cssi/SciSciGPT-SciSciNet huggingface dataset:
Changing the Faces of Academic Medical Center Leadership: Gender and Ethnicity

What does it mean when a leader looks different from the kinds of leaders we have most often seen in Academic Medical Centers? Does it mean the leader will act differently, lead differently, create change, or bring a new perspective? How much of leadership is independent of, or emerging from, the characteristics of leaders? This chapter explores those questions and invites your reflections about what diverse leadership can bring to academic medicine. It starts with a brief discussion of leadership and representation and then provides a description of the contemporary leadership picture.
Authoritarianism's Structuring of Contemporary Issues

For authoritarianism to become relevant to helping us understand political conflict, people's preferences on a wide range of salient issues must be, in some significant part, structured by it. This was not the case for the last seventy years of the twentieth century. New Deal–style conflicts mostly dominated American politics, although, as we detailed in the last chapter, the groundwork for the development of an authoritarian cleavage was being laid during this time. But the fundamental disagreements between Republicans and Democrats concerned the size of government, the amount of taxes, and government's role in assuring a minimum standard of living. As overtly racist appeals fell out of favor, even racial issues were discussed using a New Deal frame (see, e.g., Hurwitz and Peffley 1997; Peffley, Hurwitz, and Sniderman 1997; Gilens 1999; Peffley and Hurwitz 2002). Since these issues have comprised the dominant party cleavage since the 1930s, we would not have expected authoritarianism to be central in understanding New Deal–style political conflict. Especially since the dawning of the twenty-first century, the issue agenda has changed a great deal, with authoritarianism stitching together some existing patches with new ones to create the political tapestry we have described. We focus here on several issues, which on the surface do not seem to be interrelated. They include gay rights, the role of Christian fundamentalism in American politics, the use of force, and trade-offs between security and liberties.
Spectroscopy of hydrazines for laser remote sensing

The absorption spectra of hydrazine fuel gases [hydrazine (N2H4), monomethylhydrazine (MMH), unsymmetrical dimethylhydrazine (UDMH), ammonia (NH3), methanol (MeOH), dimethylamine (DMA), and trimethylamine (TMA)] buffered in nitrogen to 760 Torr were measured in the 9-12-μm spectral region using an FTIR spectrometer with a 0.05-Cm−1 resolution. For each gas, at least three measurements at different pressures were made, and it was noted that, with the possible exception of ammonia, the 0.05-cm−1 resolution was much smaller than the pressure-broadened spectral features of the gases. The FTIR-determined absorption coefficients were compared with values reported in the literature at CO2 laser wavelengths1,2 and found to agree within ~10 % for the values of MeOH, DMA, and TMA reported in Ref. 1 and the values for the hydrazines as reported in Ref. 2, thus confirming that the FTIR-determined values are useful for narrow laser lines.
Idarucizumab for Reversal of Dabigatran-Associated Anticoagulation.

Objective: To review clinical data on idarucizumab for the reversal of dabigatran-associated anticoagulation. Data Sources: Articles for this review were identified via PubMed using the MeSH term dabigatran combined with the keyword idarucizumab. Additional online searches via PubMed and Google Scholar were conducted for both prescribing and cost information. Study Selection and Data Extraction: English-language clinical trials published between 1946 and May 2016 were included for review. Bibliographies of selected articles were also manually reviewed for relevant publications that focused on reversal strategies for dabigatran-associated anticoagulation. Data Synthesis: The safety and tolerability of idarucizumab has been evaluated in 3 phase I clinical trials. The use of idarucizumab for reversing dabigatran-associated anticoagulation is also being evaluated in the phase III RE-VERSE AD study. Interim results of the RE-VERSE AD study have been published. Conclusions: Idarucizumab rapidly neutralizes the ...
Assessing pretreatment reactor scaling through empirical analysis.

Pretreatment is a critical step in the biochemical conversion of lignocellulosic biomass to fuels and chemicals. Due to the complexity of the physicochemical transformations involved, predictively scaling up technology from bench- to pilot-scale is difficult. This study examines how pretreatment effectiveness under nominally similar reaction conditions is influenced by pretreatment reactor design and scale using four different pretreatment reaction systems ranging from a 3 g batch reactor to a 10 dry-ton/days continuous reactor. The reactor systems examined were an automated solvent extractor (ASE), steam explosion reactor (SER), ZipperClave®Reactor (ZCR), and large continuous horizontal screw reactor (LHR). To our knowledge, this is the first such study performed on pretreatment reactors across a range of reaction conditions and at different reactor scales. The comparative pretreatment performance results obtained for each reactor system were used to develop response surface models for total xylose yield after pretreatment and total sugar yield after pretreatment followed by enzymatic hydrolysis. Near- and very-near-optimal regions were defined as the set of conditions that the model identified as producing yields within one and two standard deviations of the optimum yield. Optimal conditions identified in the smallest scale system (the ASE) were within the near-optimal region of the largest scale reactor system evaluated. The maximum total sugar yields for the ASE and LHR were $$95\,\%$$ , while $$89\,\%$$ was the optimum observed in the ZipperClave. The optimum condition identified using the automated and less costly to operate ASE system was within the very-near-optimal space for the total xylose yield of both the ZCR and the LHR, and was within the near-optimal space for total sugar yield for the LHR. This indicates that the ASE is a good tool for cost effectively finding near-optimal conditions for operating pilot-scale systems. Additionally, using a severity factor approach to optimization was found to be inadequate compared to a multivariate optimization method. Finally, the ASE and the LHR were able to enable significantly higher total sugar yields after enzymatic hydrolysis relative to the ZCR, despite having similar optimal conditions and total xylose yields. This underscores the importance of mechanical disruption during pretreatment to improvement of enzymatic digestibility.
PU.1 Is a Downstream Target of SOX4 in Myeloid Cells.

