cssi/SciSciGPT-SciSciNet huggingface dataset:
“I liked the town no better at our second interview”: A New Emerson Letter from Charleston in 1827

Abstract The article prints a previously unpublished four-page letter that Emerson wrote in 1827, which details his impressions of Charleston, especially its religious and cultural institutions, during his visits there. The authors have mined Charleston newspapers and unpublished Emerson family correspondence to contextualize the letter as it sheds new light on Emerson's earliest southern sojourn.
Biological Semiconductors: Structural Control of Heme Redox Potentials in PpcA, a 3-Heme Cytochrome

In an effort to tune and optimize relative bandgap potentials found in biological nanowires that form from multiheme domains of members of the cytochrome c7 family, we developed and extensively characterized 12 point mutations of PpcA, a 3-heme member of the cytochrome c7 family native to Geobacter sulfurreducens. These mutations were engineered to influence the redox potential (Em) of the middle heme (heme III) in PpcA by using four different strategies: performing charge reversal mutations, decreasing solvent access to the heme plane with bulky residues, altering the native bis-histidine axial ligation of the heme, and by attempting to form hydrogen bonds with the propionates of the heme. The latter strategy is expected not only to increase Em but also to introduce a redox Bohr effect. Out of 12 mutants, 11 were successfully expressed in E.coli and show thermal stability in temperature-dependent CD experiments comparable to the wild-type protein (Tm > 90°C). HPLC-ESI-MS was used to confirm both the purity and the mass of the expressed mutants. Small-angle X-ray scattering confirmed that the mutant proteins formed the expected compact globular structures. In addition to ongoing attempts to obtain protein crystals for X-ray crystallography, we performed extensive all-atom molecular dynamics simulations for all mutants. Formation of propionate hydrogen bonds is supported by simulations for A19R and A23R, while increased solvent access is supported for A19I, A19R, A23R, H20M, and K60E. UV/Vis and NMR redox titrations were performed in order to measure the effect of the mutations on the electrochemical properties of all 3 hemes and to understand the underlying principles and viable approaches in tuning relative heme redox potentials. Successful development of this project may lead to biological semiconductors with much smaller footprints and selectively tunable bandgap properties.
Improving the Polynomial Approximation of an Object Characteristic that is not Directly Measurable by Using Measurement Reduction

We establish the possibility of determining a characteristic that is not directly measurable of an object that is controlled by an information-measuring system using the interpretation of the results of observations on the basis of measurement reduction and polynomial approximation methods for numerical differentiation. The basis of the developed methods of improving the polynomial approximation of not directly measurable characteristics of an object constitute the proposed criteria for assessing the effectiveness of measurement reduction.
A liquid chromatographic method for determination of 20 disperse dyes in drink and wine.

A liquid chromatographic method was established for the determination of 20 disperse dyes in drink and wine. The chromatographic conditions, including analysis column types, composition of mobile phase, detection wavelengths, were optimized. The sample was extracted with dichloromethane-ethyl ether mixed solution, and the separation of 20 dyes was performed on a C18 column, by using solution of 10 mmol/L ammonium acetate as mobile phase, at detection wavelengths of 430, 570, 640 nm. Under the optimal conditions, the calibration curves were linear in the range of 0.5-5.0 mg/L with correlation coefficients higher than 0.999. The recoveries of disperse dyes from drink and wine at spiked levels of 0.1, 0.2, 0.4 mg/kg were in the range of 80%-99% with RSDs of 0.1-9.1%. The result showed that the method was simple, rapid and accurate, and was suitable for the determination of disperse dyes in drink and wine.
The Molecular Regulation of Body Weight: The Role of Leptin, Ghrelin and Hypocretin

Publisher Summary A great deal of progress has occurred toward an understanding of the molecular interactions involved in regulating appetite. These advances promise to increase one's genetic understanding of both overconsumptive and underconsumptive food-related behaviors. This chapter describes three well-characterized proteins involved in both the maintenance and disruption of the energetic balancing act. Many appetite-specific neuronal circuits are found within the brainstem and hypothalamus. These regions respond to information about energy homeostasis through an interrelated network of hormonal signals arising from tissues throughout the body. Three of the best characterized signals are leptin, ghrelin, and hypocretin. Circulating leptin, a hormone generated by adipose tissue, provides information about overall energy stores. Ghrelin, a protein secreted by the gut, communicates with the arcuate nucleus of the hypothalamus and functions as a short-term meal initiation signal. Hypocretin (also called orexin) has a wide range of functions. While it is a powerful stimulator of feeding behavior, mutations in its sequence are also responsible for narcolepsy, a disorder of arousal. Hypocretin's involvement in disparate physiological roles serves as an important example of the multi-functionality of most hormones involved in the maintenance of energy homeostasis. The chapter briefly summarizes the effects of these three proteins on the creation of feeding behaviors and the maintenance of energy balance in adult humans.
Comparing Alternate Aerobic Tests for United States Navy Physical Readiness Test

