cssi/SciSciGPT-SciSciNet huggingface dataset:
The distribution of alkaline phosphatase activity in normal and cross‐species regenerated rat and mouse taste buds

Alkaline phosphatase (ALK Pase) activity can be detected histochemically in the taste buds of rats but not mice. Since taste buds develop, regenerate and are maintained under the influence(s) of the sensory nerve it was decided to study cross-species regenerated buds of these two animals to determine whether the nerve also regulated ALK Pase development in taste cells. Grafts of rats sensory ganglion and mouse tongue or mouse ganglion and rat tongue were combined in the anterior chamber of the eyes of immunologically-deficient nude mice and the cross-species buds that developed at 35 days were examined histochemically for ALK Pase. The results revealed that the rat nerve did not cause ALK Pase to appear in any buds found in mouse tongue grafts and that mouse nerve could support buds containing ALK Pase in rat tongue tissue. Because the cross-species regenerated buds were histochemically characteristic of those normally found in rat or mouse tongue, there is no evidence that the foreign nerve altered gene expression for ALK Pase in the target organ, and the action of the nerve on gustatory epithelium appears to be that of activation and maintenance.
The use of a movable telescoping end mass system for the time-optimal control of spinning spacecraft

The time-optimal control of a spin-stabilized spacecraft with a movable telescoping appendage (boom) is considered analytically and numerically. The motion of a control mass at the end of the boom is determined such that the terminal time will be minimized for two-axis control of a symmetric spacecraft. The equations of rotational motion are linearized about the desired state of spin about the symmetry axis. The equations for the transverse angular velocity components have the form of a coupled two dimensional harmonic oscillator with boom motion as a control force. The control function which brings the system to the desired state is known to be a series of positive and negative pulses. If the initial state is such that the system can be driven to rest in a single switch, the responses, switching and final times, and required boom motion may be determined analytically. Some typical numerical results based on these solutions are discussed.
Saliency in images and video: a brief survey

Salient image regions permit non-uniform allocation of computational resources. The selection of a commensurate set of salient regions is often a step taken in the initial stages of many computer vision algorithms, thereby facilitating object recognition, visual search and image matching. In this study, the authors survey the role and advancement of saliency algorithms over the past decade. The authors first offer a concise introduction to saliency. Next, the authors present a summary of saliency literature cast into their respective categories then further differentiated by their domains, computational methods, features, context and use of scale. The authors then discuss the achievements and limitations of the current state of the art. This information is augmented by an outline of the datasets and performance measures utilised as well as the computational techniques pervasive in the literature.
The Discourse of Race and Culture in Family Therapy Supervision: A Conversation Analysis

Family therapy literature has emphasized the importance of examining contextual variables in supervision. This study explored how the talk of race, ethnicity, and culture is accomplished within the supervision session using conversation analysis. Conversation analysis is a naturalistic and descriptive methodology that examines patterns across naturally occurring conversations. The results indicated that the participants accomplished four domains of talk that involved the discourse of race, ethnicity, or culture. These domains included contextual markers, self of the therapist issues, cross cultural issues in the therapeutic relationship and cultural issues affecting the supervisory relationship. Implications for supervision and future directions are discussed.
Ultrastructure of the Heart and Pericardium of an Aplacophoran Mollusc (Neomeniomorpha): Evidence for Ultrafiltration of Blood

Transmission electron microscopy of the auricular wall in an undescribed mesopsammic mollusc of the genus Meiomenia (Class Aplacophora, Subclass Neomeniomorpha) has revealed podocytes interposed between the haemocoel and the pericardial coelom. These cells comprise the auricular epicardium and overlie a loose inner myocardium. Podocytes characterize sites of blood ultrafiltration in the Polyplacophora and most conchiferan molluscan classes, and are here described from the Aplacophora for the first time. This evidence for ultrafiltration suggests an excretory role for the neomenioid aplacophoran pericardial coelom and supports coelomic ultrafiltration of blood as a plesiomorphic molluscan trait.
Cognitive Behavioral Therapy Interventions With Sex Offenders

The majority of convicted sex offenders are eventually released back into the community. Consequently, effective treatment interventions that can lower the recidivism rates of sexual offenders are ...
Reconsideration of the Lifetime Ban on Blood Donation by Men Who Have Sex With Men

In 2013, the US Supreme Court took a historic step in United States v Windsor by striking down the Defense of Marriage Act on the grounds that it imposed a “disability on the class [of gay Americans] by refusing to acknowledge a status the State finds to be dignified and proper.”1 This milestone in gay rights stands in stark contrast to the ongoing lifetime ban imposed in 1983 on blood donation by men who have ever had sex with men (MSMs) even once.2 As it stands, the US Food and Drug Administration (FDA) continues to uphold this 30-year-old policy, unaltered, on the grounds that MSMs remain at increased risk of contracting transfusion-transmissible pathogens such as human immunodeficiency virus (HIV).2
Terahertz Optical Frequency Comb Generation by Spectral Filtering of Broadband Spontaneous Amplified Emissions From a Semiconductor Optical Amplifier

