cssi/SciSciGPT-SciSciNet huggingface dataset:
Cerebrospinal fluid shunt infectionsecondary to escherichia coli bacteriuria

Abstract A 10-year-old girl with a lumbosacral myelomeningocele, managed withclean intermittent catheterization, presented with headache, vomiting, and lethargy. The cerebrospinal fluid (CSF) and urine cultures revealed Escherichia coli , documented to be the same subtype. The organisms were subtyped and the E. coli from both the urine and CSF were noted to be of the same strain. Management consisted of intravenous antibiotics and ultimate replacement of the ventriculoperitoneal shunt. Children with myelodysplasia and CSF shunts should be carefully monitored in a multidisciplinary fashion to anticipate, correctly diagnose, and treat CSF shunt infections associated with bacteriuria.
Developments in geothermal waste treatment biotechnology

Abstract Disposal of toxic solid waste in an environmentally and economically acceptable way may be in some cases a major impediment to large geothermal development. The major thrust of the R &D effort in this laboratory is to develop low-cost processes for the concentration and removal of toxic materials and metals from geothermal residues. In order to accomplish this, biochemical processes elaborated by certain microorganisms which live in extreme environments have served as models for a biotechnology. It has been shown that 80% or better removal of toxic metals can be achieved at fast rates (e.g., 25 hours or less) at acidic pH and temperatures of about 60°C. There are several process variables which have to be taken into consideration in the development of such biotechnology. These include reactor size and type, strain of microorganisms, biomass growth, temperature, loading concentrations of residual geothermal sludge, and chemical nature of metal salts present. Recent data generated by the research and development effort associated with the emerging biotechnology will be presented and discussed.
The continuum concept remains a useful framework for studying mycorrhizal functioning

Recent studies have questioned the validity of the mutualism-parasitism continuum of mycorrhizal function. This paper re-evaluates the continuum model and analyzes these concerns. Three insights arise from this analysis. First, the continuum model defines mycorrhizal function as an emergent property of complex interactions. The model identifies resource trade and symbiotic control as key determinants of the costs and benefits of the symbiosis for plants and fungi, and the interaction of these factors with the environment ultimately controls mycorrhizal function. Second, analysis of carbon costs and phosphorus benefits is too narrow a focus to accurately predict mycorrhizal function. Analysis of plant and fungal fitness responses in ecologically and evolutionarily relevant systems are required to elucidate the full range of nutritional and non-nutritional factors embodied within mycorrhizal functioning. Finally, the definition of the term ‘parasitism’ has evolved. Some fields of science maintain the original definition of a nutritional relationship between host and parasite while other fields define it as a +/- fitness relationship. This has generated debate about whether the continuum of mycorrhizal functioning should properly be called a positive–negative response continuum or a mutualism-parasitism continuum. This controversy about semantics should be resolved, but it does not overturn the continuum concept.
Moonlighting Proteins: How the Lipid-Signaling Enzyme Phospholipase C-Beta Regulates RNA Silencing

Gene silencing by microRNAs controls the expression of large number of proteins. While many of the players of this process have been identified, their regulation is just beginning to be understood. One of the key players in RNA silencing is C3PO (Component 3 Promoter of RNA-induced silencing complex). C3PO hydrolyzes one of the strands of small duplex RNA leaving the other strand to bind to its mRNA target where it is subsequently degraded. C3PO is an asymmetric octamer containing six subunits of the RNA binding protein translin, and two subunits of the nuclease TRAX (translin-associated factor X). We have recently found that phospholipase C-beta (PLCb), a key player in transducing extracellular signals through G proteins, binds to TRAX in solution and in cultured cells. TRAX competes with G proteins for PLCb binding and in cells, over-production of TRAX quenches calcium signals generated from G protein-induced PLCb activity. Alternately, over-production of PLCb reverses RNA-interference by C3PO presumably through its interaction with TRAX. However, this link between extracellular signals through G proteins and RNA silencing is not straightforward. PLCb only reverses silencing of specific genes. Using a set of biophysical tools, we show that the specificity of gene silencing by PLCb lies in the hydrolytic rate of specific RNA structures by C3PO that are affected by PLCb binding. Understanding the molecular basis for these specific effects will allow us to understand the more vulnerable genes.
A Distributed Platform for Global-Scale Agent-Based Models of Disease Transmission

The Global-Scale Agent Model (GSAM) is presented. The GSAM is a high-performance distributed platform for agent-based epidemic modeling capable of simulating a disease outbreak in a population of several billion agents. It is unprecedented in its scale, its speed, and its use of Java. Solutions to multiple challenges inherent in distributing massive agent-based models are presented. Communication, synchronization, and memory usage are among the topics covered in detail. The memory usage discussion is Java specific. However, the communication and synchronization discussions apply broadly. We provide benchmarks illustrating the GSAM’s speed and scalability.
The effect of Planck scale space time fluctuations on Lorentz invariance at extreme speeds

