cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 1825: Jab1/Csn5 a new target in the resistant mechanism to HER2-targeted therapies for breast cancer

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Her2 positive (Her2+) breast cancer (BC) accounts for 20% of all breast cancer subtypes and is associated with high risk of death. Trastuzumab (Ttzm), first FDA-approved targeted therapy for BC, represents a key milestone in the personalized treatment of Her2+ metastatic disease (MBC). However, 75% of Her2+ MBC are or become resistant to Ttzm and experience relapse or disease progression. This suggests that tumors acquire or possess an intrinsic mechanism of resistance that prevents from Her2 inhibition. Therefore, it is important to identify novel pathway to overcome the resistance. Recent studies have proposed various potential mechanisms leading to the resistance, including p27 rapid degradation. Jab1/Csn5 a novel candidate oncogene that we identified contributes to the progression of BC and is correlated with poor prognosis. Our study demonstrated that Jab1/Csn5 degrades p27 in MBC. These findings suggest that Jab1 overexpression contributes to Ttzm-resistance by facilitating p27-degradation. Jab1/Csn5 is overexpressed in 50% of primary and 90% of MBC while its expression is low or absent in normal adult breast tissues. We previously identified that high expression of Jab1 is associated with shorter progression-free survival in MBC patients. In this study, we showed that the knockdown of Jab1 sensitizes to Ttzm-treatment. Mechanistically, we found that Jab1/Csn5 overexpression is significantly correlated with the activation of Akt pathway in Her2+ MBC and xenograft models. Interestingly, activated Akt, due to PTEN-loss or PI3K activating mutation has been widely implicated in the potential mechanism to Ttzm-resistance. Therefore, our results suggest that targeting Jab1/Csn5 overcomes the resistance to Ttzm via interfering with PI3K/Akt pathway. Our study identifies Jab1 as a novel contributor to Ttzm-resistance and elucidates its potential mechanisms of actions. Jab1 could be used as a predictive marker of tumor response to Ttzm, which could assist clinicians in selecting the best treatment modalities for patients with MBC. Note: This abstract was not presented at the meeting. Citation Format: Francois X. Claret, Thuy Vu, Terry J. Shackleford, Jennifer Allensworth, Qingxiu Zhang, Ling Tian, Ronghua Zhang. Jab1/Csn5 a new target in the resistant mechanism to HER2-targeted therapies for breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1825. doi:10.1158/1538-7445.AM2014-1825
Platelet adhesiveness and aggregation: II. Surface sialic acid, glycoprotein:N-acetylneuraminic acid transferase, and neuraminidase of human blood platelets

Abstract 1. 1. Human blood platelets were demonstrated to have 2.4·10 6 molecules of sialic acid per platelet surface in a neuraminidase susceptible linkage by biochemical and electrokinetic methods. 2. 2. The platelets were found to contain a fetuin:sialyl glycoprotein:glycosyl transferase; several pieces of evidence indicated that both a sialyl transferase and endogenous acceptors were located on the outer surface of the platelet plasma membrane. 52% of the transferase was recovered in the plasma membrane fraction of the platelet with a 54.3-fold purification. The enzyme has a pH optimum of 7.5, erquires Mn 2+ for activity and has high activity with either fetuin minus sialic acid or prothrombin minus sialic acid as acceptor. 3. 3. The fetuin:sialyl transferase utiling fetuin minus sialic acid and CMP-sialic acid as Substrates a and b, respectively, gave the following kinetic constants using the Cleland bisubstrate model: K a = 675 μ M, K b = 90 μ M, K ia = 18.5 μ M, K ib = 2.5 μ M and V 1 = 500 pmoles/mg protein per 5 min. 4. 4. At 1·10 −2 M the fetuin:sialyl transferase was inhibited by the following compounds which affect platelet adhesion by the indicated percentage: D -glucosamine, 80; aspirin, 95; UDP, 94; galactose, 37; glucose, 0; uridine, 0; and L -fucose, 0. 5. 5. The fetuin:sialyl transferase was dependent on Mn 2+ for activity; Co 2+ , Mg 2+ , Ba 2+ and Ca 2+ could substitute somewhat for the Mn 2+ . The following divalent cations inhibited the reation: Hg 2+ , Cu 2+ , Pb 2+ , and Cd 2+ . 6. 6. The platelets contained low but measurable neuraminidase activity; this activity was purified 20-fold and could release sialic acid residues from intact platelets as demonstrated by decreased platelet electrophoretic mobility after incubation of intact platelets with the platelet neuraminidase.
Chromatography of mold metabolites. I. Aflatoxins, ochratoxins and related compounds.