In this paper, we describe a fiber-optics-based system for the generation of optical frequency comb using amplified spontaneous emissions from a semiconductor optical amplifier (SOA) as signal source. The continuous-wave (CW) spectrum from the SOA ranges from 1480 nm to 1680 nm. A Solc-Sagnac birefringent interferometer filters the CW into a comb of discrete spectral lines with line spacing of 600 GHz, producing comb signals than span 182-230 THz.
Measurement of instantaneous rates of mass transfer to a small sink on a wall

A technique has been developed for measuring the average rate of transfer and the fluctuations in the rate of transfer at a small source or sink on a wall. The transfer area consists of a small polarized electrode mounted flush with the wall. An electrochemical redox reaction whose rate is limited by mass transfer is employed. The technique can be used to study the flow pattern in the vicinity of the wall. By measuring the mass transfer simultaneously to two wall electrodes at varying distances apart the extent of unsteady flows in the vicinity of the wall can be measured.
Update on Imaging for Acute Appendicitis

Acute appendicitis is a common surgical emergency and the diagnosis can often be made clinically; however, many patients present with atypical findings. For these patients, there are multiple imaging modalities available to aid in the diagnosis of suspected appendicitis in an effort to avoid a negative appendectomy. Computed tomography is the test of choice in most patients in whom the diagnosis is not certain. Ultrasonography is particularly useful in children and pregnant women. Magnetic resonance imaging is recommended when ultrasonography is inconclusive. Appropriate use of these imaging studies avoids delays in treatment, prolonged hospitalization, and unnecessary surgery.
Pragmatics in acquisition

Recent research has highlighted several areas where pragmatics plays a central role in the process of acquiring a first language. In talking with their children, adults display their uses of language in each context, and offer extensive feedback on form, meaning, and usage, within their conversational exchanges. These interactions depend critically on joint attention, physical co-presence, and conversational co-presence - essential factors that help children assign meanings, establish reference, and add to common ground. For young children, getting their meaning across also depends on realizing language is conventional, that words contrast in meaning, and that they need to observe Grice's cooperative principle in conversation. Adults make use of the same pragmatic principles as they solicit repairs to what children say, and thereby offer feedback on both what the language is and how to use it.
Phase III, Randomized, Double-Blind Study of Epoetin Alfa Compared With Placebo in Anemic Patients Receiving Chemotherapy

Purpose To determine whether weekly epoetin alfa could improve hemoglobin (HgB) levels, reduce RBC transfusions, and improve quality of life (QOL) in patients with advanced cancer and with anemia after receiving myelosuppressive chemotherapy. Patients and Methods This double-blind, placebo-controlled study randomly assigned patients to placebo or epoetin alfa (Ortho Biotech, Bridgewater, NJ) 40,000 U subcutaneous weekly for 16 weeks. QOL, HgB, and RBC transfusions were measured pretreatment and monthly. Results The study accrued 344 patients; 330 were assessable for efficacy and 305 were assessable for QOL. Placebo-treated patients had a mean increase in HgB of 0.9 g/dL (range, −3.8 to +5.3) compared with 2.8 g/dL (range, −2.2 to +7.5) for epoetin-treated patients (P < .0001). During the study, 31.7% of placebo-treated patients achieved a ≥ 2 g/dL HgB increase compared with 72.7% of epoetin-treated patients (P < .0001). The incidence of RBC transfusion for placebo and epoetin treatment arms was 39.6% and ...
Analysis of Modulation of Foxp3 Expression in CD4 CD25 Regulatory Cells from NOD Mice

CD4 + CD25 + regulatory cells control the development of autoimmunity, including type 1 diabetes, and the transcription factor Foxp3 is crucial for the development and function of these cells. The decreased effectiveness of regulatory T cell function in diabetes-prone NOD mice is due to the failure of NOD APC to activate regulatory T cells properly. In the present study, we examined the parameters that modulate Foxp3 expression in CD4 + CD25 + regulatory cells. We found that CD4 + CD25 + cells from congenic diabetes-resistant NOD mice exhibited intermediate levels of Foxp3 compared with regulatory cells from B6 mice and Sick NOD mice. Using an in vitro Foxp3 induction system, we found that APC from diabetes-resistant congenic NOD mice also exhibited an intermediate ability to maintain expression of Foxp3 in CD4 + CD25 + cells. Finally, NOD APC pre-treated with a microbial component, lipoteichoic acid, regained their ability to maintain Foxp3 expression in CD4 + CD25 + cells in vitro. APC from CFA-treated NOD mice that were transferred into recipient NOD mice could induce Foxp3 expression in CD4 + CD25 + cells in vivo. Altogether, these data suggest that Foxp3 expression in CD4 + CD25 + cells from NOD mice can be modulated by optimal stimulation by APC.
Proposed Bedside Maneuver to Facilitate Accurate Anatomic Orientation for Correct Positioning of ECG Precordial Leads V1 and V2: A Pilot Study