The starting point of this work is the axiomatic existence of a smallest measurable interval, viz. the Planck time $t_P$, set by quantum fluctuations in the vacuum metric tensor. By the Relativity Principle, the same limit must then apply to the accuracy of all clocks which register time of events in their own frames. Further, it implies that the ordinary meaning of distance also ceases in the same manner beyond a scale l_P = c t_P. We demonstrate that quantum space-time, if real, may be made manifest by observing very energetic collisions, defined as interactions which occurred with the center-of-mass frame $\Sigma'$ (of the participating bodies) moving at a high speed $v$ relative to our laboratory frame $\Sigma$. In such situations, the initial conditions of the interaction are determined from direct measurements of the ultra-energetic particles or photons by instruments aboard $\Sigma$: they gather a raw dataset ${\cal S}$ which are subject to the limiting uncertainties \~ (t_P, l_P). Yet a meaningful (i.e. experimentally verified) version of the interaction is one where the interaction is viewed from frame $\Sigma'$. Since no instruments aboard $\Sigma'$ have taken any data, the way we proceeded is by a Lorentz transformation of ${\cal S}$ from $\Sigma$ to $\Sigma'$. Beware however that the resulting ${\cal S'}$ no longer consists of raw data, i.e. Lorentz distortions of probability distributions render the uncertainties non-Planckian - in fact, it will be shown that as v -> c they are >> (t_P, l_P), and are no longer negligible. Examples will given to indicate how a proper interpretation of the most current high energy cosmic and gamma-ray data necessitates incorporation of the said effect.
Environmental and Hormonal Effects in Micropropagation

Micropropagation has become important in the latter quarter of the Twentieth Century, both in a commercial sense and as an exceedingly valuable research tool for the study of plant physiology, growth and development. A myriad of papers have been published on a wide variety of subjects related to micropropagation including the critically important areas of environment and hormones. In this paper, special attention is given to the influence of environment and hormones, and their interactions as they affect the stock plant and the subsequent performance of the explant when cultured in vitro. Explant selection (genotype, organ chosen, age and physiological stage, health), stock plant management (nutrition; light intensity, quality and photoperiod; temperature; chemical and physical manipulations), gaseous atmosphere (RH, CO2, O2, ethylene) and both conventional and novel plant growth regulating chemicals are topics presented. These topics are discussed in relation to future challenges and opportunities, such as automation and robotization of micropropagation technology.
Escape and avoidance learning in the earthworm Eisenia hortensis

Interest in instrumental learning in earthworms dates back to 1912 when Yerkes concluded that they can learn a spatial discrimination in a T-maze. Rosenkoetter and Boice determined in the 1970s that the “learning” that Yerkes observed was probably chemotaxis and not learning at all. We examined a different form of instrumental learning: the ability to learn both to escape and to avoid an aversive stimulus. Freely moving “master” worms could turn off an aversive white light by increasing their movement; the behavior of yoked controls had no effect on the light. We demonstrate that in as few as 12 trials the behavior of the master worms comes under the control of this contingency.
ASCORBATE FUNCTION AND METABOLISM IN THE HUMAN ERYTHROCYTE

Ascorbic acid, or vitamin C, is an important antioxidant in plasma, where it consumes oxygen free radicals and helps to preserve alpha-tocopherol (vitamin E) in lipoproteins. Erythrocytes, as the most plentiful cell in blood, help to preserve ascorbate in the blood plasma. In contrast to nucleated cells, which avidly concentrate ascorbate, the erythrocyte ascorbate concentration is the same as that in plasma. Erythrocytes nonetheless have a high capacity to regenerate the vitamin from its two electron-oxidized form, dehydroascorbic acid (DHA). DHA is rapidly taken up by these cells on the abundant glucose transport protein, GLUT1. Intracellular DHA is rapidly reduced to ascorbate by GSH in a direct chemical reaction, although enzyme-dependent mechanisms involving both glutaredoxin and thioredoxin reductase have also been demonstrated. Ascorbate, which carries a negative charge at physiologic pH, enters and leaves the cells slowly. Nonetheless, this slow release of ascorbate from erythrocytes can preserve both the plasma concentration of the vitamin, and prevent oxidation of alpha-tocopherol in low-density lipoprotein. In addition, intracellular ascorbate can spare and possibly recycle alpha-tocopherol in the erythrocyte membrane. In turn, alpha-tocopherol protects the cell membrane from lipid peroxidation. The ability of erythrocytes to recycle ascorbate, coupled with the ability of ascorbate to protect alpha-tocopherol in the cell membrane and in lipoproteins, provides a potentially important mechanism for preventing lipid peroxidative damage in areas of inflammation in the vascular bed, such as those involved with atherosclerosis.
A pre-post pilot study of a brief, web-based intervention to engage disadvantaged smokers into cessation treatment

Background People with low education and/or income are more likely to smoke, less likely to quit, and experience disparately poor health outcomes compared to those with education and income advantage. Cost-effective strategies are needed to inform and engage this group into effective cessation treatments. We developed a novel, web-based, motivational, decision-support system that was designed to engage disadvantaged smokers into tobacco cessation treatment. We piloted the system among smokers in a primary care safety net clinic.
Flutter of Orthotropic Panels at Arbitrary Yaw Angles— Experiment and Theory

Experimental flutter boundaries were obtained for yaw angles between 15° and 90° at Mach numbers 2 and 1.6 for panels mounted Of a remotely controlled turntable. Good definition of the flutter boundaries was obtained by rotating the panels into and out of flutter. Two types of specimens were tested: a single sheet corrugated panel having a length-to-width ratio of 5 on clamped supports; and several square doubly-corrugated panels on various flexible supports. Calculated flutter speeds based on quasi-steady aerodynamics are compared to experimental data.
Effects of anticaking agents and relative humidity on the physical and chemical stability of powdered vitamin C.

