cssi/SciSciGPT-SciSciNet huggingface dataset:
Facts versus fallacy

Since antiquity, mathematics had been an exemplar of certain knowledge. Reasoning like a mathematician meant reasoning reliably from assumptions to conclusions. Geometry, for example, was taught for centuries as a model for reasoning in general. Howard Wainer9s new book, Truth or Truthiness: Distinguishing Fact from Fiction by Learning to Think Like a Data Scientist , suggests that geometry9s role in the search for truth has been replaced by data science. Truth or Truthiness consists of a series of short, lively chapters that discuss how data scientists would approach various contemporary quandaries.
Nuremberg, Tokyo, and Other Postwar Cases

The Nuremberg Judgment correctly stated then-current law: nullum crimen sine lege was not a limitation of sovereignty. Specifically, nullum crimen sine lege did not state an international law-based human right that could be asserted by an individual against a state, group of states, or international organization. It was correct at least partly because, at the time, there was little interference by international law in the internal arrangements by which governments ruled their people, and the Nuremberg Judgment itself did not announce the violation of the principle of legality as one of the crimes against humanity and war crimes of which the accused might be convicted. Substantive international human rights and humanitarian law had not evolved to make this a right of individuals enforceable against states (or other prosecuting authorities, such as international organizations – should they come to exist). The English version of the Nuremberg Judgment was also correct in stating that nullum crimen sine lege is a principle of justice. At least it was recognized as a fundamental principle of criminal justice by many persons and nations by the time of World War II, including the principal French judge Henri Donnedieu de Vabres. The drafters of what became the Charter of the International Military Tribunal (IMT), which known as the Nuremberg Charter, struggled over the issue of legality and ex post facto legislation, and whether the issue could be defined out of existence simply by including criminal definitions in the text of the Charter.
Grapes and Urinary Bladder Function

The function of the urinary bladder is to collect and store urine at low intravesical pressure and then, periodically, to expel the urine via a highly coordinated and sustained contraction. Bladder function depends on several factors including state of innervation, vascularization, structure of the organ as a whole, contractile response of the smooth muscle (SM) elements to autonomic stimulation, availability of metabolic energy (cytosolic adenosine triphosphate [ATP] and mitochondrial oxidative metabolites), and the density and distribution of the connective tissue in the detrusor. These factors are intimately connected, and an alteration in one factor can induce substantial adaptive changes in the others.
Sorafenib in combination with transarterial chemoembolization for the treatment of hepatocellular carcinoma.

Dr Geschwind has received grant support from Philips Healthcare, BTG, Guerbet, Boston Scientific, Threshold, and the National Institutes of Health. He has been a consultant to Philips Healthcare, BTG, Terumo, Guerbet, Bayer HealthCare, and Boston Scientific. Dr Chapiro has received grant support from the German-Israeli Foundation for Scientific Research and Development, the Rolf W. Gunther Foundation for Radiological Sciences, Philips Healthcare, and Berlin Institute of Health.
3D simulation and visualization of carbonate platform stratal geometries

Three-dimensional simulation of carbonate platform stratal geometries requires a robust mathematical formulation for the growth carbonate facies, a good understanding of the spatial distribution of various facies types, and a spatial grid that will accommodate rapid lateral changes in stratal geometries and depositionalfacies. The simplest spatial grid is a rectangular (equal spacing in x and y | dx(dy) grid and in this paper, the application of simple rectangular gridding is investigated for validity. A synthetic case is constructed and several model grids are built to investigate the impact of grid-spacing. The results of the different simulations are compared using 3D visualization. 3D visualization of 3D model results is as crucial as the mathematical formulation of the model and can be done in various ways, including contour maps, and full 3D rendering of model output. The transfer of the spatial grid into a full 3D model and the advantages of utilizing 3D visualization are discussed.
Treatment of Adolescent PTSD: The Impact of Prolonged Exposure Versus Client-Centered Therapy on Co-Occurring Emotional and Behavioral Problems

The present study evaluated secondary emotional and behavioral outcomes among adolescents who received prolonged exposure (PE-A) or client-centered therapy (CCT) for posttraumatic stress disorder (PTSD) in a randomized controlled trial. Participants were 61 adolescent girls (age: M = 15.33, SD = 1.50 years) with sexual abuse related PTSD seeking treatment at a community mental health clinic. Multilevel modeling was employed to evaluate group differences on the Youth Self-Report (YSR) over acute treatment and 12-month follow-up. Both treatment groups showed significant improvements on all YSR scales from baseline to 12-month follow-up. Adolescents who received PE-A showed significantly greater reductions than those receiving CCT on the Externalizing subscale (d = 0.70), rule-breaking behavior (d = 0.63), aggressive behavior (d = 0.62), and conduct problems (d = 0.78). No treatment differences were found on the Internalizing subscale or among other YSR problem areas. Both PE-A and CCT effectively reduced many co-occurring problems among adolescents with PTSD. Although PE-A focuses on PTSD and not on disruptive behaviors, PE-A was associated with greater sustained changes in externalizing symptoms, supporting broad effects of trauma-focused treatment on associated problem areas.
Predicting student success by modeling student interaction in asynchronous online courses

Early-warning intervention for students at risk of failing their online courses is increasingly important for higher education institutions. Students who show high levels of engagement appear less ...
Sensitivity of different vascular beds in the eye to neovascularization and blood-retinal barrier breakdown in VEGF transgenic mice.