ABSTRACTThe current Navy Physical Readiness Test allows for several alternatives to test aerobic fitness. Two currently approved alternate aerobic devices (elliptical trainer and stationary bike) were tested for correlation to VO2max and measured 1.5-mile run times. Two additional devices (2-km rower and 5-km cycle ergometer) were also evaluated as possible alternates. 132 active duty military and Naval Academy midshipmen were recruited from the United States Naval Academy. Subjects participated in six testing sessions over an eight-week period. Subjects performed a VO2max test (n = 96), 1.5 mile run (n = 118), 12-minute stationary bike test (n = 115), 12-minute elliptical trainer test (n = 108), 5-km cycle ergometer test (n = 114), and 2-km rower test (n = 115). Performances in all tests were correlated with one another. The strongest correlation to VO2max existed with the 1.5-mile run (r = –0.84). The 5-km cycle ergometer test (r = –0.42), 2-km rower test (r = –0.42), 12-minute stationary bike test (r =...
Scmbug: policy-based integration of software configuration management with bug-tracking

Software configuration management(SCM) and bug-tracking are key components of a successful software engineering project. Existing systems integrating the two have failed to meet the needs of the ASU scalable computing lab, powered by open-source software. An improved solution to the integration problem, designed to accomodate both free and commercial systems alike, is presented. Scmbug offers a policy-based mechanism of capturing and handling integration of SCM events, such as committing software change-sets and labeling software releases, with a bug-tracking system. Synchronous verification checks and the flexibilty to match multiple development models separate this approach from related work. We address design limitations of existing integration efforts, suggest improvements in SCM and bug-tracking systems required to achieve a scalable solution, and document our early integration experiences.
General synthesis of pyrido[1,2-a]indoles via Pd-catalyzed cyclization of o-picolylbromoarenes

Abstract An efficient Pd-catalyzed cyclization of o-picolylbromoarenes into pyridoindoles has been developed. This novel transformation, which proceeds through a not common for Pd catalysis L-to X-type pyridine ligand swap, provides an efficient route to aryl-, as well as to cyanopyrido[1,2-a]indoles, not easily accessible by existing cyclization methods.
Cost-sensitive learning with noisy labels

We study binary classification in the presence of class-conditional random noise, where the learner gets to see labels that are flipped independently with some probability, and where the flip probability depends on the class. Our goal is to devise learning algorithms that are efficient and statistically consistent with respect to commonly used utility measures. In particular, we look at a family of measures motivated by their application in domains where cost-sensitive learning is necessary (for example, when there is class imbalance). In contrast to most of the existing literature on consistent classification that are limited to the classical 0-1 loss, our analysis includes more general utility measures such as the AM measure (arithmetic mean of True Positive Rate and True Negative Rate). For this problem of cost-sensitive learning under class-conditional random noise, we develop two approaches that are based on suitably modifying surrogate losses. First, we provide a simple unbiased estimator of any loss, and obtain performance bounds for empirical utility maximization in the presence of i.i.d. data with noisy labels. If the loss function satis_es a simple symmetry condition, we show that using unbiased estimator leads to an efficient algorithm for empirical maximization. Second, by leveraging a reduction of risk minimization under noisy labels to classification with weighted 0-1 loss, we suggest the use of a simple weighted surrogate loss, for which we are able to obtain strong utility bounds. This approach implies that methods already used in practice, such as biased SVM and weighted logistic regression, are provably noise-tolerant. For two practically important measures in our family, we show that the proposed methods are competitive with respect to recently proposed methods for dealing with label noise in several benchmark data sets.
Dexamethasone-induced immunosuppression: mechanisms and implications for immunotherapy

Corticosteroids are routinely utilized to alleviate edema in patients with intracranial lesions and are first-line agents to combat immune-related adverse events (irAEs) that arise with immune checkpoint blockade treatment. However, it is not known if or when corticosteroids can be administered without abrogating the efforts of immunotherapy. The purpose of this study was to evaluate the impact of dexamethasone on lymphocyte activation and proliferation during checkpoint blockade to provide guidance for corticosteroid use while immunotherapy is being implemented as a cancer treatment. Lymphocyte proliferation, differentiation, and cytokine production were evaluated during dexamethasone exposure. Human T cells were stimulated through CD3 ligation and co-stimulated either directly by CD28 ligation or by providing CD80, a shared ligand for CD28 and CTLA-4. CTLA-4 signaling was inhibited by antibody blockade using ipilimumab which has been approved for the treatment of several solid tumors. The in vivo effects of dexamethasone during checkpoint blockade were evaluated using the GL261 syngeneic mouse intracranial model, and immune populations were profiled by flow cytometry. Dexamethasone upregulated CTLA-4 mRNA and protein in CD4 and CD8 T cells and blocked CD28-mediated cell cycle entry and differentiation. Naive T cells were most sensitive, leading to a decrease of the development of more differentiated subsets. Resistance to dexamethasone was conferred by blocking CTLA-4 or providing strong CD28 co-stimulation prior to dexamethasone exposure. CTLA-4 blockade increased IFNγ expression, but not IL-2, in stimulated human peripheral blood T cells exposed to dexamethasone. Finally, we found that CTLA-4 blockade partially rescued T cell numbers in mice bearing intracranial gliomas. CTLA-4 blockade was associated with increased IFNγ-producing tumor-infiltrating T cells and extended survival of dexamethasone-treated mice. Dexamethasone-mediated T cell suppression diminishes naive T cell proliferation and differentiation by attenuating the CD28 co-stimulatory pathway. However, CTLA-4, but not PD-1 blockade can partially prevent some of the inhibitory effects of dexamethasone on the immune response.
About the depolymerization of cellulose propionate to segments with low DP

