cssi/SciSciGPT-SciSciNet huggingface dataset:
Targeting SYK signaling in myeloid cells protects against liver fibrosis and hepatocarcinogenesis

Liver fibrosis and fibrosis-associated hepatocarcinogenesis are driven by chronic inflammation and are leading causes of morbidity and death worldwide. SYK signaling regulates critical processes in innate and adaptive immunity, as well as parenchymal cells. We discovered high SYK expression in the parenchymal hepatocyte, hepatic stellate cell (HSC), and the inflammatory compartments in the fibrotic liver. We postulated that targeting SYK would mitigate hepatic fibrosis and oncogenic progression. We found that inhibition of SYK with the selective small molecule inhibitors Piceatannol and PRT062607 markedly protected against toxin-induced hepatic fibrosis, associated hepatocellular injury and intra-hepatic inflammation, and hepatocarcinogenesis. SYK inhibition resulted in increased intra-tumoral expression of the p16 and p53 but decreased expression of Bcl-xL and SMAD4. Further, hepatic expression of genes regulating angiogenesis, apoptosis, cell cycle regulation, and cellular senescence were affected by targeting SYK. We found that SYK inhibition mitigated both HSC trans-differentiation and acquisition of an inflammatory phenotype in T cells, B cells, and myeloid cells. However, in vivo experiments employing selective targeted deletion of SYK indicated that only SYK deletion in the myeloid compartment was sufficient to confer protection against fibrogenic progression. Targeting SYK promoted myeloid cell differentiation into hepato-protective TNFαlow CD206hi phenotype downregulating mTOR, IL-8 signaling and oxidative phosphorylation. Collectively, these data suggest that SYK is an attractive target for experimental therapeutics in treating hepatic fibrosis and oncogenesis.
Quality of Life with Late-Stage Dementia: Exploring Opportunities to Intervene

BACKGROUND/OBJECTIVES In late-stage dementia, families often prioritize quality of life (QoL) and comfort, yet little research examines factors impacting QoL. We sought to (1) describe temporal trends in QoL in late-stage dementia, and (2) explore associations between patient characteristics, care interventions, and QoL. DESIGN Secondary analysis of data from the Goals of Care clinical trial. SETTING Twenty-two nursing homes (NHs) in North Carolina. PARTICIPANTS Family decision makers for residents with late-stage dementia. MEASUREMENTS Family-reported QoL at baseline and at 9 months using the Alzheimer's Disease-Related Quality of Life Instrument (ADRQL) with five subscales scored 0 to 100 (higher scores indicate better quality). Families reported demographics, primary goal of care, and described their perceptions of residents' QoL. Chart reviews provided data on hospital transfers, treatment plans, and hospice enrollment. We ran mixed effects models of hypothesized variables and change in ADRQL over time. RESULTS The study sample was 241 dyads of residents with late-stage dementia and family decision makers. Family-reported ADRQL scores reflected moderately good QoL at baseline and at 9 months (69.1 vs 66.9; p = .106). Subscales for Awareness of Self (62.8; Global Deterioration Scale [GDS] = 5; 30.5; GDS = 7; p > .01) and Enjoyment of Activities (53.4; GDS = 5; 39.4; GDS = 7; p > .01) were lower in later stage disease. Qualitatively, family members associated better QoL for dementia with (1) activities, (2) opportunities to leave NH, (3) NH-structured activities, (4) attentiveness in NH, and (5) passive interaction. ADRQL at 9 months was associated with later dementia stage and referral to hospice (p < .01). Age (p = .004) and hospice enrollment were significantly associated with a larger decrease in ADRQL over 9 months (p = .019). A primary goal of comfort was associated with a larger increase in ADRQL (p = .022). CONCLUSION Families judge QoL to be moderately good in late-stage dementia. They perceive activities, opportunities to leave the NH, and quality of interpersonal care as ways to improve dementia-specific QoL.
"Sharing in hopes and worries"-a qualitative analysis of the delivery of compassionate care in palliative care and oncology at end of life

Purpose: To explore the methods through which physicians deliver compassionate care during end-of-life (EOL). Compassionate care provides benefits to patients and providers and is particularly important for patients with serious illnesses, yet its practice remains limited. We aim to qualitatively characterize methods utilized by physicians that facilitate the delivery of compassionate care at EOL. Methods: We conducted 13 semi-structured interviews with physicians from palliative care and medical oncology subspecialities at a rural academic medical centre in New Hampshire. Interviews were transcribed and analysed using a qualitative research design. Results: Participants described methods of compassionate care ranging from symptom control to less tangible, non-verbal methods. Primary barriers to the delivery of compassionate care were described as within the broader healthcare system and within the inherent emotional difficulty of EOL care. Physicians from both subspecialities emphasized the importance of successful inter-provider relationships. Conclusions: Methods for delivering compassionate care at EOL are wide ranging, but barriers on a systemic and individual level should be addressed to make its practice more widespread. This can be accomplished, in part, by the standardization of EOL conversations, training physicians how to have meaningful EOL conversations, and integration of such conversations into electronic medical records.
Incidence and clinical characteristics of pediatric eyelid retraction.