Neovascularization (NV) causes visual deficits in ocular disorders such as diabetic retinopathy, age-related macular degeneration, and retinopathy of prematurity. An understanding of the angiogenic factors promoting this abnormal vascular growth is necessary to devise a therapeutic approach to inhibit NV. One factor known to promote NV is vascular endothelial growth factor (VEGF), which can also induce a breakdown of the blood-retinal barrier (BRB) leading to macular edema, another major cause of visual loss in a variety of ocular disorders. To investigate the role of VEGF on ocular NV, transgenic mice have been produced that overexpress VEGF in the photoreceptors under control of the rhodopsin promoter. Eyes from these mice and from littermates not expressing the transgene were examined using immunohistochemistry, griffonia simplicifolia isolectin-B4 (GSA) staining to clearly visualize vessels, and electron microscopy. Levels of transgene expression were determined by the polymerase chain reaction. In normal mice, retinal vessels are organized into a superficial and a deep capillary bed with some vessels forming a shunt between both beds. In a transgenic line of mice that overexpresses VEGF (V-6), NV originates from the deep capillary bed at about postnatal day 10 (P10) and extends through the photoreceptor layer to form vascular complexes in the subretinal space with BRB breakdown occurring only in the area of NV. The superficial capillary bed and the choroidal vasculature are unaffected. In another line of transgenic mice with a higher expression rate of VEGF (V-24), photoreceptor degeneration begins at P7-8, soon after the onset of transgene expression, without widespread NV, as was observed in V-6 mice. In conclusion, overexpression of VEGF in transgenic mice is sufficient to cause retinal NV, but only the deep capillary bed is responsive. Increasing the expression of VEGF does not necessarily increase the amount of NV. A better understanding of the specific factors and conditions that result in a particular pattern of ocular NV may provide clues regarding the pathogenesis of ocular neovascular disease.
System integration of functionalized natural materials

The use of natural materials in paper and textiles, and in support of tunable and mechanically robust systems for sensing toxic gases, removing pollutants from water, and constructing functional biodegradable scaffolds, is a topic of great scientific and practical importance. The social, environmental, and economic impact of using natural materials to functionalize integrated systems for new designs is imperative, as the need to reuse and recycle natural resources has increased in current manufacturing. The inclusion of sustainability in the design of new materials and processes is almost a common practice; concurrently, the usage of “being more sustainable” is becoming a more conjointly used term in urban conversations. That said, systems integration and natural materials are intrinsically related to produce novel materials that can function as sensors, switches, platforms, and building blocks in a sustainable fashion. The contributions in this issue of MRS Bulletin highlight the importance and benefits to society that systems integration of functional materials can provide.
Optimized Risk Scores

Risk scores are simple classification models that let users quickly assess risk by adding, subtracting, and multiplying a few small numbers. Such models are widely used in healthcare and criminal justice, but are often built ad hoc. In this paper, we present a principled approach to learn risk scores that are fully optimized for feature selection, integer coefficients, and operational constraints. We formulate the risk score problem as a mixed integer nonlinear program, and present a new cutting plane algorithm to efficiently recover its optimal solution. Our approach can fit optimized risk scores in a way that scales linearly with the sample size of a dataset, provides a proof of optimality, and obeys complex constraints without parameter tuning. We illustrate these benefits through an extensive set of numerical experiments, and an application where we build a customized risk score for ICU seizure prediction.
FEASIBILITY OF TRANSCAVAL ACCESS FOR THE DELIVERY OF MECHANICAL CIRCULATORY SUPPORT IN CARDIOGENIC SHOCK

Vascular access for the delivery of mechanical circulatory support (MCS) in patients who present with cardiogenic shock (CS) is often challenging due to peripheral arterial disease and systemic vasoconstriction. Transcaval access for the delivery of MCS may serve as an alternative access in such
Hydrodynamic Impact-Induced Vibration Characteristics of a Uniform Euler-Bernoulli Beam

A hydroelastic analysis of slam-induced beam vibration is presented. The objective of the paper is to provide response spectra for transient water-structure dynamics subject to typical impact loads and time scales. Assuming small deflections of the Euler-Bernoulli beam, normal mode summation is used to calculate the dynamic deflections in space and time. The modal governing differential equation is non-dimensionalized in space and time, and the dynamic load factor (DLF) of the loading are numerically evaluated. The modal participation spectra relative to the dominant fundamental mode for various impact speeds is used to establish modal truncation guidelines. The effect of the fluid inertia on the DLF is examined in the two limits of dry vibrations and completely wet vibrations.
Potential Theory in the Plane

In this chapter we will continue the study of the Dirichlet problem. The emphasis here will be on finding the limits of the results and employing measure theory to do so.
Tactile-like structures in neurofibromas. An ultrastructural study.

