cssi/SciSciGPT-SciSciNet huggingface dataset:
Conservation Action Planning: Lessons learned from the St. Marys River watershed biodiversity conservation planning process

Abstract Conservation Action Planning (CAP) is an adaptive management planning process refined by The Nature Conservancy (TNC) and embraced worldwide as the Open Standards for the Practice of Conservation. The CAP process facilitates open, multi-institutional collaboration on a common conservation agenda through organized actions and quantified results. While specifically designed for conservation efforts, the framework is adaptable and flexible to multiple scales and can be used for any collaborative planning effort. The CAP framework addresses inception; design and development of goals, measures, and strategies; and plan implementation and evaluation. The specific components of the CAP include defining the project scope and conservation targets; assessing the ecological viability; ascertaining threats and surrounding situation; identifying opportunities and designing strategies for action; and implementing actions and monitoring results. In 2007, TNC and a multidisciplinary graduate student team from the University of Michigan's School of Natural Resources and Environment initiated a CAP for the St. Marys River, the connecting channel between Lake Superior and Lake Huron, and its local watershed. The students not only gained experience in conservation planning, but also learned lessons that notably benefited the CAP process and were valuable for any successful collaborative effort—a dedicated core team improved product quality, accelerated the timeline, and provided necessary support for ongoing efforts; an academic approach in preparation for engagement in the planning process brought applicable scientific research to the forefront, enhanced workshop facilitation, and improved stakeholder participation; and early and continuous interactions with regional stakeholders improved cooperation and built a supportive network for collaboration.
Dynamic mechanical relaxations in swollen elastin networks

Samples of elastin obtained from ox ligamentum nuchae were swelled with one of several glycols and then studied with regard to their dynamic mechanical properties. The glass transition temperatures of these swollen networks were substantially lower than that of dry elastin. Two low-temperature transitions were observed when longer-chain glycols were used as the diluent. The relaxation processes in elastin/triethylene glycol combinations has a higher activation energy than that reported for elastin/ethylene glycol systems. This is thought to be due to the bound diluent increasing the mass and bulk of the relaxing main-chain segments. The data are consistent with elastin being an amorphous, randomly-coiled, somewhat hydrophilic, polymeric material interacting with diluents in the same way as do non-biological polymers.
A mixed model of carcinogenesis with applications to retinoblastoma.

Abstract This paper presents a mixed model of carcinogenesis and derives the incidence functions and the first four cumulants of the number of tumors. The model is then fitted to some retinoblastoma data from the SEER (Surveillance Epidemiology End Results) project of the National Cancer Institute for the years 1973–1982. In all the cases presented, the estimated incidence functions appear to fit the observed incidence curves quite well, suggesting the usefulness of the model.
Enterovirus replication in ileal explants

Summary Porcine enterovirus 3 replicated in explants of fœtal pig intestine, as was shown using photosensitization with neutral red to distinguish between inoculum and progeny virus. Progeny virus titres reached 10 5 –10 6 /ml with 2–4 days' incubation.
Canine Pancreatic Polypeptide Complementary Deoxyribonucleic Acid Sequence: Pancreatic Polypeptide and Insulin Messenger Ribonucleic Acid Distribution in the Lobes of the Pancreas

The structure of the canine prepropancreatic polypeptide (preproPP) cDNA was determined. The nucleotide sequence conservation between human and canine preproPP is very high for the signal peptide (82%) and the region coding for the 36 amino acid pancreatic polypeptide (PP) (92%). The overall sequence homology for the C-terminal portion of proPP containing the icosapeptide and a C-terminal extension peptide is only 63% whereas the 3′-untranslated regions of human and canine PP mRNA share 73% homology after alignment for maximal homology. The only sequence conservation in icosapeptide is the region coding for the last 10 amino acids of the icosapeptide. Comparison of PP immunoactivity and PP mRNA concentrations in extracts of the developmentally distinct uncinate process and splenic lobes of the canine pancreas revealed the same ratio of mRNA concentrations (16 ± 6.5) and PP peptide concentrations (18 ± 7.0) in the uncinate process compared to the splenic lobe (n = 6). However, a similar comparison of insul...
Angular distributions of 18F from the reaction 16O(14N,18F)12C

Abstract The reaction 16O(14N, 18F)12C was investigated at incident energies of 20. 27 and 33 MeV by bombarding thin nickel oxide targets with 14N ions accelerated in the Oak Ridge Tandem Van de Graaff. Angular distributions were obtained by stopping the radioactive 18F particles in aluminium foil annuli which encompassed known angular increments. After bombardment these annuli were counted under shielded, calibrated Geiger-Mueller counters. The 18F differential cross sections were found to be peaked in the forward direction and to exhibit some structure at larger angles. From the experimental data it was concluded that the production of 18F by the evaporation of three alpha particles from the compound nucleus 30P was negligible. A distorted-wave Born approximation calculation was used in an attempt to fit the data. A good fit to the experimental results at 33 MeV was found when it was assumed that alpha-particle transfer from 16O occurred, with the residual 12C nucleus left in its 4.43 MeV state. Calculations at 20 and 27 MeV, however, did not yield satisfactory fits to the data.
Mechanism of mixed liposome solubilization in the presence of sodium dodecyl sulfate