Mice that express 20% the normal levels of the Ets transcription factor PU.1 develop AML, unlike mice that express 50% or 80% the normal levels, indicating that PU.1 is a dosage-sensitive tumor suppressor gene. In addition, 3 of 13 AMLs induced by transplanting mice with cells transduced with a Sox4 oncogene-containing retrovirus were found to carry a Sox4 retroviral integration in one PU.1 allele, suggesting that downregulation of PU.1 may cooperate with Sox4 in AML induction. Since the other PU.1 allele remains intact in these AMLs and a 50% decrease in PU.1 expression is not sufficient to induce AML, we hypothesized that Sox4 might further downregulate PU.1 expression in these AMLs. To test this hypothesis, we transfected HL60 promyelocytes with an expression vector carrying both GFP and Sox4 cDNAs or a GFP vector control. Transfected GFP+ cells were purified by flow cytometry and PU.1 mRNA levels were analyzed by real-time RT-PCR. PU.1 mRNA levels were consistently downregulated 4 to 10 fold in cells transfected with Sox4 cDNA compared to cells transfected with the vector control, while β-actin mRNA levels were maintained constant, confirming that overexpression of Sox4 downregulates PU.1 expression in myeloid cells. The decrease of PU.1 mRNA was observed as early as 8 hours after Sox4 transfection, further suggesting that Sox4 may directly repress the PU.1 promoter in myeloid cells. Consistent with this, analysis of 2 published microarray databases comprising 401 de novo AML patient samples showed that SOX4 expression is significantly negatively correlated with PU.1 expression (coefficient: −0.337, P-value: 1E-07). Interestingly, AML FAB M1 and M2 subtypes were associated with statistically significant higher SOX4 expression levels compared to AML FAB M3, M4, M5. In order to confirm that downregulation of PU.1 cooperates with Sox4 in AML induction, we infected wild type or PU.1 heterozygous knockout bone marrow cells with the Sox4 retrovirus and then monitored the time of AML development in transplanted mice. Early results show accelerated leukemogenesis in mice transplanted with Sox4-infected PU +/− bone marrow (115 days) compared to mice receiving Sox4-infected wild type marrow (160 days). We are currently trying to identify Sox4 binding sites in the PU.1 promoter, or in an upper regulatory element that may be responsible for mediating the repression of PU.1.
Performance and cost analysis of NoC-inspired virtual topologies for digital microfluidic biochips

Virtual topologies simply the process of compiling assays to execute on digital microfluidic biochips (DMFBs). This paper evaluates the performance and cost of a virtual topology inspired by networks-on-chip (NoCs). The throughput of several deadlock-free droplet routing protocols is compared on synthetic traffic patterns that are widely used to evaluate semiconductor NoCs. The cost is the number of control pins required for actuation and the number of PCB layers required to route the chip; by eliminating unused pins, the virtual topology is cheaper than a direct-addressing DMFB, especially as chip size increases.
Optimal Generalized Decision Trees via Integer Programming

Decision trees have been a very popular class of predictive models for decades due to their interpretability and good performance on categorical features. However, they are not always robust and tend to overfit the data. Additionally, if allowed to grow large, they lose interpretability. In this paper, we present a mixed integer programming formulation to construct optimal decision trees of a prespecified size. We take the special structure of categorical features into account and allow combinatorial decisions (based on subsets of values of features) at each node. Our approach can also handle numerical features via thresholding. We show that very good accuracy can be achieved with small trees using moderately-sized training sets. The optimization problems we solve are tractable with modern solvers.
Seasonal Variation in Stress Responses

Winter is energetically demanding; thermogenic requirements are high and resources are scarce. This prolonged imbalance in energy intake and expenditure causes a stress response and glucocorticoid release. A chronic stress response typically results in pathology, but anticipation of seasonal stressors allows for the reorganization of endocrine, metabolic, immune, and neural processes to reduce energetic requirements. These trade-offs are mediated by differential investment in immune function and reproduction during times of low (fall and winter) and high (spring and summer) energy availability, respectively. Many nontropical animals monitor day length (i.e., photoperiod), in order to coordinate these seasonal adaptations. Much of the photoperiodic signal is transduced by pineal melatonin, as it is secreted inversely proportional to the absolute day length. This chapter will discuss seasonal changes in glucocorticoid release, binding globulin capacity, and receptor expression and their ultimate contributions to differential stress responses.
Enhanced Anticoagulant Activity of Factor VIII Inhibitors Due to Positive Cooperativity between Two Classes of Anti-Factor VIII C2 Antibodies.