The light- and electron-microscopic features of four neurofibromas are described. In each case, whorled structures resembling tactile corpuscles were observed. Ultrastructurally, these lamellated formations were composed predominantly of perineurial cells, although many had a “central core” containing either a myelinated or unmyelinated axon, or several Schwann cells unassociated with axons. Our findings provide further evidence for the participation of perineurial cells as well as Schwann cells in the histogenesis of neurofibromas.
CHAPTER 21 – Nutritional Mechanisms of Age-Related Bone Loss

This chapter focuses on environmental(or nutritional) contributions to age-related bone loss and the maintenance of bone tissue by the elderly, with emphasis on the micronutrients that are needed to maintain bone mineral content (BMC) and bone mineral density (BMD) late in life. A balanced selection of foods is recommended for each day, but a large percentage of the elderly population fail to achieve this balance, especially in the consumption of bone-related nutrients from plant sources such as cereals, vegetables, fruits, as well as from dairy products. This failure is an age-old problem, but the solution for it is not simply the recommendation of taking a multinutrient supplement. Excessive reliance on supplements does not typically provide the non-nutrient phytochemical molecules that are rich in plant sources. Many other plant molecules may also have health-promoting effects on human skeletal tissue, but prospective studies of elderly human subjects are currently in progress. A balance of nutrient intake also implies getting the appropriate proportions of calcium and phosphate, and of sodium and potassium, so that imbalances do not contribute to calcium and bone losses. Other nutrients in excess, notably the acid-forming proteins from animal foods, may also contribute to losses of calcium and bone mineral. Typically, the nutrients consumed in excess, phosphate, sodium, and even animal protein, exert their adverse effects on calcium and bone metabolism through elevations in parathyroid hormone (PTH).
Maternal Supplementation of Low Dose Fluoride Alleviates Adverse Perinatal Outcomes Following Exposure to Intrauterine Inflammation

Maternal periodontal disease has been linked to adverse pregnancy sequelae, including preterm birth (PTB); yet, root planing and scaling in pregnancy has not been associated with improved perinatal outcomes. Fluoride, a cariostatic agent, has been added to drinking water and dental products to prevent caries and improve dental health. The objective of this study was to explore the effects of fluoride supplementation using a mouse model of preterm birth and perinatal sequalae. Pregnant mice were fed low dose fluoride (LF−) or high dose fluoride (HF−) and given intrauterine injections of lipopolysaccharide (LPS) or phosphate-buffered saline (PBS). We found that LPS + LF− significantly increased livebirths, pup survival, and litter size compared to LPS alone. Moreover, offspring from the LPS + LF− group exhibited significantly improved neuromotor performance and more neurons compared to those from the LPS group. Additionally, LF− treatment on human umbilical vein endothelial cells (HUVECs) increased cell viability and decreased oxidative stress after treatment with LPS. Collectively, our data demonstrates that maternal LF− supplementation during pregnancy postpones the onset of PTB, acts to increase the liveborn rate and survival time of newborns, and reduces perinatal brain injury in cases of intrauterine inflammation.
Practicing metacognition through the use of repeated posttest predictions.

Abstract Background Development of metacognitive skills is one method to increase self-awareness of pharmacy students. This study sought to assess students' posttest prediction (postdiction) of performance on a series of multiple-choice examinations to determine if feedback regarding predicted and actual performance could improve personal predictive abilities over time. Impact While there was a statistically significant change in the students' predictive abilities from examination one to examination three, lower scores in examination two disrupted the trend we had hoped to see. When broken down by overall course score, the highest performing students rarely overestimated their score (5–21% of the time, depending on examination), while the lowest performing students were more varied (22–56% over prediction, depending on examination). Recommendations This study used a novel assessment method of postdictions without additional data points such as predictions or grade point average (GPA), which could have helped confirm the value of the method. Additionally, we realized assessing the impact of the qualitative feedback students received could elucidate why and recommend this for future studies. Discussion While students were generally poor predictors of their performance, repeated use of this skill helped them to reduce the number of over predictions made by the end of the course. This change was greatest for the lowest performing students indicating that they may receive more benefit from this exercise than higher performing students. This method of using postdictions adds to the collection of tools that can be used to measure student metacognitive skills.
Efficacy of Epicutaneous Immunotherapy in Children With Milk-Induced Eosinophilic Esophagitis

