cssi/SciSciGPT-SciSciNet huggingface dataset:
Study of packet loss in a packet switched voice system

A study is presented of the temporal behavior of packet loss on a voice-transmitted TDM time-division multiplexed link. The mean duration is given of blocking and nonblocking periods, the variance of blocking periods, and the expected packet. The loss rate within blocking periods is derived. These measures are extended to characterize the performance of packet loss at various rates. The results provide significant information on voice packet loss and can be directly applied to the design of packet-switched voice systems. The packet loss rate in a voice system changes slowly and has large fluctuations. This temporal behavior of packet loss, especially at high rates, is basically characterized by voice correlation and system capacity. Increasing the buffer size merely extends the nonblocking periods and thereby reduces the overall average packet-loss-rate. Once a blocking period occurs, however, the length of this period as well as the behavior of packet loss within the period becomes irrelevant to the buffer size. Based on this observation, a simple tool is developed to evaluate the boundary performance of packet loss at various rates; it is especially accurate at high rates. >
U-Tube in High Bileduct Obstruction

Objective. The recent experience with U tubes at Rush-Presbyterian-St. Lukes Medical Center was reviewed in order to assess their current role in hepatobiliary surgery. Summary Background Data. Transhepatic intubation by a variety of methods has been used routinely for biliary decompression and inhibition of anastomotic stricture since the 1960s. U tubes were popularized in the early 1970s. However, little has been written about their use and efficacy in recent years. Because of the apparent benefits associated with the use of U tubes versus other stenting techniques, the authors performed this study. Methods. The hospital and office charts of all patients who had U tubes placed between 1980 and 1992 were reviewed retrospectively. Between 1980 and 1992, U tubes were placed intraoperatively in 54 patients for biliary decompression and/or stenting. Twelve patients were operated on for benign causes of obstruction. Forty-two patients with malignant tumors underwent surgery for U tube placement in conjunction with or without tumor resection and anastomotic bypass. Results. There was a 0% operative mortality rate in the benign group. In six patients, the U tube played a major role in the long-term management of their disease processes. None of these patients has had restricture since removal of the tube. In the malignant group, the 30-day operative mortality rate was 12%. After 3 months, marked clinical improvement and complete biliary decompression were achieved, with mean bilirubin levels dropping from 14.0 mg/dL to 1.3 mg/dL. No patients in the malignant group required reoperation for recurrent biliary obstruction after u tube placement. Conclusions. The use of U tubes is advocated for biliary decompression and/or anastomotic stenting in patients with benign stricture or resectable malignancy and in patients with nonresectable, malignant biliary obstruction for adequate palliation of intractable jaundice.
Novel architecture for a high performance full custom graphics processor

The design and architectural features of a 32-b microprogrammed graphics processor are discussed. A description is given of the application of datapath elements and the exploitation of VRAM hardware, to achieve state-of-the-art processor performance levels. The host interface is discussed, along with video control, screen refresh control, and emulation and testability. >
Dentist’s role in management of the cancer patient

The dentist can help his patient with cancer by understanding the patient’s emotional problems, by offering a con­ tinuing relation, by showing calm and enduring interest and effort on behalf of the patient, and by helping to alleviate anxiety and forestall depression when such feelings are related to dental care. The dentist should be aware of the com­ munity resources available to assist the cancer patient, and should not hesitate to help him obtain the necessary care and aid.
Seasonal and interannual variability in evapotranspiration of native tallgrass prairie and cultivated wheat ecosystems

Year-round measurements of evapotranspiration (ET) were made, using the eddy covariance technique, in tallgrass prairie and winter wheat ecosystems in north-central Oklahoma during 1996–2000. Seasonal and interannual variability in water vapor flux was examined in terms of relevant controlling variables. During the growing season, the daily ET was 3.5–5.0 mm day � 1 for the prairie and 2.5–7.0 mm day � 1 for wheat. Annual ET ranged 640–810 mm for the prairie, and 710–750 mm for wheat. ‘‘Non-growing’’ season ET was about 25% of the annual ET in the prairie (during November–April) and about 50% of the annual ET in wheat (during July–February). Differences in ET between the two ecosystems and the corresponding interannual variability were related mostly to the effects of soil moisture stress and variations in green foliage area, while the weather parameters had a smaller impact. The ET model of Priestley and Taylor (1972) [Priestley, C.H.B., Taylor, R.J., 1972. On the assessment of surface heat flux and evaporation using large-scale parameters. Mon. Weather Rev. 100, pp. 81–92.] was modified to incorporate the effects of soil moisture and foliage area, and tested against field measurement. The modification improved the prediction of ET significantly as compared to the original model. On average, the overestimation of the actual ET by the original model reduced from 47 to 9% at the prairie site, and from 20 to 4% at the wheat site. Improved performance of the modified Priestley–Taylor model over a wide range of environmental conditions makes it potentially a practical tool for predicting ET in grasslands and agricultural systems. # 2005 Elsevier B.V. All rights reserved.
The upper layers of the superior colliculus of the rat: A Golgi study

