cssi/SciSciGPT-SciSciNet huggingface dataset:
Foraging for trust: exploring rationality and the stag hunt game

Trust presents a number of problems and paradoxes, because existing theory is not fully adequate for understanding why there is so much of it, why it occurs, and so forth. These problems and paradoxes of trust are vitally important, for trust is thought to be the essential glue that holds societies together. This paper explores the generation of trust with two simple, but very different models, focusing on repeated play of the Stag Hunt game. A gridscape model examines creation of trust among cognitively basic simple agents. A Markov model examimes play between two somewhat more sophisticated agents. In both models, trust emerges robustly. Lessons are extracted from these findings which point to a new way of conceiving rationality, a way that is broadly applicable and can inform future investigations of trust.
Change fatigue: Development and initial validation of a new measure

Abstract Although organizational change often places strain on employees, few studies have explored the impact of multiple organizational changes on their well-being and withdrawal, including organizational commitment and turnover intentions. To provide a means of directly investigating such issues, we developed a measure of change fatigue, and then empirically examined its implications for employees. Using data from change consultants and a manufacturing organization in the United States that had undertaken a number of organizational changes over the last three years, the authors developed a six-item measurement scale, obtained initial evidence of construct validity, and then investigated the relationship between change fatigue and harmful outcomes, including exhaustion, organizational commitment and turnover intentions. Results indicated that change fatigue was positively associated with exhaustion, and exhaustion was in turn negatively related to organizational commitment and positively related to turn...
Role of calcium binding by sarcoplasmic reticulum in the contraction and relaxation of uterine smooth muscle.

The binding of calcium by isolated sarcoplasmic reticulum from cow uterus was studied. Sarcoplasmic reticulum was prepared by differential centrifugation. Three fractions were obtained: I, sedimented between 2,500–15,000 x g; II at 40,000 x g; and III, at 150,000 x g. Fraction II was further purified on a sucrose density gradient. All three fractions contained considerable amounts of intrinsic calcium, mostly in fraction I. Calcium binding in the presence of ATP1 and Mg also was greatest in fraction I, followed by fraction II, with less in fraction III. Without ATP no calcium was taken up. 5 and 10 mM sodium azide partially inhibited calcium binding in fraction I, but not in fraction II, suggesting the presence of some mitochondria or mitochondrial fragments in fraction I. Calcium binding in fraction II was completely inhibited by 3 mM salyrgan; this fraction thus appears to be sarcoplasmic reticulum. ATPase activity was found in all three fractions, highest in fraction II. It is computed that calcium binding in fractions I and II, on the basis of a 50% yield of protein, is sufficient to elicit contraction by supplying calcium to the contractile proteins of the smooth muscle cell and to regulate relaxation and contraction.
Low-memory packetized SPIHT image compression

The SPIHT image compression algorithm is modified for application to large images with limited processor memory. The subband decomposition coefficients are partitioned into small tree-preserving spatial blocks which are each independently coded using the SPIHT algorithm. The bitstreams for each spatial block are assembled into a single final bitstream through one of two packetization schemes. The final bitstream can be embedded in fidelity with a small expense in rate, SPIHT encoding and decoding of the spatial blocks can be done in parallel for real-time video compression.
CHARACTERIZATION OF METABOLISM IN THE FE(III)-REDUCING ORGANISM GEOBACTER SULFURREDUCENS BY CONSTRAINT-BASED MODELING

Geobacter sulfurreducens is a well-studied representative of the Geobacteraceae, which play a critical role in organic matter oxidation coupled to Fe(III) reduction, bioremediation of groundwater contaminated with organics or metals, and electricity production from waste organic matter. In order to investigate G. sulfurreducens central metabolism and electron transport, a metabolic model which integrated genome-based predictions with available genetic and physiological data was developed via the constraint-based modeling approach. Evaluation of the rates of proton production and consumption in the extracellular and cytoplasmic compartments revealed that energy conservation with extracellular electron acceptors, such as Fe(III), was limited relative to that associated with intracellular acceptors. This limitation was attributed to lack of cytoplasmic proton consumption during reduction of extracellular electron acceptors. Model-based analysis of the metabolic cost of producing an extracellular electron shuttle to promote electron transfer to insoluble Fe(III) oxides demonstrated why Geobacter species, which do not produce shuttles, have an energetic advantage over shuttle-producing Fe(III) reducers in subsurface environments. In silico analysis also revealed that the metabolic network of G. sulfurreducens could synthesize amino acids more efficiently than that of Escherichia coli due to the presence of a pyruvate-ferredoxin oxidoreductase, which catalyzes synthesis of pyruvate from acetate and carbon dioxide in a single step. In silico phenotypic analysis of deletion mutants demonstrated the capability of the model to explore the flexibility of G. sulfurreducens central metabolism and correctly predict mutant phenotypes. These results demonstrate that iterative modeling coupled with experimentation can accelerate the understanding of the physiology of poorly studied but environmentally relevant organisms and may help optimize their practical applications.
So What If I Dont Have An iPhone? The Unintended Consequences Of Using Arrogance In Advertising