Purpose To describe the incidence and clinical characteristics of upper and lower eyelid retraction in children. Methods The medical records of all pediatric patients ( Results A total of 85 patients were diagnosed during the 35-year period, of whom 15 were residents of Olmsted County, Minnesota, yielding an annual age- and sex-adjusted annual incidence of 1.38 per 100,000 persons (95% CI, 0.70-2.05), or 1 in 72,463. Upper eyelid retraction was documented in 38 patients (45%; 24 unilateral and 14 bilateral); lower, in 25 (29%; 12 unilateral and 13 bilateral); and both upper and lower in 18 (21%; 3 unilateral and 15 bilateral). It was not recorded in 4 patients. The most common causes of eyelid retraction were thyroid eye disease (48 [56%]), primary congenital eyelid retraction (11 [13%]), and trauma (9 [11%]). Although there were no cases of visual impairment secondary to eyelid retraction, tearing, ocular surface irritation, and photophobia were noted in 38 patients (45%). Nineteen patients (22%) underwent surgical eyelid correction. Conclusions Pediatric eyelid retraction is relatively rare, occurring in approximately 1 in 72,000. The leading causes of childhood eyelid retraction in this cohort were thyroid eye disease, primary congenital eyelid retraction, and trauma. No visual disturbances due to eyelid retraction were noted, and approximately 1 in 5 patients required corrective eyelid surgery.
An investigation of liquid metal lubrication during electrically-assisted incremental forming of titanium

Abstract Incremental Forming (IF) is a sheet material forming process that does not require the use of dedicated dies. This is accomplished through local deformations made with a forming tool. Many improvements towards the IF process are categorized into the following categories: formability, springback, surface finish, and forming forces. The addition of an electrical current to the IF process has been investigated and shown to significantly reduce springback and forming force and increase formability. Current is often applied by assigning the forming tool to be an electrode and passing the current through the workpiece to the clamping fixture. While this configuration represents a simple, yet effective solution, its main drawback is a significant degradation of the surface, resulting from spalling of the tool. Herein, the utilization of a highly conductive liquid metal is investigated for its use as a conductive medium, as well as a lubricant, in the electrically assisted incremental forming process. It was determined that this lubricant is able to improve formability and surface finish over conventional MoS2 lubricant while significantly reducing springback.
What’s my age again? The influence of subjective age on consumer health-related attitudes

AbstractWe examine how shifts in subjective age influence consumer health-related attitudes. In Study 1, participants made to feel subjectively young (vs. old) exhibited more positive attitudes aft...
Perusall: Social learning platform for reading and annotating (perusall LLC, perusall.com)

Instructors routinely and reasonably express frustration when students choose not to complete required reading assignments. Readings are chosen because they are important, and the decision to not e...
A Case of Granulomatosis with Polyangiitis: Consequences of Delayed Diagnosis in a Life-threatening Malady.

Granulomatosis with polyangiitis (GPA) is one of three described anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). Early diagnosis and treatment of GPA is paramount, as it may help prevent irreversible end-organ damage, especially renal and pulmonary failure. A 72-year-old male with a past medical history of lung adenocarcinoma in remission, chronic sinusitis status-post multiple sinus surgeries, and coronary artery disease presented with shortness of breath, dark urine, and asymmetric polyarthralgias. He had an acute kidney injury, leukocytosis, with urinalysis demonstrating pyuria and hematuria, without casts. Chest imaging showed cavitary nodular opacities in addition to interval increase of existing nodules compared to the most recent scan one month prior. His acute kidney injury progressed to renal failure requiring hemodialysis, and he developed an inflammatory polyarthritis. GPA was suspected clinically so he was started on high-dose intravenous corticosteroids, and subsequently plasmapheresis and rituximab. Serology returned with highly positive proteinase-3 antibodies, and cytoplasmic ANCA positivity on immunofluorescence. Renal biopsy demonstrated severely active pauci-immune glomerulonephritis. Several months after discharge, the patient passed away from gram positive bacteremia. This patient's recurrent sinusitis, pulmonary nodules, and subsequent renal failure were highly suggestive of GPA. A biopsy is recommended to confirm the diagnosis of GPA, but treatment should not be delayed if there is a high index of suspicion for the disease. Induction therapy with corticosteroids combined with rituximab or cyclophosphamide has significantly decreased the mortality of patients with GPA. Patients with GPA often have preceding history of nasopharyngeal and upper airway disease, and can present with fluctuating pulmonary infiltrates. Early recognition and treatment of patients with GPA can prevent life-threatening complications and reduce mortality.
Scalable implementation of polynomial filtering for density functional theory calculation in PARSEC

Abstract We present an efficient implementation of polynomial filtering methods in PARSEC, a real-space pseudopotential based Kohn–Sham density functional theory solver. The implementation described here improves upon a Chebyshev-filtered subspace iteration algorithm used in the previous version of PARSEC. We present a hybrid polynomial filtering scheme that combines Chebyshev-filtered subspace iteration and a spectrum slicing method that partitions the spectrum into several spectral slices and uses bandpass-filtered subspace iteration to compute approximate eigenpairs within each interior slice simultaneously. We describe a procedure to partition a spectrum and construct polynomial filters. We also discuss a number of practical issues such as the use of appropriate data layouts for carrying out the computation on a two-dimensional process grid and how to achieve good load balance by allocating an appropriate number of process groups to each spectral slice. Numerical examples are presented to demonstrate the effectiveness of the hybrid polynomial filtering method as well as the superior parallel scalability of spectrum slicing in comparison to that of Chebyshev-filtered subspace iteration.
179 Moving beyond ‘so what?’ into action