A number of questions deriving from a previous electron microscopic study of the superficial layers of the rat superior colliculus pointed out the need for a comprehensive study of the cell types of the superior colliculus and their detailed morphology. In the present Golgi study the cells of the superficial layers of the superior colliculus were found to be of five major types; marginal cells, horizontal cells, narrow field vertical cells, wide field vertical cells, and stellate cells. Some of these categories were further subdivided. Each cell type has a distinctive set of dendritic field characteristics, a regional distribution, and consistent axon characteristics. The horizontal cells were found to have a preference in the orientation of their dendrites along the vertical and horizontal axes of the visual field projection upon the superior colliculus. It is argued that the horizontal cells are the presynaptic elements in the majority of the dendrodendritic synapses.
Grenville foreland thrust belt hidden beneath the eastern U.S. midcontinent

Grenville foreland thrust structures are observed beneath the eastern U.S. midcontinent on COCORP (Consortium for Continental Reflection Profiling) line OH-1 and a short seismic line in southwest Ohio. These structures represent the first evidence for a significant Grenville foreland thrust belt preserved in eastern North America. On the COCORP lines, the structures include a thrust ramp that truncates layered rocks of the footwall as well as a complex hanging-wall ramp anticline and an associated asymmetric syncline. The Grenville front tectonic zone appears to truncate these foreland structures, indicating a later, second phase, expressed as a deeply penetrating, out-of-sequence thrust zone associated with the main uplift of the Grenville province on the east. A short, shallow seismic line in southwestern Ohio reveals an east-dipping sequence of prominently layered rocks that may lie above a footwall ramp to a deeper Grenville thrust fault. A drill hole into the less reflective top of this dipping sequence encountered unmetamorphosed sedimentary rocks like those increasingly reported from other drill holes in southwestern Ohio and adjacent states. Although possibly part of a late Precambrian (Keweenawan?) rift, these clastic sedimentary rocks may instead preserve evidence of a heretofore unrecognized Grenville foreland basin in eastern North America. Alternatively, these Precambrian sedimentary rocks together with an underlying, but yet undrilled, strongly layered sequence may correlate with similarly layered rocks observed on COCORP and industrial seismic lines within the Middle Proterozoic granite-rhyolite province to the west in Indiana and Illinois and indicate that unmetamorphosed sedimentary material is an important constituent of the granite-rhyolite province. The presence of a Grenville foreland thrust belt beneath the eastern U.S. midcontinent, in contrast with its absence in Canada, may suggest a deeper level of erosion of the Grenville province and its foreland in Canada or reflect important lateral differences in the geology of the foreland.
The Frank vectorcardiogram of the newborn infant.

Abstract Frank lead electrocardiograms recorded during first 24 hours of life were obtained from 113 term normal neonates. The simultaneously recorded X, Y and Z leads were analyzed by a digital computer program. Mean values for heart rate, P-R interval, QRS interval and S-T intervals were determined. Mean magnitudes of the scalar X, Y and Z (right and left, superior and inferior, and anterior and posterior, respectively) are also presented. Mean magnitude values for the successive “timed” QRS vectors, both in real time (0.01, 0.02 to 0.06 second) and “normalized time” were determined, and the angle of prevalent direction was calculated for each. Mean and maximal planar QRS vectors, as well as mean and maximal spatial QRS vectors, were determined similarly. There was considerable individual variation in magnitude of the vectors within the group. There was close clustering of the individual planar vectors about the prevalent vector for the 0.02, 0.03 and 0.05 second vectors in the horizontal and left sagittal planes only. Dispersion of individual vectors was of considerable magnitude for each of the time intervals in the frontal plane. This was also true for the maximal and mean QRS vectors in this plane. However, in the horizontal and left sagittal planes, approximately two thirds of the individual vectors were clustered closely about an anterior prevalent vector and the remaining third clustered closely about a posteriorly oriented vector of prevalent direction. The mean magnitude of the maximal spatial QRS vector was 1,521 μv, and in two thirds of the subjects this vector was oriented in an almost strictly anterior and inferior direction; in the remaining third of the subjects this vector was directed far to the right, superiorly and posteriorly. The Frank lead system does not perform very uniformly in the frontal plane, but in the left sagittal and horizontal planes uniformity of performance was apparent for the 0.02, 0.03 and 0.05 second vectors and for the planar and spatial mean and maximal QRS vectors.
Exponential integral approximations

Abstract Some radiative transfer applications involving cancellation require values of exponential integrals of very high accuracy. The well-known Maclaurin and asymptotic series become very inefficient, and many of the polynomial approximations, although efficient, do not have the necessary accuracy. Attention is called to recent work, some of it unpublished, which permits the accurate and efficient evaluation of these integrals.
Current Issues in the Diagnosis of Attention Deficit Hyperactivity Disorder, Oppositional Defiant Disorder, and Conduct Disorder

