cssi/SciSciGPT-SciSciNet huggingface dataset:
A key role for allostatic overload in ASD and other disorders. Commentary on “An integrative model of autism spectrum disorder: ASD as a neurobiological disorder of experienced environmental deprivation, early life stress, and allostatic overload” by William M. Singletary, MD

The brain is the central organ of perceiving, responding, and adapting to life experiences, and it communicates in a reciprocal manner with the rest of the body via autonomic, neuroendocrine, metabolic, and immune mediators that are essential for adaptation to stressful experiences by a process referred to as “allostasis.” Singletary reminds us that the impaired ability of the ASD-prone infant to respond to the “serve and return” interaction with parents leads to a state of frustration and chronic stress resulting in the cumulative “wear and tear” of adapting to chronic stress, called “allostatic overload,” that worsens the trajectory of the disorder and helps shape brain architecture, behavior, and systemic physiology. Singletary says that successful treatment must recognize the deviation from a normal developmental course as early as possible and intervene to redirect it. He cites examples in children where this has made a huge difference. Thus, the epigenetic plasticity of the brain is key to the devel...
Homology between the female paraurethral (Skene's) glands and the prostate. Immunohistochemical demonstration

Homology between female paraurethral glands and the prostate has often been suggested. A means was developed that would lend histochemical support to this hypothesis. Female urethra from autopsy and surgical material was serially sectioned and studied in 19 patients ranging in age from newborn to 86 years. Paraurethral glands were identified in 18 of these. The tissue was stained with antibodies to prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAcPh) using the peroxidase-antiperoxidase method. Of those cases in which paraurethral glands were seen, 83% were positive for PSA and 67% for PSAcPh. Intensity of staining was semi-quantitatively evaluated. In addition, intraluminal secretions and urethral columnar epithelium showed positive enzyme and antigen staining. There was no discernible variation of glandular development or pattern of staining with patient age. This study demonstrates the homologous nature of the female paraurethral glands and the prostate and supports speculations about functional similarity.
Determinants of Consumer Deviance

Previous psychological research in the consumer deviance area has been largely of the "trait" variety. This study tested the predictive importance of both individually and situationally based measures on the incidence of deviant consumer behavior. The results show that while both types of variables are important, situationally determined factors offer the most vitality as predictive tools.
Abstract P072: Adipocyte AT2 Receptor Suppresses UCP1 Transcription and Thereby Resting Metabolic Rate

The renin-angiotensin system (RAS) contributes to energy balance through opposing actions in the brain and periphery. We hypothesize that tissue- and receptor-specific RAS modulation may represent a novel therapeutic approach to obesity. Transgenic “sRA” mice exhibit brain-specific RAS hyperactivity through expression of human renin in neurons (synapsin promoter) and human angiotensinogen via its own promoter. Previously we documented that sRA mice exhibit a suppressed circulating RAS, and an elevated resting metabolic rate (RMR) that is sensitive to replacement of circulating angiotensin II or the AT 2 receptor (AT 2 R) agonist, CGP-42112a (CGP, 100 ng/kg/min, s.c.). sRA mice exhibit a robust and specific elevation in uncoupling protein-1 (UCP1) expression and glucose uptake in inguinal white adipose tissue (iWAT). Chronic infusion of the AT 2 R agonist, CGP-42112a (CGP) into sRA mice increased weight gain and normalized RMR and inguinal fat expression of UCP1, but had no effect on food intake or digestive efficiency. RMR suppression by CGP was not mediated through attenuation of adipose sympathetic nervous activity (SNA, measured via multifiber nerve recordings), leading to the hypothesis that AT 2 R action on the adipocyte suppresses adipose sensitivity to SNA. Cultured primary mouse adipocytes were isolated from the iWAT, and norepinephrine (NE, 1 nM) treatment induced UCP1 mRNA (597 -fold of vehicle, P 2 R also prevented the NE-induced increase in UCP1 mRNA. NE additionally significantly increased lipolysis by adipocytes (measured via free glycerol in the media; P 2 R activation had no effect (vehicle= 15.9 ug/mL; NE= 70.8 ug/mL; NE + CGP=64.7 ug/mL). These data support a suppressive action of AT 2 R upon RMR that is mediated specifically through the suppression of UCP1 expression, but not its activation by lipolysis, within subcutaneous adipocytes. Ongoing studies are examining the transcriptional regulation of UCP1 by adipose AT 2 R activation.
Hemangiomas and Vascular Malformations of Infancy and Childhood

Confusing nomenclature has impeded the understanding, diagnosis, and therapy of vascular anomalies of childhood. A biologic classification of vascular birthmarks encompasses phYSical findings, clinical behavior, and cellular kinetics. Hemangioma is a tumor, characterized by rapid cell turnover and invariable spontaneous involution. In contrast, vascular malformations are nonneoplastic anomalies of vascular morphogenesis.
Canadian National Breast Screening Study (CNBSS): Mortality (MOR), survival (SUR), and mammographic screening (MS).

e12614 Background: Among randomized trials on MS for breast cancer (BC), CNBSS is most controversial. Original CNBBS publications (CMAJ, 1992) suggest that MS may be detrimental to women age 40-49 ...
Octreotide LAR (OCT-L) among elderly patients with stage IV neuroendocrine tumors (NETs): A survival analysis of SEER-Medicare data.

