cssi/SciSciGPT-SciSciNet huggingface dataset:
A Prospective Study of Alemtuzumab as a Second-Line Agent for Steroid-Refractory Acute Graft-versus-Host Disease in Pediatric and Young Adult Allogeneic Hematopoietic Stem Cell Transplantation.

Abstract We describe a single-center prospective study of alemtuzumab as a second-line agent for steroid-refractory (SR) acute graft-versus-host disease (aGVHD) in pediatric and young adult allogeneic hematopoietic stem cell transplant recipients. Alemtuzumab was administered for grades II to IV aGVHD if patients did not improve within 5 days or worsened within 48 hours after corticosteroids. Interim analyses of alemtuzumab levels and response were performed after every 5 patients enrolled, resulting in 3 dosing cohorts, as follows: (1) .2 mg/kg alemtuzumab subcutaneously on days 1 to 5 (maximum of 31 mg over 5 days) and .2 mg/kg/dose (not exceeding 10 mg/dose) on days 15, 22, and 29; (2) .2 mg/kg alemtuzumab subcutaneously on days 1 to 5 (maximum of 43 mg over 5 days) and .2 mg/kg/dose on day 7, 10, 15, 22, and 29; and (3) .2 mg/kg subcutaneously on days 1 to 5 and .2 mg/kg/dose on day 7, 10, 15, and 22. Alemtuzumab levels were assessed before starting alemtuzumab and at days 1, 3, 6, 10, and 14 and weekly until day 99, where day 1 was the day of first alemtuzumab dose. Fifteen patients (median age, 10 years; range, 1.4 to 27) received alemtuzumab for grades II (6%), III (74%), and IV (20%) SR-aGVHD. The overall response rate was 67%, with complete response (CR) in 40%, partial response (PR) in 27%, and no response in 33%. The median day 6 alemtuzumab level was 2.79 µg/mL (interquartile range, 1.34 to 4.89) in patients with CR compared with .62 µg/mL (interquartile range, .25 to 1.45) in patients with PR + no response (P
Parenting Stress as a Mediator between Mental Health Consultation and Children’s Behavior

Early Childhood Mental Health Consultation (ECMC) focuses on enhancing adults’ (e.g., parents) skills and abilities in order to improve children’s behavior. Limited research has examined parenting factors as mechanisms of change, which is important given the bidirectional nature of parent-child interactions. Parenting stress and its influence on children’s behavioral outcomes (behavior problems and protective factors) were investigated following the implementation of an Early Childhood Mental Health Consultation (ECMHC) program. Participants included parents that participated in the ECMHC program (n = 247) and a comparison group (n = 72) in the Midwest. Overall, parents in the ECMHC group experienced fewer dysfunctional parent-child interactions and less distress. Results indicated that parent-child dysfunctional interactions mediated the relationship between ECMHC and children’s behavior problems (CI = .001, .038) and protective factors (CI = -.061, -.001). Parental distress did not mediate the relationship between ECMHC and children’s behavior problems (CI = -.001, .016) or protective factors (CI = -.020, .001). Understanding the influence of stress and parent-child interactions is beneficial as these may be malleable and responsive to change if targeted in intervention. Examining mechanisms of change related to parents will allow for refinement of services and improved behavioral outcomes for children.
Effect of chronic morphine treatment on immune responses to keyhole limpet hemocyanin in swine.

In the U.S., an estimated 2 million individuals have used heroin, including 600,000 on a daily basis [1]. Other opiate drugs are used medically in the treatment of pain. The use of opiate drugs is associated with an increased incidence and/or severity of infectious disease [2, 3, 4], respiratory infections [5] and impairment of cell-mediated immunity [6, 7, 8, 9]. Efforts to determine the effect of opiate drugs on immune response in humans is confounded by polydrug abuse and the effects of poor nutrition and poor hygiene. Therefore, we established a swine model of chronic morphine treatment that demonstrates tolerance and dependence in order to test the effect of opiate drugs on primary and recall immune responses [10]. Swine are suitable for chronic, longitudinal studies requiring repeated sample collection and can be trained to minimize handling stress.
An assay of angiogenic protein expression in human umbilical vein endothelial cells (HUVECs)

