cssi/SciSciGPT-SciSciNet huggingface dataset:
Using Propensity Scores to Help Design Observational Studies: Application to the Tobacco Litigation

Propensity score methodology can be used to help design observational studies in a way analogous to the way randomized experiments are designed: without seeing any answers involving outcome variables. The typical models used to analyze observational data (e.g., least squares regressions, difference of difference methods) involve outcomes, and so cannot be used for design in this sense. Because the propensity score is a function only of covariates, not outcomes, repeated analyses attempting to balance covariate distributions across treatment groups do not bias estimates of the treatment effect on outcome variables. This theme will the primary focus of this article: how to use the techniques of matching, subclassification and/or weighting to help design observational studies. The article also proposes a new diagnostic table to aid in this endeavor, which is especially useful when there are many covariates under consideration. The conclusion of the initial design phase may be that the treatment and control groups are too far apart to produce reliable effect estimates without heroic modeling assumptions. In such cases, it may be wisest to abandon the intended observational study, and search for a more acceptable data set where such heroic modeling assumptions are not necessary. The ideas and techniques will be illustrated using the initial design of an observational study for use in the tobacco litigation based on the NMES data set.
Weekly chemotherapy with platinum as radio-sensitizer during concomitant chemoradiotherapy for squamous cell head and neck cancer

16541 Background: CRT protocols for locally advanced HNC commonly utilize single agent cisplatinum as the radiation- sensitizing chemotherpy. This is typically administered in q 3 weekly doses of 100 mg/sq m concomitantly with XRT. However, many pts are not candidates for this dose and schedule of cisplatinum delivery due to co-morbidities. Limited data are available regarding the efficacy of alternate dosing of platinum analogues.We therefore analysed our experience with alternate dosing of cisplatin or carboplatin administered concomitantly with XRT. Methods: IRB approval was obtained for this retrospective analysis. Tumor registry and pharmacy data were reviewed to identify eligible pts. between 2004–2006 who were treated with alternate dosing of platinum with XRT. Pt characteristics recorded included: age, gender, stage, site of disease, type of chemotherpeutic agent used carboplatin or cisplatinum, number of doses administered, local disease free survival and overall survival. Results: Eleven pts wer...
A finite classification of ( x , y )-primary ideals of low multiplicity

Let S be a polynomial ring over an algebraically closed field k. Let x and y denote linearly independent linear forms in S so that \({\mathfrak {p}}= (x,y)\) is a height two prime ideal. This paper concerns the structure of \({\mathfrak {p}}\)-primary ideals in S. Huneke, Seceleanu, and the authors showed that for \(e \ge 3\), there are infinitely many pairwise non-isomorphic \({\mathfrak {p}}\)-primary ideals of multiplicity e. However, we show that for \(e \le 4\) there is a finite characterization of the linear, quadric and cubic generators of all such \({\mathfrak {p}}\)-primary ideals. We apply our results to improve bounds on the projective dimension of ideals generated by three cubic forms.
Type I Endoleak Post-Endovascular Aneurysm Repair, Successfully Treated With Excluder Cuff and Fixation Screws.

An 86-year-old woman with a medical history significant for hypertension, hyperlipidemia, dilated cardiomyopathy, remote history of coronary artery disease with a drug-eluting stent to the left anterior descending artery, permanent atrial fibrillation on warfarin, mitral and tricuspid valve repairs
Durability of Carotid Endarterectomy with Bovine Pericardial Patch.

Background Multiple studies have shown that patch angioplasty after carotid endarterectomy (CEA) reduces the risk of stroke and restenosis when compared with primary closure. Biological, synthetic, or vein patches have been traditionally used in CEA. This article reports the early and long-term outcomes of bovine pericardium (BP) for patch angioplasty in CEA. Methods A retrospective, consecutive analysis of 874 patients who underwent CEA during the past 17 years at Mayo Clinic, Florida, was performed. BP patch (BPP) was used in 680 patients. Other CEA techniques were used in 194 patients (standard without patch, 78; standard with Dacron, 74; standard with vein patch, 16; and other techniques: bypasses, 26). We defined group 1 as those who underwent BPP angioplasty and group 2 as those who underwent all other techniques. Early and late clinical outcomes and patch-related complications (restenosis, infection, and hematoma) were recorded and analyzed. Results Median follow-up for the entire series was 39.6 months. There were no statistically significant differences in 30-day mortality and morbidity between the 2 groups, except that BP group has less 30-day stroke (0.1%, 1 of 680) versus other techniques (1.5%, 3 of 194, P = 0.03). Thirty-day postoperative mortality rate was 0.1% (1 of 680) in BPP group and 1.0% (2 of 194) in other technique group (P = 0.13). No statistically significant difference was noted in 30-day postoperative major complications (transient ischemic attack [TIA], wound infection, hematoma requiring surgical evacuation, and nerve injury) between the 2 groups. Ten-year freedom from stroke/TIA were 97.8% in the BP group compared with 98.5% in the other group (P = 0.86). Ten-year freedom from restenosis was also similar between groups (89.0% BP vs. 90.4% others, P = 0.69). Ten-year survival rate was 38.4% in BP group and 45.0% in other technique group, and this was statistically significant on univariate analysis only. Conclusions CEA with BP angioplasty has excellent early and late outcomes with minor morbidity and mortality.
Effects of index client and geo-targeting on HIV case identification: an observational study