Although the effects of arrogance on relationships have been studied within the field of personality and social psychology, there is a lack of research on the effects of corporate arrogance on relationships with consumers. In the current research, the author examines the effect of corporate arrogance (operationalized through the use of arrogance in a commercial) on consumers attitudes toward the brand and on their purchase intentions toward the product. In one experiment the author demonstrates that the use of arrogance in commercials has opposite effects on attitudes depending on a consumers previous experience with the brand. Specifically, individuals who are current users of the advertised product display an increase in attitudes, while those who do not currently use the advertised product demonstrate a decrease. Interestingly, the use of arrogance in commercials has a main effect on consumers purchase intentions. Specifically, all consumers, regardless of their previous experience with the advertised product, exhibit lower purchase intentions toward said product. This work makes a significant contribution to the field as it suggests that companies need to be especially careful about utilizing arrogance in their advertising because it may generate the opposite effect than what was intended.
Rabies Oral Immunization

My interest in oral immunization dates to 1950 when I fed a child the live, attenuated polio virus vaccine. During the ensuing several years, many more children were immunized with this vaccine, and these efforts culminated in mass oral immunization of 250,000 infants in the Belgian Congo, during the epidemic of true infantile paralysis. This immunization required six weeks to perform. Our current interest in oral immunization stems from the fact that our real problem, as far as rabies is concerned, is not domestic animals, and not even vaccines for humans, but for effective vaccines for wildlife. The experience, particularly of Europeans with foxes, has indicated that the eradication of rabies in wildlife cannot be achieved by reducing the reservoir species by killing, gassing, or any other rather barbaric method. Instead, immunization of the wild reservoir animals offers an alternative approach (Steck et al. 1982). The questions are, how and what type of vaccine could be used, and how effective it would be — and this is the subject of my contribution. I will be discussing only one type of vaccine — the vaccinia-rabies glycoprotein recombinant vaccine (V-RG). I do not need to present details about the vaccine, other than that it is obtained by the cDNA derived from the mRNA for rabies glycoprotein incorporated into a construct plasmid from which it is in turn incorporated with vaccinia virus TK gene plasmid (Kieny et al. 1984). Transfection of vaccinia-infected cells with the plasmid allows double reciprocal recombination in vivo and final construction of the V-RG recombinant virus vaccine with the rabies glycoprotein gene interrupting the vaccinia TK gene sequence.
Renal Oncocytoma: Clinical and Biological Correlates

AbstractWe treated 31 patients with renal oncocytoma. Renal cell carcinoma was found existing separately within the same or contralateral kidney in 10 patients (32%). Followup of 29 patients revealed 24 alive with no evidence of disease and 1 alive with recurrent oncocytoma, while 1 with coexistent tumors died of progressive renal cell carcinoma and 3 tumor-free patients died of unrelated diseases.Quantitative deoxyribonucleic acid analysis was performed on cell suspensions of fresh tumor by flow cytometry or by image cytometry on touch preparations from frozen tissue in 16 patients with renal oncocytoma. Ploidy analysis revealed all oncocytomes to be diploid. Frozen tissue immuno-histology was performed using murine monoclonal antibody against human HLA-A, B and C (class I) antigens with the avidin-biotin peroxidase technique in 11 patients with renal oncocytoma. Ten oncocytomas did not express these self-recognition antigens and 1 was only weakly positive for antigen expression. In contrast, renal cell ...
Using SPs for Teaching and Assessing Clinical Skills for Encounters with Patients with Problems of Substance Abuse, Pain Control, and AIDS

The ability of house staff to assess standardized patients (SP) presenting in pain or with substance abuse problems, as compared to general medical problems, was studied with 24 recent graduates of U.S. medical schools (USMGs) and 65 recent graduates of international medical schools (IMGs). Their performance was compared with that of 12 physician or nurse practitioners utilizing four SP cases. The reliability of all four cases was quite good. The IMGs were found to perform significantly less well than the USMGs in all areas except the poststa-tion encounter. However, within each group the performance on the SP cases of pain control and substance abuse was considerably less than that seen in the general medical cases, suggesting that education of residents in these areas is lacking.
Towards accurate and fast evaluation of multi-stage log-structured designs

Multi-stage log-structured (MSLS) designs, such as LevelDB, RocksDB, HBase, and Cassandra, are a family of storage system designs that exploit the high sequential write speeds of hard disks and flash drives by using multiple append-only data structures. As a first step towards accurate and fast evaluation of MSLS, we propose new analytic primitives and MSLS design models that quickly give accurate performance estimates. Our model can almost perfectly estimate the cost of inserts in LevelDB, whereas the conventional worst-case analysis gives 1.8- 3.5× higher estimates than the actual cost. A few minutes of offline analysis using our model can find optimized system parameters that decrease LevelDB's insert cost by up to 9.4-26.2%; our analytic primitives and model also suggest changes to RocksDB that reduce its insert cost by up to 32.0%, without reducing query performance or requiring extra memory.
A study of the reported occurrence of mesobilirubin in human bile.