Low molecular weight cellulose propionate (CP) segments were synthesized by depolymerization with HBr under esterification conditions using either a commercial CP with residual hydroxyl groups (DSOH ca. 0.4) or a tripropionate (CTP). The depolymerization using CTP yielded segments having a minimum DP of as low as 7, whereas the depolymerization of the commercial CP resulted in segments having a minimum DP of 50. Differences were also seen in the rate of depolymerization and the Mark-Houwink exponent, which declined from 1 to 0.6 below DP 100 and 30 for commercial CP and CTP, respectively. The results are consistent with the hypothesis that branching is induced by transglycosidation when OH-containing cellulose derivatives are depolymerized with HBr in aprotic solution.
X-ray Fluorescence Nanotomography of Single Bacteria with a Sub-15 nm Beam

X-ray Fluorescence (XRF) microscopy is a growing approach for imaging the trace element concentration, distribution, and speciation in biological cells at the nanoscale. Moreover, three-dimensional nanotomography provides the added advantage of imaging subcellular structure and chemical identity in three dimensions without the need for staining or sectioning of cells. To date, technical challenges in X-ray optics, sample preparation, and detection sensitivity have limited the use of XRF nanotomography in this area. Here, XRF nanotomography was used to image the elemental distribution in individual E. coli bacterial cells using a sub-15 nm beam at the Hard X-ray Nanoprobe beamline (HXN, 3-ID) at NSLS-II. These measurements were simultaneously combined with ptychography to image structural components of the cells. The cells were embedded in small (3–20 µm) sodium chloride crystals, which provided a non-aqueous matrix to retain the three-dimensional structure of the E. coli while collecting data at room temperature. Results showed a generally uniform distribution of calcium in the cells, but an inhomogeneous zinc distribution, most notably with concentrated regions of zinc at the polar ends of the cells. This work demonstrates that simultaneous two-dimensional ptychography and XRF nanotomography can be performed with a sub-15 nm beam size on unfrozen biological cells to co-localize elemental distribution and nanostructure simultaneously.
Portfolio Assessment and Certification: Three Cases in Academic Program Administration

Technical and professional communication (TPC) are disciplines lacking universal evaluative metrics such as certification of programs, widespread certification for practitioners, and standardized testing. The locus of assessment is usually entirely within the program itself, hampering comparison and cross-pollination of ideas, but enabling local decision-making and management. Indeed, in the absence of assessment measures, good things can happen: cultural values can drive curricula; a student-centered, ethical practice can thrive; lifelong learning may be encouraged. At the same time, rigorous assessment might offer a way to measure those things which are indeed measurable, beyond the rote metrics of class sizes and technology resources. Assessment, if embraced by faculty as a means toward conscientious improvement of one’s teaching and the quality of academic programs, can be productive despite the specter of external accountability. Further, assessment may be increasingly important in defense of our curricula, as we continue to face difficulty in answering questions about what makes a specific program or department “successful”. We may also need to explain our professional disciplinary status and perform other discursive feats as we assist with marketing our students to industry. In this paper, we profile three programs with entirely different approaches to portfolios.
Non-College-Bound English Learners as the Underserved Third: How Students Graduate from High School Neither College- nor Career-Ready

Not all high school students go to college. Yet, because there is currently such a dominant emphasis on “college for all,” preparing non-college-bound students for career-readiness has received sho...
In vitro antimicrobial activity of topical otological antimicrobials and Tris-EDTA against resistant Staphylococcus pseudintermedius and Pseudomonas aeruginosa isolates from dogs

Background The value of susceptibility tests for the selection of topical otological antimicrobial agents is unclear. Laboratories test antibiotic concentrations substantially lower than concentrations supplied in topical formulations. Additionally, microbiological consensus statements are not available for topical antimicrobials. Hypothesis/objectives The primary aim of this study was to measure the minimum inhibitory and bactericidal concentrations of enrofloxacin, gentamicin, marbofloxacin, neomycin, orbifloxacin, polymyxin B and silver sulfadiazine from concentrations available in otological formulations (COF) to 1:59,000 dilution. The secondary aim was to evaluate the effect of Tris-EDTA in conjunction with these antimicrobial agents. Methods and materials Twenty resistant clinical isolates [Staphylococcus pseudintermedius (n = 10) and Pseudomonas aeruginosa (n = 10)] were tested by broth microdilution using a concentrated inoculum (3.75 × 107 cfu/mL). Results Concentrations available in otological formulations were at least 26× greater than the MICs for S. pseudintermedius and P. aeruginosa. COFs of polymyxin B and SSD were 27× greater than the MBCs for P. aeruginosa, whereas all other antimicrobial COFs were equal to or less than the MBCs for both organisms. Tris-EDTA significantly reduced the MICs of all antimicrobials, except with SSD for P. aeruginosa, and it significantly increased the MIC of SSD for S. pseudintermedius. Conclusions and clinical importance Further studies are warranted to validate the present results in vivo. COFs are inhibitory and less likely bactericidal, with few exceptions, against resistant strains of these organisms. Tris-EDTA may be advantageous for P. aeruginosa whereas no additional benefit is afforded against S. pseudintermedius. Susceptibility tests may not be useful for the selection of topical otological antimicrobial agents.
181 EVALUATION OF A PEDIATRIC OBESITY TREATMENT PROGRAM.

