cssi/SciSciGPT-SciSciNet huggingface dataset:
Selective Motor Neuron Resistance and Recovery in a New Inducible Mouse Model of TDP-43 Proteinopathy

Motor neurons (MNs) are the neuronal class that is principally affected in amyotrophic lateral sclerosis (ALS), but it is widely known that individual motor pools do not succumb to degeneration simultaneously. Because >90% of ALS patients have an accumulation of cytoplasmic TDP-43 aggregates in postmortem brain and spinal cord (SC), it has been suggested that these inclusions in a given population may trigger its death. We investigated seven MN pools in our new inducible rNLS8 transgenic (Tg) mouse model of TDP-43 proteinopathy and found striking differences in MN responses to TDP-43 pathology. Despite widespread neuronal expression of cytoplasmic human TDP-43, only MNs in the hypoglossal nucleus and the SC are lost after 8 weeks of transgene expression, whereas those in the oculomotor, trigeminal, and facial nuclei are spared. Within the SC, slow MNs survive to end stage, whereas fast fatigable MNs are lost. Correspondingly, axonal dieback occurs first from fast-twitch muscle fibers, whereas slow-twitch fibers remain innervated. Individual pools show differences in the downregulation of endogenous nuclear TDP-43, but this does not fully account for vulnerability to degenerate. After transgene suppression, resistant MNs sprout collaterals to reinnervate previously denervated neuromuscular junctions concurrently with expression of matrix metalloproteinase 9 (MMP-9), a marker of fast MNs. Therefore, although pathological TDP-43 is linked to MN degeneration, the process is not stochastic and mirrors the highly selective patterns of MN degeneration observed in ALS patients. SIGNIFICANCE STATEMENT Because TDP-43 is the major pathological hallmark of amyotrophic lateral sclerosis (ALS), we generated mice in which mutant human TDP-43 expression causes progressive neuron loss. We show that these rNLS8 mice have a pattern of axonal dieback and cell death that mirrors that often observed in human patients. This finding demonstrates the diversity of motor neuron (MN) populations in their response to pathological TDP-43. Furthermore, we demonstrate that resistant MNs are able to compensate for the loss of their more vulnerable counterparts and change their phenotype in the process. These findings are important because using a mouse model that closely models human ALS in both the disease pathology and the pattern of degeneration is critical to studying and eventually treating progressive paralysis in ALS patients.
Circling the Seas: Design of Lagrangian Drifters for Ocean Monitoring

Lagrangian drifters are oceanographic devices used to study circulation patterns in the ocean. The devices are typically passive, which means that they have no actuators to initiate motion. They are mainly driven by the ocean currents. A drifter, as depicted in Figure 1, in principle, consists of a surface float and a drogue connected via a tether. The surface float provides the necessary buoyancy to hold the drogue at a certain depth, whereas the drogue (and, thus, the whole drifter) is carried by the currents prevailing at that depth of the ocean. A main focus of oceanographers' and marine biologists' research is the complex dynamics of the ocean, the circulation patterns of water, and the induced movements of effluents, larvae, and other microorganisms [1]. Drifters are used to tag and track the ocean currents and can help to better explain both oceanographic as well as biological phenomena. Our particular interest is the monitoring task of tracking wastewater plumes in the coastal ocean. In this article, we describe the design of low-power, low-cost Lagrangian drifters for ocean monitoring, developed at the Robotic Embedded Systems Laboratory (RESL) at the University of Southern California (USC). We discuss the design challenges and present the overall system characteristics of the RESL drifters. The drifters are augmented by radio communication, which simplifies the task of drifter recovery by a research vessel and enables setting up a bidirectional wireless sensor network between drifters, autonomous underwater vehicles (AUVs), vessels, and base stations.
Dynamic control of fundamental physical interactions in strongly-correlated oxides

In this invited talk I will review the results of several recent studies wherein electronic structure and the metal-insulator transition temperature in the strongly-correlated oxide VO 2 is controlled via external stimuli, such as strain, temperature and ultrafast THz electric fields.
Maxwell: founder of theoretical physics

James Clerk Maxwell, like that other important British scientist of the 19th century Charles Darwin, was essentially a gentleman amateur. Both retired to their estates to complete their creative work. Darwin retreated from London and the Geological Society, Maxwell from university teaching. It was only out of a sense of duty that in 1871 Maxwell agreed to head the Cavendish Laboratory at Cambridge-eight years before he died aged just 47.
Nanochannel Arrays for Molecular Sieving and Electrochemical Analysis by Nanosphere Lithography Templated Graphoepitaxy of Block Copolymers.