Abstract Background Despite huge investments in HIV prevention, treatment, and care in sub-Saharan Africa, fewer than one in 10 individuals knows their HIV status, and 40% of individuals living with HIV are not cognisant of their positive status. Efforts to improve and strengthen HIV service delivery, particularly in HIV testing, are necessary to increase efficiency in HIV case finding and optimise service delivery. Standard approaches to HIV testing have not been effective in addressing this gap. Our objective was to evaluate a targeted approach for HIV case identification in a PEPFAR-supported HIV programme in Nigeria. Methods Between October, 2016, and June, 2017, we implemented a strategy that included index client testing, geo-targeted HIV testing, and provider-initiated counselling and testing in 14 local government areas in Akwa Ibom, southern Nigeria. The tests were administered in conjunction with the conventional method of testing and were in line with the PEPFAR impact agenda. We estimated the number of individuals who needed to be tested by each method in order to meet a benchmark of 8000 new diagnoses per quarter. We described dispersion using median and IQR. Findings Conventional methods in the 14 local government areas required testing of 600 000 individuals (median 50 000 [IQR 741 000]) whereas using our targeted approach, we met 60% of the benchmark in each quarter by testing 214 000 individuals on average (median 14 000 [IQR 12 000]). Interpretation We demonstrated that use of a targeted approach to HIV testing can increase the efficiency of case identification. This process can therefore help increase early initiation of treatment and retention of subjects diagnosed with HIV. Funding PEPFAR.
Guest Editorial 2017 IEEE Custom Integrated Circuits Conference

This Special Section of the IEEE Journal of Solid-State Circuits features expanded versions of key papers presented at the 2017 IEEE Custom Integrated Circuits Conference (CICC), held in the Hotel Van Zandt in Austin, TX, USA, on April 30–May 3.
Dissecting Distinct Roles of NEDDylation E1 Ligase Heterodimer APPBP1 and UBA3 Reveals Potential Evolution Process for Activation of Ubiquitin-related Pathways.

Despite the similar enzyme cascade in the Ubiquitin and Ubiquitin-like peptide(Ubl) conjugation, the involvement of single or heterodimer E1 activating enzyme has been a mystery. Here, by using a quantitative Forster Resonance Energy Transfer (FRET) technology, aided with Analysis of Electrostatic Similarities Of Proteins (AESOP) computational framework, we elucidate in detail the functional properties of each subunit of the E1 heterodimer activating-enzyme for NEDD8, UBA3 and APPBP1. In contrast to SUMO activation, which requires both subunits of its E1 heterodimer AOS1-Uba2 for its activation, NEDD8 activation requires only one of two E1 subunits, UBA3. The other subunit, APPBP1, only contributes by accelerating the activation reaction rate. This discovery implies that APPBP1 functions mainly as a scaffold protein to enhance molecular interactions and facilitate catalytic reaction. These findings for the first time reveal critical new mechanisms and a potential evolutionary pathway for Ubl activations. Furthermore, this quantitative FRET approach can be used for other general biochemical pathway analysis in a dynamic mode.
Thermodynamics and Experimental Methods for Equilibrium Studies with Lipid Monolayers

Lipid monolayers on water have long been favored as a structural model of the cell membrane. However, despite intensive efforts, the insights which the lipid films have contributed to the understanding of membrane structure and function have been largely qualitative. Thus the importance of molecular shape and orientation at water surfaces (Hardy, 1912; Langmuir, 1917) and the existence of monolayer states which are analogous to those states which exist in bulk (Devaux, 1913) were established with studies of single-component lipid films (Adam and Jessop, 1926). But questions pertaining to the energetics of the lipid-lipid and polar group interactions and the contribution of water to film structure were left largely speculative.
Carrier Scattering by Optical Phonons, Two-Phonon Processes in Photon Absorption, and Spontaneous Polarization in Wurtzites

This paper focuses on the role of phonon scattering in wurtzites, emphasizes results indicating strong carrier-phonon scattering effects in these materials, and illustrates band-bending effects in wurtzite quantum dots due to spontaneous polarization.
Agalsidase Alfa in the Treatment of Anderson-Fabry Disease

Agalsidase alfa is a formulation of the human enzyme α-galactosidase A (AGAL), generated by activation of the encoding gene in a continuous human cell line. The regular infusion of agalsidase alfa into patients with Anderson-Fabry disease (AFD), in whom AGAL deficiency can lead to multi-organ system failure, has been demonstrated to be safe. By facilitating the clearance of the substrate globotriaosylceramide, which accumulates in tissues of affected individuals, agalsidase alfa treatments have resulted in a modification of disease course. These developments are anticipated to lead to improvement in the patient’s health-related quality of life and delay or prevent the development of morbidity related to renal, cardiac and cerebrovascular disease associated with AFD. Therapeutic outcome appears to be influenced by disease stage, and possibly by antibody formation and a putative problem in the intracellular trafficking of the infused enzyme. These premises have led to the recommendation of early intervention, prior to established organ dysfunction.
Goal-relevant versus incidental similarity when choosing between multiple service providers