1141 The growth and metastatic potential of solid tumors is dependent upon vasculature formation. Numerous quantitative assays are used to measure levels of angiogenesis in ovarian cancer, including molecular expression of cytokines and their receptors, functional or molecular expression of angiogenic proteins, microvessel counts and immunohistochemistry. We have initiated a pilot study to apply state-of-the-art quantitative microproteomic lysate array technology to cultured endothelial cells in order to optimize an assay of vascular protein expression. Twenty-four hours prior to the experiment, human umbilical vein endothelial cells (HUVECs) were starved in reduced serum-containing media. HUVECs were treated with low serum-containing medium alone (control), VEGF-165 for 15 min., or CoCl2 for 1 hr. to induce hypoxia. Cells were lysed and printed onto protein microarrays. Arrays were probed with pre-validated commercial antibodies against: CD31, cKit, p-cKit (Tyr719), Cox-2, eNOS, p-eNOS (ser 116), HIF-1 alpha, PDGFR beta, p-PDGFR beta (Tyr 716) and p-VEGFR-2 (Tyr 1175). Stained arrays were scanned and quantitated. Preliminary results show detectable changes in protein expression of cKit, p-cKit, eNOS and p-eNOS in response to angiogenic stimuli. CD31 protein was detected only in the endothelial cell component of the protein microarray, while Cox-2 was measurable in both endothelial cells and A431 carcinoma cell line controls. Relatively more Cox-2 was present in HUVECs than in A431 controls. This pilot study provides proof of concept that microproteomic technologies can be used to study in situ vascular signaling events. This assay will be further optimized in ovarian cancer tissue samples and cross-validated against standing techniques for the study of angiogenesis in clinical samples. This research was made possible through the Clinical Research Training Program, a public-private partnership supported jointly by the NIH and a grant to the Foundation for the NIH from Pfizer Pharmaceuticals Group.
Integrating Mental and Physical Health Care for Low-Income Americans: Assessing a Federal Program’s Initial Impact on Access and Cost

Individuals with mental health disorders often die decades earlier than the average person, and low-income individuals disproportionately experience limited access to necessary services. In 2014, the U.S. Health Resources & Services Administration (HRSA) leveraged Affordable Care Act funds to address these challenges through behavioral health integration. The objective of this study is to assess the US$55 million program’s first-year impact on access and cost. This analysis uses multivariable difference-in-difference regression models to estimate changes in outcomes between the original 219 Federally Qualified Health Center (FQHC) Behavioral Health Integration grantees and two comparison groups. The primary outcome variables are annual depression screening rate, percentage of mental health and substance use patients served, and per capita cost. The results change when comparing the Behavioral Health Integration (BHI) grantees to a propensity score-matched comparison group versus comparing the grantees to the full population of health centers. After one year of implementation, the grant program appeared ineffective as measured by this study’s outcomes, though costs did not significantly rise because of the program. This study has limitations that must be discussed, including non-randomized study design, FQHC data measurement, and BHI program design consequences. Time will tell if FQHC-based behavioral–physical health care integration will improve access among low-income, medically-underserved populations.
Varus Thrust and Incident and Progressive Knee Osteoarthritis

Objective To determine if varus thrust, a bowing out of the knee during gait (i.e., the first appearance or worsening of varus alignment during stance), is associated with incident and progressive knee osteoarthritis (OA), we undertook an Osteoarthritis Initiative ancillary study. We further considered hypothesized associations adjusted for static alignment, anticipating some attenuation. Methods Gait was observed for the presence of thrust by 1 of 2–3 examiners per study site at 4 sites. In eligible knees, incident OA was defined as subsequent incident Kellgren/Lawrence grade ≥2, whole- and partial-grade medial joint space narrowing (JSN), and annualized loss of joint space width (JSW); progression was defined as medial JSN and JSW loss. Outcome measures were assessed for up to 7 years of follow-up. Analyses were knee-level, using multivariable logistic and linear regression with generalized estimating equations to account for between-limb correlation. Results The incident OA sample included 4,187 knees (2,610 persons); the progression sample included 3,421 knees (2,284 persons). In knees with OA, thrust was associated with progression as assessed by each outcome measure, with adjustment for age, sex, body mass index, and pain on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. In knees without OA, varus thrust was not associated with incident OA or other outcomes. After adjustment for alignment, the thrust–progression association was attenuated, but an independent association persisted for partial-grade JSN and JSW loss outcome models. WOMAC pain and alignment were consistently associated with all outcome measures. Within the stratum of varus knees, thrust was associated with an increased risk of progression. Conclusion Varus thrust visualized during gait is associated with knee OA progression and should be a target of intervention development.
Reinventing the Wheel [Basic Metrology]

The engineering of stability into a wide variety of commonly- used devices and systems is a well-known necessity. Inherently unstable mechanical systems are often stabilized by the addition of servocontrol, a well-known historical example being the addition by James Watt of a “governor” to his steam engine. The governor is a mechanical servocontrol that keeps the engine turning at a set rate, as illustrated nicely in [1].
Development of a research-oriented system for collecting mechanical ventilator waveform data.

Lack of access to high-frequency, high-volume patient-derived data, such as mechanical ventilator waveform data, has limited the secondary use of these data for research, quality improvement, and decision support. Existing methods for collecting these data are obtrusive, require high levels of technical expertise, and are often cost-prohibitive, limiting their use and scalability for research applications. We describe here the development of an unobtrusive, open-source, scalable, and user-friendly architecture for collecting, transmitting, and storing mechanical ventilator waveform data that is generalizable to other patient care devices. The system implements a software framework that automates and enforces end-to-end data collection and transmission. A web-based data management application facilitates nontechnical end users' abilities to manage data acquisition devices, mitigates data loss and misattribution, and automates data storage. Using this integrated system, we have been able to collect ventilator waveform data from >450 patients as part of an ongoing clinical study.
What is Music? The Ontological Status of Musical Works

