cssi/SciSciGPT-SciSciNet huggingface dataset:
Imatinib Mesylate for Patients (pts) with Hypereosinophilic Syndrome (HES) and Systemic Mastocytosis (SM): A Phase II Trial.

Abstract Imatinib is a potent inhibitor of the tyrosine kinases c-abl, c-kit, ARG, platelet-derived growth factor (PDGFR)-alpha and PDGFR-beta. We and others have reported on the clinical efficacy of imatinib in pts with HES and SM. We report here on 28 pts (16 HES, 12 SM) treated in a phase II study of imatinib. Pts with HES received imatinib at a starting dose of 100 mg daily with escalation to 400 mg if no response after 1 month (mo). Pts with SM were started at a dose of 400 mg with possible escalation to 800 mg. The median age was 52 years (yrs) (26–77 yrs). All pts had signs and symptoms of end-organ involvement with 10 (83%) of 12 pts with SM having skin involvement. 15 (53%) of 28 pts had received prior therapies. Imatinib was started within 34 mo from diagnosis (3–162 mo). Prior to the start of imatinib, the median eosinophil count for pts with HES was 2.2 x109/L (0.5–7 x109/L) and the median percentage of eosinophils in the bone marrow was 19% (5%–28%). 2 of the pts with SM had increased eosinophils, 9 pts have been evaluated for serum tryptase level; this was increased in 5 (0 HES, 5 SM). 6/16 (37%) pts with HES responded: 3 achieved a complete remission (CR) (defined by the disappearance of eosinophilia and signs and symptoms of disease) and 3 a partial response (PR) (defined by the reduction of eosinophilia and organomegaly by > 50%). Two pts (1 CR, 1 PR) required dose escalation to 400 mg. The median duration of response was 11+ mo (1+ to 21+). One patient died in CR at 18 mo, 1 was lost to follow-up after 1 mo in CR; 2 have ongoing response (1 PR, 1 CR) 15+ and 21+ mo, respectively; and 2 lost PR after 3 and 10 mo, respectively despite dose escalation. 7/12 pts with SM (58%) responded. Six pts achieved a major response (MR) (defined by the complete resolution of at least one clinical finding and no progression in other clinical findings): 4 CRs, 1 PR (defined by the incomplete regression of one or more clinical finding(s) without complete regression and without progress in other clinical findings) (Leuk Res 27:635,2003). One pt (MR) required imatinib escalation to 800 mg. The median duration of response was 14+ mo (7+ to 36+). At the time of response, 2 pts had normalized their tryptase levels. Only one pt has lost response (PR) after 9 mo. Overall, treatment was well tolerated. 2 pts experienced grade 3 diarrhea; one of them required imatinib dose reduction. We conclude that therapy with imatinib for patients with HES and SM appears effective and well tolerated.
Enhancing Magnetic Functionality with Scandium: Breaking Stereotypes in the Design of Rare Earth Materials

Replacement of strongly magnetic gadolinium with weakly magnetic scandium unexpectedly enhances ferromagnetic interactions in (Gd1–xScx)5Ge4. Based upon this counterintuitive experimental finding we demonstrate the unique role 3d1 electrons of scandium atoms play in mediating magnetic interactions between the gadolinium atoms from the neighboring layers in the Sm5Ge4-type crystal lattice. Scandium substitutions at and below 20% rapidly increase the Curie temperature, TC, of the Gd5Ge4 parent, eliminate both the kinetic arrest and hysteresis, and drastically improve reversibility of the first-order magnetostructural transformation at TC. In agreement with first-principles predictions, higher than 20% Sc leads to the formation of a closely related Pu5Rh4-type structure where the first-order magnetostructural transformation is replaced by a conventional second-order ferromagnetic ordering that remains accompanied by a continuous rearrangement of the crystal lattice. Comparison of two materials with similar s...
Open Tubular Heterogeneous Enzyme Reactors in Continuous-Flow Analysis

Publisher Summary This chapter discusses the development, properties, and applications of narrow bore tubes, with immobilized enzymes at the inner wall, which are used in continuous-flow analyzers of the type manufactured by Technicon Corporation. Such tubular wall reactors are appropriately termed open tubular heterogeneous enzyme reactors (OTHER). They are also described, among others, by names such as bound enzyme coils or enzyme tubes. Several types of such enzymic appliances are commercially available for continuous-flow biochemical analyzers. The use of enzymes as analytical tools for the routine analyses of a variety of compounds is based on their unique ability to catalyze reactions specifically and efficiently under generally mild conditions. These attributes have led to the development of numerous analytical methods that utilize the catalytic properties of enzymes. Nevertheless, the widespread employment of enzymes is impeded by their instability in solution and the generally high cost of enzyme reagents.
Light Activation of Calcein Inhibits Vesicle Release of Catecholamines