Background & Aims Eosinophilic esophagitis (EoE) is caused by an immune response to specific food allergens. There are no approved therapies beyond avoidance of the allergen(s) or treatment of inflammation. Epicutaneous immunotherapy (EPIT) reduces features of eosinophilic gastrointestinal disease in mice and pigs. We performed randomized, placebo-controlled study to determine the safety and efficacy of EPIT with Viaskin milk in children with milk-induced EoE. Methods In a double-blind study, 20 children (4–17 years old) with milk-induced EoE were randomly assigned to groups given EPIT with Viaskin milk (n = 15) or placebo (n = 5) for 9 months during a milk-free period, followed by milk-containing diet for 2 months with EPIT. Then, subjects underwent upper endoscopy analysis, biopsies were collected, and maximum esophageal eosinophil counts were determined and was the primary endpoint. After upper endoscopy, patients were given open-label EPIT for 11 months (open-label phase). The subjects were allowed to consume milk if they had maximum values of fewer than 10 eosinophils/high-power field (eos/hpf); otherwise, they remained on a milk-free diet until the last 2 months of the open-label phase. Results In the intent to treat population, there was no significant difference between the Viaskin milk group in mean eos/hpf (50.1 ± 43.97 eos/hpf) vs the placebo group (48.20 ± 56.98 eos/hpf). However, in the per-protocol population (7 patients given Viaskin milk and 2 patients given placebo), patients given Viaskin milk patients had a significantly lower mean eos/hpf count (25.57 ± 31.19) than patients given placebo (95.00 ± 63.64) (p = .038). At the end of the open-label phase, 9 of 19 evaluable subjects had mean values of fewer than 15 eos/hpf (47% response). The number of adverse events did not differ significantly between the Viaskin milk and placebo groups; there was 1 serious adverse event in the placebo group. Conclusions In a pilot study of pediatric patients with EoE given EPIT with Viaskin milk or placebo for 11 months, we found no significant difference between groups for the maximum eosinophil count at the end of the study. However, findings from a per-protocol analysis indicate that Viaskin milk can reduce eos/hpf. At study completion, 47% of patients who continued open-label Viaskin milk for an additional 11 months had mean values of fewer than 15 eos/hpf. ClinicalTrials.gov no: NCT02579876
If You Tweet It, They Will Come

Twitter has emerged as a widely used social media platform for medical professionals. While the character limitations of Twitter can make it challenging to discuss complicated medical conditions, the ability to include links, retweet content, comment on posts, and link tweets together makes this a very effective way to disseminate information. Medical professionals can use Twitter in various ways, not only for communicating with patients and the public but for professional networking as well. This chapter will focus on tips and practical steps to help increase one’s profile on Twitter and grow an audience.
Amnesia, Adverse Effects, and the Angel of History

In this issue, Leslie and colleagues compiled a disturbing tale of historical amnesia in which the neglect of 19th- and 20th-century information led to preventable adverse events in 21st-century pa...
The serious business of instructional humor outside the classroom: a study of elite gymnastic coaches’ uses of humor during training

ABSTRACTThis study documents the use of humor in an instructional setting outside traditional classrooms. Specifically, it studied the use of instructional humor in training elite and aspiring gymn...
Pain centrality mediates pain self-efficacy and symptom severity among individuals reporting chronic pain.

Chronic pain is consistently associated with the presence of mental health disorders. Although previous research has shown relations between low levels of self-efficacy with chronic pain severity as well as comorbid mental health symptoms, the link between self-efficacy and mental health symptoms in chronic pain is not well understood. This study examined whether pain centrality, the extent to which pain is viewed as central to self-identity, may underlie these associations. Individuals with a diagnosis of chronic pain (N = 89) recruited through MTurkcompleted self-report measures including demographics, self-efficacy, pain centrality, pain severity, depression, and anxiety. Pain severity was associated with higher levels of pain centrality, depression, anxiety, and lower levels of self-efficacy. Path analysis demonstrated pain centrality significantly mediated the relationship between self-efficacy and pain severity, depression, and anxiety. Future studies would benefit from testing whether modifying pain centrality beliefs shift perceptions of control as well as pain and psychological outcomes.
Medicinal Information Available in the Palm Leaf Manuscripts of the Eastern Sri Lanka – A Study

The Palm leaf manuscripts are seen as documents that preserve the cultural heritage of the people. In that respect, palm leaf manuscripts have been maintained by the Eastern Tamil people for a long time. These palm leaf manuscripts can be classified into three types; literature, medicine and astrology. Literary palm leaf manuscripts include Ammanai, Drama etc. Palm leaf manuscripts related to astrology contain information such as Similarly, medical palm leaf manuscripts contain much medical information. It is noted that a medical palm leaf manuscript was discovered for in the East recently. This study is intended to introduce the structure, medical information and herbs of this palm leaf manuscript. This palm leaf manuscript has solutions for many ailments such as headaches, asthma, cough peenisam, pittam and rheumatism. There is also information on the preparation of sanjeevi legiyam. Neem, Milk, Honey Basil, etc. have been identified as having high Medicinal properties.
Chondral Damage After Arthroscopic Repair Techniques for Acute Bony Bankart Lesions: A Biomechanical Study.

Background:Bony Bankart lesions can be encountered during treatment of shoulder instability. Current arthroscopic bony Bankart repair techniques involve intra-articular suture placement, but the ef...
Interpretable Trade-offs Between Robot Task Accuracy and Compute Efficiency.