Vitamin C is an essential nutrient that is widely used by the food industry in the powder form for both its nutritional and functional properties. However, vitamin C is deliquescent, and deliquescence has been linked to physical and chemical instabilities. Anticaking agents are often added to powder systems to delay or prevent caking, but little is known about their effect on the chemical stability of powders. In this study, various anticaking agents (calcium phosphate, calcium silicate, calcium stearate, corn starch, and silicon dioxide) were combined with sodium ascorbate at 2% and 50% w/w ratios and stored at various relative humidities (23%, 43%, 64%, 75%, 85%, and 98% RHs). Chemical and physical stability and moisture sorption were monitored over time. Additionally, saturated solution samples were stored at various pHs to determine the effect of surface pH and dissolution on the vitamin degradation rate. Storage RH, time, and anticaking agent type and ratio all significantly affected (P < 0.05) moisture sorption and vitamin C stability. Silicon dioxide and calcium silicate (50% w/w) and calcium stearate (at both ratios) were the only anticaking agents to improve the physical stability of powdered sodium ascorbate while none of the anticaking agents improved its chemical stability. However, corn starch and calcium stearate had the least adverse effect on chemical stability. Dissolution rate and pH were also important factors affecting the chemical and physical stability of the powders. Therefore, monitoring storage environmental conditions and anticaking agent usage are important for understanding the stability of vitamin C. Practical application: Anticaking agent type and ratio significantly affected the physical and chemical stability of vitamin C over time and over a range of RHs. No anticaking agent improved the chemical stability of the vitamin, and most caused an increase in chemical degradation even if physical stability was improved. It is possible that anticaking agents would greatly affect other chemically labile deliquescent ingredients, and therefore, anticaking agent usage and storage conditions should be monitored in blended powder systems.
Familial Thoracic Aortic Aneurysms and Dissections: Identification of a Novel Locus for Stable Aneurysms with a Low Risk for Progression to Aortic Dissection

Background— Thoracic aortic aneurysms leading to acute aortic dissections are the major diseases that affect the thoracic aorta. Approximately 20% of patients with thoracic aortic aneurysms and dissections (TAAD) have a family history of TAAD, and these patients present younger with more rapidly enlarging aneurysms than patients without a family history of aortic disease. Methods and Results— A large family with multiple members with TAAD inherited in an autosomal-dominant manner was identified. The ascending aortic aneurysms were associated with slow enlargement, a low risk of dissection, and decreased penetrance in women. Genome-wide linkage analysis was performed, and a novel locus on chromosome 12 was identified for the mutant gene causing disease in this family. Of the 12 male members who carry the disease-linked microsatellite haplotype, 9 had ascending aortic aneurysms with an average diameter of 4.7 cm at an average age of 52.4 years (range, 32 to 76 years) at the time of diagnosis; only 1 individual had progressed to acute aortic dissection, and no other members with aortic dissections were identified. Women harboring the disease-linked haplotype did not have thoracic aortic disease, including 1 aged 84 years. Sequencing of 9 genes within the critical interval at the chromosome 12 locus did not identify the mutant gene. Conclusions— Mapping a locus for ascending thoracic aortic aneurysms associated with a low risk of aortic dissection supports our hypothesis that genes leading to familial disease can be associated with less-aggressive thoracic aortic disease.
A Modern and Practical Review of Rapid-Sequence Intubation in Pediatric Emergencies

Rapid-sequence intubation is the standard for definitive airway management in the emergency department and requires multiple stepwise tasks where the sequence and timing are important. Optimal performance of this critical procedure can be challenging, and common pitfalls exist that emergency providers may encounter when performing rapid-sequence intubation in children. Prolonged and/or failed endotracheal intubation attempts and adverse effects are not infrequent, especially in neonates and young children. Formal standardization of the approach and use of technological advances in intubation and monitoring equipment can decrease variation in the process, improve team-level situational awareness, and mitigate risk to the patient. This article reviews the required planning and preparatory steps, and offers specific strategies aimed at mitigating the associated risks and potential pitfalls to enhance the likelihood of success and safety during the performance of this high-risk procedure in children.
Early Coursework and College Experience Predictors of Persistence at a Hispanic-Serving Institution.

