cssi/SciSciGPT-SciSciNet huggingface dataset:
Comprehensive interrogation of the ADAR2 deaminase domain for engineering enhanced RNA base-editing activity, functionality and specificity

ABSTRACT Adenosine deaminases acting on RNA (ADARs) can be repurposed to enable programmable RNA editing, however their exogenous delivery leads to transcriptome-wide off-targeting, and additionally, enzymatic activity on certain RNA motifs, especially those flanked by a 5’ guanosine is very low thus limiting their utility as a transcriptome engineering toolset. To address this, we explored comprehensive ADAR2 protein engineering via three approaches: First, we performed a novel deep mutational scan of the deaminase domain that enabled direct coupling of variants to corresponding RNA editing activity. Experimentally measuring the impact of every amino acid substitution across 261 residues, i.e. ~5000 variants, on RNA editing, revealed intrinsic domain properties, and also several mutations that greatly enhanced RNA editing. Second, we performed a domain-wide mutagenesis screen to identify variants that increased activity at 5’-GA-3’ motifs, and discovered novel mutants that enabled robust RNA editing. Third, we engineered the domain at the fragment level to create split deaminases. Notably, compared to full-length deaminase overexpression, split-deaminases resulted in >1000 fold more specific RNA editing. Taken together, we anticipate this comprehensive deaminase engineering will enable broader utility of the ADAR toolset for RNA biotechnology and therapeutic applications.
Public health service increased risk donor kidney grafts for transplant into children, a survey of pediatric nephrologists

Background Kidney transplant is the best treatment for end-stage renal disease (ESRD); however, access is limited by severe organ shortage. Public Health Service increased risk donors (PHS-IRD) represent a significant portion of available organs which are discarded at disproportional rates. Methods Pediatric nephrologists were surveyed regarding PHS-IRD kidneys to understand attitudes and perceived barriers to the use of these grafts in children. We sought to elucidate what methods may help increase the likelihood of PHS-IRD acceptance. Results Twenty-two responses were received from United States pediatric nephrologists representing 11 UNOS regions (response rate 5.9%). Of respondents, 50% had been practicing for 20+ years, 77% in academic hospitals, and 63% in cities with over 1 000 000 people. All respondents worked in an institution with a kidney transplant program. 41% reported that they would not accept PHS-IRD kidneys under any circumstance, 45% would accept depending on the candidate's medical status, and 14% routinely accepted PHS-IRD kidneys. Infectious transmission was the biggest disincentive reported (59%), with only 55% of respondents feeling comfortable counseling families on the associated risks. 82% of respondents did not perceive all PHS-IRD as the same, and 90% supported stratifying PHS-IRD into tiers based on risk, which would increase the likelihood of organ acceptance (82%) and assist in counseling families (91%). Conclusions With improved utilization, PHS-IRD kidneys offer a step toward decreasing the organ shortage. These findings suggest hesitance in use of PHS-IRD kidneys for pediatric recipients. Further stratification of risk could aid in provider organ acceptance and counseling patients.
Science merit function for the Kepler mission

The Kepler mission was a National Aeronautics and Space Agency (NASA) Discovery-class mission designed to continuously monitor the brightness of at least 100,000 stars to determine the frequency of Earth-size and larger planets orbiting other stars. Once the Kepler proposal was chosen for a flight opportunity, it was necessary to optimize the design to accomplish the ambitious goals specified in the proposal and still stay within the available resources. To maximize the science return from the mission, a merit function (MF) was constructed that relates the science value (as determined by the PI and the Science Team) to the chosen mission characteristics and to models of the planetary and stellar systems. This MF served several purposes; predicting possible science results of the proposed mission, evaluating the effects of varying the values of the mission parameters to increase the science return or to reduce the mission costs, and supporting quantitative risk assessments. The MF was also valuable for the purposes of advocating the mission by illustrating its expected capability. During later stages of implementation, it was used to keep management informed of the changing mission capability and support rapid design tradeoffs when mission down-sizing was necessary. The MF consisted of models of the stellar environment, assumed exoplanet characteristics and distributions, detection sensitivity to key design parameters, and equations that related the science value to the predicted number and distributions of detected exoplanet. A description of the MF model and representative results are presented. Examples of sensitivity analyses that supported design decisions and risk assessments are provided to illustrate the potential broader utility of this approach to other complex science-driven space missions.
Asian Americans’ Indifference to Black Lives Matter: The Role of Nativity, Belonging and Acknowledgment of Anti-Black Racism