National conversations about gun deaths are largely framed as community violence or mass shootings. However, gun suicides disproportionately contribute to the increase of gun deaths. Pennsylvania’s gun deaths and suicides outpace national rates, with rural communities disproportionately bearing the burden. Laws reducing gun access (e.g., ERPOS and Child Access Prevention) reduce gun suicides and overall gun deaths. Despite the evidence, Pennsylvania lawmakers fail to pass gun safety laws due to special interest pressures, ideology, and incorrect perceptions of the problem and corresponding solutions. The purpose of the study was to explore Pennsylvania lawmakers’ perceptions and understanding of gun suicides, if/how they use science to identify solutions, and their perceptions of legislative impasse. We conducted semi-structured interviews with a sample (n=9) of members of the Judiciary Committees from the Pennsylvania House of Representatives and Senate. Rural and suburban lawmakers identified suicide as a top concern in their districts. Few lawmakers relied on injury scientists to identify solutions or use it for framing the issue to colleagues and constituents. Some lawmakers relied on news stories or special interest groups, very few reported contacting researchers, despite robust local/regional expertise. Participants identified two roadblocks to law passage: 1) key colleagues captured by the NRA, and 2) rural constituents’ lack of understanding of the issue. They identified the need to message to constituents on gun suicides. Regardless of party, all lawmakers wanted to address this pressing health issue, with Republicans searching for answers outsides of scientific communities due to fears of bias. Moving the impact out of journals and into the hands of constituents and lawmakers is critical. Researchers can build relationships with news agencies and lawmakers to translate the science and build trust. Additionally, targeting messaging to rural lawmakers and constituents is critical to build support for evidence-based laws.
Abstract 249: Online Health Information for Myocardial Infarction: Trusted Source or Fake News?

Objective: As the internet is a leading destination for health information for patients, there is a need for this information to be accurate and easy to understand. In this study, we assessed the q...
Finite Dimensional Extension Fields

If Φ is a subfield of a field P, then we have seen that we can consider P as an algebra over Φ. In this chapter we shall be concerned primarily with the situation in which P is finite dimensional over the subfield Φ. We shall be concerned particularly with the general results of Galois theory that are of importance throughout algebra and especially in the theory of algebraic numbers. We shall consider the notions of normality, separability, and pure inseparability for extension fields, Galois cohomology, regular representations, traces, and norms. Also the basic results on finite fields will be derived and the notion of composites of two extension fields will be considered.
Congenital central pulmonary artery anomalies: Part 2

There is a broad spectrum of congenital anomalies of the central pulmonary arteries including abnormalities of development, origin, course and caliber. These anomalies incorporate simple lesions such as isolated pulmonary valve stenosis to very complex anomalies with many associated abnormalities. Part 1 and Part 2 of this review describe the range of anatomical variations that are encountered as well as important aspects of anatomy, physiology and surgical correction. The authors summarize and illustrate both well-recognized and more complex anomalies to provide a broad and comprehensive understanding of these lesions and their appearances on CT and MR imaging. In Part 2 the authors review abnormalities in development, origin and course of the central branch pulmonary arteries as well as abnormal pulmonary artery caliber.
Edge-to-edge repair: past challenge, current case selection and future advances

Severe mitral regurgitation (MR) is associated with heart failure and impaired survival with an annual mortality risk in excess of 5% per year for unoperated patients. Despite availability of surgical mitral valve interventions, as many as half of all patients with severe MR do not receive interventions. Transcatheter edge-to-edge repair with MitraClip has been a revolutionary therapy for MR, with over 100,000 treated patients worldwide. The usage has also expanded to different challenging anatomies as well as tricuspid regurgitation. Additionally, other transcatheter edge-to-edge repair devices are being studied. The evolution of these devices as well as what to expect in the future will be discussed here.
When and how does dilated cardiomyopathy recover in children

Abstract Background Much has been learned since the 1980s regarding the epidemiology, etiology, and outcomes of children with dilated cardiomyopathy (DCM). However, relatively little is understood about myocardial recovery in pediatric DCM: (1) when does pediatric DCM recover; (2) what are the predictors of recovery; (3) what are the clinical features of recovery; and (4) what are clinical and research gaps? Aim of Review A purpose of the Fifth International Conference on Childhood Cardiomyopathy was to update researchers and clinicians with interests in pediatric cardiomyopathy and heart failure on recent findings in myocardial recovery in DCM. This review is a summary of literature with details on cardiac recovery, not simply survival, in children with DCM. Key Scientific Concepts of Review More children with DCM are surviving without heart transplant in the current era of heart failure management, but the rate of recovery in these survivors is not widely known. Recovery of cardiac function ranges from 11-52% across multiple single and multi- center studies. Robust predictors for myocardial recovery in pediatric DCM are lacking. Future studies need to identify non-invasive markers of recovery to guide both prognostication at the time of diagnosis and to evaluate pharmaceuticals or device therapies that promote recovery. Studies of myocardial recovery in children need to include quality of life measures, long-term outcomes, and risk factors for heart failure recurrence or sudden death.
Oncostatin M Improves Cutaneous Wound Re-Epithelialization and Is Deficient under Diabetic Conditions.