Calcein, a fluorescent fluid phase marker, has been used to track and visualize cellular processes such as synaptic vesicle fusion. It is also the fluorophore for live cells in the commonly used Live/Dead viability assay. In pilot studies designed to determine fusion pore open size and vesicle movement in secretory cells, imaging analysis revealed that calcein reduced the number of vesicles released from the cells when stimulated with nicotine. Using amperometry to detect individual vesicle release events, we show that when calcein is present in the media, the number of vesicles that fuse with the cellular membrane is reduced when cells are stimulated with either nicotine or high K+. Experimentally, amperometric electrodes are not undergoing fouling in the presence of calcein. We hypothesized that calcein, when activated by light, releases reactive oxygen species that cause a reduction in secreted vesicles. We show that when calcein is protected from light during experimentation, little to no reduction of...
Species of Biocapital, 2008, and Speciating Biocapital, 2017

Many scholars in science studies have sought to theorize the conjunction of capitalism and biotechnology. A variety of terms have been forwarded to name how ‘life’ in the age of genomics, stem cell research, and reproductive technology has become enmeshed in market dynamics, and no term has become so prominent as biocapital. In this chapter, we classify articulations of this concept, arguing that definitions center on two transformations: in biotic substance and in economic speculation and sentiment. In experimenting with ways of representing diverse species of biocapital, we offer a timeline of intellectual history and a genealogy of scholarship. We conclude with an update on where biocapital conversations have headed since 2008, when the body of this chapter was originally composed.
Subpectoral Biceps Tenodesis With PEEK Interference Screw: A Biomechanical Analysis of Humeral Fracture Risk.

Purpose To quantify the torsional load to fracture for subpectoral biceps tenodesis with interference screw fixation. Methods We randomized 28 specimens from 14 matched-pair full-length humeri (mean age, 55.3 years) into 3 groups: (1) empty ream group (ERG), (2) screw-only group (SOG), and (3) screw–plus–biceps tendon group (SBG). In each group, 1 humerus of each matched pair was prepared according to group allocation and the contralateral humerus remained intact as a control. In the ERG, an 8-mm unicortical hole was reamed 1 cm proximal to the inferior border of the pectoralis major tendon insertion; in the SOG, the humerus was filled with an 8-mm × 12-mm PEEK (polyether ether ketone) screw; and in the SBG, the humerus was filled with a PEEK screw and the cadaveric long head of the biceps tendon. Humeri were tested under torsional displacement at a rate of 1°/s until fracture. Maximum torque, energy to maximum torque, and linear stiffness were used to assess humerus strength. Results Compared with contralateral intact specimens, the maximum torque to fracture was reduced by 28% in the ERG ( P = .005), 30% in the SOG ( P = .014), and 20% in the SBG ( P = .046). Energy to maximum torque was similarly reduced in the ERG ( P = .007), SOG ( P = .023), and SBG ( P = .049). Stiffness was increased by 4% in the ERG ( P = .498), 9% in the SOG ( P = .030), and 4% in the SBG ( P = .439). Conclusions Drilling an 8-mm unicortical hole in zone 3 of the bicipital tunnel for open subpectoral biceps tenodesis reduces the torsional load to humeral fracture up to 28% at time 0. The addition of a PEEK tenodesis screw alone reduced the maximum torque by 30%, and the addition of a screw with the long head of the biceps tendon reduced the maximum torque by 20%. The total load to fracture was reduced in all settings. Stiffness was not significantly different for the ERG and SBG, but stiffness was significantly higher for the SOG compared with the intact matched humeri at time 0. Clinical Relevance When performing a biceps tenodesis, humeral fracture susceptibility is increased with an applied torsional load at time 0. Thus providers must be aware of this reduced integrity when a subpectoral biceps tenodesis is used.
The alphabet soup of agreements.

What you need to know about the paperwork your institution requires when disclosing and commercializing your research.
Primary Headache Induced by the Valsalva Maneuver Is Associated with Cerebral Hyperemia due to Autoregulatory Failure. (P2.158)

Objective: To evaluate mechanisms of primary headaches triggered by the Valsalva maneuver. Background: Mechanisms underlying the Valsalva-related headache which affects 1% of population, are poorly understood. Design/Methods: This retrospective study evaluated patients with unexplained straining-related headaches. The assessments included the Valsalva maneuver with continuous monitoring of heart rate, blood pressure (BP) and cerebral blood flow (CBF) velocity in the middle cerebral artery using transcranial Doppler. Patients with symptoms reproduced by the Valsalva maneuver (symptomatic group), were compared to asymptomatic controls. ANOVA was used for group comparisons. Results: The symptomatic group (N=17, age=45.8±12.5 (mean±sd), men/woman=2/15) was matched with 17 asymptomatic patients for age, gender and BP. Baseline CBF velocities and BP were similar between the groups: systolic CBF velocity (symptomatic/controls: 112.1±22.0/110.6±13.1 cm/s, p=0.81), mean BP (symptomatic/controls: 91.2±9.1/90.7±10.7 mmHg, p=0.86). Symptoms (uniformly described as “head is going to explode”) occurred during the post straining period (phase 4) of the Valsalva maneuver and lasted several seconds. Markedly elevated systolic CBF velocities during phase 4 of Valsalva maneuver were observed in symptomatic group (201.1±6.8 cm/s) but not in controls (124.9±15.7 cm/s), p Conclusions: Elevated CBF velocities triggered by the Valsalva maneuver in symptomatic group indicate reactive cerebral hyperemia during the poststraining period (the phase 4) which is due to the excessive vasodilation. Hyperemia may contribute to explosive headache and dizziness. Exaggerated vasodilation of cerebral vessels provoked by the Valsalva maneuver is suggestive of cerebral autoregulation failure. Clinical efficacy of indomethacin, a cerebral vasoconstrictor, in prevention of the Valsalva-related headaches supports these mechanisms. Disclosure: Dr. Novak has nothing to disclose.
An Electrically Actuated Liquid-Metal Gain-Reconfigurable Antenna