A robot can invoke heterogeneous computation resources such as CPUs, cloud GPU servers, or even human computation for achieving a high-level goal. The problem of invoking an appropriate computation model so that it will successfully complete a task while keeping its compute and energy costs within a budget is called a model selection problem. In this paper, we present an optimal solution to the model selection problem with two compute models, the first being fast but less accurate, and the second being slow but more accurate. The main insight behind our solution is that a robot should invoke the slower compute model only when the benefits from the gain in accuracy outweigh the computational costs. We show that such cost-benefit analysis can be performed by leveraging the statistical correlation between the accuracy of fast and slow compute models. We demonstrate the broad applicability of our approach to diverse problems such as perception using neural networks and safe navigation of a simulated Mars rover.
Convergence rate of a rectangular subdivision-based optimization algorithm for smooth multivariate functions

In Zheng (J. Glob. Opt. 79:431-445;2021) the authors described a global optimization algorithm for multivariate continuous functions and applied it to an image processing problem. While the algorithm was shown to converge for all continuous functions, the convergence rate was not established. In this paper we assume that the objective function is smooth, and establish the asymptotic convergence rate when the algorithm is applied to such a function.
Cancer. New link in a web of human genes.

ATM and NBS1 are genes that are mutated in two different human diseases. Cells from patients with these diseases show similarities, including increased chromosome breakage, so ATM and NBS1 might work together in DNA repair. Indeed, ATM phosphorylates NBS1 in several places — events needed for the cellular response to DNA breaks.
Preliminary findings: Contingency management targeting psycho‐stimulant use results in secondary decreases in smoking for severely mentally ill adults

Background Treatments for drug addiction and smoking in severely mentally ill (SMI) adults are needed. Objectives To investigate the effect of a contingency management (CM) intervention targeting psycho-stimulant on cigarette smoking. Methods 126 stimulant dependent SMI smokers were assigned to CM or a non-contingent control condition. Rates of smoking-negative (<3 ppm) carbon monoxide breath-samples were compared. Results Individuals who received CM targeting psycho-stimulants were 79% more likely to submit a smoking-negative breath-sample relative to controls. Conclusions and Scientific Significance This study provides initial evidence that a behavioral treatment for drug use results in reductions in cigarette smoking in SMI adults. (Am J Addict 2014;23:407–410)
Isolated Membranes and Organelles from Vascular Smooth Muscle

The sections in this article are: 1 Isolation Techniques 1.1 Homogenization 1.2 Fractionation 2 Identification of Isolated Fractions of Vascular Smooth Muscle 2.1 Mitochondria 2.2 Microsomal and Plasma Membrane Fractions 3 Functional Studies of Isolated Fractions of Vascular Smooth Muscle 3.1 Mitochondria 3.2 Microsomal and Plasma Membrane Fractions 4 Summary
Propagation of activity-dependent synaptic depression in simple neural networks

Triple whole-cell recordings from simple networks of cultured hippocampal neurons show that induction of long-term depression at glutamatergic synapses is accompanied by a back propagation of depression to input synapses on the dendrite of the presynaptic neuron. The depression also propagates laterally to divergent outputs of the presynaptic neuron and to convergent inputs on the postsynaptic neuron. There is no forward propagation of depression to the output of the postsynaptic neuron and no presynaptic propagation accompanying long-term depression at GABAergic synapses. Activity-induced synaptic modification is therefore not restricted to the activated synapse, but selectively propagates throughout the neural network.
Generalized Fuzzy and Matrix Associative Holographic Memories

We discuss matrix associative memories. We also introduce holographic matrix associative memories. We show how the first class allows for interpolation while the holographic kind does not. We provide a general class of matrix associative memories that allows us to move between these two extremes. We next look at fuzzy associative memories and introduce a general fuzzy holographic memory. Finally, we describe a number of methods for measuring the degree of association between an input and a primary memory stimulus.
The Penaeid Shrimp Viruses TSV, IHHNV, WSSV, and YHV: Current Status in the Americas, Available Diagnostic Methods, and Management Strategies

ABSTRACT Viral diseases have emerged during this decade as serious economic impediments to successful shrimp farming. While nearly 20 distinct viruses or groups of viruses are known to infect penaeid shrimp, only four, WSSV, YHV, IHHNV, and TSV, pose a threat to the future of penaeid shrimp culture in the Western Hemisphere. TSV and IHHNV have caused serious disease epizootics throughout the Americas and Hawaii. IHHNV was described nearly 20 years ago when it was found to be responsible for cumulative losses of cultured Penaeus stylirostris that often exceed 90%. The threat of high mortalities posed by IHHNV has historically curtailed interest in the culture of this species in favor of the more IHHNV-resistant P. vannamei. While relatively resistant, IHHNV nonetheless infects P. vannamei and causes runt deformity syndrome (RDS) in which affected shrimp display reduced growth, highly variable sizes, lower production, and sometimes reduced survival. Taura Syndrome in P. vannamei is the virtual “mirror image...
Mammary pathology of the genetically engineered mouse