Abstract Impaired re-epithelialization characterized by hyperkeratotic non-migratory wound epithelium is a hallmark of non-healing diabetic wounds. In chronic wounds, copious release of oncostatin M (OSM) from wound macrophages is evident. OSM is a potent keratinocyte activator. This work sought to understand the signal transduction pathway responsible for wound-re-epithelialization, the primary mechanism underlying wound closure. Daily topical treatment of full-thickness excisional wounds of C57bl/6 mice with recombinant murine OSM improved wound re-epithelialization and accelerated wound closure by bolstering keratinocyte proliferation and migration. OSM activated the JAK-STAT pathway as manifested by STAT3 phosphorylation. Such signal transduction in the human keratinocyte induced TP63, the master regulator of keratinocyte function. Elevated TP63 induced integrin beta 1, a known effector of keratinocyte migration. In diabetic wounds, OSM was more abundant compared to the level in non-diabetic wounds. However, in diabetic wounds OSM activity was compromised by glycation. Aminoguanidine, a deglycation agent, rescued compromised keratinocyte migration caused by glycated OSM. Finally, topical application of recombinant OSM improved keratinocyte migration and accelerated wound closure in db/db mice. This work recognizes that despite its abundance at the wound-site, OSM is inactivated by glycation and topical delivery of exogenous OSM is likely to be productive in accelerating diabetic wound closure.
The environmental psychology of prisons and jails : creating humane spaces in secure settings

This book distils thirty years of research on the impacts of jail and prison environments. The research program began with evaluations of new jails that were created by the US Bureau of Prisons, which had a novel design intended to provide a non-traditional and safe environment for pre-trial inmates and documented the stunning success of these jails in reducing tension and violence. This book uses assessments of this new model as a basis for considering the nature of environment and behavior in correctional settings and more broadly in all human settings. It provides a critical review of research on jail environments and of specific issues critical to the way they are experienced and places them in historical and theoretical context. It presents a contextual model for the way environment influences the chance of violence.
The effect of vitamin D on linear growth in infancy: II. The effect of intakes above 1,800 U.S.P. units daily

Summary The rate of linear growth of nine infants given from 1,800 to 4,600 units of vitamin D daily has been compared with standard rates of growth, and with the growth of infants given the same dietary regimen but amounts of vitamin D varying from 135 to 340 units daily. The rates of growth with the very high vitamin D intake were similar to or less than those of infants given 135 units daily, and definitely lower than the growth rates of infants given 340 units of vitamin D daily. It is concluded that the effect of vitamin D on increasing linear growth reaches a maximum when the vitamin D intake is greater than 135 and less than 1,800 units, probably in the neighborhood of 340 to 600 units daily. Vitamin A in amounts exceeding those of the food (milk, vegetable, and fruit purees) apparently does not affect linear growth of infants. Factors affecting growth rates of individual infants are discussed. It is concluded that in order to determine the effect of the dietary regimen, growth should be studied well past 6 months of age, preferably during the greater part of infancy. Growth during the first 8 weeks of life may be affected by factors other than the dietary regimen of the infant.
Fluorescent Antibody Studies on the Immunopathology of Schistosomiasis Mansoni

The first fluorescent antibody studies in schistosomiasis were concerned with the use of this procedure as a diagnostic aid and for the determination of antibody titer in experimental animals. Sadun and co-workers [10–13] using preserved miracidia and cercariae as antigens showed that the fluorescent antibody test is both sensitive and specific and is a practical survey procedure. This subject is discussed by Sadun elsewhere in this volume. Sadun and co-workers demonstrated that schistosomulae removed from the skin of infected animals showed specific immunofluorescence.
Fever and rash in a 7-month-old infant.

Apreviouslywell 7-month-oldmale infant presented toour emergencydepartmentwith 1 week of loose stools, 4 days of fever up to 39.2°C, and 2 days of skin rash. His parents reported several pink papules that first appeared on his trunk and spread to his extremities within 24 hours. His increasing irritability and poor oral intake ledtohisadmission for furtherevaluation.Thepatient’s vaccinations were up to date. He had no history of perinatal infections, sick contacts, recent travel, or pets. The family lives in an apartment in New York City. Onphysical examination, thepatienthad fewer than20pinkpapulovesicles, somewith hemorrhagic crust, scattered on the upper chest, abdomen, lower back, and extremities (Figure, A and B). His palms, soles, and oropharynx were otherwise unremarkable. Laboratory test resultswerenotable for amild leukopeniawithawhitebloodcell count of4.6 × 109/L(normal,6.0-18.0 × 109/L)with18%monocytes.C-reactiveproteinwasslightly elevatedat3.38mg/L(normal, <2.9mg/L).Hewasstartedtreatmentwith intravenousceftriaxone and intravenous acyclovir. Blood, urine, and wound cultures were taken, and a skin punch biopsy was performed (Figure, C). Quiz at jamapediatrics.com A B
Microstructure characterization of granular materials