Abstract We have reviewed the literature describing the chromatography of various mold metabolites of major importance as potential health hazard for man ( e.g. , aflatoxins, ochratoxins) and have stressed procedures for their isolation, identification and study of their metabolic pathways.
Primary Structure of Alfalfa Ferredoxin

The amino acid sequences of the six peptides obtained from tryptic digests of alfalfa ferredoxin were determined by chemical and enzymic degradations. The order of tryptic peptides was established from the properties of the two segments of the succinylated protein obtained by tryptic hydrolysis at the single arginyl residue. Alfalfa ferredoxin consists of a polypeptide chain of 97 residues, characterized by clusters of acidic and hydrophobic amino acids. It is suggested that this type of distribution of hydrophobic and strongly hydrophilic residues implies a low α-helical content of the native structure. Of the 5 cysteinyl residues only 2, separated by 2 serine residues, show a grouped arrangement similar to that observed in clostridial ferredoxins. Alfalfa ferredoxin differs from spinach ferredoxin at 19 residue positions. The over-all effect of these substitutions is largely conservative in terms of the total numbers of charged, hydroxy- and hydrophobic residues. Most of the variant positions are clustered in the vicinity of Ala-Ala sequences, leaving several long stretches unaltered. Comparisons of peptide segments based on minimal mutation distances indicate the occurrence of internal repetitions of similar sequences 27 and 14 residues long in alfalfa ferredoxin. A rigorous statistical comparison of alfalfa and clostridial ferredoxins demonstrates a degree of amino acid sequence similarity clearly greater than would be expected on the basis of random occurrences. Although this raises the possibility of a common evolutionary origin for all ferredoxins, without knowledge of the minimal number of invariant residues required for function, such analyses cannot conclusively prove ancestral homology.
Text-message reminders to improve sunscreen use: a randomized, controlled trial using electronic monitoring.

Objective To evaluate the effectiveness of cellular telephone text messaging as a reminder tool for improving adherence to sunscreen application. Design We conducted a randomized, controlled trial of the effect of an electronic text-message reminder system on adherence to sunscreen application. Adherence to daily sunscreen use was evaluated using a novel electronic monitoring device. Setting Participants were recruited from the general community. Participants Seventy participants constituted a volunteer sample from the general community. The inclusion criteria required participants to be 18 years or older, to own a cellular telephone with text-message features, and to know how to retrieve text messages. Intervention Half of the participants received daily text-message reminders via cellular telephone for 6 weeks, and the other half did not receive reminders. The text-message reminders consisted of 2 components: a “hook” text detailing daily local weather information and a “prompt” text reminding users to apply sunscreen. Main Outcome Measure The primary end point of the study was adherence to sunscreen application measured by the number of days participants applied sunscreen during the 6-week study period. Results All 70 participants completed the 6-week study. There were no statistically significant differences in baseline characteristics between the 2 study groups. At the end of the study period, the 35 participants who did not receive reminders had a mean daily adherence rate of 30.0% (95% confidence interval, 23.1%-36.9%). In comparison, the 35 participants who received daily text-message reminders had a mean daily adherence rate of 56.1% (95% confidence interval, 48.1%-64.1%) ( P Conclusions Despite awareness of the benefits of sunscreen, adherence is low, even in this population, for whom adherence was knowingly monitored. Short-term data demonstrate that using existing cellular telephone text-message technology offers an innovative, low-cost, and effective method of improving adherence to sunscreen application. The use of ubiquitous communications technology, such as text messaging, may have implications for large-scale public health initiatives. Trial Registration clinicaltrials.gov Identifier:NCT00535769
Superior mesenteric vein thrombosis after colectomy for inflammatory bowel disease: a not uncommon cause of postoperative acute abdominal pain.

PURPOSE: Thromboembolism is a significant cause of morbidity and mortality in inflammatory bowel disease. Several prothrombotic conditions have been investigated in inflammatory bowel disease. The aim of this study was to evaluate the incidence of symptomatic postoperative superior mesenteric vein thrombosis in inflammatory bowel disease patients undergoing colonic resections and to identify and characterize their clinical presentation. METHODS: Between January 1999 and December 2001, 83 consecutive patients undergoing total colectomy for inflammatory bowel disease were studied retrospectively. Patients who developed new-onset postoperative acute abdominal pain were evaluated by CT scan of the abdomen. A complete coagulation profile, including thrombin time, platelet count, protein C, protein S, antithrombin III, homocysteine level, factor V Leiden mutation, plasminogen, and prothrombin G20210A mutation, was obtained in patients diagnosed with superior mesenteric vein thrombosis. RESULTS: Four patients (4.8 percent; 3 females; 3 patients with ulcerative colitis and 1 with Crohn’s colitis) developed symptomatic postoperative superior mesenteric vein thrombosis. Two of these patients had extension of the clot into the portal vein. Their presenting symptom was abdominal pain, with a median interval of ten days from the index surgery. The hematologic workup was negative in three patients, with one heterozygous for prothrombin G20210A mutation. All patients were treated with systemic anticoagulation for at least six months. One ulcerative colitis patient was diagnosed after abdominal colectomy and underwent an uneventful ileal pouch-anal anastomosis after systemic anticoagulation. CONCLUSION: Postoperative superior mesenteric vein thrombosis is a more frequent occurrence than previously reported in patients with inflammatory bowel disease. Direct surgical trauma to the middle colic veins, with resulting thrombosis, is likely to be the precipitating factor in a borderline intrinsically hypercoagulable environment. All patients became asymptomatic after systemic anticoagulation and recovered uneventfully.
Optimizing Math Curriculum to Meet the Learning Needs of Students.