Objective Obesity and overweight-related disease are an increasing problem in the pediatric and adolescent populations. The prevalence of overweight pediatric patients is up to 20% in the United States. Our objective was to evaluate the efficacy of our pediatric weight management program to determine how to further improve the program. Background The weight management program was a 12-week multidisciplinary program including physicians, nurses, physical therapists, and a nutritionist. Patients aged 6 to 16 with no or mild comorbidities were referred to the program, which included weekly weights, blood pressure checks, dietary counseling, and supervised exercise. Our pilot program was composed of 97 patients with a mean age of 11.7 years (6.1-17), including 40 boys (41%) and 58 girls (59%.). Methods Evaluation of our pilot program included retrospective chart review and follow-up telephone surveys. Eighty-four patients were selected for review. Thirteen patients did not follow up after initial evaluation and are excluded from this analysis. Initial and ending body mass index (BMI) and blood pressures were compared. Because the patient9s height was recorded only at the beginning of the program, end-point BMIs were recalculated using the initial height adjusted for age-appropriate growth velocity. Blood pressures were compared before and after the program. Telephone surveys sought feedback and follow-up data. Results Initial mean BMI was 37.1 kg/m2 (21.4-54.4.) Final mean BMI was 36.9 kg/m2 for a mean difference of −0.208 (−2.87 to +2.38, p = .057). Changes in blood pressure were also evident, with a higher percentage of children having normal blood pressure or prehypertension at program end compared with the initial visit (initial vs end: 31 vs 55% normal blood pressure; 15 vs 27% prehypertension; 53 vs 18% hypertension). Telephone surveys resulted in 24.6% patients reporting weight maintenance, 17.5% further weight loss, 54.3% weight gain, and 3.6% unsure of weight status following the program. Conclusions Although dramatic reductions of BMI were not seen, weight maintenance can be an important end point in reducing weight-related comorbidity. The pilot program used progressive improvement of nutrition and physical activity, so only modest improvements were expected. Both the reductions in prehypertension/hypertension and reported continued weight loss/maintenance are encouraging.
High Voltage Devices, Topologies and Gate Drivers

Presents a collection of slides covering the following topics: semiconductor growth; high voltage applications; power electronics; high voltage power device market; AC-DC power supply; power system topologies; gate drivers; power switch; buck converter; and wide bandgap.
Out-Of-Network Billing And Negotiated Payments For Hospital-Based Physicians.

When physicians whom patients do not choose and cannot avoid can bill out of network for care delivered within in-network hospitals, it exposes patients to financial risk and undercuts the function...
Validation of “patient-reported outcomes via online questionnaire” as a urinary continence assessment and quality improvement tool following radical prostatectomy

Abstract Background Securing reliable data on functional outcomes following radical prostatectomy (RP) is paramount to patient follow-up and management. Objective To validate an email-based patient-reported outcomes tracking system in assessing pad-free continence rates and time-to continence recovery following RP. Patients and Methods 483 men undergoing RP by a single surgeon from November 2013 to March 2019 were prospectively assigned to 1 of 3 tracking systems: 1) a preaddressed paper packet containing a pad-free card and daily urinary pad log, (N = 249); 2) an automated email questionnaire, (N = 234) or 3) both (N = 51). Patients tracked electronically received electronic Research Electronic Data Capture surveys 30 days after catheter removal, with up to 3 reminders sent automatically if no response was received within 2 days. Response rates and continence rates were compared in group 1 vs. group 2 via student t-tests; time-to pad-free status was assessed for concordance among men in group 3 via linear regression. Results Thirty-day response rates in group 1 (paper) vs. group 2 (electronic) were 80.7% (201/249) and 94.0% (220/234), (P In group 3, time to pad-free continence recovery assessed via Patient Reported Outcomes via Online Questionnaire (PROVOQ) was highly concordant in 89.6% (43/48) of patients ± 5 days (Figure 1, R2 = 0.9893). No significant bias was found for subsequent reporting in either group. Conclusion The use of automated email survey questionnaires via PROVOQ for the assessment of patient-reported post-RP continence recovery facilitates increased response rates, timeliness of response, and accuracy. PROVOQ significantly reduce the labor of tracking continence outcomes, improve quality improvement efforts, and enables surgeons to more clearly differentiates risk of long-term incontinence.
Research on Network Topology Model of Tactical Communication System