Abstract Jiang, Hoegg, Dahl, and Chattopadhyay (2009) demonstrated that customers prefer a service provider who shares incidental similarity, such as having the same birthday. However, customers often choose from multiple service providers simultaneously. It is unclear which specific shared characteristics will influence choice in any given buying situation. Although all similarity may lead to a personal connection, goal-relevant similarity also provides diagnostic information that is related to customer buying goals while incidental similarity does not. This research consists of four experimental studies that demonstrate specific benefits and limitations of incidental similarity. When there are multiple service providers, customers will prefer providers with goal-relevant similarity over incidental similarity. However, when customers share goal-relevant similarity with multiple providers, customers then use incidental similarity to further narrow down their choice. Finally, characteristics are not inherently “goal-relevant” or “incidental,” but rather vary based on customer buying need and situational factors.
Predictive factors for prolonged operative time in head and neck patients undergoing free flap reconstruction

Abstract Purpose Defining the predictive factors associated with prolonged operative time may reduce post-operative complications, improve patient outcomes, and decrease cost of care. The aims of this study are to 1) analyze risk factors associated with prolonged operative time in head and neck free flap patients and 2) determine the impact of lengthier operative time on surgical outcomes. Methods This retrospective cohort study evaluated 282 head and neck free flap reconstruction patients between 2011 and 2013 at a tertiary care center. Perioperative factors investigated by multivariate analyses included gender, age, American Society of Anesthesiologists class, tumor subsite, stage, flap type, preoperative comorbidities, and perioperative hematocrit nadir. Association was explored between operative times and complications including flap take back, flap survival, transfusion requirement, flap site hematoma, and surgical site infection. Results Mean operative time was 418.2 ± 88.4 (185–670) minutes. Multivariate analyses identified that ASA class III (beta coefficient + 24.5, p = .043), stage IV tumors (+34.8, p = .013), fibular free flaps (−44.8, p = .033 for RFFF vs. FFF and − 67.7, p = .023 for ALT vs FFF) and COPD (+36.0, p = .041) were associated with prolonged operative time. History of CAD (−43.5, p = .010) was associated with shorter operative time. There was no statistically significant association between longer operative time and adverse flap outcomes or complications. Conclusion As expected, patients who were medically complex, had advanced cancer, or underwent complex flap reconstruction had longer operative times. Surgical planning should pay special attention to certain co-morbidities such as COPD, and explore innovative ways to minimize operative time. Future research is needed to evaluate how these factors can help guide planning algorithms for head and neck patients.
Multi-layer Born multiple-scattering model for 3D phase microscopy: publisher’s note

This publisher’s note reports typographical corrections to Optica7, 394 (2020)OPTIC82334-253610.1364/OPTICA.383030.
Altered type 1 interferon responses in alloimmunized and nonalloimmunized patients with sickle cell disease

Patients with sickle cell disease (SCD) have a high prevalence of RBC alloimmunization. However, underlying mechanisms are poorly understood. Given that proinflammatory type 1 interferons (IFNα/β) and interferon stimulated genes (ISGs) promote alloimmunization in mice, we hypothesized that IFNα/β may contribute to the increased frequency of alloimmunization in patients with SCD. To investigate this, expression of ISGs in blood leukocytes and peripheral blood mononuclear cells (PBMCs) of previously transfused SCD patients with or without alloimmunization and race‐matched healthy controls were quantified, and IFNα/β gene scores were calculated. IFNα/β gene scores of SCD leukocytes and plasma cytokines were elevated, compared to controls (gene score, p < 0.01). Upon stimulation with IFNβ, isolated PBMCs from patients with SCD had elevated ISGs and IFNα/β gene scores (p < 0.05), compared to stimulated PBMCs from controls. However, IFNβ‐stimulated and unstimulated ISG expression did not significantly differ between alloimmunized and non‐alloimmunized patients. These findings indicate that patients with SCD express an IFNα/β gene signature, and larger studies are needed to fully determine its role in alloimmunization. Further, illustration of altered IFNα/β responses in SCD has potential implications for IFNα/β‐mediated viral immunity, responses to IFNα/β‐based therapies, and other sequelae of SCD.
Ethnicity and Student Engagement

The underachievement of African American, Latino, and American Indian students in the United States has been partially attributed to poor engagement in school (e.g., Connell, Spencer & Aber, 1994; Steele, 1997). In this chapter, we consider the role of ethnicity in student engagement. A number of factors have been posited to influence minority students’ engagement in school. Okagaki (2001) conceptualized these factors into three broad domains: the roles of the student, the family, and the school. We begin with a discussion of factors within the student, such as students’ ethnic identity beliefs, experiences with discrimination, and bicultural efficacy, and the relations of these factors to students’ engagement in school. In the second section, we examine the role that parents’ beliefs, expectations, and behaviors play in ethnic minority students’ engagement in school, paying particular attention to beliefs and values that can be attributed to parents’ cultural models of education (Gallimore & Goldenberg, 2001; Lareau, 1996). Third, we consider how factors associated with teachers, peers, and friends relate to ethnic minority students’ engagement in school. In particular, we focus on students’ access to same ethnic teachers and peers, the quality of relationships with teachers and friends, and pedagogical practices that may facilitate ethnic minority students’ engagement in school. Finally, we identify the need for stronger empirical research around the identification and amelioration of the discontinuities between home and school cultures.
Affinity labeling of Escherichia coli glutamine synthetase by β, γ-Cr(III)(H2O)4ATP