Summary and conclusions1. Paper and column chromatographic methods of separating bilirubin and mesobilirubin are described. 2. Use of these methods permits detection of mesobilirubin at the 0.5 mg % level in the presence of much larger amounts of bilirubin. 3. The spectroscopic distinction of biliverdin and mesobiliverdin (glaucobilin), and of their respective zinc complexes, is discussed. 4. Glaucobilin is readily formed from d- or i-urobilin, in addition to mesobilirubin: glaucobilin formation on FeCl3 oxidation is thus not specific for mesobilirubin as suggested by others. 5. Mesobilirubin has not been detected in human bile but was definitely identified in a urine sample containing larger amounts of bilirubin. Its occurrence in the urine is believed to relate to an enterohepatic circulation.
A role for Dehalobacter spp. in the reductive dehalogenation of dichlorobenzenes and monochlorobenzene.

Previously, we demonstrated the reductive dehalogenation of dichlorobenzene (DCB) isomers to monochlorobenzene (MCB), and MCB to benzene in sediment microcosms derived from a chlorobenzene-contaminated site. In this study, enrichment cultures were established for each DCB isomer and each produced MCB and trace amounts of benzene as end products. MCB dehalogenation activity could only be transferred in sediment microcosms. The 1,2-DCB-dehalogenating culture was studied the most intensively. Whereas Dehalococcoides spp. were not detected in any of the microcosms or cultures, Dehalobacter spp. were detected in 16S rRNA gene clone libraries from 1,2-DCB enrichment cultures, and by PCR using Dehalobacter-specific primers in 1,3-DCB and 1,4-DCB enrichments and MCB-dehalogenating microcosms. Quantitative PCR showed Dehalobacter 16S rRNA gene copies increased up to 3 orders of magnitude upon dehalogenation of DCBs or MCB, and that nearly all of bacterial 16S rRNA genes in a 1,2-DCB-dehalogenating culture belonged...
Volume Overview: Introduction

The origins and history of the study of teratology and developmental toxicology span centuries of human experience. Anatomical malformations observed at birth have been described across many generations but the root causes of these events have been enigmatic and difficult to understand. Many factors may contribute to the lack of mechanistic understanding, but the miniscule size, inaccessibility, and the consequences of ethical concerns contribute heavily to the unique restrictions on developmental toxicology research. Classic teratogens, such as vitamin A, Rubella virus, thalidomide, and methyl mercury, have provided many insights into understanding the modes of chemical action that are responsible for causing defects but the specific mechanisms remain unclear. Developmental toxicology research has benefitted greatly in the past decades from discoveries made in related fields of study, including those from cancer research, stem cell biology, and developmental biology. New methods created and adapted for studies in developmental toxicology have taken on greater importance as gestational lesions can now be shown to have developmental and health consequences across the entire lifespan.
Cocaine and the Developing Brain

The effects of cocaine on corticogenesis in the developing murine brain were examined at the University of Louvain Medical School, Brussels, Belgium, and the Massachusetts General Hospital, Boston, MA.
Propagating buoyant mantle upwelling on the Reykjanes Ridge

Crustal features of the Reykjanes Ridge have been attributed to mantle plume flow radiating outward from the Iceland hotspot. This model requires very rapid mantle upwelling and a “rheological boundary” at the solidus to deflect plume material laterally and prevent extreme melting above the plume stem. Here we propose an alternative explanation in which shallow buoyant mantle upwelling instabilities propagate along axis to form the crustal features of the ridge and flanks. As only the locus of buoyant upwelling propagates this mechanism removes the need for rapid mantle plume flow. Based on new geophysical mapping we show that a persistent sub-axial low viscosity channel supporting buoyant mantle upwelling can explain the current oblique geometry of the ridge as a reestablishment of its original configuration following an abrupt change in opening direction. This mechanism further explains the replacement of ridge-orthogonal crustal segmentation with V-shaped crustal ridges and troughs. Our findings indicate that crustal features of the Reykjanes Ridge and flanks are formed by shallow buoyant mantle instabilities, fundamentally like at other slow spreading ridges, and need not reflect deep mantle plume flow.
Lipid Changes Around the Final Menstrual Period Predict Carotid Subclinical Disease in Postmenopausal Women.

Background and Purpose—Atherogenic changes in lipids occur among women around the time of the natural menopause, that is, within 1 year of the final menstrual period (FMP). We investigated whether ...
Shape sensitivity analysis for non-differentiable performance measures in multiscale crack propagation simulation using regression hybrid method

ABSTRACTIn this paper, we present a regression hybrid method that calculates shape sensitivity coeﬃcients for multiscale crack propagation problems with performance measures that are non-differentiable in numerical implementation. These measures are crack propagation speed (or crack speed) defined at atomistic level obtained by solving coupled atomistic/continuum structures using the bridging scale method (BSM). The major contributions of this paper are: first, by analyzing the characteristics of the performance measures of crack speed in design space, this paper verifies for the first time that these measures are theoretically continuous and differentiable with respect to design variables, and as a result, the sensitivity coeﬃcients exist in theory; second, to overcome the non-differentiability of the performance measures in numerical computation due to the finite size of integration time step, this paper proposes a regression hybrid method that calculates the shape sensitivity coeﬃcients of crack speed ...
Nuclear matter effects on J/$\psi$ production in Cu+Au and $U$+$U$ collisions in PHENIX