The ability to design, fabricate, and manipulate materials at the nanoscale is fundamental to the quest to develop technologies to assemble nanometer-scale pieces into larger-scale components and materials, thereby transferring unique nanometer-scale properties to macroscopic objects. In this work, we describe a new approach to the fabrication of highly ordered, ultrahigh density nanochannel arrays that employs nanosphere lithography to template the graphoepitaxy of polystyrene–polydimethylsiloxane, diblock copolymers. By optimizing the well-controlled solvent vapor annealing, overcoating conditions, and the subsequent reactive ion etching processes, silica nanochannel (SNC) arrays with areal densities, ρA, approaching 1000 elements μm–2, are obtained over macroscopic scales. The integrity and functionality of the SNC arrays was tested by using them as permselective ion barriers to nanopore-confined disk electrodes. The nanochannels allow cations to pass to the disk electrode but reject anions, as demonst...
Maternal Employment and Child Day Care

The number of mothers, particularly those with young children, entering the labor force is increasing each year. Human development researchers, public policy decision makers, and taxpayers are justifiably concerned with the potential effects of maternal employment and the relative success or failure of various child-care environments. As maternal employment increases and utilization of out-of-home child-care services continues to expand, a thorough understanding of the long-term cognitive and psychosocial consequences to the child is crucial. The Danish sample presents an opportunity to describe common maternal work and child-care patterns and to determine their association with subsequent child and adolescent development.
Tear levels of insulin-like growth factor binding protein 3 correlate with subbasal nerve plexus changes in patients with type 2 diabetes mellitus

Purpose This study investigated the expression of insulin-like growth factor binding protein-3 (IGFBP-3) in basal tears of patients with type 2 diabetes mellitus compared to nondiabetic controls; and correlated tear levels of IGFBP-3 with morphologic changes in the subbasal nerve plexus and density of basal corneal epithelial cells. Methods This was a single visit, cross-sectional study. Diabetic and control subjects were matched for age, sex, smoking status, and body mass index. Tear levels of IGFBP-3 were measured using ELISA. Corneal nerve and basal epithelial cell changes were measured using in vivo confocal microscopy. Results Tear levels of IGFBP-3 were 3.5-fold higher in those with diabetes. Patients with diabetes also showed a reduction in nerve fiber layer, nerve branch density, and corneal basal epithelial cell density. There was no significant difference in corneal sensitivity. IGFBP-3 levels were highly correlated with nerve fiber length and branch density; while hemoglobin (Hb)A1c was only moderately correlated. There were no significant differences in the clinical or subjective signs of dry eye between groups, indicating that tear levels of IGFBP-3 and corneal nerve changes were not due to the presence of mild dry eye. Conclusions These findings indicate that tear levels of IGFBP-3 are more tightly correlated to nerve fiber changes in diabetes than HbA1c. Future studies that stratify the severity of diabetic disease with tear levels of IGFBP-3 are needed to validate this finding.
Phylogeny of the Agathidinae (Hymenoptera: Braconidae) with a Revised Tribal Classification and the Description of a New Genus

Abstract. The phylogeny of the Agathidinae is analyzed employing 45 agathidine genera, 172 Agathidinae operational taxonomic units, and sequences from the mitochondrial gene COI and the nuclear ribosomal gene 28S. The tribal classification is revised; two new tribes are proposed, i.e., Lytopylini and Agathirsini. Mesocoelini n. stat., is included as a tribe of Agathidinae for the first time. The concepts of Earinini and Agathidinini are revised. Biroia Szepligeti, 1900, is synonymized with Megalagathis Schulz, 1906 (emendation for Megagathis Krechbaumer 1894). A new genus and species from Colombia, Smithagathis davidsmithi Sharkey are erected. The currently recognized 61 genera of Agathidinae are presented in a list which includes their tribal placement. Biroia Szepligeti, 1900, and its junior synonym Isoptronotum Enderlein, 1920 are synonymized with Megalagathis Schulz, 1906, new synonymies. The species of Biroia are moved to Megalagathis as new combinations.
PYP IMAGING WITH CZT CAMERAS IS A SENSITIVE AND SPECIFIC IMAGING MODALITY TO DIAGNOSE TTR CARDIAC AMYLOIDOSIS

The basal ganglia (BG) have been hypothesized to implement a reinforcement learning algorithm. However, it is not clear how information is processed along this network, thus enabling it to perform its functional role. Here we present three different encoding schemes of visual cues associated with rewarding, neutral, and aversive outcomes by BG neuronal populations. We studied the response profile and dynamical behavior of two populations of projection neurons [striatal medium spiny neurons (MSNs), and neurons in the external segment of the globus pallidus (GPe)], and one neuromodulator group [striatal tonically active neurons (TANs)] from behaving monkeys. MSNs and GPe neurons displayed sustained average activity to cue presentation. The population average response of MSNs was composed of three distinct response groups that were temporally differentiated and fired in serial episodes along the trial. In the GPe, the average sustained response was composed of two response groups that were primarily differentiated by their immediate change in firing rate direction. However, unlike MSNs, neurons in both GPe response groups displayed prolonged and temporally overlapping persistent activity. The putamen TANs stereotyped response was characterized by a single transient response group. Finally, the MSN and GPe response groups reorganized at the outcome epoch, as different task events were reflected in different response groups. Our results strengthen the functional separation between BG neuromodulators and main axis neurons. Furthermore, they reveal dynamically changing cell assemblies in the striatal network of behaving primates. Finally, they support the functional convergence of the MSN response groups onto GPe cells.
Cylindrical microlenses for increasing the radiance of high-power laser diode stacks

We are fabricating diffraction limited cylindrical microlenses that can increase the effective radiance of high power laser diode stacks by two orders of magnitude.
The Nusc Windwave And Turbulence Observation Program (Wavtop); A Status Report