A tunable liquid-metal antenna demonstrating gain reconfigurability is presented. This antenna uses a reconfigurable stub made with the liquid metal Galinstan. Using continuous electrowetting, a 60 Hz signal with an amplitude of 1 Vpp and 75% duty cycle can actuate the Galinstan continuously along a channel, tuning the stub length and antenna gain. Zero external power is required to maintain the position of the slug. The 5 GHz antenna offers more than 10 dB of analog gain tuning, from −5.90 to 4.43 dB.
Pitfalls of CT Perfusion Imaging in Acute Ischemic Stroke: A Case Series (P3.206)

Objective: To demonstrate a potential significant pitfall in reliance on computed tomography perfusion (CTP) imaging to estimate core infarct and its impact on decisions regarding mechanical thrombectomy (MT). Background: Dynamic perfusion studies, including CTP, are commonly utilized in the evaluation of acute ischemic stroke. Particularly, CTP is used to assess ischemic penumbra in order to determine the potential utility of MT in cases of large vessel occlusion (LVO). CTP is susceptible to multiple technical and diagnostic challenges, and there remains disagreement in the literature regarding its ability to accurately and consistently assess core infarct. In spite of this, CTP along with CTA is heavily relied upon in decisions regarding eligibility for acute intervention by MT. Design/Methods: Case Series Results: We present a case series of three patients in which CTP demonstrated an overestimated core infarct with appropriate clinical correlate, while follow up MRI (DWI and FLAIR) showed a much smaller affected territory. In two cases, the patients were not taken for MT due to unfavorable CTP in spite of being within the FDA approved window of 6–8 hours. Conclusions: There are currently no guidelines regarding reliance on CTP in decisions regarding MT and whether patients presenting within the FDA approved therapeutic time window should be exempt from this imaging, which could potentially make them ineligible for the procedure. Increasing data suggests that MT is safe up to a certain volume of infarct, and despite increased incidence of hemorrhagic conversion in recanalized core infarct, overall functional outcome is better than those who were not recanalized. This case series demonstrates that further research is needed to help define appropriate utilization of this technology. Until then, cautious and judicious use of these imaging modalities is recommended. Disclosure: Dr. Bacharach has nothing to disclose. Dr. Niazi has nothing to disclose. Dr. Ermak has nothing to disclose.
No Way Out: Dealing with the Consequences of Changes in Family Composition

A review of four decades of trend data from the decennial census shows that marriage rates have declined and nonmarital birth rates have increased. As a result, the share of children living in female-headed families has increased greatly. Research shows that children in female-headed families are more likely to live in poverty, have suboptimal development and have behavioral problems than children reared by their married parents. Because the trend data provide little reason to think any of the trends in family composition will change in the near future, the chapter reviews evidence on policies that might reduce the growth of female-headed families and the policies that can support single-parent families and their children. The review shows that interventions to reduce the growth of female-headed families are mostly ineffective. It follows that reforms to better support female-headed families and their children, many of which are proposed, are of vital national interest.
Relation of Living in a “Food Desert” To Recurrent Hospitalizations in Patients With Heart Failure

Food deserts (FD), low-income areas with low access to healthful foods, are associated with higher burden of cardiovascular risk factors. Few studies have examined the impact of FD on clinical outcomes in heart failure (HF). FD status was assessed in 457 HF patients (mean age 55.9 ± 12.5 years; 50.3% Black) using the Food Desert Research Atlas. The Andersen-Gill extension of Cox model was used to examine the association of living in a FD with risk of repeat hospitalization (all-cause and HF-specific). Patients living in a FD were younger (p = 0.01), more likely to be Black (p <0.0001), less educated (p = 0.003), and less likely to have commercial insurance (p = 0.003). During a median follow-up of 827 (506, 1,379) days, death occurred in 60 (13.1%) subjects, and hospitalizations occurred in 262 (57.3%) subjects. There was no difference in the risk of death based on FD status. The overall frequency of all-cause (94.1 vs 63.6 per 100 patient-years) and HF-specific (59.6 vs 30.5 per 100 patient-years) hospitalizations was higher in subjects who lived in a FD. After adjustment for covariates, living in a FD was associated with an increased risk of repeat all-cause (hazard ratio 1.39, 95% confidence interval 1.19 to 1.63; p = 0.03) and HF-specific (hazard ratio 1.30, 95% confidence interval 1.02 to 1.65; p = 0.03) hospitalizations. In conclusion, patients living in a FD have a higher risk of repeat all-cause and HF-specific hospitalization.
Genomic Characterization of the Zinc Transcriptional Regulatory Element Reveals Potential Functional Roles of ZNF658.

