesis regulates glycolysis and oxidative metabolism in breast and ovarian cancer cells

Heme is an essential cofactor for enzymes of the electron transport chain (ETC) and ATP synthesis in mitochondrial oxidative phosphorylation (OXPHOS). Heme also binds to and destabilizes Bach1, a transcription regulator that controls expression of several groups of genes important for glycolysis, ETC, and metastasis of cancer cells. Heme synthesis can thus affect pathways through which cells generate energy and precursors for anabolism. In addition, increased heme synthesis may trigger oxidative stress. Since many cancers are characterized by a high glycolytic rate regardless of oxygen availability, targeting glycolysis, ETC, and OXPHOS have emerged as a potential therapeutic strategy. Here, we report that enhancing heme synthesis through exogenous supplementation of heme precursor 5-aminolevulinic acid (ALA) suppresses oxidative metabolism as well as glycolysis and significantly reduces proliferation of both ovarian and breast cancer cells. ALA supplementation also destabilizes Bach1 and inhibits migration of both cell types. Our data indicate that the underlying mechanisms differ in ovarian and breast cancer cells, but involve destabilization of Bach1, AMPK activation, and induction of oxidative stress. In addition, there appears to be an inverse correlation between the activity of oxidative metabolism and ALA sensitivity. Promoting heme synthesis by ALA supplementation may thus represent a promising new anti-cancer strategy, particularly in cancers that are sensitive to altered redox signaling, or in combination with strategies that target the antioxidant systems or metabolic weaknesses of cancer cells.
Summary of the Volume

Publisher Summary This chapter presents a summary of the content presented in the book. The introductory chapter describes the language disturbances associated with aphasia and the brain areas compromised when these symptoms appear. The chapter highlights four patterns of breakdown in naming, and reviews the variety of error types that occur in naming attempts: semantic, phonological, multicomponential, and perseverations. Chapter 2 points out that virtually all contemporary models of naming include at least three basic stages: that of visual processing of a stimulus to be named, a stage of semantic appreciation of the object, and a stage of phonological retrieval. Chapter 5 focuses on naming of “unique entities.” Chapters 6 and 7 depart from the search for general models of the cognitive and anatomic basis of the naming process, to focus on naming across the life span. Chapter 6 addresses problems related to the development of naming in children, and Chapter 7 deals with the decline of naming proficiency with aging. Chapter 8 considers three approaches to the treatment of naming disorders.
The relationship of genital tract actinomycetes and the development of pelvic inflammatory disease.

Abstract As a corollary to a case-control study evaluating the risk of pelvic inflammatory disease (PID) among users of an intrauterine countraceptive device (IUD), Papanicolaou smears were studied to detect the presence of actinomycetes. Forty-six PID case patients and 108 control patients were included in the corollary study. The presence of actinomycetes was noted only among current or past wearers of an IUD. Women with actinomycetes present on Papanicolaou smear had a 3.6-fold risk of hospitalization for PID, as compared to women without actinomycetes. This trend persisted when only IUD users were evaluated. Of patients with PID who had actinomycetes noted on the Papanicolaou smear, 87½% had a tuboovarian abscess, compared to 28.9% of patients without actinomycetes. In addition, patients with actinomycetes present had PID treated surgically more frequently.
Molecular analysis of the prokaryotic ubiquitin‐like protein (Pup) conjugation pathway in Mycobacterium tuberculosis

Proteins targeted for degradation by the Mycobacterium proteasome are post-translationally tagged with prokaryotic ubiquitin-like protein (Pup), an intrinsically disordered protein of 64 residues. In a process termed 'pupylation', Pup is synthesized with a terminal glutamine, which is deamidated to glutamate by Dop (deamidase of Pup) prior to attachment to substrate lysines by proteasome accessory factor A (PafA). Importantly, PafA was previously shown to be essential to cause lethal infections by Mycobacterium tuberculosis (Mtb) in mice. In this study we show that Dop, like PafA, is required for the full virulence of Mtb. Additionally, we show that Dop is not only involved in the deamidation of Pup, but also needed to maintain wild-type steady state levels of pupylated proteins in Mtb. Finally, using structural models and site-directed mutagenesis our data suggest that Dop and PafA are members of the glutamine synthetase fold family of proteins.
Kinetic mechanism for p38 MAP kinase alpha. A partial rapid-equilibrium random-order ternary-complex mechanism for the phosphorylation of a protein substrate.

