cssi/SciSciGPT-SciSciNet huggingface dataset:
Interleukin-7 and -15 maintain pathogenic memory Th17 cells in autoimmunity.

Th17 cells are principal mediators of many autoimmune conditions. Recently, memory Th17 cells have been revealed as crucial in mediating the chronicity of various refractory autoimmune disorders; however, the underlying mechanisms maintaining memory Th17 cells have remained elusive. Here, using a preclinical model of ocular autoimmune disease we show that both IL-7 and IL-15 are critical for maintaining pathogenic memory Th17 cells. Neutralization of these cytokines leads to substantial reduction of memory Th17 cells; both IL-7 and IL-15 provide survival signals via activating STAT5, and IL-15 provides additional proliferation signals via activating both STAT5 and Akt. Topical neutralization of ocular IL-7 or IL-15 effectively reduces memory Th17 cells at the inflammatory site and draining lymphoid tissues, while topical neutralization of IL-17 alone, the major pathogenic cytokine secreted by Th17 cells, does not diminish memory Th17 cells at the draining lymphoid tissues. Our results suggest that the effective removal of pathogenic memory Th17 cells via abolishing environmental IL-7 or IL-15 is likely to be a novel strategy in the treatment of autoimmune diseases.
Super-resolution imaging of silver nanostructures on plasmonic grating

We utilized different super-resolution techniques to image silver nanostructures with the assist of grating-based surface plasmon resonance. We can identify the shape and size of nanoparticles in epi-fluorescence mode and image single-molecule using a smartphone.
Flute physics from a flutist’s perspective

The basic physics of the flute is presented from the perspective of a professional flutist. The flutist can control loudness, pitch and to some extent timbre. Oscilloscope images are provided to compare changes in these three fundamental sound characteristics. Readers can view a video (Ruiz 2017 Video: The Flute http://mjtruiz.com/ped/flute/) where coauthor, flutist Erika Boysen, demonstrates the topics covered in this paper.
The Role of Thermal Activation and Molecular Structure on the Reaction of Molecular Surfaces

Though surface modifications of organic thin films dramatically improve optoelectronic device performance, chemistry at organic surfaces presents new challenges that are not seen in conventional inorganic surfaces. This work demonstrates that the subsurface of pentacene remains highly accessible, even to large adsorbates, and that three distinct reaction regimes (surface, subsurface, and bulk) are accessed within the narrow thermal range of 30–75 °C. Progression of this transition is quantitatively measured via polarization modulation infrared reflection absorption spectroscopy, and atomic force microscopy is used to measure the thin-film morphology. Together, they reveal the close relationship between the extent of the reaction and the morphology changes. Finally, the reaction kinetics of the pentacene thin film is measured with a series of adsorbates that have different reactivity and diffusivity in the thin film. The results suggest that reaction kinetics in the thin film is controlled by both the reac...
Social Intuition and Social Information in Physical Child Abuse Evaluation and Diagnosis

BACKGROUND: Poor and minority children with injuries concerning for abuse are evaluated and diagnosed for abuse differentially. We hypothesized that 2 steps in the decision-making process would influence evaluation and diagnosis: social intuition from meeting the family and objective social information associated with child abuse risk. METHODS: Between 2009 and 2013, 32 child abuse pediatricians (CAPs) submitted 730 child abuse consultations including original medical evaluations and diagnoses. CAPs evaluated and diagnosed each other’s cases. Comparisons of evaluations and diagnoses were made by levels of social understanding available to the CAP: meeting the family (social intuition and information), reading the case (social information), and reading the case without social information. Evaluations were compared with a consensus gold standard by using logistic regression modeling adjusting for child and CAP characteristics. Diagnostic categories were compared by level of social understanding and diagnostic certainty by using contingency tables. RESULTS: CAPs without access to social intuition were approximately twice as likely to perform gold standard evaluations for neurotrauma and long bone fracture compared with CAPs who met families. Diagnostic agreement fell from 73.3% (95% confidence interval [CI]: 70.1%–76.5%) when social information was present to 66.5% (95% CI: 63.1%–70.0%) when social information was restricted. In cases with less certainty, agreement dropped to 51.3% (95% CI: 46.0%–56.7%). CONCLUSIONS: Social intuition and information play a role in the physical child abuse decision-making process, which may contribute to differential diagnosis. Simple interventions including decision tools, check lists, and peer review may structure evaluations to ensure children’s equal treatment.
Mechanism of iodine release from iodoapatite in aqueous solution

Safe disposal of nuclear waste is essential to ensure the sustainability of nuclear energy. This is especially true for the volatile radionuclide iodine-129 due to its long half-life (15.7 Ma) and high mobility in most disposal environments. The dissolution behaviour of lead vanadium iodoapatite (Pb5(VO4)3I) synthesized to evaluate its possible use for immobilizing iodine-129 was investigated to understand the mechanism by which iodide is released. Experiments using a semi-dynamic method were carried out in cap-sealed Teflon vessels at a constant temperature 90 ± 0.5 °C with a fixed sample surface area-to-solution volume ratio of 16 m−1. The leachates were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) and the leached surfaces were examined by X-ray diffraction (XRD), scanning electron microscopy (SEM) and infrared spectroscopy (IR). The results show that lead and vanadium dissolved congruently at a constant rate, while the iodine was initially released at a significantly higher rate than suggested by its stoichiometry with respect to lead and vanadium. The iodine-to-lead molar ratio in the solution gradually decreased over time, but iodine release remained superstoichiometric. The results suggest the release of iodide occurs by an ion-exchange process that is faster than the dissolution rate of the Pb–V–O framework. Analysis of the leached samples shows that the spectroscopic signature of OH groups in the leached samples is consistent with an ion exchange mechanism.
Peri-ictal psychiatric phenomena