This paper assesses how ongoing historical racism and nativism as embedded within U.S. culture requires new and important dialogues about the omnipresence of White supremacy and its interconnected mechanisms that divide communities along the lines of race and perceived in-group status. To assess the role of immigration as it is understood through paradigms of White supremacy and systemic racism, the current study examines individual-level predictors of indifference to the BLM movement based on nativity status among Asian Americans—a racialized pan-ethnic group that is comprised of predominantly foreign-born members. Using the 2016 Collaborative Multiracial Post-Election Survey, one of the few nationally representative surveys that include detailed information about the Black Lives Matter movement, our study includes 1371 Asian immigrants (i.e., foreign-born Asian Americans) and 1635 U.S.-born Asian Americans. Results demonstrate that reporting indifference to the BLM movement differ by nativity such that foreign-born Asian Americans were significantly more likely to report indifference to the BLM movement compared to their U.S.-born Asian American counterparts. However, the impact of nativity disappears once we account for sense of belonging and acknowledgement of anti-Black racism. The sense of belonging was significant in predicting indifference to the BLM movement among U.S.-born Asian Americans only. The findings contribute to our understanding of racial sense making for Asian Americans as well as an understanding of how White supremacy translates to anti-Black racism through multiple and interconnected mechanisms for the maintenance of White supremacy.
Can a Machine Correct Option Pricing Models

We introduce a novel approach to capture implied volatility smiles. Given any parametric option pricing model used to fit a smile, we train a deep feedforward neural network on the model's orthogonal residuals to correct for potential mispricings and boost performance. Using a large number of recent S&P500 options, we compare our hybrid machine-corrected model to several standalone parametric models ranging from ad-hoc corrections of Black-Scholes to more structural no-arbitrage stochastic volatility models. Empirical results based on out-of-sample fitting errors - in cross-sectional and time-series dimensions - consistently demonstrate that a machine can in fact correct existing models without overfitting. Moreover, we find that our two-step technique is relatively indiscriminate: regardless of the bias or structure of the original parametric model, our boosting approach is able to correct it to approximately the same degree. Hence, our methodology is adaptable and versatile in its application to a large range of parametric option pricing models. As an overarching theme, machine corrected methods, guided by an implied volatility model as a template, outperform pure machine learning methods.
Using the US National Air Toxics Assessment to benchmark the USEtox inhalation-mediated carcinogenic impacts of air emissions

Regional air quality models generate a high-resolution prediction of pollutant concentrations using sophisticated treatments of atmospheric fate and transport processes, speciation, and chemistry. By comparison, the multi-media box modeling underpinning the USEtox model is far simpler but allows for broad coverage of hazardous air pollutants. The purpose of the present article is to benchmark USEtox results via inhalation against a state-of-the-science regulatory model and investigate methodological areas that drive differences in results. The 2014 US National Air Toxics Assessment (NATA) used a linked dispersion-regional air quality model to evaluate human health risk from emissions of air toxics, a prescribed list of hazardous air pollutants that can cause cancer and severe human health effects. We compare the NATA results for human health risk from carcinogenic emissions to characterization factors generated by running the USEtox model on the same starting emissions inventory, namely, the US National Emissions Inventory (NEI), using the North American model parameterization. We have also decomposed characterization factors into intake fractions and effect factors. The separate comparison analysis allows us to trace the driving force for cancer risk differences. Statistical analysis is applied to determine the significance of pollutant characteristics in driving differences in results, including molecular weight, vapor pressure, octanol–water partitioning, compartment half-lives in air, and chemical composition. Comparative analysis shows a good concordance for carcinogenic impacts between the two models, with a factor of ~10 difference. The difference in effect factors is ~1.4, which is within an expected range. However, intake fraction is the major cause of cancer risk divergence. Intake fractions in NATA tend to have large variations due to the high-resolution air dispersion model and including secondary pollutants. NATA and USEtox results have consistent levels of statistical significance across the pollutant characteristics evaluated, with the greatest level of significance (p < 0.05) for molecular weight and vapor pressure, which strongly influence atmospheric fate. Formaldehyde is the dominant contributor to the total burden of diseases with 5000 to 20,000 cases of cancer per year. It is critical to benchmark LCIA results against current state-of-the-science models in order to ensure that LCA results can be reliably used for decision support. The USEtox model was not designed to mimic the complexity of full-scale air quality modeling, but still manages to produce a relative scaling of carcinogenic impacts that is consistent with NATA. Further regionalization, calibration, or inclusion of additional chemical transformations within the USEtox model may yield further performance improvements.
Understanding the role of social media in caring for patients with gynecologic cancers