This review evaluates the diagnostic criteria for three of the most common disorders for which children and adolescents are referred for mental health treatment: attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD). Although research supports the validity and clinical utility of these disorders, several issues are highlighted that could enhance the current diagnostic criteria. For ADHD, defining the core features of the disorder and its fit with other disorders, enhancing the validity of the criteria through the lifespan, considering alternative ways to form subtypes of the disorder, and modifying the age-of-onset criterion are discussed relative to the current diagnostic criteria. For ODD, eliminating the exclusionary criteria of CD, recognizing important symptom domains within the disorder, and using the cross-situational pervasiveness of the disorder as an index of severity are highlighted as important issues for improving classification. Finally, for CD, enhancing the current subtypes related to age of onset and integrating callous-unemotional traits into the diagnostic criteria are identified as key issues for improving classification.
Mesoscale Meteorology and High Ozone in the Northeast United States

Abstract This study examines the relationship between mesoscale meteorological conditions and high-ozone days in the northeastern United States. It is proposed that the leeside trough and the sea-breeze front are two mesoscale features that can be important on these high-ozone days. The 19 June and 4 July 1995 case studies are presented to illustrate the role of each feature, respectively. The 19 June case revealed that the leeside trough initially formed to the lee of the high terrain from southeast Pennsylvania to the Maine coast but shifted southeastward during the course of the day. As the trough advanced toward the coast, the surface winds ahead of the trough remained southwesterly, paralleling the source regions of the major metropolitan areas. It appears that the surface flow near the trough acted to elevate and concentrate ozone and its precursors in a narrow band along and just south of the trough, with much lower values north and west of the trough, where cleaner trajectories were encountered. I...
Cardiac Arrest and Resuscitation

In the cardiac intensive care unit (ICU) staff should be mentally and physically equipped to deal with sudden cardiac arrest and initiate prompt resuscitative efforts. Such efforts fundamentally involve a coordinated system to provide artificial ventilation and artificial circulation (i.e., basic cardiopulmonary resuscitation [CPR]) that may be supplemented by advanced cardiac life support systems (e.g., oxygen, defibrillation, specialized medications). Many of the elements of advanced cardiac life support are reviewed in detail in other chapters of this book, as follows : 1 Recognition and treatment of arrhythmias (chapters 4, 5, and 6). 2 Cardioversion and defibrillation (chapter 7). 3 Recognition and treatment of conduction disorders (chapters 8 and 9). 4 Recognition and treatment of hemodyna-mic disorders, including heart failure and car-diogenic shock (chapters 11 and 12).
Software reliability issues: an experimental approach

In this thesis, we present methodologies involving a data structure called the debugging graph whereby the predictive performance of software reliability models can be analyzed and improved under laboratory conditions. This procedure substitutes the averages of large sample sets for the single point samples normally used as inputs to these models and thus supports scrutiny of their performances with less random input data. Initially, we describe the construction of an extensive database of empirical reliability data which we derived by testing each partially debugged version of subject software represented by complete or partial debugging graphs. We demonstrate how these data can be used to assign relative sizes to known bugs and to simulate multiple debugging sessions. We then present the results from a series of proof-of-concept experiments. We show that controlling fault recovery order as represented by the data input to some well-known reliability models can enable them to produce more accurate predictions and can mitigate anomalous effects we attribute to manifestations of the fault interaction phenomenon. Since limited testing resources are common in the real world, we demonstrate the use of two approximation techniques, the surrogate oracle and path truncations, to render the application of our methodologies computationally feasible outside a laboratory setting. We report results which support the assertion that reliability data collected from just a partial debugging graph and subject to these approximations qualitatively agrees with those collected under ideal laboratory conditions, provided one accounts for optimistic bias introduced by the surrogate in later prediction stages. We outline an algorithmic approach for using data derived from a partial debugging graph to improve software reliability predictions, and show its complexity to be no worse than $O(n\sp2).$ We summarize some outstanding questions as areas for future investigations of and improvements to the software reliability prediction process.
Oral chemotherapeutic agents in elderly acute myeloid leukemia (AML) patients, a study from a developing country

7057 Background: Almost 60% of the patients with Acute Myeloid Leukemia (AML) are over the age of 60 years. Age is one of the strongest adverse prognostic factor for AML, both for induction remissi...
Graft shape affects midfoot correction and forefoot loading mechanics in lateral column lengthening osteotomies.