This introduction presents an overview of the concepts discussed in this book The Neuropsychiatry of Epilepsy. In the intervening years, there has been a clear appreciation in biological psychiatry of the neurobiological bases of psychopathologies as major depressive disorder, obsessive-compulsive disorder and other anxiety-related conditions, and there has been further development of psychotropic and anticonvulsant drugs (AEDs). The second edition starts with epidemiology, which has become a prominent discipline in research attempting to disentangle the extent and variety of psychiatric comorbidities in epilepsy. The clinical presentations and the wide spectrum of peri-ictal disorders are then discussed. Depression in epilepsy may not be quite like depression in the absence of epilepsy, the neuroanatomy giving a special stamp on the phenomenology. The book concludes with a discussion on the brain mechanisms of consciousness as may be revealed through investigations of patients with seizure disorders.
Increasing Racial Isolation and Test Score Gaps in Mathematics: A 30-Year Perspective

Background/ContextAlthough there has been progress in closing the test score gaps among student groups over past decades, that progress has stalled. Many researchers have speculated why the test sc...
Optimization of selenium in cell culture media to maximize selenoenzyme activity

Selenium plays an essential role in redox biology and redox toxicology. It is found at the active site of redox enzymes such as, glutathione peroxidases (GPx) and thioredoxin reductases (TrxR). Cell culture media is typically deficient in selenium; this deficiency could limit seleno-enzyme expression and activity, compromising the translation of data from in vitro experiments to in vivo settings. The level of selenium in cell culture media should always be a consideration. However, any supplementation must be within a range to overcome deficiency and yet not induce toxicity. The optimal level of supplementation has not been well characterized. To determine optimal levels of Se-supplementation of cell culture media we introduced varying levels of sodium selenite (Na2SeO3) or seleno-L-methionine (SLM). We established, that the window to avoid potential toxicity can be widened by using SLM instead of selenite. We assessed the expression and activity of GPx1 and GPx4 to determine the level of optimal selenium supplementation for a variety of cells. Supplementing cell culture media containing 10% FBS with 100 – 300 nM SLM, we were able to maximize GPx1 and GPx4 enzyme expression and activity. Interestingly, data from a clinical trial at The University of Iowa indicates that supplementing Se in humans does not increase GPx1 activity in blood. Subjects received ~30x the RDA (55 mg d-1) of Se as SLM daily for more than 7 mo. The level of total Se in blood increased about 50-fold. However, the activity of GPx1 in blood remained constant. Our cell culture data show the importance of supplementing cell culture media with Se to insure full activity of these enzymes. This simple maneuver will increase the rigor and reproducibility of cell culture experiments and may lead to better translation of data addressing basic redox biology.
Timing of Local Therapy Affects Survival in Ewing Sarcoma.

Purpose We aimed to investigate the relationship between survival and time to local therapy after initiation of up-front chemotherapy in the treatment of patients with localized Ewing sarcoma. Methods and Materials The National Cancer Database was queried for patients with localized Ewing sarcoma treated with primary chemotherapy and subsequent local therapy. Kaplan-Meier survival curves were generated for patients initiating local therapy 6 to 15 weeks and ≥16 weeks after chemotherapy initiation. Multivariable binomial logistic regression was used to identify factors associated with prolonged time to local therapy. A multivariable Cox proportional hazards model was used to identify factors associated with overall survival (OS). Results The final cohort included 1318 patients. A higher proportion of patients initiating local therapy 6 to 15 weeks after chemotherapy initiation versus ≥16 weeks after chemotherapy initiation were ≤21 years old (79.5% vs 72.0%; P = .004). Age >21 years ( P 8 cm ( P = .016), and time to local therapy ≥16 weeks ( P = .005; hazard ratio, 1.41; 95% confidence interval, 1.11-1.80) were associated with reduced OS; after review of margin status, negative margins were associated with improved OS compared with gross disease ( P = .029). Patients initiating local therapy at 6 to 15 weeks versus ≥16 weeks had a 5-year OS of 78.7% versus 70.4% and a 10-year OS of 70.3% versus 57.1%, respectively ( P 21 years and treatment by radiation therapy alone were associated with delayed time (>16 weeks) to local therapy, whereas private insurance and income >$48,000 were less likely to be associated with delayed local therapy. Conclusions Delayed time to local therapy ≥16 weeks after chemotherapy initiation was independently associated with worse survival in patients with localized Ewing sarcoma.
Relative contributions of adipose-resident CD146 + pericytes and CD34 + adventitial progenitor cells in bone tissue engineering.