Objectives: To examine the prevalence of social media use by patients with gynecologic cancers and its impact on patient education and decision making. Methods: A 10 question survey approved by our institution's Institutional Review Board was administered to patient's being followed outpatient by a gynecologic oncologist for the diagnosis of a gynecologic cancer. Patients were excluded from this study included new office visits, post-operative visits, and patients diagnosed with a pre-cancerous lesion or low-malignant potential tumors. Descriptive statistics and Likert Scale were used to analyze the data. Results: Forty percent (40%) of the patients surveyed were 61-70-years-old; 31% were 71-years-old. After correcting for patient mis-identification of their cancer diagnosis, the majority of patients had a Type I or Type II uterine cancer (63%). The majority of patients (83%) had regular access to the internet or Wi-Fi, and 64% were actively using social media. The most popular social media platforms utilized by these patients, regardless of the search history, were Facebook (80%), Google (75%) and YouTube (45%). Only 2% of the patients reported using a social media platform to document their cancer journey. The majority of patients (59%) reported using social media platforms, such as Google to research and better understand their respective diagnosis. A few patients (19%) used the healthcare system's Gynecologic Oncology website to better understand their diagnosis. Only 28% used social media/Google to help make decisions regarding their recommended treatment options. Sixty-seven percent (67%) of patients found their gynecologic oncologist through their primary gynecologist. Forty-one percent (41%) of patients would not change their timing of presentation for evaluation had information regarding their symptoms been more prevalent on social media. The majority of these patients (79%) were able to choose their diagnosis from the listed cancers (uterine, cervical, ovarian, fallopian tube, peritoneal, vulvar, vaginal, other). Of those who did not correctly identify their cancer site or choose a cancer site as listed: 52% chose their cancer as ‘other’ and specified this choice as ‘endometrial’ or ‘leiomyosarcoma,’ 29% chose the wrong cancer site (e.g., identified cervix as cancer site, diagnosed with uterine as cancer site), and 19% chose not to answer or did not know where their cancer was. Download : Download high-res image (411KB) Download : Download full-size image Conclusions: This data suggests that patients are not fully comprehending their cancer diagnosis in their doctor's offices as the majority of these patients used social media platforms to research their diagnosis. Approximately one-fifth of the patients surveyed did not appropriately identify their primary cancer site. As health care providers we need to better educate our patients. Correct diagnosis and management information in the office and through social media platforms will improve the knowledge and management options in women with gynecologic cancers.
Corpus cardiacum as a metabolic regulator in Blaberus discoidalis serville (Blattidae): I. Long-term effects of cardiatectomy on whole body and tissue respiration and on trophic metabolism

Abstract By using manometric measurements it has been shown that removal of the corpora cardiaca depresses respiratory metabolism in adult, male Blaberus discoidalis. This effect is seen within 10 days after the operation and does not change over the next 20 days. Studies on dry body weights indicate that 30-day cardiatectomized-allatectomized animals are equivalent to control animals with respect to dry matter and water content. Therefore, it is concluded that cardiatectomized-allatectomized animals are trophically normal at this time, and that lowered respiration rates have a more fundamental origin. Manometric studies on intact, excised tissues indicate that fat body of the 30-day cardiatectomized-allatectomized roach has an endogenous respiratory rate significantly lower (47%) than controls. Addition of glucose does not stimulate a return to normal respiratory levels. Muscle tissue does not show respiratory differences between cardiatectomized-allatectomized and control animals. Added glucose causes a significant decrease in muscle respiration similar to a Crabtree effect. The implications of these results relative to a mechanism of metabolic control are discussed.
Sex differences in microglial colonization of the developing rat brain

Microglia are the resident immune cells within the brain and their production of immune molecules such as cytokines and chemokines is critical for the processes of normal brain development including neurogenesis, axonal migration, synapse formation, and programmed cell death. Notably, sex differences exist in many of these processes throughout brain development; however, it is unknown whether a sex difference concurrently exists in the colonization, number, or morphology of microglia within the developing brain. We demonstrate for the first time that the number and morphology of microglia throughout development is dependent upon the sex and age of the individual, as well as the brain region of interest. Males have overall more microglia early in postnatal development [postnatal day (P) 4], whereas females have more microglia with an activated/amoeboid morphology later in development, as juveniles and adults (P30-60). Finally, gene expression of a large number of cytokines, chemokines and their receptors shifts dramatically over development, and is highly dependent upon sex. Taken together, these data warrant further research into the role that sex-dependent mechanisms may play in microglial colonization, number, and function, and their potential contribution to neural development, function, or potential dysfunction.
Physiological effects of microgravity on osteoblast morphology and cell biology.

Publisher Summary Cell growth and differentiation are fundamental in bone development, and as such they act as master regulators of bone development and remodeling. In space flight there are numerous effects on tissues and cells, some of which, such as bone and muscle loss, could be related to cell proliferation and development anomalies in microgravity. Bone proliferation and mineralization are two of the most tightly regulated processes in the cell and multiple checkpoints during the cell cycle and development ensure that cells have normal development. Among those checkpoints are growth inhibitors that cause DNA transcription arrest and programmed matrix organization. Studies have demonstrated that cell proliferation is not constitutive; it requires promoters, such as the extracellular matrix and serum growth factors that activate mitogenic kinase signaling pathways. The role of the cytoskeleton in growth and its relationship to cell cycle and the MAPK pathway is being actively investigated in many laboratories. Results from several investigators suggest that the actin cytoskeleton is a necessary component of the cell cycle, especially for the transition from G1-S phase and for anchorage-dependent DNA synthesis.
Intra-arterial Thrombolysis in Acute Ischemic Stroke

Acute stroke treatment has evolved rapidly in the last two decades with systemic thrombolysis and endovascular interventions for intracranial large artery occlusions. Neurointerventional techniques to achieve reperfusion in ischemic stroke initially involved local intra-arterial infusion of thrombolytic agents. The subsequent development of mechanical thrombectomy devices has resulted in better and faster arterial recanalization while maintaining patient safety. This approach has recently taken a large step forward with the introduction of “stent retriever” technology. In this chapter we discuss various endovascular recanalization techniques in acute ischemic stroke with illustrative cases.
SOCIAL REACTIONS TO SEXUAL ASSAULT DISCLOSURE, COPING, PERCEIVED CONTROL, AND PTSD SYMPTOMS IN SEXUAL ASSAULT VICTIMS