Utilizing survival analysis, we examined two key first year courses, mathematics and English, and tested whether they were predictive for long-term student success as measured by persistence to graduation at a Hispanic-serving research university. While first math and first English courses were significant, SAT score was not for Hispanic and Black students. High school grade point average (GPA) was significant for Hispanic students but not for White or Black students.
Persistent Discharge in a Premenarchal Child

The patient is a 7-year-old girl who initially presented with an 18-month history of vaginal discharge. The discharge is quite profuse on occasion necessitating that she wear a maxi pad. It does completely disappear at times for as long as several months. The discharge is white odorless and does not cause itching. Evaluation until presentation in the clinic has included negative genital cultures multiple courses of antifungals and an exam under anesthesia which was reported normal. She has no other complaints and is healthy and developing normally. There is no concern of abuse. Physical exam is normal: breasts are Tanner stage 1 gynecologic exam reveals normal external genitalia and there is no presence of discharge. Rectal exam is unremarkable and reveals no discharge. (excerpt)
African American Males in Foreign Affairs

The making and implementation of American foreign policy is a process that involves many actors, including the president, his advisers, legislators, nongovernmental organizations, and private citizens. Absent, for the most part, have been African Americans. During recent decades, however, some progress has been made in including them. A major purpose of this article is to determine the extent to which African American males have been and are involved in the foreign affairs arena, including the military. Likewise, it will seek to determine the impact that foreign policy has had and continues to have on African American males and the extent to which their involvement in the military can be considered a curse or blessing.
Cheering on the Collegiate Model: Creating, Disseminating, and Imbedding the NCAA’s Redefinition of Amateurism

In January 2012, during his “State of the Association” address, National Collegiate Athletic Association (NCAA) President Mark Emmert urged members to fix the “collegiate model.” Imbedded in the sp...
Nkx2.2 Regulates β-Cell Function in the Mature Islet

Nkx2.2 is a homeodomain transcription factor that is critical for pancreatic endocrine cell specification and differentiation in the developing mouse embryo. The purpose of this study was to determine whether Nkx2.2 is also required for the maintenance and function of the mature β-cell in the postnatal islet. We have demonstrated previously that a repressor derivative of Nkx2.2 can functionally substitute for endogenous Nkx2.2 to fully restore α- and immature β-cells in the embryonic islet; however, Nkx2.2 activator functions appear to be required to form a functional β-cell. In this study, we have created transgenic mouse lines to express the Nkx2.2-repressor derivative in the mature β-cell in the presence of endogenous Nkx2.2. The transgenic mice were assessed for β-cell function, overall islet structure, and expression of β-cell–specific markers. Using this transgenic approach, we have determined that the Nkx2.2-repressor derivative disrupts endogenous Nkx2.2 expression in adult mice and causes downregulation of the mature β-cell factors, MafA and Glut2. Consistently, the Nkx2.2-repressor mice display reduced insulin gene expression and pancreatic insulin content and impaired insulin secretion. At weaning, the male Nkx2.2-repressor mice are overtly diabetic and all Nkx2.2-repressor transgenic mice exhibit glucose intolerance. Furthermore, the loss of β-cell function in the Nkx2.2-repressor transgenic mice is associated with disrupted islet architecture. These studies indicate a previously undiscovered role for Nkx2.2 in the maintenance of mature β-cell function and the formation of normal islet structure.
A Complex Translational Program Generates Multiple Novel Proteins from the Latently Expressed Kaposin (K12) Locus of Kaposi’s Sarcoma-Associated Herpesvirus

The most abundantly expressed latent transcripts encoded by the Kaposi’s sarcoma (KS)-associated herpesvirus derive from the genomic region surrounding open reading frame (ORF) K12 (kaposin A). Here we show that these transcripts, initially described as limited to ORF K12 itself, more frequently encompass upstream sequences spanning two sets of 23-nucleotide GC-rich direct repeats (DRs) (DR1 and DR2). Although the DRs lack AUG codons and were previously presumed to be noncoding, a monoclonal antibody raised to infected cells detected multiple polypeptides encoded by this region. These proteins are expressed during latency and upon induction of lytic viral replication in both primary effusion lymphoma (PEL) cell lines and KS tumors. Biochemical and genetic analyses reveal that these proteins are derived from variant translational initiation at CUG codons. The predominant translation product in the PEL cell line BCBL-1 derives from the 5′-most CUG codon in the transcript, resulting in a protein (termed kaposin B) which is encoded largely by the repeats themselves and which does not include K12 sequences. Other non-AUG codons in alternate reading frames are also used at lower efficiency, including one that initiates translation of a DR-K12 fusion protein (kaposin C) that is predicted to sort to a different subcellular locale than kaposin B. Thus, the products of the K12 region, which is the most abundantly transcribed region in latency, are surprisingly complex and may encompass multiple biological functions.
A new algorithm for multirate digital control law synthesis