With the passage of the No Child Left Behind Act of 2001 and the reauthorization of the Individuals with Disabilities Education Act of 2004, educators are under tremendous pressure to increase the academic performance of all students. The concern over student performance is not overstated. The 2003 National Association of Education Progress reported that 23% and 32% of students in 4th and 8th grade scored below the basic level. Because 75% of a teacher's instructional decisions regarding content sequence and instructional objectives are determined by a district's adopted mathematics textbook, there is a need to develop effective strategies to better implement mathematics curricula and materials. The authors' purpose in this article was to describe an 8-step strategy, OPTIMIZE, to help teachers maximize the effectiveness of their current mathematics curriculum by designing adequate and appropriate modifications to increase the mathematical achievement of all students.
The effect of environmental temperature on the immune response of a marine teleost (Paralichthysdentatus)

The kinetics of the primary immune response to horse erythrocytes were studied in summer flounder (Paralichthysdentatus). This species produced antibody over a wide temperature range. The fish were divided into five groups and the experiments carried out at environmental temperatures of 27, 22, 17, 12, and 7.5°C. At the lower environmental temperatures, a corresponding delay in the appearance of circulation antibody occurred, although the magnitude and duration of the response was not appreciably affected. After immunizing at 12°C, lowering the environmental temperature gradually to 8°C, did not appear to inhibit an ongoing primary response. Typical secondary responses were seen in fishes kept at warmer temperatures, but when the temperature was lowered to 8°C, no anamnestic response was seen. Individual variation was most noticeable at middle temperature ranges.
X-ray absorption spectroscopy of Pt-ReAl2O3 catalysts

Abstract The state of Re in reduced Pt-Re Al 2 O 3 catalysts has been a subject of controversy for some years. X-ray absorption spectroscopy at the Stanford Synchrotron Radiation Laboratory was used to examine two laboratory-prepared, commercial-type catalysts after reduction. Data from the Re LIII absorption edge show that Re is neither zero valent nor significantly associated with Pt. The data also suggest that the Re is in the 4+ valence state.
Assessment of Acculturation in Hispanic Populations

Professional psychologists who serve Hispanic populations do not routinely use acculturation instruments. Recommendations for use of five adequately conceptualized and validated acculturation measu...
Optimal response to a shift in regulatory regime: The case of the US nuclear power industry

This paper studies the impact of the March 1979 Three Mile Island (TMI) accident on the regulation of nuclear power plants (NPPs) and its consequences for the operating behaviour and profitability of the US nuclear power industry. We treat the TMI accident as a ‘natural experiment’ that caused a sudden, unexpected, and permanent increase in the intensity of safety regulation by the US Nuclear Regulatory Commission (NRC) and a shift towards increased disallowances of operating costs by state and local public utility commissions (PUCs). We analyse the nuclear power industry's reaction to this shift in regulatory regime using detailed monthly data on NPP operations collected by the NRC. One of the industry's responses was to increase the planned durations between refuellings from 12 months in the pre-TMI period to 18 months in the post-TMI period. We estimate a simple dynamic programming (DP) model of NPP operations that shows how an operator optimally balances the potential increases in capacity utilization rates associated with longer operating cycles against the increased costs of unplanned and forced outages associated with longer cycles. Under the maintained hypothesis that NPP operators seek to maximize expected discounted profits, we use the NPP operating data to infer profit functions for NPPs in the pre- and post-TMI periods. The estimated profit functions reveal that utilities have been responsive to NRC regulation insofar as they impute a significantly higher cost to ‘imprudent’ operation of a reactor in the post-TMI period than in the pre-TMI period. The results show that utilities responded optimally to the change in regulatory regime since the DP model predicts that optimal planned operating cycles were approximately 12 months in the pre-TMI period and 18 months in the post-TMI period. We find that while NPPs appear safer in the post-TMI period (in terms of having a lower rate of forced outages), they are also substantially less profitable: over 90% of the expected discounted profits from continued operation of existing NPPs have been eliminated in the post-TMI period. However, since most of the investments in existing NPPs are already sunk and given the high costs of plant decommissioning, the DP model predicts that utilities will continue to operate NPPs rather than shut them down. Interestingly, we find that the hypothesis of expected discounted profit maximization provides a much better approximation to NPP operating behaviour in the post-TMI period than in the pre-TMI period.
Phase 1B study to improve immune responses in head and neck cancer patients using escalating doses of 25-hydroxyvitamin D3