Pericytes and other perivascular stem/stromal cells are of growing interest in the field of tissue engineering. A portion of perivascular cells are well recognized to have MSC (mesenchymal stem cell) characteristics, including multipotentiality, self-renewal, immunoregulatory functions, and diverse roles in tissue repair. Here, we investigate the differential but overlapping roles of two perivascular cell subsets in paracrine induction of bone repair. CD146+CD34−CD31−CD45−pericytes and CD34+CD146−CD31−CD45−adventitial cells were derived from human adipose tissue and applied alone or in combination to calvarial bone defects in mice. In vitro, osteogenic differentiation and tubulogenesis assays were performed using either fluorescence activated cell sorting-derived CD146+ pericytes or CD34+ adventitial cells. Results showed that CD146+ pericytes induced increased cord formation in vitro and angiogenesis in vivo in comparison with patient-matched CD34+ adventitial cells. In contrast, CD34+ adventitial cells demonstrated heightened paracrine-induced osteogenesis in vitro. When applied in a critical-size calvarial defect model in NOD/SCID mice, the combination treatment of CD146+ pericytes with CD34+ adventitial cells led to greater re-ossification than either cell type alone. In summary, adipose-derived CD146+ pericytes and CD34+ adventitial cells display functionally distinct yet overlapping and complementary roles in bone defect repair. Consequently, CD146+ pericytes and CD34+ adventitial cells may demonstrate synergistic bone healing when applied as a combination cellular therapy. Different kinds of cells found surrounding blood vessels in fat play a complementary and synergistic role in bone healing. Aaron James from Johns Hopkins University in Baltimore, MD, USA, and colleagues derived two subsets of cells from human fat tissue: contractile cells known as pericytes that wrap around cellular lining of capillaries and tiny veins; and connective tissue cells known as adventitial cells that surrounds larger vessels. Under isolated culture conditions, pericytes stimulated the development of primitive blood vessels, whereas adventitial cells promoted early bone formation. The researchers applied the cells to the sites of bone defects in mice and saw that combined treatment with both pericytes and adventitial cells led to greater bone repair than treatment with either cell type alone.
Barrett's Esophagus and Esophageal Carcinoma: Can Biomarkers Guide Clinical Practice?

Despite gastrointestinal societal recommendations for endoscopic screening and surveillance of Barrett’s esophagus, the rates of esophageal adenocarcinoma continue to rise. Furthermore, this current practice is costly to patients and the medical system without clear evidence of reduction in cancer mortality. The use of biomarkers to guide screening, surveillance, and treatment strategies might alleviate some of these issues. Incredible advances in biomarker identification, biomarker assays, and minimally-invasive modalities to acquire biomarkers have shown promising results. We will highlight recently published, key studies demonstrating where we are with using biomarkers for screening and surveillance in clinical practice, and what is on the horizon regarding novel non-invasive and minimally invasive methods to acquire biomarkers. Proof-of principle studies using in silico models demonstrate that biomarker-guided screening, surveillance, and therapeutic intervention strategies can be cost-effective and can reduce cancer deaths in patients with Barrett’s esophagus.
Oxidative Cross-Esterification and Related Pathways of Co-Adsorbed Oxygen and Ethanol on Pd–Au

Ethanol is one of the most important industrial chemicals considering its wide range of uses. From ultrahigh vacuum (UHV) experiments, we were able to effectively produce acetaldehyde and ethyl acetate on a Pd–Au model catalyst. The presence of oxygen at the Pd–Au interface sites was found to be highly reactive for ethanol dehydrogenation, significantly increasing acetaldehyde production and promoting cross-esterification to produce ethyl acetate. Density functional theory calculations show that compared to the bare PdAu(111) surface, the presence of preadsorbed oxygen and the subsequently formed hydroxyl group leads to highly active and selective initial ethanol dehydrogenation at the O–H and α–C-H position, which was corroborated by isotope-labeling experiments. Specifically, using temperature-programmed desorption with the isotope CD3CH2OH, we identified C–C bond breakage through methane production. Furthermore, the simultaneous desorption of D2 with ethyl acetate from the oxidation of CD3CD2OD suggest...
Impact of CAR T-cell product viability on B-cell lymphoid malignancy outcomes

Background & Aim CTL019 (tisagenlecleucel) is an anti-CD19 genetically modified autologous T-cell therapy approved for treatment of relapsed/refractory pediatric and young adult B-cell acute lymphoblastic leukemia (ALL) and adult diffuse large B-cell lymphoma (DLBCL). For CTL019 manufactured at Penn, the product release criteria include a viability assessment. In clinical trials, viability specification for product release was ≥ 70% viable cells; whereas, for commercial tisagenlecleucel, viability specification for product release was ≥ 80%. We examined the relationship between CTL019 viability release testing and clinical outcomes. Methods, Results & Conclusion We analyzed CTL019 viability release testing in patients (pts) treated on prospective single institution clinical trials for non-Hodgkin lymphomas (NHL) (NCT02030834) and pediatric ALL clinical trials (NCT01626495, NCT02906371). The relationship of CTL019 product viability release testing and overall response, progression-free survival, overall survival, sensitivity/specificity of viability testing to predict complete response, and CAR T-cell expansion were examined. For 39 NHL pts, the median product viability was 89.8% (range: 73.7%-97.7%) and 3 pts had products with These results suggest that there is no dose-response relationship between CTL019 product viability (70-98%) and clinical outcomes.
Traveling through the liminal: mixed reality simulations in educational leadership preparation