Abstract Wind generated white caps have been identified as providing the key mechanism by which a floating oil slick is fragmented and injected as droplets beneath the sea surface. Ambient motions of the wind waves and smaller scale turbulence then mix the oil further downward. After the initial' breaking, the degree of downward oil mixing is dependent upon the kinetic energy and Reynolds stresses of the wind wave motions. Our wave and turbulence observation program (WAVTOP) has developed instrumentation and techniques to gather field data of the wind generated motions in the upper 5-10 m. The sensor package (BLT) includes small fastresponse impellors, and a capacitance wave staff system. The impellor systems, which were calibrated in ship wave-tow tank, are configured in arrays to record velocities at several depths simultaneously for estimates of kinetic energy content, Reynolds stresses, and mean shear of the motions. The system is battery powered and self recording, utilizing a microprocessor and digitizer. Preliminary measurements were made in Narragansett Bay with the BLT mounted on a free drifting AESOP Stable Spar Buoy and from an extended boom on Gould Island. Measurements were made to relate the local wind with the growth of wind waves and their turbulent kinetic energy. Preliminary results portray the energy attenuating with depth following classical theory, where changes are highly correlated with the local wind speed. Also there appear phase lags of energy with wind changes and evidence of a downward propagating rate of energy at 0.5 cm/sec. Fluctuations in variance appear to occur in curious pulses over 3-5 minute periods and wave energy appears to “advect” downwind in packets. Vertically integrated energy content appears to correlate with the cube of the wind speed.
Enteral Nutrition Initiation in Children Admitted to Pediatric Intensive Care Units After Traumatic Brain Injury.

Traumatic brain injury (TBI) is the leading cause of death and long-term disability among injured children. Early feeding has been shown to improve outcomes in adults, with some similar evidence in children with severe TBI. We aimed to examine the current practice of initiation of enteral nutrition in children with TBI and to evaluate the risk factors associated with delayed initiation of enteral nutrition. This retrospective, multicenter study used the Pediatric Trauma Assessment and Management Database including all children with head trauma discharged from five pediatric intensive care units (PICU) at pediatric trauma centers between January 1, 2013 and December 31, 2013. We compared demographics, injury and procedure data, time to initiation of nutrition, and injury and illness severity scores between patients who received enteral nutrition early (≤ 48 h) and late (> 48 h). Fisher’s exact and Mann–Whitney U tests compared discrete and continuous variables. Univariate and multivariable analyses evaluated variables associated with delayed initiation of feeding. Outcomes of interest included mortality, complications, ventilator days, hospital and ICU length of stay, and functional status at ICU discharge. In the 416 patients in the study, the overall mortality was 2.6%. The majority of patients (83%; range 69–88% between five sites, p = 0.0008) received enteral nutrition within 48 h of PICU admission. Lower Glasgow Coma Scale scores and higher Injury Severity Score (ISS) were independently associated with delayed initiation of enteral nutrition. Delayed enteral nutrition was independently associated with worse functional status at PICU discharge (p = 0.02) but was not associated with mortality or increased length of stay. Children with severe TBI and higher ISS were more likely to have delayed initiation of enteral nutrition. Delayed enteral nutrition was an independent risk factor for worse functional status at ICU discharge for the entire cohort, but not for the severe TBI group.
Subtle and reversible interactions of ambient pressure H2 with Pt/Cu(111) single-atom alloy surfaces

Abstract Pt-Cu single-atom alloys (SAA) have been identified as promising hydrogenation catalysts with an ability to activate H2 better than the individual metals alone. We studied the interaction between H2 and Pt/Cu(111) SAA model surface using ambient pressure X-ray photoelectron spectroscopy (AP-XPS). A binding energy shift in the Pt 4f spectrum indicates the presence of adsorbed H at 350 K, occurring because of H H bond activation. No evidence was found of either surface segregation, subsurface diffusion of Pt atoms, or any effects on the thermal stability of the surface, likely due to the subtle interaction between Pt and H. This shift is reversible upon evacuation of H2, which is a sign of a weak interaction. In addition, we studied the effect of H2 and CO co-adsorption and found that while the surface is unaffected by poisoning by a small amount of CO at 350 K, CO can displace adsorbed H on almost half of the surface Pt sites at 300 K. The susceptibility to CO poisoning increases after the surface was heated to 450 K due to changes in the structure of the subsurface layer that enhance the binding of CO to the surface Pt sites.
Effects of virtual reality on theme park visitors' experience and behaviors: A presence perspective

Abstract Advances in virtual reality (VR) technology exert increasingly influential impacts on tourism. Drawn upon a presence perspective and a process theory, this research aims to explore how VR technology may help enhance theme park visitors' experience and behaviors. Data was collected from 396 theme park visitors who had experienced VR roller coaster over the past twelve months. Results of stepwise regression analysis suggest that users' sense of presence is predominantly driven by their feeling of control, followed by participation, effectiveness, curiosity, vividness, temporal association, and enjoyment provided by VR system. Results of simple linear regression analyses reveal positive impacts of sense of VR presence on visitors' overall theme park experience and intentions to revisit and recommend. Further sensitivity tests are performed using Hayes’ PROCESS model to accommodate the potential influence of two individual factors (i.e., personal innovativeness and VR familiarity) on the results. Theoretical and managerial implications are presented.
THE CELLULAR BASIS FOR ESTABLISHING TOLERANCE OR IMMUNITY TO BOVINE γ-GLOBULIN IN MICE