Abstract Background Misplacement of right precordial electrocardiogram (ECG) electrodes superiorly is a prevalent procedural error that may lead to false findings of T-wave inversion or QS complexes in V2—possibly triggering wasteful utilization of health care resources. Standard technique for proper placement of V1–V2 entails initial palpation for the sternal angle, pointing to the second intercostal space (ICS), followed by lead fixation at the fourth ICS. Study Objective Because adherence to this approach may be limited by lack of a visual landmark for the second ICS, we assessed an alternative technique. Methods The evaluated technique involved placement of the patient’s hand up against the base of his/her neck (H→N maneuver) to help demarcate visually a specific point “X” on the chest. Results Of 112 patients studied, “X” landed on the first rib in 2.7%, first ICS in 7.1%, second rib in 56.3%, second ICS in 33.0%, and third rib in 0.9%. Thus, in 89.3% (95% confidence interval 83.6–95.0%) of cases (93.3% of men, 84.6% of women; p = 0.13), the second ICS could be identified by H→N via the following simple rule: Utilize “X” if it overlies an ICS; or the immediately subjacent ICS if “X” overlies a rib. Conclusion The H→N maneuver provides a primarily visual approach to identifying the second ICS and, thereby, the fourth ICS for affixing V1–V2. If the present initial experience is confirmed, H→N might merit consideration as an educational tool to promote anatomically correct placement of these precordial leads, a prerequisite to diminishing the incidence of ECG procedure-related “septal ischemia/infarction.”
Comparative genomics as a time machine: How relative gene dosage and metabolic requirements shaped the time-dependent resolution of yeast polyploidy

Using a phylogenetic model of evolution after genome duplication (i.e., polyploidy) and 12 yeast genomes with a shared genome duplication, I show that the loss of duplicate genes after that duplication occurred in three phases. First, losses that occurred immediately after the event were biased toward genes functioning in DNA repair and organellar functions. Then, the main group of duplicate losses appear to have been shaped by a requirement to maintain balance in protein levels: There is a strong statistical association between the number of protein interactions a gene's product is involved in and its propensity to have remained in duplicate. Moreover, when duplicated genes with interactions were lost, it was more common than expected for both members of an interaction pair to have been lost on the same branch of the phylogeny. Finally, in the third phase of the resolution process, overretention of duplicated enzymes carrying high flux and of duplicated genes involved in transcriptional regulation became dominant. I speculate that initial retention of such genes by a requirement to maintain gene dosage set the stage for the later functional changes that then maintained these duplicates for long periods.
Harmonic moment dynamics in Laplacian growth.

Harmonic moments are integrals of integer powers of $z=x+iy$ over a domain. Here, the domain is an exterior of a bubble of air growing in an oil layer between two horizontal closely spaced plates. Harmonic moments are a natural basis for such Laplacian growth phenomena because, unlike other representations, these moments linearize the zero surface tension problem [S. Richardson, J. Fluid Mech. 56, 609 (1972)], so that all moments except the lowest one (the area of the bubble) are conserved in time. In our experiments, we directly determine the harmonic moments and show that for nonzero surface tension, all moments (except the lowest one) decay in time rather than exhibiting the divergences of other representations. Further, we derive an expression that relates the derivative of the ${k}^{th}$ harmonic moment ${M}_{k}$ to measurable quantities (surface tension, viscosity, the distance between the plates, and a line integral over the contour encompassing the growing bubble). The laboratory observations are in good accord with the expression we derive for $d{M}_{k}/dt$, which is proportional to the surface tension; thus in the zero surface tension limit, the moments (above $k=0$) are all conserved, in accord with Richardson's theory. In addition, from the measurements of the time evolution of the harmonic moments we obtain a value for the surface tension that is within 20% of the accepted value. In conclusion, our analysis and laboratory observations demonstrate that an interface dynamics description in terms of harmonic moments is physically realizable and robust.
Interprofessional Education In Healthcare: Establishing A Successful Dialogue For Students And Faculty

Effective healthcare today is built on interprofessional, population- and evidence-based approaches to provide care that is safe, timely, equitable, patient-centered, and efficient. As a result, there is increasing recognition by faculty, administrators, and community professionals of the importance of providing students with ongoing opportunities to problem-solve and learn together in interprofessional teams. In order to document baseline data on the interprofessional activities underway in a College of Health Professions, faculty and staff in each of the College’s departments completed a published survey, Interprofessional Education Assessment and Planning Instrument for Academic Institutions. Faculty comments showed they viewed interprofessional education and collaborative clinical practice as important. However, survey data showed interprofessional education generally was limited to discipline-specific activities. Data were important in encouraging faculty to begin a productive dialogue as to how interprofessional education opportunities could be implemented more effectively for students.
Permanent Reorganization of Ia Afferent Synapses on Motoneurons After Peripheral Nerve Injuries