Abstract The interaction of Escherichia coli glutamine synthetase with β, γ-Cr(III)(H2O)4ATP (CrATP) has been studied. This substitution inert nucleotide functioned as an active site directed irreversible inhibitor of glutamine synthetase in solutions containing 15 mM MgCl2, 100 mM KCl, and 10 mM Pipes(pH 6.6). The inactivation reaction followed pseudo-first order saturation kinetics which demonstrated reversible binding of CrATP prior to the formation of inactive enzyme. CrATP was shown to be a competitive inhibitor versus MgATP. Also, significant protection was afforded by MgATP indicating that CrATP inactivates at the active site. Partial protection was afforded by glutamate or inorganic phosphate while inactivation was enhanced by Mn(II). The stoichiometry of CrATP incorporation was approximately one molecule per enzyme subunit, determined spectrophotometrically. Both the Δ and Λ isomers of CrATP bound to glutamine synthetase, but only the Λ isomer was an active site directed irreversible inhibitor.
Chronic Graft-Versus-Host Disease

Chronic graft-versus-host disease (cGvHD) is the single major factor influencing long-term outcome and quality of life after allogeneic transplantation. However, the presence of cGvHD has been linked to decrease in relapse rate of patients with CML, ALL, and AML. In a recent CIBMTR/NMDP analysis of ∼3500 transplant patients with cGvHD, risk of relapse was reduced by 50%. Traditionally, cGvHD has been defined as occurring after day + 100, this entity has been documented as early as 50 days to years after the transplant procedure. Chronic GvHD can emerge during or immediately following taper of immune suppressive agents or may occur as part of a continuous spectrum merging acute GvHD into cGvHD (progressive GvHD).
Los Angeles' Clean Air Saga - Spanning the Three Epochs

Tracing the path that Los Angles has followed in significantly curbing its air pollution under the Federal and State Clean Air Acts over the course of four decades, this chapter illuminates both the struggle this has entailed and the importance of the three epochs developed in Chapter 1 of the book in interpreting it. The chapter focuses primarily on the evolution of the region’s efforts through the regulator and market-based epochs of the modern environmental movement, and its recent aspiration to enter into a more sustainable third epoch. The relative success of the effort is placed in the context of the tremendous growth in the size of the region’s population, economic growth, and continuously increasing number of cars, trucks, ships, and planes experienced during thedecades covered.
Inhibition of human immunodeficiency virus by using an oligonucleoside methylphosphonate targeted to the tat-3 gene.

Abstract Antiviral effects were characterized for two oligodeoxyribonucleoside methylphosphonates synthesized in an antisense (3'-TCTTAACC-5') or a sense (5'-AGAATTGG-3') orientation, based on the RNA sequence of the first splice acceptor site of the tat-3 gene of human immunodeficiency virus (HIV) (5'...AGAAUUGG...3'). The development of syncytial cells and supernatant reverse transcriptase was inhibited by a single exposure to the antisense HIV, and HIV RNA synthesis was inhibited by both antisense and sense methylphosphonates but not by a control herpes simplex virus antisense sequence.
Learning from Others: Sustaining the Internationalization and Globalization of U.S. Law School Curriculums

This address has three principal points: (1) An overview of how we are going about internationalizing the law school curriculum today in the United States; (2) Whether we are making as much progress as we should and how learning from others is central to sustaining our progress such as it is; and (3) What some of the obstacles to such learning are.
Relationships between active element patterns and mutual impedance matrices in phased array antennas

In the context of phased array antennas an active element pattern is the radiation pattern of an array when only one element in the array is excited and all of the others are terminated in some specified impedance, typically the output impedance of the sources that normally drive the elements. It is shown here that a combination of two types of active element patterns can be used to find the mutual impedance matrix that relates the element terminal voltages of a phased array to the terminal currents. The first type is found by forcing the terminal voltage of the active element to be unity at zero phase while the terminals of all the other elements are shorted. The second type is obtained by forcing the terminal current to be unity while the undriven feed points are open-circuited. The former is called the short-circuit active element pattern and the latter the open-circuit active element pattern.
Cast heatsink design advantages

IC power dissipation requirements have been rising faster than the technology needed to economically cool them. Die casting of low cost materials, especially Al doped Zn, creates a porosity free, low cost, efficient heatsink. Hand poured Al and brass alloys are also useful in special circumstances, but with a cost penalty. Airfoil shapes can be made to take full advantage of true 3D casting shapes and direct airflow as required, greatly reducing back pressure by creating turbulence only where needed. Assembly clues such as arrows can be located along with stops and alignment pins, and turbulence enhancing grooves and attachment points can be added with little per piece cost penalty. Our particular design utilizes a Zn-Al material. Its shape was optimized from CFD and FEA thermal simulations for minimum back pressure and even heat distribution. This investigation is based from the work of cooling PXFL, licensed to Hewlett Packard as the Visualize PXFL, the world's fastest graphics computer, dissipating about 450 W per board. The cooling problem in this project stemmed from the electrical design, requiring 3 closely spaced rows of processors 8 to 10 deep. Nine of these double-sided boards were placed side by side with spacing of only 50 mm between boards, all to be forced air-cooled. The back pressure using standard fin or turned heatsinks was unacceptable. A custom shape heatsink was designed to provide adequate cooling to all 44 processors mounted on both sides of the board while controlling airflow to minimize back pressure.
In vivo gamma measurements at very low levels with 4Π liquid scintillation detectors