Human breast cancer has been modeled in well over 100 types of genetically engineered mice (GEM). Many of the mutated or overexpressed genes found in human breast cancer also initiate mammary cancer in GEM. The histopathology of GEM models of breast cancer have proved to be unique. Most GEM tumors do not resemble the spontaneous tumors induced by the mouse mammary tumor virus (MMTV) or by carcinogenic agents. The pattern of some GEM tumors closely resembles that seen in some human breast cancers. The most provocative and most thoroughly studied GEM group belongs to the ERBB2 (HER2) signal transduction pathway. GEM bearing ERBB2, various forms of mutated ERBB2 and ERBB2-related genes produce tumors via similar molecular mechanisms, and also have a remarkable morphological resemblance to some forms of human breast cancer. Tumors associated with tumor suppressor genes, such as Brca1 and SV40 Tag (that suppresses expression of Rb and p53) tend to resemble poorly differentiated tumors and, in some cases, medullary carcinoma of the human breast. Many of the GEM develop mammary tumors with characteristic or unique gene-specific 'signature' phenotypes that readily can be identified microscopically. The principle that genotype predicts phenotype can be applied to other GEM and extended to include entire molecular pathways. Studies of tumor kinetics in bi-transgenic mice suggest that some combinations of genes are synergistic while others are inhibitory. Although the majority of breast cancer models have been induced using the MMTV-LTR as a promoter, C3(1), WAP, and BLG promoters frequently have been used. Tumors retain the phenotype characteristic of the oncogene, for the most part, regardless of promoter. In some cases, inserting the transgene behind the native promoter or 'knocking-in' an oncogenic variant at the normal gene locus has also resulted in tumors characteristic of the oncogene. GEM with inactivation of tumor suppressor genes generally die with tumors other than mammary tumors. The mammary tumors that do develop tend to be more poorly differentiated, aneuploid tumors with a wider range of phenotypes. However, when crossed with GEM bearing activated transgenes, the tumors are most likely to resemble the phenotype of the transgene. The tumors in bigenic mice do, however, have more pleomorphic and aneuploid cells. The great majority of mouse mammary tumors are hormone independent. This is in contrast to human breast carcinomas, 50% of which express the receptors for estrogen and progesterone, and are dependent (at least partially) on these hormones for growth. The biology of metastasis is also quite different with mouse carcinomas displaying a hematogeneous spread almost exclusively to the lung and with human carcinomas displaying regional lymph node involvement with preferential systemic spread to the bone, brain and liver.
Abstract 4837: Tumor microenvironment contributes to RAF-inhibitor resistance through HGF secretion

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Drug resistance remains a vexing problem in the treatment of cancer patients. While many studies have focused on cell autonomous mechanisms of drug resistance, we hypothesized that the tumor microenvironment may confer innate resistance to therapy. We employed a novel co-culture assay to systematically assay the ability of 23 stromal cell types to influence the sensitivity of 45 cancer cell lines to 35 anti-cancer drugs testing more than 15,000 cancer-stroma-drug combinations. We found that stroma-mediated resistance is surprisingly common - particularly to targeted chemotherapies. We decided to further characterize the stroma-mediated resistance of BRAF-mutant melanoma to RAF inhibition because most patients exhibit some degree of innate resistance. Proteomic analysis showed that stromal secretion of the growth factor hepatocyte growth factor (HGF) resulted in activation of the HGF receptor MET, reactivation of the MAPK and PI3K/AKT pathways, and immediate resistance to RAF inhibition. Immunohistochemistry confirmed tumor stromal HGF expression in 11 out of 15 patients with BRAF-mutant melanoma. Among these patients, only one experienced a complete response, and that patient was negative for stromal HGF, consistent with our prediction of HGF-mediated RAF-inhibitor resistance. In contrast, of 6 evaluable patients with stable disease 4 had particularly high levels of stromal HGF expression. Dual inhibition of RAF and MET in BRAF-mutant melanoma cell lines resulted in reversal of drug resistance, suggesting RAF/MET combination therapy as a potential therapeutic strategy for BRAF-mutant melanoma. A similar resistance mechanism was uncovered in a subset of BRAF-mutant colorectal and glioblastoma cell lines. Interestingly, the activation of MET in these cell lines was cell autonomous, caused, for example, by autocrine secretion of HGF and resulting in complete resistance to RAF inhibitors even in the absence of stromal cells. Treatment with a MET inhibitor re-sensitized these cell lines to RAF inhibitors suggesting the same RAF/MET combination therapy for non-melanoma BRAF mutant cancers as well. More generally, these studies indicate that the systematic dissection of tumor-microenvironment interactions may reveal important mechanisms underlying drug resistance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4837. doi:1538-7445.AM2012-4837
Emotional Storytelling in the Classroom: Individual versus Group Interaction between Children and Robots

Robot assistive technology is becoming increasingly prevalent. Despite the growing body of research in this area, the role of type of interaction (i.e., small groups versus individual interactions) on effectiveness of interventions is still unclear. In this paper, we explore a new direction for socially assistive robotics, where multiple robotic characters interact with children in an interactive storytelling scenario. We conducted a between-subjects repeated interaction study where a single child or a group of three children interacted with the robots in an interactive narrative scenario. Results show that although the individual condition increased participant’s story recall abilities compared to the group condition, the emotional interpretation of the story content seemed more dependent on the difficulty level rather than the study condition. Our findings suggest that, despite the type of interaction, interactive narratives with multiple robots are a promising approach to foster children’s development of social-related skills.
Photoreduction of tetrakis (1,10-phenanthroline)-μ-oxodiiron(III) complexes in aqueous and acetonitrile solution