The zinc transcriptional regulatory element (ZTRE) is a newly reported binding motif for human zinc finger protein ZNF658, which alters gene expression in response to cellular zinc. The ZTRE has two nucleotide components—the palindromic flanking pairs and the bridging “N” bases between these flanks that range in number from 0 to 100. There are 12 pairs of ZTRE flanks (designated A-L). Three thousand five hundred twenty-five genes contain one or more ZTREs − 1000 to + 200 bp from their transcriptional start site (TSS). ZTRE-E is observed at a greater frequency, and ZTRE containing 25 bridging bases are less frequent, within − 200 bp from the TSS. The genes with ZTREs in this range are enriched in processes that may compensate zinc deficiency, while other genes with ZTREs outside this range are enriched in transcriptional activation processes. The division of ZTREs into two groups may imply a dual role of ZNF658, similar to the homologous yeast protein Zap1, via binding to low or high affinity sequences dependent upon cellular zinc. The KLF/Sp1-family binding motif is prevalent within the ZTRE “N” bridging bases, suggesting ZNF658 may compete with Sp1-like transactivators to suppress transcription.
Results from the randomized controlled IHOPE trial suggest no effects of oral protein supplementation and exercise training on physical function in hemodialysis patients.

Few long-term studies have assessed whether changes in both diet and exercise can improve the health and quality of life (QOL) of hemodialysis (HD) patients. Here we examined whether 12 months of intradialytic protein supplementation and endurance exercise improves physical function, risk of cardiovascular disease (CVD), and QOL in HD patients in a randomized controlled trial (RCT). A total of 138 HD patients (average age 58 years) were assigned for 12 months to control, intradialytic protein, or protein plus exercise groups. The protein and protein plus exercise groups consumed an oral protein supplement (30 grams of whey) three days/week during dialysis. The protein plus exercise group cycled for 30-45 minutes during dialysis treatment. The primary outcome was change in physical function at 12 months, assessed by a shuttle walk test. Secondary outcomes included arterial stiffness, blood pressure, body composition, muscle strength, markers of nutritional status, and QOL. Assessments were conducted at baseline, 6 and 12 months. In total, 101 patients completed the intervention. There were no significant differences between groups in shuttle walk test performance from baseline to 12 months. There were trends for improvements in some secondary measures of physical function and strength in the protein and protein plus exercise groups at six or 12 months, but these did not reach statistical significance. Thus, our trial did not demonstrate significant improvements in markers of physical function, risk of CVD or QOL after one year of intradialytic oral OPS and aerobic exercise training. More comprehensive lifestyle management may be needed to uncover robust improvements in the health and QOL of HD patients.
Translation of Standardized Patient Encounter Performance and Reflection to Clinical Practice

Context Standardized patient (SP) encounters have been incorporated into many healthcare education programs, including professional athletic training programs, yet there is little exploration about...
Exploration of Designability of Proteins Using Graph Features of Contact Maps: Beyond Lattice Models

Highly designable structures can be distinguished based on certain geometric graphical features of the interactions confirming the fact that the topology of a protein structure and its residue-residue interaction network are important determinants of its designability. The most designable structures and poorly designable structures obtained for sets of proteins having the same number of residues are compared, and it is shown that the most designable structures predicted by the graph features of the contact diagrams are more densely packed whereas the poorly designable structures are more open loop type structures or structures that are loosely packed. Interestingly enough, it can also be seen that these highly designable structures obtained are also common structural motifs found in nature.
Universal School Meals and Associations with Student Participation, Attendance, Academic Performance, Diet Quality, Food Security, and Body Mass Index: A Systematic Review

The school environment plays an important role in children’s diets and overall health, and policies for universal free school meals have the potential to contribute to positive child health outcomes. This systematic review evaluates studies examining the association between universal free school meals and students’ school meal participation rates, diets, attendance, academic performance, and Body Mass Index (BMI), as well as school finances. The search was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). A search for studies published in economically developed countries published through December 2020 was performed in PubMed, Education Resources Information Center (ERIC), Thomson Reuters’ Web of Science, and Academic Search Ultimate, followed by examining the references in the resultant literature. A total of 47 studies were identified and the Newcastle-Ottawa Scale (NOS) was applied to assess bias. Nearly all studies examining universal free school meals found positive associations with school meal participation. Most studies examining universal free school meals that included free lunch found positive associations with diet quality, food security, and academic performance; however, the findings of studies examining only universal free breakfast were mixed. Research findings were similarly mixed when examining attendance as an outcome. Concerns about adverse outcomes on student BMI were not supported by the literature; in fact, several studies detected a potentially protective effect of universal free school meals on BMI. Research examining the impact of universal free meals on school finances was limited, but suggest that lower-income school districts in the U.S. may have positive financial outcomes from participation in universal free school meal provisions. Additionally, providing free meals to students may be associated with improved household incomes, particularly among lower-income families with children. Further research is needed to examine the financial implications of universal free meals for both school districts and families. Overall, universal free school meals may have multiple benefits for students and countries should consider universal free school meal provisions with strong nutrition guidelines. (PROSPERO registration: CRD42020221782).
An Application of Homogeneous Anisotropic Hardening Model to the Prestrained Hole-Expansion Experiment