p38 Mitogen-activated protein kinase alpha (p38 MAPKα) is a member of the MAPK family. It is activated by cellular stresses and has a number of cellular substrates whose coordinated regulation mediates inflammatory responses. In addition, it is a useful anti-inflammatory drug target that has a high specificity for Ser-Pro or Thr-Pro motifs in proteins and contains a number of transcription factors as well as protein kinases in its catalog of known substrates. Fundamental to signal transduction research is the understanding of the kinetic mechanisms of protein kinases and other protein modifying enzymes. To achieve this end, because peptides often make only a subset of the full range of interactions made by proteins, protein substrates must be utilized to fully elucidate kinetic mechanisms. We show using an untagged highly active form of p38 MAPKα, expressed and purified from Escherichia coli[Szafranska AE, Luo X & Dalby KN (2005) Anal Biochem336, 1–10) that at pH 7.5, 10 mm Mg2+ and 27 °C p38 MAPKα phosphorylates ATF2Δ115 through a partial rapid-equilibrium random-order ternary-complex mechanism. This mechanism is supported by a combination of steady-state substrate and inhibition kinetics, as well as microcalorimetry and published structural studies. The steady-state kinetic experiments suggest that magnesium adenosine triphosphate (MgATP), adenylyl (β,γ-methylene) diphosphonic acid (MgAMP-PCP) and magnesium adenosine diphosphate (MgADP) bind p38 MAPKα with dissociation constants of KA = 360 µm, KI = 240 µm, and KI > 2000 µm, respectively. Calorimetry experiments suggest that MgAMP-PCP and MgADP bind the p38 MAPKα–ATF2Δ115 binary complex slightly more tightly than they do the free enzyme, with a dissociation constant of Kd ≈ 70 µm. Interestingly, MgAMP-PCP exhibits a mixed inhibition pattern with respect to ATF2Δ115, whereas MgADP exhibits an uncompetitive-like pattern. This discrepancy occurs because MgADP, unlike MgAMP-PCP, binds the free enzyme weakly. Intriguingly, no inhibition by 2 mm adenine or 2 mm MgAMP was detected, suggesting that the presence of a β-phosphate is essential for significant binding of an ATP analog to the enzyme. Surprisingly, we found that inhibition by the well-known p38 MAPKα inhibitor SB 203580 does not follow classical linear inhibition kinetics at concentrations > 100 nm, as previously suggested, demonstrating that caution must be used when interpreting kinetic experiments using this inhibitor.
Numerical analysis of the quantum states of optical and RF systems containing quantum well and superlattice devices

The authors present a numerical method for calculating optical and electronic operating parameters of systems containing quantum well and/or superlattice devices. These devices use the quantum mechanical characteristics of confined electrons to realize novel optical and electronic properties. These novel properties allow for the construction of customizable infrared detectors and RF oscillators. In order to determine critical engineering parameters, the quantum mechanical state of electrons in the system must be determined. The authors provide a fast numerical method for accomplishing this. Simulation results are shown to be comparable with experimental outcomes. >
Border-crossing with competition then collaboration in a challenge-driven design and communication experience for engineering and science students

The authors (professors of mechanical engineering, physics, and professional communication) are collaboratively designing and teaching an intensive multidisciplinary design program in which undergraduate engineering and science students will tackle one of the National Academy of Engineering's Grand Challenges during ten weeks in the summer. The first offering of the program will focus on designing and building an inexpensive and locally manufacturable system that utilizes solar energy for power. The Summer 2013 program is a brand new offering and has been inspired by both our own and our students' yearnings for broader interdisciplinary experiences, where classroom knowledge can be applied to a `real world', humanitarian problem. The borders we expect our students and ourselves to cross in this program include borders of culture and of disciplinary major. Stakeholders for the design will come from cultures outside of the student's own; in particular, students will be asked to design for implementation in Kenya. An undergraduate student from Kenya will be joining us on campus to advise and serve as a representative client for the project design. From among our own student applicants, we have accepted a cross-cultural and cross-disciplinary group. During the summer program, students will be organized into multidisciplinary teams based on two different models. After a shared class-wide problem-definition phase, each multidisciplinary team initially will propose competing designs for evaluation. At this midpoint, the class will choose a winning design for further development and teams will be reassigned into collaborative subsystem groups, each building a component of the final product. This structure - due to the interdependent nature of each team's subsystem design on performance capability of the entire system-will emphasize to students the importance of communication throughout the program.
Clinical utility research: An introduction

Clinical utility research is concerned with how one develops knowledge that can be directly used for improving clinical practice. Some have referred to this domain as "effectiveness" research, but clinical utility implies much more than clinical effectiveness. It also addresses issues of access, transferability, sample specificity, and the uniqueness of each human condition. This special series of papers describe several research programs that have been conducted in applied settings and that illustrate research on clinical utility. These descriptions are modestly representative of the wide applicability of research methods that address the uniqueness of each setting and population and the nature of findings that can be used to guide clinical practice. The papers bridge cultures, countries, settings, and problems. They illustrate some of the advantages of, and some of the knowledge to be gained from conducting controlled research in settings that are devoted to clinical service.
REALITY COMES THROUGH A PRISM: METHOD CHOICES IN LEISURE RESEARCH