After peripheral nerve injuries to a motor nerve, the axons of motoneurons and proprioceptors are disconnected from the periphery and monosynaptic connections from group I afferents and motoneurons become diminished in the spinal cord. Following successful reinnervation in the periphery, motor strength, proprioceptive sensory encoding, and Ia afferent synaptic transmission on motoneurons partially recover. Muscle stretch reflexes, however, never recover and motor behaviors remain uncoordinated. In this review, we summarize recent findings that suggest that lingering motor dysfunction might be in part related to decreased connectivity of Ia afferents centrally. First, sensory afferent synapses retract from lamina IX, causing a permanent relocation of the inputs to more distal locations and significant disconnection from motoneurons. Second, peripheral reconnection between proprioceptive afferents and muscle spindles is imperfect. As a result, a proportion of sensory afferents that retain central connections with motoneurons might not reconnect appropriately in the periphery. A hypothetical model is proposed in which the combined effect of peripheral and central reconnection deficits might explain the failure of muscle stretch to initiate or modulate firing of many homonymous motoneurons.
HOW TO STUDY THE CITY: ARGUMENTS FOR A NEW APPROACH

(1990). HOW TO STUDY THE CITY: ARGUMENTS FOR A NEW APPROACH. Urban Geography: Vol. 11, Review Symposium on Logan and Molotch's Urban Fortunes: The Political Economy of Place, pp. 200-205.
System-of-systems security engineering

There is an increasing trend to treat a collection of individual systems that support a common mission as a single entity and to perform systems engineering activities for that entity. A security engineering process is proposed for systems-of-systems. This process addresses such issues as how to identify and mitigate risks resulting from connectivity, how to integrate security into a target architecture, and how to address the constraints associated with legacy systems. >
Hydroformylation by rhodium zeolite A catalysts

Abstract A direct comparison of rhodium zeolite A catalysts for vapor- and liquid-phase 1-hexene hydroformylation is reported. Rhodium zeolite A catalysts prepared by ion exchange (surface rhodium) and by the synthesis procedure of Rossin and Davis ( J. Chem. Soc. Chem. Commun. 234 , 1986) (intrazeolitic rhodium) hydroformylate 1-hexene in the vapor phase at 150°C and 2 atm total pressure and in the liquid phase at 20 atm and 50–120 °C. Similar vapor-phase hydroformylation activity is obtained from the two preparations and both show rhodium loss after exposure to the reaction environment. The liquid-phase activity is somewhat different on these catalysts. The exchanged rhodium zeolite A elutes rhodium into the reaction mixture and the observed catalysis occurs via solution rhodium. The synthesized rhodium zeolite A does not elute rhodium as significantly as the exchanged catalyst. In the presence of cyclohexylmercaptan, a poison for solution and zeolite surface rhodium, the synthesized rhodium zeolite A catalyst reacted 1-hexene exclusively to heptanal at 120°C and 20 atm (H 2 : CO 1:1).
Thyristor voltage drop in the on-state

When a thyristor is in the forward-conducting state, all device junctions are forward biased and the device presents a minimum resistance to the forward current flow. At moderate and high injection levels, two of the three forward-biased junctions usually exhibit nearly equal but opposite potentials. Consequently, one junction contributes to the total device voltage drop. Since the junction voltage is a logarithmic function of the current, it varies only very slowly and its value is typically 0.8 to 1.0 V. for moderate or high current levels.
Future Research Directions of Software Engineering and Knowledge Engineering

Software Engineering (SE) and Knowledge Engineering (KE) are closely related disciplines with goals of turning the development process of software systems and knowledge-based systems, respectively, into engineering disciplines. In particular, they together can provide systematic approaches for engineering intelligent software systems more efficiently and cost-effectively. As there is a large overlap between the two disciplines, the interplay is vital for both to be successful. In this paper, we divide the intersection of SE and KE into three subareas, namely Knowledge-Supported Software Engineering (KSSE), Engineering Knowledge as a Software (EKaaS), and Intelligent Software System Engineering (ISSE). For each subarea, we describe the challenges along with the current trends, and predict the future research directions that may have the most potential for success.
How Does the Probability of a 'Successful' Retirement Differ Between Participants in Final-Average Defined Benefit Plans and Voluntary Enrollment 401(k) Plans?