Abstract Photochemical reduction of Fe 2 (phen) 4 OX 2 Y 2 ( X − or Y − = Cl − , Br − , NCS − , ClO 4 − ) in aqueous and acetonitrile media is reported. The products of the photochemical reaction are Fe(phen) 3 2+ and Fe 3+ . The results of quantum-yield measurements, chemical scavenging experiments and flash photolyses are reported. It is concluded that, preceding photolyses, the anions are rapidly displaced by H 2 O in aqueous solution; the primary photochemical process in aqueous solution is postulated to involve homolytic cleavage of an Fe(III)O “bridge” bond. Similar conclusions obtain in acetonitrile for all complexes except the thiocyanate; in acetonitrile, the NCS − ions remain coordinated to Fe(III), and the primary photochemical process involves homolytic scission of an Fe(III)—NCS − bond. The active excited stale in these complexes is concluded to be an intramolecular charge-transfer state. Because several types of intramolecular charge-transfer electronic excitation are possible in these complexes, the observed photodecomposition mode depends critically upon the identity of the spin-allowed charge-transfer excited state of lowest energy.
Optimized built-in self-test technique for CAEN-based nanofabric systems

We propose a built-in self-test (BIST) technique for testing and diagnosis of molecular electronic based nanofabrics. The nanofabric architectures are reconfigurable in nature thus making it possible to utilize general methods similar to those employed for testing of FPGAs. However, a high defect rate in nanofabrics renders the traditional techniques ill-suited. Moreover, the nanoblocks offer potential for using a partially damaged nanoblock due to inherent redundancy of the architecture. This paper presents the design and analysis of testing configurations and optimization scheme that minimizes testing time while improving the utilization of the nanofabric. The proposed procedure identifies the defective nanoblocks in a nanofabric and generates a defect map, which can be used during design to avoid defective components in a nanofabric to increase the yield. The proposed BIST technique results in a less number of test configurations compared to other proposed methods and a significant reduction in the test time. This technique is suitable for architectures with a defect rate as high as 10% since all the components are tested in parallel.
THE POLITICAL ECOLOGY OF GEOPIETY: NATURE CONSERVATION IN TIBETAN COMMUNITIES OF NORTHWEST YUNNAN

Abstract Diqing Tibetan Autonomous Prefecture (DTAP) marks the southeastern limit of the Tibetan culture region and the abode of Kawakarpo, a principal holy mountain in Tibetan Buddhism. This and other sacred landforms reinforce indigenous territorial identity but are increasingly circumscribed by state and global nature conservation schemes. Transnational NGOs attract global donors and tourists by heralding sacred geography as “stewardship of nature,” but is this representation commensurable with Tibetan geopiety? Village-based research reveals more complex traditions, as well as local re-interpretation (exegesis) of sacred landscapes that can potentially enhance community land tenure, maintain indigenous sacred space, and meet modern conservation goals.
A nitrocellulose-filter assay for the binary complex of 5-fluorodeoxyuridylate and Lactobacillus casei thymidylate synthetase

Abstract The interaction of 5-fluorodeoxyuridylate (FdUMP) with thymidylate synthetase to form a binary complex has been widely reported, yet previous attempts to detect this complex by nitrocellulose filtration have failed. In contrast, a nitrocellulose-filter-binding assay utilizing [6- 3 H]FdUMP which measures the interaction of the enzmme with the nucleotide is reported. Extensive washing of the nitrocellulose-filtered complex between FdUMP and the enzyme resulted in no loss of bound ligand. Following denaturation with trichloroacetic acid, intact complex was detected by nitrocellulose filtration. No binding was observed between 5-fluorodeoxyuridine and the enzyme or between FdUMP and the N -ethylmaleimide-modified enzyme. As measured by the nitrocellulose filtration method, at least a 600-fold excess of FdUMP to enzyme was required to achieve saturation. The stoichiometry of FdUMP bound to the enzyme detected at saturation was 0.5–0.6 for native samples. When identical samples were subjected to denaturation prior to filtration, the stoichiometry of nucleotide binding was 0.3–0.4.
Evaluation of antimicrobial peptides as novel bactericidal agents for room temperature–stored platelets

BACKGROUND: A single cost-effective pathogen inactivation approach would help to improve the safety of our nation's blood supply. Several methods and technologies are currently being studied to help reduce bacterial contamination of blood components. There is clearly need for simple and easy-to-use pathogen inactivation techniques specific to plasma, platelets (PLTs), and red blood cells. STUDY DESIGN AND METHODS: In this report, we introduce a novel proof of concept: using known therapeutic antimicrobial peptides (AMPs) as bactericidal agents for room temperature–stored PLT concentrates (PCs). Nine synthetic AMPs, four from PLT microbicidal protein-derived peptides (PD1-4) and five Arg-Trp (RW) repeat peptides containing one to five repeats, were tested for bactericidal activity in plasma and PC samples spiked with Staphylococcus aureus, S. epidermidis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Bacillus cereus. A 3-log reduction of viable bacteria was considered as the bactericidal activity of a given peptide. RESULTS: In both plasma alone and PCs, RW3 peptide demonstrated bactericidal activity against S. aureus, S. epidermidis, E. coli, P. aeruginosa, and K. pneumoniae; PD4 and RW2 against P. aeruginosa; and RW4 against K. pneumoniae. The activity of each of these four peptides against the remaining bacterial species in the test panel resulted in less than a 3-log reduction in the number of viable bacteria and hence considered ineffective. CONCLUSIONS: These findings suggest a new approach to improving the safety of blood components, demonstrating the potential usefulness of screening therapeutic AMPs against selected bacteria to identify suitable bactericidal agents for stored plasma, PCs, and other blood products.
A Czech Researcher and Pneumocystis