Abstract Structural transformations of vesicles to micelles that take place during the interaction of sodium dodecyl sulfate (SDS) with individual and mixed vesicles of phosphatidyl choline (PC) and phosphatidic acid (PA), have been studied by monitoring changes in optical density and in the concentration of free SDS monomer in the respective systems. Incorporation of the surfactant monomers (SDS) in the bilayers was found to result in an initial increase in concentration of the mixed vesicles up to its saturation. Subsequently a progressive relaxation of these structures together with a simultaneous formation of mixed micelles was found to occur. The breakup of bilayer and the formation of mixed micelles were completely dependent on the structure of the individual phospholipid. The solubilization of the anionic phosphatidic acid vesicle was very fast in the presence of SDS, due to its simple structure and its compatibility with the SDS molecule. But solubilization of the zwitter ionic phosphatidyl choline vesicle was very complicated in the presence of SDS, possibly due to its complex structure and the zwitterionic nature. On the other hand, solubilization of the mixed vesicle (mixed liposome) and formation of mixed micelle was found to be relatively easier. This may be attributed to one of the phospholipid component preferentially coming out first through interaction with SDS, thereby making the overall system unstable and enhancing the micellization processes.
Liability for groundwater contamination from pesticides

Abstract This paper considers the extent to which farmers should be held liable for groundwater contamination from agricultural pesticides. The problem is first viewed as a standard tort and then as a case of product liability, where the question of shifting liability to the manufacturer of the pesticide is considered. The results suggest that, when the problem is viewed as a case of product liability, farmer exemptions from liability can still lead to efficient levels of pesticide use, provided appropriate application methods keyed to site characteristics can be ensured through regulation or other means.
Aldrin, dieldrin, and mercury profiles in recent lake sediments at the Rocky Mountain Arsenal, Colorado

Sediment cores from two lakes at the U.S. Army Rocky Mountain Arsenal, Colorado, where chemical compounds were manufactured and stored for over 40 years, were examined to determine the distribution of aldrin, dieldrin, and mercury in sediments and their probable dates of deposition. Sedimentation rates, based on direct and indirect (137Cs) measures, were estimated to be 1.91 and 1.23 cm/yr in the two lakes. Contaminant deposition dates, as judged by these sedimentation rates, varied between and within lakes; levels of contaminants were relatively high before 1970. The presence of elevated concentrations of all three contaminants in more recent sediments in one lake (Ladora) suggested migration within the sediments or delayed discharges from the manufacturing facility.
Steroid-responsive polyneuropathy with subacute onset in childhood.

Five pediatric patients with subacute onset polyneuropathy are presented, with electrophysiologic and pathologic data. All patients improved, the majority to resolution, with administration of prednisone. Distinguishing factors included (1) subacute onset polyneuropathy progressing gradually over weeks to months, (2) primarily motor neuropathy with little cranial nerve involvement, (3) elevated CSF protein concentration, (4) markedly delayed nerve conduction velocities, and (5) tendency toward relapse and recurrence. Although this disorder may share characteristics with the Guillain-Barre syndrome, its steroid responsiveness sets it apart clinically from the acute form of the disease. Because of the steroid responsiveness, it is important to recognize this entity.
Contrasting Procedures for Empirical Support of Traditional and Population-based Mental Health Services.

The emergence of population-based services is occurring simultaneous with a growing expectation that psychological services be justified by empirical evidence that they are effective in improving the mental health of children and adolescents. This paper describes fundamental conflicts that exist when existing standards for empirical support are generalized to population-based mental health services. While evidence of treatment effectiveness must be required of population-based services as well as traditional mental health services, the different service delivery strategies demand the development of different evaluation strategies to meet this requirement. Recommendations are made for adjusting procedures for empirical support so that these also accommodate population-based service delivery models. The continued development of population-based service models and evaluation procedures suitable for these models will demand collaborative efforts from those expert in treatment and those expert in evaluation. © 2000 John Wiley & Sons, Inc.
Epigenetic changes in renal genes dysregulated in mouse and rat models of type 1 diabetes