The purpose of this study was to explore how aspiring school leaders grappled with threshold concepts related to educational leadership within mixed reality simulations. An exploratory collective c...
Detection of Data Anomalies in Fog Computing Architectures

Fog computing architectures provide a new platform for distributed stream processing in Internet of Things (IoT) applications. In a hierarchical infrastructure, processing of stream data arriving from sensors starts at the lowest level edge nodes and proceeds to the intermediate level fog nodes and eventually to the top-level cloud node. The goal is to do as much processing as possible at the lower level nodes and react to unexpected or interesting input values as early as possible. The unexpected values are referred to as anomalies. They may occur due to malfunctioning of sensors, which may be due to accidents or intentional attacks, or changes in the environment. The anomalies must be detected and proper actions must be taken quickly to bring the application to a steady state. We describe a generic framework for detection of data anomalies in a fog hierarchy in this paper. Our framework can be adapted to any application and other fog architectures.
166 Maladaptive mechanisms for coping with the direct costs of injuries: foregoing medical care in Vietnam and Kenya

Statement of Purpose Uninsured patients may attempt to cope with the costs of an injury through various financial and non-financial coping mechanisms. Certain coping mechanisms, such as reducing health care utilization, may minimize direct medical costs while increasing indirect costs. Methods/Approach The Health, Economic and Long-term Social Impact of Injuries (HEALS) project was a hospital-based longitudinal study of patients conducted in four countries, including Vietnam and Kenya, in 2015–2016. Using baseline survey data, we compared differences in length of hospital stay by health insurance status using a multivariable linear regression, and conducted a multivariable logistic regression to evaluate the relationship between insurance and foregoing additional health care. Results The sample included 1022 patients in Vietnam and 994 in Kenya. Of these, 56.2% and 68.8% lacked insurance and 21.5% and 3.7% left against medical advice in Vietnam and Kenya, respectively. In Vietnam, uninsured patients left 2.4 days earlier than those with insurance, controlling for injury severity and mechanism; patient demographics; pre-injury household poverty status and the patient’s contribution to household income (β=-2.441, p Conclusions Patients without health insurance may be foregoing health care in order to avoid additional direct health care costs, and in the process increasing indirect costs if leaving against medical advice prolongs a period of disability. Significance and Contributions to Injury and Violence Prevention Science Improving the breadth of health insurance can protect against both direct and indirect costs of injuries.
Association of Age, Sex, Race, and Geographic Region With Variation of the Ratio of Basal Cell to Cutaneous Squamous Cell Carcinomas in the United States.

Importance Defining which populations are affected by basal cell carcinoma (BCC) vs cutaneous squamous cell carcinoma (cSCC) may inform targeted public health strategies. Incidence of BCC and cSCC is not reported to national cancer registries, but claims data for the treatment of BCC and cSCC provide insights into the epidemiology of keratinocyte carcinoma. Objective To define differences in the ratio of BCC to cSCC in adults (age, ≥18 years) in a large database of patients with commercial insurance and Medicare Advantage coverage. Design, Setting, and Participants This cross-sectional analysis used deidentified data derived from the Optum Clinformatics Data Mart to perform a retrospective evaluation of a large commercially insured cohort based on treatment claims from January 1, 2012, to December 31, 2016. Patients with a diagnosed and treated BCC or cSCC as determined by codes from theInternational Classification of Diseases, Ninth Revision,International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, andCurrent Procedural Terminologywere included. Data were analyzed from November 30, 2019, to March 20, 2020. Exposure Diagnosis and treatment of BCC or cSCC. Main Outcomes and Measures The ratio of BCC to cSCC based on age, sex, race, and geographic location. Multivariable logistic regression was used to assess how demographics were associated with the odds of a treated keratinocyte carcinoma being a BCC. Results Among the 985 317 claims for patients included in the analysis (61.59% for men; mean [SD] age, 69.82 [12.58] years), BCCs were 1.69 (95% CI, 1.6899-1.6901) times more likely than cSCCs to be treated in the United States from 2012 to 2016. Basal cell carcinomas were significantly more prevalent than cSCCs in younger patients (18-39 years, 9.63 [95% CI, 9.6088-9.6574] BCCs per cSCC; 40-64 years, 2.92 [95% CI, 2.9171-2.9187] BCCs per cSCC; and ≥65 years, 1.33 [95% CI, 1.3289-1.3291] BCCs per cSCC;P Conclusions and Relevance In the absence of a national registry, claims data can improve our understanding of the epidemiology of keratinocyte carcinomas. In this cross-sectional study, basal cell carcinomas were more common than cSCCs for all demographics, including in Black patients. In populations younger than 40 years, BCCs were 12.6 times more likely for women and 7.2 times more likely for men. These demographic groups may benefit from public health education focused on the presentation and management of BCCs.
Experience shapes activity dynamics and stimulus coding of VIP inhibitory and excitatory cells in visual cortex