The Phenix experiment at RHIC has produced high quality J/ψ measurements in heavy ion interactions for various energies and collision systems. These measurements allow us to study the mechanisms which may modify the charmonium production in the nucleus. During 2012 run, the flexibility of RHIC to provide collisions with different nuclei have led to the first experimental study of two new collision systems with unique initial collision geometries. The initial asymmetry of the Cu+Au system leads to differences in the J/ψ suppression along the beam axis. The Phenix detector, with its extensive kinematic coverage, is well suited to measure the J/ψ production in both forward and backward rapidities, 1.2 <y< 2.2 and –2.2 <y< –1.2. Such studies, along with a comparison to the d+Au and Au+Au systems, provide insight into the interplay of cold and hot nuclear matter on the J/ψ modification, and whether such effects could be factorized. The second system, U+U , extends further the maximum energy density reached in heavy ion collisions at RHIC and presents the possibility to study how this increase may alter the particle production.
Rediagnosis of the Tuckasegee Darter, Etheostoma gutselli (Hildebrand), a Blue Ridge Endemic

In 1932, the Tuckasegee Darter was originally described as Poecilichthys gutselli, from the Tuckasegee River (Little Tennessee River system), North Carolina. In 1968, Miller, citing perceived areas of intergradation, relegated it to a subspecies of Etheostoma blennioides. Recent authors, however, re-elevated E. gutselli to the species level without providing any supporting data. We present morphological, meristic, and nuptial male pigmentation data that support the distinctiveness of E. gutselli. Etheostoma gutselli can be distinguished from proximal populations E. blennioides newmanii in the Tennessee River system by lower lateral-line (49–63 vs. 63–81) and caudal-peduncle (18–24 vs. 23–29) scale counts and differences in nuptial male pigmentation. Etheostoma gutselli primarily is restricted to the upper (Blue Ridge) portions of the Little Tennessee and Pigeon river drainages, generally upstream of the Tennessee-North Carolina state line.
Conjugate Polyplexes with Anti-Invasive Properties and Improved siRNA Delivery In Vivo

This study reports on a simple method to prepare siRNA-polycation conjugate polyplexes by in situ thiol–disulfide exchange reaction. The conjugate polyplexes are prepared using thiol-terminated siRNA and a bioreducible branched polycationic inhibitor of the CXCR4 chemokine receptor (rPAMD). The rPAMD-SS-siRNA conjugate polyplexes exhibit improved colloidal stability and resistance against disassembly with heparin, serum, and physiological salt concentrations when compared with control conventional rPAMD/siRNA polyplexes. Coating the polyplexes with human serum albumin masks the positive surface charge and contributes to the enhanced in vitro gene silencing and improved safety in vivo. The conjugate polyplexes display improved in vivo reporter gene silencing following intravenous injection in tumor-bearing mice. Because the conjugate polyplexes retained the ability of rPAMD to inhibit CXCR4 and restrict cancer cell invasion, the developed systems show promise for future combination anti-metastatic siRNA th...
Africans and the Colonial Economy

This chapter maps the general economic policy trajectories of colonial regimes as well as the active agency of Africans in engaging with these policies. Africans tried to cope and thrive in an economy calibrated to serve metropolitan interests. How did Africans, as individuals and groups, react to the strictures and unintended opportunities of colonial policies on land, agriculture, and labor? The chapter demonstrates the ways in which farmers, laborers, women, and other African economic actors engaged with the closures and openings presented by colonial land, labor, and agricultural regimes. It argues that we need to write the initiatives and self-interested creativity of African economic actors into our evaluations of the impacts and outcomes of colonial economic policies and structures.
Invitro synthesis of L-pipecolate from L-lysine: Inconsistent with ϵ-N-acetyl-L-lysine as an obligatory intermediate

In vitro synthesis of 14C-L-pipecolic acid from L-[U-14C]lysine was demonstrated for the first time in the rat tissues. Acetyl donor was not required for this synthesis. No labeling of ϵ-N-acetyl-L-lysine was detected during 14C-pipecolate synthesis. When ϵ-N-acetyl-L-[U-14C]lysine was substrate, large quantities of 14C-lysine but only very small quantities of 14C-pipecolate were detected, indicating the synthesis of L-pipecolate from ϵ-N-acetyl-L-lysine to be by way of L-lysine. Although the present data are inconsistent with the hypothesis that removal of α-NH2 group from L-lysine in preparation for L-pipecolate formation requires ϵ-N-substitution, the involvement of an enzyme-bound ϵ-N-substitutedL-lysine in this pathway cannot be ruled out.
Technical Basis for Proposed Code Case of Using a Master Curve in Lieu of the Code KIc Curve in ASME Boiler and Pressure Vessel Code

The Master Curve method for determination of fracture toughness in the transition range in ASTM standard E1921 [1] brought an opportunity for the ASME Code to adopt a much better fracture toughness curve based on directly measured fracture toughness data. This also enables obtaining statistically based fracture toughness data. The industry, through PVRC Task Group (subsequently Section XI Task Group on Master Curve Fracture Toughness), took a two-phase approach to implement the adoption of the Master Curve method in the ASME Code. First, Phase I was completed with the issuance of ASME Code Cases N-629/N-631 [9, 10], published in 1999 which allowed the existing Code KIc curve to be used by means of an alternate indexing reference temperature RTT0 . This provided an important new approach to allow material specific, measured fracture toughness curves for ferritic steels in the code applications. However, this only rectified part of the shortcomings of the present Code KIc curve. In Phase II, it is intended to develop a direct means to utilize a tolerance bound of the Master Curve itself in place of the ASME KIc curve. This paper summarizes a proposal for such a procedure whereby a Master Curve fracture toughness tolerance bound is made usable in the ASME flaw evaluation processes, i.e. in Appendix A and Appendix G to Section XI of the ASME Boiler and Pressure Vessel Code. A draft code case is presented in Appendix in this paper.Copyright © 2008 by ASME
Effect of Interface Roughness on the Reflection Coefficient