A novel algorithm for multirate digital control law synthesis is presented. The algorithm accommodates a generalized controller structure, and all sampling rates for sensor sample-and-hold circuits, digital processor circuits, and control sample-and-hold circuits can be chosen independently. The algorithm uses a gradient-type numerical search to determine the controller matrices so that a finite-time, linear, quadratic, cost function is minimized. The finite time avoids problems with destabilizing sets of controller matrices. To speed the numerical search, closed-form expressions are used to calculate the cost and gradient of the cost with respect to the controller matrices exactly. >
Study of particle and γ decays of the Ex = 12.00 MeV 63+ level in 24Mg

Abstract Direct coincidence observation of α- and γ-decays of the Ex = 12.0 MeV level populated in the 12 C ( 16 O , α) 24 Mg reaction has been used to show that both 6+ and 3− levels exist near this excitation energy. Comparison of the present work with previous radiative capture studies permits the conclusion that the 63+ level in 24Mg decays primarily by γ-emission, in agreement with recent shell-model calculations using an (sd)8 basis. Absolute E2 and M1 strengths deduced from the data are not, however, in good quantitative agreement with the predictions of the shell model.
Genetic susceptibility to advanced retinopathy of prematurity (ROP)

Retinopathy of prematurity (ROP) is a vascular vitreoretinopathy that affects infants with short gestational age and low birth-weight. The condition is a multifactorial disease and is clinically similar to familial exudative vitreoretinopathy (FEVR), which is a bilateral hereditary eye disorder affecting full-term infants. Both of them are characterized by the abnormal vessel growth in the vitreous that can lead to vitreoretinal traction, retinal detachment and other complications resulting in blindness. Despite the recent advances in diagnosis and treatment, ROP remains a major cause of childhood blindness in developed countries. The etiology of pathogenesis of advanced ROP is currently unknown. In the past, many causative factors such as length of time exposed to supplemental oxygen, excessive ambient light exposure and hypoxia have been suggested but evidence for these as independent risk factors in recent years is not compelling. It is not clear why ROP in a subset of infants with low birth-weight progresses to a severe stage (retinal detachment) despite timely intervention whereas in other infants with similar clinical characteristics ROP regresses spontaneously. Recent research with candidate gene approach, higher concordance rate in monozygotic twins and other clinical and experimental animal studies, suggest a strong genetic predisposition to ROP besides environmental factors such as prematurity. Three genes, which are involved in the Wnt signaling pathway, are mutated in both FEVR and in a small percentage of ROP disorder. However, none of the genetic factors identified thus far in ROP, account for a substantial number of patient population. Future studies involving genomics, bioinformatics and proteomics may provide a better understanding of the pathophysiology and management of ROP.
Nonspecific Inhibition of Growth of Intracellular Listeria monocytogenes by Lymphocyte Culture Products

Supernatant fluids from mycobacteria-immune and mitogen-stimulated lymphocyte cultures were able to inhibit the intracellular growth of listeria in listeria-infected macrophages.
The effects of orthotic intervention and 9 holes of simulated golf on gait in experienced golfers

Background: This investigation evaluated the effects of orthotic intervention on gait patterns and fatigue associated with 9 holes of simulated golf among a group of experienced golfers. Setting: Northwestern Health Sciences University, Bloomington, Minn. Participants: Twelve experienced golfers. Method: By means of video freeze-frame analysis, gait was assessed in each subject before and after 9 holes of simulated golf. Subjects wore custom-made, flexible orthotics daily for 6 weeks, and gait was then reassessed through use of the same objective measurement parameters. Fatigue was introduced by having participants complete 9-hole rounds of simulated golf before and after wearing custom-made, flexible orthotics for 6 weeks. Main Outcome Measure: Parameters associated with gait (ie, stride length and pelvic rotation) were measured in all subjects before and after they used custom-fit, flexible orthotics for 6 weeks and before and after they completed 9 holes of simulated golf. Results: The data indicate that for experienced golfers, wearing the custom-fit, flexible orthotics used in this study for 6 weeks influenced the parameters associated with gait and reduced the effects of fatigue associated with 9 holes of simulated golf. Conclusion: The use of custom-fit, flexible orthotics in this study had a significant influence on the elements of gait measured in the investigation—specifically, pelvic rotation and stride length. There was an average increase in pelvic rotation of between 29% and 36%, and there were concomitant changes in stride length after subjects had used the orthotics for 6 weeks. In addition, use of these custom orthoses reduced the effects of fatigue associated with playing 9 holes of simulated golf; they could thus improve the likelihood of more consistent performance, possibly as a result of a more efficient gait pattern. (J Manipulative Physiol Ther 2001;24:279-87) Key Indexing Terms: Biomechanics; Gait; Golf; Sports; Fatigue; Orthotic Devices
Design, implementation and control of a sparse aperture imaging satellite