The social reactions that sexual assault victims receive when they disclose their assault have been found to relate to posttraumatic stress disorder (PTSD) symptoms. Using path analysis and a large sample of sexual assault survivors (N = 1863), we tested whether perceived control, maladaptive coping, and social and individual adaptive coping strategies mediated the relationships between social reactions to disclosure and PTSD symptoms. We found that positive social reactions to assault disclosure predicted greater perceived control over recovery, which in turn was related to less PTSD symptoms. Positive social reactions to assault disclosure were also associated with more adaptive social and individual coping; however, only adaptive social coping predicted PTSD symptoms. Negative social reactions to assault disclosure were related to greater PTSD symptoms both directly and indirectly through maladaptive coping and marginally through lower perceived control over recovery.
A protein kinase-A recognition sequence is structurally linked to transformation by p59v-rel and cytoplasmic retention of p68c-rel.

Abstract The Rel family of proteins includes a number of proteins involved in transcriptional control, such as the retroviral oncoprotein v-Rel, c-Rel, the Drosophila melanogaster developmental protein Dorsal, and subunits of the transcription factor NF-kappa B. These proteins are related through a highly conserved domain of approximately 300 amino acids, called the Rel homology domain, that contains dimerization, DNA binding, and nuclear targeting functions. Also within the Rel homology domain, there is a conserved consensus sequence (Arg-Arg-Pro-Ser) for phosphorylation by cyclic AMP-dependent protein kinase (PKA). We used linker insertion mutagenesis and site-directed mutagenesis to determine the importance of this sequence for the transformation of avian spleen cells by v-Rel and the subcellular localization of c-Rel in chicken embryo fibroblasts (CEF). The insertion of 2 amino acids (Pro-Trp) within this sequence completely abolished transformation and transcriptional repression by v-Rel and resulted in a shift in the localization of c-Rel from cytoplasmic to nuclear in CEF. When the conserved Ser within the PKA recognition sequence was replaced by Ala, there was no significant effect on transformation and transcriptional repression by v-Rel or on cytoplasmic retention of c-Rel. However, when this Ser was changed to Asp or Glu, transformation and transcriptional repression by v-Rel were significantly inhibited and c-Rel showed a diffuse nuclear and cytoplasmic localization in CEF. Although a peptide containing the recognition sequence from v-Rel can be phosphorylated by PKA in vitro, this site is not constitutively phosphorylated to a high degree in vivo in transformed spleen cells incubated with okadaic acid. Our results indicate that the transforming and transcriptional repressing activities of v-Rel and the cytoplasmic retention of c-Rel are dependent on the structure of the conserved PKA recognition motif. In addition, they suggest that phosphorylation at the conserved PKA site could have a negative effect on transformation and transcriptional repression by v-Rel and induce the nuclear localization of c-Rel.
Photomagnetism and photoluminescence (PL) of (Pb-Fe-e - ) complex in lead magnesium niobate-lead titanate (PMN-PT) crystals containing β-PbO nanoclusters

Abstract We present electron paramagnetic resonance (EPR)—evidence of photomagnetism under the conditions of in situ green laser illumination (photo-EPR) in lead magnesium niobate–lead titanate, Pb(Mg,Nb)O 3 –PbTiO 3 (PMN–PT), containing nanoparticles/wires of orthorhombic β-PbO as identified by Raman spectroscopy. Photo-EPR studies of the sample containing β-PbO, brownish red in color, have shown intense line at g = 2.00, and its yield increased when produced in the presence of 7.5 kG external magnetic field suggesting the formation of magnetic polaron. This was identified as due to interaction between Fe 3+ , photoinduced Pb 3+ and unpaired electron trapped at oxygen vacancies. The photoinduced growth and decay of magnetic polaron has shown a non-exponential behavior. Photoluminescence (PL) studies were conducted with excitation at 308 nm (XeCl laser) and also at 454.5, 488 and 514.5 nm using Ar + laser. The excitation with 308 nm gave broad PL centered at 500 and 710 nm the latter being quite prominent in β-PbO containing crystals, along with cooperative luminescence at 350 nm involving two emitting centers. The excitation with Ar + laser lines, close to the electronic absorption in samples containing β-PbO gave richer and sharp PL emission in red region from the constituents of the magnetic polaron and also intense anti-Stokes emission on excitation with 514.5 nm radiation. This appears to be due to phototransfer optically stimulated luminescence (PT-OSL) involving electron–hole recombination at photoinduced magnetic polaron site.
Preconditioning potentiates redox signaling and converts death signal into survival signal.