ABSTRACT The goal of social research is to discover, understand, and communicate truth about people in society. The dimensions surrounding this goal are the nature of truth and how one knows what truth is. The dominant paradigm that has surrounded social science, and particularly the study of leisure, has been positivism. Today, a number of researchers are questioning the dominant positivist assumptions that have been guiding their lives and research. In leisure research, a revolution is quietly beginning as leisure researchers are suggesting that new questions need to be asked and new methods employed to better understand leisure behavior. A new world of understanding and study awaits leisure researchers if leisure reality is viewed through a prism that reflects expanding paradigmatic and methodological choices.
Phosphorylase: A New Isozyme in Rat Hepatic Tumors and Fetal Liver

A third set of phosphorylase a and b isozymes, distinguishable kinetically and immunologically from liver and muscle forms, is present in various rat hepatomas, and is also present, together with the adult liver form, in fetal rat liver. This is one of several striking examples of suppression of isozymes of adult liver coupled with the appearance of fetal isozymes in hepatomas.
Limnology and oceanography: two estranged twins reuniting by global change

The twin fields of limnology and oceanography have been raised apart since birth. Both were born from geology, geography, and biology but were raised separately by the immediate need for water supplies to fuel civilizations (limnology) and by the need for fish and by curiosity about the virgin great unknown (oceanography). I explore differences between inland waters and the sea but conclude that oceans are fast becoming “large saline lakes.” Two irresistible forces are drawing these twins back together. First, there is a strong and growing realization that many aquatic ecosystems function in similar ways and thus can productively share a common theoretical foundation. Second, there is the growing understanding that most oceans are now suffering the same insults at the hands of civilization as inland waters have been for centuries. I support these ideas with an analysis of the top-10 most important problems and paradigms in these sister fields and gauge their prevalence in the burgeoning published literature. I suggest that in the coming years limnologists will be able to assist oceanographers in learning to understand, manage, and mitigate the impacts of growing global change. Oceanographers will assist limnologists in questions of salinity and physical scale that have been less prevalent topics in inland waters. Limnologists and oceanographers have much more to gain by uniting than by competing. Water is our common strategic resource, and we have much to learn from each other.
Rapid gene cloning using terminator primers and modular vectors

We seek to create useful biological diversity by exploiting the modular nature of genetic information. In this report we describe experiments that focus on the modular nature of plasmid cloning vectors. Bacterial plasmids are modular entities composed of origins of replication, selectable markers and other components. We describe a new ligation-independent cloning method that allows for rapid and seamless assembly of vectors from component modules. We further demonstrate that gene cloning can be accomplished simultaneously with assembly of a modular vector. This approach provides considerable flexibility as it allows for ‘menu driven’ cloning of genes into custom assembled modular vectors.
The critical velocity behavior of superfluid 4He in a micron-size aperture at two different frequencies of oscillatory flow

Ac measurements of an effective critical velocity v scof superfluid 4He flow through a rectangular aperture 5 Μm × 0.3 Μm in a foil 0.2 Μm thick were made between 0.35 and 2.15 K. These measurements involved oscillatory flow in two different ranges of frequency, 70–118 Hz and 1818–1899 Hz. At temperatures T above 1.7 K, v sc(T) measured in the two frequency ranges coincided, decreasing with increasing T. Above 1.9 K, downward curvature toward V sc = 0 at T λoccurred in proportion to (ϱ s )/(T)0.83. At temperatures below 1.7 K, differences appeared between the critical velocity behaviors in the two frequency ranges. As temperature decreased, V sc(T) at the lower frequencies continued to rise in a nearly linear fashion, while at the higher frequencies V sc(T) tended to level off. At the same time, a pronounced increase in noise and metastability in the supercritical region was seen at the higher frequencies. Possible explanations for this divergence of behavior are discussed.
Synthetic Peptides Derived from the Fourth Domain of CD4 Antagonize CD4 Function and Inhibit T Cell Activation

Abstract We have developed synthetic peptide analogs to analyze novel surface structures of the human CD4 protein potentially involved in T cell activation. Linear and cyclic peptides derived from the FG and CC′ loops of the membrane proximal fourth domain of CD4 displayed inhibitory activities in a CD4-dependent immunological assay. These results suggest that the fourth domain of CD4 plays an important role in T cell activation. In addition, we report the synthesis of a highly stable CD4 peptide analog cyclized by the formation of an amide bond between amino and carboxyl termini. Serum stability studies showed that this main-chain cyclic CD4 peptide was highly resistant to proteolytic degradation while the linear and disulfide cyclic peptides were much less stable. The strategy of main chain cyclization of CD4 peptides may represent a promising approach to generate proteolytically stable, orally active immunoregulatory agents.
In vitro effects of osteotomy angle and osteotomy reduction on tibial angulation and rotation during the tibial plateau-leveling osteotomy procedure.