ABSTRACT Cortical circuits are flexible and can change with experience and learning. However, the effects of experience on specific cell types, including distinct inhibitory types, are not well understood. Here we investigated how excitatory and VIP inhibitory cells in layer 2/3 of mouse visual cortex were impacted by visual experience in the context of a behavioral task. Mice learned to perform an image change detection task with a set of eight natural scene images, viewing these images thousands of times. Subsequently, during 2-photon imaging experiments, mice performed the task with these familiar images and three additional sets of novel images. Novel images evoked stronger overall activity in both excitatory and VIP populations, and familiar images were more sparsely coded by excitatory cells. The temporal dynamics of VIP activity differed markedly between novel and familiar images: VIP cells were stimulus-driven by novel images but displayed ramping activity during the inter-stimulus interval for familiar images. Moreover, when a familiar stimulus was omitted from an expected sequence, VIP cells showed extended ramping activity until the subsequent image presentation. This prominent shift in response dynamics suggests that VIP cells may adopt different modes of processing during familiar versus novel conditions. HIGHLIGHTS Experience with natural images in a change detection task reduces overall activity of cortical excitatory and VIP inhibitory cells Encoding of natural images is sharpened with experience in excitatory neurons VIP cells are stimulus-driven by novel images but show pre-stimulus ramping for familiar images VIP cells show strong ramping activity during the omission of an expected stimulus
Advances in Implantable Microelectrode Array Insertion and Positioning.

Objectives Microelectrode arrays offer a means to probe the functional circuitry of the brain and the promise of cortical neuroprosthesis for individuals suffering from paralysis or limb loss. These devices are typically comprised of one or more shanks incorporating microelectrode sites, where the shanks are positioned by inserting the devices along a straight path that is normal to the brain surface. The lack of consistent long-term chronic recording technology has driven interest in novel probe design and approaches that go beyond the standard insertion approach that is limited to a single velocity or axis. This review offers a description of typical approaches and associated limitations and surveys emergent methods for implantation of microelectrode arrays, in particular those new approaches that leverage embedded microactuators and extend the insertion direction beyond a single axis. Materials and methods This review paper surveys the current technologies that enable probe implantation, repositioning, and the capability to record/stimulate from a tissue volume. A comprehensive literature search was performed using PubMed, Web of Science, and Google Scholar. Results There has been substantial innovation in the development of microscale and embedded technology that enables probe repositioning to maintain quality recordings in the brain. Innovations in material science have resulted in novel strategies for deployable structures that can record from or stimulate a tissue volume. Moreover, new developments involving magnetically steerable catheters and needles offer an alternative approach to "pull" rather than "push" a probe into the tissue. Conclusion We envision the emergence of a new generation of probes and insertion methodologies for neuromodulation applications that enable reliable chronic performance from devices that can be positioned virtually anywhere in the brain.
The urban archetypes of Jane Jacobs and Ebenezer Howard: Contradiction and meaning in city form, by Abraham Akkerman: Toronto, Canada, University of Toronto Press, 2020

The Garden City, as invented and described by Ebenezer Howard (1850–1928) in 1898, is one of the foundational ideas of modern city planning. Howard had witnessed the destructive impact of the indus...
Agnathia-otocephaly complex diagnosed by prenatal ultrasound: a case report

Agnathia-otocephaly complex (AOC) is a rare and complex craniofacial malformation characterized by mandibular hypoplasia or agnathia, auricular fusion (synotia), and microstomia with oroglossal hypoplasia or aglossia. It can occur alone or in combination with forebrain anomalies and cardiac malformations and has an extremely poor prognosis. Here, we report a case of AOC diagnosed by systemic fetal screening at a gestational age of 25+4 weeks. Ultrasound revealed that the S-curve formed by the normal lower jaw and lower lip had disappeared, the lower jaw and mandible were invisible, the mouth was extremely small, and the oral fissure was "pinhole-shaped". There was a cone-shaped perioral bulge. Both ears were located in the front side of the neck, and the right foot was inverted. Excessive amniotic fluid was observed. The absence of a mandible was confirmed on X-ray examination after induced abortion. Specimen observation showed that the ear positions were extremely low, and both earlobes were connected in the front side of the neck. It was particularly challenging to identify the development of the mandible and locate auricles during prenatal ultrasound diagnosis, and the prenatal diagnosis of AOC was confirmed by combining two-dimensional and three-dimensional ultrasound in our current case.
The association of motoric cognitive risk with incident dementia and neuroimaging characteristics: The Atherosclerosis Risk in Communities Study.