Epigenetic processes are increasingly being recognized as factors in the pathophysiology of diabetes complications, but few chromatin studies have been done in diabetic nephropathy (DN). We hypothesized that changes in mRNA expression of DN-related genes are associated with epigenetic alterations and aberrant expression of histone-modifying enzymes. RT-PCR and a matrix–chromatin immunoprecipitation platform were used to examine renal mRNA expression, RNA polymerase II (Pol II) recruitment, and epigenetic marks at DN-related genes in the mouse (OVE26) and streptozotocin-induced rat models of type 1 diabetes. Diabetes induced renal expression of Cox2, S100A4/FSP-1, and vimentin genes in both the mouse and the rat models of DN. Mcp-1 and laminin γ1 (Lamc1) expression were increased in diabetic mice but not in rats. Comparison of mRNA and Pol II levels suggested that the diabetes-induced expression of these transcripts is mediated by transcriptional and posttranscriptional processes. Decreases in histone H3 lysine 27 tri-methylation (H3K27m3, silencing mark) and increases in H3 lysine 4 di-methylation (H3K4m2, activating mark) levels were the most consistent epigenetic alterations in the tested genes. In agreement with these results, immunoblot analysis showed increased protein abundance of renal H3K27m2/3 demethylase KDM6A, but no changes in cognate methyltransferase Ezh2 in kidneys of the OVE26 mice compared with controls. In diabetic rats, Ezh2 expression was higher without changes in KDM6A, demonstrating that mechanisms of DN-induced H3K27m3 loss could be species specific. In summary, we show that altered mRNA expression of some DN-related genes is associated with changes in Pol II recruitment and a corresponding decrease in repressive H3K27m3 at the selected loci, and at least in mice with equivalent changes in renal expression of cognate histone-modifying enzymes. This pattern could contribute to diabetes-mediated transitions in chromatin that facilitate transcriptional changes in the diabetic kidney.
Evaluating competence in psychotherapy.

Background: The Residency Review Committee (RRC) for Psychiatry has recently charged psychiatry training programs with developing methods to demonstrate competence of trainees in five areas of psychotherapy. Each program must decide what specific skills are essential for competence in each of the five listed psychotherapies. This requires determining whether those skills that are necessary are also sufficient for effective psychotherapy and whether additional specific skills are required for each one. Method: Two lists of general skills for psychotherapy are compared, one from the perspective of specific “schools” of psychotherapy and one from a more eclectic “integrative” approach. The issue of measuring competence is addressed by placing ratings of “competent” midway on a continuum from “novice” to “expert.” Thirteen methods for measuring competence from the Accreditation Council for Graduate medical Education (ACGME) “tool-box” are described and reviewed with respect to applicability to psychotherapy. Examples of toolbox implementation are described based on a functioning psychotherapy evaluation program at the University of Missouri. Results and Conclusions: The authors found both theoretical as well as practical problems in measuring competence in psychotherapy. We propose that global rather than highly specific assessment methods may be more practical in these early stages of development, and we offer specific suggestions for assessment components that can currently be implemented.
Temperature dependence of oxygen atom recombination in nitrogen after ozone photolysis

Abstract Oxygen atom decays in nitrogen were measured by laser induced fluorescence following complete photodissociation of ozone at 248 nm. Rate coefficients determined for O + O + N 2 are 2.5, 4.6, and 19.5 × 10 −33 cm 6 /molecule 2 /s at 316, 262, and 171 K, with estimated 30% uncertainty. Results are in excellent agreement with the Baulch et al. [D.L. Baulch, D.D. Drysdale, J. Duxbury, S.J. Grant, Evaluated Kinetic Data for High Temperature Reactions, vol. 3, Butterworths, London, 1976, p. 33–64] recommended Arrhenius expression.
Radioimmunoassay of insulin

The powerful nuclear medicine tool ofradioimmunoassay was very rapidly developed because of the favorable properties of insulin in such a procedure. The current method of insulin immunoassay in our laboratory is described, with emphasis on the details of the separation of bound and free using talc tablets; emphasis is also given to the correction for tracer damage. The clinical usefulness of the insulin radioimmunoassay is somewhat less than had been anticipated, although its use as a research tool has had immeasurable impact upon the study of metabolism. The presence of proinsulin in plasma is a factor that has to be considered during the radioimmunoassay. Radioimmunoassays for the connecting peptide of proinsulin have also been developed. A preliminary evaluation of two radioimmunoassay kits is described.
Urokinase regulates embryonic cardiac cushion cell migration without converting plasminogen.

Urokinase-type plasminogen activator (uPA) activation of plasminogen is an important mediator of cell migration in many cell types. In the developing avian heart, uPA has been implicated as a mediator of atrioventricular (AV) cushion cell migration; however, the role of the plasminogen/plasmin system has not been examined. The purpose of this study was to test the hypothesis that uPA conversion of plasminogen to plasmin mediates AV cushion cell migration in vitro. Stage 17/18 chicken atrioventricular tissue lysates converted plasminogen into plasmin through uPA activity but no tissue-type plasminogen activator activity was detected. Zymograms on living cultured AV explants also activated plasminogen producing plasmin that degraded extracellular protein. The migratory capacity of cushion cells was assessed in the presence or absence of various test reagents known to alter the plasminogen/plasmin system. Addition of either human or chicken plasminogen or aprotinin (an inhibitor of plasmin) had no effect on cell migration. However, an anti-catalytic uPA antibody that blocked AV uPA activity, significantly decreased cell migration at all concentrations tested. These results showed that uPA mediated a portion of cushion cell migration in vitro. Although AV segments activated plasminogen and degraded extracellular proteins, uPA's functional role in cushion cell migration did not involve the plasminogen/plasmin system.
Microwave Generation Using Nonlinear Optics in High-Q Resonators

High Q optical resonators can easily access nonlinear optical mechanisms at remarkably low power levels to produce frequency micro combs and stimulated Brillouin lasers. Progress towards stable microwave generation using these devices will be reviewed.
Sub-Doppler light amplification in a coherently pumped atomic system