In this work, the plastic anisotropy of AA6022-T4 in hole-expansion is investigated focusing on prestraining effect, and its numerical solution is predicted by Homogeneous Anisotropic Hardening (HAH) model combined with an anisotropic yield function. For the prestraining, the material is subjected to a prestrain of 8% in uniaxial tension in the RD. Then, hole-expansion is conducted in a fully instrumented hydraulic press with a flat-headed punch. In both experiments, Digital Image Correlation (DIC) is used, to confirm the prevalence of uniaxial loading in the prestraining step and to measure thickness strain in the hole-expansion. The results show that the plastic anisotropy is manifested as a non-axisymmetric strain distribution around the hole. The prestraining, leading to non-proportional loading, changes the location of failure from ~45° to RD. The simulation shows the current version of HAH model is limited in capturing the thickness contours and the failure location.
Residential Water Meters as Edge Computing Nodes: Disaggregating End Uses and Creating Actionable Information at the Edge.

We present a new, open source, computationally capable datalogger for collecting and analyzing high temporal resolution residential water use data. Using this device, execution of water end use disaggregation algorithms or other data analytics can be performed directly on existing, analog residential water meters without disrupting their operation, effectively transforming existing water meters into smart, edge computing devices. Computation of water use summaries and classified water end use events directly on the meter minimizes data transmission requirements, reduces requirements for centralized data storage and processing, and reduces latency between data collection and generation of decision-relevant information. The datalogger couples an Arduino microcontroller board for data acquisition with a Raspberry Pi computer that serves as a computational resource. The computational node was developed and calibrated at the Utah Water Research Laboratory (UWRL) and was deployed for testing on the water meter for a single-family residential home in Providence City, UT, USA. Results from field deployments are presented to demonstrate the data collection accuracy, computational functionality, power requirements, communication capabilities, and applicability of the system. The computational node’s hardware design and software are open source, available for potential reuse, and can be adapted to specific research needs.
Rates and patterns of clonal oncogenic mutations in the normal human brain.

While oncogenic mutations have been found in non-diseased, proliferative non-neural tissues, their prevalence in the human brain is unknown. Targeted sequencing of genes implicated in brain tumors in 418 samples derived from 110 individuals of varying ages, without tumor diagnoses, detected oncogenic somatic single-nucleotide variants (sSNVs) in 5.4% of the brains, including IDH1 R132H. These mutations were largely present in subcortical white matter and enriched in glial cells, and surprisingly, were less common in older individuals. A depletion of high-allele frequency sSNVs representing macroscopic clones with age was replicated by analysis of bulk RNAseq data from 1,816 non-diseased brain samples ranging from fetal to old age. We also describe large clonal copy number variants, and that sSNVs show mutational signatures resembling those found in gliomas, suggesting that mutational processes of the normal brain drive early glial oncogenesis. This study helps understand the origin and early evolution of brain tumors.
Indications for Adult Spinal Deformity Surgery

Shifting demographics and aging populations have resulted in a rise in adult spinal deformity (ASD). ASD refers to abnormal spinal curvature in the coronal, axial, or sagittal planes in patients over the age of 18. A recent publication found that the prevalence of ASD ranges from 2 % to 32 % in the general population but exceeds 60 % for adults greater than 60 years of age [1]. With a simultaneous shift in expectations for quality of life (QOL), the demand for treatment of ASD has dramatically increased. ASD is most commonly caused by untreated adolescent idiopathic scoliosis, adult-onset degenerative scoliosis, or primary sagittal imbalance [2]. While some cases of ASD can be managed with conservative care and nonoperative procedures, many ASD cases require surgical intervention. Unlike adolescent idiopathic scoliosis (AIS), there is no widely accepted classification system that provides guidelines for the surgical treatment of ASD [3]. Therefore, the decision to undergo surgical treatment of ASD must carefully consider clinical symptoms, radiographic parameters, coexisting medical comorbidities, and the patient’s physiologic status. The potential benefits and risks associated with the surgical treatment of ASD must also factor into the treatment decision. This chapter provides an overview of current indications for the surgical treatment of ASD and highlights the significance of using a combination of both clinical symptomatology and radiographic imaging to propose the optimal treatment plan for patients with ASD.
Postmenopausal Breast Surveillance

Publisher Summary Breast cancer is the most common cancer of postmenopausal women. The incidence of breast cancer is more than twice the combined incidence of cervical, endometrial, and ovarian cancer in this age group. At menopause, with its subsequent estrogen deficiency, the breasts begin to atrophy; the glandular tissue continues to diminish and be progressively replaced by fat; benign breast diseases, including neoplasms, subside; and tenderness and palpable nodularity clear. Estrogen replacement therapy (ERT) can reverse or delay these breast-aging changes in some cases. However, the incidence of cancer continues to rise with advancing age. Annual screening mammography is the most important tool in the surveillance of the breasts of postmenopausal women. To detect small cancers, which have an excellent prognosis when treated, physicians who care for postmenopausal women should obtain annual mammograms for and perform complete annual breast examinations on all their patients.
Molecular Cloning and Characterization of a Mouse Ouabain Resistance Gene: A Genetic Approach to the Analysis of the Na+, K+-ATPase