In this paper, the characteristics of tactical communication system’s network topology structure are analyzed firstly, such as flexible node networking, multiplechannel transmission and hierarchical distribution mode, which are taken as the basic requirements of network topology model construction. And then the system connection matrix and network path function, which form the network topology model of tactical communication system, are constructed by graph theory. It can effectively solve the problem of designing optimal routing tactical communications business. Finally the feasibility of the model is verified item by item according to the network topology characteristics, which provides reference for the establishment of simulation model of tactical communication system.
Salmonella Typhimurium and inflammation: a pathogen-centric affair

Microbial infections are controlled by host inflammatory responses that are initiated by innate immune receptors after recognition of conserved microbial products. As inflammation can also lead to disease, tissues that are exposed to microbial products such as the intestinal epithelium are subject to stringent regulatory mechanisms to prevent indiscriminate signalling through innate immune receptors. The enteric pathogen Salmonella enterica subsp. enterica serovar Typhimurium, which requires intestinal inflammation to sustain its replication in the intestinal tract, uses effector proteins of its type III secretion systems to trigger an inflammatory response without the engagement of innate immune receptors. Furthermore, S. Typhimurium uses a different set of effectors to restrict the inflammatory response to preserve host homeostasis. The S. Typhimurium–host interface is a remarkable example of the unique balance that emerges from the co-evolution of a pathogen and its host. In this Review, Galan discusses the mechanisms by which Salmonella enterica subsp. enterica serovar Typhimurium triggers inflammation in the intestinal tract through the activities of effector proteins as well as the mechanisms that are aimed at recovering host homeostasis after the inflammatory response.
Zyzzyva: speculative Byzantine fault tolerance

A longstanding vision in distributed systems is to build reliable systems from unreliable components. An enticing formulation of this vision is Byzantine fault-tolerant (BFT) state machine replication, in which a group of servers collectively act as a correct server even if some of the servers misbehave or malfunction in arbitrary ("Byzantine") ways. Despite this promise, practitioners hesitate to deploy BFT systems at least partly because of the perception that BFT must impose high overheads. In this article, we present Zyzzyva, a protocol that uses speculation to reduce the cost of BFT replication. In Zyzzyva, replicas reply to a client's request without first running an expensive three-phase commit protocol to agree on the order to process requests. Instead, they optimistically adopt the order proposed by a primary server, process the request, and reply immediately to the client. If the primary is faulty, replicas can become temporarily inconsistent with one another, but clients detect inconsistencies, help correct replicas converge on a single total ordering of requests, and only rely on responses that are consistent with this total order. This approach allows Zyzzyva to reduce replication overheads to near their theoretical minima and to achieve throughputs of tens of thousands of requests per second, making BFT replication practical for a broad range of demanding services.
The role of stimulated emission in luminescence decay

The effect of stimulated emission on observed fluorescence dynamics was demonstrated. Experimental results show that the decay of strong transitions in four level systems is significantly changed by stimulated emission even under conditions where the upper excited level population density is not noticeably altered. A new method for measuring the stimulated emission cross-section of a transition results and is presented.
Carson Strong's "Positive killing and the irreversibly unconscious patient": a commentary.

There is general agreement that death of the entire brain results in death of the person, and that such a condition can exist in a body which is still technically “alive.”1,2 Dr. Strong additionally contends that in cases of irreversible coma, since cognitive abilities characteristic of the person are no longer manifest and cannot be expected to reappear, such an individual no longer has the “right to life” and somatic death can be initiated by “positive killing.” This, the author claims, can be considered a logical and morally acceptable extension of the conceptual framework now in force for dealing with cases of isolated brain death.
Deficits in axonal transport in hippocampal-based circuitry and the visual pathway in APP knock-out animals witnessed by manganese enhanced MRI.

Mounting evidence implicates axonal transport defects, typified by the presence of axonal varicosities with aberrant accumulations of cargo, as an early event in Alzheimer's disease (AD) pathogenesis. Work identifying amyloid precursor protein (APP) as a vesicular motor receptor for anterograde axonal transport further implicates axonal transport in AD. Manganese-enhanced MRI (MEMRI) detects axonal transport dynamics in preclinical studies. Here we pursue an understanding of the role of APP in axonal transport in the central nervous system by applying MEMRI to hippocampal circuitry and to the visual pathway in living mice homozygous for either wild type or a deletion in the APP gene (n = 12 for each genotype). Following intra-ocular or stereotaxic hippocampal injection, we performed time-lapse MRI to detect Mn^(2+) transport. Three dimensional whole brain datasets were compared on a voxel-wise basis using within-group pair-wise analysis. Quantification of transport to structures connected to injection sites via axonal fiber tracts was also performed. Histology confirmed consistent placement of hippocampal injections and no observable difference in glial-response to the injections. APP−/− mice had significantly reduced transport from the hippocampus to the septal nuclei and amygdala after 7 h and reduced transport to the contralateral hippocampus after 25 h; axonal transport deficits in the APP−/− animals were also identified in the visual pathway. These data support a system-wide role for APP in axonal transport within the central nervous system and demonstrate the power of MEMRI for assessing neuronal circuitry involved in memory and learning.
Association of variant ABCG2 and the pharmacokinetics of epidermal growth factor receptor tyrosine kinase inhibitors in cancer patients.