We report the observation of steady-state amplification of a weak probe laser without population inversion in the bare states in a Doppler-broadened \ensuremath{\Lambda}-type Rb atomic system. The probe amplification was observed with the Rabi frequency of a coupling laser much smaller than the Doppler width and can be viewed as due to the dressed-state inversion. A 10% single-pass amplification of a weak probe laser was obtained, and the measured linewidth of the gain spectral feature approaches the Rb natural linewidth. A theoretical analysis based on a three-level Doppler-broadened \ensuremath{\Lambda} system is presented, and qualitative agreement with the experiment results is achieved. \textcopyright{} 1996 The American Physical Society.
Witnessing spouse abuse and experiencing physical abuse: A "double whammy"?

Child witnesses to parental violence, both abused (N =40) and nonabused (N =44), who were temporarily residing in a battered women's shelter were compared with children from a similar economic background (N =66) on measures of anxiety, depression, and behavior problems. Mothers of the three groups of children (comparison, witness, abused/witness) across the age range from 4 to 12 years completed a behavior problem inventory; the youngsters responded to paper-and-pencil self-report measures. Results indicated that the abused/witness children were manifesting significantly more distress on the behavior problem measure than the comparison youngsters, with the witness children showing a moderate amount and the comparison children the least. However, these patterns were mediated by the age of the child. Implications of these differential findings are discussed.
POSTHOC: A FORTRAN program for conducting post hoc multiple comparisons among means

POSTHOC is a FORTRAN program designed to con­ duct post hoc multiple comparisons (pairwise com­ parisons, non pairwise comparisons, or both) among means of interest following analysis of variance. Such post hoc comparisons are useful in understanding the nature and patterns of cell mean differences implied by any significant omnibus F tests reported by analysis of variance (Kirk, 1968; Winer, 1971). The program can perform any of seven types of multiple-comparison tests, depending upon the needs of the user. These seven tests include (I) the I.s.d. procedure, (2) Tukey's HSD procedure, (3) the Newman-Keuls procedure, (4) Duncan's new multiple range test, (5) Scheffe's procedure for all pairwise contrasts, (6) Scheffe's pro­ cedure for specified nonpairwise contrasts, and (7) Dunnett's test for comparing treatment groups with a control (one- or two-tailed tests permitted). All seven of these procedures have been thoroughly reviewed by Keppel (1973), Kirk (1968), and Winer (1971).
The effect of routine income withholding of child support collections

Recent federal legislation requires states to make substantial improvements in paternity establishment, enact numeric child support standards for determining child support awards, update those awards at least every three years, and adopt routine income withholding of all child support obligations. Data gathered for the purpose of evaluating the Wisconsin Child Support Assurance System make it possible to examine the effects of routine income withholding on the size and regularity of child support payments. The data consisted of court records of child support cases that entered the court system in 20 Wisconsin counties between 1980 and 1986. Our estimates suggest routine income withholding increases child support payments by between 11 and 30 percent.
Effect of age on sensitivity of Daphnia Magna to cadmium, copper and cyanazine

Daphnia magna were exposed to cadmium, copper, and cyanazine to determine the relative sensitivities of several age groups: less than 4 h, less than 24 h, 1 d, 2 d, 3 d, 4 d, 5 d, and 6 d old. Mean cadmium 48-h EC50 values for each age group ranged from 23 to 164 micrograms/L. Mean copper EC50 values ranged from 6 to 18 micrograms/L. Cyanazine EC50 values ranged from 53 to 106 micrograms/L. The 1-d-old Daphnia mean EC50s were 48 and 49 micrograms/L for cadmium, 10 and 10 micrograms/L for copper and 84 and 86 microgram/L for cyanazine, respectively. These similar sensitivities indicate that older animals can be used in tests equally as well as younger animals, thus simplifying the recovery of daphnids in acute sediment toxicity tests.
North–South Trade Liberalization and Economic Welfare

We consider a general equilibrium model of a developing economy (the South) that opens to trade with a developed economy (the North). The southern economy is characterized by open urban unemployment and rural–urban migration, a competitive agricultural sector and a monopolistically competitive manufacturing sector. Hence, there is potential for both inter- and intra-industry trade to arise on liberalization, in addition to distortionary effects of duality. Southern comparative advantage in agriculture may arise from the labor market distortion and the basis for intra-industry trade is love for variety. We characterize various configurations of the trade pattern, and the resulting welfare consequences of opening to trade in this context. We illustrate a new mechanism under which in some circumstances it may be possible for trade liberalization to lower economic welfare in the South.
Measuring the sea breeze from QuikSCAT Scatterometry

[1] Differences between morning and evening winds from QuikSCAT scatterometer measurements are analyzed to diagnose the diurnal variability of the wind over the ocean. A statistically significant signal, associated with the sea breeze, is present along most of the world's coastlines. Significant diurnal variability is also present mid-ocean in the easterly trade wind belts.
Periodontal Terminology Revisited