This paper begins with a review of the previous academic literature and summarizes previous Employee Benefit Research Institute (EBRI) research analyzing the conditions under which voluntary-enrollment (VE) 401(k) plans are likely to provide an accumulation of retirement assets at least equivalent to those provided under a counterfactual final-average defined benefit (DB) plan. New research is then presented to show the percentage of “successful” retirements by income quartile for workers currently ages 25-29 who will have more than 30 years of simulated eligibility for participation in a 401(k) plan. Results are first presented for both voluntary-enrollment 401(k) plans and final-average DB plans with a 1.5 percent accrual rate. Sensitivity analysis is provided by also analyzing the comparative success rates of final-average DB plans with accrual rates of 1.0 and 2.0 percent. Using baseline assumptions (defined in the study), it appears that the DB plan has a higher probability of achieving a real replacement rate (when combined with Social Security payments) of 60 percent than the VE 401(k) plans for the first three income quartiles. If a 70 percent replacement rate is used as a threshold, participants in the third- and fourth-income quartiles have a much higher probability of success with the 401(k) plans than the DB plans. When the threshold is set at a higher (and according to many financial planners, more realistic) replacement rate of 80 percent, the 401(k) plans have a much higher probability of success than the counterfactual DB plans for all groups except for the lowest-income quartile (where the results are virtually even).
The Effect of Independent Expenditures on Congressional Elections following Citizens United v. Federal Elections Commission (2010)

Independent expenditures can greatly influence campaigns and the outcome of elections, a phenomenon that many expect will become more evident following the U.S. Supreme Court’s ruling in Citizens United v. FEC (2010). Corporations first had the chance to flex their free speech muscle in the 2010 elections, and as expected, spending on campaigns appears to have increased. What patterns are emerging? How has increased spending influenced electoral results? In this paper I will examine this increase and the subsequent effects of corporate independent expenditures on all 2010 House races. Using multivariate analysis, I will show that corporate independent expenditures substantially increased following Citizens United and how this monetary surge affected electoral outcomes in the 2010 Congressional election.
Tuning Glass Transition in Polymer Nanocomposites with Functionalized Cellulose Nanocrystals through Nanoconfinement.

Cellulose nanocrystals (CNCs) exhibit impressive interfacial and mechanical properties that make them promising candidates to be used as fillers within nanocomposites. While glass-transition temperature (Tg) is a common metric for describing thermomechanical properties, its prediction is extremely difficult as it depends on filler surface chemistry, volume fraction, and size. Here, taking CNC-reinforced poly(methyl-methacrylate) (PMMA) nanocomposites as a relevant model system, we present a multiscale analysis that combines atomistic molecular dynamics (MD) surface energy calculations with coarse-grained (CG) simulations of relaxation dynamics near filler–polymer interfaces to predict composite properties. We discover that increasing the volume fraction of CNCs results in nanoconfinement effects that lead to an appreciation of the composite Tg provided that strong interfacial interactions are achieved, as in the case of TEMPO-mediated surface modifications that promote hydrogen bonding. The upper and lowe...
Machine learning based parametric image estimation for Analyzer-based phase contrast imaging

An X-ray beam passing through biological tissue is deflected (i.e., refracted) by a small angle typically <10 µrad. Analyzer-based phase contrast imaging (ABI) systems are capable of measuring this tinny refraction by sampling the intensity of the beam at different propagation directions. An Analyzer crystal is the key element for this task as it acts as a narrow angular filter. Since refraction effects are highly dependent of the radiation wavelength, X-ray beam must be quasi-monochromatic. Therefore the amount of photons that reach the object and detector is much lower then that in traditional radiography. Using a reasonable exposure time, noisy reconstructions of refraction images are obtained. In this manuscript, we present a machine learning parametric image estimation approach to obtain accurate refraction images from noisy raw data.
Lidar reflectance from snow at 2.05 μm wavelength as measured by the JPL Airborne Laser Absorption Spectrometer.

We report airborne measurements of lidar directional reflectance (backscatter) from land surfaces at a wavelength in the 2.05 μm CO2 absorption band, with emphasis on snow-covered surfaces in various natural environments. Lidar backscatter measurements using this instrument provide insight into the capabilities of lidar for both airborne and future global-scale CO2 measurements from low Earth orbit pertinent to the NASA Active Sensing of CO2 Emissions over Nights, Days, and Seasons mission. Lidar measurement capability is particularly useful when the use of solar scattering spectroscopy is not feasible for high-accuracy atmospheric CO2 measurements. Consequently, performance in high-latitude and winter season environments is an emphasis. Snow-covered surfaces are known to be dark in the CO2 band spectral regions. The quantitative backscatter data from these field measurements help to elucidate the range of backscatter values that can be expected in natural environments.
Effects of Temperature on the Survival and Development of the Morrill Lace Bug (Heteroptera: Tingidae) on Guayule

The rate of development of Corythucha morrilli Osborn and Drake was measured at seven temperatures on guayule, Parthenium argentatum Gray. At 60% RH and 16-h light cycle the time required for development from egg to adult ranged from 34.7 days at 20°C to 17.3 days at 30°C. Little nymphal development occurred at 17.8°C, and no eggs or nymphs developed at temperatures exceeding 34.4°C. Egg and nymphal survival were greatest at the median temperatures.
Control of the California Oakworm with Bacillus thuringiensis Preparations