Background:Adult acquired flatfoot deformity is characterized by midfoot abduction and collapse of the medial longitudinal arch. Lateral column lengthening osteotomies primarily correct the abducti...
Closing the Food Gap: Resetting the Table in the Land of Plenty

First paragraph: Mark Winne’s book Closing the Food Gap: Resetting the Table in the Land of Plenty comes as a welcome contrast to the volumes by intellectuals about their quests to eat locally as part of their mission to expose the industrial food system. While equally personal and situated in the structural, Mark Winne describes and analyzes his efforts to close the food gap through providing healthy food for the urban poor. As personal as the foodquest books by Kingsolver and by Pollan, Winne shares his attempts to reduce poverty by increasing access to healthy food by people who are food-insecure. He takes us through his first efforts at gardening and organizing community gardens, reminding us that the most important word in that phrase is “community.” He illustrates his premise that the best programs link members of the community to each other as well as to programs that increase access to good food. He introduces us to teenagers, parents, farmers, and organizers who are part of the food- and social-justice movement. And he demonstrates the many barriers to healthy eating in the food deserts of inner cities and the various attempts — few of which have been successful — to make healthy food available to the food-insecure people who live there....
Testicular and kidney masses in a HIV-infected man

A 37-year-old Caucasian male presented with what appeared clinically and diagnostically as testicular and kindey tomour's. However, syphilis serology and histology confirm that the lesions were gumma's. Without routine syphilis serology, the correct diagnosis may have been missed.
Anti-Comparative Advantage:A Puzzle in China-U.S.Bilateral Trade

This paper reveals an"Anti-Comparative Advantage"puzzle in U.S.-China trade.That is:the U.S.exports less to China in sectors it has greater technological comparative advantage,and the more its technology exceeds China,the less it exports to China than to the rest of the world;while China's export to the U.S.is the opposite.To further test this puzzle,we extend Eaton-Kortum model to multi-sector and apply it to analyze the determinants of U.S.-China trade structure empirically.It's shown that after controlling for production capacity,trade costs,etc.,comparative advantage still plays asymmetric roles in their bilateral trade,and survives robustness checks.
The resident death underreporting survey analysis of Chaoyang District from 2009 to 2011

Objective To understand the degree of difference of reported death and actual death and underreporting reasons of Chaoyang District residents,to improve the integrity of the Death report,and to promote national chronic disease prevention and control demonstration area of Chaoyang District.Methods To Take a random cluster sampling method,in the region of 43 parastic collected 2-3 each neighborhood committees to conduct investigations to obtain the death of the survey period,each death information was checked with electronic database of conventional medical death registration system of cdc,to take home survey method to suspicious underreporting list,to check the underreporting death information again,and to calculate the underreporting rate.Results The total death underreporting rate of Chaoyang district residents in 2009 - 2011 was 8.47%,which for men was 9.38%and for women was 7.23%.the male death underreporting rate was higher than the female.There was no death underreporting in children under 5 years old.The city underreporting rate was 10.01%,which for rural was 5.44%,the difference was statistically significant,the rate for the urban areas was higher than which in rural areas.Conclusions The death underreporting of Chaoyang district residents was evidenced.The comprehensive measures should be taken to further improve the reporting rate and the quality of reporting of Resident Deaths.
Analysis on effect of AIDS control and prevention in program areas in Anhui

Objective To evaluate the effectiveness of health promotion and intervention in China Global Fund AIDS program Round 3 counties,in order to provide foundation for selecting scientific preventive measures and making reasonable work plan.Methods Guidelines from reports of GF3 in 10 counties and the specific investigated results in 2008 were analyzed,compared with the guidelines of ME on national HIV/AIDS control and prevention etc.Results All 15 guidelines accomplished 85% rear-ranged objectives,86.67% guidelines accomplished 90% rear-ranged objectives,60% guidelines accomplished all rear-ranged objectives,and 80% guidelines accomplished 85% final objectives.The proportion of knowing AIDS facts among PLWHAs,FSW,migrant population were still at a low level.The levels of knowledge and behavior were significantly different among groups in different program counties.Conclusions The mid-objectives is effective,especially the guidelines of VCT,ART and CARE and behavior intervention.But the proportion of knowing AIDS facts among PLWHAs,FSW,migrant population is still at a low level.The levels of knowledge and behavior are significantly different among groups in different program counties.Further health promotion and intervention campaign should be oriented to the needs of different target populations.
Agricultural Prices and the Use of Resources

As noted in Chapter 2, many governments attempt to use prices as means of achieving income objectives for their farmers. It has been hoped that higher output prices would result in higher and more satisfactory farm incomes. As argued later (Chapter 9), such an expectation has little realism. The aim in this chapter is to illustrate some of the effects of distortions in prices upon the use of farm resources. As has already been shown, there are wide differences in the level of farm product prices among the various industrial nations. If farmers did not respond to prices of outputs and inputs, these wide differences would primarily reflect differing degrees of income transfers to the various producer groups within agriculture.
H3K27 methylation: a promiscuous repressive chromatin mark

Polycomb Repressive Complex 2 (PRC2) is a multiprotein complex that catalyzes the methylation of lysine 27 on histone H3 (H3K27me). This histone modification is a feature of facultative heterochromatin in many eukaryotes and maintains transcriptional repression established during early development. Understanding how PRC2 targets regions of the genome to be methylated remains poorly understood. Different cell types can show disparate patterns of H3K27me, and chromatin perturbations, such as loss of marks of constitutive heterochromatin, can cause redistribution of H3K27me, implying that DNA sequence, per se, is not sufficient to define the distribution of this mark. Emerging information supports the idea that the chromatin context-including histone modifications, DNA methylation, transcription, chromatin structure and organization within the nucleus-informs PRC2 target selection.
Feature Selection Methods for Zero-Shot Learning of Neural Activity.