The body of knowledge that was the basis of the science and therapy of periodontics can be found in the literature of the 1950s and 60s. This information conveniently was presented in various textbooks. The evolution of research utilizing histochemistry and electron microscopy, along with disciplined clinical studies, has resulted in an exponential increase in information. A by-product of this worldwide effort is confusion resulting from the misuse and interchangeable application of terms disregarding the definitions originally accepted. Even with workshops designed in part to arrive at consensus to preclude confusion, the literature is replete with misleading use of nomenclature. The lack of attention to the appropriate use of terms is, at best, confusing to the student, researcher, and clinician. In the worst case, it may result in poor performance on examinations and improper evaluation of techniques and materials. Many periodontal terms are used inappropriately or are not completely understood, probably because these words have not been adequately described in the literature. Some of the more commonly used and confused terms will be discussed using literature to support the definitions.
Pediatric hospitalists: report of a leadership conference.

OBJECTIVES. To summarize a meeting of academic pediatric hospitalists and to describe the current state of the field. METHODS. The Ambulatory Pediatric Association sponsored a meeting for academic pediatric hospitalists in November 2003. The purpose of the meeting was to discuss and to define roles of academic pediatric hospitalists, including their roles as clinicians, educators, and researchers, and to discuss organizational issues and unique hospitalist issues within general academic pediatrics. Workshops were held in the areas of organization and administration, academic life, research, and education. A literature review was also conducted in the areas discussed. RESULTS. More than 130 physicians attended. Thirteen workshops were held, and all information was summarized in large-group sessions for all attendees. CONCLUSIONS. Pediatric hospital medicine is a rapidly growing field, with an estimated 800 to 1000 pediatric hospitalists currently practicing. Initial work has defined the clinical environment and has begun to stake out a unique knowledge and skill set. The Pediatric Hospitalists in Academic Settings conference demonstrated the audience for additional development and the resources to move forward.
Quantitation of CD8+ T-Lymphocyte Responses to Multiple Epitopes from Simian Virus 40 (SV40) Large T Antigen in C57BL/6 Mice Immunized with SV40, SV40 T-Antigen-Transformed Cells, or Vaccinia Virus Recombinants Expressing Full-Length T Antigen or Epitope Minigenes

The cytotoxic T-lymphocyte response to wild-type simian virus 40 large tumor antigen (Tag) in C57BL/6 (H2b) mice is directed against three H2-Db-restricted epitopes, I, II/III, and V, and one H2-Kb-restricted epitope, IV. Epitopes I, II/III, and IV are immunodominant, while epitope V is immunorecessive. We investigated whether this hierarchical response was established in vivo or was due to differential expansion in vitro by using direct enumeration of CD8+ T lymphocytes with Tag epitope/major histocompatibility complex class I tetramers and intracellular gamma interferon staining. The results demonstrate that epitope IV-specific CD8+ T cells dominated the Tag-specific response in vivo following immunization with full-length Tag while CD8+ T cells specific for epitopes I and II/III were detected at less than one-third of this level. The immunorecessive nature of epitope V was apparent in vivo, since epitope V-specific CD8+ T cells were undetectable following immunization with full-length Tag. In contrast, high levels of epitope V-specific CD8+ T lymphocytes were recruited in vivo following immunization and boosting with a Tag variant in which epitopes I, II/III, and IV had been inactivated. In addition, analysis of the T-cell receptor β (TCRβ) repertoire of Tag epitope-specific CD8+ cells revealed that multiple TCRβ variable regions were utilized for each epitope except Tag epitope II/III, which was limited to TCRβ10 usage. These results indicate that the hierarchy of Tag epitope-specific CD8+ T-cell responses is established in vivo.
Genetic mutations in head and neck cancer: utilizing existing treatments.

Head and neck cancer is a group of malignancies of the upper aerodigestive tract. A large majority of these cancers are head and neck squamous cell carcinomas (HNSCCs), which arise from the squamous epithelium at these anatomic sites. HNSCC is characterized by high morbidity and mortality, with low survival rates that vary depending on primary tumor site [1]. Risk factors for HNSCC include tobacco use, alcohol use and human papillomavirus (HPV) infection, where patients with HPV-positive cancers tend to have fewer genetic mutations and improved survival relative to patients with HPVnegative tumors [2,3]. In 2006, the US FDA approved cetuximab, a mono clonal antibody targeting EGFR, for HNSCC patients. Unfortunately, the success of cetuximab has been limited, at least in part, owing to the lack of predictive biomarkers of sensitivity or resistance. As survival rates have remained stagnant, even with the advent of cetuximab, HNSCC patients would likely benefit from therapeutic strategies developed in connection with emerging high-throughput genomic analyses. In 2011, two studies were published that made available whole-exome sequencing results from more than 100 HNSCC patients [3,4]. Several hundred additional tumors have now been analyzed as part of The Cancer Genome Atlas (TCGA), affording the opportunity to analyze the genetic underpinnings of HNSCC in a large number of primary tumors. In general, HNSCC does not appear to be principally driven by activating kinase mutations, but rather by lossof-function (LOF) of tumor suppressors such as TP53, CDKN2A, CASP8 and NOTCH1. This situation presents several opportunities and challenges, including technical barriers to the development of pharmacologic agents that reactivate signaling pathways in the context of genetic LOF. It will therefore be necessary to determine the downstream signaling consequences of LOF events in order to identify targetable pathway components. A key opportunity presented by this wealth of data is the ability to identify infrequent and novel mutations that may be actionable as targets and/or biomarkers. For example, we recently identified frequent LOF mutations of the protein tyrosine phosphatase receptor family, where PTPRT mutations in particular may indicate sensitivity to STAT3 pathway inhibition in HNSCC [5]. One notable exception to the general trend of LOF mutations driving HNSCC is mutational activation of the PI3K pathway, where hotspot PIK3CA mutation may predict sensitivity to PI3K inhibitors [6]. As cetuximab represents the only approved targeted therapy for HNSCC, many clinical trials are investigating cetuximab in combination with other available chemotherapeutics and/or targeted agents. For example, one recent study reported an 11.1% improvement in 2-year disease-free survival Genetic mutations in head and neck cancer: utilizing existing treatments
Lipids, lipases, and obesity: does race matter?