Publisher Summary This chapter presents the cellular basis for establishing tolerance or immunity to bovine γ-globulin (BGG) in mice. In an experiment discussed in the chapter, the capacity of the reticuloendothelial systems of BALB/c and DBA/2 mice is compared to remove immunogenic material by studying biologic filtration in vivo . Large amounts of l25 I-trace labeled BGG were given to groups of mice of either strain. Two days later they were bled out and the amount of residual BGG in the serum was estimated by scintillation counting. Various doses of this biologically-filtered BGG were given to normal BALB/c mice and their subsequent development of tolerance or immunity was assessed in the usual way. The cell responsible for resistance to tolerance induction in BALB/c mice is especially capable of filtering out an immunogenic fraction of ultracentrifuged BGG; this ability is undiminished by lethal irradiation, is abrogated by a macrophage-toxic substance, and resides in an adherent cell population.
Targeting NEK2 Kinase In Drug-Resistant Multiple Myeloma with Small Molecule Inhibitors

Abstract 788 Background: Treatment failure in malignant diseases, including multiple myeloma (MM), is due to drug resistance of a minor population of cancer cells, already present de novo. Gene expression profiling (GEP) data can be obtained repeatedly during different phases of treatment. Thus, it is possible to monitor newly acquired genetic changes in the drug-resistant MM clone. Materials and Methods: Nineteen primary MM patients enrolled in protocol 25009, provided 59 samples, obtained at baseline, pre-1st, pre-2nd, post-2nd stem cell transplant, and in consolidation. GEP was performed using Affymetrix U133Plus2 chips. In addition, a total of 2552 samples with GEP and clinical data, obtained from published studies, were analyzed. We induced NEK2 over-expression and knockdown using a lentiviral delivery system. A NEK2 inhibitor, NI-2, was identified by screening a kinase inhibitor library including 160 compounds and was used for our in vitro and in vivo studies. Results: By comparing serial GEP samples at baseline versus after treatment or at rapid relapse, we defined 56 genes associated with drug resistance. Ten of the top 20 genes belong to the well established chromosomal instability (CIN) signature. The mean expression levels of CIN genes define a high-risk score present in 10% of newly diagnosed MM patients, which is associated with shorter durations of response, event-free (EFS) (HR = 4.8; P Conclusion: We conclude that NEK2 is an important indicator of drug resistance, and therefore, of poor prognosis in MM and many other cancers. It represents a logical target to overcome drug resistance. In combination with other chemotherapies, it may result in the curing of previously incurable neoplasias, including MM. Our future work will aim at modifying NEK2 inhibitors to optimize activity and decrease toxicity of NEK2 kinase inhibitors in collaboration with our medicinal chemistry colleagues. Disclosures: No relevant conflicts of interest to declare.
Direct Imprinting of Quasi‐3D Nanophotonic Structures into Colloidal Quantum‐Dot Devices

Three-dimensional (3D) subwavelength nanostructures have emerged and triggered tremendous excitement because of their advantages over the two-dimensional (2D) counterparts in fields of plasmonics, photonic crystals, and metamaterials. However, the fabrication and integration of 3D nanophotonic structures with colloidal quantum dots (CQDs) faces several technological obstacles, as conventional lithographic and etching techniques may affect the surface chemistry of colloidal nanomaterials. Here, the direct fabrication of functional quasi-3D nanophotonic structures into CQD films is demonstrated by one-step imprinting with well-controlled precision in both vertical and lateral directions. To showcase the potential of this technique, diffraction gratings, bilayer wire-grid polarizers, and resonant metal mesh long-pass filters are imprinted on CQD films without degrading the optical and electrical properties of CQD. Furthermore, a dual-diode CQD detector into an unprecedented mid-wave infrared two-channel polarization detector is functionalized by embedding an imprinted bilayer wire-grid polarizer within the CQDs. The results show that this approach offers a feasible pathway to combine quasi-3D nanostructures with colloidal materials-based optoelectronics and access a new level of light manipulation.
Updating the Constitution: Amending, Tinkering, Interpreting