Objective To determine the effect of osteotomy angle, reduction technique, and tibial plateau rotation angle on angular and rotational limb deformities. Study design Geometric comparison using bone models. Methods Rotational osteotomies were made in the proximal metaphysis of artificial tibias at 0 degrees, 10 degrees, 20 degrees, -10 degrees, and -20 degrees from perpendicular with respect to either the proximodistal and craniocaudal tibial axes. Negative-numbered angles represented osteotomies made from distal to proximal or caudal to cranial. Changes in tibial angulation and torsion were measured using a 3-dimensional digitizing instrument at tibial plateau rotation angles from 0 degrees to 30 degrees at 5 degrees increments. Two osteotomy reduction techniques were used: complete osteotomy reduction and alignment of the medial cortex. The mean of 5 measurements of torsional and angular tibial deformity for each of the 9 osteotomy orientations in each reduction technique group was obtained. Results All had increasing angular and rotational deformity as tibial plateau rotation angle increased. In the medially aligned cortex group, all tibias had valgus deformity, and 8 of 9 tibias were internally rotated. In the reduced osteotomy group, minimal angular deformity was seen in tibias with osteotomy variation along the proximodistal axis; however, tibias with osteotomy variation along the craniocaudal axis had angular deformity ranging from 6.0 degrees of varus deformity to 14.3 degrees of valgus deformity. Rotational deformity was affected similarly by osteotomy variation along either axis. Reduction technique had greater affect on angular and rotational deformity than osteotomy angle variation. Clinical relevance These results suggest that osteotomy reduction may play a greater role in angular and rotational deformity than osteotomy angle, although extreme osteotomy angles should be avoided. To decrease the severity of deformity, we recommend that the osteotomy be made perpendicular to the craniocaudal and proximodistal axes and be completely reduced with less regard for alignment of the medial cortex.
There is an energy cost for catalytic turnover which arises due to enzyme degradation.

Abstract A method for calculating the energy cost per catalytic turnover which results from enzyme synthesis and degradation is presented. Applying the method to published data on 20 rat liver enzymes yields values ranging from 9.48 × 10 −8 to 5.56 ATP per catalytic turnover. The majority of the values are between 10 −5 and 10 −2 ATP per turnover. A possible role for the expenditure of this energy in regulating enzyme activity in particular cases is discussed.
Outcomes of Laparoscopic Donor Nephrectomy Without Intraoperative Systemic Heparinization

Purpose: Intravenous heparin has traditionally been given during living donor laparoscopic nephrectomy despite the paucity of evidence supporting its use. We present the results of our experience with laparoscopic donor nephrectomy done without intraoperative systemic heparinization.Materials and Methods: We retrospectively reviewed the records of 167 consecutive laparoscopic donor nephrectomies done without intravenous heparin from July 2005 to October 2007 at our institution. We evaluated preoperative donor characteristics, intraoperative and postoperative complications, recipient renal function and graft outcomes.Results: All 138 left nephrectomies were done using a conventional laparoscopic approach while 25 of 29 right nephrectomies were done using the hand assisted technique. Warm ischemia time was approximately 3.0 minutes in each group. Mean ± SE estimated blood loss was 183 ± 29 ml for left and 115 ± 16 ml for right nephrectomy. Postoperatively hematocrit decreased an average of 4.5%. There were ...
Observing Extrasolar Planetary Systems with ALMA

ALMA will observe extrasolar planetary systems in various stages of formation. From young, planet-forming (protoplanetary), dusty disks, to mature solar-system analogs, ALMA will produce transformational science. We investigate the imaging capabilities of ALMA to infer structure in protoplanetary disks created by a protoplanet, as well as possible direct detection of the protoplanet itself. In addition, ALMA will be able to perform high-accuracy astrometry of main sequence stars, allowing us to search for the astrometric wobble caused by orbiting planets.
Modification of Low Self-Confidence in Elementary School Children

AbstractThis study investigates changing the behavioral self-confidence of low self-confident elementary school students within a classroom setting. The procedure involves playing a game which is scored both for number of response attempts (operationally defined as a measure of self-confidence) and percentage correct by each player. The treatments varied either the structuring of the teams or the rules under which the game was played in an effort to increase response attempts. Significant gains were found in the confidence of low confident children in the treatment group which involved playing students only against other low confident players during the treatment period. Correlations between gains in behavioral confidence and the variables of percentage correct and grades were also examined.
Fast path planning using motion graphs

We present our ongoing work on a novel method for navigating humanoid characters through an unstructured complex environment by the help of a fast path planning algorithm integrated with motion graphs. Our main goal is to achieve characters showing human-like motions provided by motion capture and at the same time being able to compose complex realistic motions for executing path following in real-time. Current methods that solve the path planning problem with motion graphs are not real-time and do not guarantee that the humanoid character is walking on a collision-free path. Furthermore there are no guarantees on how close the composed motion is to the path being followed. Our method addresses these issues by employing a fast path planning and execution mechanism whenever possible and only employing motion graph search when needed. Our method is directly applicable to video games.
Billions and billions of constraints: whitebox fuzz testing in production