The ontological status of musical works is a controversial topic among those in the field. This paper aims to argue for a nominalist and non-reductive approach to musical works that differentiates musical works from the sound structures commonly equated with them. The difference between sound structures and musical works is heavily emphasized and I conclude that musical works have emergent attributes sound structures do not. These attributes being creatability, fine individuation, and the inclusion of performance means. After establishing this I begin to build an argument for a nonreductive approach to musical works by rejecting the extreme view held by compositional nihilists. Once I establish that musical works are entities in our ontology I argue against them being abstract. I end by defending the nominalist approach.
Tuning Inner-Ear Tip-Link Affinity Through Alternatively Spliced Variants of Protocadherin-15

Human hearing relies upon the tip-to-tip interaction of two nonclassical cadherins, protocadherin-15 (PCDH15) and cadherin-23 (CDH23). Together, these proteins form a filament called the tip link that connects neighboring stereocilia of mechanosensitive hair cells. As sound waves enter the cochlea, the stereocilia deflect and tension is applied to the tip link, opening nearby transduction channels. Disruption of the tip link by loud sound or calcium chelators eliminates transduction currents and illustrates that tip-link integrity is critical for mechanosensing. Tip-link remodeling after disruption is a dynamic process, which can lead to the formation of atypical complexes that incorporate alternatively spliced variants of PCDH15. These variants are categorized into six groups (N1–N6) based upon differences in the first two extracellular cadherin (EC) repeats. Here, we characterized the two N-terminal EC repeats of all PCDH15 variants (pcdh15(N1) to pcdh15(N6)) and combined these variants to test complex ...
Protein and Taste

If the high-quality protein that meat yields up to the successful hunter or scavenger were the “nutrient among nutrients” in our evolutionary climb to modernity, one might reasonably assume that we should have developed some clear-cut, hardwired taste for it. Curious, then, that study after study characterizes uncooked fresh meat as essentially tasteless (Bender and Ballance 1961; Calkins and Hodgen 2007; Cambero et al. 2000; Crocker 1948; Cross et al. 1986; Farmer 1994; Geay et al. 2001:12; Landmann and Batzer 1966; Macleod and Ames 1986; Mottram 1998; Mottram et al. 2004; Ramarathnam et al. 1991; Rhee 1989; Shahidi et al. 1986; Stetzer et al. 2008; Wang et al. 1996; see also Hart and Sussman 2008:228). One of the first scientific studies to demonstrate the tasteless character of fresh raw meat was published over half a century ago by Crocker (1948:180):
Retrospective comparison of Velcro ® and twill tie outcomes following pediatric tracheotomy

Abstract Objectives To compare the rates of skin-related complications and accidental decannulation in pediatric patients who received Velcro® ties versus twill ties during the early postoperative period following tracheotomy. The rates of skin-related complications and accidental decannulation in patients with Velcro® ties was hypothesized to differ from those in patients with twill ties. Methods Medical records of 109 patients ≤18 years old who underwent elective tracheotomy were reviewed: 70 received twill ties and 39 received Velcro® ties. Patients were followed for the first seven postoperative days. The primary outcome was skin-related complications, which were further categorized into mild (irritation) and severe (breakdown). The secondary outcome was accidental decannulation. Rates of skin-related complication and accidental decannulation were compared across the two groups using chi-square analysis. Results Skin irritation occurred in 32 patients (45.7%) with twill ties and 10 patients (25.6%) with Velcro®. Skin breakdown occurred in 20 patients (28.6%) with twill ties and 6 patients (15.4%) with Velcro®. There were no accidental decannulation events. The use of Velcro® ties was associated with a decreased rate of skin irritation (OR: 0.41; 95% CI: 0.17–0.97; P = 0.039). Conclusions The use of Velcro® ties was associated with a decrease in the rate of skin irritation. There were no accidental decannulation events. These findings support the use of Velcro® ties at the time of pediatric tracheotomy placement.
Degradation Analysis of PV Modules After Long-Term Exposure in Florida

Field exposure is essential for evaluating the reliability and durability of PV modules. In this work we characterize three crystalline silicon PV systems that have been deployed in Florida. Detailed characterization of module performance was carried out to quantify degradation rates and identify root cause degradation mechanisms.
Characterization and Traversal of Pliable Vegetation for Robot Navigation

Outdoor mobile robots currently treat vegetation as obstacles that need to be avoided. In order to have less conservative robots that fully exploit their motion capabilities, it is required to obtain models of the interaction of vegetation with the vehicle. This work proposes and experimentally verifies models of interaction of wheeled and tracked vehicles with pliable vegetation. In addition, a methodology to map perceptual features of the environment to resistive forces experienced by the robots is presented.
42nd Annual Foulston-Siefkin Lecture: The Next Wave of Fourth Amendment Challenges After Carpenter