Commercial Bacillus thuringiensis Berliner preparations were effective for control of the California oakworm, Phryganidia californica Packard, in field trials conducted in 3 different climatic areas of northern California. The preparations tested were Biotrol® Dustable BTB 183 2.5 D, Biotrol® Wettable BTB 183 25 w, and Thuricide® 90 TS 950-T. Application was timed to coincide with the 3rd larval instar, when a change in feeding behavior increased the exposure of the larvae to the B. thuringimsis deposits.
Arrhythmias in Acute Myocardial Infarction

Almost all of the controversies about the management of arrhythmias during acute infarction have now been resolved. With initiation of early thrombolytic therapy, both bradyarrhythmia and tachyarrhythmia will often accompany the reperfusion. However, the principles that have evolved should provide adequate therapeutic guidelines. The primary persisting challenge is to identify the patients during the convalescent phase who are at high risk for ventricular tachycardia or fibrillation and to institute the appropriate prophylactic therapy.
Time course of recovery of endothelial cell surface thrombin receptor (PAR-1) expression

We studied dynamics of cell surface expression of proteolytically activated thrombin receptor (PAR-1) in human pulmonary artery endothelial cells (HPAEC). PAR-1 activation was measured by changes i...
Bioanalytical inspections: organizational changes and regulatory perspectives

During January 2015, several offices within the Center for Drug Evaluation and Research (CDER) were re-organized to improve consistency of decision-making, and to streamline policy, procedures and communications. Some Divisions were elevated to Office status because of the increased number of personnel resulting from the passage of the Generic Drug User Fee Amendments of 2012 (GDUFA). The resources provided by the new user fees supported hiring more personnel to address the significantly increased workload and newly imposed timelines. The Division of Bioequivalence and GLP Compliance (DBGLPC), responsible for CDER’s Bioavailablity/Bioequivalence (BA/BE) Inspection Program and the Good Laboratory Practice (GLP) Inspection Program, became the Office of Study Integrity and Surveillance (OSIS). Additionally, OSIS became the newest suboffice under CDER’s Office of Translational Sciences. Previously, this group was in the Office of Scientific Investigations under CDER’s Office of Compliance. OSIS currently includes the Division of Generic Drug Bioequivalence Evaluation conducting and reviewing work under the BA/BE Inspection Program, and the Division of New Drug Bioequivalence Evaluation, which, in addition to the BA/BE program, also conducts and reviews inspections under the GLP Inspection Program. Concurrent with the reorganization, OSIS began to implement a surveillance approach to inspections in conjunction with the application-based inspections, conducted previously. This commentary provides an overview of changes in procedures within OSIS; it will also briefly discuss topics of interest that came up during the past year, including assays related to therapeutic biologics and immunogenicity testing.
Collaborative Problem Solving in Minnesota

Over the past five years remarkable progress has been made in creating both the policy structure and funding to comprehensively address impaired waters in the state and meet Federal “total maximum daily load” (TMDL) requirements through a unique collaboration among business, agriculture, NGOs, and state and local governments. The collaboration resulted in the passage of the Clean Water Legacy Act by overwhelming margins and a constitutional amendment that dedicated a portion of a sales tax increase to clean water. Another collaborative problem-solving process produced a state-wide mercury TMDL that is making significant progress toward reducing mercury emissions, one of the leading causes of impairment to water in Minnesota. This collaborative problem-solving work extends well beyond water quality issues, however. In 2001, the Minnesota Center for Environmental Advocacy (MCEA) (Minnesota’s leading environmental advocacy organization) joined the Minnesota Chamber of Commerce to create Clean Air Minnesota (CAM). CAM originally focused on reducing volatile organic compounds and nitrogen oxide emissions (ozone pre-cursors) so that air quality in the Twin Cities region would continue to meet Federal standards. Since its founding in 2001, CAM has grown to encompass one of the leading diesel retrofit programs in the country - Project Green Fleet - that is well on its way to installing pollution control equipment on all eligible diesel school buses in Minnesota. These are collaborations that work - they have facilitated new legislation, helped obtain new funding, provided a forum for ongoing communications and produced measurable emissions and risk reductions related to important environmental goals.
On Community Autonomy and the Change of Government Functions

In the current construction of communities, there’s a grave tendency of administrative interference. Some other problems have also arisen in the selection of administers and in the process of administration. All these have run counter to the initial idea that the government should instruct rather than control the community in the construction of a community. Therefore, the government ought to transfer power to the community, change its own functions and promote working methods with an effort to build government-leading type of communities.
Clinical Investigation of Respiratory Syncytial Virus Infection in Children With Congenital Heart Disease