We report experiences with constraint-based whitebox fuzz testing in production across hundreds of large Windows applications and over 500 machine years of computation from 2007 to 2013. Whitebox fuzzing leverages symbolic execution on binary traces and constraint solving to construct new inputs to a program. These inputs execute previously uncovered paths or trigger security vulnerabilities. Whitebox fuzzing has found one-third of all file fuzzing bugs during the development of Windows 7, saving millions of dollars in potential security vulnerabilities. The technique is in use today across multiple products at Microsoft. We describe key challenges with running whitebox fuzzing in production. We give principles for addressing these challenges and describe two new systems built from these principles: SAGAN, which collects data from every fuzzing run for further analysis, and JobCenter, which controls deployment of our whitebox fuzzing infrastructure across commodity virtual machines. Since June 2010, SAGAN has logged over 3.4 billion constraints solved, millions of symbolic executions, and tens of millions of test cases generated. Our work represents the largest scale deployment of whitebox fuzzing to date, including the largest usage ever for a Satisfiability Modulo Theories (SMT) solver. We present specific data analyses that improved our production use of whitebox fuzzing. Finally we report data on the performance of constraint solving and dynamic test generation that points toward future research problems.
SU‐E‐T‐59: A Computer Program for Second Physics Manual Calculations in HDR Brachytherapy

Purpose: To create and implement a calculation tool to perform second check dose calculations for HDR brachytherapy treatment plans. Methods: One of the pre‐treatment requirements of HDR brachytherapy treatments [1] is that the physicist verifies the calculations of the treatment planningsystem (TPS). The TG‐59 report summarizes several methods for gross error checks. In order to calculate dose at a given point, one of the methods is the implementation of the TG‐43 [2] dose calculation formalism for a point source and its application to all source positions and dwell times in a treatment plan. Most TPSs generate reports summarizing dwell positions and times in a tabulated form. However, utilization of the data in these reports usually involves the transfer of this information into a spreadsheet to perform the calculation. This process requires several copy/paste operations and is prone to errors. We have developed a computer code, written in MATLAB, which reads the necessary information (source position and dwell times, reference calculation point locations) directly from the DICOM RT plan generated by the TPS hence eliminating the manual transfer of the information from the TPS into a spreadsheet. For dose calculations, the code uses the source specific radial dose function, which can be modified for different source types. Results: The developed program was benchmarked against the manual calculation spreadsheet already in use for several different applicators and treatment geometries. It was found to be in perfect agreement, demonstrating its accuracy and reliability. Conclusions: The developed program was implemented for use in the clinic and streamlined the manual second calculation process for HDR brachytherapy treatment plans.
Mycobacterium avium paratuberculosis and Crohn's Disease: an association requiring more research.

Dear Sir, I wish to respond to Dr. Van Kruiningen's recent viewpoint article entitled, “Where are the weapons of mass destruction-the Mycobacterium paratuberculosis in Crohn's disease?” 1 By emphasizing the studies which do not find an association of Crohn's disease (CD) and Mycobacterium avium paratuberculosis (Map) and dismissing the positive studies he implies that this association is still controversial. At this point, two meta analyses have concluded that this association is established.2,3 The debate has shifted to whether Map is causative of CD or inconsequential in the disease. Van Kruiningen suggests that only two possibilities exist …
The payment system and domestic exchange rates: Technological versus institutional change

Abstract This paper presents an institutional and empirical description of domestic exchange in the United States between 1840 and 1918, within the context of the structural evolution of the payments mechanism. Just as the need to tender payments internationally gives rise to foreign exchange, so the necessity for inter-regional payments gives rise to domestic exchange. Rates on domestic exchange flactuated within limits defined by the cost of shipping gold or currency between cities within the United States. The variability of these rates depended on the cost of transportation and on the sophistication of institutional arrangements of the payments system. Our paper seeks to assess the relative importance of these two factors for the diminution of domestic exchange rates over the period of observation. In addition, we try to isolate the welfare implications of improvements in the payments system, in particular, the importance of the diminution in exchange rates for inter-regional integration of the short-term money markets.
Bridging the Gap between Human Factors and Environmental Design: A Universal Bathroom Case Study

This user-centered design project highlights the importance of human factors in product development. It introduces two adjustable bathrooms, Movable Fixtures Bathroom and Movable Panels Bathroom, which resulted from this research and design project. Unlike existing bathrooms, which are designed primarily for independent users, these bathrooms consider the needs of the human life cycle and address dependent use and care-providing alongside independent use in the bathroom. These bathrooms reflect the social and inclusive philosophy of universal design and they have the potential to unify diverse population groups so no one user is excluded by their design.
Cell-Type Localization of Platelet-Derived Growth Factors and Receptors in the Postnatal Rat Ovary and Follicle