Reactive oxygen species (ROS) play a crucial role in the pathophysiology of ischemic heart disease by causing cardiac dysfunction and cell death. Several redox-sensitive anti- and pro-apoptotic transcription factors including NFκB and AP-1 progressively and steadily increase in the heart as a function of the duration of ischemia and reperfusion. When the heart is preconditioned to ischemic stress by repeated short-term ischemia and reperfusion, NFκB remains high while AP-1 is lowered to almost baseline value. The anti-apoptotic gene Bcl-2 is downregulated in the ischemic/reperfused heart, while it is upregulated in the adapted myocardium. Cardioprotective abilities of the preconditioning are abolished when heart is pre-perfused with N-acetyl cysteine, a scavenger for ROS, suggesting the role of ROS in redox signaling. Mammalian heart is protected by several defense systems which include among others, redox-regulated protein, thioredoxin. Reperfusion of ischemic myocardium results in the downregulation of thioredoxin 1 (Trx 1) expression, which was upregulated in the preconditioned myocardium. The increased expression of Trx 1 is completely blocked with an inhibitor of Trx 1, CDDP, which also abolished cardioprotection afforded by ischemic adaptation. The cardioprotective role of Trx 1 is confirmed further with transgenic mouse hearts overexpressing Trx 1. The Trx 1 mouse hearts displayed significantly improved post-ischemic ventricular recovery and reduced myocardial infarct size and apoptosis as compared to the corresponding wild-type mouse hearts. Taken together, preconditioning appears to potentiate redox signaling, which converts the “death signal” into “survival signal.”
The effect of bovine growth hormone on formation of RNA by rat liver slices

Abstract 1. Rat-liver slices incubated with [ 3 H]orotic acid incorporated label into RNA at a linear rate for at least 4 h. Labelled orotic acid was incorporated almost exclusively into 45–55-S RNA during the first 2 h incubation. Ribosomal RNA (18-S and 28-S RNA) as well as soluble RNA became labelled after 4–6 h incubation. 2. Actinomycin D (10 μg/ml) reduced the incorporation of labelled orotic acid into the 45–55-S RNA approx. 75 %. 3. Liver slices from hypophysectomized rats sacrificed 6 or 12 h after bovine growth hormone administration incorporated significantly more label during a 1-h incubation than did slices from untreated animals. Addition of growth hormone directly to the incubation medium had no demonstrable effect on the incorporation of labelled orotic acid into the 45–55-S RNA by liver slices from hypophysectomized rats. 4. Liver slices from hypophysectomized rats sacrificed 12 h after growth hormone administration incorporated approximately five times more label into ribosomal RNA (18 S and 28 S) during a 6-h incubation than did slices from untreated hypophysectomized rats. Growth hormone added directly to the incubation medium did not increase labelled orotic acid incorporation into ribosomal RNA of liver slices.
Diurnal variations in mood as asserted by self-report and verbal content analysis.

ADJECTIVE check lists (ACLs) and similar self-rating scales have been used extensively in the analysis of mood. Such devices consisting of adjectives and descriptive phrases grouped into relatively unitary scales have been found sensitive to changes in mood under experimental conditions and in real life situations .ld4 In contrast to the self-report procedure with its complete reliance upon the subject’s overt responses as an index of mood, GOTTSCHALK and GLESER~ developed content analysis scales for inferring affect level from 5 min spontaneous speech samples. Numerous studies have shown that the Gottschalk-Gleser scales are a valid measure of transient affective fluctuations resulting from natural and experimentally induced psychological, psychophysiological, psychopharmacological and psychobiochemical changes.5 It could be argued that the use of ACLs to measure mood is unwise since the validity of self-report of subjective states is difficult to establish. For example, it is unknown exactly to what extent ACLs are affected by experimental “demand characteristicz? and other response set phenomena. The Gottschalk-Gleser approach being comparably unobtrusive is probably less apt to be influenced by response sets and social demand characteristics of an experiment. There is evidence from a number of studies of a tendency for mood to vary throughout the day.?--11 The aim of this study was to compare the relative sensitivities and utilities of ACLs and the Gottschalk-Gleser scales as instruments for assessing mood, while at the same time confirming the existence of diurnal variations in mood. With time of day as an independent variable there should be a relative absence of social demand characteristics in subjects naive concerning diurnal variations in psychobiological functions. KLEITMAN~~ described diurnal performance on a number of subject-paced tasks to be characterized by minimal efficiency late at night and early in the morning with maximum eficiency 4-8 hr after awakening. It was, therefore, hypothesized that variations in mood would parallel these previously found circadian variations in efficiency of performance. * Supported in part by a National Institutes of Health Fellowship MH47945 to J. M. Taub and by a PHS Research Grant MH18928 from the National Institute of Mental Health. t The advice and encouragement of Dr. BARRY MCLAUGHLIN in the preparation of this paper is gratefully acknowledged. We thank CAROLYN WINGET for scoring the verbal samples.
Tools review: Serius-a visual programming environment

Serius Programmer 2.2 from Serius Corporation is a visual programming system that allows users to build application programs by linking together programming modules on a Macintosh. Each programming module, either an object or a function, represents programming code that has already been written. By linking these modules together in graphical chains, the user can create an application that can be executed from the Macintosh desktop.
Modulation of protein kinase C by adenosine: Involvement of adenosine A1 receptor-pertussis toxin sensitive nucleotide binding protein system