In 1909, two years after the birth of Otto Jirovec (figure 1) in Bohemia, Carlos Chagas described an organism in the lungs of infected guinea pigs that he named Schizotrypanum cruzi [1, 2]. In 1912, Antonio Carini noted these same organisms in the lungs of rats. Both researchers were convinced that what they had observed was a type of trypanosome. However, later that year, at the Pasteur Institute, the husband-and-wife team of Delanoe and Delanoe [3] demonstrated that the cysts observed in the lungs of Carini's rats were unrelated to trypanosomes and named the organism Pneumocystis carinii. In the 1930s and 1940s, an epidemic form of pneumonia was recognized in European infants who were born prematurely [1]. This pneumonia, called "interstitial plasma cell pneumonia," was associated with death by the age of 6 months [4]. It was not until 1951 that Otto Jirovec, along with Joseph Vanek, demonstrated that the etiologic agent of interstitial plasma cell pneumonia was Pneumocystis. Otto Jirovec started out as a zoologist studying microsporidia and later contributed to the understanding of Trichomonas vaginalis, Toxoplasma, and Leptospira [5]. However, he is most famous for his work on Pneumocystis, both for his initial description of the species that infects humans and later for his studies of its development and epidemiology. In 1976, four years after Otto Jirovec's death, Jacob Frenkel proposed to use the name of Pneumocystis carinii for the species that infects rats and to use Pneumocystis jerovici for the species that infects humans, on the basis of the knowledge that interspecies infection was not experimentally possible [2]. In the late 1980s, RNA analysis demonstrated that Pneumocystis was a fungus, not a protozoa [6, 7]. Ironically, it was not until 1999, after this change in taxonomy, that the species of Pneumocystis that infects humans was renamed Pneumocystis jiroveci after the great Czech parasitologist [2].
Apparent movement in tridimensional space

The space-time relationships satisfying Korte’s third law of apparent movement were studied in three experiments. The results generally confirm and extend Corbin’s conclusion that apparent movement is not a projection-level phenomenon, but one involving spatial constancy, i.e., some representation of tridimensional space. Between situations in which the stimuli were retinally matched, the time interval necessary, for apparent movement varied w~th their phenomenal separation, whether the latter was determined by the distance of stimuli from the O, deviation of sttmuli from the frontal plane, or illusory slant of the stimulus plane produced by a perspective gradient.
Controversies in the Assessment of Minimal Residual Disease in Multiple Myeloma: Clinical Significance of Minimal Residual Disease Negativity Using Highly Sensitive Techniques

Minimal residual disease (MRD) assessment has gained importance in the response evaluation of multiple myeloma. As discussed in part 1 of this two-part series, techniques such as multiparameter flow cytometry, polymerase chain reaction, and next-generation sequencing, of both bone marrow and peripheral blood, have the potential to achieve a high level of sensitivity, up to 1 in 10(-6) cells, enabling analysis of genetically diverse subclones. Here, we review the clinical utility of MRD assessment using these techniques. Specifically, we review the association between MRD-negativity and progression-free or overall survival in various clinical settings (post-induction, post-auto or allo-stem cell transplant, transplant ineligible, maintenance, and relapsed/refractory). Currently, the goal of assessing MRD in multiple myeloma (MM) is to allow for a risk-stratified approach to therapy and for earlier identification of response to novel agents, particularly in the setting of clinical trials.
Sustained Dialogue in Managing Intractable Conflict

In the warn-torn new nation of Tajikistan, the author has been part of a five-stage “dialogue” for peace since 1993. The focus of the dialogue has been on transforming relationships and changing relationship dynamics so that this “intractable” conflict can be addressed positively. The author briefly describes this multilevel peace process both historically and substantively. He also discusses the continual process of evaluation of the Inter-Tajik dialogue effort as well as focuses on a series of questions that apply to intractable conflicts in general.
Hp Ge: Purification, Crystal Growth, and Annealing Properties

The prospects for growing HP Ge crystals of increased size and purity are examined. One interesting approach is to grow dislocation-free crystals, which must then be annealed to reduce the concentration of V2H traps. The phenomena which occur during annealing are discussed and compared with experiment. Hydrogen, present in atomic form at the growth temperature, forms H2 molecules during cooling, causing the effective diffusion coefficient to decrease rapidly. Models representing the reactions between H and the V2H, A(H, Si), and D(H, O) complexes are presented and analyzed.