cssi/SciSciGPT-SciSciNet huggingface dataset:
A Zebrafish Model Of PMM2-CDG Reveals Altered Neurogenesis And A Substrate-Accumulation Mechanism For N-Linked Glycosylation Deficiency

Congenital disorder of glycosylation (PMM2-CDG) results from mutations in pmm2, which encodes the phosphomannomutase (Pmm) that converts mannose-6-phosphate (M6P) to mannose-1-phosphate (M1P). Patients have wide-spectrum clinical abnormalities associated with impaired protein N-glycosylation. Although it has been widely proposed that Pmm2 deficiency depletes M1P, a precursor of GDP-mannose, and consequently suppresses lipid-linked oligosaccharide (LLO) levels needed for N-glycosylation, these deficiencies have not been demonstrated in patients or any animal model. Here we report a morpholino-based PMM2-CDG model in zebrafish. Morphant embryos had developmental abnormalities consistent with PMM2-CDG patients, including craniofacial defects and impaired motility associated with altered motor neurogenesis within the spinal cord. Significantly, global N-linked glycosylation and LLO levels were reduced in pmm2 morphants. Although M1P and GDP-mannose were below reliable detection/quantification limits, Pmm2 depletion unexpectedly caused accumulation of M6P, shown earlier to promote LLO cleavage in vitro. In pmm2 morphants, the free glycan by-products of LLO cleavage increased nearly twofold. Suppression of the M6P-synthesizing enzyme mannose phosphate isomerase within the pmm2 background normalized M6P levels and certain aspects of the craniofacial phenotype and abrogated pmm2-dependent LLO cleavage. In summary, we report the first zebrafish model of PMM2-CDG and uncover novel cellular insights not possible with other systems, including an M6P accumulation mechanism for underglycosylation.
Use of the Tower of London - Drexel University, Second Edition (TOLDX) in adults with traumatic brain injury.

The Tower of London – Drexel University, Second Edition (TOLDX) was investigated in order to determine the efficacy of using this instrument in evaluating the impact of traumatic brain injury on cognitive functioning in adults. Performance on the TOLDX was compared among 56 individuals with complicated mild to severe traumatic brain injury (“sTBI”), 68 individuals with uncomplicated, mild traumatic brain injury (“mTBI”), and 124 demographically matched, healthy controls. Both TBI groups performed worse than controls on TOLDX measures of executive time (ET) and number of moves used (TMS), but only patients with sTBI were more likely to be impaired on TMS (i.e., performing at least 1.5 SD below the mean). Poorer performance on TMS was associated with increasing length of coma. Although poor sensitivity of this measure limits its use in isolation, the TOLDX may provide a complementary measurement of aspects of problem-solving deficit in TBI that may not be captured by other tests.
Shared and unshared barriers to cancer symptom management among urban and rural American Indians.

Purpose Before the end of the 20th century, American Indians (AIs) primarily resided in non-metropolitan areas. Shifting demographic trends have led to a majority of AIs now living in urban areas, leading to new health care barriers for AIs. AIs experience the poorest survival from all cancers combined compared to all other racial groups. Identifying and classifying barriers to cancer care may facilitate supportive interventions and programs to improve access and treatment.
Mori Dream Spaces

We explore the circle of ideas connecting finite generation of the Cox ring, Mori dream spaces and invariant theory.
Evaluation of Futurebus+ for a GMMP multiprocessor

One of the most popular approaches for increasing computer performance is parallel computations using specialized hardware. Clearly, the authors would like to use standardized technology wherever possible in such multiprocessors, in order to minimize the number of unique components that must be (re)designed for each generation of the machine. This paper presents the result of a modelling study that was undertaken to estimate the performance achievable by an implementation of the virtual port memory multiprocessor architecture using the Futurebus+ backplane bus structure. Discrete event simulation and analytical queueing network models concur that peak performance occurs, for typical workloads, at approximately 30 processors on the bus. >
Physics-based animation of a trotting horse in a virtual environment

In this paper we describe the implementation of a physics-based animation of a trotting horse in real-time. The horse is modelled as a collection of connected bodies using the open dynamics engine library to simulate gravity. The animation is created by comparing the current state of the horse with a desired state and applying torques proportionally to the errors present between the two. The desired state is obtained from frames of video footage of a trotting horse. P-controllers are used to minimise the error between current and desired angle positions as well as global positioning and orientation of the horse's trajectory. Results show realistic movement patterns as compared to the video footage and realistic ground reaction force patterns of each individual leg.
Feedback control of the nuclear magnetization state: experimental results

In a previous paper (Proc. Soc. Magn. Reson. Med., San Francisco, CA, USA, 1991), the authors investigated feedback control of the nuclear magnetization state. This strategy facilitates the optimization of the pulse parameters during the imaging sequence. In this work, results from a series of experiments used to test the theoretical predictions are presented. Two groups of experiments were performed using a commercial imager and a small sample of distilled water. In the first group of experiments the control objective is to regulate the magnetization orientation to a constant reference angle. The results show that a closed-loop system produces the desired orientation. In contrast, an open-loop input results in an appreciable error between desired and measured orientation. A second group of experiments shows that a closed-loop system can force the magnetization orientation to track a desired trajectory. In both groups, the closed-loop experimental and simulation results are in excellent agreement. The application of feedback control to MRI and spectroscopy is discussed. >
The thermodynamics of protein interactions with essential first row transition metals.