Abstract This paper presents techniques and algorithms to compute microstructure properties of irregular-shaped granulate assemblies utilizing 3D images. The techniques are capable of extracting microstructure properties of particles such as centeroid, particle size distribution, shape indices (i.e., sphericiy and angularity), number of contacts (i.e., distribution of coordination numbers), contact network, packing efficiency, distribution of local void ratio and radial distribution function. Such properties are critical parameters for micromechanical-based numerical models to capture micro- and macromechanical behavior of geomaterials. X-ray microtomography was used to reconstruct high-resolution 3D image of a natural sand system to represent granular materials. Microstructure properties of the sand system were computed and compared with properties of a computer-simulated image of periodic random spheres. Findings indicate that the use of simplified systems of idealized spheres to model micro- and macromechanical behavior of granular systems can lead to inaccurate results due to the differences in the microstructure between both systems. Methods presented in this paper enabled capturing a more realistic microstructure that can be incorporated in micromechanical models to better simulate, understand, or explain macroscale behavior of granular materials based on their actual microstructure.
ADAMTS13 promotes angiogenesis and modulates VEGF-induced angiogenesis

Plasma ADAMTS13 deficiency results in the clinical disorder thrombotic thrombocytopenic purpura. However, other potential pathophysiological roles of ADAMTS13 in endothelial cell biology remain unexplored. To assess the possible role of ADAMTS13 and its interactions with VEGF-mediated angiogenesis, the effects of ADAMTS13 on human umbilical vein endothelial cell (HUVEC) were studied in Matrigel tube formation, proliferation, cell migration, and scratch wound assays. Treatment of endothelial cells with exogenous recombinant full-length ADAMTS13 alone promoted angiogenesis in a dose-dependent manner. HUVEC incubated with 200 ng/mL ADAMTS13 (1.4 nM) resulted in a 65% increase in cell tube formation when compared to the EBM-2 control. HUVEC treated with 30 ng/mL ADAMTS13 (204.1 pM) resulted in an 83% increase in proliferation in a visual counting assay, whereas HUVEC treated with 10 ng/mL ADAMTS13 (68.0 pM) yielded a 295% increase in EC migration in a Boyden chamber assay. In contrast, ADAMTS13 inhibited VEGF-induced angiogenesis in a dose-dependent manner, with 200ng/mL inhibiting tube formation by 35%. HUVEC co-incubated with ADAMTS13 and an antibody to the ADAMTS13 thrombospondin domains 5-7 reversed the inhibition of tube formation. HUVEC treated with 30 ng/mL ADAMTS13 and 6.2 ng/mL (323.0 pM) VEGF proliferated 40% slower than the VEGF control after 24 h of incubation as measured by visual counting assay. Treatment of HUVEC with 6.2 ng/mL VEGF and 10 ng/mL ADAMTS13 inhibited cell migration by 48%, compared to the VEGF control. Substitution of ADAMTS13 with truncated ADAMTS13 (deletion of C-terminal TSP1 domain) did not significantly increase angiogenesis or suppress VEGF-induced angiogenesis, suggesting that the TSP1 domain is involved in ADAMTS13 angiogenic activities. Co-immunoprecipitation experiments provided further evidence that ADAMTS13 binds to VEGF via its TSP1 domain.
Partial agonist properties of rauwolscine and yohimbine for the inhibition of adenylyl cyclase by recombinant human 5-HT1A receptors.

Previous studies by another group have suggested that the α2-adrenergic receptor antagonist rauwolscine may function as an agonist at the serotonini1A (5-HT1A) receptor expressed in human brain. To directly test that hypothesis, we transfected the human 5-HT1A receptor cDNA into CHO cells and examined the ability of rauwolscine and its isomer, yohimbine, to inhibit ligand binding of [3H]-(±)-8- hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) and the activity of adenylyl cyclase in membranes derived from a single transformant that stably expresses ≈225 fmol of 5-HT1A receptor/mg of membrane protein. Both ligands competitively antagonized the binding of [3H]8-OH-DPAT (Ki = 158 ± 69 nM for rauwolscine and 690 ± 223 nM for yohimbine), yielding shallow displacement curves consistent with agonist activity (Hill values = 0.69 ± 0.2 for rauwolscine and 0.63 ± 0.06 for yohimbine). Both ligands also inhibited forskolin-stimulated adenylyl cyclase activity in membranes derived from transfected (but not nontransfected) cells. For rauwolscine, the IC50 was 1.5 ± 0.2 μM, and for yohimbine 4.6 ± 1.0 μM, with activity ratios of 0.70 and 0.59, respectively, when compared to the full agonist serotonin. These studies demonstrated that rauwolscine and yohimbine are partial agonists for the human 5-HT1A receptor.
A Re-programmable Receiver Architecture for Wireless Signal Interception