Abstract We recently identified 5 distinct structural classes of anti-human factor VIII (fVIII) C2 domain monoclonal antibodies (MAbs) in a murine model of hemophilia A. Three classes, Groups A, B, and C, consist of MAbs with non-overlapping epitopes. Group AB MAbs overlap epitopes of Group A and B MAbs, and Group BC MAbs overlap epitopes of Group B and C MAbs. Concentration dependent binding of biotinylated Group A MAbs to fVIII bound to a microtiter plate was studied in the presence and absence of Group BC MAbs by ELISA. Surprisingly the binding of all 3 Group A antibodies tested, ESH4, 3E6, and I54, was increased in the presence of Group BC antibodies. Group A antibodies block the binding of fVIII to von Willebrand factor (VWF) and phospholipid. Group BC antibodies inhibit the proteolytic activation of fVIII but do not block the binding of fVIII to VWF and phospholipid. To establish functional relevance, the effect of Group BC MAbs on the ability of Group A MAbs to block fVIII binding to VWF was determined by ELISA. Group A MAbs were serially diluted into fixed concentrations of Group BC MAbs and then incubated with fVIII in solution for 2 hours. The fVIII - antibody mixtures were added to microtiter wells coated with VWF, and fVIII binding to VWF was measured. Group BC MAbs increased the ability of ESH4 and 3E6 to inhibit the binding of fVIII to VWF, consistent with the observation that the binding of Group A and Group BC antibodies is positively cooperative. We previously have shown that antibody-mediated inhibition of fVIII binding to VWF is correlated with inhibition of fVIII binding to phospholipid and with fVIII inhibitor titers. Although most Group BC MAbs have high inhibitory titers against fVIII, Group BC MAb D105 is only minimally inhibitory at 0.8 Bethesda units/mg IgG. Because D105 increased the binding of ESH4 to fVIII like other Group BC MAbs, the effect of D105 on the inhibitor titer of ESH4 was investigated using the Bethesda assay. The inhibition of fVIII was significantly increased by the presence of D105 (Fig. 1). This study identifies increased binding of Group A MAbs to fVIII in the presence of Group BC MAbs using 3 different assays. Our results suggest that the cooperative interaction of fVIII antibody epitopes affects the overall inhibitor patient phenotype and that inhibitors with very low inhibitor titers can significantly increase the inhibitory effects of other anti-fVIII antibodies. Download : Download high-res image (67KB) Download : Download full-size image Figure
Establishing the Diagnosis of GERD

Gastroesophageal reflux disease (GERD) is a highly prevalent disorder with worldwide distribution [1]. However, GERD may present with a variety of symptoms, including heartburn, dysphagia, and even chronic cough. In 2006, the Montreal classification was created as a global consensus definition for GERD to encourage diagnostic standardization for clinical management and research [2]. This defined GERD as a condition resulting from reflux of stomach contents and causing troublesome symptoms or complications, occurring at least 2 times per week, with an adverse effect on an individual’s well-being. The Montreal classification further defines symptoms as esophageal, including typical symptoms of heartburn and regurgitation, and dysphagia as a manifestation of esophageal injury; and extraesophageal, including cough, laryngitis, and asthma (Fig. 2.1). Generally, esophageal symptoms are more clearly associated with GERD, while extraesophageal symptoms are often multifactorial [2].
Transformative phases in el duende process painting art-based supervision

• Participants reported increased trust in the art making process leading to professional growth.
MDM2 SNP 309 Is Not Associated with Increased Expression Levels of MDM2 Nor Clinical Significance in Childhood Acute Lymphoblastic Leukemia

Abstract Previously, we reported that MDM2 overexpression by pediatric acute lymphoblastic leukemia (ALL) cells is linked to a poor response to chemotherapy and early relapse of disease. It was recently shown that a single nucleotide polymorphism (SNP) in the MDM2 promoter, SNP309, was related to increased MDM2 expression and poor outcomes for various malignancies. The present retrospective study investigates the association of SNP 309 with MDM2 expression levels and clinical significance in pediatric ALL. Data obtained from 81 children with ALL showed a similar genotype distribution of SNP 309 as seen in other types of cancer and healthy populations: 37 T/T (46%), 37 T/G (46%) and 7 G/G (8%). However, this SNP did not seem to control MDM2 mRNA expression in ALL. We observed that 20 of the 81 ALL cases overexpressed MDM2 mRNA (> 10-fold higher than in normal bone marrow mononuclear cells), of which 8 were SNP 309 T/T, while 12 were T/G (10) or G/G (2) (p>0.5). Furthermore, we found that both MDM2 mRNA and protein were undetectable in 10 of 37 T/G and 3 of the 7 G/G cases. In addition, there were no associations found between SNP 309 and the in vitro response to doxorubicin, nor and early relapse in the 81 ALL patients. Upon review of 23 ALL cell lines, we found there was a relatively higher percentage of T/G (57%) than in fresh ALL samples (46%). However, the expression level of MDM2 was not related to SNP 309, but was rather closely associated with p53 status: All 11 ALL lines with wild-type p53 overexpressed MDM2 and all 12 ALL lines with mutant p53 or with a p53-null phenotype expressed no or low levels of MDM2, regardless of their SNP 309 status. These results suggest that in pediatric ALL, the SNP 309 status affects neither the expression of MDM2 nor the clinical prognosis.
Mortality salience increases death-thought accessibility and worldview defense among high Broad Autism Phenotype (BAP) individuals