Abstract Background The binding of metal ions to proteins is a crucial process required for their catalytic activity, structural stability and/or functional regulation. Isothermal titration calorimetry provides a wealth of fundamental information which when combined with structural data allow for a much deeper understanding of the underlying molecular mechanism. Scope of review A rigorous understanding of any molecular interaction requires in part an in-depth quantification of its thermodynamic properties. Here, we provide an overview of recent studies that have used ITC to quantify the interaction of essential first row transition metals with relevant proteins and highlight major findings from these thermodynamic studies. General significance The thermodynamic characterization of metal ion–protein interactions is one important step to understanding the role that metal ions play in living systems. Such characterization has important implications not only to elucidating proteins' structure-function relationships and biological properties but also in the biotechnology sector, medicine and drug design particularly since a number of metal ions are involved in several neurodegenerative diseases. Major conclusions Isothermal titration calorimetry measurements can provide complete thermodynamic profiles of any molecular interaction through the simultaneous determination of the reaction binding stoichiometry, binding affinity as well as the enthalpic and entropic contributions to the free energy change thus enabling a more in-depth understanding of the nature of these interactions. This article is part of a Special Issue entitled Microcalorimetry in the BioSciences — Principles and Applications, edited by Fadi Bou-Abdallah.
A Possible Role of Copper in the Regulation of Heme Biosynthesis Through Ferrochelatase

Drugs and heavy metals may alter the synthesis of hemo-proteins by either inducing or inhibiting various enzymes in the heme biosynthetic pathway (Fig. 1) (Tephly et al., 1971; Tephly et al., 1973). Porphyrogenic drugs and inducers of the hepatic hemo-protein, cytochrome P-450, such as phenobarbital, induce hepatic δ-aminolevulinic acid synthetase (ALAS), the initial and proposed rate-limiting enzyme of this pathway (Granick and Urata, 1963; Baron and Tephly, 1969; Tephly et al., 1973). Ferrochelatase (heme synthetase, protoheme ferro-lyase, EC 4.99.1.1), the terminal enzyme in the heme pathway, is located on the inner mitochondrial membrane (Jones and Jones, 1968; McKay et al., 1969) and catalyzes the formation of heme from protoporphyrin IX and ferrous iron (Labbe and Hubbard, 1960). This enzyme, like ALAS, is inducible (Hasegawa et al., 1970; Tephly et al., 1971), and may be subject to product inhibition by heme (Jones and Jones, 1970). Heme which is formed through ferrochelatase is then available for synthesis of cytochrome P-450 and other hemoproteins. Tephly and co-workers (Tephly and Hibbeln, 1971; Tephly et al., 1972) have reported that cobalt treatment produces a substantial decrease in the level of hepatic cytochrome P-450.
“As long as I See You on Facebook I Know You Are Safe”: Social Media Experiences as Humanizing Pedagogy

Understanding different peoples and cultures is a central aim of education for global citizenship. Unfortunately, many social studies courses emphasize the academic acquisition of content knowledge, but fail to offer opportunities for students to develop personal, humanizing connections with people of different cultures. Fortunately, the rise of social media like Facebook and Skype offer new possibilities for global connections. In this case study, the authors explore the interactions of 16 students enrolled in a middle/high school social studies pedagogy course and 16 counterparts in the Gaza Strip via Skype and Facebook. The authors interpreted these mediated experiences through the lens of Lan’s framework for democratic media literacy, including media literacy conceptions like transmedia judgment, mediated identity reflection, and social action with/through new media. The authors hope this chapter will offer social studies teacher educators’ insights for cultivating humanizing experiences appropriate to their contexts.
Azido, triazolyl, and alkynyl complexes of gold(I): syntheses, structures, and ligand effects.

Gold(I) triazolyl complexes are prepared in [3 + 2] cycloaddition reactions of (tertiary phosphine)gold(I) azides with terminal alkynes. Seven such triazolyl complexes, not previously prepared, are described. Reducible functional groups are accommodated. In addition, two new (N-heterocyclic carbene)gold(I) azides and two new gold(I) alkynyls are described. Eight complexes are crystallographically authenticated; aurophilic interactions appear in one structure only. The packing diagrams of gold(I) triazolyls all show intermolecular hydrogen bonding between N-1 of one molecule and N-3 of a neighbor. This hydrogen bonding permeates the crystal lattice. Density-functional theory calculations of (triphenylphosphine)gold(I) triazolyls and the corresponding alkynyls indicate that the triazolyl is a stronger trans-influencer than is the alkynyl, but the alkynyl is more electron-releasing. These results suggest that trans-influences in two-coordinate gold(I) complexes can be more than a simple matter of ligand doni...
Semisimple Artinian Rings of Quotients