Dimensionality is a serious challenge in human neuroimaging. Across imaging modalities, large pools of potential neural features (e.g. responses from particular voxels, electrodes, and temporal windows) have to be related to typically limited sets of stimuli and samples. To deal with limited stimulus sets, zero-shot encoding and decoding models have been introduced to classify classes outside the training set. However, these models have been found to be particularly susceptible to the curse of dimensionality and the risk of over-fitting. While no systematic study of feature selection for these models has been reported, a relatively straightforward feature stability approach has been successfully applied across models and imaging modalities. To characterize the tradeoffs in feature selection for encoding and decoding models, we compared correlationbased stability to several other feature selection techniques on comparable data sets from two distinct imaging modalities: functional Magnetic Resonance Imaging and Electrocorticography. Semantic attribute encoding and decoding models were trained and tested with five distinct feature selection methods: correlation-based stability, a wrapper method, Fisher’s Method, Mutual Information-based stability, and a novel attribute/feature correlation technique. Results demonstrate that correlation-based stability performs well across imaging modalities, but other methods result in qualitatively different patterns of selected features while achieving similar levels of performance, and performance can be maintained with fewer features. Choices about feature selection can have a substantial impact when closed-set accuracy, open-set robustness, and runtime are competing design objectives.
Zoning reform for advancing sustainability: insights from Denver’s form-based code

Many municipalities are adopting form-based codes (FBCs) for advancing the sustainability of development and for facilitating sustainable design criteria that are difficult to achieve under conventional zoning codes (CZCs). The City of Denver recently adopted a citywide FBC. A case-study method was used to examine the extent to which Denver’s FBC differs from the CZC in integrating sustainable design criteria included in the LEED-ND rating system. The results indicate that Denver’s FBC addresses most LEED-ND criteria more strongly than does the CZC; however, some criteria deserve more attention. The paper concludes with recommendations for Denver’s FBC and for other municipalities that are considering zoning reform.
Le bloc interscalénique continu est corrélé avec une durée d'hospitalisation plus courte après l'arthroplastie totale d’épaule

Abstract Background Catheter-delivered continuous interscalene anesthesia has demonstrated improved pain control in randomized clinical trials. The purpose of this study is to determine whether the introduction of continuous catheter anesthesia was associated with a change in length of stay (LOS), readmission, rates of discharge home without home health or nursing services, or opioid administration. We hypothesized that the introduction of continuous catheter anesthesia would be associated with a decrease in LOS, readmission, non-home discharge, and opioid administration. Methods During 2012, our center transitioned from ultrasound-guided single-dose interscalene regional anesthesia to combined single-dose anesthesia and additional continuous catheter anesthesia over 48–72 hours. This retrospective chart review compared primary shoulder arthroplasties with single-dose anesthesia to those with continuous catheter anesthesia, after excluding the learning curve, with univariate and multivariate analyses. Results One thousand six hundred and ninety-seven patients met criteria, 41 % with single-dose anesthesia and 59 % with continuous catheter anesthesia. On univariate analysis, the continuous catheter group LOS was 2.2 ± 0.7 day and single-dose group LOS was 2.5 ± 0.8 days ( P ≤ 0.001). One day LOS's comprised 1 % of the single-dose group and 27 % of the continuous catheter group ( P P P = 0.091 and 0.576), and home discharge ( P = 0.456) were not different. Opioid administration was higher in the continuous catheter group on univariate analysis ( P P = 0.607). Conclusion In this retrospective review of 1697 primary shoulder arthroplasties performed at our high-volume, referral center, continuous catheter anesthesia was associated with reduced length of stay when compared to single-dose anesthesia. Level of evidence Therapeutic, level IV.
Nurture thru Nature: Creating natural science identities in populations of disadvantaged children through community education partnership

In this article we describe the development, implementation, and some of the early impacts of Nurture thru Nature (NtN), an American after-school and summer program designed to introduce elementary...
Mixed-integer optimization of distillation column tray positions in industrial practice

We present an outer approximation algorithm tailored to the optimization of distillation column feed and side draw tray positions. A new fallback rule based on a generalization of an integer cut for integer parameters is presented. This fallback rule turned out to be a key ingredient to successful application to real-world problems. As an example, a process design optimization of an natural gas treatment plant is presented.
The Use of Micro-Electro-Mechanical Systems (MEMS) in the Construction Industry