All surfaces and interfaces between dissimilar materials are rough. The extent to which this roughness affects the reflection of elastic waves has been the subject of study for many decades. A recent book by Ogilvy [1] provides a comprehensive review and summary of this subject. The problem is of particular interest in ultrasonic nondestructive evaluation. For example, it has been shown that for typical inspection geometries, rough surfaces degrade the signal-to-noise ratio for scattering defects [2] – [3].
Nutrition Therapy for the Child and Adolescent with Type I Diabetes Mellitus

The author enumerates the objectives of nutritional instruction and therapy for the child with diabetes mellitus and examines some of the principles upon which this therapy is based. Also discussed are the methods used to formulate meal plans, stressing the fact that instruction and counseling in nutritional principles is a continuous process that must be enthusiastically supported by the pediatrician and the physician who follows the diabetic patient during adult life.
A unified GenomeSpace recipe to identify essential genes and associated subnetworks from Genome-Scale CRISPR-Cas9 knockout screens

We present a unified GenomeSpace recipe that combines the results of a high throughput CRISPR genetic screen and a biological network to return a subnetwork that suggests a mechanistic explanation of the screen’s results. The explanatory subnetwork is found by network propagation, a popular systems biology approach. We demonstrate our pipeline on an alpha toxin screen, revealing a subnetwork that is both highly interconnected and highly enriched for hits in the screen.
Association of Vision Loss With Hospital Use and Costs Among Older Adults.

Importance Patients with vision loss who are hospitalized for common illnesses are often not identified as requiring special attention. This perception, however, may affect the outcomes, resource use, and costs for these individuals. Objective To assess whether the mean hospitalization lengths of stay, readmission rates, and costs of hospitalization differed between individuals with vision loss and those without when they are hospitalized for similar medical conditions. Design, Setting, and Participants This analysis of health care claims data used 2 sources: Medicare database and Clinformatics DataMart. Individuals with vision loss were matched 1:1 to those with no vision loss (NVL), on the basis of age, years from initial hospitalization, sex, race/ethnicity, urbanicity of residence, and overall health. Both groups had the same health insurance (Medicare or a commercial health plan), and all had been hospitalized for common illnesses. Vision loss was categorized as either partial vision loss (PVL) or severe vision loss (SVL). Data were analyzed from April 2015 through April 2018. Main Outcomes and Measures The outcomes were lengths of stay, readmission rates, and health care costs during hospitalization and 90 days after discharge. Multivariable logistic and linear regression models were built to identify factors associated with these outcomes among the NVL, PVL, and SVL groups. Results Among Medicare beneficiaries, 6165 individuals with NVL (with a mean [SD] age of 82.0 [8.3] years, and 3833 [62.2%] of whom were female) were matched to 6165 with vision loss. Of those with vision loss, 3401 (55.2%) had PVL and 2764 (44.8%) had SVL. In the Clinformatics DataMart database, 5929 individuals with NVL (with a mean [SD] age of 73.7 [15.1] years, and 3587 [60.5%] of whom were female) were matched to 5929 individuals with vision loss. Of the commercially insured enrollees with vision loss, 3515 (59.3%) had PVL and 2414 (40.7%) had SVL. Medicare enrollees with SVL, compared with those with NVL, had longer mean lengths of stay (6.48 vs 5.26 days), higher readmission rates (23.1% vs 18.7%), and higher hospitalization and 90-day postdischarge costs ($64 711 vs $61 060). Compared with those with NVL, Medicare beneficiaries with SVL had 4% longer length of stay (estimated ratio, 1.04; 95% CI, 1.01-1.07;P = .02), 22% higher odds of readmission (odds ratio, 1.22; 95% CI, 1.06-1.41;P = .007), and 12% higher costs (estimated cost ratio, 1.12; 95% CI, 1.06-1.18;P Conclusions and Relevance These findings suggest that opportunities for improving outcomes and reducing costs exist in addressing patients’ vision loss and concomitant functional difficulties during hospitalization and thereafter.
Algorithmic Control in Platform Food Delivery Work

Building on an emerging literature concerning algorithmic management, this article analyzes the processes by which food delivery platforms control workers and uncovers variation in the extent to wh...
Nonmyeoablative Allogeneic Conditioning with Bendamustine in Combination with Fludarabine and Rituximab for Lymphoid Malignancies: Immunosuppression without Myelosuppression and without Acute Gvhd