A large 4Π liquid scintillation counter for the rapid measurement of total internal gamma contamination of the human body at concentrations 1000 times less than the maximum permissible levels is described. A counting time of only 100 seconds per subject is required to obtain a sensitivity of 5 × 10-10 curies for 1.5 mev gamma rays. Because of the high counting efficiency and the great stability of operation, the magnitude of counter background is of comparatively little importance so that elaborate shielding precautions are not required. Energy resolution is sufficient to distinguish between gamma rays of markedly different energy, but not adequate for the identification of individual nuclides. The operating characteristics of the counter are discussed including the spectrum and stability of background, energy resolution, and the spectra and limits of sensitivity for nuclides of interest in connection with nuclear power stations and uranium mining operations.
The appropriateness method has acceptable reliability and validity for assessing overuse and underuse of surgical procedures.

Abstract Objective To summarize the findings of methodological studies on the RAND/University of California Los Angeles (RAND/UCLA) appropriateness method, which was developed to assess if variation in the use of surgical procedures is because of overuse and/or underuse. Study Design and Setting A MEDLINE literature search was performed. Studies were included if they assessed the reliability or validity of the RAND/UCLA appropriateness method for a surgical procedure or the effect of altering panelist composition or eliminating in-person discussion between rating rounds. Information was abstracted on procedure, study design, and findings. Results One thousand six hundred one titles were identified, and 37 met the inclusion criteria. The test–retest reliability is good to very good (kappa, 0.64–0.81) for total knee and hip joint replacement, coronary artery bypass grafting (CABG), and carotid endarterectomy (CEA). The interpanel reliability is moderate to very good (kappa, 0.52–0.83) for CABG and hysterectomy. Construct validity has been demonstrated by comparing the appropriateness method with guidelines and/or evidence-based approaches for endoscopy, colonoscopy, CABG, hysterectomy, and CEA. Predictive validity has been studied for cardiac revascularization, in which concordance with appropriateness classification is associated with better clinical outcomes. Conclusion Our findings support use of the appropriateness method to assess variation in the rates of the procedures studied by identifying overuse and underuse. Further methodological research should be conducted as appropriateness criteria are developed and implemented for a broader range of procedures.
Use of Electronic Geometry Transfer and FEM Simulation in the Design of Hot Forming Dies for a Gear Blank

Summary The increased utilization of computer aided design and manufacturing (CAD/CAM) in forging technology requires that the design of a machined part to be forged or that of a forging is transferred from one CAD/CAM system to the other. The first system may be located at the design department of the end user and the second system may be located in a forge company or in the forge shop owned by the forging user. Metalflow simulation using the FEM based program ALPID has been applied in the past to forging of various round parts and plane strain sections of non-round forgings. This paper reports the results of an example die design procedure that is expected to be routine in the future. In this study the 2-D section geometries of a gear blank (machined part, finish forging and the suggested blocker geometry) were transferred from Eaton Corporation's ANVIL 4000 CAD/CAM system to Battelle's Computervision. At Battelle forging load and stresses were estimated and the forging process was simulated using ALPID. The results helped to optimize the design of the finisher and blocker dies as well as the estimation of the stock volume.
Overpressure and fluid flow in dipping structures of the offshore Gulf of Mexico (E.I. 330 field)

Abstract Estimated pressures in overpressured Plio-Pleistocene muds of the Eugene Island 330 (E.I. 330) field (offshore Louisiana) differ from pressure measurements in adjacent sands in a consistent manner. At structural highs, fluid pressure in sand exceeds pressure in the adjacent mud; at structural lows, the relationship is reversed. Two physical models describe the origin of these pressure differences: rapid loading and steady-flow. Observation and theory suggest that stratigraphic layering focuses fluid flow toward structural highs.
Testicular Androgen and Estrogen Secretion and Benign Prostatic Hyperplasia in the Beagle