Abstract The Broad Autism Phenotype (BAP) is an individual difference whereby persons exhibit mild characteristics of autism spectrum disorder (ASD), including being socially aloof and having a rigid personality. Given that individuals high in BAP rigidity have difficulty adjusting to change, the present research examined whether rigid persons report greater concerns about death and adhere to their cultural beliefs following mortality salience (MS). In Study 1, we found that BAP rigidity was positively associated with greater mortality-related concerns. In Study 2, high rigid individuals evidenced increased death-thought accessibility following MS. Finally, Study 3 found that MS led to heightened worldview defense for individuals high in rigidity, while decreasing defensiveness for those low in rigidity. These results provide evidence for the moderating role of individual differences in terror management effects. Specifically, ASD characteristics in young adults, particularly in the area of rigidity, contribute to heightened death concerns and greater defensiveness.
X-Ray Diffraction Studies on Biological Membranes

Publisher Summary This chapter discusses the results of recent X-ray diffraction studies on cell membranes. Membrane ultra-structure is more often studied by electron microscopy, but the X-ray diffraction method has an important advantage in that membranes can be maintained in a living condition during the X-ray experiment. X-Ray studies on membranes have their own rules and do not follow the step-by-step procedures used in the study of crystals. It is widely recognized that structural interpretations of X-ray diffraction data from biological systems are especially difficult. The main reason for this difficulty is that a continuous electron density distribution is sought. Before a correct electron density description can be obtained, a solution to the phase problem is required. Although as a rule, the phase problem cannot be directly solved, by making a few plausible assumptions, often a possible solution can be found. This kind of situation is not ideal as it would be desirable to have an exact answer
Measuring quality of outpatient cardiovascular care

Accurately measuring the quality of cardiovascular care and attempting to determine the sources of quality deficits are difficult challenges, particularly in the outpatient setting. Clinical trials have documented the benefits of warfarin in atrial fibrillation, angiotensin-converting enzyme (ACE)
A gene from human chromosomal band 3p21.1 encodes a highly conserved arginine-rich protein and is mutated in renal cell carcinomas

We have identified a gene, called ARP for Arginine-rich protein, in human chromosomal band 3p21. It is approximately 600 Kb telomeric to the ACY1 locus (Miller et al., 1989) and encodes a previously unidentified 234 amino acid long, highly basic protein. This gene is highly conserved at the DNA and RNA level. It is found in all species including hamster, rat, mouse, bovine and yeast. We have detected a point mutation (ATG50 to AGG) or deletion of ATG50 in 10 of 21 sporadic renal cell carcinomas. The mutable region is in an imperfect trinucleotide repeat in the coding region which is non-polymorphic among 50 normal individuals examined. The point mutation (ATG50 to AGG) or deletion of codon 50 removes a methionine and increases the stretch of arginines encoded by the AGG repeats in the ARP gene.
Bargaining, Negotiations, and Personal Selling

This chapter examines the important human interactions called bargaining and negotiation in the setting of personal selling. Economics and psychology provide important concepts and variables which, when combined, produce favorable insights to bargaining, negotiations, and personal selling. Whenever the terms of a sales transaction are determined, or a business deal is settled, bargaining is likely. In a sense, everyone becomes a bargainer at one time or another. Bargaining occurs between all forms of human groupings: individuals, groups, organizations, and countries. The conditions under which “bargaining” takes place are when two or more parties have divergent interests or goals and communication between the parties is possible. Three additional conditions must also exist in order for bargaining to occur (Chertkoff and Esser, 1976): 1. Mutual compromise must be possible. If one of the parties must choose between total victory or complete loss, no bargaining occurs. Bargaining situations require intermediate solutions for the parties involved. 2. The possibility must exist for provisional offers to be made by those involved in the situation. 3. The provisional offers must not determine the outcome of the situation, until the terms are accepted by all parties.
Equivalences between quadratic admissibility and generalized quadratic stability for uncertain singular systems

The robust stability and robust stabilization of uncertain singular systems are more complicated than those for normal state-space systems. For norm bounded uncertain singular systems, there exist two different quadratic admissibility definitions. This paper considers the relationship of quadratic admissibility and so called generalized quadratic stability of uncertain continuous singular systems. The equivalence between the above definitions is proven. Further­more, the new criteria of quadratic admissibility of closed loop system through feedback and quadratic stabilizability of uncertain continuous singular systems are obtained by the equivalence relationship. The criteria are directly solved the feasible solutions with LMI toolbox and are much more tractable and reliable in numerical computation than existing results which involve semi positive definite LMIs with equality constraints. Numerical example is given to show the effectiveness of the proposed approaches.
Erectile Dysfunction in Male Survivors of Childhood Cancer.