It is easy to be too busy to pay attention to what anyone else is doing, but not good. All of us should know, and want to know, what has been discovered since our formal education ended, but new words, and relations between them, are growing too fast to keep up. It is possible for a person to learn of the title of a recent work and of the key words used in it and still not have the faintest idea of what the subject is. Progress Reports is to be an almost periodic column intended to increase everyone's mathematical information about what others have been up to. Each column will report one step forward in the mathematics of our time. The purpose is to inform, more than to instruct: what is the name of the subject, what are some of the words it uses, what is a typical question, what is the answer, who found it. The emphasis will be on concrete questions and answers (theorems), and not on general contexts and techniques (theories). References will be kept minimal: usually they will include only one of the earliest papers in which the answer appears and a more recent exposition of the discovery, whenever one is easily available. Everyone is invited to nominate subjects to be reported on and authors to prepare the reports. The ground rules are that the principal theorem should be old enough to have been published in the usual sense of that word (and not just circulated by word of mouth or in preprints); it should be of interest to more than just a few specialists; and it should be new enough to have an effect on the mathematical life of the present and near future. In practice most reports will probably be on progress achieved somewhere between 5 and 15 years ago.
Biotin nutriture and the enzymatic incorporation of NaHC14O3 into acetoacetate.

SummaryThe quantity of acetoacetic acid produced metabolically from pyruvate, caprylate, and caproate by rat liver homogenate systems is not affected by the state of biotin nutrition of the animals. However, biotin treatment of deficient animals increased by 10-100 fold the incorporation of C14 bicarbonate into the carboxyl group of acetoacetate metabolically formed from pyruvate, caproate, caprylate or isovalerate.
Seismic Acquisition Design Using 3D Target-Oriented Visibility Analysis

Summary Two-way wave equation based seismic visibility analysis is applied to 3D target-oriented acquisition design for extracting optimal acquisition parameters. An analysis work flow based on a stacked energy rose diagram is used to evaluate offset and azimuth distribution for a particular shot geometry. The energy rose diagram is then used in conjunction with shot visibility maps to guide selection of optimal 3D acquisition parameters. The primary objective of this case study is to evaluate alternative acquisition geometries for imaging a target under a seismic obscured gas zone. The visibility studies support wide azimuth and long offset acquisition geometries to provide imaging uplift for the target under the seismic obscured zone.
On the Constitution of the Regulations of Social-Security for Farmer-Workers

With the economic development in our society more and more farmers move into cities for work,thus it becomes an important work force in city construction.They have created great benefit for the society,while their social security has not been cared for,which not only prevents the process of industrialization and urbanization,but also brings about many hidden problems for the society.Therefore,it is urgent to constituter necessary regulations of social security for those people.
Study of User-centered Design and Development Methods

The steps,methods,and advantages of applying persona to product concept design were analyzed.The methods and rules of creating persona were introduced.It was put forward that product concept design should be centered by user prototype,configure according to user's partiality,and carry through the whole product development process to meet user's aims and requirements.
Research into the inner influencing factors of internationalization management performance of China's private enterprises

Firstly,according to theoretical analysis,this paper constructes a system of standards to measure the internationalization management performance of China's private enterprises and chooses 16 inner influencing factors.Then,this paper uses the method of ONE-WAY ANOVA and CORRELATE to study the 49 private enterprises by case study.The results show that there are 12 factors that will affect the internationalization management performance of China's private enterprises.We get a four-factor structure model by the method of factor analysis to study the 12 factors.Finally,tihis paper suggests some ways to enhance the internationalization management perfirmance.
Couples' coping with chronic illness: What's gender got to do with it?

Over the past decade, the lion's share of research on coping has focused on individual coping efforts and adaptation outcomes. However, major life stressors are not experienced in a social vacuum. When one family member is experiencing ongoing, complex stressors or life strains, other family members are affected by both the stressor itself, its psychological impact on the affected individual, and its effect on the family's functioning. At this juncture in stress and coping research, it is important to move past a dominant focus on individual-level processes into a social ecological or family systems framework. Marriage is a primary relationship often considered distinct from other family relationships because it is long-term, affords a central role identity, and provides a fundamental resource of social support and coping assistance (Revenson, 1994). Much research has demonstrated the beneficial effects of social support from family on patients' coping, across a number of chronic conditions (e.g., Cutrona, 1996; Lyons, Sullivan, Ritvo, & Coyne, 1996; Revenson, 2003). Far less research has focused on the effect of illness on the healthy spouse, children, the marriage, or the family (Pedersen & Revenson, in press). Husbands and wives experience unique stresses as a result of living with a chronically ill person (see chap. 6, this volume; Hagedoorn, Kuijer, Buunk, DeJong, Wobbes, & Sanderman, 2000; Revenson & Gibofsky, 1995; Revenson & Majerovitz, 1990, 1991). Some stresses emanate directly from caregiving in which spouses are inextricably involved in decision making about treatment and day-to-day care if the patient is disabled. Other stresses emerge from the need to restructure family roles and responsibilities as the disease progresses
Coronary MRI: more pretty pictures or present-day value?