The natural history of benign prostatic hyperplasia (BPH) in the dog is characterized by a slow progression through two phases. The early phase of the disease process is characterized by glandular hyperplasia and occurs as early as 2.5 yr of age. The late phase of the disease is characterized by cystic hyperplasia and occurs after 4 yr. The results of the present study are the first to compare Leydig cell structure and steroidogenic function in dogs with BPH with those in age-matched controls. It was discovered that glandular BPH can occur in young dogs (2.5 yr) in which Leydig cell mass and ultrastructure and maximally stimulated androgen secretion are indistinguishable from those in age-matched controls. These results support the concept that the early phase of BPH (glandular hyperplasia) is not related temporally to some defect in the Leydig cell. In contrast, the late phase of BPH (cystic hyperplasia) in beagles 6 yr of age is associated with diminished smooth endoplasmic reticulum in the Leydig cell and with diminished production of androgens by perfused testes in vitro. During the course of these studies, we discovered that the testes of young beagles with BPH, but not age-matched controls or old beagles with BPH, secrete an unidentified molecule (putative estrogen). This molecule was characterized partially in that it is extractable from testicular venous effluent with diethyl ether, elutes in a discrete fraction in several different high performance liquid chromatographic systems, reacts with an antibody that recognizes 17 beta-estradiol, estrone, and estriol, and competes with 17 beta-[3H]estradiol for the rat uterine estrogen receptor. Based on the elution volume from high performance liquid chromatography, the unknown molecule (putative estrogen) is not estriol, estradiol, or estrone.
A Ternary Complex of Transcription Factors, Nishéd and NFATc4, and Co-activator p300 Bound to an Intronic Sequence, Intronic Regulatory Element, Is Pivotal for the Up-regulation of Myosin Light Chain-2v Gene in Cardiac Hypertrophy

Transcriptional up-regulation of the myosin light chain-2 (MLC-2v) gene is an established marker for hypertrophic response in cardiomyocytes. Despite the documentation on the role of several cis-elements in the MLC-2v gene and their cognate proteins in transcription, the mechanism that dictates the preferential increase in MLC-2v gene expression during myocardial hypertrophy has not been delineated. Here we describe the properties of a cardiac specific intronic activator element (IRE) that shares sequence homology with the repressor element, the cardiac specific sequence, in the chicken MLC-2v gene. The transcription factor, Nished, that recognizes both IRE and the cardiac specific sequence potentiates the transcription of the MLC-2v gene via interaction with another transcription factor, nuclear factor of activated T cells, and the co-activator p300 at the IRE site. Angiotensin II (Ang II), a potent agonist of hypertrophy, causes induction of the MLC-2v gene transcription, which correlates well with the enhanced binding of Nished-nuclear factor of the activated T cells-p300 complex to IRE in the gel mobility shift assay. Losartan, an antagonist of Ang II receptor (AT1), abolishes the agonist-dependent stimulation of IRE/protein interaction and the consequent increase in MLC-2v gene transcription. These results together have thus established a transcriptional role of IRE as a direct target sequence of Ang II-mediated signaling that appears to be pivotal in the mechanism underlying the up-regulation of the MLC-2v gene during cardiac hypertrophy.
Kinetics of CN radical reactions with selected cycloalkanes: CN reactivity towards secondary CH bonds

Abstract The kinetics of the reaction of CN radicals with four molecules containing only secondary CH bonds, cyclopropane (c-C3H6), cyclopentane (c-C5H10), cyclohexane (c-C6H12) and cyclooctane (c-C8H16), have been studied with the two-laser pump-probe laser photolysis/laser induced fluorescence technique in the temperature range 219 to 740 K. The rate constant for CN + c-C3H6 was found to increase monotonically with temperature. However, a small negative temperature dependene of the rate was observed for CN + c-C5H10, c-C6H12, and c-C8H16. The rate constants for these reactions can be effectively represented, in units of cm3/s, by kc-C3H6 = 1.26 × 10−15 T1.50 exp(174/T), kc-C5H10 = 10−9.76±0.06 exp(40±19/T), kc-C6H12 = 10−9.67±0.08 exp(69±12/T), and kc-C8H16 = 10−9.56±0.05 exp(73±13/T). The reactivity per secondary CH bond for c-C3H6 is significantly smaller than that for c-C5H10, c-C6H12, and c-C8H16, the latter three of which have essentially the same reactivity. This is primarily due to the significant differences between the CH bond strength in c-C3H6 and the other cyclocompounds. The small negative temperature dependences in the larger cycloalkanes observed here are attributed to long-range dipole-induced-dipole attractive interactions.
Cortical activity blockade prevents ocular dominance plasticity in the kitten visual cortex

Recordings from single units in kitten primary visual cortex show that a reversible blockade of the discharge activities of cortical neurons and geniculocortical afferent terminals by intracortical infusion of the sodium channel blocker tetrodotoxin (TTX) completely prevented the ocular dominance shift that would normally be seen after monocular deprivation. The blockade of cortical plasticity, like the blockade of discharge activity, was reversible, and plasticity was restored following recovery from the effects of TTX. These results extend previous work suggesting involvement of electrical activity at the level of the cortex in the phenomenon of cortical plasticity by demonstrating an absolute requirement for discharge activities in the primary visual cortex.
THE IMPACT OF LOCAL CONTENT RULES ON GLOBAL SOURCING DECISIONS

Many governments have established, for various reasons, local confent purchasing rules for companies that wish to operate in their country. These requirements force firms to purchase a certain amount of components from suppliers located in that country. This paper describes local content rules and develops models to select suppliers while satisfying local content provisions. The single plant model can be transformed into a knapsack problem that is solved by a ranking procedure, and the solution provides insight as to the manner in which local content rules impact more generalized models. Furthermore, we illustrate possible negative effects to local industry that may result when governments set the local content percentage too high, and we discuss methods for companies to circumvent local content rules. Finally, we address the issue of local content rules in the context of multi-plant global sourcing decisions, and we provide an efficient solution procedure for the classical plant location model extended to include local content rules at each site
Kinetic and X-ray structural studies of a mutant Escherichia coli alkaline phosphatase (His-412-->Gln) at one of the zinc binding sites.