This is a revised version of a presentation made at the annual Constitutional Law Symposium at Drake University School of Law in April 2019. The U.S. Constitution is now 230 years old, and it is showing its age. Its text, taken in the sense that its enactors understood it, is, unsurprisingly, inadequate to the needs of a large, populous twenty-first century nation. The Constitution creates a government that is carefully insulated from the democratic preferences of the population. It fails to vest the central government with the tools needed to manage and regulate a vast, complicated, and interrelated society and economy. On the other hand, it guarantees its citizens protection of only a limited set of human rights. Notwithstanding these blatant defects, the means provided in the constitutional text to change it, to improve it, are insufficient to make it appropriate for current conditions. There is reason to be skeptical of studies purporting to measure the difficulty of constitutional amendment procedures. But combined with an inspection of the text and the history of amendment, this research is persuasive and supports the claim that reliance on Article V’s procedures are unlikely to successfully reform the Constitution. On top of these objective measures, moreover, constitutional revision in the United States is hampered by a widely held, though uninformed, opinion that the current Constitution is still protecting national welfare and that any change—any tinkering—with the rules in that document bears a heavy burden of persuasion. Reform by amendment, that is, appears to be a dead end. The U.S. judiciary, however, has, in an important way, come to the rescue of a polity that would otherwise be in a perpetual thrall to the principles of the eighteenth century. In “interpreting” the Constitution, the courts have gone a long way to correct the defects listed. But their “interpretations” have little relationship to the fixed rules installed by the constitutional enactors. Judges have assumed what amounts to a power of constitutional amendment. But such an amendment technique is irregular, unpredictable, and devoid of the sanction of the “people,” past or present, whose assent is usually thought essential to constitutional legitimacy. The United States has escaped the disadvantages of an outdated Constitution but at the price of subverting the constitutional rule of law.
Synthetic MRI-aided pelvic multi-organ segmentation in cone-beam computed tomography.

CBCT-guided adaptive prostate radiotherapy requires the accurate and rapid segmentation of the prostate and organs-at-risk from on-board CBCT images. Automatic segmentation based solely on CBCT can eliminate the need for registration to the planning CT, but has not been widely studied. Soft tissue contrast, such as prostate, is poor on CBCT images, which is often further degraded by CBCT artifacts. In this study, a new segmentation strategy is proposed for pelvic multi-organ segmentation aided by CBCT-based synthetic MRI. We tested our proposed method using 20 prostate cancer patients’ who underwent radiotherapy. The mean Dice similarity coefficient (DSC) of bladder, prostate and rectum were 95%, 86%, and 91%, which demonstrated the detection and segmentation accuracy of the proposed method. Methods for the accurate and fast segmentation of the prostate, bladder and rectum warrants further development in support a CBCT-guided adaptive radiotherapy workflow for prostate cancer.
Laser-Assisted coating techniques and surface modifications: a short review

A wide variety of coating methods and materials are available for different applications while the common purpose of all of them is protecting a part or structure exposed to mechanical or chemical damage. Decreased manufacturing cost is another important advantage of having a coating layer on substrate materials when there is a need for a high-performance and expensive material on the exposed surfaces of a part. In such cases, the part body may be manufactured out of less expensive materials and coated by the desired expensive material only at the exposed surfaces. Laser-assisted processes, such as laser cutting, laser welding, laser-assisted coating, etc. are a revolutionary set of processes in fabricating mechanical parts using a laser as the heat source. Laser-based processes have also been employed to create material deposition on selected areas to provide a protective layer. Depending on the deposited materials, these protective layers can serve to enhance corrosion and wear resistance, heat transfer, and mechanical behavior of substrates. To date, numerous laser-assisted processes have been introduced and investigated. Although each of these processes provides advantages, there are always drawbacks limiting their applications. In this article, laser-assisted coating methods are categorized, and a comparative study of these techniques is presented. It is likely to see higher qualities of protection by evolving more advanced techniques and materials in the future.
Parkinson’s Disease: Debunking an old theory

Recording the neural activity of cells in the brain of patients with Parkinson's disease challenges long-standing assumptions about how this disease manifests at the cellular level.
Cellular Automata and Recursive Growth

When we stroll across the quad, we feel we move through unbroken space that smoothly connects our beginning and ending points and that time flows continuously without interruption during our walk. When we pour water from one container to another, it is a continuous stream of water that flows. Yet, we know that water, at one level, is composed of discrete molecules. And we know that organisms reproduce discretely; each female produces an integer number of offspring or each asexually dividing cell results in exactly two cells. In the space and time scales of the quad, we are a distinct entity that moves, not an amorphous, diffuse electromagnetic field. Moreover, our neurons fire at discrete intervals, with finite recovery periods, and, more or less, in an on-off manner that prevents our observing the world at arbitrarily small time intervals. In this way, our senses and perceptions are digital; it is something else that makes us think reality is continuous. It could be reality itself that gives us this idea, even if we base our beliefs on incomplete knowledge. Indeed, many of our earlier models and techniques used a discrete representation that was justified as an abstraction to simplify our computations or analysis of what we believed to be the true, underlying continuous physical reality. But given the particulate nature of our perceptions of nature and the underlying discreteness of many biological processes, we have to ask: Which is the reality and which the abstraction: continuous or discrete -analog or digital? Given that the world includes the observers and that, to a certain extent, the world is as we observe it, the answer is probably “both.”
Fictions of Feminine Citizenship: Sexuality and the Nation in Contemporary Caribbean Literature

Introduction Charting Atlantic Modernities' Desire Lines Postcard and Policies: Stories behind the American Occupation Silences Too Horrific to Disturb in Haiti and the Dyaspora Independence Romances Novel Insights: Sex Work, Secrets, and Depression Coda
Constructive Design of Robust Optimal Regulators