4112 Background: OCT-L is approved in the US for the management of secretory syndromes among patients with NETs. Two placebo-controlled studies have recently demonstrated that somatostatin analogue...
Vibrational Sum Frequency Generation (SFG) Analysis of Ferroelectric Response of PVDF-Based Copolymer and Terpolymer

In poly(vinylidene difluoride) (PVDF)-based polymers, the alignment of dipoles of the crystalline β phase with all-trans conformations is responsible for ferroelectricity; however, there is a lack of direct spectroscopic evidence for this phenomenon. We report in situ monitoring of the molecular orientations associated with ferroelectric responses of PVDF-based polymers using vibrational sum frequency generation (SFG) spectroscopy. The orientation of CH2 groups with respect to the −(CH2CF2)n– chain axis of the poled β domains in a PVDF copolymer was determined from the SFG dependence of an uniaxially aligned sample on the laser polarization and azimuthal angle. The relative intensities of CH2 symmetric and asymmetric stretch modes as well as their total intensities revealed the transformation of the all-trans conformation domains during the electrical poling of PVDF based co- and terpolymer films.
Complications of Peripheral Venous Access Devices: Prevention, Detection, and Recovery Strategies

Most hospitalized patients have placement of a peripheral venous access device, either a short peripheral catheter or a peripherally inserted central catheter. Compared with central venous catheters that are not peripherally inserted, the other 2 types are generally perceived by health care providers as safer and less complicated to manage, and less emphasis is placed on the prevention and management of complications. Expertise of nurses in inserting, managing, and removing these devices may reduce the likelihood of complications, and increased recognition of complications associated with use of the devices is important to ensure continued improvements in the safety, quality, and efficiency of health care. Complications associated with short peripheral catheters and peripherally inserted central catheters include tourniquet retention, tubing and catheter misconnections, phlebitis, air embolism, device fragment embolization, and inadvertent discharge with a retained peripheral venous access device. Integration of prevention, detection, and recovery strategies into personal nursing practice promotes the quality and safety of health care delivery.
Thirty-Day Hospital Readmission After Restorative Proctocolectomy and Ileal Pouch Anal Anastomosis for Chronic Ulcerative Colitis at a High-Volume Center.

Ileal pouch anal anastomosis (IPAA) is associated with a high 30-day hospital readmission rate. Risk factors and etiology of readmission remain poorly defined. We sought to determine the 30-day hospital readmission rate following IPAA at a high-volume center and identify any modifiable perioperative factors. A retrospective review of all patients undergoing two- or three-stage IPAA for chronic ulcerative colitis at our institution between 2002 and 2013 was performed. Analysis was performed on rate of readmission, readmission diagnosis, intervention performed upon readmission, and risk factors for readmission. Thirty-day primary and secondary readmission rates after IPAA were 20.3% (n = 185) and 2.1% (n = 19), respectively. The leading etiologies for readmission included partial small bowel obstruction/ileus (n = 52, 21.9%), pelvic sepsis (n = 43, 18.1%), dehydration (n = 42, 17.7%), and venous thromboembolism (n = 31, 13.1%). While the majority of readmissions were managed medically (n = 119, 65.4%), 19.2% (n = 35) required radiologic intervention and 15.3% (n = 28) required a return to the operating room. On univariate analysis, younger age (p = 0.03) and female sex (p = 0.04) had a significantly increased risk of readmission. On multivariable analysis, BMI ≥ 30 (OR 0.51; 95% CI, 0.25–0.97, p = 0.04) was protective of readmission. Thirty-day hospital readmission following IPAA remains a common problem. Preventable etiologies of readmission include dehydration and venous thromboembolism (VTE). Future quality improvement efforts should focus on education regarding stoma output and extended VTE prophylaxis to decrease hospital readmission rates following IPAA.
Multivariable analysis of the association between electrolyte disturbances and mortality in cats.

ObjectivesElectrolyte disorders have been individually associated with mortality in small populations of cats with specific conditions, but the associations and interactions between electrolyte dis...
Optical Conductivity and Spatial Inhomogeneity in Cuprate Superconductors

We present an overview of the microwave and millimeter wave response of cuprate superconductors, emphasizing two basic types of low-frequency optical conductivity, σ( ω), that these materials exhibit. The first type, exemplified by ultra-pure and stoichiometric YBa2Cu3O7−δ (YBCO) single crystals, is well described by a single component originating from the Drude response of thermal quasiparticles. In other cuprate systems that have been studied σ( ω)has an additional component beyond the quasiparticle contribution, also centered at ω = 0. The existence of this peak has not been widely appreciated because most of its spectral weight lies in the “terahertz gap” between microwave and infrared regimes. After reviewing the evidence for this spectral feature in a wide variety of cuprate compounds, we trace its origin to quenched spatial variation in the superfluid density, ρs. We show that the trends in optical conductivity as a function of hole carrier concentration in a series of Bi2Sr2Ca1−yDyyCu2O8+δ (BSCCO) thin films can be understood by adding a component generated by spatial inhomogeneity to the quasiparticle Drude peak. We conclude by discussing the role of optical conductivity measurements in investigating the existence, origin, and importance of inhomogeneity in cuprate superconductors.
Toward a science of history.