The objective of this study was to determine whether adenosine A1 or A2 receptor was responsible for the regulation of protein kinase C (PKC) in porcine coronary artery and its coupling to G-protein. Endothelium denuded arterial rings were incubated with PDBu (200 nM) in the presence or absence of adenosine receptor agonists and antagonists for 1 day. Following incubation, the arterial rings were contracted with increasing concentrations of endothelin-1 (ET-1) (10-10-10-7 M). Arteries incubated with PDBu alone failed to produce contraction in response to ET-1. On the contrary, inclusion of A1 receptor agonist ENB A at 10-9M in the incubation media with PDBu protected against the PDBu induced blunting of the ET-1 contractions by 50%. Incubation with ENBA alone increased ET-1 dependent contractions by about 2 fold. Inclusion of A1 receptor antagonist, N0861 at 10-6 M along with PDBu and ENBA, completely blocked the protective effect of ENBA against the PDBu induced attenuation of ET- 1 contractions. N0861 also completely blocked the increase in ET-1 contractions in the arterial rings incubated with ENBA alone. Another A1 receptor antagonist DPCPX also produced similar results as N0861. On the contrary, arterial rings incubated with relatively specific A2 receptor agonist CGS 21680 at 10-4 M did not produce any protection against PDBu induced blunting of the ET-1 contractions. Incubation with CGS 21680 alone also did not significantly alter the ET-1 contractions. Interestingly, inclusion of A2 receptor antagonist DMPX at 10-4 M in the incubation media along with CGS 21680 mimicked the effects of ENBA alone i.e. produced protection against PDBu and enhanced ET-1 contractions. Incubation of the arteries with ENBA alone caused an accumulation of PKC levels, whereas, incubation with CGS 21680 had no significant effect on PKC levels. To study the coupling of adenosine receptor with G-protein, the tissue was incubated for one day with cholera (CT) or pertussis toxin (PT) in the presence or absence or ENBA and PDBu as described above. Incubation with PT blocked the protective effect of ENBA against PDBu as well as the elevation of ET-1 response when incubated with ENBA alone. On the contrary, incubation with CT did not produce any significant effect on ENBA responses. These results indicate that PKC is modulated by adenosine via A1 adenosine receptors and through a PT sensitive G-protein.
Surgical outcomes and national comprehensive cancer network compliance in advanced ovarian cancer surgery in a low volume military treatment facility.

Abstract Objective To evaluate the optimal cytoreduction (OPT) rate, National Comprehensive Cancer Network (NCCN) treatment guideline compliance rate and patient outcomes for advanced stage epithelial ovarian cancer (EOC) patients at our low volume institution. Methods Following IRB approval, records of patients with Stage III-IV EOC, primary peritoneal, or fallopian tube carcinoma completing both primary surgery and adjuvant chemotherapy were reviewed. Patient demographics, clinicopathologic variables, cytoreduction status (optimal or suboptimal), NCCN treatment guideline compliance, and survival were reviewed. Standard statistical tests including the t -test, Chi-square or Fisher's exact test and Kaplan–Meier Survival curves were utilized. Results Overall, 48 patients met all inclusion criteria. 35(73%) and 13 (27%) achieved optimal and suboptimal cytoreduction, respectively. Median overall survival (OS) for all patients was 37.1months (95% CI 23.2 – 51.1months) and NCCN treatment guideline compliance was 85.4%. Compared to sub-optimally cytoreduced patients the optimally cytoreduced patients were significantly older (62.2 vs. 53.5yrs; p =0.015); no other significant clinicopathologic differences were observed between the two groups. 19 of 48 (39.6%) patients enrolled in an upfront cooperative group trial. Median OS was 43.4months for optimally compared to 15.6months in sub-optimally cytoreduced patients ( p =0.012). Conclusions NCCN treatment guideline compliance, OPT, and median OS rates in our low volume institution are similar to those reported nationally, and argue against using volume alone as a rationale for centralization of care.
Minimizing total flow time in permutation flow shop scheduling with improved simulated annealing

For the past two decades simulated annealing has been playing a crucial role in the design of optimization strategies for flow shop scheduling applications. This paper presents an efficient simulated annealing algorithm for minimizing the total flow time in permutation flow shop scheduling problems. Empirical results demonstrate the improvement in solution quality obtained by the proposed approach over state-of-the-art methods in the literature.
Clinical, histopathological and immunohistochemical characterization of a novel equine ocular disorder: heterochromic iridocyclitis with secondary keratitis in adult horses.