Abstract 894 Background: We previously reported the use of fludarabine, cyclophosphamide and rituximab as a nonmyeloablative allogeneic conditioning for CLL and non-Hodgkin9s lymphomas (Khouri et al, Blood 2008;111:5530). Bendamustine is a novel compound which was found to be effective in pts who were refractory to alkylating agents. In order to improve outcomes in nonmyeloablative stem cell transplantation (NST), we substituted cyclophosphamide with bendamustine in the conditioning. Methods: Bendamustine was given iv in an escalated dose of 70, 90, 110, 130 mg/m 2 daily on days −5 to - 3 prior to NST, together with 30 mg/m 2 of fludarabine given on the same days. Rituximab was given at a dose of 375 mg/m 2 on day –13 and 1000 mg/m 2 on days −6, +1, and +8, as previously described. Tacrolimus and methotrexate was used for GVHD prophylaxis. In addition, thymoglobulin of 1 mg/kg was given on days −2, and −1 in pts receiving an unrelated donor. Results: The study included 23 pts [Mantle cell=9, CLL=6 (2 with 17p- and 1 Richter9s), Follicular =4, Diffuse large cell =3]. All pts had relapsed disease after the best conventional therapy (-ies) available. Median age was 60 (range, 30–70) years. Median prior treatments was 2 (range, 1–5); 3 pts (13%) had failed a prior autotransplant. At NST, 11 pts (48%) were in CR, 7 (31%) in PR, 1 (4%) induction failure/sensitive, and 4 pts (17%) had refractory disease. Fifteen pts (65%) received their transplants from HLA-compatible siblings and 8 (35%) from unrelated donors. Continual Reassessment Method based on target toxicity at day 30 post NST was used for dose finding. The number of pts who received the 70, 90, 110, 130 mg/m 2 daily doses of bendamustine were 2, 3, 3, and 15 pts, respectively. No dose-limiting toxicity was observed. Fourteen pts (61%) did not nadir to an ANC 3 . All pts engrafted donor cells. Median donor T cells at day 30 was 93%. Only one pt developed acute GVHD (it was grade 3); none had acute grade 2 or 4. Chronic extensive GVHD was observed in 2 of 22 (9%) evaluable pts. Fungal infection was the cause of the only death observed. Twenty pts (87%) achieved CR, 2 (9%) have ongoing PR, and 1 (4%) had SD. With a median follow-up time of 8 months (range, 3–25 months), the OS and PFS rates were 92% and 79%, respectively. Conclusions: Our results represent the first report to suggest that combining bendamustine at a dose up 130 mg/m 2 daily × 3 days, together with fludarabine and rituximab is safe and constitutes a well tolerated conditioning for NST. We are treating pts with this regimen in the outpatient setting. The study is currently ongoing to assess its efficacy in a larger cohort of pts. Disclosures: Khouri: Cephalon: Research Funding. Off Label Use: Bendamustine use in SCT.
Nurturing Joyful Teaching in an Era of Standardization and Commodification

Low teacher morale suggests a need for a renewed focus on joyful teaching. Moreover, mechanical lesson planning can discourage teacher candidates whose aspirations to teach pivot around their desir...
Quel Test for Two Linear Restrictions in the Nonlinear Models

An alternative Wald type test called the quel test is developed for two linear restrictions by finding the critical region based on the quel utilizing the repeated values of estimated parameters of interest under the null. Simulation shows evidence that the full quel test performs best in that it holds nominal level well and shows monotonic increasing power properties.
The Limits of Individualism: Potential Societal Harms from the EAP for Convalescent Plasma.

This issue features a set of articles addressing allocation issues for drugs for COVID-19 that have not been approved by the FDA but are available through either Emergency Use Authorization or Expa...
Stress Singularities in Laminated Composites

The singular nature of the stress distribution near the free edge of an interface in a laminated composite is analyzed by using the method originally due to Stroh for solving dislocation problems. With this approach, the degenerate case of uncoupling between the displacement components U3 and u1, u2 presents no difficulties in finding the eigenvalues and eigenvectors of the elasticity constants. Numerical examples are presented for the order of singularity at the interface of an angle-ply graphite/epoxy laminated composite in which each layer is assumed to be orthotropic material with the direction of the fibers inclined at various angles θ with the x3-axis.
Colloidal stability of cellulose nanocrystals in aqueous solutions containing monovalent, divalent, and trivalent inorganic salts.

Aggregation kinetics and surface charging properties of rod-like sulfated cellulose nanocrystals (CNCs) have been investigated in aqueous suspensions containing monovalent, divalent, or trivalent inorganic salts. Electrophoresis and time-resolved dynamic light scattering (DLS) were used to characterize the surface charge and colloidal stability of the CNCs, respectively. The surface charge and aggregation kinetics of the sulfated CNCs were found to be independent of solution pH (pH range 2-10). For the monovalent salts (CsCl, KCl, NaCl, and LiCl), the critical coagulation concentration (CCC) followed the order of Cs+ Ca2+ > Ba2+, which is in the reverse order of the counterion ionic size. For the trivalent salts (LaCl3, AlCl3, and FeCl3), the CNCs suspension was destabilized much more effectively. The observed complex stability curves with AlCl3 and FeCl3 are attributed to charge neutralization and charge reversal imparted by the adsorption of aluminum and ferric hydrolysis species on the CNC surface. The significant charge reversal induced by the ferric hydrolysis species led to the restabilization of suspensions. Our results on the colloidal stability of CNCs are of central importance to the nanotechnology and materials science communities working on various applications of CNCs.
Using Data for Program Improvement in Teacher Education: A Study of Promising Practices