Abstract The scientific status of History was compared to other sciences in the critical areas event selection, investigative operations, and theory construction. First, in terms of events studied, history is regarded as a quasi-scientific study of past events. However, viewed from the science of behavior's perspective of what historians actually do, history becomes a study of current records. As a study of currently existing records, not the non-existent past, history has potential to become a science. Second, like other scientists, historians may undertake manipulative investigations: they can locate the presence and absence of a condition in records and thereby determine its relation to other recorded phenomena. A limitation has been the lack of quantification that results from emphasis on the uniqueness of things rather than on their communality. Scientific training would facilitate viewing similar things as instances of a larger class that could be counted. Another limitation that cannot be easily overcome is the inability to produce raw data. This limitation has created problems in theoretical practices, the third area of comparison, because theoretical constructions have frequently been substituted for missing data. This problem too could be reduced through scientific training, particularly in other behavior sciences. An authentic science of history is possible.
Vegetable Individuality: The Organismal Self

Organismal unity has always been a third thing, between physics and mind. In the twentieth century, biologists proposed regulation and replication, reflecting nutrition and reproduction, as defining features of life. Recent discoveries show that the two categories yield different answers when we try to identify individuals. The mechanical philosophy and Darwinian population thinking lead to pragmatic, non-exclusive and context dependent definitions of organisms: a biological nominalism. Such arbitrary formal causes create a departure from Aristotle. The intertwined character of organisms makes linguistic and conceptual clarity important. Godfrey-Smith’s Darwinian populations and Millikan’s historical kinds provide insights into how to find linguistic and conceptual clarity amidst the overlapping processes.
Third Order Mock Theta Functions: Partial Fraction Expansions

Partial fractions arise again and again in the Lost Notebook. Indeed, we have already seen instances of partial fractions (e.g. [32, p. 271]) that specialize to mock theta functions. On pages 2 and 17 in his Lost Notebook [232], Ramanujan recorded four identities involving the rank generating function. Of course, Ramanujan would not have used this terminology, because the rank of a partition was not defined until 1944 by F.J. Dyson [130]. He defined the rank of a partition to be the largest part minus the number of parts.
The infection of its insect vector by bacterial plant pathogen "Candidatus Liberibacter solanacearum" is associated with altered vector physiology.

Abstract Many bacterial and viral plant pathogens are transmitted by insect vectors, and pathogen-mediated alterations of plant physiology often influence insect vector behavior and fitness. It remains largely unknown for most plant pathogens whether, and how, they might directly alter the physiology of their insect vectors in ways that promote pathogen transmission. Here we examined whether the presence of “Candidatus Liberibacter solanacearum” (“Ca. L. solanacearum”), an obligate bacterial pathogen of plants and of its psyllid vector alters the physiochemical environment within its insect vector, the potato psyllid (Bactericera cockerelli). Microelectrodes were used to measure the local pH and oxygen tension within the abdomen of “Ca. L. solanacearum”-free psyllids and those infected with “Ca. L. solanacearum”. The hemolymph of infected psyllids had higher pH at 9.09 ± 0.12, compared to “Ca. L. solanacearum”-free psyllids (8.32 ± 0.11) and a lower oxygen tension of 33.99% vs. 67.83%, respectively. The physicochemical conditions inside “Ca. L. solanacearum”-free and –infected psyllids body differed significantly with the infected psyllids having a higher hemolymph pH and lower oxygen tension than “Ca. L. solanacearum”-free psyllids. Notably, the bacterial titer increased under conditions of higher pH and lower oxygen tension values. This suggests that the vector’s physiology is altered by the presence of the pathogen, potentially, resulting in a more conducive environment for “Ca. L. solanacearum” survival and subsequent transmission.
The Use of Precision-Cut Kidney Slices (PCKS) to Investigate Intracellular Calcium Signaling and Contraction in Small Renal Arteries of Heathy and Diabetic Nephropathy Rats

Diabetic nephropathy (DN) is a leading cause of mortality and morbidity in diabetic patients. Hyperglycemia-induced metabolic stimuli and hemodynamic factors including elevated glomerular capillary...
Emotion regulation difficulties, but not negative urgency, are associated with attention-deficit/hyperactivity disorder and eating disorder symptoms in undergraduate students