Site-specific mutagenesis has been used to replace His-412 with glutamine in Escherichia coli alkaline phosphatase. In the wild-type enzyme His-412 is a direct ligand to one of the catalytically important zinc atoms (Zn1) in the active site. The mutant enzyme (H412Q) exhibited about the same kcat, but a 50-fold increase in Km compared to the corresponding kinetic parameters for the wild-type enzyme. Furthermore, the H412Q enzyme had a lower zinc content than the wild-type enzyme. In contrast to the wild-type enzyme, Tris was less effective in the transferase reaction and dramatically inhibited the hydrolysis reaction of the H412Q enzyme. The addition of zinc to the mutant enzyme increased the kcat value above that of the wild-type enzyme, partially restored the weak substrate and phosphate binding, and also alleviated the inhibition by Tris. The structure of the H412Q enzyme was also determined by X-ray crystallography. The overall structure of the H412Q enzyme was very similar to that of the wild-type en...
A Mixed-up Sun and Solar Neutrinos

FOWLER1 has suggested that the negative result of the Davis et al.2 effort to detect neutrinos from the Sun might be due to the Sun being in a transient phase after having been mixed some millions of years ago. Here I examine that hypothesis in greater detail with stellar evolutionary calculations.
15N Chemical Shielding in Glycyl Tripeptides: Measurement by Solid-State NMR and Correlation with X-ray Structure

15N chemical shielding parameters are reported for central glycyl residues in crystallographically characterized tripeptides with α-helix, β-strand, polyglycine II (31-helix), and extended structures. Accurate values of the shielding components (2−5 ppm) are determined from MAS and stationary spectra of peptides containing [2-13C,15N]Gly. Two dipolar couplings, 1H−15N and 13Cα−15N, are used to examine 15N shielding tensor orientations in the molecular frame and the results indicate that the δ11, δ33 plane of the shielding tensor is not coincident with the peptide plane. The observed isotropic shifts, which vary over a range of 13 ppm, depend on hydrogen bonding (direct and indirect) and local conformation. Tensor spans, δspan = δ11 − δ33, and their deviations from axial symmetry, δdev = δ22 − δ33, vary over a larger range and are grouped according to 2° structure. Augmented by previously reported 13Cα shielding parameters, a prediction scheme for the 2° structure of glycyl residues in proteins based on sh...
Note on Angular Distributions in Nuclear Reactions

A proof is given of the physically plausible theorem that in a nuclear reaction produced with an unpolarized beam of given orbital angular momentum incident on an unpolarized target, the angular distribution of the outgoing intensity cannot be more complicated than that of the incoming intensity.
Cloning and Characterization of Sialidases with 2-6′ and 2-3′ Sialyl Lactose Specificity from Pasteurella multocida

Pasteurella multocida is a mucosal pathogen that colonizes the respiratory system of susceptible hosts. Most isolates of P. multocida produce sialidase activity, which may contribute to colonization of the respiratory tract or the production of lesions in an active infection. We have cloned and sequenced a sialidase gene, nanH, from a fowl cholera isolate of P. multocida. Sequence analysis of NanH revealed that it exhibited significant amino acid sequence homology with many microbial sialidases. Insertional inactivation of nanH resulted in a mutant strain that was not deficient in sialidase production. However, this mutant exhibited reduced enzyme activity and growth rate on 2-3′ sialyl lactose compared to the wild type. Subsequently, we demonstrated the presence of two sialidases by cloning another sialidase gene that differed from nanH in DNA sequence and substrate specificity. NanB demonstrated activity on both 2-3′ and 2-6′ sialyl lactose, while NanH demonstrated activity only on 2-3′ sialyl lactose. Neither enzyme liberated sialic acid from colominic acid (2-8′ sialyl lactose). Recombinant E. coli containing the sialidase genes were able to utilize several sialoconjugants when they were provided as sole carbon sources in minimal medium. These data suggest that sialidases have a nutritional function and may contribute to the ability of P. multocida to colonize and persist on vertebrate mucosal surfaces.
The variable structure servomechanism

A new class of variable structure feedback systems capable of rejecting a persistent disturbance is developed. This type of system which is called a variable structure servomechanism has structure similar to the linear multivariable servomechanism. Its internal stability and output regulation properties are examined using the theory of variable structure systems and sliding modes.
Development of Artificial Diets for Rearing the Angoumois Grain Moth

The present exploratory investigation examined the physical and chemical feeding requirements of Sitotroga cerealella (Olivier). Larvae which normally feed within kernels accepted nutritionally adequate test diets compacted into gelatine capsules. A nutritional bioassay was developed based on larval growth and adult emergence. Various combinations of natural products were tested as dietary media. Of those tested, a modified Haydak medium in which corn meal, whole wheat flour, yeast, hone), and glycerol were the essential components, was found to be best. Further experiments designed to formulate more refined diets proved reasonably successful, and the most satisfactory relined diet contained corn starch, casein, glycerol, and yeast as its major components. Although the insect developed on this medium, the overall results were not comparable to those obtained with the best diets of natural products. The future of mass-rearing this species on artificial diets and its nutritional chemistry are discussed.
Separation of associative from non-associative short latency changes in medial geniculate and inferior colliculus during differential conditioning and reversal in rats.