In this paper, a re-programmable receiver architecture, based on software-defined-radio concept, for wireless signal interception is presented. The radio-frequency (RF) signal that the receiver would like to intercept may come from a terrestrial cellular network or communication satellites, which their carrier frequency are in the range from 800 MHz (civilian mobile) to 15 GHz (Ku band). To intercept signals from such a wide range of frequency in these variant communication systems, the traditional way is to deploy multiple receivers to scan and detect the desired signal. This traditional approach is obviously unattractive due to the cost, efficiency, and accuracy. Instead, we propose a universal receiver, which is software-driven and re-configurable, to intercept signals of interest. The software-defined-radio based receiver first intercepts RF energy of wide spectrum (25MHz) through antenna, performs zero-IF down conversion (homodyne architecture) to baseband, and digital channelizes the baseband signal. The channelization module is a bank of high performance digital filters. The bandwidth of the filter bank is programmable according to the wireless communication protocol under watch. In the baseband processing, high-performance digital signal processors carry out the detection process and microprocessors handle the communication protocols. The baseband processing is also re-configurable for different wireless standards and protocol. The advantages of the software-defined-radio architecture over traditional RF receiver make it a favorable technology for the communication signal interception and surveillance.
The case for DSM‐IV subtypes in ADHD

This article selectively reviews research that has examined the three DSM-IV attention deficit-hyperactivity disorder (ADHD) subtypes. Data relevant to the validity of the subtyping system, including demographic, comorbidity, cognitive/attentional, and social correlates of the three subtypes are presented. The majority of relevant research has examined the ADHD/C and ADHD/IA subtypes, with less information available for the newly identified ADHD/HI subtype. Findings support the existence of the ADHD/IA subtype; children so diagnosed show impairment and patterns of dysfunction unique from those with the ADHD/C subtype. Further research on many aspects of ADHD/IA is needed to clarify whether it is best considered a separate disorder or an ADHD subtype, however, and to determine the most appropriate diagnostic criteria. Although the scant existing data also suggest that the ADHD/HI subtype is associated with impairment and a different pattern of deficits relative to the other two subtypes, further elucidation of its developmental course is needed to clearly determine its validity. MRDD Research Reviews 1999;5:199–206 © 1999 Wiley-Liss, Inc.
Quantification of the Differences in Flesh Fatty Acid Components between Farmed and Wild Fish

Inconclusive results on the effect of farming on fatty acid composition of fish prevent the application of this possible variable in studies related to human health and environmental policies. The current meta-analysis used results from 39 studies to produce compelling quantitative results on differences in fatty acid components related to human health between farmed and wild fish. With seawater fish, mean effect sizes (Hedges' d) for differences in contents of EPA + DHA, total n-3 fatty acids, and the n-3:n-6 ratio were virtually zero. However, farmed freshwater fish showed a lower total n-3 fatty acid content than their wild counterparts.
The insertion of gas molecules into polyhedral oligomeric silsesquioxane (POSS) cages: understanding the energy of insertion using quantum chemical calculations

Density functional theory (DFT) calculations using the B3LYP and ωB97XD functionals and Moller–Plesset (MP2) calculations have been used to determine the energy of insertion of seven molecules (CO2, N2, O2, CO, CH4, He and H2O) into two sizes of polyhedral oligomeric silsesquioxane (POSS) cages, T10 and T12. Geometry optimization results of each molecule inserted into the center of the POSS cage and transition-energy searches of the molecules in the largest face of both T10 and T12 (identified as the Si5 face) are discussed. The main factors that affect the energy of a molecule in a particular POSS cage are the size (number of atoms) and shape of the POSS cage and the strength of dispersion and electrostatic interactions. The largest of the molecules, CO2 and CH4, have the largest interaction energies within the center and the face of the T10 and T12 cages. Interaction energies for the diatomic molecules increase in the order H2 < O2 < N2 ∼ CO and differences between interaction energies can be attributed, in part, to differences in electron transfer between the cage and molecule. Electrostatic interactions also play a significant role in determining the interaction energy. For example, H2 and He are only slightly charged when inside the POSS cages, providing little repulsive or attractive interactions, while polar CO provides significant repulsive interaction. In the case of water, the interaction energies are low because of hydrogen bonding between the water hydrogen atoms and the POSS oxygen atoms. The interaction energies of the absorbates at the center of T12 are typically smaller than for T10 due to the larger cavity size of T12. The Si5 face has the same basic structure for both T10 and T12 cages and, consequently, the interaction energies of the absorbate molecules at the face are similar. Interaction energies obtained using MP2 calculations are lower than those obtained from DFT calculations depending on the choice of the functional. For example, use of the ωB97XD functional that treats dispersion interactions more completely than the B3LYP functional, produces values closer to the MP2 values. These results, therefore, suggest that dispersion is important in the interaction between small molecules and POSS cages.
Risk Factors for Heart Failure in Young Adults

Heart failure (HF) is now recognized as a progressive disorder that typically begins with an asymptomatic state in patients with risk factors (Stage A), proceeds to developing structural abnormalities (Stage B), following which symptoms commonly develop (Stages C and D) unless treatment is initiated. Risk factors for developing HF include hypertension, diabetes mellitus, obesity, and risk factors for coronary artery disease including smoking and hypercholesterolemia. Although the incidence of HF in young adults is very low, they have a high lifetime incidence of developing HF (approximately one in five). The landmark CARDIA study found that risk factors for HF in young adults were similar to those seen in older adults. To decrease the future burden of HF it is essential to identify and intervene in those patients at risk, namely those in Stages A and B.
941. Manganese Superoxide Dismutase-Plasmid Liposome (MnSOD-PL) Transgenic Effects on Irradiation-Induced Reactive Oxygen Species (ROS) in Normal Tissue Also Destabilize Antioxidant Pools in Orthotopic Oral Cavity Tumors