This survey study evaluates the presence of erectile dysfunction in men who had experienced cancer during childhood.
Genetic moderation of the effects of the Family Check-Up intervention on children's internalizing symptoms: A longitudinal study with a racially/ethnically diverse sample

Development involves synergistic interplay among genotypes and the physical and cultural environments, and integrating genetics into experimental designs that manipulate the environment can improve understanding of developmental psychopathology and intervention efficacy. Consistent with differential susceptibility theory, individuals can vary in their sensitivity to environmental conditions including intervention for reasons including their genotype. As a consequence, understanding genetic influences on intervention response is critical. Empirically, we tested an interaction between a genetic index representing sensitivity to the environment and the Family Check-Up intervention. Participants were drawn from the Early Steps Multisite randomized prevention trial that included a low-income and racially/ethnically diverse sample of children and their families followed longitudinally (n = 515). As hypothesized, polygenic sensitivity to the environment moderated the effects of the intervention on 10-year-old children's symptoms of internalizing psychopathology, such that children who were genetically sensitive and were randomly assigned to the intervention had fewer symptoms of child psychopathology than genetically sensitive children assigned to the control condition. A significant difference in internalizing symptoms assessed with a clinical interview emerged between the intervention and control groups for those 0.493 SD above the mean on polygenic sensitivity, or 25% of the sample. Similar to personalized medicine, it is time to understand individual and sociocultural differences in treatment response and individualize psychosocial interventions to reduce the burden of child psychopathology and maximize well-being for children growing up in a wide range of physical environments and cultures.
3D-printed magnetic tweezers for dorsal traction force measurement.

In this study, economic magnetic tweezers (EMT) with a sharp gradient field were designed and built, in order to facilitate accurate force measurement. Our design costs less than 40 USD and is easy...
Michigan's Mandatory Beverage-Container-Deposit Law: Economic Effects of a Public Policy on Industry Sales:

The following is an estimate of the effect of mandatory beverage container deposit legislation, or “bottle bills” on beer sales. Demand models are defined over a thirty-year series for industry sal...
Hybrid integration of active semiconductor devices with passive micro/nano optical structures for emerging applications

We show a fully integrated, coherently combined laser system in the InP-Si3N4 hybrid platform. Coherent combining of two InP-based gain chips is obtained with a combining efficiency of ~92%. Besides, we demonstrate narrow-linewidth, tunable diode lasers in InP/GaAs-Si3N4 platform. The Si3N4 photonic integrated circuit performs as a tunable external cavity for both InP and GaAs gain chips simultaneously. Single frequency lasing at 1.55 and 1 um is simultaneously obtained on a single chip with the spectral linewidths of 18-kHz and 70-kHz respectively. We also obtain wide-angle beam steering by using the wide wavelength tuning range provided by dual-band diode lasers.
Transfeminine Gender Confirmation Surgery with Penile Inversion Vaginoplasty: An Initial Experience.

To detail the early experience with and results of a transfeminine (TF) genital reconstruction at an established plastic surgery practice in Western New York. Methods Between June 2016 and June 2019, 30 patients underwent penile inversion vaginoplasty for TF gender reassignment. All patients fulfilled World Professional Association for Transgender Health and NY State criteria for reassignment surgery. All surgeries were carried out at a large, government-owned tertiary care center. Results There were 30 patients in this retrospective study, with a mean age of 37 years (SD 5.4) and a mean body mass index of 27.3 kg/m2 (SD 3.2 kg/m2). Nineteen patients never smoked, 4 were former smokers, and 7 were current smokers. Primary surgery was an orchiectomy and modified single-stage penile inversion vaginoplasty. Mean operative time was 6.0 hours. Mean initial hospital stay was 8.2 days. Three of the 30 (10%) patients required transfusion. There were 6 (20%) complications. Three complications (10%) required reoperation: 1 patient for wound dehiscence on postoperative day 7, 1 for rectal perforation identified on postoperative day 10, and 1 for urethrovaginal fistula. All complications were addressed without sequalae. Twenty of the 30 (66%) patients have undergone revision surgery. Indications for revision were prolapse correction/deepening, labiaplasty, clitoral hood construction/revision, meatal asymmetry, urinary fistula repair, and posterior vaginal flap revision. Twenty-one of 28 (75%) revisions were outpatient surgeries. There were no complications from these procedures. Overall satisfaction via survey was 92% (24 respondents). Conclusions TF gender reassignment is a novel, challenging set of procedures for the specialty of plastic surgery. With appropriate consideration and technique, penile inversion vaginoplasty is a safe, effective means of achieving this goal.
Intrapulmonary inoculation of multicellular spheroids to construct an orthotopic lung cancer xenograft model that mimics four clinical stages of non-small cell lung cancer.

Abstract Introduction Lung cancer leads in mortality among all types of cancer in US and Non-small cell lung cancer (NSCLC) is the major type of lung cancer. Mice models of lung cancer based on subcutaneous or orthotopic inoculation of cancer cell suspension do not adequately mimic the progression of lung cancer in clinic. Methods A549-iRFP cells (human NSCLC adenocarcinoma) were cultured to form multicellular spheroids (MCS), which were then inoculated intrapulmonarily into male athymic nude mice. The xenograft cancer development was monitored by in vivo fluorescent imaging and validated by open-chest anatomy, ex vivo fluorescent imaging, and histological studies. Results The newly developed orthotopic xenograft model of lung cancer simulated all four clinical stages of NSCLC progression over one month: Stage 1) localized tumor at the inoculation site, Stage 2) multiple tumor nodules or larger tumor nodule on the same side of the lung, Stage 3) cancer growth on heart surface, and Stage 4) metastatic cancer on both sides of the lung. The model yielded high rates of postoperative survival (100%) and parenchymal tumor establishment (88.9%). The roughness of the inoculated MCS associated negatively with the time needed to develop metastatic cancer (p = .0299). Discussion This new orthotopic xenograft model of NSCLC would facilitate the development of medications to treat lung cancer.
River Microbiome Composition Reflects Macroscale Climatic and Geomorphic Differences in Headwater Streams