Objective To describe the clinical, histopathologic and immunohistochemical characteristics of an equine ocular inflammatory disease resulting in anterior uveitis and corneal endothelial inflammation associated with iris pigment dispersion and retrocorneal fibrous membrane (RFM) formation. Design Retrospective study. Animals studied Sixteen horses with evidence of pigmented keratic precipitates (KPs), corneal edema, and/or iris depigmentation. Information collected from the medical records included signalment, clinical signs, prereferral treatment duration and response to therapy, ophthalmic examination findings, postreferral treatment, response to therapy, and outcome. Results Twenty-one eyes from 16 horses were affected. Age ranged between 9 and 25 years (Average 16.1 years). Blepharospasm, epiphora, and/or corneal opacification were the first clinical signs noted. At the time of referral pigmented KPs, corneal edema, iridal depigmentation, and retrocorneal membranes were commonly seen. Treatment included topical and/or systemic anti-inflammatories and antibiotics with variable response. Reduction or cessation of anti-inflammatory therapy resulted in worsening of clinical signs and disease progression. Eight eyes ultimately required enucleation. Histopathology changes include iridal pigment loss and dispersion, RFM formation, and keratitis. Variable degrees of lymphoplasmacytic inflammation were dominated by T-cells within the corneal stroma, RFM, iris, and ciliary body with occasional multinucleated giant cells. Conclusions Heterochromic iridocyclitis with secondary keratitis (HIK) is characterized by uveal inflammation with pigment dispersion and suspected corneal endothelial dysfunction. Horses being treated for HIK require diligent and frequent follow-up examinations in combination with aggressive local immune suppression to control the disease. However, HIK may not respond to therapy and enucleation may ultimately be required to ensure the horse's comfort.
Studies on pharmaceutical powders and the state of subdivision. II. Surface area measurements of some pharmaceutical powders by the low-temperature nitrogen adsorption isotherm technique†

The practicability of the nitrogen adsorption method in determining the specific surface area of pharmaceutical powders has been illustrated in a previous paper. In this report the application of this technique to a number of nonrefractory pharmaceutical powders not previously investigated is presented. Comparisons are made of the specific surface areas of differently prepared forms of the same drug powders in order to provide a basis for interpreting the pharmacological, bacteriological, and pharmaceutical behaviors of these different forms. Other powders were investigated to extend the available quantitative data pertaining to the particle size and surface areas of some common pharmaceutical materials. The usefulness, characteristics, and limitations of this method in analysis of drug powders are discussed. Data are presented for measurements on bismuth subnitrate, bismuth subcarbonate, mercuric sulfide, and sulfanilamide. Also these studies include three different forms of sulfur, two forms of ammoniated mercury, two forms of sulfadiazine, and two forms of sulfathiazole.
Off the map: a critical geography of intellectual disabilities

A "critical geography of intellectual disabilities" is outlined. Drawing on personal experience and borrowing poetic inspiration, claims about the end of the institutional era for intellectual disabled people are disputed, and the continuing eugenic legacy, complete with its multiple stigmatizing effects, is emphasized. The extent of the social exclusion experienced by many people with intellectual disabilities in the wider community, linked to various poor quality of life indicators, is also given attention. Finally, speculations are raised about how to move beyond the "asylum" and the "ghetto", empowering intellectually disabled people in the process.
On the maximal correlation coefficient

A well-known theorem states that the maximal correlation between a pair of bivariate normal random variables equals the absolute value of their ordinary (Pearson) correlation. This work provides a short new proof, besides establishing some results regarding the maximal correlation coefficient in general.
Laparoscopic colon resection for colon cancer

Abstract Introduction Laparoscopic colon resection for cancer is as yet an unproven operation. This review article summarizes current data on the topic. Methods A Medline review identified articles published since 1990 summarizing patients with potentially curable colon cancer who underwent a laparoscopic-assisted colon resection. Only articles that were randomized or had a control group with historical or matched open cases were used. Results Very few prospective randomized controls exist. Several clinical trials are under way with one completed. Data thus far support some patient benefits with a laparoscopic approach. No differences in morbidity, oncologic data, or survival appear to exist. Conclusions The results of ongoing clinical trials are still needed to further evaluate the role of laparoscopic assisted colon resection in patients with potentially curable colon cancer.
Tissue integration of growth factor-eluting layer-by-layer polyelectrolyte multilayer coated implants

Drug eluting coatings that can direct the host tissue response to implanted medical devices have the potential to ameliorate both the medical and financial burden of complications from implantation. However, because many drugs useful in this arena are biologic in nature, a paucity of delivery strategies for biologics, including growth factors, currently limits the control that can be exerted on the implantation environment. Layer-by-Layer (LbL) polyelectrolyte multilayer films are highly attractive as ultrathin biologic reservoirs, due to the capability to conformally coat difficult geometries, the use of aqueous processing likely to preserve fragile protein function, and the tunability of incorporation and release profiles. Herein, we describe the first LbL films capable of microgram-scale release of the biologic Bone Morphogenetic Protein 2 (BMP-2), which is capable of directing the host tissue response to create bone from native progenitor cells. Ten micrograms of BMP-2 are released over a period of two weeks in vitro; less than 1% is released in the first 3 h (compared with commercial collagen matrices which can release up to 60% of BMP-2, too quickly to induce differentiation). BMP-2 released from LbL films retains its ability to induce bone differentiation in MC3T3 E1S4 pre-osteoblasts, as measured by induction of alkaline phosphatase and stains for calcium (via Alizarin Red) and calcium matrix (via Von Kossa). In vivo, BMP-2 film coated scaffolds were compared with film coated scaffolds lacking BMP-2. BMP-2 coatings implanted intramuscularly were able to initiate host progenitor cells to differentiate into bone, which matured and expanded from four to 9 weeks as measured by MicroCT and histology. Such LbL films represent new steps towards controlling and tuning host response to implanted medical devices, which may ultimately increase the success of implanted devices, provide alternative new approaches toward bone wound healing, and lay the foundation for development of a multi-therapeutic release coating.
Emergence Profile of Overwintered Boll Weevils and Entry into Cotton