This is an edited and adapted version of the 42nd Annual Foulston Siefkin Lecture, delivered at Washburn University School of Law. The lecture discusses the future of Fourth Amendment law following the Supreme Court’s enormously important decision in Carpenter v. United States. It analyzes Carpenter and argues that its detailed account of the privacy harms caused by government surveillance will be its most important legacy. Moreover, the Court’s emphasis on the risk of privacy harm is not a one-off or a sharp break from previous practice. Carpenter is consistent with a long line of Supreme Court decisions ignoring or reshaping previous Fourth Amendment doctrines when necessary to protect citizens against unchecked surveillance. It also echoes previous cases that focus on the revealing, extensive, or intimate nature of surveillance when assessing whether a Fourth Amendment search has occurred. The lecture then details some of the novel surveillance technologies that are likely to reach the Supreme Court over the next several years. These technologies include drones, smart homes and devices, web surfing surveillance, and pole cameras targeting a specific suspect’s home. Many of these technologies have already been used in police investigations and evaluated by judges in lower court cases. The lecture assesses how the Supreme Court is likely to resolve these cases and uses the framework of Carpenter and its predecessors to make predictions about the future direction of Fourth Amendment law.
University of California Cannabis Research Workshop May 2019 Meeting Summary

On May 30, 2019, the University of California Office of the President, in partnership with University of California, Irvine, hosted a daylong University of California Cannabis Research Workshop designed to explore ways to advance research collaborations on a range of relevant topics, develop a common understanding of the current regulatory framework for conducting cannabis-related research, and formulate next steps for facilitating synergistic cannabis research. This report provides a summary of that meeting.
Cold hardiness in Spathius galinae (Hymenoptera: Braconidae), a larval parasitoid introduced for biocontrol of emerald ash borer in North America

Abstract The ability of a biocontrol agent to acclimate to and survive the climate of intended introduction locations is a critical attribute for successful biological control of an invasive pest. We evaluated the cold tolerance of Spathius galinae Belokobylskij & Strazanac, a braconid parasitoid native to the Russian Far East introduced to the United States for biocontrol of the ash (Fraxinus spp.) pest, emerald ash borer (EAB), Agrilus planipennis Fairmaire, by measuring the supercooling point (SCP) of mature S. galinae larvae exposed to winter temperatures at four different field locations that span a gradient of plant hardiness zones. We observed a significant effect of overwintering location on SCPs of S. galinae larvae collected from field populations, with lower SCPs observed at locations with lower average minimum ambient temperatures. We also tested the SCP of three stages (early-instar, late-instar, and mature cocooned larvae) of lab-reared parasitoids and found that SCP did not significantly differ between stages of lab-reared S. galinae. Our findings provide strong evidence that S. galinae can reduce SCP in response to below-freezing temperatures. The increase in cold hardiness of S. galinae in response to below-freezing temperatures should be considered in delineation of the optimal geographic range for biocontrol releases against EAB in North America.
PFKP phenotype in lung cancer: prognostic potential and beyond.

Rapid utilization of glucose is a functional marker of cancer cells, and has been exploited in the clinical diagnosis of malignancies using imaging technology. Biochemically, an increase in the rate of glycolysis, (i.e.) the process of conversion of glucose into pyruvate accelerates the net rate of glucose consumption. One of the critical determinants of glycolytic flux is the enzyme, phosphofructokinase (PFK) which converts fructose-6-phosphate into fructose 1,6, bisphosphate. PFK activity is allosterically inhibited or upregulated by cellular ATP or AMP, respectively. In a recent report of Cellular Oncology, Shen et al., have investigated one of the forms of PFK known as the platelet-type PFK (PFKP) in lung cancer. Using clinical samples as well as experimental models the authors unravel the cancer-related roles of PFKP and demonstrate that PFKP phenotype may predict the prognosis of lung cancer. In this letter, the findings are discussed in the light of recent research to expand the potential application and clinical impact of PFKP phenotype in lung cancer.
Effect of Overeating Dietary Protein at Different Levels on Circulating Lipids and Liver Lipid: The PROOF Study.

Background: During overeating, a low protein diet slowed the rate of weight gain and increased the energy cost of the added weight, suggesting that low protein diets reduced energy efficiency. The Protein Overfeeding (PROOF) study explored the metabolic changes to low and high protein diets, and this sub-study examined the changes in body composition and blood lipids when eating high and low protein diets during overeating. Methods: Twenty-three healthy volunteers (M = 14; F = 9) participated in an 8-week, parallel arm study where they were overfed by ~40% with diets containing 5% (LPD = low protein diet), 15% (NPD = normal protein diet), or 25% (HPD = high protein diet) protein. Dual energy X-ray absorptiometry (DXA) and computer tomography (CT) were used to quantify whole body and abdominal fat and intrahepatic lipid, respectively. Metabolites were measured by standard methods. Results: Protein intake and fat intake were inversely related since carbohydrate intake was fixed. Although overeating the LPD diet was associated with a significant increase in high density lipoprotein (HDL)-cholesterol (p < 0.001) and free fatty acids (p = 0.034), and a significant decrease in fat free mass (p < 0.0001) and liver density (p = 0.038), statistical models showed that dietary protein was the main contributor to changes in fat free mass (p = 0.0040), whereas dietary fat was the major predictor of changes in HDL-cholesterol (p = 0.014), free fatty acids (p = 0.0016), and liver fat (p = 0.0007). Conclusions: During 8 weeks of overeating, the level of dietary protein intake was positively related to the change in fat free mass, but not to the change in HDL-cholesterol, free fatty acids, and liver fat which were, in contrast, related to the intake of dietary fat.
The effect of topical lidocaine on intradermal testing in atopic dogs.