For >20 years, researchers have reported that American blacks tend to have lower triglyceride and higher HDL cholesterol (HDL-C) levels compared with whites at a similar level of corpulence.1 2 Early studies focused on potential environmental explanations and concluded that differences in exercise, alcohol intake, leanness, and undernutrition did not readily account for the higher HDL-C levels.3 It was also noted that the propensity toward more favorable HDL-C and triglyceride levels was absent in highly educated blacks.4 More recent reports have shown that socioeconomic status was positively correlated with HDL-C in white men and women, a negative association was present in black men, and no association was evident in black women.5 Autopsy reports have also demonstrated differences in atherosclerosis in blacks versus whites. The Bogalusa Study6 reported that young blacks had more fatty streaks than did whites but that middle-aged blacks had less evidence of fibrous plaques. The authors concluded that the transition of fatty streaks to advanced atherosclerotic lesions may differ in whites and blacks.6 Similar results were obtained in the Pathobiological Determinants of Atherosclerosis in Youth study,7 an autopsy investigation of young adults who died from trauma between the ages of 15 to 34 years. Adolescent blacks in that study had a greater extent of fatty streaks than did whites, but older blacks and whites …
Human Mitochondrial DNA Variation and Evolution: Analysis of Nucleotide Sequences from Seven Individuals

We have analyzed nucleotide sequence variation in an approximately 900-base pair region of the human mitochondrial DNA molecule encompassing the heavy strand origin of replication and the D-loop. Our analysis has focused on nucleotide sequences available from seven humans. Average nucleotide diversity among the sequences is 1.7%, several-fold higher than estimates from restriction endonuclease site variation in mtDNA from these individuals and previously reported for other humans. This disparity is consistent with the rapidly evolving nature of this noncoding region. However, several instances of convergent or parallel gain and loss of restriction sites due to multiple substitutions were observed. In addition, other results suggest that restriction site (as well as pairwise sequence) comparisons may underestimate the total number of substitutions that have occurred since the divergence of two mtDNA sequences from a common ancestral sequence, even at low levels of divergence. This emphasizes the importance of recognizing the large standard errors associated with estimates of sequence variability, particularly when constructing phylogenies among closely related sequences. Analysis of the observed number and direction of substitutions revealed several significant biases, most notably a strand dependence of substitution type and a 32-fold bias favoring transitions over transversions. The results also revealed a significantly nonrandom distribution of nucleotide substitutions and sequence length variation. Significantly more multiple substitutions were observed than expected for these closely related sequences under the assumption of uniform rates of substitution. The bias for transitions has resulted in predominantly convergent or parallel changes among the observed multiple substitutions. There is no convincing evidence that recombination has contributed to the mtDNA sequence diversity we have observed.
Heterogeneous data fusion for brain tumor classification.

Current research in biomedical informatics involves analysis of multiple heterogeneous data sets. This includes patient demographics, clinical and pathology data, treatment history, patient outcomes as well as gene expression, DNA sequences and other information sources such as gene ontology. Analysis of these data sets could lead to better disease diag- nosis, prognosis, treatment and drug discovery. In this report, we present a novel machine learning framework for brain tumor classification based on heterogeneous data fusion of metabolic and molecular datasets, including state-of-the-art high-reso- lution magic angle spinning (HRMAS) proton ( 1 H) magnetic resonance spectroscopy and gene transcriptome profiling, obtained from intact brain tumor biopsies. Our experimental results show that our novel framework outperforms any analysis using individual dataset.
Regulating gene expression using self-inactivating lentiviral vectors containing the mifepristone-inducible system.