†In order to better understand the technological difficulties involved in designing and building a sparse aperture array, the challenge of building a white light Golay-3 telescope was undertaken. The MIT Adaptive Reconnaissance Golay-3 Optical Satellite (ARGOS) project exploits wide-angle Fizeau interferometer technology with an emphasis on modularity in the optics and spacecraft subsystems. Unique design procedures encompassing the nature of coherent wavefront sensing, control and combining as well as various system engineering aspects to achieve cost effectiveness, are developed. To demonstrate a complete spacecraft in a 1-g environment, the ARGOS system is mounted on a frictionless air-bearing, and has the ability to track fast orbiting satellites like the ISS or the planets. Wavefront sensing techniques are explored to mitigate initial misalignment and to feed back real-time aberrations into the optical control loop. This paper presents the results and the lessons learned from the conceive, design, implement and operate phases of ARGOS. A preliminary assessment shows that the beam combining problem is the most challenging aspect of sparse optical arrays. The need for optical control is paramount due to tight beam combining tolerances. The wavefront sensing/control requirements appear to be a major technology and cost driver.
Novel Approaches to Advanced Breast Cancer: Bevacizumab and Lapatinib

New biological therapies continue to emerge in breast cancer. Recent advances with anti-angiogenesis therapies and anti-HER2 therapies highlight the next generation of treatments that will be entering clinical practice. Important questions regarding these targeted treatments remain, however. There are uncertainties as to how best to integrate new drugs into existing treatment algorithms, whether to use monotherapy or combination therapy with chemotherapy, and how to manage novel side effects seen with these agents. This review highlights recent advances with the anti-vascular endothelial growth factor antibody, bevacizumab, and the dual kinase inhibitor, lapatinib, in the treatment of metastatic breast cancer.
Presence of low molecular weight inhibitors of protein synthesis in the developing embryo. 1.

SummaryLow molecular weight substances isolated from 8-day-old chick embryos inhibited incorporation of lysine and isoleucine into TCA-precipitable protein. One of these, moreover, blocked the uptake of uridine into nucleic acid.They were heat stable and dialyzable. Inhibitor I had an approximate mol wt of 600-700; II had an approximate mol wt of 450; III was under 500. Treatment with RNAse, DNAse, trypsin and pronase did not result in loss of activity of the inhibitors. None of the inhibitors manifested proteolytic activity.
A Proxy Signature Scheme Based on Hyperelliptic Curve

To strengthen proxy signature security,and based on the analysis of blind signature scheme in being,this paper proposed a proxy signature scheme based on the hyperelliptic curve cryptography.Furthermore,it analyzed the security problem.Through transplanting a proxy signature arithmetic into hyperelliptic curve cryptography,it proposed a proxy signature arithmetic which was based on the hyperelliptic curve cryptography.Proxy signature scheme based on the hyperelliptic curve cryptography is better than that of elliptic curve cryptography on performance of security.It plays a better role in electronic commerce and network security.
Mapping the Trimethoprim-Induced Secondary Metabolome of Burkholderia thailandensis

While bacterial genomes typically contain numerous secondary metabolite biosynthetic gene clusters, only a small fraction of these are expressed at any given time. The remaining majority is inactive or silent, and methods that awaken them would greatly expand our repertoire of bioactive molecules. We recently devised a new approach for identifying inducers of silent gene clusters and proposed that the clinical antibiotic trimethoprim acted as a global activator of secondary metabolism in Burkholderia thailandensis. Herein, we report that trimethoprim triggers the production of over 100 compounds that are not observed under standard growth conditions, thus drastically modulating the secondary metabolic output of B. thailandensis. Using MS/MS networking and NMR, we assign structures to ∼40 compounds, including a group of new molecules, which we call acybolins. With methods at hand for activation of silent gene clusters and rapid identification of small molecules, the hidden secondary metabolomes of bacteria...
Thinking Spatially, Speaking Visually

In the early 1970s, international stage director Robert Wilson began working with a young autistic poet, Christopher Knowles (b. 1959). Knowles’s approach to language as a spatial, pictorial, and sonic art form shaped Wilson’s 1974 piece, A Letter for Queen Victoria and his later opera, Einstein on the Beach (1976).
Surface micromachined differential piezoelectric shear-stress sensors

The ability to measure viscous wall shear stress in high-speed flows is important for verifying simulated results typically obtained from direct numerical simulation in the aerodynamics research community, and robust sensors are required to measure wall shear reliably under such high-speed conditions. This letter summarizes the design, fabrication, and testing of a surface micromachined piezoelectric shear-stress sensor which uses a thin piezoelectric film to generate a voltage proportional to an applied shear stress without additional moving parts. A differential-cell architecture is used to enhance selectivity to shear stress while canceling normal-stress sensitivity. The conceptual design, fabrication details, and experimental measurements of device sensitivity are presented. A finite element model is used to validate the device performance against measurements, and to provide insight into the potential and electric fields underlying the device concept. The potential for understanding device behavior and optimization through modeling is illustrated using finite element analysis results. The minimum detectable shear stress for the sensor is estimated to be 52.9 mPa √Hz−1 at 1.5 kHz.
Usefulness of Dilute Russell’s Viper Venom Clotting Time (DRVVT) for the Routine Monitoring of New Oral Anticoagulants