Background Intradermal testing (IDT) most often requires sedation. Topical lidocaine offers an adjunct or alternative to sedation. Hypothesis/objectives We hypothesized that topical lidocaine would significantly reduce reactions to intradermal injections and that atopic dogs treated with topical lidocaine would have similar results with IDT to atopic dogs tested without topical lidocaine. Animals Fifteen client-owned atopic dogs. Methods In Part I, a 5% lidocaine patch, 5% lidocaine cream and a control with no active ingredients were compared. The lowest pain score during intradermal injection was established in six atopic dogs. Fifteen atopic dogs were enrolled in Part II, and lidocaine cream (found to be most effective in Part 1) was applied randomly to a single side of the thorax. An IDT was performed on each side of the chest. Subjective and objective scores of the control and lidocaine treatment sides were compared 15 and 30 min post-injection. Results The 5% lidocaine cream had the greatest reduction in pain score associated with intradermal injection. There were no significant differences in mean wheal diameter for any evaluated allergen at any time point between the control and lidocaine-treated sides. There was high agreement between the two groups when assessing the subjective score for all but one allergen. Conclusions and clinical importance Topical lidocaine may be used as adjunctive analgesia during IDT with caution in interpretation of subjective house dust scoring. Lidocaine cream appeared to reduce pain score and may allow reduction in concurrent sedation.
Video sequence querying using clustering of objects' appearance models

In this paper, we present an approach for addressing the 'query by example' problem in video surveillance, where a user specifies an object of interest and would like the system to return some images (e.g. top five) of that object or its trajectory by searching a large network of overlapping or non-overlapping cameras. The approach proposed is based on defining an appearance model for every detected object or trajectory in the network of cameras. The model integrates relative position, color, and texture descriptors of each detected object. We present a 'pseudo track' search method for querying using a single appearance model. Moreover, the availability of tracking within every camera can further improve the accuracy of such association by incorporating information from several appearance models belonging to the object's trajectory. For this purpose, we present an automatic clustering technique allowing us to build a multi-valued appearance model from a collection of appearance models. The proposed approach does not require any geometric or colorimetric calibration of the cameras. Experiments from a mass transportation site demonstrate some promising results.
Risk, Disability, and Citizenship: U. S. Railroaders and the Federal Employers' Liability Act

This paper examines how a developing work culture shaped by death and disability created a distinct federal policy approach to workplace accidents in the U. S. railroad industry. Railroaders argued that only men willing to bravely confront risks as individuals would succeed in their occupation. As railroading's dangers increased at the end of the nineteenth century, this individualistic approach was replaced by cooperative efforts to campaign for railroad safety. Railroaders, however, were still able to make claims on the government based on their relationship with danger. They argued that since their work was similar to warfare, they should be awarded federal pensions. Although this did not happen, railroaders did successfully claim a privileged citizenship status through the passage of the Federal Employers Liability Act of 1908, which recognized their argument that the dangers with which they grappled and their resulting physical sacrifices made them more than mere wage workers.
Systolic time intervals in patients with artificial pacemakers

Systolic time intervals were measured in 11 patients with a transvenous ventricular demand pacemaker. There was a close relation between atrioventricular conduction time (P-R interval) and both left ventricular ejection time and preejection period; a P-R interval of 180 to 200 msec was associated with a maximal left ventricular ejection time, a minimal preejection period and an optimal stroke volume. Thus, by employing the noninvasive technique of measuring systolic time intervals, we were able to confirm that a properly timed atrial contraction makes an important contribution to the enhancement of stroke volume of the left ventricle.
Hash-merge join: a non-blocking join algorithm for producing fast and early join results

We introduce the hash-merge join algorithm (HMJ, for short); a new nonblocking join algorithm that deals with data items from remote sources via unpredictable, slow, or bursty network traffic. The HMJ algorithm is designed with two goals in mind: (1) minimize the time to produce the first few results, and (2) produce join results even if the two sources of the join operator occasionally get blocked. The HMJ algorithm has two phases: The hashing phase and the merging phase. The hashing phase employs an in-memory hash-based join algorithm that produces join results as quickly as data arrives. The merging phase is responsible for producing join results if the two sources are blocked. Both phases of the HMJ algorithm are connected via a flushing policy that flushes in-memory parts into disk storage once the memory is exhausted. Experimental results show that HMJ combines the advantages of two state-of-the-art nonblocking join algorithms (XJoin and Progressive Merge Join) while avoiding their shortcomings.
Ultrasound imaging beyond the vasculature with new generation contrast agents