Intraovarian growth factors play a significant role in the regulation of follicular selection and growth. In this study, the presence and localization of all members of the family of platelet-derived growth factors (PDGF) and receptors (PDGFR) were identified and characterized in the rat ovary. In addition, a role was identified for members of this family in contributing towards growth of preantral follicles. Real-time PCR revealed the presence of mRNA for all platelet-derived growth factors (Pdgfa, Pdgfb, Pdgfc and Pdgfd) and receptors (Pdgfra and Pdgfrb) in the rat ovary from birth until 4 wk. In situ hybridization and immunohistochemistry were utilized to identify cell-type expression of PDGFs and PDGFRs in rat ovaries from birth until 4 wk. Shortly after birth, expression of PDGFRA and PDGFC was observed in and around oocyte clusters, and PDGFRB in stromal cells surrounding oocyte clusters. All members were identified in oocytes of primordial and primary follicles, and in cells of the theca layer of primordial to antral follicles. PDGFRA and PDGFA were also localized to some granulosa cells of secondary and antral follicles in ovaries from rats at Days 20 and 24. Thus, localization data suggest both theca-theca and theca-granulosa cell interactions of PDGFs and receptors. Preantral follicles cultured in vitro over 5 days in serum-free medium plus recombinant PDGFAA, PDGFAB, or PDGFBB increased in follicle diameter by 18.32%+/-2.18%, 17.72%+/-2.3%, and 17.6%+/-1.81%, respectively, representing significantly greater increases than for follicles incubated in serum-free medium alone (11%+/-1.57%), and suggesting a role for these growth factors in positively influencing early follicle growth.
Parathyroid hormone regulation of proline uptake by cultured neonatal mouse osteoblastlike cells

Regulation of proline uptake by the synthetic amino-terminal fragment of bovine parathyroid hormone [bPTH-(1-34)] has been studied in confluent primary cultures of osteoblastlike cells isolated from neonatal mouse calvaria. The initial velocity of proline transport was increased by 85% in cultures treated with 24 nM bPTH-(1-34) for 6 h. Cycloheximide, at a concentration that inhibited protein synthesis by 97%, did not prevent this effect. However, adding the inhibitor during the first 1-2 h of hormone treatment did significantly reduce its magnitude. Exposure of cells to the inhibitor alone caused a time-dependent decrease in the basal rate of proline uptake. In the absence of protein synthesis, the maximal velocity (Vmax) of transport was 60% greater in cultures treated with 24 nM bPTH-(1-34) than in controls. The concentration of proline at which half-maximal transport occurred (Km) was unchanged. In cultures treated with cycloheximide alone, proline transport decreased as a first-order exponential with a half-life of 250-280 min. Parathyroid hormone significantly reduced this decline, increasing the half-life of proline transport activity about fourfold. These effects were duplicated by 1 mM DBcAMP. It is concluded that bPTH-(1-34) increases proline transport in osteoblastlike cells by decreasing the degradation of amino acid transport system A proteins. The hormone may also affect the synthesis of these molecules. These effects appear to be mediated by cAMP.
Regional trends in mercury distribution across the Great Lakes states, north central USA

CONCENTRATIONS of mercury in the environment are increasing as a result of human activities, notably fossil-fuel burning and incineration of municipal wastes. Increasing levels of mercury in aquatic environments and consequently in fish populations are recognized as a public-health problem1,2. Enhanced mercury concentrations in lake sediments relative to pre-industrial values have also been attributed to anthropogenic pollution. It is generally assumed that atmospheric mercury deposition is dominated by global-scale processes, consequently being regionally uniform. Here, to the contrary, we report a significant gradient in concentrations and total amounts of mercury in organic litter and surface mineral soil along a transect of forested sites across the north central United States from northwestern Minnesota to eastern Michigan. This gradient is accompanied by parallel changes in wet sulphate deposition and human activity along the transect, suggesting that the regional variation in mercury content is due to deposition of anthropogenic mercury, most probably in particulate form.
Language matches: Illuminating or confounding?

The practice of matching younger, language-matched controls, in addition to age-matched controls, is often used in studies of language-disordered children to examine the role of "language level" on performance. However, the interpretation of the relative performance of subjects in studies using such dual control groups is problematic. Conceptual concerns arise with the use of language matches because language is a multidimensional skill that is not reflected equivalently for the language-disordered children and their language-matched controls. Furthermore, matching by language level inevitably introduces an extraneous age effect that confounds interpretation. In addition, erroneous interpretations of null findings can occur when no differences are found between language-disordered and language-matched groups.
Residual casein fractions in ripened cheese determined by polyacrylamide-gel electrophoresis.