Patients with head and neck squamous cell carcinoma (HNSCC) have profound immune defects. These defects are associated with a poor prognosis and are mediated, in part, by immune inhibitory CD34(+) progenitor cells, whose numbers are increased in the peripheral blood of HNSCC patients. Immune inhibitory CD34(+) cells are also present within HNSCC tumors. A phase IB clinical trial was conducted with HNSCC patients to determine if treatment with the differentiation-inducer 25-hydroxyvitamin D(3) could diminish CD34(+) cell levels and improve a panel of immune parameters. Here we present the results of treatment with orally administered escalating doses (20, 40, 60 microg) of 25-hydroxyvitamin D(3), with an emphasis on the six patients who received the maximum dosage of 60 microg per day. Peripheral blood was collected at 0, 1, 2, 4, and 6 weeks, and assessed for markers of immune activity. Although no clinical responses were observed, results of this pilot study demonstrated that treatment of HNSCC patients with 25-hydroxyvitamin D(3 )reduces the number of immune suppressive CD34(+) cells, increases HLA-DR expression, increases plasma IL-12 and IFN-gamma levels, and improves T-cell blastogenesis. In contrast, 25-hydroxyvitamin D(3) treatment did not modulate plasma IL-1beta, IL-2, IL-4, IL-6, IL-10, GM-CSF, or TGF-beta levels.
Considerations in planning a clinical trial with fast neutrons.

Abstract The problems of instituting a clinical trial are discussed and some qualities of a cyclotron at Texas A. & M. University are outlined. It is clearly impossible to test all possible dose fractionation regimes before beginning a clinical trial. Therefore, selection of a treatment regime must be based on previous clinical and radiobiological experience, without certainty that the regime chosen is the best. However, the main problem in a clinical trial lies in the difficulty of proving with statistical satisfaction the superiority of one form of treatment.
Monogamy Agreements in Male Same-Sex Couples: Associations With Relationship Quality and Individual Well-Being

In this study, the authors explored whether type of sexual agreement (for monogamy, unrestricted nonmonogamy, or restricted nonmonogamy) is associated with the relationship quality and psychological well-being of men in same-sex relationships. A geographically diverse sample of 219 U.S. men in cohabiting same-sex relationships reported on sexual agreement type, several relationship characteristics central to long-term couple health, and two indices of psychological well-being (depressive symptoms and internalized heterosexism). Results indicated no differences by sexual agreement type in the majority of indices of relationship health, including self-reported relationship satisfaction, hostile conflict, felt constraint, confidence in the relationship, and perceived instability. There were also no group differences in depressive symptoms or internalized heterosexism. However, men in relationships with nonmonogamous agreements reported higher perceived quality of alternatives to their relationship and lower ...
Rayleigh Law Response in Ferroelectric Ceramics: Quantifying Domain Wall Dynamics and Structural Relationships

The polarization and strain responses in ferroelectric materials are non-linear and hysteretic. A number of mathematical and phenomenological approaches have been used to describe and quantify this behavior. In order to fully describe this response dielectric and piezoelectric coefficients must include real and imaginary components and suitable non-linear terms. The Rayleigh Law has been shown to provide a suitable description of the non-linear dielectric and piezoelectric response in bulk, single crystal, and thin film piezoelectrics. It has also been shown to be mathematically consistent with physical models for domain wall motion. The Rayleigh Law fitting of the polarization-field and strain-field hysteresis loops at subswitching fields (E<1/2EC) provides a straightforward and compact approach to quantify of this complex response. The coefficients obtained from this analysis can be applied to quantify variations in extrinsic domain-wall response. Rayleigh coefficients will be used to discuss the role of crystal structure, and symmetry on the dielectric and piezoelectric properties ferroelectric ceramic materials.
Photochemical reaction of a dye precursor 4-chloro-1,2-phenylenediamine and its associated mutagenic effects

Abstract 4-Chloro-1,2-phenylenediamine (4-Cl-o-PDA) is an aromatic diamine used as a precursor for manufacture of hair dyes and dyes of other purposes. 4-Cl-o-PDA has been found to be photomutagenic in bacteria when concurrently exposed to simulated sunlight irradiation. Irradiation of 4-Cl-o-PDA by either outdoor sunlight or indoor lamp, one main photoproduct appeared and it was found to be 2,3-diamino-7-chlorophenazine, a dimerized product through the excited state reaction of 4-Cl-o-PDA in the presence of oxygen. The isolated yield of 13% for 2,3-diamino-7-chlorophenazine is far better than the oxidation reaction of 4-Cl-o-PDA by H2O2 and may therefore be used as a synthetic method. The half live of transformation for 4-Cl-o-PDA in water (100 μM) is 39 min when exposed to outdoor sunlight. The photomutagenicity of 4-Cl-o-PDA and its photoproduct were tested in Salmonella typhimurium TA102. Under the same conditions, both compounds are photomutagenic. In addition, 2,3-diamino-7-chlorophenazine is both phototoxic and mutagenic.
First-principles calculations and tight-binding molecular dynamics simulations of the palladium-hydrogen system