The purpose of the study was to determine if the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, are substrates for the efflux transporter ABCG2, and to investigate the relevance of the ABCG2 421C>A (Q141K) polymorphism to the pharmacokinetics of gefitinib. Gefitinib and erlotinib transport in vitro was studied using HEK293 cells transfected with wild-type ABCG2 or a Q141K clone. Gefitinib pharmacokinetics was determined in 27 cancer patients. was. ABCG2 421C>A and ABCB1 3435C>T genotypes were determined using direct sequencing. Cells expressing wild-type ABCG2 exhibited lower intracellular accumulation of gefitinib and erlotinib at concentrations of 0.1 and 1 microM, and higher efflux at 1 microM than cells lacking ABCG2 (p A locus than those with a wild-type genotype (median, 5.07 vs. 3.60, p = 0.004). No significant associations were observed between the ABCB1 3435C>T genotype and gefitinib pharmacokinetics. In conclusion, gefitinib and erlotinib are ABCG2 substrates, while they inhibit ABCG2 at higher concentrations. A functional variant of ABCG2 is associated with greater gefitinib accumulation at steady-state and may be relevant to toxicity and antitumor activity of EGFR TKIs.
Cystine Knot of the Gonadotropin α Subunit Is Critical for Intracellular Behavior but Not for in Vitro Biological Activity

The common α subunit of glycoprotein hormones contains five disulfide bonds. Based on the published crystal structure, the assignments are 7–31, 59–87, 10–60, 28–82, and 32–84; the last three comprise the cystine knot, a structure also seen in a variety of growth factors. Previously, we demonstrated that the efficiency of secretion and the ability to form heterodimers by α subunits bearing single cysteine residue mutants in the cystine knot were significantly reduced. These results suggested that the cystine knot is critical for the intracellular integrity of the subunit. To assess if the presence of the free thiol affected the secretion kinetics, we constructed paired cysteine mutants of each disulfide bond of the α subunit. The secretion rate for these monomers was comparable with wild type except for the α-10–60 mutant, which was 40% lower. The recovery of the α7–31 and α59–87 mutants was greater than 95%, whereas for the cystine knot mutants, it was 20–40%. Co-expression of the wild-type chorionic gonadotropin β subunit with double cysteine mutants did not enhance the recovery of α mutants in the media. Moreover, compared with wild-type, the efficiency of heterodimer formation of the α10–60 or α32–84 mutants was less than 5%. Because subunit assembly is required for biological activity, studies on the role of these disulfide bonds in signal transduction were not possible. To bypass the assembly step, we exploited the single chain model, where the α and β subunits are genetically fused. The recovery of secreted tethered gonadotropins bearing mutations in the cystine knot was increased significantly. Although dimer-specific monoclonal antibodies discriminated the conformation of single chain α10–60 and α32–84 mutants from the native heterodimer, these mutants were nevertheless biologically active. Thus, individual bonds of cystine knot are important for secretion and heterodimer formation but not for in vitro bioactivity. Moreover, the data suggest that the native heterodimer configuration is not a prerequisite for receptor binding or signal transduction.
The ab initio gradient revolution in structural chemistry: The importance of local molecular geometries and the efficacy of joint quantum mechanical and experimental procedures

Abstract The use of ab initio gradient calculations to determine structural information is reviewed. The significance of local geometries is discussed. Many calculated structural trends in local geometries are often unobservable by direct quantitative experimental techniques, presenting a challenge to develop more powerful experimental methods. The applications of calculated structural data in interpreting experimental results in microwave spectroscopy and electron diffraction are discussed.
Comparison of histidine-tryptophan-ketoglutarate solution and University of Wisconsin solution in extended criteria liver donors.

Liver, pancreas, and kidney allografts preserved in histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) solutions have similar clinical outcomes. This study compares HTK and UW in a large number of standard criteria donor (SCD) and extended criteria donor (ECD) livers at a single center over 5 years. All adult, cadaveric liver and liver-kidney transplants performed between July 1, 2001 and June 30, 2006 were reviewed (n = 698). There were 435 livers (62%) categorized as ECD for severe physiologic stress and 70 (10%) because of old age. Recipient outcomes included perioperative death or graft loss and overall survival. Liver enzymes were analyzed for the first month post-transplant. Biliary complications were assessed through chart review. Overall, 371 donor livers were preserved in HTK (53%), and 327 were preserved in UW (47%). There were no statistically significant differences in any of the primary outcome measures comparing HTK and UW. The HTK group overall had a higher day 1 median aspartate aminotransferase and alanine aminotransferase, but the two groups were similar in function thereafter. HTK was superior to UW in protection against biliary complications. Kaplan-Meier graft survival curves failed to demonstrate a significant difference in SCD or ECD livers. In conclusion, HTK and UW are not clinically distinguishable in this large sample of liver transplants, although HTK may be protective against biliary complications when compared to UW. These findings persisted for both SCD and ECD livers. Given the lower cost per donor for HTK, this preservation solution may be preferable for general use. Liver Transpl 14:365–373, 2008. © 2008 AASLD.
Distance weighted 'inside disc' classifier for computer-aided diagnosis of colonic polyps