Abstract Polyacrylamide-gel electrophoresis (PAE) of ripened-cheese caseins provides an ideal means of studying cheese-ripening by detecting small changes in the specific casein fractions. Properties, such as molecular sieving, and the facility to use simultaneously casein standards, apparently are important advantages of PAE. Rennet enzymes appear specifically to alter α s1 -casein after curd formation in Cheddar cheese manufacture. β -Casein evidently is unaltered by the rennet enzymes. The caseins were hydrolyzed to different extents in the cheese varieties examined. The α s1 -fraction is degraded in every cheese; however, β -casein appears largely intact in some varieties, whereas its content is appreciably diminished in others. This reflects important differences in the proteolytic abilities of microorganisms peculiar to a given variety of cheese. An elucidation of these microbial enzymes should lead to a better understanding of the ripening process.
Experiments and numerical simulations on beam bending and transverse beam encoding by spatial self- and cross-phase modulation in ruby

Abstract Experiments and numerical simulations are performed on the nonlinear beam evolution of simultaneously propagating cw argon-ion and HeNe laser beams through a ruby rod. The HeNe probe beam exhibits a deflection of nearly 12 mrad when a 1.5 W, 514.5 nm laser beam is injected into the ruby rod at an angle to the probe. The copropagating geometry is also studied where the azimuthally symmetric transverse beam encoding leads to complex ring structures in both the HeNe and argon-ion laser beams. The numerical simulations are compared with the experimental data to obtain the cross-phase modulation term. Using previously reported values for the saturable nonlinear index of ruby and a nonlinear index for cross-phase modulation n c = 1.35Re( n 2 ), the nonlinear wave equation in two transverse dimensions is numerically solved to predict the bending angles and emerging beam profiles. These findings are discussed in light of previous experiments in ruby as well as the possibility of using these effects for producing nanosecond optical switching systems.
Contributions of tryptophan side chains to the far-ultraviolet circular dichroism of proteins

It has often been assumed that the role of aromatic side chains in the far-ultraviolet region of protein circular dichroism (CD) is negligible. However, some proteins have positive CD bands in the 220-230 nm region which are almost certainly due to aromatic side chains. The contributions to the CD of interactions between tryptophan side chains and the nearest neighbor peptide groups have been studied, focusing on the indole Bb transition which occurs near 220 nm. Calculations on idealized peptide conformations show that the CD depends strongly on both backbone and side-chain conformation. Because of the low symmetry of indole, rotation about the C beta C gamma bond (dihedral angle chi 2) by 180 degrees generally leads to large changes in the CD, often causing the Bb band to reverse sign. When side-chain conformational preferences are taken into account, there is no strong bias for either positive or negative Bb rotational strengths. The observation that simple tryptophan derivatives such as N-acetyl-L-tryptophan methylamide have positive CD near 220 nm implies either that these derivatives prefer the alpha R region over the beta region, or that there is little preference for chi 2 180 degrees. Nearest-neighbor-only calculations on individual tryptophans in 15 globular proteins also reveal a small bias toward positive Bb bands. Rotational strengths of the Bb transition for some conformations can be as large as approximately 1.0 Debye-Bohr magnetons in magnitude, corresponding to maximum molar ellipticities greater than 10(5) deg cm2/dmol. Although a substantial amount of cancellation occurs in most of the examples considered here, such CD contributions could be significant, especially in proteins of low helix content.
Asymptotic behavior near planar transition fronts for the Cahn–Hilliard equation

Abstract We consider the asymptotic behavior of perturbations of planar wave solutions arising in the Cahn–Hilliard equation in space dimensions d ≥ 2 . Such equations are well known to arise in the study of spinodal decomposition, a phenomenon in which rapid cooling of a homogeneously mixed binary alloy causes separation to occur, resolving the mixture into regions in which one component or the other is dominant, with these regions separated by steep transition layers. A critical feature of the Cahn–Hilliard equation in one space dimension is that the linear operator that arises upon linearization of the equation about a standing wave solution has essential spectrum extending onto the imaginary axis, a feature that is known to complicate the step from spectral to nonlinear stability. The analysis of planar waves in multiple space dimensions is further complicated by the fact that the leading eigenvalue for this linearized operator (leading in the case of stability) moves into the negative-real half plane with cubic scaling λ ∼ | ξ | 3 , where ξ ∈ R d − 1 denotes a Fourier variable associated with spatial components transverse to the planar wave. Under the assumption of spectral stability, described in terms of an appropriate Evans function, we develop detailed asymptotics for perturbations from planar wave solutions, establishing asymptotic stability for initial perturbations decaying at an appropriate algebraic rate in an L 1 norm of the transverse variables.
Further notes on public response to uncertainty in risks and science.

Given the prevalence of uncertainty and variability in estimates of environmental health risks, it is important to know how citizens interpret information representing uncertainty in risk estimates. Ranges of risk estimates from a hypothetical industry source elicited divergent evaluations of risk assessors' honesty and competence among New Jersey residents within one mile of one or more factories. A plurality saw ranges of risk estimates as both honest and competent, but with most judging such ranges as deficient on one or both dimensions. They wanted definitive conclusions about safety, tended to believe the high end of the range was more likely to be an accurate estimate of the risk, and believed that institutions only discuss risks when they are "high." Acknowledgment of scientific, as opposed to self-interested, reasons for uncertainty and disputes among experts was low. Attitude toward local industry seemed associated with, if not a cause of, attitudes about ranges of risk estimates. These reactions by industry neighbors appear to replicate the findings of Johnson and Slovic (1995, 1998), despite the hypothetical producer of risk estimates being industry instead of government. Respondents were older and less educated on average than were the earlier samples, but more diverse. Regression analyses suggested attitude toward industry was a major factor in these reactions, although other explanations (e.g., level of scientific understanding independent of general education) were not tested in this study.
Reversal of enterocolitis-associated combined immunodeficiency by plasma therapy.