Current commercially available ultrasound contrast agents are gas-filled, lipid- or protein-stabilized microbubbles larger than 1 µm in diameter. Because the signal generated by these agents is highly dependent on their size, small yet highly echogenic particles have been historically difficult to produce. This has limited the molecular imaging applications of ultrasound to the blood pool. In the area of cancer imaging, microbubble applications have been constrained to imaging molecular signatures of tumor vasculature and drug delivery enabled by ultrasound-modulated bubble destruction. Recently, with the rise of sophisticated advancements in nanomedicine, ultrasound contrast agents, which are an order of magnitude smaller (100-500 nm) than their currently utilized counterparts, have been undergoing rapid development. These agents are poised to greatly expand the capabilities of ultrasound in the field of targeted cancer detection and therapy by taking advantage of the enhanced permeability and retention phenomenon of many tumors and can extravasate beyond the leaky tumor vasculature. Agent extravasation facilitates highly sensitive detection of cell surface or microenvironment biomarkers, which could advance early cancer detection. Likewise, when combined with appropriate therapeutic agents and ultrasound-mediated deployment on demand, directly at the tumor site, these nanoparticles have been shown to contribute to improved therapeutic outcomes. Ultrasound's safety profile, broad accessibility and relatively low cost make it an ideal modality for the changing face of healthcare today. Aided by the multifaceted nano-sized contrast agents and targeted theranostic moieties described herein, ultrasound can considerably broaden its reach in future applications focused on the diagnosis and staging of cancer.
Dynamic Regulation of IFN-γ Signaling in Antigen-Specific CD8+ T Cells Responding to Infection

IFN-gamma plays a critical role in the CD8(+) T cell response to infection, but when and if this cytokine directly signals CD8(+) T cells during an immune response is unknown. We show that naive Ag-specific CD8(+) T cells receive IFN-gamma signals within 12 h after in vivo infection with Listeria monocytogenes and then become unresponsive to IFN-gamma throughout the ensuing Ag-driven expansion phase. Ag-specific CD8(+) T cells regain partial IFN-gamma responsiveness throughout the contraction phase, whereas the memory pool exhibits uniform, but reduced, responsiveness that is also modulated during the secondary response. The responsiveness of Ag-specific CD8(+) T cells to IFN-gamma correlated with modulation in the expression of IFN-gammaR2, but not with IFN-gammaR1 or suppressor of cytokine signaling-1. This dynamic regulation suggests that early IFN-gamma signals participate in regulation of the primary CD8(+) T cell response program, but that evading or minimizing IFN-gamma signals during expansion and the memory phase may contribute to appropriate regulation of the CD8(+) T cell response.
The first example of a lariat ether that forms a pseudo-sandwich complex

Abstract A lariat ether having a five-oxygen sidearm, forms a mono-potassium complex that appears to be more closely related to a bis(crown), sandwich complex than to a lariat ether. The lariat ether based on aza-15-crown-5, having attached to nitrogen the five-oxygen sidearm -CH2CH2OCH2CH2OCH2CH2OCH2CH2OCH2CH2OCH3, forms a mono-potassium complex that appears to be more closely related to a bis(crown), sandwich complex than to a lariat ether but full involves all of the sidearm as well as macroring oxygen donor atoms.
EFFECTS OF GAIN VERSUS LOSS OF REWARD ON ACTUAL AND PERCEIVED ALTRUISM

Sammary.-The effects of loss versus gain of reward on altruistic responding and subsequent self-ratings of altruism were examined for 46 male subjects. Subjects who lost reward were told they would lose experimental credit for helping. .Subjects who gained reward were told they would receive full credit and do less work for helping. Control subjects were not asked for assistance. Subjects who lost reward were significantly less likely to help than subjects who gained reward. Subjects who lost reward and helped rated themselves significantly higher in altruism than all other subjects who did not differ.
Arterial Muscle Myosin Heavy Chains and Light Chains in Spontaneous Hypertension

Increased maximum velocity of shortening (Vmax), increased shortening ability (ΔLmax) and decreased relaxation rate have been reported for arterial smooth muscle from 16- to 18-week-old spontaneously hypertensive rats (SHR) compared with age-matched normotensive Wistar-Kyoto rats (WKY). Vmax is dependent on actomyosin ATPase activity, and this activity is in turn dependent on the level of phosphorylation of the 20-kDa myosin light chain (MLC20) normally a function of calcium concentration. In this article, methods are described and data are presented from studies addressing possible intracellular regulatory mechanisms that might lead to the altered contractility of the SHR arterial muscle. In one study, myofibrillar protein was extracted from 16- to 18-week-old SHR and WKY caudal arterial muscle. The Mg2+-activated ATPase activity was measured under conditions where the Ca2+ concentration was controlled. In another study, the amount of myosin present and relative proportions of the myosin heavy chain (MHC) isoforms were determined by quantitative SDS-PAGE using heavy molecular weight standards and bovine serum albumin as the standard for concentration. In a third study, MLC20 phosphorylation levels in electrically stimulated arterial muscle were determined by urea glycerol gel electrophoresis and Western blot analyses. The SHR (n = 6) myofibrillar ATPase liberated 0.011 ± 0.003 μmol Pi/mg myosin/min, which was significantly more than the 0.006 ± 0.001 μmol Pi/mg myosin/min liberated by the WKY (n = 4) myofibrillar ATPase (P < 0.05). Consistent with the increased ATPase activity, phosphorylation of MLC20 was increased by 2.8 times as much in the SHR compared with the WKY electrically stimulated arterial muscle. However, there was no difference in MHC isoform pattern in the SHR compared with the WKY arterial muscle in contrast to the findings of at least one other laboratory. This discrepancy is discussed. The data reviewed in this article lead to the conclusions that an increased actin-activated myosin ATPase activity and MLC20 phosphorylation are likely responsible for the increased velocity of shortening previously reported in SHR arterial muscle and the increased ATPase activity is not a function of an increased myosin content or of altered MHC isoform pattern in the SHR muscle.
Optimizing Endocrine Therapy for Metastatic Breast Cancer