Objective: To explore the risk and prognosis of respiratory syncytial virus infection in children with congenital heart disease(CHD) and to summarize the clinical experience of treatment. Methods: We retrospectively reviewed 2104 CHD patients received surgery in our hospital from January to December 2011. We found 32 patients with RSV infection, set as RSV group, and randomly took 50 patients without RSV infection, set as Control group. In RSV group, there 26 patients were improved and 6 died. The different indexes before, during, after the operation and the risk factors for prognosis were analyzed and compared between 2 groups. Results: Compared with Control group, the RSV group had prolonged mechanical ventilation time, in-hospital ICU stay time and higher mortality. The patients with RSV infection diagnosed before the operation were all alive. The patients with RSV infection diagnosed after the operation presented prolonged mechanical ventilation time, with higher incidences of combining bacterial infection and pulmonary arterial hypertension(PAH), all P0.01. Single factor analysis indicated that combining with post operative PAH was the risk factor for prognosis. Multivariate regression analysis demonstrated that combining with post operative PAH was positively related to prognosis in CHD patients with RSV infection(RR=74.969, P=0.004).The risk of post operative death in patients with PAH was 74.969 times higher than those without PAH. Conclusion: CHD patients with RSV infection may cause prolonged mechanical ventilation time, in-hospital ICU stay time with the increased mortality. The pre-operative virus screening may improve the patient's survival rate.
War-gaming application for future space systems acquisition

Recently the U.S. Department of Defense (DOD) released the Defense Innovation Initiative (DII) [1] to focus DOD on five key aspects; Aspect #1: Recruit talented and innovative people, Aspect #2: Reinvigorate war-gaming, Aspect #3: Initiate long-range research and development programs, Aspect #4: Make DOD practices more innovative, and Aspect #5: Advance technology and new operational concepts. Per DII instruction, this paper concentrates on Aspect #2 and Aspect #4 by reinvigorating the war-gaming effort with a focus on an innovative approach for developing the optimum Program and Technical Baselines (PTBs) and their corresponding optimum acquisition strategies for acquiring future space systems. The paper describes a unified approach for applying the war-gaming concept for future DOD acquisition of space systems. The proposed approach includes a Unified Game-based Acquisition Framework (UGAF) and an Advanced Game-Based Mathematical Framework (AGMF) using Bayesian war-gaming engines to optimize PTB solutions and select the corresponding optimum acquisition strategies for acquiring a space system. The framework defines the action space for all players with a complete description of the elements associated with the games, including Department of Defense Acquisition Authority (DAA), stakeholders, warfighters, and potential contractors, War-Gaming Engines (WGEs) played by DAA, WGEs played by Contractor (KTR), and the players’ Payoff and Cost functions (PCFs). The AGMF presented here addresses both complete and incomplete information cases. The proposed framework provides a recipe for the DAA and USAF-Space and Missile Systems Center (SMC) to acquire future space systems optimally.
Microbiological Safety of Cheese Made from Heat-Treated Milk, Part III. Technology, Discussion, Recommendations, Bibliography.

Heat treatment or pasteurization does not adversely affect the cheesemaking process or the resulting physical properties of the cheese. Both types of heat-treatments can correct chemical changes that occur in cold stored raw milk. Thermization on the farm may help control psychrotrophic bacteria in cold stored milk. Some denaturation of whey protein does occur during pasteurization. Heat treatments slightly above current minimum pasteurization requirements can cause body/texture and moisture control problems in cheese. Loss of functionality can adversely affect the marketing of whey protein products. Cheeses made from pasteurized milk ripen more slowly and usually do not exhibit the flavor intensity of cheeses made from raw or heat-treated milk. Swiss and hard Italian type cheese, whose traditional flavor results in part from native milk enzymes and microflora, would also be adversely affected if milk pasteurization for cheesemaking were mandatory. The quality of cheese made from pasteurized milk is consistently better than cheese made from raw milk as evidenced by fewer body and flavor defects consequent to the growth of undesirable bacteria. Either pasteurization or heat-treatment enables improved uniform process control and quality during cheesemaking. Pathogens were prioritized as high, medium, or low risk in cheese. Three organisms, Salmonella , Listeria monocytogenes and enteropathogenic Escherichia coli were judged to be high risk threats to the cheese industry. Staphylococcus aureus was listed as low risk because growth and toxin production is readily suppressed by lactic cultures and acidity (pH) control in cheese. Three actions are recommended: Establish a guideline for minimum heat-treatment of milk for cheesemaking: 64.4°C (148°F) for 16 s or equivalent with adequate process control. Evaluate current safety technology and practices used for cheese manufacture. Support research with primary emphasis on the combined effect of heat-treatment and other current cheese technologies. Evaluate technologies not currently utilized in cheese manufacture for safety potential.
Editorial: Unraveling Neuroprotective and Neurodegenerative Signals in Neurodegeneration.