Small plots of cotton and pheromone traps were used to study the emergence profile of overwintered boll weevils, Anthonomus grandis Boheman, and their entry into cotton. Boll weevil movement into cotton was closely related to the phenology of the plant. Very few overwintered weevils entered presquaring cotton but immigration increased with increasing size and number of squares. Results of this study indicate that overwintered weevil colonization is not a result of random entry into cotton followed by pheromone production. Rather, overwintered weevil immigration into cotton appears to be a positive response to squaring cotton, with attraction greatly intensified by pheromone production after weevils feed on squares. Overwintered weevil response to pheromone traps appeared to provide a relatively accurate index of population size and activity. In the study area pheromone traps indicated that the major portion of the overwintered population was active several weeks before weevil colonization occurred in cotton. These data indicated that ca. the last 10% of boll weevils emerging from overwintering habitat contributed the major portion of the population that entered cotton. The relationship between the number of weevils responding to pheromone traps and the number entering the cotton plots indicates that pheromone traps can be used to predict the degree of overwintered boll weevil infestation which will occur in cotton.
Opposite effects of unmodified prolactin and a molecular mimic of phosphorylated prolactin on morphology and the expression of prostate specific genes in the normal rat prostate.

BACKGROUND In the current study, we have investigated the individual roles of unmodified, wild-type prolactin (WT PRL) and a molecular mimic of phosphorylated prolactin (S179D PRL) in the normal rat prostate. METHODS In the first animal experiment, recombinant WT PRL and S179D PRL were delivered to adult male rats at a rate of 14 μg/kg per day for 3 weeks. In the second animal experiment, two subcutaneous (200 μg/kg) injections of long-acting forms of the two PRLs were given to adult male rats on day 1 and day 22 for a total of 5.5 weeks of treatment. RESULTS The different forms of PRL had opposite effects on the normal rat prostate, independently of androgens. WT PRL promoted morphologic changes in prostate epithelium consistent with preparation for cell proliferation, whereas S179D PRL produced morphologic evidence of a more differentiated epithelium. Northern blot analysis of expression of the two major prostate specific proteins, prostatein and probasin, showed that WT PRL decreased, whereas S179D PRL increased, the expression of the mRNAs for these two proteins. At the same time, S179D PRL reduced both testosterone and dihydrotestosterone levels. CONCLUSION We conclude that PRL is an important modulator of normal rat prostate biology and that different forms of PRL have specific functions. The molecular mimic of phosphorylated PRL, S179D PRL, is the most important in terms of epithelial cell differentiation. Prostate 54: 25–33, 2003. © 2002 Wiley-Liss, Inc.
Impairment of phenylalanine conversion to tyrosine in end-stage renal disease causing tyrosine deficiency.

Impairment of phenylalanine conversion to tyrosine in end-stage renal disease causing tyrosine deficiency. Background Tyrosine is not considered an indispensable amino acid because in humans phenylalanine is converted to tyrosine. Recent human studies demonstrated that tyrosine production from phenylalanine occurs not only in liver but also in kidney. Methods Here we report results from studies, performed in end-stage renal disease (ESRD) patients and in healthy controls using [ 15 N] phenylalanine and [ 2 H 4 ] tyrosine as tracers demonstrating the mechanism of tyrosine deficiency in patients with renal failure. Results Phenylalanine flux (an index of protein breakdown) was identical in both groups either before or during an infusion of amino acid mixture. In contrast, tyrosine flux (representing protein breakdown and tyrosine appearance from phenylalanine) and conversion of phenylalanine to tyrosine were lower in ESRD patients [2.05 ± 0.30 μmol/kg fat-free mass (FFM)/hour and 2.59 ± 0.52 μmol/kg FFM/hour, before and during amino acid infusion, respectively] than in the control subjects (4.07 ± 0.54 μmol/kg FFM/hour and 5.53 ± 0.86 μmol/kg FFM/hour, P Conclusion We conclude that reduced conversion of phenylalanine to tyrosine causes tyrosine deficiency in patients with ESRD prompting to propose that tyrosine replacement is potentially required in patients with ESRD.
Effects of heavy-atom substituents on matrices used for matrix-assisted laser desorption-ionization mass spectrometry

The data reported show that heavy-atom substitution on matrices that are used for matrix-assisted laser desorption-ionization mass spectrometry enhance [M + H]+ ion yields of both Leu—enkephalin and vitamin B12. Heavy-atom substitution alters the excited state relaxation dynamics of the matrices as indicated by measured decreases in the measured luminescence (fluorescence and/or phosphorescence) observed for heavy atoms that contain matrices relative to the nonheavy-atom-substituted matrices. The results presented are consistent with the direct involvement of an electronically excited state of the matrix in the formation of analyte [M + H]+ ions.