Methods to regulate gene expression in vitro and in vivo are currently areas of intense research. The present study, therefore, was designed to determine the efficacy of transgene expression using the GeneSwitch mifepristone-regulatable system within the context of an integrating HIV-1 vector. Lentiviral transfer plasmids expressing the red (DsRed2) and green fluorescent protein (EGFP) markers were constructed for in vitro assessment on the basal and mifepristone-induced cell activation levels by FACS analyses. In our design, efficient cell activation and transgene expression were found using a binary lentivector system i.e., the trans-activator, Switch, and the inducible promoter-transgene expression cassette were cloned into separate vectors. Note that the Switch trans-activator performed optimally when cloned into the reverse-orientation, but the inducible promoter containing lentivector did not appear to be dependent upon the orientation within the lentivector backbone. This binary lentivector system resulted in tightly regulated transgene expression, with low basal cell activation in the absence of mifepristone (MFP). Upon induction, a 41- to 275-fold increase in the number of DsRed2- and EGFP-positive cells were detected (n=3). To determine the inducing ability of the GeneSwitch, we cloned the human alpha(1)-antitrypsin cDNA into the optimal lentiviral vector and transduced HeLa and Huh7 cells at increasing lentivector doses as determined by p24 Gag ELISA. We found that MFP could induce the expression of hAAT protein in HeLa cells from 310 to 15,000 ng hAAT/10(6) cells/24 h, which was a 48-fold induction. Similar results were observed in huH7 cells. In all, this study demonstrates that the GeneSwitch system can be designed within the context of a lentiviral vector for in vitro gene transfer, and this may also provide a viable method for temporally regulating gene expression for therapeutic applications in vivo or ex vivo.
Biome representational in silico karyotyping

Metagenomic characterization of complex biomes remains challenging. Here we describe a modification of digital karyotyping-biome representational in silico karyotyping (BRISK)-as a general technique for analyzing a defined representation of all DNA present in a sample. BRISK utilizes a Type IIB DNA restriction enzyme to create a defined representation of 27-mer DNAs in a sample. Massively parallel sequencing of this representation allows for construction of high-resolution karyotypes and identification of multiple species within a biome. Application to normal human tissue demonstrated linear recovery of tags by chromosome. We apply this technique to the biome of the oral mucosa and find that greater than 25% of recovered DNA is nonhuman. DNA from 41 microbial species could be identified from oral mucosa of two subjects. Of recovered nonhuman sequences, fewer than 30% are currently annotated. We characterized seven prevalent unknown sequences by chromosome walking and find these represent novel microbial sequences including two likely derived from novel phage genomes. Application of BRISK to archival tissue from a nasopharyngeal carcinoma resulted in identification of Epstein-Barr virus infection. These results suggest that BRISK is a powerful technique for the analysis of complex microbiomes and potentially for pathogen discovery.
Myopathy in Children Receiving Chronic Corticosteroid Therapy for Asthma

Approximately 7 million American children have asthma. First line therapy for the treatment of persistent asthma is inhaled corticosteroid (ICS) medications for long-term control. Oral corticostero...
Generation of a transgenic mouse model with chondrocyte‐specific and tamoxifen‐inducible expression of Cre recombinase

Postnatal cartilage development and growth are regulated by key growth factors and signaling molecules. To fully understand the function of these regulators, an inducible and chondrocyte-specific gene deletion system needs to be established to circumvent the perinatal lethality. In this report, we have generated a transgenic mouse model (Col2a1-CreER(T2)) in which expression of the Cre recombinase is driven by the chondrocyte-specific col2a1 promoter in a tamoxifen-inducible manner. To determine the specificity and efficiency of the Cre recombination, we have bred Col2a1-CreER(T2) mice with Rosa26R reporter mice. The X-Gal staining showed that the Cre recombination is specifically achieved in cartilage tissues with tamoxifen-induction. In vitro experiments of chondrocyte cell culture also demonstrate the 4-hydroxy tamoxifen-induced Cre recombination. These results demonstrate that Col2a1-CreER(T2) transgenic mice can be used as a valuable tool for an inducible and chondrocyte-specific gene deletion approach.
Ecological stability and community diversity during mormon colonization of the Little Colorado River Basin

By describing the ecological implications of Mormon settlement in the Little Colorado River Basin, the paper demonstrates: (1) the application of general ecological concepts in human ecology, (2) the ecological basis for the evolution of complex human communities, (3) the interactive, hierarchical relationship between community diversity and environmental stability, and (4) the positive contribution that human ecology can make to the general discussion of diversity and stability in ecological systems. The paper gives a brief description of Mormon colonization in the Little Colorado River Basin. Local differences in community development are then related to environmental variation within the basin and compared to general ecological research expectations. The implications of community development in this region for explaining the relationship between diversity and stability in ecological systems are discussed.
The Temporal Control of Wee1 mRNA Translation during Xenopus Oocyte Maturation Is Regulated by Cytoplasmic Polyadenylation Elements within the 3′-Untranslated Region