The noninvasive evaluation of the coronary arteries has been a major goal of cardiovascular imaging. This has been difficult to accomplish because the coronary arteries are small, have similar imaging characteristics to the surrounding myocardium and cardiac veins, and are in constant motion. Two
Induced pluripotent stem cells, past and future

Ten years ago, Shinya Yamanaka and his student Kazutoshi Takahashi did an experiment of exquisite simplicity and elegance that changed biomedical research forever ( 1 ). By showing that a set of transcription factors could reprogram somatic cells to acquire a pluripotent stem cell state, they ushered in the era of induced pluripotent stem cells (iPSCs). The discovery made it crystal clear that cell identity is much more malleable than previously thought, and provided an invaluable tool for disease-oriented and translational researchers, bridging reductionism with patient-derived relevance. Combined with other maturing technologies, most notably genome editing and three-dimensional (3D) cell culture systems, iPSC technology has enabled investigation that was hitherto only possible in model organisms ( 2 , 3 ).
Image enhancement with weighted histogram equalization and heap transforms

In this paper, the enhancement of the gray scale and color images, by using the weighted histogram equalization and also discrete signal-induced heap transforms (DsiHT), which are composed by elementary rotations or Givens transformations, is described. In weighted histogram equalization method, the well known histogram equalization method has been manipulated with polynomial weights to perform the better enhanced images in both gray scale and color images. In the DsiHT as a novel method of image enhancement, the angles of rotations are defined by a given signal, which is called the generator. Due to construction of the heap transform, the latter eliminates an additive component in the signal, which is similar to the generator, but transfers the energy of this component to a specific location, for instance the first point of the signal. This property of the DsiHT can effectively be used in enhancing different classes of images. The DsiHT transforms are fast and can be applied for signals of any length. Examples of enhancement of gray scale and color images by the DsiHT are described and compared with the known methods such as the histogram equalization and α-rooting method.
Photosensitive dry film solder mask

The new photopolymer solder mask described here combines the properties of photographic selectivity, mechanical strength, and ease of reproducible application. It provides improved circuit protection during soldering operations and subsequent handling. The new solder mask offers substantial cost and performance advantages over screened masks to designers, printed wiring board fabricators, component assemblers, and end users.
Tongue base schwannoma: differential diagnosis and imaging features with a case presentation

Schwannomas are slow growing, encapsulated neoplasms that arise from the nerve sheath. A vast majority of these benign neoplasms occur in the head and neck region, most commonly involving the 8th cranial nerve. Schwannomas arising from the base of tongue are very rare and, thus, can easily escape the list of differential diagnosis for a posterior tongue mass. A systematic approach is recommended for diagnosis of a posterior tongue mass, with neoplastic, infectious, and congenital categories. We report a case of a 24-year-old female, who presented with pressure sensation in the throat. On imaging, she was found to have a mass in the right posterior tongue with follow-up biopsy results yielding a schwannoma. Characteristic imaging features for various possible etiologies of a posterior tongue mass are also discussed.
Modulation of HIF-2 Function with Small Molecules: Did Nature Beat Us to It?

Abstract Abstract SCI-39 Hypoxia inducible factors (HIFs) govern a mammalian cellular hypoxic response, regulating the transcription of hundreds of genes in response to low oxygen levels. Though this pathway performs critical functions under physiological conditions, increased levels of HIFs are also highly correlated with several disease states. As such, the development of artificial compounds that directly and selectively regulate HIF function is of interest. We have used a combination of biophysical, biochemical, and chemical approaches to study the structure and function of the Per-ARNT-Sim (PAS) domains of human HIFs, which serve as critical protein/protein interaction modules in assembling the functional HIF heterodimer. These studies have revealed the presence of a putative ligand-binding site within one of the HIF-2α PAS domains. A series of biased and unbiased approaches were undertaken to identify compounds that bind at this site and trigger conformational changes within the domain, leading to dissociation of the HIF-2 heterodimer in vitro and in living cells. Consequently, the expression of many hypoxia-inducible genes can be coordinately downregulated by a single agent. Despite its high amino acid identity, HIF-1α lacks a comparable ligand-binding site, indicating that these agents will be useful in deciphering differences in the biological roles of the HIF-1 and HIF-2 isoforms. The presence of a preformed cavity within HIF-2α is particularly as exciting as it suggests the potential for direct physiological regulation of HIF-2 by endogenous metabolite(s). Together, these studies offer further insight into HIF function and regulation while providing chemical tools that advance therapeutic applications. Disclosures: No relevant conflicts of interest to declare.
ORCON - a tool for analysis of ordinal consistency in a pairwise comparison matrix