Abstract Eating disorders and attention deficit/hyperactivity disorder (ADHD) are highly comorbid. The majority of research on this comorbidity has focused on impulsivity, which is a shared vulnerability between ADHD and eating disorders characterized by binge eating. Less is known about which shared factors may contribute to the co-occurrence of other eating disorders (i.e., anorexia nervosa, restricting subtype) and ADHD. Furthermore, little research has focused on other potential overlapping vulnerabilities, though deficits in emotion regulation have been implicated as an additional shared vulnerability. The current study (N = 306 undergraduate students) uses path analysis to examine if emotion regulation difficulties and negative urgency (i.e., impulsivity during negative mood state) are unique or shared vulnerabilities for ADHD symptoms (inattention, hyperactivity-impulsivity) and eating disorder symptoms (bulimic symptoms, drive for thinness). Emotion regulation difficulties were uniquely associated with all dimensions of ADHD and eating disorder symptoms, and negative urgency was uniquely associated with global eating disorder symptoms, bulimic symptoms, and drive for thinness. These results suggest that emotion regulation difficulties are a shared vulnerability factor for the development of diverse presentations of ADHD and eating disorder symptoms, and may be an important prevention target. Additionally, our results support a unique relationship between negative urgency and drive for thinness. Future research should examine these associations prospectively and experimentally to determine directionality and inform preventative interventions for ADHD and eating disorders.
Demon: Momentum Decay for Improved Neural Network Training

Momentum is a popular technique in deep learning for gradient-based optimizers. We propose a decaying momentum (Demon) rule, motivated by decaying the total contribution of a gradient to all future updates. Applying Demon to Adam leads to significantly improved training, notably competitive to momentum SGD with learning rate decay, even in settings in which adaptive methods are typically non-competitive. Similarly, applying Demon to momentum SGD improves over momentum SGD with learning rate decay in most cases. Notably, Demon momentum SGD is observed to be significantly less sensitive to parameter tuning than momentum SGD with learning rate decay schedule, critical to training neural networks in practice. Results are demonstrated across a variety of settings and architectures, including image classification, generative models, and language models. Demon is easy to implement and tune, and incurs limited extra computational overhead, compared to the vanilla counterparts. Code is readily available.
CD33 directed bispecific antibodies in acute myeloid leukemia

Despite the approval of a number of new targeted therapies for acute myeloid leukemia (AML), median overall survival still remains poor, ranging from 12 to 18 months in most patients. Based on the success of blinatumomab, the CD19-targeted bispecific antibody for the treatment of acute lymphoblastic leukemia, the development of several CD33-targeted bispecific antibodies for AML are being investigated in clinical trials. In this review article of CD33-targeted bispecific antibodies, we describe the rationale for targeting CD3 x CD33, summarize the data from four ongoing phase 1 studies, review the major toxicity associated with CD33-targeted bispecific antibody therapy of cytokine release syndrome (CRS) and steps to mitigate CRS, and describe possible mechanisms of resistance to CD33-targeted bispecific antibody therapy. Future development to try to improve outcomes include combination therapies to reduce the tumor burden prior to starting treatment, combining with immune checkpoint inhibition therapy such as anti-PD-1/PDL1 antibodies, and the use of second generation bispecific antibodies that target two different antigens and recruit other effector cells such as nature killer cells and macrophages.
Partnering for Success: Leveraging Legislation for Transitioning Students with Intellectual Disabilities

Students with intellectual and developmental disabilities (IDD) are incredibly vulnerable to poor post-school outcomes. Two mandates, the Higher Education Opportunity Act and Workforce Innovation and Opportunity Act, have emerged that may provide avenues to counter the discrepancy between the desire for career and college paths and actualization of employment and enrollment. The authors explore these legislative acts, their impact on transition services for students with IDD, and how school personnel can collaborate to create family, school, and community partnerships. Based on these acts, a practice framework, and the unique transition needs of students with IDD, practice recommendations are provided. Specific strategies for promoting application of these laws in the school setting are offered. Special attention is given to the partnership between special educators and school psychologists to help them navigate the legal implications for students with IDD and their families.
Role of Microstructure on the Potential of MAX and MAB Phases and Their Derivative-Based Composites: A Review

In this brief review, I have classified MAX phase-based composites according to connectivity patterns. In type-I composites, MAX phases act as reinforcement in metal, ceramic, or polymer matrix composites to form 3-0 composites. In these composites, metal or ceramic or polymer forms the main matrix and the MAX phases are dispersed in the structure as reinforcements. In type-II composites, MAX phase particulates are bonded via a 3D network of metallic channel which cement the structure to form 3-0 composites. In type-III composites, MAX and metal for interpenetrating network with 3-3 connectivity. In type-IV composites, the MAX phase matrix can be also reinforced with ceramic additives to form composites with 0-3 connectivity. MAX phases can be oriented in different matrices to form 3-0 composites (Type-V). Composites with multiple layers of metal-MAX and metal can be designed with 3-0 connectivity (Type-VI). By reviewing the literature, the manufacturing method and properties of these different types of composites have been summarized. In addition, a case study has been presented to engineer the surface of Ti3AlC2 particles by etching. It is hypothesized that these engineered particles can be used for manufacturing next-generation MAX phase-based composites.
Contesting the Postwar City: Working-Class and Growth Politics in 1940s Milwaukee