We present a study of palladium-hydrogen system by the linearized augmented plane-wave (LAPW) and Naval Research Laboratory (NRL) tight-binding (TB) methods. We constructed a TB Hamiltonian by fitting to first-principles LAPW data for the electronic energies of a large range of palladium and palladium hydride structures differing in symmetry and compositions as a function of volume. This TB Hamiltonian was then used to calculate phonon frequencies and elastic constants. Our calculations show good agreement with experiments and demonstrate the efficiency of the NRL-TB scheme. In addition, we performed tight-binding molecular dynamics simulations to calculate the density of states, mean-squared displacement, and the formation energy as a function of hydrogen content. We found a relative dip in the lattice energy of structures near the experimental limit of hydrogen content. We calculated the nearest hydrogen-hydrogen distance for various compositions of palladium hydride and confirmed the Switendick criterion.
A novel subnetwork alignment approach predicts new components of the cell cycle regulatory apparatus in Plasmodium falciparum

According to the World Health organization, half the world's population is at risk of contracting malaria. They estimated that in 2010 there were 219 million cases of malaria, resulting in 660,000 deaths and an enormous economic burden on the countries where malaria is endemic. The adoption of various high-throughput genomics-based techniques by malaria researchers has meant that new avenues to the study of this disease are being explored and new targets for controlling the disease are being developed. Here, we apply a novel neighborhood subnetwork alignment approach to identify the interacting elements that help regulate the cell cycle of the malaria parasite Plasmodium falciparum. Our novel subnetwork alignment approach was used to compare networks in Escherichia coli and P. falciparum. Some 574 P. falciparum proteins were revealed as functional orthologs of known cell cycle proteins in E. coli. Over one third of these predicted functional orthologs were annotated as "conserved Plasmodium proteins" or "putative uncharacterized proteins" of unknown function. The predicted functionalities included cyclins, kinases, surface antigens, transcriptional regulators and various functions related to DNA replication, repair and cell division. The results of our analysis demonstrate the power of our subnetwork alignment approach to assign functionality to previously unannotated proteins. Here, the focus was on proteins involved in cell cycle regulation. These proteins are involved in the control of diverse aspects of the parasite lifecycle and of important aspects of pathogenesis.
Large-Scale Adeno-Associated Viral Vector Production Using a Herpesvirus-Based System Enables Manufacturing for Clinical Studies

The ability of recombinant adeno-associated viral (rAAV) vectors to exhibit minimal immunogenicity and little to no toxicity or inflammation while eliciting robust, multiyear gene expression in vivo are only a few of the salient features that make them ideally suited for many gene therapy applications. A major hurdle for the use of rAAV in sizeable research and clinical applications is the lack of efficient and versatile large-scale production systems. Continued progression toward flexible, scalable production techniques is a prerequisite to support human clinical evaluation of these novel biotherapeutics. This review examines the current state of large-scale production methods that employ the herpes simplex virus type 1 (HSV) platform to produce rAAV vectors for gene delivery. Improvements have substantially advanced the HSV/AAV hybrid method for large-scale rAAV manufacture, facilitating the generation of highly potent, clinical-grade purity rAAV vector stocks. At least one human clinical trial employing rAAV generated via rHSV helper-assisted replication is poised to commence, highlighting the advances and relevance of this production method.
Structure-Based Development of Small Molecule PFKFB3 Inhibitors: A Framework for Potential Cancer Therapeutic Agents Targeting the Warburg Effect

Cancer cells adopt glycolysis as the major source of metabolic energy production for fast cell growth. The HIF-1-induced PFKFB3 plays a key role in this adaptation by elevating the concentration of Fru-2,6-BP, the most potent glycolysis stimulator. As this metabolic conversion has been suggested to be a hallmark of cancer, PFKFB3 has emerged as a novel target for cancer chemotherapy. Here, we report that a small molecular inhibitor, N4A, was identified as an initial lead compound for PFKFB3 inhibitor with therapeutic potential. In an attempt to improve its potency, we determined the crystal structure of the PFKFB3•N4A complex to 2.4 A resolution and, exploiting the resulting molecular information, attained the more potent YN1. When tested on cultured cancer cells, both N4A and YN1 inhibited PFKFB3, suppressing the Fru-2,6-BP level, which in turn suppressed glycolysis and, ultimately, led to cell death. This study validates PFKFB3 as a target for new cancer therapies and provides a framework for future development efforts.
Bis-Salicylaldiminato Complexes of Zinc. Examination of the Catalyzed Epoxide/CO2 Copolymerization

A series of salicylaldimine ligands of the general formula (NR2C7H5-x(R1)xOH) [x = 1 or 2; R1 = Me, tBu, Cl, OMe; R2 = 2,6-iPr2C6H3, or 3,5-(CF3)2C6H3] have been synthesized and characterized via 1H and 13C NMR, elemental analysis, and X-ray crystallography. The concomitant series of zinc bis(salicylaldiminato) complexes of the general formula have been synthesized and characterized in the solid state by X-ray crystallography. All complexes crystallized as four coordinate monomers with distorted tetrahedral geometry about the zinc center. The O−Zn−O angles range between 105 and 112.5°, and the N−Zn−N bond angles were more obtuse spanning the range 122.9−128.9°. The only deviation from distorted tetrahedral geometry occurred when R2 = 3,5-(CF3)2C6H3 which crystallized as a distorted trigonal bipyramidal dimeric species with Oax−Zn−Oax bond angles of 165.00(15)°. The equatorial angles approach 120° except for the Neq−Zn−Neq angle of 110.54(16)° which is attributed to the strain of the bridging ligands. The ...
Dose uncertainties for large solar particle events: Input spectra variability and human geometry approximations