An algorithm is developed that determines the parameters of a robust dynamic linear regulator which is optimal in the sense that it minimizes a quadratic cost function. Robustness is achieved by constraining the solution to a set of controllers which satisfy an inequality based on the small gain theorem. The resulting closed loop system will remain stable even when plant dynamics deviate from the nominal by perturbations within some prescribed set.
Focus on . . . COBRA Continuation Coverage Requirements for Group Health Plans (Part II)

In February 1999 the IRS issued final and proposed regulations providing guidance on COBRA continuation coverage. Part I of this article, in the previous issue of this journal, provided background information on COBRA and discussed key definitions and special rules found in the final and proposed regulations. Part II continues this discussion.
URREF for veracity assessment in query-based information fusion systems

The uncertainty representation and reasoning evaluation framework (URREF) ontology discusses an organization, categorization, taxonomy and definitions of uncertainty. Uncertainty can be either subjective or objective pending its source. For example, the information's origin can affect the evaluation, processing, and results from information fusion systems. In this paper we explore the coordination of a user and machine, and its effects on the ontology; our focus is on query-based systems. A user requesting information provides refinement of the analysis via queries which are typically semantic in nature. A query that is continuously refined reduces uncertainty and the information can be used in the ontology as part of the source, evaluation, and information quality. For example, a user receiving a response to a query can determine if the response meets the quality, evaluation, and source criteria. The user response (i.e. relevance feedback) to “did this answer your question,” can subsequently alter the uncertainty values. Together with the URREF ontology, query-based information fusion systems can work synergistically to reduce decision uncertainty.
The Evolution of Forms of Water Users Organizations in California

The statutory means available to Californians to acquire, conserve, or distribute water as public corporations are many and varied.' There are hundreds of public water organizations now existing in this state2 and there are more to come. Of these the vast majority are organized under established and familiar general statutes. No more than forty were created by or organized under special district acts. Special act districts are a fairly recent development, not to say fashion, in legislation. The dominating group here is the county-wide type, usually titled "county flood control," or "county flood control and water conservation" districts. All of them reflect generally the first statute, which was the Los Angeles County Flood Control Act, enacted in 1915.3 Not until twelve years later was that lead followed in a neighboring county when, in 1927, the Orange County Flood Control Act was made law.4 Another twelve years passed and in 1939 the San Bernardino County Flood Control District was formed by a special act., Thereafter, in the ten-year period of the 40's such districts were formed in the following nine counties: Ventura,6 San Luis Obispo,7 San Diego," Riverside,9 Humboldt,'o Monterey," Mendocino,'2
A Pluronic® micelle formulation increases the anti-leukemic activity of the novel anti-cancer nitric oxide prodrug JS-K.

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA 3293 We have developed a class of O 2-arylated diazeniumdiolate nitric oxide (NO) generators that release NO upon activation by the glutathione S-transferases (GST). This drug design exploits the upregulation of GST in malignant cells as compared to normal tissue and thus provides selective delivery of NO to targeted tumors. O2 -(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate or JS-K is a lead compound from this family. JS-K induces apoptosis and differentiation in human myeloid leukemia HL-60 cells, and inhibits HL-60 cell growth in NOD/SCID mice xenografts. JS-K also has potent anti-neoplastic activity in vitro and in vivo against multiple myeloma, prostate cancer and liver cancer. JS-K is sparingly soluble in aqueous media. Preliminary pharmacokinetic studies have shown that JS-K has a short in vivo half-life due to its reactivity with blood components. We therefore used polymers made of polyethylene oxide and polypropylene oxide (Pluronics®) in order to develop a nanoscale micelle formulation for the clinical development of JS-K. JS-K loading in Pluronics® P123 micelles did not affect micelle stability (particle size of 19.18 ± 5.64 and 19.75 ± 5.84 nm at 2 and 45 minutes, respectively). JS-K loaded in Pluronic® P123 micelles had increased in vitro cytoxicity against HL-60 cells (IC50 of 0.45 and 0.09 μM at 72 hours after JS-K addition for free JS-K and JS-K formulated in P123 micelles, respectively) while empty P123 micelles did not affect cell growth. Administration of free JS-K to NOD/SCID mice at a dose of 5 μmol/kg induced a sustained 25% drop in systolic blood pressure. Administration of JS-K formulated in P123 micelles to NOD/SCID IL2R γ null at the same dose did not induce hypotension. This suggests stabilization of JS-K in the bloodstream by the micelles and therefore slower intravascular release of NO. We then studied the anti-leukemic activity of JS-K formulated in P123 micelles in NOD/SCID IL2R γ null mice implanted subcutaneously with HL-60 cells. Loading of JS-K in P123 micelles led to significantly better anti-tumor activity than free unformulated JS-K administered at the same dose and schedule (4 μmol/kg IV thrice weekly). We fit a linear mixed model using SAS PROC MIXED to the data, using a random effect to account for correlation among measurements within the same animal. In this model, rate of tumor growth, as fit by a linear and quadratic effect of time, was found to be significantly higher (p=0.01 by F-test) among animals treated with free JS-K compared to animals treated with JS-K formulated in P123 micelles. Mice treated with empty P123 micelles had significantly greater tumor growth than mice treated with either free JS-K or JS-K formulated in P123 micelles. JS-K establishes a new class of cancer chemotherapeutic agents. Formulation of JS-K in Pluronic® micelles will speed its clinical development.
Improved Guarantees for Learning via Similarity Functions