In the decade and a half following the collapse of the Soviet Union and the end of the Cold War, research on American political history has shifted towards greater emphasis on the history of ‘conse...
Elements of Computer System Organization

Publisher Summary This chapter reviews the architecture and organization of computer systems in light of abstraction, naming, and layering. The systems perspective provides some new insights into the familiar concepts of software and hardware. It describes the three fundamental abstractions, a model for naming, and explains how names are used in computer systems. It discusses how a designer combines the abstractions, using names and layers, to create a typical computer system, presenting the file system as a concrete example of the use of naming and layering for the memory abstraction. Designers use layers and names in many other ways in computer systems. The chapter shows the typical organization of a computer system as three distinct layers. The bottom layer consists of hardware components, such as processors, memories, and communication links. The middle layer consists of a collection of software modules, called the operating system, that abstracts these hardware resources into a convenient application-programming interface. The hardware layer of a typical computer is constructed of modules that directly implement low-level versions of the three fundamental abstractions.
Modern Technology and the Flight from Architecture

As a graduate student at Duquesne University in the 1970s, I had the good fortune to study phenomenology and Continental philosophy of science with Lester Embree. In seminars that covered both the human and natural sciences I was exposed to philosophical issues and problems – primarily in the works of Alfred Schutz – that continue to shape and influence my research and teaching. When I asked Embree to direct my doctoral dissertation, he suggested I consider writing on a related field of studies that was then emerging in philosophy and other disciplines as arguably equal in importance to philosophy of science. After immersing myself in the works of Hans Jonas, Don Ihde, and Edward Ballard, I became convinced that the burgeoning philosophy of technology was in fact the logical outcome of my philosophical concerns, which had revolved around the occlusion of the lifeworld in the wake of the undeniable successes of the natural sciences since Galileo.
The State of Nutrition Education at US Medical Schools

Purpose. To assess the state of nutrition education at US medical schools and compare it with recommended instructional targets. Method. We surveyed all 133 US medical schools with a four-year curriculum about the extent and type of required nutrition education during the 2012/13 academic year. Results. Responses came from 121 institutions (91% response rate). Most US medical schools (86/121, 71%) fail to provide the recommended minimum 25 hours of nutrition education; 43 (36%) provide less than half that much. Nutrition instruction is still largely confined to preclinical courses, with an average of 14.3 hours occurring in this context. Less than half of all schools report teaching any nutrition in clinical practice; practice accounts for an average of only 4.7 hours overall. Seven of the 8 schools reporting at least 40 hours of nutrition instruction provided integrated courses together with clinical practice sessions. Conclusions. Many US medical schools still fail to prepare future physicians for everyday nutrition challenges in clinical practice. It cannot be a realistic expectation for physicians to effectively address obesity, diabetes, metabolic syndrome, hospital malnutrition, and many other conditions as long as they are not taught during medical school and residency training how to recognize and treat the nutritional root causes.
Altitude/Path-Angle Transitions in Fuel-Optimal Problems for Transport Aircraft

Altitude/path angle transitions to fuel-optimal, energy climb and descent paths are examined for subsonic transport aircraft. These transitions are termed boundary layers in singular perturbation theory, the framework used herein to simplify solutions to the state-Euler system. The energy climb and descent paths provide equilibrium or stationary points for the boundary Layer system, and thus for moderate transitions, presumed valid for the class of aircraft considered, the boundary layer system may be linearized. This simplification allows derivation of an explicit solution to the two-point boundary-value, boundary layer problem and, as a consequence, yields a nearly optimal control law, in feedback form, for the transitions. Numerical simulation results using the feedback control law are presented for a Boeing 737 airframe (NASA-ATOPS Vehicle) employing twin JT8D-7-7A engines.
Amicus Curiae Brief of Administrative Law Scholars in Support of the Petitions Mortgage Bankers Association v. Harris

In Mortgage Bankers Association v. Harris, the D.C. Circuit held that an agency can not change an interpretation of one of its rules without engaging in notice and comment rulemaking. In this amicus brief filed on behalf of 72 professors of administrative law, Professors Pierce, Morrison, and Glicksman argue that the Supreme Court should grant cert. in the case and reverse the D.C. Circuit.
Acute Decompensated Cardiac Failure

Heart failure (HF) is a serious condition affecting an estimated two million Americans and is a common reason for hospitalization. The prognosis of patients admitted to hospital with HF is poor with up to 64 % being re-admitted within the first 90 days after discharge and with a 1 year mortality approximating 20 % [1]. HF can present in patients without previously recognized cardiac dysfunction or as the acute decompensation of chronic congestive HF. Acute Decompensated Heart Failure (ADHF) refers broadly to new or worsening of signs and symptoms of HF that is progressing rapidly, whereby unscheduled medical care or hospital evaluation is necessary. A number of national registries have been developed in the last few decades which have provided invaluable epidemiological and clinical information to help guide the management of patients with ADHF. Currently the total number of patients in the Acute Decompensated Heart Failure National Registry (ADHERE), [2] the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) [3] and the EuroHeart Failure Survey (EHFS) [4] exceeds 250,000. The mean age of the patients in these registries is around 72 years with 50 % being women. Evidence of mild or no impairment of systolic function was found in approximately 45 % of patients. The most common co-morbid conditions were hypertension, coronary artery disease, chronic obstructive pulmonary disease (COPD) and diabetes. In-hospital mortality was approximately 4 % and the median hospital length of stay was 4.5 days.
Gene Expression Profiling in Alzheimer's Disease Brain Microvessels