Abstract The true uncertainties in estimates of body organ absorbed dose and dose equivalent, from exposures of interplanetary astronauts to large solar particle events (SPEs), are essentially unknown. Variations in models used to parameterize SPE proton spectra for input into space radiation transport and shielding computer codes can result in uncertainty about the reliability of dose predictions for these events. Also, different radiation transport codes and their input databases can yield significant differences in dose predictions, even for the same input spectra. Different results may also be obtained for the same input spectra and transport codes if different spacecraft and body self-shielding distributions are assumed. Heretofore there have been no systematic investigations of the variations in dose and dose equivalent resulting from these assumptions and models. In this work we present a study of the variability in predictions of organ dose and dose equivalent arising from the use of different parameters to represent the same incident SPE proton data and from the use of equivalent sphere approximations to represent human body geometry. The study uses the BRYNTRN space radiation transport code to calculate dose and dose equivalent for the skin, ocular lens and bone marrow using the October 1989 SPE as a model event. Comparisons of organ dose and dose equivalent, obtained with a realistic human geometry model and with the oft-used equivalent sphere approximation, are also made. It is demonstrated that variations of 30–40% in organ dose and dose equivalent are obtained for slight variations in spectral fitting parameters obtained when various data points are included or excluded from the fitting procedure. It is further demonstrated that extrapolating spectra from low energy (⩽30 MeV) proton fluence measurements, rather than using fluence data extending out to 100 MeV results in dose and dose equivalent predictions that are underestimated by factors as large as 2–3. Finally, it is also demonstrated that the use of equivalent sphere approximations to represent body organ self-shielding distributions results in organ doses and dose equivalent predictions that are 2–3 times larger than values obtained with anthropomorphic shielding configurations.
Do Abortion Attitudes Lead to Party Switching

The notion that issues and ideology can move partisanship remains controversial. The authors explore the stronger claim that issues can lead people to switch political parties and whether the effect of abortion attitudes is asymmetrical (i.e., abortion attitudes may influence party switching in only one direction). They show that in several short-term National Election Studies panels, pro-life Democrats were significantly more likely than other Democrats to become Republicans, but pro-choice Republicans were not likely to become Democrats. However, using panel data over a long time frame, 1982 to 1997, the authors also demonstrate that the cumulative effect of abortion attitudes led pro-life Democrats and pro-choice Republicans to switch parties.
Paleontological Patterns, Macroecological Dynamics and the Evolutionary Process

Here we consider evolutionary patterns writ large in the fossil record. We argue that Darwin recognized but downgraded or de-emphasized several of these important patterns, and we consider what a renewed emphasis on these patterns can tell us about the evolutionary process. In particular, one of the key patterns we focus on is the role geographic isolation plays in fomenting evolutionary divergence; another one of the key patterns is stasis of species; the final pattern is turnovers, which exist at several hierarchical scales, including regional ecosystem replacement and pulses of speciation and extinction. We consider how each one of these patterns are related to the dynamic of changing ecological and environmental conditions over time and also investigate their significance in light of other concepts including punctuated equilibria and hierarchy theory. Ultimately, we tie each of these patterns into a framework involving macroecological dynamics and the important role environmental change plays in shaping evolution from the micro- to macroscale.
Preparation of Linear and Star-Shaped Block Copolymers by ATRP Using Simultaneous Reverse and Normal Initiation Process in Bulk and Miniemulsion

Well-defined linear and star-shaped block copolymers were synthesized using halogenated ATRP macroinitiator via a simultaneous reverse and normal initiation (SRN Mw/Mn = 1.08) was extended with styrene to form star-shaped block copolymer, poly(methyl acrylate)-b-polystyrene, with Mn = 24 700 g/mol and Mw/Mn = 1.41 in bulk condition (yield = 72%) and Mn = 22 100 g/mol and Mw/Mn = 1.37 in miniemulsion (yield = 72%). This newly developed ATRP process requires a significantly reduced amount of highly active ATRP catalyst complex in its oxidatively stable high oxidation state (e.g., CuIIBr2/ligand), while the predominant initiating species was a normal halogen-containing macroinitiator. The compositiona...
Characterization of Elastographic Noise Using the Envelope of Echo Signals