Abstract The Wee1 protein tyrosine kinase is a key regulator of cell cycle progression. Wee1 activity is necessary for the control of the first embryonic cell cycle following the fertilization of meiotically mature Xenopus oocytes. Wee1 mRNA is present in immature oocytes, but Wee1 protein does not accumulate in immature oocytes or during the early stages of progesterone-stimulated maturation. This delay in Wee1 translation is critical since premature Wee1 protein accumulation has been shown to inhibit oocyte maturation. In this study we provide evidence that Wee1 protein accumulation is regulated at the level of mRNA translation. This translational control is directed by sequences within the Wee1 mRNA 3′-untranslated region (3′ UTR). Specifically, cytoplasmic polyadenylation element (CPE) sequences within the Wee1 3′ UTR are necessary for full translational repression in immature oocytes. Our data further indicate that while CPE-independent mechanisms may regulate the levels of Wee1 protein accumulation during progesterone-stimulated oocyte maturation, the timing of Wee1 mRNA translational induction is directed through a CPE-dependent mechanism.
Oolite Shoal Reservoirs in Pettet Formation (Lower Cretaceous), Southeast Shelby County, Texas: ABSTRACT

The Pettet Formation is a southward-thickening carbonate wedge, deposited during Aptian (Early Cretaceous) time in the region that is now the Gulf coastal plain of east Texas, Arkansas, and Louisiana. Within the Pettet are characteristic oolite sequences which formed in a northwest-southeast-striking belt paralleling the shelf edge. In southeast Shelby County, Texas, the Pettet oolite shoals were studied, using available well cores and induction-electric logs. The oolite shoals appear to have formed on top of remnant topographic highs in the underlying Travis Peak Formation, in series of vertically stacked cycles of grainstone development. The oolite shoals display five constituent lithofacies: (1) mudstone, (2) oolitic packstone, (3) skeletal-oolitic packstone, (4) skeletal-oolitic grainstone, and (5) oolitic grainstone. The oolitic grainstone lithofacies is the most volumetrically significant constituent of the Pettet oolite shoal reservoirs, comprising approximately 95% of each sequence. Three diagenetic environments are seen in the oolite shoals: marine phreatic zone, vadose zone, and freshwater phreatic zone. Porosity is mainly primary interparticle, with some secondary intraparticle and vuggy porosity also being important. The freshwater phreatic diagenesis appears to have had the most effect on the Pettet reservoirs, creating minor recrystallization-induced porosity occlusion and excellent porosity-enhanced dissolution zones. Hydrocarbon reserves in the Pettet Formation are related to certain structurally modified oolite shoals. Salt swelling and diapirism in the underlying Jurassic Louann Salt appear to be the mechanism responsible for the formation of locally developed anticlinal noses and domes. These small anticlinal features, when occurring beneath or adjacent to an oolite shoal, result in the upward tilting of the strata with subsequent migration and stratigraphic trapping of oil and gas. End_of_Article - Last_Page 146------------
Nanobarcoded superparamagnetic iron oxide nanoparticles for nanomedicine: Quantitative studies of cell–nanoparticle interactions by scanning image cytometry

Oligonucleotide-functionalized nanoparticles (NPs) are promising agents for nanomedicine, but the potential in vitro nanotoxicity that may arise from such conjugates has yet to be evaluated in a dose response manner. Since nanomedicine functions on the single-cell level, measurements of nanotoxicity should also be performed as such. In vitro single-cell nanotoxicity assays based on scanning image cytometry are used to study a specific type of oligo-functionalized NP, “nanobarcoded” superparamagnetic iron oxide NPs (NB-SPIONs). The selected panel of single-cell assays measures well-known modes of nanotoxicity—apoptosis, necrosis, generation of reactive oxygen species (ROS), and cell number. Using these assays, the cytotoxicity of two sizes of NB-SPIONs (10 nm and 30 nm core size) was compared to the parent NP, carboxylated SPIONs (COOH-SPIONs). The results suggest that the conjugated NB confers a biocompatible coating that protects against cytotoxicity at very high SPION doses, but both NB- and COOH-SPIONs of either size generally have low in vitro cytotoxicity at physiologically relevant doses. © 2015 International Society for Advancement of Cytometry
A machine-learning approach to detecting unknown bacterial serovars

Technologies for rapid detection of bacterial pathogens are crucial for securing the food supply. A light-scattering sensor recently developed for real-time identification of multiple colonies has shown great promise for distinguishing bacteria cultures. The classification approach currently used with this system relies on supervised learning. For accurate classification of bacterial pathogens, the training library should be exhaustive, i.e., should consist of samples of all possible pathogens. Yet, the sheer number of existing bacterial serovars and more importantly the effect of their high mutation rate would not allow for a practical and manageable training. In this study, we propose a Bayesian approach to learning with a nonexhaustive training dataset for automated detection of unknown bacterial serovars, i.e., serovars for which no samples exist in the training library. The main contribution of our work is the Wishart conjugate priors defined over class distributions. This allows us to employ the prior information obtained from known classes to make inferences about unknown classes as well. By this means, we identify new classes of informational value and dynamically update the training dataset with these classes to make it increasingly more representative of the sample population. This results in a classifier with improved predictive performance for future samples. We evaluated our approach on a 28-class bacteria dataset and also on the benchmark 26-class letter recognition dataset for further validation. The proposed approach is compared against state-of-the-art involving density-based approaches and support vector domain description, as well as a recently introduced Bayesian approach based on simulated classes. Copyright © 2010 Wiley Periodicals, Inc. Statistical Analysis and Data Mining 3: 289-301, 2010