Publisher Summary This chapter focuses on the experimental approach that uses DNA-mediated gene transfer for isolating the DNA sequence coding for the Na+,K+-ATPase subunit responsible for ouabain resistance. The plasma membrane Na+ ,K+-ATPase is the enzymatic activity responsible for the maintenance of the high internal K+ and low internal Na+ concentrations characteristic of most living cells. The ability to isolate the gene coding for the ATPase represents an important technical step toward elucidating the primary structure of the Na+,K+-ATPase. The approach considered for isolating the Na+,K+-ATPase gene is essentially based on three main considerations: (1) the cardiac glycoside ouabain is a specific inhibitor of the Na+,K+-ATPase and cell lines of different species vary considerably with respect to ouabain sensitivity, (2) ouabain-resistant mutants exhibit decreased affinity for ouabain, and (3) ouabain resistance can be transferred from ouabain-resistant to ouabain-sensitive cells by direct DNA transfer, metaphase chromosome transfer, or by microcell fusion. This approach takes the advantage of the species-specific differences in ouabain sensitivity in order to develop a gene transfer and selection system for isolating the mouse gene responsible for ouabain resistance. The chapter outlines the methodologies used to isolate the ouabain resistance gene and explores how this DNA sequence can be used to facilitate genetic studies of the Na+,K+-ATPase and the ouabain resistance locus.
Galactose regulation in Saccharomyces cerevisiae: The enzymes encoded by the GAL7, 10, 1 cluster are co-ordinately controlled and separately translated

Abstract The enzymes for galactose metabolism in Saccharomyces cerevisiae are encoded by three tightly linked genes. Data presented in this paper show that, in contrast to enzymes encoded by other gene clusters in yeast, these three enzymes are translated as separate polypeptides. First, two of the enzymes encoded by the cluster, galactokinase and uridylyl transferase. purified to near homogeneity, are separate polypeptides. Second, no precursor polypeptide-containing sequences common to both these enzymes is detectable in extracts from galactose-induced yeast cells. Third, no partial or absolute polarity of expression of the enzymes is observed in strains containing nonsense mutations in any of the genes of the cluster. Expression of the three galactose metabolic enzymes is co-ordinate, both during induction and during steady-state synthesis. This is true both for wild-type yeast strains and for strains carrying the long-term galactose adaptation mutation, gal 3. In GAL 3 + strains mutations within the galactose gene cluster have no effect on this co-ordinate expression. However, in gal 3 − strains, mutations in any of the genes of the cluster completely eliminate expression of the other two genes. These results suggest that the GAL 3 gene product is responsible for inducer synthesis and that the actual inducer is an intermediate in galactose metabolism.
Acoustic component and social context of the wing display of the walnut fly Rhagoletis juglandis

Courtship signaling via wing vibration, accompanied by sound production, has been reported in several species of tephritids. In this large family of flies, sound communication as well as complex courtship displays appears to be restricted to species with lekking mating systems (i.e., Mediterranean fruit fly, Anastrepha and Dacus species). In contrast, in tephritid species with resource-defense mating systems, such as species in the genus Rhagoletis, little or no courtship behavior, acoustical or otherwise, has been described. Wing displays in Rhagoletis species have been considered to play a visual role. This study describes a distinctive wing display performed by males of the walnut fly, Rhagoletis juglandis. Laboratory experiments and field observations demonstrate that the male wing display plays a role in courtship. We used sound and vibration detectors to record the signals produced by this wing display. Using a combination of techniques, we were able to record both the very low-frequency vibration and its accompanying airborne infrasound (12–22 Hz) produced by the males.
Expression and processing of mouse proopiomelanocortin in bovine adrenal chromaffin cells. A model system to study tissue-specific prohormone processing