Micro-electro-mechanical systems (MEMS) have been identified as one of the most promising technologies and will continue to revolutionize the industry as well as the industrial and consumer products by combining silicon-based microelectronics with micro-machining technology. All the spheres of industrial application including robots conception and development will be impacted by this new technology. If semiconductor microfabrication was contemplated to be the first micro-manufacturing revolution, MEMS is the second revolution. The paper reflects the results of a study about the state of the art of this technology and its future influence in the development of the construction industry. The addressed questions are: technical and economical effects of MEMS application in the industry and analysis of their use in Japan, Europe, and the USA. Also several examples of MEMS applications in construction are presented.
Advanced Topics in Fluorescence Quenching

In the previous chapter we described the basic principles of quenching. A wide variety of quenchers are known. Quenching requires molecular contact between the fluorophore and the quencher. This contact can be due to diffusive encounters (dynamic quenching), or to complex formation (static quenching). Because of the close-range interaction required for quenching, the extent of quenching is sensitive to molecular factors that affect the rate and probability of contact, including steric shielding and charge—charge interactions.
Central Processing Time for a Conditioned Response in a Vertebrate Model System

For some years we have been developing visually conditioned heart rate change in the pigeon as a vertebrate model system for cellular analyses of associative learning. The behavioral model is now well-established, and substantial progress has been realized in delineating the neuronal circuitry mediating the conditioned response. With this information as a foundation we have been able to initiate cellular neurophysiological studies to (a) describe the temporal properties of the information flow along the identified pathways during conditioned responding, and (b) identify sites of training-induced modification. This report deals with the temporal properties of the information flow, and the results indicate that central latencies and processing time are surprisingly short. Thus, the system may be considerably more “analyzable” than might have been anticipated.
Pediatric high-grade glioma: aberrant epigenetics and kinase signaling define emerging therapeutic opportunities

Supratentorial pediatric high-grade gliomas (pHGGs) are aggressive malignancies that lack effective treatment options. Deep genomic sequencing by multiple groups has revealed that the primary alterations unique to pHGGs occur in epigenetic and kinase genes. These mutations, fusions, and deletions present a therapeutic opportunity by use of small molecules targeting epigenetic modifiers and kinases that contribute to pHGG growth. Using a targeted search of the pre-clinical literature and clinicaltrials.gov for kinase and epigenetic pathways in pHGG, we collectively describe how these mechanisms are being targeted in pre-clinical animal models and in current clinical trials, as well as propose unexplored therapeutic possibilities for future investigations. Relevant pHGG kinases are targetable by several FDA-approved or clinical-stage kinase inhibitors, including altered BRAF/MET/NTRK/ALK and wild-type PI3K/EGFR/PDGFR/VEGF/AXL. Epigenetic proteins implicated in pHGG are also clinically targetable and include histone erasers, writers and readers such as HDACs, demethylases LSD1/JMJD3, methyltransferase EZH2, chromatin reader bromodomains, and chromatin remodeler subunit BMI-1. Crosstalk between these pathways can occur involving kinases such as EGFR and AMPK interacting with epigenetic modifiers such as HDACs or EZH2. Single agent trial results of kinase inhibitors or epigenetic targets alone are underwhelming and hampered by poor pharmacokinetics, adaptive resistance, and broad inclusion criteria. The genetic and phenotypic diversity of pHGGs is now well characterized after large-scale sequencing studies on patient tissue. However, clinical treatment paradigms have not yet shifted in response to this information. Combination therapies targeting multiple kinases or epigenetic targets may hold more promise, especially if attempted in selected patient populations with hemispheric pHGG tumors and relevant targeted therapeutic biomarkers.
An Analytic Approach to Very High Speed Flat Ship Theory

This paper defines an asymptotic procedure for analytic solutions to the linearized low-aspect-ratio problem of flow past a flat ship (with monotonic planform) traveling at very high speeds. (The extension to planforms whose maximum beam is not at the trailing edge is still an unresolved problem.) Relatively simple lift and drag formulas can be worked out for classes of hull shapes in such a way as to give insight into their relative performance. While the formulas presented in this paper were worked out by hand, the solution technique lends itself readily to computer evaluation.
Engine Mount Optimization

Recent work in design optimization has led to software which allows the designer to indicate frequency bands which are undesirable. The software determines the optimal amount of several design alterations which will move system natural frequencies from undesirable bands. This design procedure is shown to be effective in selecting stiffness, orientation, and location of engine mounts which remove engine natural frequencies from the range excited at idle.
Alternative Diagnoses in Pediatric Fecal Microbiota Transplant Referral Patients.