Background/ContextContemporary accountability policies in teacher education often require that programs systematically use data for program improvement. However, social science research from multip...
A JOINT MODEL OF X-RAY AND INFRARED BACKGROUNDS. II. COMPTON-THICK AGN ABUNDANCE *

We estimate the abundance of Compton-thick (CT) active galactic nuclei (AGN) based on our joint model of X-ray and infrared backgrounds. At Lrest2−10keV > 10 42 erg/s, the CT AGN density predicted by our model is a few ×10 −4 Mpc −3 from z=0 up to z=3. CT AGN with higher luminosity cuts (> 10 43 , 10 44 & 10 45 erg/s) peak at higher z and show a rapid increase in the number density from z=0 to z�2-3. The CT to all AGN ratio appears to be low (2-5%) at f2−10keV > 10 −15 erg/s/cm 2 but rises rapidly toward fainter flux levels. The CT AGN account for � 38% of the total accreted SMBH mass and contribute � 25% of the cosmic X-ray background spectrum at 20 keV. Our model predicts that the majority (90%) of luminous and bright CT AGN (Lrest2−10keV > 10 44 erg/s or f2−10keV > 10 −15 erg/s/cm 2 ) have detectable hot dust 5-10 µm emission which we associate with a dusty torus. The fraction drops for fainter objects, to around 30% at Lrest2−10keV > 10 42 erg/s or f2−10keV > 10 −17 erg/s/cm 2 . Our model confirms that heavily-obscured AGN (NHI > 10 23 cm −2 ) can be separated from unobscured and mildly-obscured ones (NHI < 10 23 cm −2 ) in the plane of observed-frame X-ray hardness vs. mid-IR/X-ray ratio. Subject headings: galaxies: nuclei – galaxies: active
Cardiometabolic consequences of maternal hyperandrogenemia in male offspring

Polycystic ovary syndrome (PCOS) in women is characterized by hyperandrogenemia, obesity, and oligo- or anovulation. In addition, women with PCOS are often obese, with insulin resistance, hyperlipidemia, and elevated blood pressure. The cardiometabolic consequences for the male offspring of maternal hyperandrogenemia are unclear. The present studies tested the hypothesis that male offspring of a rat model of PCOS would develop cardiometabolic disease as adults. Female Sprague-Dawley rats (hyperandrogenemic females (HAF)) were implanted with dihydrotestosterone or placebo pellets (controls) at 4 weeks of age, and were mated at 10-12 weeks and allowed to lactate their offspring after birth. Body weights in male HAF offspring were lower at birth than in controls until postnatal day 4, but body weights remained similar between male control and HAF offspring from 2 to 8 weeks of age. However, at 16 weeks of age, body weight was lower in HAF male offspring, but there were no differences in fat mass or lean mass factored for body weight in HAF males, compared to controls. Plasma total cholesterol and HDL and proteinuria were higher and nitrate/nitrite excretion was lower in male HAF offspring than in controls. Baseline blood pressure was similar between HAF male offspring and controls, but HAF offspring had an exaggerated pressor response to angiotensin II infusion. These data suggest that adult sons of PCOS mothers may be at increased risk of cardiometabolic disease.
Realism and State Behaviour

Realism, the dominant school of international relations throughout the Cold War, is a theory that has been built up over many hundreds of years, tracing some of its earliest writings from Thucydides starting in 431BCE, through Machiavelli's Il Principe in 1532, and ending up with the modern schools of realism: Human Nature Realism; Offensive and Defensive Realism (Neorealism); Neoclassical Realism. This paper compares their views, predominantly those of the structural school (offensive and Defensive Realism) due to its adoption as the mainstream school of realism, on the major determinants of realist state behaviour: the anarchic international system, the security dilemma, and how states react in their desire for security. It further compares the realist points of view with those of the constructivist and liberal schools of international relations.
Assimilation of Reduced Nitrogen in Tropical Legume Nodules: Regulation of De Novo Purine Biosynthesis and Peroxisome Proliferation

The symbiotically reduced nitrogen is assimilated in the host cytoplasm with the help of cytosolic glutamine synthetase. We have shown that this enzyme is induced directly in response to ammonia. The glutamine formed in the cytoplasm is funneled to the plastids where it is converted to purines. The latter are synthesized via de novo biosynthesis pathway. The purines are then oxidized into ureides inside the uninfected cells of root nodules. We have demonstrated that the de novo purine biosynthesis pathway is induced prior to the onset of nitrogen fixation, apparently due to high demand for purines for DNA endoreduplication in the infected cells. We have also demonstrated that glutamine enhances the expression of PRAT gene, encoding the first enzyme of the pathway. Because the level of uricase increases prior to that of PRAT, it suggests that purine catabolism may begin prior to the increase in de novo purine biosynthesis and the commencement of nitrogen fixation. The access of purines, exported to the uninfected cells, apparently induce peroxisome proliferation for the oxidation of uric acid to ureides. We have demonstrated that purines are able to induce peroxisome proliferation in yeast. Using urate as a source of nitrogen, we have been able to isolate several yeast mutants defective in peroxisome proliferation/assembly. We have complemented one of these mutants with a soybean gene encoding a putative peroxisome proliferation transcriptional factor with similarity to G-box binding proteins. In addition, we have determined two independent pathways for the conversion of uric acid to ureides in root nodules and have isolated corresponding genes involved in these pathways.
Superconductor-Semiconductor Devices