Many neuroendocrine precursor proteins, such as proopiomelanocortin (POMC), are cleaved in a tissue specific manner at distinct pairs of basic amino acids. Elucidating the specificity of the prohormone endoprotease(s) is essential to understanding cleavage specificity. However, isolation of these enzymes has been difficult, due to the inability to distinguish authentic maturation enzyme from the many other trypsin-like activities present in tissue homogenates. Recently, a "signature" of the insulin cell endoprotease(s) was defined in vivo by assessing the processing of a series of mutant cleavage sites in a model prohormone, mouse POMC (mPOMC) (Thorne, B. A., and Thomas, G. (1990) J. Biol. Chem. 265, 8436-8443. To investigate mechanisms of tissue-specific processing, we sought to identify the endoprotease signature of a cell having a processing phenotype distinct from insulinoma cells. In this report, the cleavage site specificity of the endoprotease(s) expressed in bovine adrenal chromaffin cells is examined. High levels of mPOMC (1.6 pmol/10(6) cells) were expressed in these cells using a vaccinia virus vector, and the precursor was targeted to the regulated secretory pathway. Analysis of POMC-derived peptides revealed that chromaffin cells processed the prohormone to a set of peptides highly similar to anterior pituitary corticotrophs, including adrenocorticotropin hormone (ACTH) and beta-lipotropin, gamma-lipotropin, and beta-endorphin. This processing contrasted with the pattern of cleavage site utilization in Rin m5F insulinoma cells, which more closely resembled that of the intermediate pituitary melanotrophs. However, the processing preference for the sequences of pairs of basic amino acids (as tested using the entire series of mutant cleavage sites; -LysArg- (native), -ArgArg-, -ArgLys-, -LysLys-, -HisArg-, -MetArg- at the ACTH/beta-lipotropin junction and -LysLys- (native), -LysArg-, -ArgArg-, -ArgLys- in beta-endorphin) was the same in both insulinoma and adrenal chromaffin cells, suggesting recognition and cleavage by similar enzymes in both cell types. The cell-specific processing of mPOMC may thus result from expression of a common core set of processing enzymes and factors unique to each cell type affecting the enzyme accessibility to precursor cleavage sites.
SYNTHESIS AND DEGRADATION OF POLY-β-HYDROXYBUTYRIC ACID IN CONNECTION WITH SPORULATION OF BACILLUS MEGATERIUM

Slepecky, Ralph A. (Northwestern University, Evanston, Ill.), and John H. Law. Synthesis and degradation of poly-beta-hydroxybutyric acid in connection with sporulation of Bacillus megaterium. J. Bacteriol. 82:37-42. 1961.-The production of poly-beta-hydroxybutyrate has been followed in Bacillus megaterium, a sporulating strain, and B. megaterium strain KM, a nonsporulating strain, by an improved assay procedure and by the use of C(14)-acetate. The production of polymer in the KM strain follows the growth curve very slowly and reaches a peak at the time the cells are entering the stationary phase of growth. Slow utilization of polymer follows. When the sporulating strain is grown under conditions favorable for polymer production, no spores are formed; polymer production and utilization follow kinetics similar to those observed with asporogenous strains. When the sporulating strain is grown under conditions unfavorable for polymer production but favorable for sporulation, less polymer is produced and peak production occurs during the log phase of growth. Rapid utilization of the polymer precedes sporulation. If the medium is made favorable for polymer production by the addition of glucose and acetate and vigorous aeration conditions are used, sporulation can be obtained after good polymer production and subsequent utilization.
Simulation of Capacitor Charging Power Supplies

Electrical equipment such as flash lamps and lasers require short but intense bursts of energy which can be obtained from rapidly discharging a capacitor. The energy released to this equipment must first be supplied to the discharge capacitor by a capacitor charging power supply (CCPS). This paper develops a simplified model for a particular CCPS topology which gives insight into some of the problems faced by designers of these circuits.
Fracture Between Self-Assembled Monolayers

While it is intuitive that molecular interaction should correlate to the mechanical properties of a material, it has only recently become possible to make the measurements necessary to trace the effects of molecular interaction across length scales to properties at the level of the material. The utility of “classical” polymeric adhesives is underscored by their widespread use in primary structural applications ranging from aerospace, automotive, and civil structures to biomedical implants and microelectronic devices. To date, the vast majority of the efforts directed toward improving the strength and durability of adhesives have been largely empirical. At the same time, the drive towards miniaturization in MEMS and NEMS devices and nano patterning means that an understanding of adhesion and fracture at smaller and smaller scales needs to be developed. This actually provides an opportunity to decrease the amount of empiricism as the number of variables is essentially decreased.
Tracking performance with advanced and delayed visual displays.

Human operator performance in continuous pursuit tracking when the stimulus either disappeared prior to the appropriate response time or appeared subsequently to that time was investigated. Tracking was one-dimensional, the stimulus appeared to vary randomly, and feedback of results wasn't provided. The stimulus, consisting of the sum of three low-frequency sine waves, appeared on recording paper tape, moving at 1.0 cm/sec. Masks hid the display in steps up to 1.0 secs, before or 0.5 secs. after the position of a manually-controlled pointer. Timing performance was measured by the peaks of cross-correlations of stimulus/response data pairs which had been successively shifted in time. Tracking performance was measured by RMS error. Timing was increasingly too early for advanced displays but followed closely the actual appearance time of delayed displays. RMS tracking error increased with increasingly advanced and delayed displays. Practice effects were negligible.
Retinoic Acid Modulates Hepatic Iron Homeostasis in Rats by Attenuating the RNA-Binding Activity of Iron Regulatory Proteins