ABSTRACT The incidence of Clostridioides difficile infection (CDI) has been increasing in the United States. About 10-20% recur after initial treatment, with increasing recurrence following subsequent treatment courses. This sequence can lead to recurrent CDI (rCDI), refractory to conventional therapeutics resulting in the most common indication for fecal microbiota transplantation (FMT). FMT is the most effective microbial therapeutic to date and can cure rCDI in 80-90% of cases. There is growing concern, however, for pathogen transmission through FMT, underscoring the importance of careful recipient selection. In adults referred for FMT with a tentative diagnosis of rCDI, alternative diagnoses were recognized in 25% of patients, but such observation in children is lacking. In this single-center retrospective study, alternative diagnoses (eg, constipation/overflow diarrhea, inflammatory bowel disease) were found in 13 (22.4%) of 58 children who were referred for FMT evaluation for rCDI. Of the patients who were diagnosed with rCDI, 16 (27.6%) did not require FMT.
A testbed for learning by demonstration from natural language and RGB-depth video

We are developing a testbed for learning by demonstration combining spoken language and sensor data in a natural real-world environment. Microsoft Kinect RGB-Depth cameras allow us to infer high-level visual features, such as the relative position of objects in space, with greater precision and less training than required by traditional systems. Speech is recognized and parsed using a "deep" parsing system, so that language features are available at the word, syntactic, and semantic levels. We collected an initial data set of 10 episodes of 7 individuals demonstrating how to "make tea", and created a "gold standard" hand annotation of the actions performed in each. Finally, we are constructing "baseline" HMM-based activity recognition models using the visual and language features, in order to be ready to evaluate the performance of our future work on deeper and more structured models.
Phase 2 study of neoadjuvant docetaxel plus bevacizumab in patients with high-risk localized prostate cancer: a Prostate Cancer Clinical Trials Consortium trial.

BACKGROUND: Treatment of high-risk localized prostate cancer remains inadequate. The authors performed a phase 2 multicenter trial of neoadjuvant docetaxel plus bevacizumab before radical prostatectomy. METHODS: Eligibility included any of the following: prostate-specific antigen (PSA) >20 ng/mL or PSA velocity >2 ng/mL/y, cT3 disease, any biopsy Gleason score 8 to 10, and Gleason score 7 with T3 disease by endorectal magnetic resonance imaging (MRI) at 1.5 T. Also, those with ≥50% biopsy cores involved and either Gleason score 7, PSA >10, or cT2 disease were eligible. Patients were treated with docetaxel 70 mg/m2 every 3 weeks for 6 cycles and bevacizumab 15 mg/m2 every 3 weeks for 5 cycles. The primary endpoint was partial response by endorectal MRI. RESULTS: Forty-one patients were treated. Median age was 55 years (range, 40-66 years). Baseline characteristics included: median PSA, 10.1 ng/mL; cT2, 49%, cT3, 32%; and Gleason score 8 to 10, 73%. Thirty-eight of 41 (93%) patients completed all 6 cycles. Grade ≥3 adverse events were rare, although 3 of 41 (7%) experienced febrile neutropenia. Twelve patients (29%; 95% confidence interval [CI], 16%-45%) achieved a >50% reduction in tumor volume, and 9 patients (22%; 95% CI, 11%-38%) achieved a >50% post-treatment decline in PSA. Thirty-seven of the 41 patients underwent radical prostatectomy; there were no complete pathologic responses. CONCLUSIONS: Neoadjuvant docetaxel and bevacizumab is safe, and results in reductions in both tumor volume and serum PSA, in men with high-risk localized prostate cancer. The role of neoadjuvant chemotherapy in prostate cancer, and perioperative antiangiogenic therapy in general, requires further elucidation through ongoing and planned trials. Cancer 2012. © 2012 American Cancer Society.
Abstract 112: FTY720-P is a potent inhibitor of class I histone deacetylases that enhances histone acetylation, reactivates ERα expression, and increases hormonal therapeutic sensitivity of breast cancer

Hormonal therapies, including ovarian ablation, ER antagonists, and aromatase inhibitors, are the standards of care for treatment of ERα positive breast cancer. However, development of resistance to hormone therapies in advanced breast cancer is a major obstacle. Moreover, estrogen receptor-α (ERα)-negative breast cancer is clinically aggressive and does not respond to conventional estrogen targeted therapies. Strategies that lead to re-expression of ERα could sensitize breast cancers to selective ER modulators. FTY720/Fingolimod, a sphingosine analog, is an FDA-approved pro-drug for treatment of multiple sclerosis that also has anticancer actions that are not yet well understood. We have now found that FTY720 is phosphorylated in breast cancer cells by nuclear sphingosine kinase 2 and accumulates there. Nuclear FTY720-P in turn is a potent inhibitor of class I histone deacetylases (HDACs) that enhances histone acetylations and gene expression independently of its known effects on canonical signaling through sphingosine-1-phosphate receptors. In ERα negative human and murine breast cancer cells, FTY720 reactivated expression of silenced ERα and sensitized them to tamoxifen. Moreover, oral administration of clinically relevant doses of FTY720 to mice bearing ERα negative syngeneic breast tumors also re-expressed ERα and increased therapeutic sensitivity to tamoxifen in vivo more potently than a known HDAC inhibitor. Our work suggests that FTY720 is a promising strategy for effective treatment of conventional hormonal therapy-resistant breast cancer and triple-negative breast cancer. Supported by NIH grant RO1CA061774 and the Department of Defense BCRP program award W81XWH-14-1-0086 (S. Spiegel). Citation Format: Nitai C. Hait, Dorit Avni, Akimitsu Yamada, Sheldon Milstien, Kazuaki Takabe, Sarah Spiegel. FTY720-P is a potent inhibitor of class I histone deacetylases that enhances histone acetylation, reactivates ERα expression, and increases hormonal therapeutic sensitivity of breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 112. doi:10.1158/1538-7445.AM2015-112
Systems approach to the study of drug transport across membranes using suspension cultures of mammalian cells: I. Theoretical diffusion models