The new oral anticoagulants such as rivaroxaban (Bayer Healthcare) (R) apixaban (BMS/Pfizer) (A) and dabigatran (Boehringer Ingleheim) (D) have been approved to manage thrombotic and cardiovascular disorders in the US and Europe. Initially it was thought that these agents would not require monitoring at the approved dosages for specific indications. However, there have been reported bleeding complications with some of these agents suggesting that monitoring of these drugs to optimize therapy in some patient populations may be needed. The purpose of this study was to determine which of the available clotting assays could be used to determine the circulating concentration of these new oral anticoagulants in plasma. Materials: Citrated blood was drawn from ten donors and spun at 3000 rpm to obtain platelet poor plasma (PPP). The PPP was supplemented with A, R and D in a concentration range of 0-1.0 ug/ml. In addition, five plasma samples, for each agent, containing varying concentrations of either A, R or D were also blindly analyzed. The plasma samples were analyzed using PT/INR (Innovin, Seimens, Deerfield,IL), APTT reagent (Platelin, TCoag, Ireland) dilute Russell’s viper venom time (DRVVT) and DRVVT confirm (HemosIL, Instrumentation Laboratories (Bedford, MA). Results: In the PT and APTT assays a concentration dependent increase in clotting time was observed, however the slope of the line was flatter than with the slope observed in the DRVVT and DRVVT confirm assays. In both the DRVVT and DRVVT confirm assays the concentration-response curves for A,D and R were straight lines with a steep slope. Therefore, it was possible to extrapolate the concentrations of the unknown samples using both of these assays. When using the DRVVT and DRVVT confirm assays , there was a good correlation between the calculated concentration and the actual concentration in the range of 50-1000 ng/ml (r2=0.82). At concentrations Conclusions: These results suggest that the PT and APTT assays are not sensitive to the new oral anticoagulants and therefore cannot be used to determine the circulating concentrations of these agents. However, the dRVVT and DRVVT confirm assays are sensitive to A, D and R at concentrations > 50 ng/ml, therefore, A,D and R can be monitored by these assays. Both of these assays are commercially available and can be readily adapted to any automated instrument. These studies warrant clinical validation of these tests in patients populations treated with the newer oral anticoagulant drugs. Disclosures No relevant conflicts of interest to declare.
Estimating Market Power in Iranian Dairy Processing Industry with Dynamic Imperfect Competition Model

Kenya's dairy industry is the largest and one of the most successful in Africa. Private sector dominates the sector and milk production is majorly from small-scale farms. Despite the policies in place for the dairy inefficiencies and inadequacies in production and commercialization that differs from farmer to farmer. This study established the smallholder dairy farming typologies and their underlying determinants. The study obtained data from a cross section survey of farmers in Nyandarua and Nakuru counties of Kenya, where dairy activities are predominant. Data was collected from 380 smallholder dairy farmers identified using stratified random sampling. Data analysis was conducted by Principal Components Analysis and Cluster Analysis. Results of Principal Component Analysis showed that the smallholders’ dairy farming differed because of output, land, household assets and infrastructure components. Cluster analysis results indicated three significantly different smallholder dairy farming typologies, i.e., Low resource endowed and lower market oriented, moderate resource endowed and moderate market oriented and high resource endowed and high market oriented. The determinants of smallholder dairy typologies were land factors, years of dairy farming, stock of dairy animals kept, labor engaged, household income, farming assets, dairy output and consumption levels and costs of production. The study recommended policies that would increase access to land through land reform processes, financial accessibility and adequate infrastructure needed by the smallholder dairy farmers.
Time Trends and Characteristics of Prevalent Dementia among Patients Hospitalized for Stroke in the United States.

Background Little is known about how prevalent dementia rates among patients with stroke have evolved over the last decade or how this relationship varies by gender, race ethnicity, stroke type, or dementia type. We assessed time trends and demographic predictors of coexisting dementia in a large cohort of patients hospitalized for stroke. Materials and Methods Patient admission data between 1999 and 2012 were sourced from the National Inpatient Sample. Patient admission records were included in the retrospective analysis if they were diagnosed with ischemic or hemorrhagic stroke during admission. Predictors of dementia subtype were analyzed using unadjusted and adjusted multinomial logistic regression. Results Of 1,170,051 patients hospitalized for stroke between 1999 and 2012, 66,703 (5.7%) had a coexisting diagnosis of dementia. Female gender was associated with increased odds of Alzheimer's dementia (AD) (adjusted odds ratio [aOR] 1.15, 95% confidence interval [CI] 1.11-1.19) but decreased odds of both vascular dementia (VaD) (aOR .50, 95% CI .44-.58) and non-Alzheimer's–nonvascular dementia (aOR .79, 95% CI .79, 95% CI .74-.83). Relative to whites, African-Americans had higher odds of AD (aOR 1.25, 95% CI 1.18-1.32) and VaD (aOR 1.51, 95% CI 1.40-1.64). Similarly, Hispanics had increased odds of AD (aOR 1.40, 95% CI 1.30-1.50). Conclusions Rates of coexisting dementia among patients hospitalized for stroke in the United States have risen over the last decade. Prevalence of dementia among these patients varies by gender and race-ethnicity. Key demographic groups may need to be targeted to reduce disparities in dementia occurrence.
Feasibility of constructing multi-dimensional genomic maps of juvenile idiopathic arthritis