Decision makers are often asked to make pairwise comparisons in the process of decision analysis with multiple criteria. Experiences show that decision makers make errors in expression of their judgements leading to ordinal and/or cardinal inconsistency in the comparison of objects. If results are highly inconsistent, the revision of a decision maker's comparisons should be carried out. The process may be quite complicated and usually is not part of the method. Ordinal consistency is often the first step to the success in many decision processes. We propose ORCON - an Excel-based tool that provides: 1) record of all cycles in the matrix of pairwise comparisons; 2) a list of all possible changes leading to consistency; 3) way to carry out those changes. The process is illustrated through ORCON application in a multi-criteria selection task.
Disseminated intravascular coagulation-like reaction following rituximab infusion

Rituximab generally is a well-tolerated medication used in a variety of haematological and autoimmune conditions. The safety profile of the medication has been reviewed in the literature. Infusion reactions due to cytokine release are the most common side effects. With the increased use of rituximab, there is an increase incidence of cytopenias, most commonly thrombocytopenia and leucopenia. Coagulopathy is quite rare, reported previously in four cases in the literature. We highlighted the clinical course of a 39-year-old patient with precursor B-cell acute lymphoblastic leukaemia who was started on rituximab infusion. The patient developed a cytokine-release syndrome with haemodynamic instability, followed by rapid-onset cytopenias and disseminated intravascular coagulation abnormalities characterised by coagulopathy with fibrinolysis and mucocutaneous bleeding. The report is followed by a review of the literature. It is important to recognise rituximab-induced coagulopathy early as part of the differential diagnosis of thrombocytopenia and disseminated intravascular coagulation following rituximab administration.
First Report of Dengue Virus Infection in a Bone Marrow Transplant Patient.

Dengue virus infections are a frequent cause of morbidity and mortality in certain endemic areas of the world but it has never been reported to occur in a bone marrow transplant patient. We describe a pediatric patient with ALL on her first bone marrow relapse undergoing allogeneic bone marrow transplant who developed sepsis and irreversible shock that on postmortem autopsy proved to be secondary to dengue virus infection Type 4. A 6 years old female with ALL underwent an allogeneic bone marrow transplant from her sibling (6/6 match) on Nov 10, 1994. She received TBI (1200 rads) and ARA-C (3gm/m2 per dose per 12 doses) as preparative regimen. She developed generalized skin erythema on day +5 followed by fever on day +6. The following days were characterized by continued fever spikes, severe mucositis, persistence of the erythematous skin rash (first degree burn like) and gross hematuria in spite of broad spectrum antibiotic coverage. Blood cultures were reported negative. She developed irreversible shock and finally died on day +11 post-transplant. At autopsy (Nov 22, 1994), Dengue virus type 4 was isolated from blood, ascitic fluid, liver and spleen by routine viral culture at San Juan C.D.C. Dengue Branch. Results were confirmed by polymerase chain reaction. Her donor also developed low grade fever the day after bone marrow donation. Further blood testing on donor (Dec 2, 1994) showed positive IgM antibodies against Dengue virus Type 4. The recipient viral cultures matches with donor acute titers for Dengue Type 4, suggesting infection through bone marrow transplant. Dengue virus infection may cause significant morbidity and mortality to blood and bone marrow recipients in endemic areas of the world.
Structurally Preserved Permian and Triassic Floras from Antarctica

The Permian and Triassic floras of Gondwana are known almost exclusively from impression/compression specimens. Generally, Permian floras from the southern hemisphere demonstrate a low diversity and are often poorly preserved as impressions. By comparison, floras of Triassic age display much greater diversity and are often better preserved, some with cuticular remains.The reconstruction of reproductive organs in this group is based almost completely on impression remains. Dictyopteridium has been interpreted by some as representing a three-dimensional cone bearing helically arranged ovules (Surange and Chandra 1975; Rigby 1978); others believe it should more accurately be depicted as a flattened, somewhat fleshy structure with bilateral symmetry (e.g.,Pant 1987).
Calcitonin receptor increases invasion of prostate cancer cells by recruiting zonula occludens-1 and promoting PKA-mediated TJ disassembly.

Abstract Almost all primary prostate cancers (PCs) and PC cell lines express calcitonin (CT) and/or its receptor (CTR), and their co-expression positively correlates with their invasiveness. Activation of the CT–CTR axis in non-invasive LNCaP cells induces an invasive phenotype. In contrast, silencing of CT/CTR expression in highly metastatic PC-3M cells markedly reduces their tumorigenicity and abolishes their ability to form distant metastases in nude mice. Our recent studies suggest that CTR interacts with zonula occludens 1 (ZO-1) through PDZ interaction to destabilize tight junctions and increase invasion of PC cells. Our results show that CTR activates AKAP2-anchored cAMP-dependent protein kinase A, which then phosphorylates tight junction proteins ZO-1 and claudin 3. Moreover, PKA-mediated phosphorylation of tight unction proteins required CTR-ZO-1 interaction, suggesting that the interaction may bring CTR-activated PKA in close proximity of tight junction proteins. Furthermore, inhibition of PKA activity attenuated CT-induced loss of TJ functionality and invasion, suggesting that the phosphorylation of TJ proteins is responsible for TJ disassembly. Finally, we show that the prevention of CTR-ZO-1 interaction abolishes CT-induced invasion, and can serve as a novel therapeutic tool to treat aggressive prostate cancers. In brief, the present study identifies the significance of CTR-ZO-1 interaction in progression of prostate cancer to its metastatic form.
On Writing Teaching Notes Well