Abstract Some general physical models are described for the diffusional transport of drugs across membranes of cells in culture suspensions. The models provide a basis for the design and analysis of experiments that are aimed to describe (a) the nature of the principal transport barrier, (b) the kinds of drug species being transported, (c) whether, where and how much solute binding occurs, and (d) the influences of pH, partition co-efficient and numerous other factors. The cell is treated as a sphere with non-homogeneous phase compartments. Both rigorous and approximate mathematical expressions have been derived for the quasi-steady-state diffusion through the membrane followed by three cases accounting for the distribution of drug in the heterogeneous cell interior, that is, (a) the non-steady-state situation, (b) establishment of instantaneous distribution and (c) instantaneous distribution in the aqueous interior with slow permeation of drug into the cytoplasmic bodies and nucleus.
Lupus erythematosus panniculitis in children: report of three cases and review of previously reported cases.

Abstract: Lupus erythematosus panniculitis (LEP) is a rare finding in children, with only 12 fully reported prior cases in the English literature. We describe three cases of LEP in children younger than 18 and compare them to previous cases reported in the literature. We examine laboratory tests performed, biopsy results, age at onset and diagnosis, presence or absence of systemic symptoms, and outcomes after treatment. It is unknown what the risk is of these patients developing future systemic lupus erythematosus. We also discuss the relevance of subcutaneous panniculitis-like T-cell lymphoma, because the clinical and pathologic pictures are similar in presentation.
Mu-opioid antagonists for opioid-induced bowel dysfunction.

Background Opioid-induced bowel dysfunction (OBD) is characterized by constipation, incomplete evacuation, bloating, and increased gastric reflux. OBD occurs both acutely and chronically, in multiple disease states, resulting in increased morbidity and reduced quality of life. Objectives To compare the efficacy and safety of traditional and peripherally active opioid antagonists versus conventional interventions for OBD. Search methods We searched MEDLINE, the Cochrane Central Register of Controlled Trials and EMBASE in January 2007. Additional reports were identified from the reference lists of retrieved papers. Selection criteria Studies were included if they were randomized controlled trials that investigated the efficacy of mu-opioid antagonists for OBD. Data collection and analysis Data were extracted by two independent review authors and included demographic variables, diagnoses, interventions, efficacy, and adverse events. Main results Twenty-three studies met inclusion criteria and provided data on 2871 opioid antagonist-treated patients. The opioid antagonists investigated were alvimopan (nine studies), methylnaltrexone (six), naloxone (seven), and nalbuphine (one). Meta-analysis demonstrated that methylnaltrexone and alvimopan were better than placebo in reversing opioid-induced increased gastrointestinal transit time and constipation, and that alvimopan appears to be safe and efficacious in treating postoperative ileus. The incidence of adverse events with opioid antagonists was similar to placebo and generally reported as mild-to-moderate. Authors' conclusions Insufficient evidence exists for the safety or efficacy of naloxone or nalbuphine in the treatment of OBD. Long-term efficacy and safety of any of the opioid antagonists is unknown, as is the incidence or nature of rare adverse events. Alvimopan and methylnaltrexone both show promise in treating OBD, but further data will be required to fully assess their place in therapy.
Influence of sound-conditioning on noise-induced susceptibility of distortion-product otoacoustic emissions.

Cochlear damage caused by loud sounds can be attenuated by “sound-conditioning” methods. The amount of adaptation for distortion product otoacoustic emissions (DPOAEs) measured in alert rabbits previously predicted an ear's susceptibility to a subsequent noise exposure. The present study investigated if sound-conditioning influenced the robustness of such DPOAE adaptation, and if such conditioning elicited more protection by increasing the amount of DPOAE adaptation. Toward this end, rabbits were divided into two study groups: (1) experimental animals exposed to a sound-conditioning protocol, and (2) unconditioned control animals. After base-line measures, all rabbits were exposed to an overstimulation paradigm consisting of an octave band noise, and then re-assessed 3 weeks post-exposure to determine permanent changes in DPOAEs. A major result was that prior sound-conditioning protected reductions in DPOAE levels by an average of 10–15 dB. However, DPOAE adaptation decreased with sound-conditioning, so that such conditioning was no longer related to noise-induced reductions in DPOAEs. Together, these findings suggest that sound-conditioning affected neural pathways other than those that likely mediate DPOAE adaptation (e.g., medial olivocochlear efferent and/or middle-ear muscle reflexes).