Two 6-month-old male infants with diarrhea, malabsorption, and hypoproteinemia, who were initially diagnosed as having combined immunodeficiency syndrome, recovered with intensive plasma therapy. Prior to the onset of diarrhea, they had normal serum protein and lymphocyte values. Immunologic features of combined immunodeficiency included lymphopenia, diminished B and T cells, cutaneous anergy, low immunoglobulin levels, and poor lymphocyte proliferative responses in vitro. Prior to therapy, both children had rectal ulcerations by proctosigmoidoscopy, colitis by rectal biopsy, and moderate to severe intestinal villus abnormalities by small bowel biopsy; plasma cells were absent. Both had generalized malabsorption of all nutrients. Both infants were given irradiated fresh-frozen plasma for one to two months at 11 to 20 ml/kg/day to replace intestinal protein losses. During this time, diarrhea slowed, biopsy morphology improved, and immunoglobulin levels and T-cell function became normal. After discontinuance of plasma therapy, normal immune function and a normal stool pattern with reversal of malabsorption continued. Since intensive plasma therapy may have contributed to the reversal of the immunodeficiency state, a trial of such therapy is recommended in similar patients.
Production of antisera to steroids coupled to proteins directly through the phenolic A ring.

Abstract A method is presented to render low molecular weight steroids containing an aromatic A ring immunogenic when coupled to proteins. The steroid molecule is entered at C-2 or C-4 by diazotized PABA which is coupled by its carboxyl group to an amino group of a protein carrier under alkaline conditions. Analysis of substituted proteins disclosed 5–29 steroid residues per molecule of protein under conditions described. Serum of rabbits immunized with β-estradiol coupled to BSA or KLH were tested by quantitative precipitin and gel diffusion experiments against a variety of steroid haptens coupled to HGG. Maximum antibody protein was 700 μg/ml. Slight cross reactivity occured between estradiol, estriol and estrone. This may be real or due to contamination. Testosterone and progesterone treated in identical fashion did not couple and showed no antigenicity by quantitative precipitin, gel diffusion, and immunoelectrophoresis experiments.
A technical note on endonasal combined microscopic endoscopic with free head navigation technique of removal of pituitary adenomas

Pituitary surgery exemplifies the continuous refinement of surgical techniques. The transsphenoidal approach is the approach of choice to treat most pituitary adenomas. We report here, as a technical note, an operative nuance that represents an encompassment of various technical steps that we utilize in our current surgery, including the corroboration of navigation system on a free head with combined use of endoscope and microscope techniques.
The High‐Pressure Characterization of Energetic Materials: 1,4‐Dimethyl‐5‐Aminotetrazolium 5‐Nitrotetrazolate

In-situ high-pressure room temperature synchrotron X-ray diffraction and infrared microspectroscopy were used to examine the structural and vibrational properties and the equation of state of 1,4-dimethyl-5-aminotetrazolium 5-nitrotetrazolate (DMATNT). The X-ray measurements show a smoothly varying pressure-volume relationship to 20 GPa. However, the anisotropic ratios of the unit cell parameters reveal a discontinuity near 3.3 GPa, which can be attributed to an irreversible isostructural phase transition. A significant increase in the Infrared spectral intensity near this pressure coupled with Dayvdov splitting of the NO2 bending and scissoring modes suggest the transition results in a skewing of the NO2 groups and increasing asymmetry of the hydrogen bonding sublattice.
Oxidation of oleic and elaidic acids in rat and human heart homogenates.

Parallel incubations with uniformly 14C-labeled oleic and elaidic acids were conducted to compare oxidation rates in tissue homogenates prepared from rat and human hearts. Radioactivity in 14CO2 and 14C-labeled chain-shortened acid-soluble products was used to measure the extent of oxidation. Oxidation rates (pmol/min per mg heart protein) determined on 14C-labeled acid-soluble products suggest that oleic acid was oxidized 35–40% faster than elaidic acid by both male and female rat heart homogenates, whereas human heart homogenates oxidized these fatty acids at equal rates. Rates for female heart homogenates were somewhat higher than those for males in rats and humans. Rates of formation of 14CO2 were the same for each acid in rat and human heart tissue. Comparative rates of formation of oxidation products expressed as oleic/elaidic ratios from parallel incubations confirm that preferential oxidation of oleic acid occurred with rat heart homogenates, but not with the human heart homogenates. These data suggest that the presence of the trans double bond in elaidic acid does not impair its utilization for energy by human heart muscle.