Maintaining the quality and quantity of water resources in light of complex changes in climate, human land use, and ecosystem composition requires detailed understanding of ecohydrologic function within catchments, yet monitoring relevant upstream characteristics can be challenging. In this study, we investigate how variability in riverine microbial communities can be used to monitor the climate, geomorphology, land-cover, and human development of watersheds. We collected streamwater eDNA and used 16S rRNA sequencing to profile microbiomes from headwaters to outlets of the Willamette and Deschutes basins, two large watersheds prototypical of Pacific Northwest region of the United States. Within each watershed, microbial community composition correlated strongly (mean Mantel test statistic r = 0.24 in Willamette, 0.17 in Deschutes) with development-related characteristics, including percentage impervious area and percentage of low, medium, and high density developed area. In the temperate Willamette basin, percentage of forest and shrublands (r = 0.34) and percentage of medium density developed area (r = 0.30) were among the strongest correlates with microbial community composition. In the arid Deschutes basin, however, geomorphic characteristics were the most strongly correlated to microbial community composition (e.g., r = 0.33 for topographic index, 0.29 for topographic relief). In headwater sub-catchments across both watersheds, microbial community assemblages correlated with catchment-scale climate and geomorphology (r = 0.45 and 0.23, respectively), but these relationships were weaker downstream. Our results build on previous work relating the streamwater microbiome to hydrologic regime and demonstrate that microbial eDNA in headwater streams additionally reflects the structural configuration of landscapes as well as other natural and anthropogenic processes upstream. Our results offer an encouraging indication that streamwater eDNA carries information not only about microbial ecology, but also can be a useful tool for monitoring multiple upstream watershed characteristics.
Investigations of Yeast l-Lactate Dehydrogenase (Cytochrome b2) III. CYTOCHROME b2-HEMOPROTEIN 557; REACTION OF CYTOCHROME b2 WITH p-CHLOROMERCURIBENZENESULFONATE

Abstract Cytochrome b2, the l-(+)lactate dehydrogenase of bakers' yeast (EC 1.1.2.3), contains both protoheme and flavin mononucleotide prosthetic groups. The heme protein obtained by dissociating the flavin with (NH4)2SO4 at low pH is unable to accept electrons directly from l-lactate, and is a much less effective electron acceptor for the active enzyme than is ferricytochrome c. Cytochrome b2 reacts with p-chloromercuribenzenesulfonate with eventual loss of activity and dissociation of the flavin mononucleotide prosthetic group. In the reduced form of the enzyme, approximately 6 thiol groups per heme unit bind the mercurial, while in the oxidized form approximately 5 groups react. In the presence of 0.2% dodecyl sulfate, an additional thiol group becomes available in the oxidized enzyme. All available —SH groups can be reacted without complete loss of activity or immediate dissociation of the FMN; however, the enzyme is much less stable after treatment with the mercurial and soon becomes completely inactive, and the binding of the flavin group is very much weakened. If the enzyme is allowed to react with excess mercurial, the FMN can be removed by Sephadex filtration; it is possible to secure nearly complete recovery of activity by treatment with excess mercaptoethanol and FMN with Sephadex filtration to remove the excess of the reagents. The reaction of cytochrome b2 with p-chloromercuribenzenesulfonate follows complex kinetics which indicates that the reactive —SH groups are not all of equal reactivity. The initial rate is proportional to the p-chloromercuribenzenesulfonate concentration up to about 200 µm and then appears to reach a saturation plateau at about 1000 µm. It is concluded that the —SH groups which can react with p-chloromercuribenzenesulfonate are not directly involved in the catalytic mechanism or in binding the FMN groups. Introduction of the mercurial groups appears to cause a conformational change which labilizes the enzyme, decreases the strength of binding of the FMN groups, and interferes with the heme-FMN interaction which is necessary for catalytic activity.
A 35 MHz linear ultrasonic array for medical imaging

Ultrasound backscatter microscope (UBM) imaging systems operating above 20 MHz are capable of achieving the axial and lateral resolutions needed for applications in ophthalmology and dermatology. Unfortunately these systems rely upon mechanically scanned single element transducers and suffer from a fixed focus, low frame rate and cumbersome scanning hardware. High frequency arrays are therefore desirable for several reasons, including the ability to dynamically focus the sound beam, increase frame rates and clinical convenience. This study investigates the design tradeoffs involved in the development of a high frequency (35 MHz) 64-element linear array. This array was designed primarily for human eye and skin imaging, and features monolithic elements mechanically diced out of a fine grain high density PZT-5H ceramic. Array elements were spaced with a 50 /spl mu/m pitch, interconnected via a flexible circuit and matched to the 50 /spl Omega/ system electronics via a 85 /spl Omega/ transmission line coaxial cable. Several prototype arrays were constructed with promising results. An average center frequency of 34 MHz with a -6 dB bandwidth of at least 45% per element was achieved. The maximum combined electrical and acoustical crosstalk for nearest and next nearest elements was less than -29 dB, and the average 40 dB pulse length was 105 ns.
Weber-Christian disease with facial involvement: Report of a case