Our understanding of the etiology of human neurodegenerative disorders is limited by the necessity to infer an active sequence of events, often expressed over protracted periods of time, from a collection of still-life images that often represent the end of the sequence with no clear view of how we got there. Adding to the collective confusion, it often is not clear whether our measures of nervous system structure and function at a given point in time represent active contributors to degeneration, the tombstones reflecting consequences of degeneration, active attempts to protect the nervous system, products of failed protection, or unrelated events. As a result, we rely on observations and manipulations of fragments of the process in experimental models and human samples, pieced together to create versions of what is possible. In this collection of articles, the iterative process is on full display, with a focus on Alzheimer's disease, Parkinson's disease, and related disorders, and reports ranging from tools to mechanisms to treatment.
4.42 – Odor Plumes and Animal Orientation

The distribution of chemicals resulting from the interaction of flowing fluid with a source of volatile chemicals is commonly called a plume, which has a discontinuous patchy structure. The internal structure of odor plumes changes predictably with both distance downstream from the source and distance from centerline across the plume, and behavioral experiments indicate that odor-tracking animals alter their tracking behavior in response to these changes. In most organisms tested, odor-tracking behavior requires the intermittent olfactory stimulation generated by the patchy structure of the plume to generate upstream movement and successful location of the source. Neurons at all levels of the olfactory system are sensitive to intermittent stimulation, and some circuits appear to preserve the temporal activation patterns experienced in a plume and relay them to higher processing centers in the brain. Recent studies using simulation models and odor-guided robots are leading to tests of biological hypotheses that would be difficult or impossible to address with living organisms, and are also leading to the first man-made plume-tracking systems.
MaxWeight scheduling: “Smoothness” of the service process

The model is a “generalized switch”, serving multiple traffic flows in discrete time. The switch uses MaxWeight algorithm to make a service decision (scheduling choice) at each time step, depending on the current queue lengths. In some applications, it is not important to keep the queue lengths/delays small (e.g., when queues are virtual, rather than physical), but is important that the service processes provided to each flow remains “smooth” (i.e., without large gaps in service) even when the switch is heavily loaded. Addressing this question reduces to the analysis of the asymptotic behavior of the unscaled queue-differential process in heavy traffic. We prove that the stationary regime of this process converges to that of a positive recurrent Markov chain, whose structure we explicitly describe. This in turn implies “smoothness” of the service processes.
Biosynthesis of Characteristic Flavours in Plants

The characteristic flavours in plant-, leaf alcohol, cis-3-hexenol, and leaf aldehyde, trans- 2- hexenal, are widely distributed in fresh leaves, vegetables and fruits and are responsible for the odor characteristic of the leaf. Also, both are found in some insect excretions as functioning attractants and repellents.The investigation of leaf alcohol has been carried out by Takei and Ohno et al. since 1938; from 1957, we have been studying leaf alcohol and leaf aldehyde from a number of angles : synthetic chemistry, natural products chemistry, and plant biochemistry.Recently, we focused our attention on the biosynthesis of leaf alcohol and leaf aldehyde and have demonstrated the biosynthetic pathway using Thea sinensis leaves. We know now that leaf alcohol and aldehyde are produced from cis-3-hexenal. This C6-compound, cis-3-hexenal and the C12-compound, 11-formyl-cis-9-undecenoic acid, are biosynthesized from linolenic acid by enzymatic oxygenative splitting through the addition of oxygen to the double bond between C-12 and C-13. This C12-fragment isomerizes to give 11-formyl-trans-10-undecenoic acid, traumatic half aldehyde, which is known as the “Wound Hormone”.
An Online Survey of Family Members' Beliefs and Attitudes About Smoking and Mental Illness.

ABSTRACTObjective: Family beliefs about smoking and cessation may influence whether individuals with mental illness who smoke use effective cessation treatment. We surveyed family members online regarding beliefs about smoking and cessation among people with mental illness. Method: Two hundred fifty-six family members of individuals with mental illness completed an online survey. Responses were summarized and t tests were used to compare responses based on the family member's smoking status. Results: One-quarter of respondents agreed that people with mental illness must smoke to manage mental health symptoms, nearly half (48%) expressed uncertainty about the whether nicotine replacement therapy is harmful for this population, and 69% believed that family members do not have the skills to help an individual with mental illness quit smoking. Conclusions: Misconceptions about smoking and mental illness and uncertainty about the safety of cessation treatment may interfere with family support for quitting smok...
Ultrastructure of Senile Dementia and of Experimental Analogs

The morphologic changes of age which concern the neuropathologist must be not only those he can correlate with clinical signs and symptoms, but also those he can relate to fundamental biology. It is the purpose of this paper to provide as much of this structural correlation as is currently possible in regard to Alzheimer’s disease.
Bayesian Optimal Analysis for Meteorological Data

ABSTRACT Purser, R.J. 1985. Bayesian optimal analysis for meteorological data. An approach to the assimilation at a single time of meteorological data based on the statistical principles of Bayesian estimation theory is described. Emphasis is given to the non-linear features of the scheme and a particular way of implicitly specifying the adaptive structure-functions of the analysis scheme is presented by expressing the analysis problem in terms of high-order elliptic differential equations.