Overexpression of MnSOD has been demonstrated to sensitize tumor cells to irradiation. To determine the mechanism, we injected SCC-VII murine squamous cell carcinoma cells into the cheeks of C3H/HeNsd mice. Seven days later, the mice were injected eitherintravenously (I.V.) or intraorally (I.O.) with MnSOD-PL (100 |[mu]|g plasmid DNA). Twenty-four hours later, the mice were irradiated to 18 Gy to both tumor and oral cavity. The mice were sacrificed 15 minutes later, tumor and normal oral mucosa excised, frozen in liquid nitrogen, and stored in a |[minus]|80|[deg]| freezer. Total protein thiols as well as total glutathione were measured. We also measured the production of nitric oxide and peroxynitrite utilizing small electroprobes in tissues in situ. Following irradiation oral mucosa showed no detectable changes in total protein thiols if mice were injected with MnSOD- PL I.V. or I.O. There were no significant changes in total protein thiols or GSH from tumors of irradiated control mice or mice injected with MnSOD-PL I.O. However, irradiated SCC-VII tumors from mice injected with MnSOD-PL I.V. showed decreased total protein thiols and GSH compared to tumors from control mice (p = 0.0008 or 0.0103, respectively). Measurements of reactive oxygen species (ROS) in SCC-VII cells in vivo following irradiation revealed increased nitric oxide production accompanied by increased peroxynitrite and superoxide production. SCC-VII tumors in mice administered MnSOD-PL I.V. showed no irradiation-induced increase in superoxide or peroxynitrite production. Overexpression of MnSOD- PL in orthotopic squamous oral tumors sensitizes to irradiation by increased hydrogen peroxide production, from the conversion of superoxide to H2O2, and reduces antioxidant levels in tumor tissue. Thus, MnSOD-PL I.V. administration may be radioprotective for normal tissue while radiosensitizing tumors in the same field by altering antioxidant levels in the tumors.
Phase transformations during microcutting tests on silicon

Controlled slow‐speed microcutting tests were made on single crystal silicon. Micro‐Raman spectroscopy confirmed the presence of amorphous silicon within the microcutting grooves as well as in the debris particles removed from the grooves. These results indicate that pressure‐induced transformation to metallic silicon can occur during microcutting and the ductile metallic phase will facilitate the cutting process. Raman spectroscopy further indicated the presence of large residual tensile strains in some areas of the microcutting grooves.
Retiming with non-zero clock skew, variable register, and interconnect delay

A retiming algorithm is presented which includes the effects of variable register, clock distribution, and interconnect delay. These delay components are incorporated into retiming by assigning Register Electrical Characteristics (RECs) to each edge in the graph representation of the synchronous circuit. A matrix (called the Sequential Adjacency Matrix or SAM) is presented that contains all path delays. Timing constraints for each data path are derived from this matrix. Vertex lags are assigned ranges rather than single values as in standard retiming algorithms. The approach used in the proposed algorithm is to initialize these ranges with unbounded values and continuously tighten these ranges using localized timing constraints until an optimal solution is obtained. The algorithm is demonstrated on modified MCNC benchmark circuits and both increased clock frequencies and elimination of all race conditions are observed.
Mutation matrices and physical‐chemical properties: Correlations and implications

To investigate how the prop- erties of individual amino acids result in pro- teins with particular structures and functions, we have examined the correlations between previously derived structure-dependent muta- tion rates and changes in various physical- chemical properties of the amino acids such as volume, charge, a-helical and b-sheet propen- sity, and hydrophobicity. In most cases we found the DG of transfer from octanol to water to be the best model for evolutionary con- straints, in contrast to the much weaker corre- lation with the DG of transfer from cyclohex- ane to water, a property found to be highly correlated to changes in stability in site- directed mutagenesis studies. This suggests that natural evolution may follow different rules than those suggested by results obtained in the laboratory. A high degree of con- servation of a surface residue's relative hydro- phobicity was also observed, a fact that cannot be explained by constraints on protein stability but that may reflect the consequences of the reverse-hydrophobic effect. Local pro- pensity, especially a-helical propensity, is rather poorly conserved during evolution, indi- cating that non-local interactions dominate protein structure formation. We found that changes in volume were important in specific cases, most significantly in transitions among the hydrophobic residues in buried locations. To demonstrate how these techniques could be used to understand particular protein fami- lies, we derived and analyzed mutation matri- ces for the hypervariable and framework re- gions of antibody light chain V regions. We found a surprisingly high conservation of hy- drophobicity in the hypervariable region, pos- sibly indicating an important role for hydro- phobicity in antigen recognition. Proteins 27:
Lateglacial and Holocene cosmogenic surface exposure age glacial chronology and geomorphological evidence for the presence of cold‐based glaciers at Nevado Sajama, Bolivia