New therapies and advances in molecular biology provide opportunities for progress in the management of patients with advanced estrogen receptor-positive breast cancer. The near universal exposure of patients with early stage disease to endocrine therapy poses challenges of resistance when disease recurs. Analysis of tumor tissue at the time of recurrence, and after subsequent endocrine therapy where possible, is critical to understanding the most productive strategies for development and ultimately for individual patients.
Introduction to biomedical imaging

This lecture will cover the basic image formation principles underlying various imaging modalities (such X-ray CT, MRI, etc.). Issues from data acquisition, image reconstruction, and image processing will be discussed, along with various application examples.
Palliative Medicine Death Rounds: Small Group Learning on a Vital Subject:

Background. The medical student's experience with patients' dying and death has profound impact on personal and professional development. Death Rounds at the University of New Mexico School of Medicine is a small group educational model that promotes student self-reflection, metacognition, professional growth, and collegial support.Objective. To describe the implementation and evaluation activities of a third year clerkship Death Rounds which are a structured, institutionally supported resource for helping students to understand the clinical, ethical, legal, professional, cultural, and spiritual aspects of death.Design. Medical students attend 2 to 3 small group palliative medicine Death Rounds sessions, facilitated by the attending clerkship director, chief residents, and a palliative care physician.Conclusions. The students' assessment of their palliative medicine knowledge and skills in 5 categories before and after participation in Death Rounds rated their skills after Death Rounds higher with effect ...
The Geographies of Online Job Search: Preliminary Findings from Worcester, MA

For those who have online access, the Internet significantly reduces the cost and time of transferring information over distance. This paper explores the potential of the Internet to improve people's employment opportunities by increasing their access to job information beyond that provided via their grounded social networks. Information circulating through grounded social networks is biased socially and geographically toward the life experiences of network members. The tendency for those members to have similar life experiences dampens the variability in the information exchanged in such networks. What is the potential for the Internet to expand people's access to information about jobs and employers' information about workers? We report on a pilot study undertaken in Worcester, Massachusetts, that examined employers' use of Internet recruiting for employees. The results of this qualitative study indicate that these employers use the Internet strategically to enhance the volume of applications when the l...
Reticulospinal connections with limb and axial motoneurons.

Responses of motoneurons supplying muscles of the forelimbs, hindlimbs, back, and neck to stimulation of the medial pontomedullary reticular formation were studied with intracellular recording in cere-bellectomized cats under chloralose anesthesia.
Electron photoejection from sodium salts of perylenide (Pe⨪,Na+) and its dianion (Pe2–,2Na+) in tetrahydrofuran. A new transient involving the ejected electron and its nature

Abstract Flash photolysis of sodium salts of perylene radical-anions (Pe?,Na + ) and dianions (Pe 2– ,2Na + ) revealed the formation of a new transient X involving a photoejected electron; its spectrum and kinetic behavior suggest its tentative structure.
Immunoaffinity Purification Using Anti-PEG Antibody Followed by Two-Dimensional Liquid Chromatography/Tandem Mass Spectrometry for the Quantification of a PEGylated Therapeutic Peptide in Human Plasma

Quantification of a PEGylated peptide in human plasma using LC-MS/MS to support clinical studies presented challenges in terms of assay sensitivity, selectivity, and ruggedness. To ensure specific recognition of PEGylated species, an immunoaffinity purification method (IAP) using anti-PEG antibody followed by two-dimensional (2D) LC-MS/MS was developed for MK-2662, an investigational peptide containing 38 amino acids with a 40 kDa branched PEG [poly(ethylene glycol)] at C-terminus. Biotinylated anti-PEG antibody, bound to streptavidin-coated magnetic beads, was used to capture MK-2662 and its stable-isotope-labeled internal standard from human plasma. After on-bead digestion with trypsin, the supernatant was injected on a 2D high-performance liquid chromatography (HPLC) system constructed with strong cation-exchange and reversed-phase columns, followed by MS/MS detection of the surrogate N(1-12)-mer of MK-2662 on an API5000. The assay ruggedness was improved by optimizing the trypsin digestion and sample storage conditions. The intraday validation, conducted in parallel with protein precipitation (PPT) assay, demonstrated 94.8-105.8% accuracy with <9.76% coefficient of variation (CV) for IAP, and 99.0-101.0% accuracy with <3.43% CV for PPT, over a dynamic range of 2-200 nM and 1-1000 nM, respectively. A cross comparison, performed using clinical samples, showed that the values obtained from IAP assay were about 15-30% lower than those from PPT method, which supports more specific PEG recognition provided by IAP.
The effects of pH on Ca2+-activated force in frog skeletal muscle fibers.