What material should be included in a teaching note, the instructional tool that accompanies your business school case study—and makes its use far more likely? All good teaching notes have several characteristics in common. This technical note can help any business school professor, case writer, or collaborator create a teaching note that helps an instructor use your case to its fullest potential. Excerpt UVA-PHA-0062 Rev. May 9, 2014 ON WRITING TEACHING NOTES WELL If you want to stimulate discussion, knowing everything about the subject is only half the battle. Equally important, if not more so, is the need to have organized your thoughts well in advance. A good teaching note helps instructors do exactly that: prepare. It also helps the instructor evaluate the appropriateness of a given case. Every well-written business case study should come with an equally well-written teaching note. Sometimes called an instructor's manual, a teaching note suggests how the case may be used—not the only way, but the way the author planned to use it as he or she wrote it (see Exhibit1 for a template). Indeed, even with a road map, many instructors will choose their own routes. There is some debate about whether the optimal time to write a teaching note is before or after the case is taught. In fact, the most effective teaching notes are written both before and after. A solid teaching plan provides a framework for reviewing the case and determining whether enough information is provided for a good analysis and discussion. This note offers suggestions on when to write each part. . . .
Graduate medical education competencies for international health electives: A qualitative study.

AbstractBackground: Residency programs offer international health electives (IHEs), providing multiple educational benefits. This study aimed to identify how IHEs fulfill the Accreditation Council for Graduate Medical Education (ACGME) core competencies.Methods: We conducted a thematic analysis of post-rotation reflective reports from residents who participated in IHEs through the Mayo International Health Program. We coded reports using a codebook created from the ACGME competencies. Using a constant comparative method, we identified significant themes within each competency.Results: Residents from 40 specialties participated in 377 IHEs in 56 countries from 2001 to 2014. Multiple themes were identified within each of the six ACGME core competencies: Patient Care and Procedural Skills (4), Medical Knowledge (5), Practice-Based Learning and Improvement (3), Interpersonal and Communication Skills (5), Professionalism (4), and Systems-Based Practice and Improvement (3). Themes included improving physical ex...
Abstract 391: The Pathophysiological Role of MYBPHL in Dilated Cardiomyopathy

Background: Cardiomyopathy is a leading cause of heart failure and is highly heritable. One common form of cardiomyopathy is dilated cardiomyopathy (DCM), which currently has over 70 identified gen...
Exploring affection-oriented virtual pet game design strategies in VR attachment, motivations and expectations of users of pet games

Pets in real life and pets in virtual worlds play two different roles in a human's life. To date, the relationships between humans and virtual pets, especially in virtual reality environments (VRE), remain uninvestigated and relatively unexploited in designing virtual pet games. This paper examines the perceptions, motivations and expectations of people who play games involving pets, and how emotional connection with real pets affect their expectation for pets in VREs. To investigate this, we analyzed data collected from (i) an online survey of 774 people and (ii) observations and interviews with 30 people who played VR pet games in a lab study. Differences in perception, motivation and expectation in virtual reality pet games were found between players who have pets or do not. These findings deepen our understanding of the formation of emotion connections in VREs and provide a basis for studying individual differences in emotion in virtual pet games.
Characteristics and the Cross-Section of Covariances

We propose a new, minimally parameterized way of modeling stock-level covariances as a function of firm characteristics. Our model uses a large number of indicator functions to approximate the surface mapping two firms' characteristics to the correlation of their returns. We show that the method performs better than existing methods both in and out of our sample period. In truly out of sample tests, we show that using the information in firm characteristics, we can predict future covariances better than when using common asset pricing models. Correspondingly, we discuss how one can use our model as an avenue for understanding how characteristics relate to stock returns in the context of linear asset pricing models.
The tamoxifen derivative ridaifen-B is a high affinity selective CB 2 receptor inverse agonist exhibiting anti-inflammatory and anti-osteoclastogenic effects.