Abstract A case of Weber-Christian disease with facial involvement has been presented. The oral surgeon should be aware of the possibility of this disease.
Inhibition of the denaturation of human gamma globulin by a mixture of d-penicillamine disulfide and copper: A possible mechanism of action of d-penicillamine in rheumatoid arthritis

Abstract Mixtures of d -penicillamine disulfide and copper(II) mimicked sulfhydryl-blocking reagents (viz. gold thiomalate, N -ethylmaeimide and p -chloromercuribenzoic acid) in inhibiting the formation of acetic acid-insoluble heat-denatured human gamma globulin and hyperviscous heat-denatured bovine serum albumin and diluted human serum. These studies suggest a mechanism by which d -penicillamine, after oxidation to d -penicillamine disulfide, could inhibit the denaturation of synovial fluid gamma globulin and in this way possibly suppress rheumatoid arthritis.
The 630-kb Lung Cancer Homozygous Deletion Region on Human Chromosome 3p21.3: Identification and Evaluation of the Resident Candidate Tumor Suppressor Genes

We used overlapping and nested homozygous deletions, contig building, genomic sequencing, and physical and transcript mapping to further define a approximately 630-kb lung cancer homozygous deletion region harboring one or more tumor suppressor genes (TSGs) on chromosome 3p21.3. This location was identified through somatic genetic mapping in tumors, cancer cell lines, and premalignant lesions of the lung and breast, including the discovery of several homozygous deletions. The combination of molecular manual methods and computational predictions permitted us to detect, isolate, characterize, and annotate a set of 25 genes that likely constitute the complete set of protein-coding genes residing in this approximately 630-kb sequence. A subset of 19 of these genes was found within the deleted overlap region of approximately 370-kb. This region was further subdivided by a nesting 200-kb breast cancer homozygous deletion into two gene sets: 8 genes lying in the proximal approximately 120-kb segment and 11 genes lying in the distal approximately 250-kb segment. These 19 genes were analyzed extensively by computational methods and were tested by manual methods for loss of expression and mutations in lung cancers to identify candidate TSGs from within this group. Four genes showed loss-of-expression or reduced mRNA levels in non-small cell lung cancer (CACNA2D2/alpha2delta-2, SEMA3B [formerly SEMA(V), BLU, and HYAL1] or small cell lung cancer (SEMA3B, BLU, and HYAL1) cell lines. We found six of the genes to have two or more amino acid sequence-altering mutations including BLU, NPRL2/Gene21, FUS1, HYAL1, FUS2, and SEMA3B. However, none of the 19 genes tested for mutation showed a frequent (>10%) mutation rate in lung cancer samples. This led us to exclude several of the genes in the region as classical tumor suppressors for sporadic lung cancer. On the other hand, the putative lung cancer TSG in this location may either be inactivated by tumor-acquired promoter hypermethylation or belong to the novel class of haploinsufficient genes that predispose to cancer in a hemizygous (+/-) state but do not show a second mutation in the remaining wild-type allele in the tumor. We discuss the data in the context of novel and classic cancer gene models as applied to lung carcinogenesis. Further functional testing of the critical genes by gene transfer and gene disruption strategies should permit the identification of the putative lung cancer TSG(s), LUCA, Analysis of the approximately 630-kb sequence also provides an opportunity to probe and understand the genomic structure, evolution, and functional organization of this relatively gene-rich region.
On legitimalaise in the United States : A Weberian analysis

This article argues that Weberian principles of rational/legal legitimacy do not presently support American political institutions effectively. Instead, these institutions are characterized by “legitimalaise,” a condition that Weber himself foresaw. This article provides evidence to support this thesis. It then discusses the distinctive political consequence of legitimalaise, that is, structural innovation, or the more or less permanent reform of American political institutions. It concludes with doubt that structural innovation will establish rational/legal legitimacy anew or that new forms of political legitimacy will emerge in the twenty-first century.
EuPaGDT: a web tool tailored to design CRISPR guide RNAs for eukaryotic pathogens

Recent development of CRISPR-Cas9 genome editing has enabled highly efficient and versatile manipulation of a variety of organisms and adaptation of the CRISPR-Cas9 system to eukaryotic pathogens has opened new avenues for studying these otherwise hard to manipulate organisms. Here we describe a webtool, Eukaryotic Pathogen gRNA Design Tool (EuPaGDT; available at http://grna.ctegd.uga.edu), which identifies guide RNA (gRNA) in input gene(s) to guide users in arriving at well-informed and appropriate gRNA design for many eukaryotic pathogens. Flexibility in gRNA design, accommodating unique eukaryotic pathogen (gene and genome) attributes and high-throughput gRNA design are the main features that distinguish EuPaGDT from other gRNA design tools. In addition to employing an array of known principles to score and rank gRNAs, EuPaGDT implements an effective on-target search algorithm to identify gRNA targeting multi-gene families, which are highly represented in these pathogens and play important roles in host–pathogen interactions. EuPaGDT also identifies and scores microhomology sequences flanking each gRNA targeted cut-site; these sites are often essential for the microhomology-mediated end joining process used for double-stranded break repair in these organisms. EuPaGDT also assists users in designing single-stranded oligonucleotides for homology directed repair. In batch processing mode, EuPaGDT is able to process genome-scale sequences, enabling preparation of gRNA libraries for large-scale screening projects.
A morphological and histochemical study of the subcommissural organ of young and old sheep.