The enigma that is Alzheimer's disease (AD) continues to present daunting challenges for effective therapeutic intervention. The lack of disease-modifying therapies may, in part, be attributable to the narrow research focus employed to understand this complex disease. Most studies into disease pathogenesis are based on a priori assumptions about the role of AD lesion-associated proteins such as amyloid-β and tau. However, the complex disease processes at work may not be amenable to single-target therapeutic approaches. Genome-wide expression studies provide an unbiased approach for investigating the pathogenesis of complex diseases like AD. A growing literature suggests a role for cerebrovascular contributions to the pathogenesis of AD. The objective of the current study is to examine human brain microvessels isolated from AD patients and controls by microarray analysis. Differentially expressed genes with more than 2-fold change are used for further data analysis. Gene ontology analysis and pathway analysis algorithms within GeneSpringGX are employed to understand the regulatory networks of differentially expressed genes. Twelve matched pairs of AD and control brain microvessel samples are hybridized to Agilent Human 4 × 44 K arrays in replication. We document that more than 2,000 genes are differentially altered in AD microvessels and that a large number of these genes map to pathways associated with immune and inflammatory response, signal transduction, and nervous system development and function categories. These data may help elucidate heretofore unknown molecular alterations in the AD cerebromicrovasculature.
Process induced damages from various integrated circuit interconnection designs - limitations of antenna rule under practical integrated circuit layout practice

The accelerated process induced damage (PID) effect on MOS integrated circuit (IC) devices is observed depending on various IC interconnection line layout/design configurations related to non-gate transistor terminals - such as source, drain, well, and substrate. This phenomenon can occur even when the antenna sizes of the interconnection lines connected to each of the gate terminals (i.e. gate antennas) are small and meet the antenna rule. Without these various interconnection configurations to other terminals, no PID effect occurs. To analyze this phenomena in depth, a set of test structures is designed utilizing basic IC building block circuits - such as inverter, logic gates, registers and amplifiers - with small antennas connected to the specific circuit node(s) at various distances from each transistor. IC process induced charging is observed to activate transistors electrically and, hence, operates the circuits erratically. This phenomenon causes the accelerated PID effect. A set of selected examples of these test structures based on inverter circuits is presented. The test data show the accelerated PID effect on MOS transistors even with small gate antennas with a 5 0 to 1 antenna ratio.
A modified collagen gel dressing promotes angiogenesis in a preclinical swine model of chronic ischemic wounds

We recently performed proteomic characterization of a modified collagen gel (MCG) dressing and reported promising effects of the gel in healing full-thickness excisional wounds. In this work, we test the translational relevance of our aforesaid findings by testing the dressing in a swine model of chronic ischemic wounds recently reported by our laboratory. Full-thickness excisional wounds were established in the center of bipedicle ischemic skin flaps on the backs of animals. Ischemia was verified by laser Doppler imaging, and MCG was applied to the test group of wounds. Seven days post wounding, macrophage recruitment to the wound was significantly higher in MCG-treated ischemic wounds. In vitro, MCG up-regulated expression of Mrc-1 (a reparative M2 macrophage marker) and induced the expression of anti-inflammatory cytokine interleukin (IL)-10 and of fibroblast growth factor-basic (β-FGF). An increased expression of CCR2, an M2 macrophage marker, was noted in the macrophages from MCG treated wounds. Furthermore, analyses of wound tissues 7 days post wounding showed up-regulation of transforming growth factor-β, vascular endothelial growth factor, von Willebrand's factor, and collagen type I expression in MCG-treated ischemic wounds. At 21 days post wounding, MCG-treated ischemic wounds displayed higher abundance of proliferating endothelial cells that formed mature vascular structures and increased blood flow to the wound. Fibroblast count was markedly higher in MCG-treated ischemic wound-edge tissue. In addition, MCG-treated wound-edge tissues displayed higher abundance of mature collagen with increased collagen type I : III deposition. Taken together, MCG helped mount a more robust inflammatory response that resolved in a timely manner, followed by an enhanced proliferative phase, angiogenic outcome, and postwound tissue remodeling. Findings of the current study warrant clinical testing of MCG in a setting of ischemic chronic wounds.
The Number of Alleles That Can Be Maintained in a Finite Population