Abstract Results obtained in a recent experiment in this laboratory drew attention to the possible contribution of subtle non-associative processes to changes in the early latency unit responses obtained in MGB and IC of the rat during the learning of a differential appetitive conditioning task. An important possible source of such non-associative effects was shown to arise from differences in the interval between a previous food pellet presentation and the following CS+ or CS−. To determine whether previously reported changes in MGB and IC were due to associative processes or to non-associative ones, the present experiments were carried out using a counterbalanced stimulus presentation schedule which placed the CS+ and CS− at the same average time following a previous food pellet. Criteria adopted for characterizing a change as associative required that the response to the CS+ be enhanced relative to that to the CS− throughout repeated reversal sessions. The results obtained support previous findings of early latency associative changes in MGB, and are consistent with the idea that such changes are most likely to occur in the medial division of this nucleus. The findings in the IC thus far do not support the notion that this nucleus participates in this process. However, in view of the complex structure of the IC and the fact that not all of its subdivisions were sampled, these negative findings must be viewed with caution. The results also support the view that the anatomical distribution of neurons participating in the elaboration of associative changes may be more restricted than that of neurons participating in non-associative ones.
Oxygen K-edge absorption spectra of O2, CO and CO2

Abstract Using a recently developed scheme for soft X-ray detection, we have recorded the oxygen K-edge absorption spectra of O2, CO and CO2 to ≈ 500 eV above the ionization threshold at the National Synchrotron Light Source (NSLS). Extended X-ray absorption fine structures (EXAFS) are observed in these molecules. The O2 and CO spectra are only in qualitative accord with the single scattering theory and the CO2 spectrum exhibits strong multiple scattering (focusing) effects.
Infiltrating lobular carcinoma of the breast treated with segmental and modified radical mastectomy

Conservative treatment of infiltrating lobular carcinoma (ILC) has previously been examined only in terms of general breast carcinoma studies. However, this lesion has been shown to differ from the more common infiltrating ductal carcinoma (IDC) in estrogen receptor (ER) status, metastatic patterns, and bilaterality. Therefore, it is necessary for the physician to consider these distinctions when planning both pre- and post-operative treatment. To determine the effectiveness of both segmental and modified radical mastectomies, the medical records of 26 patients with ILC were reviewed, and follow-up information was obtained. In addition to surgical treatment, hormonal manipulation and/or radiotherapy were used when appropriate. We found the results of a conservative approach in the treatment of this disease to be comparable to the more radical procedures with respect to overall survival and disease-free intervals. The single factor that most affected a patient's prognosis was involvement of the axillary nodes.
Quantitation ofin VivoGene Delivery by Restriction Enzyme PCR Generated Polymorphism

The Multiple intestinal neoplasia (Min) mouse develops multiple polyps in the intestine, due to a heterozygous mutation of the Apc locus. Our laboratory has been introducing normal human adenomatous polyposis coli (APC) gene into the Min mouse through liposome enema to prevent or reverse polyp formation. We have quantitated the amount of normal human APC gene delivered in vivo by a restriction enzyme site specific quantitative PCR. Adult Min and BALB/C mice were treated with lipofectant and human APC complementary DNA (cDNA) plasmid. Min colonic DNA was amplified using primers for Apc nucleotide 2524F (5'2524-TCTCGTTCTGAGAAAGACAGAAGCT) and 2679R (5"2679-TGATACTTCTTCCAAAGCTTTGGCTAT). Highlighted primer sequences were purposely different so as to generate two HindIII restriction enzyme sites in the presence of normal mouse Apc (Apc+). Genomic DNA from untreated Min colonic epithelium revealed two bands: 144 bp for ApcMin and 123 bp for Apc+. BALB/C DNA was amplified using primers flanking a region within the APC gene containing a HindIII site on the human APC, which is absent in the murine APC (Apc). Min's DNA extracted 24 hr after treatment demonstrated a plasmid content of 3% due to a relative increase in the Apc+ (123 bp) band. Six weeks of treatments increased delivery to 10%. APC gene therapy of colonic epithelium can be quantitatively measured through restriction enzyme quantitative PCR. Long-term treatment further increases gene delivery. PCR generated polymorphism is a reliable and reproducible technique to initially optimize transfection conditions and ultimately quantitate efficacy in an in vivo gene delivery model.
Free operant response reinstatement during extinction and time-contingent (DRO) reward.

3 experiments are reported on the reinstatement of a bar-press response by rats during free operant extinction. After extended training on a VR schedule of food reward, an extinction procedure in which reward was negatively correlated with the bar-press response was initiated, i.e., reward was presented after 4 min of no bar presses. Results indicated that pause-contingent reward served to increase the rate of responding beyond what could be explained by the eliciting properties of reward-correlated stimuli or the “novelty” of stimulus change.