Cytologic alterations with age are evident in the subcommissural organ of sheep, but evidence of a secretory function has not been found. In young lambs the cytoplasm has numerous, irregular, interconnecting, endoplasmic sacs with electron dense material. Lamellar cytoplasmic lipid bodies (lipid surrounded by membranous whorls) are scattered throughout the deep layer.
A longitudinal study of the corpus callosum in chronic schizophrenia.

Background Decreased callosal size and anisotropy have been described in schizophrenia patients but their longitudinal progression remains poorly understood.
Maytansine inhibits nucleotide binding at the exchangeable site of tubulin.

Abstract The antineoplastic drug maytansine inhibits the binding of exogenously added radiolabeled GDP and GTP to tubulin (50% inhibition at 9–10 μM drug at 0°). Vinblastine was 1 10 - th as inhibitory. Neither maytansine nor vinblastine displaced GDP from tubulin, and both drugs virtually eliminated dissociation of radiolabeled GDP from the exchangeable site. Maytansine also inhibits binding of nucleotides to a vacant exchangeable site. Maytansine thus prevents nucleotide exit and entry at the exchangeable site because of a direct physical obstruction or a conformational change in the tubulin molecule.
Spontaneous echocardiographic contrast in the thoracic aorta: Factors associated with its occurrence and its association with embolic events

Spontaneous echocardiographic contrast is associated with embolic events when it occurs in the left atrium. Because little is known about spontaneous echocardiographic contrast in the aorta, we investigated this association retrospectively in 343 patients without aortic dissection or aneurysm who had undergone transesophageal echocardiography. Two independent readers concurred on the presence of spontaneous echocardiographic contrast in the aorta in 93% of the study patients, with the remainder agreed on by consensus. Spontaneous echocardiographic contrast was found in 65 patients (19%) and was associated with older age (p < 0.0001), male sex (p < 0.0001), slightly larger aortas (p < 0.0001), and complex aortic atherosclerosis (p = 0.0001). Thirty-four (28.6%) of 119 patients with clinical embolic events had spontaneous echocardiographic contrast in the aorta in contrast to 31 (13.8%) of 224 patients referred for other reasons (p = 0.0001). This finding remained significant when spontaneous echocardiographic contrast in the aorta was the only abnormality allowed (n = 207, p = 0.0065) or when other echocardiographic variables known to be related to embolic events were included in a multivariate analysis. Thus, spontaneous echocardiographic contrast in the aorta can often be detected by transesophageal echocardiography and is associated with a higher prevalence of embolic events.
The mode of vasorelaxing action of melatonin in rabbit aorta.

Abstract 1. 1. The vasorelaxing effect of melatonin on the contractile response to 5-hydroxytryptamine (5-HT) was investigated in rabbit isolated aorta. 2. 2. Melatonin (10 −5 –10 −3 M) caused relaxation of the 5-HT (10 −7 M) response, in a concentration-dependent manner. Nifedipine (10 −6 M) did not affect the relaxing action of melatonin. 3. 3. Pretreatment with methylene blue (10 −5 M) or nitroglycerin (3 × 10 −8 M) inhibited or potentiated, respectively, the relaxing action of melatonin. 4. 4. Pretreatment with melationin (10 −3 M) or M&B 22,948 (10 −5 M) potentiated the relaxing effect of nitroglycerin (10 −9 –10 −5 M) on the contraction induced by PGF 2α (4 × 10 −6 M). The effect of a combined treatment with melatonin and M&B 22,948 was not significantly different from that of a single treatment with M&B 22,948. 5. 5. Melatonin (10 −5 –10 −3 M) inhibited the activity of cGMP-phosphodiesterase, in a concentration-dependent manner. 6. 6. These results suggest that the vasorelaxing action of melatonin may be due to an increase in the level of cGMP.
Select Biomarkers for Tumors of the Gastrointestinal Tract: Present and Future

Context.— Advances in molecular biomarkers of the gastrointestinal tract have contributed to a decline in the incidence of and mortality from diseases of the gastrointestinal tract. The discovery and clinical validation of new biomarkers are important to personalized cancer therapy, and numerous clinical trials are currently ongoing to help identify individualized therapy affecting these biomarkers and molecular mechanisms they represent. Distinct molecular pathways leading to cancers of the colorectum, esophagus, stomach, small bowel, and pancreas have been identified. Using biomarkers in these pathways to direct patient care, including selection of proper molecular testing for identification of actionable mutations and reporting the results of these biomarkers to guide clinicians and genetic counselors, is paramount. Objective.— To examine and review select clinically actionable biomarkers of the colon, esophagus, stomach, small bowel, and pancreas, including present and future biomarkers with relevant ...