T has sometimes been suggested that the wild-type allele is not a single entity, I but rather a population of different isoalleles that are indistinguishable by any ordinary procedure. With hundreds of nucleotides, each presumably capable of base substitutions and with additional permutations possible through sequence rearrangements, gains, and losses, the number of possible gene states becomes astronomical. It is known that a single nucleotide substitution can have the most drastic consequences, but there are also mutations with very minute effects and there is the possibility that many are so small as to be undetectable. It is not the purpose of this article to discuss the plausibility of such a system of isoalleles, or the evidence for and against. Instead, we propose to examine some of the population consequences of such a system if it does exist. The probability seems great enough to warrant such an inquiry. If a large number of different states can arise by mutation, this doesn't necessarily mean that a large fraction of these would coexist in a single population. Some will be lost by random drift and others may be selectively disadvantageous. On the other hand, some may persist by being beneficial in heterozygous combinations. We shall consider three possibilities: ( 1 ) A system of selectively neutral isoalleles whose frequency in the population is determined by the mutation rate and by random drift. (2) A system of mutually heterotic alleles. ( 3 ) A mixture of heterotic and harmful mutants.
Pharmacogenetics of Tamoxifen: Who Should Undergo CYP2D6 Genetic Testing?

Many women with hormone receptor-positive breast cancer will receive tamoxifen at some point in their treatment course. Tamoxifen is biotransformed to the potent antiestrogen endoxifen almost exclusively through the cytochrome P450 (CYP) 2D6 isoform. Although prospective data are lacking, the balance of evidence available currently suggests that a single nucleotide polymorphism in the CYP2D6 gene, particularly the presence of 2 null alleles, predicts for reduced tamoxifen metabolism and possibly poorer outcome than expected in patients with a wild-type genotype. Studies evaluating the impact of genetic polymorphisms that result in CYP2D6 with reduced or no activity on long-term outcome have been mostly retrospective and conducted on archival tissues or those obtained previously in prospective studies of tamoxifen. Until data are available from retrospective examinations of the large prospective trials already conducted, or adequately powered prospective analyses, transforming this information into guidelines for individual patients remains challenging. The authors do not currently recommend routine testing for CYP2D6 genotype for making clinical decisions regarding tamoxifen. Use of concomitant strong or intermediate inhibitors of CYP2D6 should be avoided when alternate medications are available. Ongoing research is directed toward identifying other polymorphisms that may influence the efficacy and safety of tamoxifen, other hormonal agents, and chemotherapies used to treat breast cancer. The hope is that in the future, not only tumor-associated factors but also germ-line host genetics can be used to determine whether a woman should receive treatment, and with which specific agents, to prevent breast cancer recurrence or death or avoid drug-related toxicities.
Thymocyte Development in Early Growth Response Gene 1-Deficient Mice

Early growth response gene 1 (Egr1) codes for a transcriptional regulator that contains a zinc-finger DNA binding domain. Egr1 expression is induced by a variety of extracellular stimuli including TCR-ligand interactions. Its pattern of expression in the thymus and dependence on ERK activation have led to speculation that it has a role in T cell development, but the exact nature of this role has been undefined. To more clearly define the role of Egr1 in thymocyte development, we have analyzed thymocytes from Egr1-deficient mice. We find that thymuses from Egr1-deficient mice contain twice as many cells as age-matched controls, and the increase in thymocyte number is apparent at the early CD4/CD8 double negative stage of development. Subsequent maturation to the CD4/CD8 double positive stage and survival of the double positive cells both appear normal in Egr1-deficient animals. We also find that Egr1 promotes positive selection of both CD4 and CD8 single positive cells without playing a major role in negative selection. Egr1 influences positive selection by enhancing expression of the helix-loop-helix inhibitor Id3 and the anti-apoptosis molecule bcl-2. Thus, Egr1 translates developmental signals into appropriate changes in gene expression at multiple stages of thymocyte development.
ALK‐positive (2p23 rearranged) anaplastic large cell lymphoma with localization to the skin in a pediatric patient

Anaplastic large cell lymphoma (ALCL) either as primary cutaneous or nodal disease is rare in children and difficult to distinguish, which is important both prognostically and for treatment purposes. We present a case of anaplastic lymphoma kinase (ALK)+ skin-limited ALCL that highlights this challenge and draws attention to pitfalls in assessing ALK status. The patient was an 11-year old girl with a twice recurrent nodule on her right shoulder. Each biopsy revealed a deep infiltrate of atypical lymphocytes that expressed CD3, CD4, CD43, CD45RO and CD30. The initial biopsy was epithelial membrane antigen (EMA)+ with vague cytoplasmic ALK-1 positivity by immunohistochemistry, while the second biopsy was EMA+ and nuclear ALK-1+. Fluorescence in situ hybridization analysis for an ALK (2p23) rearrangement of the first specimen was negative, while an ALK gene rearrangement was present in the second specimen. Therefore, this case was treated as nodal ALCL, despite negative bone marrow and radiographic imaging studies. The patient was treated with combination chemotherapy and remains disease-free. Demonstration of nuclear ALK-positivity, ALK (2p23) gene rearrangement is suggestive of systemic ALCL. Without evidence of systemic disease, this case highlights challenges of skin-limited ALCL, whose clinical behavior as either cutaneous ALCL systemic ALCL may not be immediately apparent.
The pathogenesis of obesity: Stress and the brain-gut axis.