Introduction Motoric cognitive risk (MCR), a clinical syndrome characterized by slow gait speed and subjective cognitive complaints, has been associated with dementia risk. The neuropathological features underlying MCR remain poorly understood. Methods The Atherosclerosis Risk in Communities (ARIC) community-based cohort study classified participants using standardized criteria as MCR+/- and mild cognitive impairment (MCI)+/- at study baseline (2011-2013). We examined the 5-year dementia risk and baseline brain structural/molecular abnormalities associated with MCR+ and MCI+ status. Results Of 5023 nondemented participants included, 204 were MCR+ and 1030 were MCI+. Both MCR+ and MCI+ participants demonstrated increased dementia risk. The pattern of structural brain abnormalities associated with MCR+ differed from that of MCI+. Whereas MCI+ was associated with comparatively smaller volumes in brain regions vulnerable to Alzheimer's disease pathology, MCR+ status was associated with smaller volumes in frontoparietal regions and greater white matter abnormalities. Discussion MCR may represent a predementia syndrome characterized by prominent white matter abnormalities and frontoparietal atrophy.
Adenovirus 5 vaccination elicits IL-27, which impairs CD4 and CD8 T cell functionality (VAC12P.1113)

In pre-clinical studies Ad26 has shown increased protective efficacy compared to Ad5. We hypothesize this is due, in part, to differences in phenotype and function of the elicited CD4 and CD8 T cell responses. Thus, our goal is to elucidate the phenotypic differences of the CD4 and CD8 T cell repertoire following Ad5 or Ad26 vaccination and the underlying mechanism. B6 mice vaccinated with Ad5 upregulate PD1 and Tim3 (p in vitro with Ad5 showed a four-fold increase on Il27 mRNA compared to Ad26 stimulated cells. Immunization of IL-27ra KO mice with Ad5 resulted in downregulation of IL-10 (p
A human anti-insulin IgG autoantibody apparently arises through clonal selection from an insulin-specific "germ-line" natural antibody template. Analysis by V gene segment reassortment and site-directed mutagenesis

We analyzed the structural correlates underlying the insulin-dependent selection of the specific anti-insulin IgG1 kappa mAb13-producing cell clone, derived from a patient with insulin-dependent diabetes mellitus treated with recombinant human insulin. First, we cloned the germ-line genes that putatively gave rise to the expressed VH and V kappa segments and used them to generate the full (unmutated) "germ-line revertant" of the "wild-type" (somatically mutated) mAb13, using recombinant PCR methods and an in vitro human C gamma 1 and C kappa expression system. The full "germ-line revertant" bound insulin specifically and in a dose-saturable fashion, but with a relative avidity (AVrel) more than three-fold lower than that of its wild-type counterpart (Avrel, 1.69 x 10(-8) vs 4.91 x 10(-9) g/microliters). Second, we established, by reassorting wild-type and germ-line revertant forms of the mAb13 VH and V kappa segments, that the increased Avrel for insulin of mAb13 when compared with its full "germ-line revertant" counterpart was entirely dependent on the mutations in the VH not those in the V kappa chain. Third, we determined, by site-directed mutagenesis experiments, that of the three mutations in the mAb13 VH segment (Ser-->Gly, Ser-->Thr, and Ser-->Arg at positions 31, 56, and 58, respectively), only Arg58 was crucial in increasing the mAb13 Avrel (from 1.44 x 10(-8) to 5.14 x 10(-9) g/microliters) and affinity (Kd, from 189 to 59 nM) for insulin. The affinity enhancement mediated by the VH segment Arg58 residue reflected about a threefold decrease in dissociation rate constant (Koff, from 4.92 x 10(-3) to 1.54 x 10(-3) s-1) but not an increase in association rate constant (Kon, from 2.60 x 10(4) to 2.61 x 10(4) M-1 s-1), and it contrasted with the complete loss of insulin binding resulting from the substitution of the VH segment Asn52 by Lys. The present findings suggest that human insulin, a self Ag, has the potential to recruit a natural autoantibody-producing cell precursor expressing a specific surface receptor for Ag in unmutated configuration, and drive it through affinity maturation. They also show that binding of insulin by such a receptor can be enhanced or completely abrogated by a single amino acid change.
Shape-based interpolation of porous and tortuous binary objects

This paper presents a feature-guided approach for shape-based interpolation of porous and tortuous binary objects. The feature points derived from the boundaries of the candidate source objects are matched non-linearly. The intermediate objects are obtained by appropriately blending the warped source objects. A robust outlier-rejecting, non-linear point matching algorithm based on thin-plate splines is used for establishing the feature correspondence. The proposed scheme correctly handles objects with holes, large offsets and drastic invaginations. Preliminary results suggest that this approach could be used to significantly enhance the sparse Talairach-Tournoux brain atlas.
Orthogonal transforms for digital signal processing

A tutorial-review paper on discrete orthogonal transforms and their applications in digital signal and image (both monochrome and color) processing is presented. Various transforms such as discrete Fourier, discrete cosine, Walsh-Hadamard, slant, Haar, discrete linear basis, Hadamard-Haar, rapid, lower triangular, generalized Haar, slant Haar and Karhunen-Loeve are defined and developed. Pertinent properties of these transforms such as power spectra, cyclic and dyadic convolution and correlation are outlined. Efficient algorithms for fast implementation of these transforms based on matrix partitioning or matrix factoring are presented. The application of these transforms in speech and image processing, spectral analysis, digital filtering (linear, nonlinear, optimal and suboptimal), nonlinear systems analysis, spectrography, digital holography, industrial testing, spectrometric imaging, feature selection, and patter recognition is presented. The utility and effectiveness of these transforms are evaluated in terms of some standard performance criteria such as computational complexity, variance distribution, mean-square error, correlated rms error, rate distortion, data compression, classification error, and digital hardware realization.
The Chicago School's Foundation is Flawed: Antitrust Protects Consumers, Not Efficiency