Selective estrogen receptor modulators (SERMs) target estrogen receptors (ERs) to treat breast cancer and osteoporosis. Several SERMs exhibit anti-cancer activity not related to ERs. To discover novel anti-cancer drugs acting via ER-independent mechanisms, derivatives of the SERM tamoxifen, known as the "ridaifen" compounds, have been developed that exhibit reduced or no ER affinity, while maintaining cytotoxicity. Tamoxifen and other SERMs bind to cannabinoid receptors with moderate affinity. Therefore, ER-independent effects of SERMs might be mediated via cannabinoid receptors. This study determined whether RID-B, a first generation ridaifen compound, exhibits affinity and/or activity at CB1 and/or CB2 cannabinoid receptors. RID-B binds with high affinity (Ki = 43.7 nM) and 17-fold selectivity to CB2 over CB1 receptors. RID-B acts as an inverse agonist at CB2 receptors, modulating G-protein and adenylyl cyclase activity with potency values predicted by CB2 affinity. Characteristic of an antagonist, RID-B co-incubation produces a parallel-rightward shift in the concentration-effect curve of CB2 agonist WIN-55,212-2 to inhibit adenylyl cyclase activity. CB2 inverse agonists are reported to exhibit anti-inflammatory and anti-ostoeclastogenic effects. In LPS-activated macrophages, RID-B exhibits anti-inflammatory effects by reducing levels of nitric oxide (NO), IL-6 and IL-1α, but not TNFα. Only reduction of NO concentration by RID-B is mediated by cannabinoid receptors. RID-B also exhibits pronounced anti-osteoclastogenic effects, reducing the number of osteoclasts differentiating from primary bone marrow macrophages in a cannabinoid receptor-dependent manner. In summary, the tamoxifen derivative RID-B, developed with reduced affinity for ERs, is a high affinity selective CB2 inverse agonist with anti-inflammatory and anti-osteoclastogenic properties.
A Single Amino Acid Switch Alters the Isoprene Donor Specificity in Ribosomally Synthesized and Post-Translationally Modified Peptide Prenyltransferases

Mutation at a single amino acid alters the isoprene donor specificity of prenyltransferases involved in the modification of ribosomally synthesized and post-translationally modified peptides (RiPPs). Though most characterized RiPP prenyltransferases carry out the regiospecific transfer of C5 dimethylallyl donor to the side chain atoms on macrocyclic acceptor substrates, the elucidation of the cyanobactin natural product piricyclamide 70005E1 identifies an O-geranyl modification on Tyr, a reaction with little prior biochemical precedence. Reconstitution and kinetic studies of the presumptive geranyltransferase PirF shows that the enzyme utilizes a C10 donor, with no C5 transferase activity. The crystal structure of PirF reveals a single amino acid difference in the vicinity of the isoprene-binding pocket, relative to the C5 utilizing enzymes. Remarkably, only a single amino acid mutation is necessary to completely switch the donor specificity from a C5 to a C10 prenyltransferase, and vice versa. Lastly, we...
Chapter 4 Visual Aids: Your Supporting Cast

In the mid-nineteenth century, chalkboards were a novelty. Institutions would boast about having the only chalkboard in a 100-mile radius. At fi rst, audiences were excited just to have a chalkboard as part of the presentation. Over time, though, presenters started using the boards in more sophisticated ways: rulers to make lines, chalk tied to string to make circles, and colored chalk to show features. Some scientists and engineers were admired for the way they used the chalkboard. For instance, Ludwig Boltzmann was considered a master of board work, using one large board for main equations and two smaller boards for intermediate steps. 2 Another master was Richard Feynman. He planned many of his lectures such that the writing for the lecture began in one corner and ended in the opposite one.
Glycosyltransferase homologs prevent promiscuous cell aggregation and promote multicellular development in the choanoflagellate S. rosetta

The mechanisms underlying multicellular development in the earliest animals may be revealed through the study of the closest living relatives of animals, choanoflagellates. The emerging model choanoflagellate S. rosetta can develop from a single cell into a multicellular rosette through a process of serial cell divisions. Through a screen for rosette defect mutants, we have uncovered multiple S. rosetta mutants in which single cells fail to develop into orderly rosettes but instead aggregate promiscuously into amorphous clumps of cells. By mapping the genetic lesions underlying two of these clumping/rosette defect mutants, Jumble and Couscous, we found that both are monogenic and caused by mutations in genes encoding glycosyltransferases, enzymes that transfer activated sugars to donor molecules. These are only the second and third genes to be implicated in the regulation of multicellularity in choanoflagellates to date. Animal glycosyltransferases contribute to the production of the polysaccharide-rich glycocalyx that covers nearly all animal cells, regulate the activity of integrins and cadherins (proteins critical for development and cell-cell adhesion), and, when disrupted, can contribute to tumorigenesis. Our finding that glycosyltransferases in S. rosetta are required to prevent spurious cell adhesion in single cells and to promote proper cell adhesion during rosette development suggests a pre-metazoan role for glycosyltransferases in regulating development and preventing abnormal tumor-like multicellularity.
Assessment of Racial Disparities in Biomarkers for Alzheimer Disease.