Energy balance, stress, and eating It has become fashionable to view the world through “stress-colored glasses” as new technology has enabled studies of molecular pathways and functional neuroimaging. The thesis of this review is that any challenge to the nutritional integrity of any form of life is the most important stressor and the ultimate stimulus for evolutionary adaptation. Although opinions might differ regarding the level of “evolutionary adaptation” of homo sapiens, it is fair to propose that among mammals, man has demonstrated the most advanced capacity for adaptation to nutritional challenges. Whereas ingestive behavior is quantitatively the most important contributor to positive energy balance, the focus of this review is on pathogenetic mechanisms related to ingestive behavior. Appetitive signals can be grossly categorized as central or peripheral, the latter being gastrointestinal- or adipose tissue–related. Lean body mass also contributes, but less prominently and only under extreme conditions. Ergostatic theory
A new approach to mathematical modeling of host-parasite systems

Abstract We propose a new approach to mathematical modeling of host-parasite systems by using partial differential equations where the degree of parasitism in a host is represented by a continuous variable p. This contrasts with the standard approach found in the literature of using a countable number of ordinary differential equations, one for each nonnegative integer, corresponding to the class of hosts having exactly that number of parasites. The new model bears some similarity with size-structured models of population dynamics. We specialize the model to a specific pair of helminth macroparasites infecting sea bass. We show that the model is well posed and we study its asymptotic behavior. Finally, we present results from some simulations.
Hydraulic Hybrid and Conventional Parcel Delivery Vehicles’ Measured Laboratory Fuel Economy on Targeted Drive Cycles

This research project compares laboratory-measured fuel economy of a medium-duty diesel powered hydraulic hybrid vehicle drivetrain to both a conventional diesel drivetrain and a conventional gasoline drivetrain in a typical commercial parcel delivery application. Vehicles in this study included a model year 2012 Freightliner P100H hybrid compared to a 2012 conventional gasoline P100 and a 2012 conventional diesel parcel delivery van of similar specifications. Drive cycle analysis of 484 days of hybrid parcel delivery van commercial operation from multiple vehicles was used to select three standard laboratory drive cycles as well as to create a custom representative cycle. These four cycles encompass and bracket the range of real world in-use data observed in Baltimore United Parcel Service operations. The NY Composite cycle, the City Suburban Heavy Vehicle Cycle cycle, and the California Air Resources Board Heavy Heavy-Duty Diesel Truck (HHDDT) cycle as well as a custom Baltimore parcel delivery cycle were tested at the National Renewable Energy Laboratory's Renewable Fuels and Lubricants Laboratory. Fuel consumption was measured and analyzed for all three vehicles. Vehicle laboratory results are compared on the basis of fuel economy. The hydraulic hybrid parcel delivery van demonstrated 19%-52% better fuel economy than the conventional diesel parcel more » delivery van and 30%-56% better fuel economy than the conventional gasoline parcel delivery van on cycles other than the highway-oriented HHDDT cycle. « less
Optimal Output Feedback for Linear Time-Periodic Systems

An approach is developed for applying optimal output feedback control theory to the design of fixed gain controllers for time-periodic systems. Constant feedback gains based on plant outputs are calculated by minimizing a linear quadratic performance cost functional. A solution algorithm is developed using Floquet- Lyapunov theory and a generalized harmonic expansion technique. The theory is applied to the control of a helicopter rotor blade in forward flight through individual blade control. It is shown that constant gain output feedback can be used to augment the stability of the resulting time-periodic system, with the potential for greatly reducing the implementation complexity. HE primary purpose of this paper is to present a general framework for applying output feedback techniques to linear time-periodic systems. The motivation for such an ap- proach is, in part, to reduce the control implementation re- quirements. The use of constant gain optimal output feedback in designing active feedback controllers provides many advan- tages over existing linear quadratic Gaussian (LQG) design methods. In particular, an on-line observer is not required, and the method can be extended to include compensator de- sign wherein the order of the compensator may be prespecified during the design process. Unneeded feedback channels may also be eliminated. 1 The number of sensors may be reduced while eliminating the need to estimate all of the unmeasurable states in real time. Recently, efficient compensator design formulations have been developed for linear time-invariant systems including robustness considerations for both unstruc- tured uncertainty and parametric uncertainty.2'3 The potential advantages of designing a fixed-order linear time-invariant controller are especially appealing for systems whose equations of motion are characterized by linear peri- odic coefficient dynamics. Aerospace applications include he- licopter forward flight stability and control and satellite or- bital stability problems. For helicopter aeromechanical and aeroelastic stability and control applications, the number of states required to model the system accurately continues to increase as research in structural elasticity, dynamic inflow, and aeroelasticity progresses. However, the feasibility and cost effectiveness of measuring/est imating all of the higher frequency structural elastic and dynamic inflow positions and rates for helicopter rotors in real time in an operational envi- ronment is questionable. This also drives the need for poten- tial alternatives to the full state feedback solution. An output feedback approach provides additional flexibility in that higher fidelity state space physical models may be used for the