Vitamin A deficiency has been widely associated with perturbations of iron homeostasis, a consequence that can be reversed by retinoid supplementation. Despite the numerous studies that demonstrate an interaction between these 2 nutrients, the mechanistic basis for this relation has not been well characterized. Because iron regulatory proteins (IRP) have been established as central regulators of iron homeostasis, we investigated the potential role of IRP in the regulation of iron homeostasis under conditions of vitamin A deficiency and supplementation with all-trans-retinoic acid (atRA). Rats were fed a control diet or a diet deficient in either vitamin A or iron or both micronutrients. Four parallel groups of rats were supplemented with atRA daily (30 micromol/kg body weight) during the final week of this study. As expected, iron-deficient (-Fe) rats exhibited a decrease in hepatic nonheme iron levels and a subsequent increase in IRP RNA-binding activity, resulting in diminished ferritin abundance. Interestingly, atRA supplementation inhibited the increase in IRP RNA-binding activity in -Fe rats to a level that was not significantly (P = 0.139) different from control values, and it partially restored ferritin abundance. This inhibition of IRP RNA-binding activity by atRA supplementation was also associated with a 40% reduction in transferrin receptor abundance. Taken together, these results indicate that IRP represent a mechanistic link between vitamin A and the regulation of iron homeostasis, a key finding toward further understanding this important nutrient-nutrient interaction.
Atrial fibrillation and stroke: four treatment controversies.

Atrial fibrillation is an important cause of disabling ischemic stroke, and adjusteddose warfarin is highly effective for prevention and remains the therapy of choice for high-risk patients. Ximelagatran, a novel oral anticoagulant, is clinically equivalent to warfarin for preventing stroke in patients with atrial fibrillation, but concerns about potential hepatic toxicity have precluded US Food and Drug Administration approval. Many patients with low-risk atrial fibrillation do not benefit substantially from anticoagulation, and these patients can be reliably identified using the CHADS2 stroke risk stratification scheme. A target International Normalized Ratio (INR) range of 2 to 3 is usually recommended for anticoagulation of patients with atrial fibrillation, but a lower INR target (2, range 1.6–2.5) may be a reasonable benefit/risk trade-off for primary prevention in those aged older than 75 years. Adding aspirin to adjusted-dose anticoagulation increases bleeding (including central nervous system bleeding), is of uncertain value, and should only be done after careful consideration and with vigorous efforts to control blood pressure.
The relationship between characteristics of sexual abuse and dissociative experiences

Childhood sexual abuse has been associated with adult dissociative symptomatology. The purpose of this study was to examine the relationship between specific characteristics of sexual abuse and dissociative experiences in adulthood. Fifty-six female inpatients with a history of physical abuse and severe sexual abuse reported on their history of abuse and dissociative experiences. A logistic regression that controlled for physical revictimization showed that sexual abuse by a greater number of different sex abuse offenders was significantly related to an elevated level of dissociation. In exploring how many sex abuse offenders are associated with dissociative experiences, a logistic regression revealed a significant relationship between four or more sex abuse offenders and greater dissociative symptomatology. The reported age of onset of the sexual abuse was not a significant predictor of dissociation when sexual revictimization was included in the analysis. These findings suggest that severely traumatized patients with a history of multiple sex abuse offenders are highly likely to use dissociation as a primary psychological defense. The implications of the study are discussed.
Neurotherapy and the Challenge of Empirical Support: A Call for a Neurotherapy Practice Research Network

This paper summarizes a review of the empirical support for neurotherapy (NT) as a treatment for psychological and neurological disorders according to the criteria for efficacious treatments set forth by Chambless and Hollon (1998). The review classifies the level of efficacy established for five of ten disorders examined according to the evidence reported in the literature. Specific suggestions for two distinct future research strategies are given. The first of these is in the area of mechanism research and efficacy; the second is a proposal for the creation of an observational study Practitioner Research Network (PRN) aimed at providing data on the effectiveness of neurotherapy as practiced in the field.
II. The form of the QRS complex in bundle branch block and in anterolateral infarction

Abstract The form and interrelations of the component phases of the QRS complexes in the six Wilson precordial leads are demonstrated through a diagrammatic reconstruction of the portion of the QRS complex registered in each lead at fixed intervals after the onset of the initial deflection. This method of analysis is offered as a teaching aid and is employed to bring out the characteristic features of the QRS complex in left bundle branch block, right bundle branch block, and anterolateral myocardial infarction.
A preliminary validation of Attention, Relevance, Confidence and Satisfaction model-based Instructional Material Motivational Survey in a computer-based tutorial setting

This paper describes a preliminary validation study of the Instructional Material Motivational Survey (IMMS) derived from the Attention, Relevance, Confidence and Satisfaction motivational design model. Previous studies related to the IMMS, however, suggest its practical application for motivational evaluation in various instructional settings without the support of empirical data. Moreover, there is a lack of discussion regarding the validity of the instrument. Therefore, this study empirically examined the IMMS as a motivational evaluation instrument. A computer-based tutorial setting was selected owing to its wide application in teaching large entry-level college courses. Data collected from 875 subjects were subjected to exploratory and confirmatory factor analyses, and measurement modelling LISREL. Findings suggested that 16 original items should be excluded from the IMMS; the retained 20 items were found to fall into different constructs, indicating that instructional features of the tutorial may influence the validity of the survey items. The implication of the study supports the situational feature of the IMMS. Therefore, a preevaluation adjustment on the IMMS items is recommended to identify suitable items before the full motivational evaluation. Future research should focus on the further validation of the IMMS based on this preliminary evidence.
An improved method of preparation of inosinic acid and ribose 5-phosphate.

Summary Improved directions for the isolation of inosinic acid and ribose-5-phosphoric acid are reported.