Background - Juvenile idiopathic arthritis (JIA) is one of the most common chronic conditions of childhood. Like many common chronic human illnesses, JIA likely involves complex interactions between genes and the environment, mediated by the epigenome. Such interactions are best understood through multi-dimensional genomic maps that identify critical genetic and epigenetic components of the disease. However, constructing such maps in a cost-effective way is challenging, and this challenge is further complicated by the challenge of obtaining biospecimens from pediatric patients at time of disease diagnosis, prior to therapy, as well as the limited quantity of biospecimen that can be obtained from children,particularly those who are unwell. In this paper, we demonstrate the feasibility and utility of creating multi-dimensional genomic maps for JIA from limited sample numbers. Methods - To accomplish our aims, we used an approach similar to that used in the ENCODE and Roadmap Epigenomics projects, which used only 2 replicates for each component of the genomic maps. We used genome-wide DNA methylation sequencing, whole genome sequencing on the Illumina 10x platform, RNA sequencing, and chromatin immunoprecipitation-sequencing for informative histone marks (H3K4me1 and H3K27ac) to construct a multi-dimensional map of JIA neutrophils, a cell we have shown to be important in the pathobiology of JIA . Results - The epigenomes of JIA neutrophils display numerous differences from those from healthy children. DNA methylation changes, however, had only a weak effect on differential gene expression. In contrast, H3K4me1 and H3K27ac, commonly associated with enhancer functions, strongly correlated with gene expression. Furthermore, although unique/novel enhancer marks were associated with insertion-deletion events (indels) identified on whole genome sequencing, we saw no strong association between epigenetic changes and underlying genetic variation. The initiation of treatment in JIA is associated with a re-ordering of both DNA methylation and histone modifications, demonstrating the plasticity of the epigenome in this setting. Conclusions These findings, generated from a small number of patient samples, demonstrate how multidimensional genomic studies may yield new understandings of biology of JIA and provide insight into how therapy alters gene expression patterns.
Spectrophotometric evidence for the formation of an Escherichia coli B B12s methyltransferase

Abstract Upon the addition of AMe to a 10 μM solution of B 12 enzyme in a FH 4 + DTT reducing system containing homocysteine, the absorption spectrum of the cobalamin chromophore changed from a B 12r type of spectrum (470–475 mμ peak) to a B 12s spectrum (maxima at 385 mμ and 460 mμ). These spectral changes began immediately after the injection of AMe at 37° and became maximal 6–12 minutes later. The original B 12r spectrum was restored after approximately 24 minutes but was converted back to a B 12s spectrum upon a second addition of exogenous AMe. In a parallel experiment the transient appearance of the B 12s -like absorption spectrum was correlated with the metabolism of methyl- 14 C-AMe, i. e., the transfer of methyl- 14 C groups to homocysteine. Steady-state catalysis of N 5 -methyl- 14 C-FH 4 -homocysteine transmethylation in the FH 4 + DTT reducing system was dependent on exogenous AMe and a non-enzymatic reduction of free hydroxy-B 12 to B 12s was not observed in this reducing system.
Modeling Subaqueous and Subaerial Muddy Debris Flows

AbstractDebris flows are notorious geohazards existing in both subaerial and subaqueous environments. They may cause catastrophic destructions to adjacent life and properties along their overriding...
Cost Effectiveness of the Oncotype DX Genomic Prostate Score for Guiding Treatment Decisions in Patients With Early Stage Prostate Cancer.

Abstract Objective To determine the cost-effectiveness of using the Oncotype DX Genomic Prostate Score (GPS), a 17-gene expression assay that can be used to inform decisions regarding active surveillance (AS) vs immediate treatment. Methods We developed a Markov model simulating 20-year outcomes for 65-year-old men with very low-, low-, or favorable intermediate-risk prostate cancer undergoing AS vs immediate treatment using GPS vs no testing. Utilities, costs, and probabilities were extracted from the literature and National Medicare Fee Schedules to determine incremental cost-effectiveness ratios (ICER) from a payer perspective. Results In the overall cohort, the ICER of GPS-guided therapy was $31,394 per quality-adjusted life-year (QALY). When stratified by risk group, the ICER was $25,343 per QALY in very low-risk, $28,911 per QALY in low-risk, and $39,695 per QALY in favorable intermediate-risk patients. On sensitivity analysis, findings were robust against a willingness-to-pay of $100,000 per QALY to variations in key model parameters, including the cost of annual management of AS, probability of exiting AS to treatment, cost of treatment, and probability of biochemical failure post-treatment. However, the cost-effectiveness was sensitive to small differences in the utility of AS and the utility of no evidence of disease post-treatment states. Conclusion The use of the GPS was cost-effective in guiding treatment decisions regarding AS vs immediate treatment. The cost-effectiveness was sensitive to small differences in the utilities of the AS and no evidence of disease post-treatment states, highlighting the importance of assessing patient preferences.