Chicago School antitrust policy rests on the premise that the purpose of the antitrust laws is to promote economic efficiency. That foundation is flawed. The fundamental goal of antitrust law is to protect consumers. This essay defines the relevant economic concepts, summarizes the legislative histories, and analyzes recent case law. All these factors indicate that the ultimate goal of antitrust is not to increase the total wealth of society, but to protect consumers from behavior that deprives them of the benefits of competition and transfers their wealth to firms with market power. When conduct presents a conflict between the welfare of consumers and total welfare (e.g., a merger that raises prices but reduces costs), no court in recent years has chosen economic efficiency over consumer protection. For a more extensive discussion of these issues, see The Fundamental Goal of Antitrust: Protecting Consumers, Not Increasing Efficiency, 84 Notre Dame L. Rev. 191 (2008), http://ssrn.com/abstract=1113927
Prostaglandin endoperoxide synthase. The aspirin acetylation region.

Aspirin selectively acetylates Ser-530 of prostaglandin endoperoxide (PGH) synthase-1. This causes inactivation of the cyclooxygenase activity of the enzyme, but does not appreciably affect its peroxidase activity. Although the aspirin-acetylated enzyme is inactive, we found that PGH synthase-1 in which Ser-530 had been replaced with an alanine was catalytically active; accordingly, we proposed that aspirin inhibits cyclooxygenase activity by placing a larger than normal side chain at position 530 thereby interfering with arachidonate binding (DeWitt, D.L., El-Harith, E. A., Kraemer, S. A., Andrews, M. J., Yao, E. F., Armstrong, R. L., and Smith, W. L. (1990) J. Biol. Chem. 265, 5192-5198). As a further test of this hypothesis we have used site-directed mutagenesis and transient expression in cos-1 cells to prepare and characterize five additional substitutions of Ser-530. Consistent with our proposal, the presence of amino acids with bulky side chains at position 530 inhibited cyclooxygenase activity and decreased the apparent affinity of the enzyme for arachidonate. In related work, we characterized a series of mutant PGH synthases-1 having substitutions at residues adjoining Ser-530, including Phe-529, Leu-531, Lys-532, and Gly-533, in order to evaluate the contributions of each residue to cyclooxygenase catalysis. The most significant conclusion of this part of the study is that residues 529-533 all are important for the peroxidase activity as well as the cyclooxygenase activity of PGH synthase-1. Phe-529, in particular, was found to be critical for PGH synthase-1 structure and catalysis; some substitutions at this position led to the production of proteins lacking about 100 amino acids from their COOH termini.
Differential Staining of Bacteria: Capsule Stain

Bacterial capsules are composed of high-molecular-weight polysaccharides and/or polypeptides, and are associated with virulence and biofilm formation. Unfortunately, capsules do not stain well with crystal violet, methylene blue, or other simple stains. This unit describes two methods of capsule staining. The first is a wet-mount method using india ink; the capsule is visualized as a refractile zone surrounding a cell. The second is a direct-staining dry-mount method that precipitates copper sulfate and leaves the capsule as a pale blue zone. Both methods are easily performed within approximately 5 min.
SUSTAINABLE FOOD SYSTEMS AT URBAN PUBLIC UNIVERSITIES: A SURVEY OF U‐21 UNIVERSITIES

Urban communities are challenged by the conventional food system in diverse ways. To mitigate these challenges, a growing sustainable food system (SFS) movement mobilizes existing resources—includi...
Tuberous Sclerosis Complex: Perioperative Considerations

ABSTRACT Background: Tuberous sclerosis complex (TSC), also known as Bourneville disease, is an inherited, progressive neurocutaneous disorder characterized by the potential for hamartoma formation throughout the body. TSC is an autosomal dominant genetic disorder, but more than two-thirds of cases are sporadic. Methods: Clinical manifestations and treatment options are discussed. Both surgical and anesthetic perioperative considerations are described in this review. Results: Routine monitoring is appropriate for minor surgical procedures for patients with TSC who have mild disease manifestations. More extensive monitoring is indicated for major procedures that have the potential for significant blood loss and for patients with more severe pathology. Postoperatively, TSC patients should be admitted for monitoring and treatment after more extensive procedures or if significant organ dysfunction occurs. Postoperative complications, which may be related to either the surgery or the TSC pathology itself, may ...
Separate LTM and STM systems

This study investigated the effects of a previously learned item (LTM) and a newly learned item (STM) on the growth of within list proactive inhibition. It is shown that an item in LTM has a different effect on the within list PI than does an item in STM, thus supporting a dual theory of memory.
Solderability and Surface Mounting