A theoretical formulation characterizing the noise performance of strain estimation using envelope signals is presented for the cross-correlation based strain estimator in elastography, using a modified strain filter approach. The strain filter describes the relationship among the elastographic signal-to-noise ratio (SNRe), sensitivity, contrast-to-noise ratio and dynamic range for a given resolution in the elastogram, as determined by the cross-correlation window length and window overlap. Theoretical results indicate that the envelope strain filter noise performance (SNRe level) is about half that obtained in the ratio frequency (RF) case (fo = 7.5 MHz). Simulation results corroborate the trend predicted using the strain filter. Experimental SNRe vs. strain plots presented in this article illustrate the same trend as the theoretical results. These plots allow a quantitative comparison of the elastograms obtained with RF and envelope signal processing. For small strains, the performance obtained using RF signals is superior to that obtained for envelope signals (since jitter errors are smaller due to the utilization of phase information in RF signals). However, for large tissue strains, envelope analysis provides an accurate estimate of the tissue strain (since envelope signal decorrelation is smaller than RF signal decorrelation at large strains). An algorithm that combines the low-noise characteristics of the cross-correlation analysis using RF signals at small strains and envelope signals for estimation of large tissue strains is proposed to improve the dynamic range in the elastogram.
Comparison of identification criteria for machine inductive inference

Abstract A natural ωpLω+1 hierarchy of successively more general criteria of success for inductive inference machines is described based on the size of sets of anomalies in programs synthesized by such machines. These criteria are compared to others in the literature. Some of our results are interpreted as tradeoff results or as showing the inherent relative-computational complexity of certain processes and others are interpreted from a positivistic, mechanistic philosophical stance as theorems in philosophy of science. The techniques of recursive function theory are employed including ordinary and infinitary recursion theorems.
Peroxisome proliferator-activated receptor γ1 expression is induced during cyclic adenosine monophosphate-stimulated differentiation of alveolar type II pneumonocytes

The primary function of lung alveolar type II cells is to synthesize pulmonary surfactant, a lipoprotein enriched in dipalmitoylphosphatidylcholine. Because type II pneumonocytes are highly lipogenic, we considered the possible role of the adipogenic nuclear hormone receptor, peroxisome proliferator-activated receptorγ (PPARγ), in their differentiation from epithelial cell precursors. A degenerate PCR-screening strategy revealed that multiple PPARs, including PPARγ, are present in differentiated type II cells. A PCR-amplified PPARγ DNA-binding domain was used to isolate a full-length PPARγ1 complementary DNA clone from a rabbit type II cell complementary DNA library. Although another PPARγ isoform, PPARγ2, is known to be highly expressed in adipocytes, only PPARγ1 was detected in rabbit type II cells by use of RT-PCR and by library screening. Rabbit PPARγ1 has 90% nucleotide sequence identity and 95% amino acid identity to mouse PPARγ1. PPARγ1 messenger RNA was readily detected in total RNA isolated from ...
Coherence theory of radio-astronomical measurements

A unified theory of radio-astronomical measurements is presented within the framework of the theory of partial coherence. It is shown how different coherence functions are related to the spectrum, the brightness distribution, and the polarization of statistical electromagnetic fields, and to their measurement. These coherence functions can be derived from the space-time coherence tensor. Various radio-astronomical techniques for measuring the spectrum, the brightness distribution, and the polarization are discussed with special reference to correlation techniques. The connection between the theory of antennas and that of optical systems is discussed. In both cases the theory of partial coherence provides a unified theoretical foundation and an important framework for future research and development.
Role of colon cancer genes in development

Dr. Kucherlapati is the Lola and Saul Kramer Professor and Chairman of the Department of Molecular Genetics at Albert Einstein College of Medicine in Bronx, New York. He received his Ph.D. degree in Genetics from the University of Illinois. After conducting post-doctoral work at Yale University, he joined the faculty at Princeton University. Dr. Kucherlapati was a Professor of Genetics at the University of Illinois College of Medicine prior to joining the faculty of the Albert Einstein College of Medicine. Dr. Kucherlapati's current research interests include structural and functional genomics and the development of mouse models for human disease.
Comparison of techniques for determination of boundary layer transition in shock wave induced flows

Three methods of determining transition times in shock wave-induced boundary layers are compared. Experimental transition data for these comparisons were obtained in two different shock tube facilities for shock wave Mach numbers from 3.0 to 5.5. Bias in determining transition times by the conventional thin-film temperature history and difficulty in reading schlieren photographs suggest the use of a new heat-flux technique for determining transition. It is suggested that the heat-flux technique be used when possible, because of better sensitivity and a view of the entire transition process and because it reveals important information concerning departures from theoretical laminar boundary-layer development. Transition results presented extend the range of data available in the literature and are in good agreement with existing data through transition Reynolds numbers of 1,000,000.
A Game of Inches: Spontaneous Use of Counterfactuals by Broadcasters During Major League Baseball Playoffs1

We tested whether counterfactuals are made spontaneously outside of the laboratory by coding sportscasters’ online verbalizations during 1998 and 1999 Major League Baseball (MLB) playoff broadcasts, and we assessed whether naturally occurring game features relating to closeness (score closeness, series closeness, game end, and playoff end) delineated some conditions under which counterfactuals were more likely. Sportscasters made counterfactuals quite frequently during these MLB playoff games. In addition, sportscasters uttered greater numbers of counterfactuals as games progressed from early to late innings, which was particularly true when scores were close. Counterfactuals were also uttered in greater numbers with closer scores when series were tied than when one team had a lead. Results are discussed in terms of spontaneous counterfactuals, closeness as an antecedent, and the ecological validity of such thoughts.
Isolation and preliminary characterization of rat liver cells resistant to 7-ketocholesterol