We continue the investigation of natural conditions for a similarity function to allow learning, without requiring the similarity function to be a valid kernel, or referring to an implicit high-dimensional space. We provide a new notion of a “good similarity function” that builds upon the previous definition of Balcan and Blum (2006) but improves on it in two important ways. First, as with the previous definition, any large-margin kernel is also a good similarity function in our sense, but the translation now results in a much milder increase in the labeled sample complexity. Second, we prove that for distribution-specific PAC learning, our new notion is strictly more powerful than the traditional notion of a large-margin kernel. In particular, we show that for any hypothesis class C there exists a similarity function under our definition allowing learning with O(log |C|) labeled examples. However, in a lower bound which may be of independent interest, we show that for any class C of pairwise uncorrelated functions, there is no kernel with margin γ ≥ 8/ √ |C| for all f ∈ C, even if one allows average hinge-loss as large as 0.5. Thus, the sample complexity for learning such classes with SVMs is Ω(|C|). This extends work of BenDavid et al. (2003) and Forster and Simon (2006) who give hardness results with comparable margin bounds, but at much lower error rates. Our new notion of similarity relies upon L1 regularized learning, and our separation result is related to a separation result between what is learnable with L1 vs. L2 regularization.
Life in Ice-Covered Oceans

Recent reports that Jupiter's satellites Europa and Callisto may have ice-covered oceans have fueled speculation that they may be inhabited by living organisms. Gaidos et al. analyze the thermodynamic requirements for life on Europa by analogy with life on Earth today and during past "snowball" Earth episodes. They conclude that nearly all metabolic life-styles on the present Earth will be denied to organisms on Europa and indicate which types of organisms, if any, are most likely to be found there.
Description of the Plasma Diagnostics Package (PDP) for the OSS-1 Shuttle Mission and JSC Plasma Chamber Test in Conjunction with the Fast Pulse Electron Gun (FPEG)

The Plasma Diagnostics Package (PDP) and support systems are being readied for flight on the OSS-1 Space Shuttle Mission (STS-4 in 1982) and on the Spacelab-2 Shuttle Mission (1983 or 1984). In March 1981 in the Johnson Space Center Plasma Chamber A, the PDP was utilized to measure the state of the ambient plasma and of phenomena induced by operation of the Utah State University Fast Pulse Electron Gun (FPEG). The FPEG is an element of the Vehicle Charging and Potential (VCAP) investigation on the OSS-1 Mission. On the OSS-1 Mission, the PDP will make plasma measurements as it is swept through the FPEG beam region by the Shuttle Remote Manipulator System (RMS).
Selective mu and kappa Opioid Agonists Inhibit Voltage-Gated Ca2+ Entry in Isolated Neonatal Rat Carotid Body Type I Cells

It is known that opioids inhibit the hypoxic ventilatory response in part via an action at the carotid body, but little is known about the cellular mechanisms that underpin this. This study's objectives were to examine which opioid receptors are located on the oxygen-sensing carotid body type I cells from the rat and determine the mechanism by which opioids might inhibit cellular excitability.Immunocytochemistry revealed the presence of μ and κ opioid receptors on type I cells. The μ-selective agonist DAMGO (10 μM) and the κ-selective agonist U50-488 (10 μM) inhibited high K(+) induced rises in intracellular Ca(2+) compared with controls. After 3 h incubation (37 °C) with pertussis toxin (150 ng ml(-1)), DAMGO (10 μM) and U50-488 (10 μM) had no significant effect on the Ca(2+) response to high K(+).These results indicate that opioids acting at μ and κ receptors inhibit voltage-gated Ca(2+) influx in rat carotid body type I cells via G(i)-coupled mechanisms. This mechanism may contribute to opioid's inhibitory actions in the carotid body.
Ownership Structure and Top Management Turnover

We report a significant negative relation between the fractional equity ownership of top executives and the likelihood of top management turnover. In addition, the relation between prior firm performance and the likelihood of turnover is statistically insignificant for firms in which the top executive owns more than 1% of the firm's shares. These findings suggest that managers become entrenched at very low ownership levels. Consistent with this interpretation, we find that the stock price reaction to a management change is significantly greater in firms in which the departing manager owns more than 1% of the firm's shares. Moreover, in these firms, the incoming manager's fractional ownership is typically less than 1% and the firm is subject to a higher rate of post-turnover corporate control activity. We also examine the influence of other aspects of ownership structure and find that turnover rates are higher in firms with unaffiliated blockholders and lower in firms with blockholders that are affiliated with incumbent managers.
Association of the histamine N-methyltransferase C314T (Thr105Ile) polymorphism with atopic dermatitis in Caucasian children.