Ca2+-activated isometric force was recorded in skinned (sarcolemma mechanically removed) segments of frog skeletal muscle fibers immersed in bathing solutions of different pH (5.0–10.5) and Ca2+ concentrations. Force in maximally activated fibers was near zero at pH 5.5, increased as pH increased to 7.5 remained relatively constant until pH 9.0 and then rapidly declined to zero by pH 10.5. The Ca2+ concentration at which 50% of maximum force was developed decreased 25-fold as pH increased from 5.5–7.5. The data also indicate that, while the fibers remain viable with acidosis, they deteriorate rapidly with alkalosis. These observations may be relevant clinically, since the parallel known effects of acidosis on cardiac contractility. The possible sites of action of H+ on the Ca2+-activated force generating mechanisms are discussed.
Mouse Models for Efficacy Testing of Agents against Radiation Carcinogenesis—A Literature Review

As the number of cancer survivors treated with radiation as a part of their therapy regimen is constantly increasing, so is concern about radiation-induced cancers. This increases the need for therapeutic and mitigating agents against secondary neoplasias. Development and efficacy testing of these agents requires not only extensive in vitro assessment, but also a set of reliable animal models of radiation-induced carcinogenesis. The laboratory mouse (Mus musculus) remains one of the best animal model systems for cancer research due to its molecular and physiological similarities to man, small size, ease of breeding in captivity and a fully sequenced genome. This work reviews relevant M. musculus inbred and F1 hybrid animal models and methodologies of induction of radiation-induced leukemia, thymic lymphoma, breast, and lung cancer in these models. Where available, the associated molecular pathologies are also included.
Microscale Phase Separation Through Nanoporous Membranes

This paper presents an experimental study on bubbles extraction from a two-phase flow in microchannels. The bubbles were extracted through a hydrophobic porous membrane covering the microchannels. The two-phase flow was generated through mixing water and air at a T-junction positioned before a microchannel on a microfabricated device. To study the effect of different parameters on the extraction rate, an extensive parametric study was conducted. The parametric space included variations of the channel depth, pressure difference across the membrane, and water and air flow rates. Differential pressure across the membrane was found to be the most critical factor impacting the bubbles extraction rate. Also, the effect of flow quality on the extraction rate was determined to be insignificant. Furthermore, it was found that at a critical velocity a liquid layer forms between the bubbles and the membrane and consequently the bubbles cease to extract.Copyright © 2013 by ASME
Impulsiveness and compulsiveness in alcoholics and nonalcoholics

Impulsiveness and compulsiveness questionnaires were completed by recovering alcoholics (n = 54) and by a community sample (n = 351). No relationship was found, indicating these traits are independent, distinct constructs. Alcoholics scored significantly higher on impulsiveness than nonalcoholics, and impulsiveness was negatively associated with age for both groups. Interestingly, the significant difference between the two groups on impulsiveness was maintained across age groups. Alcoholic and nonalcoholic compulsiveness scores showed no difference; however, compulsiveness was negatively related to age in nonalcoholics, but not alcoholics.
Cyclic 3', 5'-nucleotide phosphodiesterase. The extent of reversibility of the reaction and the enthalpy of hydrolysis of cyclic AMP☆

Abstract 1. 1. The reversibility of the reaction catalyzed by cyclic 3',5'-nucleotide phosphodiesterase was studied from both the forward and reverse directions using labeled cyclic 3',5'-adenosine monophosphate and 5'-adenosine monophosphate, respectively. 2. 2. Cyclic AMP was quantitatively converted to 5'-AMP, but no synthesis of radioactive cyclic AMP was detected from labeled 5'-AMP, even in the presence of added nonlabeled cyclic AMP. These results indicate that the reverse reaction of phosphodiesterase was not measurable with our isotopic technique, and that the reaction is essentially unidirectional. 3. 3. The enthalpy of hydrolysis of cyclic AMP was measured microcalorimetrically and was found to be — 13.3 Kcal/mole. The high energy content thus provides a thermo-dynamic barrier against a reversal of the phosphodiesterase reaction.
Poster: Data intensive uncertainty quantification: applications to climate modeling

In October of 2009, LLNL began a three-year Strategic Initiative, "The Advance of Uncertainty Quantification Science with Application to Climate Modeling, Inertial Confinement Fusion Design, and Stockpile Stewardship Science." The goal of the project is to advance the Uncertainty Quantification (UQ) of multi-physics simulations with large collections of uncertain input parameters. The initial focus is on the UQ of global climate model simulations. This work will allow the uncertainty in climate simulations to be characterized, with the potential to reduce the uncertainties in the predictions of future climate change. Already, using two of the most widely-used community climate models, the most comprehensive set of U.S. ensemble-based UQ simulations of present-day climate has been produced: over 52,000 simulated years have been run and some 72 TB of data generated. This poster presents the approach and challenges associated with the generation and analysis of such a large ensemble data set, as well as the key role that the LLNL UQ Pipeline software plays.