Abstract Two clones of the rat liver cell line, GAI, were selected and propagated in 4 μg/ml of the cholesterol analogue, 7-ketocholesterol. One of the variants was also found to be resistant to another toxic analogue, 25-hydroxycholesterol. 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34) activity was elevated in both variant clones, but was not increased substantially upon incubation of the cells in lipid-depleted medium. The reductase activity was increased 3-fold in the wild type cells under the same conditions. Incubation of the cells in lipid-depleted medium resulted in a 3-fold increase in the rate of sterol synthesis from [14C]acetate in all three cell types. In the presence of 2 μg/ml 7-ketocholesterol, the reductase activity in all three cell lines decreased at an equal rate, but activity of the enzyme was still measurable after 48 h in the presence of the analogue. Sterol synthesis was reduced almost to zero in the wild type cells under these conditions, while the variant cells retained 12–15% of their capacity for sterol synthesis. These results are interpreted to indicate that 7-ketocholesterol, besides affecting sterol synthesis at the level to 3-hydroxy-3-methylglutaryl coenzyme A reductase, must also affect sterol synthesis at another step further along the synthetic pathway.
Pharmacogenetics of antipsychotic-induced weight gain.

Rationale Antipsychotic medications have been associated with considerable weight gain. The degree of inter-individual variability and known genetic contributions to obesity suggest a combination of genetic and environmental factors. In the absence of established mechanisms and valid predictors for this relevant adverse effect, pharmacogenetic studies may provide the basis for the development of individualized treatment and preventive interventions.
13C-NMR studies of the effects of the carcinogen acetylaminofluorene on the conformation of dinucleoside monophosphate

13C-NMR spectra are obtained in aqueous solution of dinucleoside monophosphates (ApG and GpA) and of their adducts formed by the addition of the carcinogen acetylaminofluorene (AAF) to the C8 position of the guanine. The base and sugar carbons of all dimers and adducts are assigned. The task of assigning base and carbohydrate resonances was accomplished using a series of reference compounds. Significant changes in many of the carbon resonances of the adducts are observed suggesting three general conformational changes, namely: (1) chemical shift changes are noted in base carbon atom resonances as a function of temperature and adduct formation which are indicative of stacking effects; (2) large upfield shifts of the furanose C2' resonance of the guanosine-adduct indicate a shift to higher populations of the syn conformation. Other shifts of carbohydrate resonances are indicative of a change in conformation of the carbohydrate itself. (3) Large temperature effects on linewidth of several fluorine and furanose resonances indicate interconversion of various conformers in the dimer adduct.
A Comparison of Multiplicity Adjustment Strategies for Correlated Binary Endpoints

Several Bonferroni-type adjustments have been proposed to control for family wise type I error among multiple tests. However, many of the approaches disregard the correlation among endpoints. This can result in a conservative hypothesis testing strategy. The James procedure is an alternative approach that accounts for multiplicity among correlated continuous endpoints. Here a simulation study compares four Bonferroni-type alpha-adjustments (Bonferroni, Dunn-Sidak, Holm, and Hochberg) and the James p-value adjustment when used for multiple correlated binary variables. These procedures provided adequate protection against familywise type I error for correlated binary endpoints, albeit, at times, in an overly cautious manner. That is, when correlations among endpoints exceed 0.60, the result is somewhat conservative for the approaches that do not account for those correlations. Among the adjustments examined, the James approach appears to be the uniformly preferred method. Analyses of data from a randomized controlled clinical trial of treatments for mania in bipolar disorder are used to illustrate the application of the multiplicity adjustments.
Union legislative records during president reagan’s first term

It has been assumed that organized labor’s political record has declined markedly since President Reagan was elected in 1980. This study shows this contention to be only partly true. While organized labor’s political influence has declined somewhat, particularly in the executive branch, there is considerable variation in the legislative agendas, objectives, and successes across a sample of eight major unions studied. This suggests that union legislative activity should be studied on a union-by-union basis.
Application site dependent ocular absorption of timolol.

ABSTRACT Ocular absorption of timolol in rabbits was studied after topical ocular administration of 3H-timolol in an eyedrop or in silicone cylindrical devices that released timolol at 7.2 μg/h. The devices were applied in either the inferior or superior conjunctival sac. Timolol concentrations were nearly equal in the inferior and superior portions of ocular tissues when the drug was administered in an eyedrop. Administration in the devices resulted in unequal timolol distribution in the cornea, conjunctiva, sclera, and iris-ciliary body. Timolol concentrations were higher in the part of each tissue that was closer to the site of the device application. Unequal concentrations of timolol in the superior and inferior part of the eye and very low timolol concentrations in the aqueous humor indicated that timolol was absorbed mainly via a noncorneal route from the device placed in the inferior conjunctival sac. Induced blinking at one minute intervals did not change ocular absorption of timolol. Compared wit...