Importance Racial differences in molecular biomarkers for Alzheimer disease may suggest race-dependent biological mechanisms. Objective To ascertain whether there are racial disparities in molecular biomarkers for Alzheimer disease. Design, Setting, and Participants A total of 1255 participants (173 African Americans) were enrolled from January 1, 2004, through December 31, 2015, in longitudinal studies at the Knight Alzheimer Disease Research Center at Washington University and completed a magnetic resonance imaging study of the brain and/or positron emission tomography of the brain with Pittsburgh compound B (radioligand for aggregated amyloid-β) and/or cerebrospinal fluid (CSF) assays for the concentrations of amyloid-β42, total tau, and phosphorylated tau181. Independent cross-sectional analyses were conducted from April 22, 2016, to August 27, 2018, for each biomarker modality with an analysis of variance or analysis of covariance including age, sex, educational level, race, apolipoprotein E (APOE) e4allele status, and clinical status (normal cognition or dementia). All biomarker assessments were conducted without knowledge of the clinical status of the participants. Main Outcomes and Measures The primary outcomes were hippocampal volumes adjusted for differences in intracranial volumes, global cerebral amyloid burden as transformed into standardized uptake value ratios (partial volume corrected), and CSF concentrations of amyloid-β42, total tau, and phosphorylated tau181. Results Of the 1255 participants (707 women and 548 men; mean [SD] age, 70.8 [9.9] years), 116 of 173 African American participants (67.1%) and 724 of 1082 non-Hispanic white participants (66.9%) had normal cognition. There were no racial differences in the frequency of cerebral ischemic lesions noted on results of brain magnetic resonance imaging, mean cortical standardized uptake value ratios for Pittsburgh compound B, or for amyloid-β42 concentrations in CSF. However, in individuals with a reported family history of dementia, mean (SE) total hippocampal volumes were lower for African American participants than for white participants (6418.26 [138.97] vs 6990.50 [44.10] mm3). Mean (SE) CSF concentrations of total tau were lower in African American participants than in white participants (293.65 [34.61] vs 443.28 [18.20] pg/mL;P Conclusions and Relevance The results of this study suggest that analyses of molecular biomarkers of Alzheimer disease should adjust for race. The lower CSF concentrations of total tau and phosphorylated tau181in African American individuals appear to reflect a significant race byAPOEe4interaction, suggesting a differential effect of this Alzheimer risk variant in African American individuals compared with white individuals.
Exploiting the Oral Microbiome to Prevent Tooth Decay: Has Evolution Already Provided the Best Tools?

To compete in the relatively exposed oral cavity, resident microbes must avoid being replaced by newcomers. This selective constraint, coupled with pressure on the host cultivate a beneficial microbiome, has rendered a commensal oral microbiota that displays colonization resistance, protecting the human host from invasive species, including pathogens. Rapid increases in carbohydrate consumption have disrupted the evolved homeostasis between the oral microbiota and dental health, reflected by the high prevalence of dental caries. Development of novel modalities to prevent caries has been the subject of a breadth of research. This minireview provides highlights of these endeavors and discusses the rationale and pitfalls behind the major avenues of approach. Despite efficacy, fluoride and other broad-spectrum interventions are unlikely to further reduce the incidence of dental caries. The most promising methodologies in development are those that exploit the exclusive nature of the healthy oral microbiome. Probiotics derived from the dental plaque of healthy individuals sharply antagonize cariogenic species, such as Streptococcus mutans. Meanwhile, targeted antimicrobials allow for the killing of specific pathogens, allowing reestablishment of a healthy microbiome, presumably with its protective effects. The oral microbiota manufactures a massive array of natural products, some of which are correlated with health, are likely to antagonize pathogens, and await further exploration. The prohibitive cost associated with sufficiently rigorous clinical trials, and the status of dental caries as a non-life-threatening condition will likely continue to impede the advancement of new therapeutics to market. Nevertheless, there is room for optimism, as it appears evolution may have already provided the best tools.
Current and emerging biologic and small molecule therapies for atopic dermatitis

Introduction Atopic dermatitis (AD) is the most common inflammatory skin disease, yet until recently there were no safe systemic therapies approved for the long-term management of AD in adult patients. A deeper understanding of disease pathogenesis and identification of molecular and cellular changes has resulted in a rapidly evolving pipeline of therapeutics that holds promise for safer long-term control. Areas covered In this review, we highlight the growing arsenal of biologic and small molecule antagonists that target pathways implicated in AD pathogenesis. Evidence that AD is driven by multiple immune axes extending beyond the Th2 polarization has resulted in therapies targeting additional pathways, including the Th22, Th17/IL-23, and JAK-STAT pathways. Pruritus, a hallmark of AD, has been linked to multiple mechanisms and various therapeutics have emerged in response to alternative hypotheses. Expert opinion Despite the assumption that AD has a common disease mechanism, recent studies indicate that the disorder is characterized by several phenotypes and therapy may need to be tailored to the unique immune traits of specific phenotypes. Targeted therapy should complement and expand our molecular map of AD across the various phenotypic iterations and help push AD pharmacotherapy into a new era of personalized medicine.
Approximating local properties by tensor network states with constant bond dimension

Suppose we would like to approximate all local properties of a quantum many-body state to accuracy $\delta$. In one dimension, we prove that an area law for the Renyi entanglement entropy $R_\alpha$ with index $\alpha<1$ implies a matrix product state representation with bond dimension $\mathrm{poly}(1/\delta)$. For (at most constant-fold degenerate) ground states of one-dimensional gapped Hamiltonians, it suffices that the bond dimension is almost linear in $1/\delta$. In two dimensions, an area law for $R_\alpha(\alpha<1)$ implies a projected entangled pair state representation with bond dimension $e^{O(1/\delta)}$. In the presence of logarithmic corrections to the area law, similar results are obtained in both one and two dimensions.