Comparisons of palaeo-equilibrium line altitudes between the Western and Eastern Cordilleras in the Central Andes are commonly based on the assumption that the tall outermost moraines visible in remotely sensed images of the Western Cordillera date to the Last Glacial Maximum (LGM). However, field investigation and geomorphic mapping at Nevado Sajama, Bolivia, indicates the tall moraines are relic features with shorter moraines overlying and in some cases extending beyond them. 36Cl exposure ages from the shorter moraines suggest that they date to Lateglacial times ca. 16.9–10.2 ka. Although Lateglacial deposits have been found throughout the Central Andes, the extent of these deposits relative to LGM deposits varies both between the Western and Eastern Cordilleras and north-to-south along the Western Cordillera. In the Western Cordillera in the zone of easterly winds, the Lateglacial appears to be the most extensive glacial advance of the last glacial cycle. Geomorphic evidence also suggests that some Lateglacial moraines were deposited by cold-based ice, a previously unreported finding in the tropical Andes. Retreat from other glacial features occurred at about 7.0–4.4 ka and 4.7–3.3 ka. These are the first directly dated Holocene glacial deposits in the Western Cordillera of Bolivia, and their presence suggests that the mid Holocene may not have been as warm and dry as previously thought. Copyright © 2008 John Wiley & Sons, Ltd.
The effects of fluorescent probes on model membrane organization: photo-induced lipid sorting and soft structure formation

Liquid crystalline phase behaviour in model cell membranes prepared in-vitro has generated an enormous amount of interest in recent years and the phase diagrams of various bio-mimetic mixtures explored. Most recently photo-induced oxidation in fluorescently labelled membranes has been shown to influence these phase diagrams and can be used to generate interesting membrane-based geometries based on differences in membrane composition. In this article the different phases observed in model membranes will be discussed. Methods used to study these systems and recent developments in photo-stimulated phase changes are described along with areas for future investigation.
Antigenic Variation of Varicella Zoster Virus Fc Receptor gE: Loss of a Major B Cell Epitope in the Ectodomain

Varicella zoster virus (VZV) is considered to possess a genetically stable genome; only one serotype is recognized around the world. The 125-kbp genome contains approximately 70 open reading frames. One that has received particular attention is open reading frame 68, which codes for glycoprotein gE, the predominant 623-residue viral envelope product that harbors both B and T cell epitopes. This report describes the initial characterization of a community-acquired VZV isolate that was a distinguishable second serotype (i.e., it had lost a major B cell epitope defined on the gE ectodomain by a murine monoclonal antibody called mAb 3B3). The mAb 3B3 epitope was found not only on the prototype sequenced Dumas strain from Holland and all previously tested North American isolates but also on the varicella vaccine Oka strain originally attenuated in Japan. Sequencing of the mutated gE ectodomain demonstrated that codon 150 exhibited a single base change that led to an amino acid change (aspartic acid to asparagine). Observation of the monolayers infected with the mutant VZV strain also led to the surprising discovery that the topography of egress was altered. Wild-type VZV emerges along distinctive viral highways, whereas the mutant strain virions were nearly uniformly distributed over the cell surface in a pattern more closely resembling egress of herpes simplex virus 1. The mutant VZV strain was designated VZV-MSP because it was isolated in Minnesota.
Accurate approximations of stress intensity factors of EDGE cracks in notating disks

The stress intensity factors of cracks in rotating disks though not trivial can be determined analytically [1,2], numerically [3,4], and experimentally [5,6]. However, the utility of published results are limited since the nature of the stresses in rotating disks makes the solutions Poisson's ratio specific. The purpose of this report is to communicate an accurate approximation of stress intensity factors of edge cracks in rotating disks.
Relativistic cross sections for excitation of highly charged ions to specific magnetic sublevels by an electron beam

A program has been developed for making calculations of fully relativistic distorted-wave cross sections for excitation of highly charged ions to specific magnetic sublevels ${M}_{f}$ by a beam of electrons. The approach uses the same Dirac-Fock-Slater potential for all electrons and is expected to be accurate for nuclear charge number Z\ensuremath{\gtrsim}2.5N, where N is the number of bound electrons per ions. To our knowledge there is at present no other fully relativistic program available with which we could compare results for this type of cross section. However, the present results for He-like, Li-like, and Ne-like iron and for Ne-like molybdenum are compared with other partially relativistic results, and generally good agreement is obtained for these ions. It is expected that the present program will be useful for comparison with and interpretation of experimental results for very highly charged ions, such as those obtained in electron-beam ion-trap experiments at Livermore [R. E. Marrs et al., Phys. Rev. Lett. 60, 1715 (1988)].
Targeting eosinophils in allergy, inflammation and beyond

Eosinophils can regulate local immune and inflammatory responses, and their accumulation in the blood and tissue is associated with several inflammatory and infectious diseases. Thus, therapies that target eosinophils may help control diverse diseases, including atopic disorders such as asthma and allergy, as well as diseases that are not primarily associated with eosinophils, such as autoimmunity and malignancy. Eosinophil-targeted therapeutic agents that are aimed at blocking specific steps involved in eosinophil development, migration and activation have recently entered clinical testing and have produced encouraging results and insights into the role of eosinophils. In this Review, we describe recent advances in the development of first-generation eosinophil-targeted therapies and highlight strategies for using personalized medicine to treat eosinophilic disorders.