Feature classification plays an important role in computer-aided diagnosis (CADx) of suspicious lesions or polyps in this concerned study. As one of the simplest machine learning algorithms, the k-nearest neighbor (k-NN) classifier has been widely used in many classification problems. However, the k-NN classifier has a drawback that the majority classes will dominate the prediction of a new sample. To mitigate this drawback, efforts have been devoted to set weight on each neighbor to avoid the influence of the “majority” classes. As a result, various weighted or wk-NN strategies have been explored. In this paper, we explored an alternative strategy, called “distance weighted inside disc” (DWID) classifier, which is different from the k-NN and wk-NN by such a way that it classifies the test point by assigning a corresponding label (instead a weight) with consideration of only those points inside the disc whose center is the test point instead of the k-nearest points. We evaluated this new DWID classifier with comparison to the k-NN, wk-NN, support vector machine (SVM) and random forest (RF) classifiers by experiments on a database of 153 polyps, including 116 neoplastic (malignance) polyps and 37 hyperplastic (benign) polyps, in terms of CADx or differentiation of benign from malignancy. The evaluation outcomes were documented quantitatively by the Receiver Operating Characteristics (ROC) analysis and the merit of area under the ROC curve (AUC), which is a well-established evaluation criterion to various classifiers. The results showed noticeable gain on the polyp differentiation by this new classifier according to the AUC values, as compared to the k-NN and wk-NN, as well as the SVM and RF. In the meantime, this new classifier also showed a noticeable reduction of computing time.
Phencyclidine (PCP) reduces the intensity of caffeine-induced convulsions in rats.

Abstract The effects of phencyclidine (PCP) on the threshold and intensity of caffeine-induced convulsions in rats were examined. There was a dose-dependent effect of PCP on convulsion intensity with significant reduction in intensity at 4.0 and 8.0 mg/kg PCP. At 16.0 mg/kg PCP, convulsants intensity was reduced in 50% of subjects but potentiated to the point of death in the remaining 50%. PCP had no significant effect on threshold for caffeine-induced convulsions.These results suggest that PCP antagonizes caffeine-induced convulsions and further suggests that the mechanisms involved in onset of caffeine-induced convulsion and the decrease of convulsion intensity are pharmacologically dissociable.
Prenatal Betamethasone Therapy in the Infant with Birth Weight Below 750 Grams. 963

Betamethasone (B) administration prior to delivery was associated with significantly improved outcome of infants born with birth weight less than 750g. The clinical course of 56 infants (BW 621 +/- 82g, GA 24.9 +/- 1.9 wks) pretreated with a full course of B was compared to 51 control (C) infants (BW 591 +/- 90g; GA 24.1 +/- 2.0 wks). The B group was significantly (p<0.05) heavier and more mature and were more likely to be delivered by Cesarean section (71.2 vs. 28.9%).
Split-course versus continuous thoracic radiation therapy for limited-stage small-cell lung cancer: final report of a randomized phase III trial.

The optimal integration of radiation and chemotherapy for limited-stage small-cell lung cancer (SCLC) remains unclear. This phase III trial was conducted to determine whether chemotherapy plus interdigitating split-course thoracic radiation therapy (RT) improved survival compared with standard-dose continuous thoracic RT. One hundred fourteen patients were randomized to receive 50 Gy thoracic RT delivered in 2.0-Gy fractions given continuously (5 weeks) concurrent with the first 2 cycles of chemotherapy (arm A) or 50 Gy delivered via an interdigitating split course in 2.5-Gy fractions (8 weeks) concurrent with the first 3 cycles of chemotherapy (arm B). During the split-course RT, once-daily radiation was delivered on days 8-17 of each of the first two 21-day cycles and days 8-11 of the third 21-day cycle. All patients received the following chemotherapy: cisplatin/etoposide on cycles 1, 2, and 5 and cyclophosphamide/vincristine/ doxorubicin on cycles 3, 4, and 6. Prophylactic cranial irradiation was recommended after a complete response to all therapy. One hundred ten eligible patients were randomized. Grade 3/4 esophagitis was reported in 9% of patients receiving continuous thoracic RT versus 4% of patients receiving split-course RT. Grade 3/4 hematologic toxicity was common in both treatment arms. Complete/partial response was observed in 80% of patients on arm A versus 84% on arm B. Overall survival rates at 5 years were 18% and 17% for arms A and B, respectively. Interdigitating split-course thoracic RT delivered in 2.5-Gy fractions was tolerable in patients with limited-stage SCLC but did not provide a survival advantage.
Building climate change resilience through bottom-up adaptation to flood risk in Warri, Nigeria:

The problem of flooding in Warri, Nigeria is as old as the city itself. What has changed in recent years is the rapidly increasing magnitude and frequency of floodwater retention pools on urban str...
Minimally Invasive Total Hip Arthroplasty With Two Incisions

Minimally invasive surgery has the potential for minimizing surgical trauma, pain, and recovery. This manuscript discusses minimally invasive hip arthroplasty through a two-incision technique: one incision is for the acetabular component, the other is for the femoral component. Specialized instruments and fluoroscopy ensure the proper starting points for the incisions and accurate component position and alignment. In 200 consecutive patients that were carefully selected, a comprehensive perioperative management pathway was developed and implemented around this two-incision technique of minimally invasive hip replacement. Of the 200 patients in this study, 192 (96%) were discharged to home the day of surgery. The minimally invasive two-incision total hip technique described here, where muscle and tendon trauma is minimized, shows substantial short-term pain and functional improvement over traditional hip replacement. While this minimally invasive two-incision technique shows great promise, this technique requires meticulous surgical technique, specialized instrumentation, and special instruction.
Bowman-Birk inhibitor and genistein among soy compounds that synergistically inhibit nitric oxide and prostaglandin E2 pathways in lipopolysaccharide-induced macrophages.

Inflammation has an important role in the development of chronic diseases. In this study, we evaluated the anti-inflammatory properties of eight soybean bioactive compounds using lipopolysaccharide-induced RAW 264.7 macrophages. Genistein, daidzein, a mix of isoflavone glucosides, saponin A group glycosides (saponin A), saponin B group glycosides (saponin B), sapogenol B, Bowman−Birk inhibitor (BBI), lunasin, and pepsin−pancreatin glycinin hydrolysates were tested by measuring their ability to inhibit cyclooxygenase-2/prostaglandin E2 (PGE2) and inducible nitric oxide synthase (iNOS)/nitric oxide (NO) inflammatory pathways. Of the eight soy bioactive compounds (SBCs) tested, BBI and sapogenol B resulted in the highest inhibition of pro-inflammatory responses at a concentration 10 times lower than the one used for the other compounds. Also, sapogenol B and genistein (molar ratio 1:1) synergistically inhibited NO and additively inhibited PGE2. Saponin A group glycosides showed inhibition of the iNOS/NO path...
Physics as natural philosophy

Memoirs of a Physicist in the Atomic Age. By W. M. Elsasser. (Adam Hilger: Bristol, 1978.) $15.
Expansion formulae in canonical transformations depending on a small parameter

The theory of perturbation based on Lie transforms is considered. Deprit's equation is reduced to a form which enables us to generate simplified general recursion formulae. These expansions are then modified to speed up the implementation of such perturbation theory in the computerized symbolic manipulation.
On the use of ANN interconnection weights in optimal structural design

The present paper describes the use of interconnection weights of a multilayer, feedforward network, to extract information pertinent to the mapping space that the network is assumed to represent. In particular, these weights can be used to determine an appropriate network architecture, and an adequate number of training patterns (input-output pairs) have been used for network training. The weight analysis also provides an approach to assess the influence of each input parameter on a selected output component. The paper shows the significance of this information in decomposition driven optimal design.
Chemically accurate thermochemistry of cadmium: An ab initio study of Cd + XY (X = H, O, Cl, Br; Y = Cl, Br).

Using a composite coupled cluster method employing sequences of correlation consistent basis sets for complete basis set (CBS) extrapolations and with explicit treatment of core−valence correlation and scalar and spin−orbit relativistic effects, the 0 K enthalpies of a wide range of cadmium−halide reactions, namely, Cd + (HCl, HBr, ClO, BrO, Cl2, BrCl, Br2) have been determined to an estimated accuracy of ±1 kcal/mol. In addition, accurate equilibrium geometries, harmonic frequencies, and dissociation energies have been calculated at the same level of theory for all the diatomic (e.g., CdH, CdO, CdCl, CdBr) and triatomic (CdHCl, CdHBr, CdClO, CdBrO, CdCl2, CdBrCl, CdBr2) species involved in these reactions, some for the very first time. Like their mercury analogues, all of the abstraction reactions are predicted to be endothermic, while the insertion reactions are strongly exothermic with the formation of stable linear, Cd-centric complexes. With the exception of CdH and the reactions involving this speci...
Inducing a blockmodel structure of two-mode binary data using seriation procedures

Abstract We show that seriation of the rows and columns of a two-mode, binary matrix can be an effective method for producing a reordering of the matrix that reveals a blockmodel structure of the data. The objective criterion of the seriation process is based on Robinson patterning of matrix elements. The key advantages of the proposed method are: (a) it can be used in conjunction with existing two-mode blockmodeling algorithms by facilitating selection of the number of classes for the rows and columns of the matrix and the appropriate types of ideal blocks; (b) the model uses a well-grounded index based on Robinson structure, (c) guaranteed optimal solutions can be obtained for problems of practical size, and (d) the seriation method is frequently capable of producing a solution that has a substantive interpretation with respect to the orderings of the row objects and column items.