Study Objective To investigate potential associations between the histamine N-methyltransferase (HNMT) C314T (Thr105Ile) polymorphism and atopic dermatitis (AD) in a cohort of Caucasian children.
Nondestructive characterization of the mechanical strength of diffusion bonds. II. Application of a quasi-static spring model

It has been shown that the acoustic response of imperfect interfaces may be described by a quasi-static spring model. In the present paper, experimental data on the geometry of the contacts between two diffusion-bonded blocks have been used to determine the “spring stiffness” of such interfaces which have been correlated with experimentally determined ultrasonic reflection coefficients. The correlation between the theoretical reflection coefficient and the “spring stiffness” was found to be in excellent agreement with experimentally-observed values, if the disbonds are of infinitesimally small thickness. For disbonds of finite thickness, the agreement is less satisfactory. Reasons for the discrepancy in the latter case are unknown at the present time.
Microcomputer simulation systems

Abstract This study provides information as to general nature, hardware requirements, price and range of applications of approximately 20 simulation software packages. In addition, more detailed information on the use, documentation, etc., of GPSS/PC, SIMAN, PC SIMSCRIPT II.5 and SLAM II PC is included.
Numerical investigation on thermal performance and correlations of double skin façade with buoyancy-driven airflow

Abstract This paper briefly reviews the primary parameters for a double skin facade (DSF) design. The research presents an integrated and iterative modeling process for analyzing the thermal performance of DSF cavities with buoyancy-driven airflow by using a building energy simulation program (BESP) along with a computational fluid dynamics (CFD) package. A typical DSF cavity model has been established and simulated. The model and the modeling process have been calibrated and validated against the experimental data. The validated model was used to develop correlations that can be implemented in a BESP, allowing users to take advantage of the accuracy gained from CFD simulations without the required computation time. Correlations were developed for airflow rate through cavity, average and peak cavity air temperature, cavity air pressure, and interior convection coefficient. The correlations are valuable for “back of the envelope” calculation and for examining accuracy of zonal-model-based energy and airflow simulation programs.
Use of cellulase from Pseudomonas fluorescens for the hydrolysis of waste paper in an attrition bioreactor : scientific note

Segregated waste-paper products could be an ideal feed material for biological conversion to sugars with the possibility of subsequent conversion to ethanol. The approach in this scientific note represents an alternative to simultaneous saccharification and fermentation (SSF). The idea is to optimize the enzymatic hydrolysis and fermentating steps separately. For waste-paper hydrolysis, our approach is to provide an attriting force that constantly creates fresh surface area for enzymatic attack. This is accomplished by using an external centrifugal pump that provides a constant shearing of the wastepaper to create solid-liquid surface area. Another important aspect of this study is the production of cellulase systems by bacteria. The overall intent is to be able to produce low-cost cellulase sources, and then use them in reactors that provide for the most efficient interaction between enzyme and solid substrate. This article describes preliminary findings for the use of a bacterial cellulase in an attrition bioreactor for the purpose of enhancing the hydrolysis of cellulose in waste paper.
Frequencies of hprt mutant lymphocytes in marijuana-smoking mothers and their newborns

Reports of increases in the prevalence of marijuana smoking, especially among young people, have led to concerns about possible genotoxic effects from marijuana use due to exposure to the mutagenic and carcinogenic agents present in marijuana smoke. Prior studies of the adverse healt consequences of marijuana smoking, using disease outcomes, have sometimes been confounded by the fact that most marijuana smokers also smoke tobacco. In the present study, the potential mutagenic effects of marijuana smoking were investigated with a somatic cell mutation assay that detects mutations occurring in vivo in the hprt gene. Subjects were volunteers recruited from a prenatal clinic that performs urine drug screens on all consenting patients. Blood samples were collected from 17 subjects whose drug screens indicated marijuana use, but who did not smoke tobacco or use cocaine or opiates, and 17 non-smokers with negative drug screens. Absence of tobacco use was confirmed by plasma cotinine tests. Cord blood sampes were collected from newborns of 5 of the marijuana smokers and 5 non-smokers. Lymphocytes were isolaed, cryopreserved, and later thawed and assayed with the autoradiographic hprt assay. The frequency of variant (mutant) lymphocytes (Vf) in the 17 non-smokers (+- standard error) was 1.93 (±0.17) per million evaluatable cells. The Vf of 17 marijuana smokers was more than three-fold higher, 6.48 (±0.48) × 10−6, a significant difference, p < 0.001. Cord blood lymphocytes from 5 newborns of non-smokers had a Vf of 0.85 (±0.23) × 10−6, compared to 2.55 (±0.60) × 10−6 for 5 newborns of marijuana smokers, significantly higher, p < 0.05. Because of the known association between increases in somatic mutations and the development of malignancies, this study indicates that marijuana smokers may have an elevated risk of cancer. For pregnant marijuana smokers, there is also concern for the possibility of genotoxic effects on the fetus, resulting in heightened risk of birth defects or childhood cancer.
Active Sample Anticoincidence Guarded Ge(Li) Spectrometer for Low Level Radionuclide Analysis

The problem of spectral interference in large volume radioactive samples counted in a guarded Ge(Li) spectrometer is attacked by a new approach. By making the sample itself a liquid scintillator detector, and using coincidence and anticoincidence gating, the detrimental effects of self absorption can be eliminated. In addition, this technique (denoted gamma-beta coincidence and gamma-beta anticoincidence spectrum analysis) allows discrimination between modes of decay. The system design, logic, performance, and significance to low level radionuclide analysis is presented.