It has long been recognized that electronic devices operating at reduced temperatures—including both semiconductor and superconductor devices—can often offer much higher performance (by several criteria) than room-temperature devices. But the need for cooling has greatly retarded their use, and there exists an almost-universal persistent belief that low-temperature devices just don’t have a chance to find significant practical applications.
Delayed matching-to-sample trained with retractable levers is impaired by lesions of the intralaminar or ventromedial but not the laterodorsal thalamic nuclei

Rats were trained to perform a delayed matching-to-sample (DMS) task with retractable levers and were then given one of four treatments: control surgery or lesions of the intralaminar (ILn), ventromedial (VMn), or laterodorsal (LDn) thalamic nuclei. The ILn and VMn lesions affected response accuracy in a delay-independent fashion and were associated with slower response times for both the sample and the choice responses of the DMS task. The LDn lesion had little effect on this task. The effects of ILn and VMn lesions on DMS speed and accuracy are consistent with the findings of other studies on the effects of lesioning this area of thalamus and with impairments observed for human Korsakoff syndrome patients. It is argued that the effects of ILn and VMn lesions on DMS may be related to the function of these nuclei in the recurrent feedback pathways that connect functionally related areas of the basal ganglia and frontal cortex.
Identification of 4th intercostal space using sternal notch to xiphoid length for accurate electrocardiogram lead placement.

Abstract Objective Precordial ECG lead placement is difficult in obese patients with increased chest wall soft tissues due to inaccurate palpation of the intercostal spaces. We investigated whether the length of the sternum (distance between the sternal notch and xiphoid process) can accurately predict the location of the 4th intercostal space, which is the traditional location for V1 lead position. Materials and Methods Fifty-five consecutive adult chest computed tomography examinations were reviewed for measurements. Results The sternal notch to right 4th intercostal space distance was 67% of the sternal notch to xiphoid process length with an overall correlation of r = 0.600 (p Conclusion The above measurement may be utilized to locate the 4th intercostal space for accurate placement of the precordial electrodes in adults in whom the 4th intercostal space cannot be found by physical exam.
The Role of Proof in Comprehending and Teaching Elementary Linear Algebra.

We describe how elementary Linear Algebra can be taught successfully while introducing students to the concept and practice of ‘mathematical proof’.This is done badly with a sophisticated Definition–Lemma–Proof–Theorem–Proof–Corollary(DLPTPC) approach; badly – since students in elementary Linear Algebra courses have very little experience with proofs and mathematical rigor. Instead, the subjects and concepts of Linear Algebra can be introduced in an exploratory and fundamentally reasoned way. One seemingly successful way to do this is to explore the concept of solvability of linear systems first via the row echelon form (REF). Solvability questions lead to row and column criteria for a REF that can be used repeatedly to: compute subspaces, settle linear (in)dependence, find inverses, perform basis change, compute determinants, analyze eigensystems etc. If these subjects are explained heuristically from the first principles of linear transformations, linear equations, and the REF, students experience the power of a concept–built approach and reap the benefit of deep math understanding. Moreover, early ‘salient point’ proofs lead to an intuitive understanding of ‘math proof’. Once the basic concept of ‘proof’ is ingrained in students, more abstract proofs, even DLPTPC style expositions, on normal matrices, the SVD etc. become accessible and understandable to sophomore students. With the help of this gentle early approach, the concept and construct of a ‘math proof’ becomes firmly embedded in the students' minds and helps with future math courses and general scientific reasoning.
Studying Effects of Primary Care Physicians and Patients on the Trade-Off Between Charges for Primary Care and Specialty Care Using a Hierarchical Multivariate Two-Part Model

Objective. To examine effects of primary care physicians (PCPs) and patients on the association between charges for primary care and specialty care in a point-of-service (POS) health plan.Data Source. Claims from 1996 for 3,308 adult male POS plan members, each of whom was assigned to one of the 50 family practitioner-PCPs with the largest POS plan member-loads.Study Design. A hierarchical multivariate two-part model was fitted using a Gibbs sampler to estimate PCPs' effects on patients' annual charges for two types of services, primary care and specialty care, the associations among PCPs' effects, and within-patient associations between charges for the two services. Adjusted Clinical Groups (ACGs) were used to adjust for case-mix. Principal Findings. PCPs with higher case-mix adjusted rates of specialist use were less likely to see their patients at least once during the year (estimated correlation: .40; 95% CI: .71, .008) and provided fewer services to patients that they saw (estimated correlation: .53; 95% CI: .77, .21). Ten of 11 PCPs whose case-mix adjusted effects on primary care charges were significantly less than or greater than zero (p < .05) had estimated, case-mix adjusted effects on specialty care charges that were of opposite sign (but not significantly different than zero). After adjustment for ACG and PCP effects, the within-patient, estimated odds ratio for any use of primary care given any use of specialty care was .57 (95% CI: .45, .73).Conclusions. PCPs and patients contributed independently to a trade-off between utilization of primary care and specialty care. The trade-off appeared to partially offset significant differences in the amount of care provided by PCPs. These findings were possible because we employed a hierarchical multivariate model rather than separate univariate models.