In the last decade through‐hole mounting to printed wiring boards has matured and people now have the tools to diagnose and correct any solderability problems which might arise. Such is not the case with surface mount soldering technology. In surface mount the connections are smaller and are often hidden from view. Therefore when a solderability problem does occur it may never be known until the assembly fails. The solution to the situation is to understand the nature of the problems and provide assurance that they will not occur during assembly soldering. This paper is structured in two parts. The first details the types of solderability problems unique to surface mounting. Examples of these problems will be shown and discussed with reference to solder joint life. The second part of the paper discusses the solderability testing of surface mount devices and printed wiring boards intended for surface mounting. This discussion will concentrate on the new quantitative solderability test methods being developed in this company's laboratory for leadless devices and printed wiring boards. As part of this development, new solderability criteria have been defined which reflect the unique problems associated with surface mounting.
Monologger: visualizing engagement in doctor-patient conversation

Monologger is a tool that helps doctors become more empathic communicators by visualizing clinical conversations between doctors and patients. Monologger analyzes medical transcripts and provides feedback on clinicians' conversation patterns in an efficient, report card-like visual format for use in training and clinical settings.
Three-dimensional structure of echistatin and dynamics of the active site.

The snake venom protein echistatin contains the cell recognition sequence Arg-Gly-Asp and is a potent inhibitor of platelet aggregation. The three-dimensional structure of echistatin and the dynamics of the active RGD site are presented. A set of structures was determined using the Distance Geometry method and subsequently refined by Molecular Dynamics and energy minimization. Disulfide pairings are suggested, based on violations of experimental constraints. The structures satisfy 230 interresidue distance constraints, derived from nuclear Overhauser effect measurements, five hydrogen-bonding constraints, and 21 torsional constraints from vicinal spin-spin coupling constants. The segment from Gly5 to Cys20 and from Asp30 to Asn42 has a well-defined conformation and the Arg-Gly-Asp sequence, which adopts a turn-like structure, is located at the apex of a nine-residue loop connecting the two strands of a distorted β-sheet. The mobility of the Arg-Gly-Asp site has been quantitatively characterized by 15N relaxation measurements. The overall correlation time of echistatin was determined from fluorescence measurements, and was used in a model-free analysis to determine internal motional parameters. The active site has order parameters of 0.3–0.5, i.e., among the smallest values ever observed at the active site of a protein. Correlation of the flexible region of the protein as characterized by relaxation experiments and the NMR solution structures was made by calculating generalized order parameters from the ensemble of three-dimensional structures. The motion of the RGD site detected experimentally is more extensive than a simple RGD loop ‘wagging’ motional model, suggested by an examination of superposed solution structures.
Left ventricular papillary muscles. Description of the normal and a survey of conditions causing them to be abnormal.

The left ventricular papillary muscles appear to be the last portions of the heart to be perfused by coronary arterial blood. As a consequence they are sensitive anatomic markers of myocardial ischemia. Foci of necrosis or fibrosis therefore are commonly seen in these structures, particularly the posteromedial papillary muscle, which has a poorer blood supply than does the anterolateral muscle. Coronary arterial luminal narrowing is the most common cause of necrosis or fibrosis of the left ventricular papillary muscles. Other conditions, all associated with inadequate cardiac output, which may produce these lesions include left ventricular outflow tract obstruction, especially that resulting from congenitally malformed aortic valves, acute valvular regurgitation (infective endocarditis), various cardiomyopathies, and primary endocardial fibroelastosis with or without anomalous origin of one or both coronary arteries from the pulmonary trunk. Various infiltrative diseases, including inflammation (Aschoff b...
A Joint Association Test for Multiple SNPs in Genetic Case-Control Studies

For a dense set of genetic markers such as single nucleotide polymorphisms (SNPs) on high linkage disequilibrium within a small candidate region, a haplotype-based approach for testing association between a disease phenotype and the set of markers is attractive in reducing the data complexity and increasing the statistical power. However, due to unknown status of the underlying disease variant, a comprehensive association test may require consideration of various combinations of the SNPs, which often leads to severe multiple testing problems. In this paper, we propose a latent variable approach to test for association of multiple tightly linked SNPs in case-control studies. First, we introduce a latent variable into the penetrance model to characterize a putative disease susceptible locus (DSL) that may consist of a marker allele, a haplotype from a subset of the markers, or an allele at a putative locus between the markers. Next, through using of a retrospective likelihood to adjust for the case-control sampling ascertainment and appropriately handle the Hardy-Weinberg equilibrium constraint, we develop an expectation-maximization (EM)-based algorithm to fit the penetrance model and estimate the joint haplotype frequencies of the DSL and markers simultaneously. With the latent variable to describe a flexible role of the DSL, the likelihood ratio statistic can then provide a joint association test for the set of markers without requiring an adjustment for testing of multiple haplotypes. Our simulation results also reveal that the latent variable approach may have improved power under certain scenarios comparing with classical haplotype association methods.
Low temperature x-ray diffraction study of stage 1 graphite-FeCl3

Abstract The temperature dependence of the (00l) X-ray reflections in graphite-FeCl3 is reported. The c-axis unit cell, Ic, shows a large expansion with increasing temperature, associated with a large relative expansion of the Fe-Cl interplanar distances and a smaller expansion of the graphite-intercalant interplanar distances. The expansion of the Fe-Cl interlayer distance in the stage 1 graphite-FeCl3 compound is in good agreement with that of pristine FeCl3. Within experimental accuracy, no changes in Ic were observed in the temperature range where magnetic transitions have been reported.