cssi/SciSciGPT-SciSciNet huggingface dataset:
The effect of pasteurization on transforming growth factor alpha and transforming growth factor beta 2 concentrations in human milk.

Transforming growth factor alpha (TGF-a) and beta 2 (TGF-s2) are present in human milk and are involved in growth differentiation and repair of neonatal intestinal epithelia. Heat treatment at 56°C has been shown effective for providing safe banked donor milk, with good retention of other biologically active factors. The purpose of our study was to determine the effect of heat sterilization on TGF-a and TGF-s2 concentrations in human milk. Twenty milk samples were collected from 20 lactating mothers in polypropylene containers and frozen at -20°C for transport or storage. Before heat treatment by holder pasteurization, the frozen milk was thawed and divided into 1-mL aliquots. All samples were heated in an accurately regulated water bath until a holding temperature was achieved, then held for 30 minutes using constant agitation. Holding temperature ranged from 56.5°C to 56.9°C. The milk was then stored at 4°C overnight for analysis the following day. The concentration of TGF-a was measured by radioimmunoassay. Mean concentration ± SD of TGF-a in raw milk samples was 119 ± 50 pg/mL, range 57 to 234. The mean concentration ± SD of TGF-a in heat treated samples was 113 ± 50 pg/mL, range 51 to 227. TGF-a concentration was minimally affected by pasteurization, with an overall loss of 6.1%. Of 19 samples, 4 had increased and 15 had decreased concentrations after pasteurization (mean percent ± SEM: 94% ± 7% of raw milk, range 72%-107%). The concentration of acid-activated TGF- 32 was measured by enzyme-linked immunosorbent assay. Mean concentration ± SD of TGF- 32 in raw milk samples was 5624 ± 5038 pg/mL, range 195 to 15480. The mean concentration ± SD of TGF-s2 in heat-treated samples was 5073 ± 4646pg/mL, range 181 to 15140. TGF-s2 survived with relatively little loss (0.6%): of 18 samples, 11 had increased and 7 had decreased concentrations after pasteurization (mean percent ± SEM: 99.4 ± 6.7% of raw milk, range 79%-120%). In conclusion, both TGF-a and TGF-132 were well-preserved in whole milk after holder pasteurization at 56.5°C. The relative increase in growth factor concentration in some of the samples may be attributable to the release of that factor from the cellular and/or fat compartments into the aqueous fraction of human milk These findings have implications regarding use of donor milk as an alternate source of growth factors and cytokines for the newborn gut when mother’s milk is unavailable.
The era of transition: 1980 to 1996

In the early 1980s, the first cases of acquired immunodeficiency syndrome (AIDS) were diagnosed. It became evident that these were not isolated cases but that the world was dealing with a pandemic. Unfortunately, as expressed by 15.1% of the questionnaire respondents (Table 3, Appendix A), AIDS and the induction of immunosuppression during cancer and transplantation chemotherapy became important events for the development of medical mycology. Opportunistic and classic fungal pathogens cause severe and fatal disease in increasing numbers in AIDS, cancer, and transplantation patients and the field of medical mycology can no longer be neglected. Difficulty in the management of opportunistic infections in these patients spurred the development of new therapies, laboratory diagnostic tests, and initiated studies of pathogenesis and immunology.
Supporting distributed execution of smartphone workloads on loosely coupled heterogeneous processors

Modern smartphones are embracing asymmetric, loosely coupled processors that have drastically different performance-power tradeoffs. To exploit such architecture for energy proportionality, both application and OS workloads need to be distributed. We propose Kage, a combination of runtime and OS support, to replicate application execution and OS functions over asymmetric processors. Kage selectively creates replicas of application and OS services and maintains state consistency for them with low overhead. By doing so, it is able to reduce processor energy consumption of light-loaded smartphones manyfold. While enabling energy-proportionality, Kage simplifies application programming by providing the illusion of a single system image and per-process address spaces.
The Interaction of Naloxone with Striatal Dopaminergic Mechanisms

ABSTRACT An analysis was made of the interaction between naloxone (NX) and striatal dopaminergic (DA) mechanisms in an attempt to elucidate the complex action of this drug on behavior. In doses ranging from 0.20-0.80 mg/kg, NX inhibited the stereotyped behavior induced by the directly acting DA agonist apomorphine (AISB), in a dose-dependent manner. NX (0.40 mg/kg) also produced a sigmoidal inhibition of the stereotypy induced by successive low doses of apomorphine (0.10-0.25 mg/kg). Since the effect of NX on behavior has been shown to be species dependent, an identical study was also undertaken in the guinea pig. Though NX exerted similar effects on AISB in both the rat and guinea pig and the stereotypy curves plotted for both species were of nearly identical configuration, low doses of apomorphine produced considerably more stereotypy in the guinea pig than did identical doses in the rat. The concomitant administration of the indirect DA agonist d-amphet-amine (0.50-5.0 mg/kg) resulted in an effect opposite to that seen with NX and apomorphine. NX potentiated amphetamine induced stereotypy (AmISB) with the amphetamine + NX curve significantly above and virtually parallel to the amphetamine + saline curve. To test the hypothesis that these effects were the result of an action exerted by NX on the release of striatal DA, the effect of NX on AISB was assessed in the presence and absence of drugs that inhibit DA release non-specifically (MPT) and specifically (-hydroxybutyric acid). Pretreatment with either drug significantly reversed the inhibitory effect of NX on AISB relative to saline pretreated animals. This was consistant with previous observations that drugs enhancing striatal DA levels also inhibit AISB in a dose-dependent manner, and potentiate AmISB. These results are also in agreement with our recent findings that NX (10−6 M) can significantly enhance the release of 3H-DA stimulated by d-amphet amine (10−6 M) in rat striatal slices in vitro . NX appears to enhance striatal DA levels only if the nigrostriatal pathway is in a state of arousal (e.g. by amphetamine). This effect is probably not mediated by a direct action of NX on presynaptic DA receptors, but rather appears to be produced indirectly by an action on presynaptic opioid receptors localized on striatal DA nerve terminals.
Main Symptom that Led to Medical Evaluation and Diagnosis of Vestibular Schwannoma and Patient-Reported Tumor Size: Cross-sectional Study in 1,304 Patients.

Objectives Although vestibular schwannomas (VS) are known to cause cranial nerve deficits, cerebellar symptoms, and hydrocephalus, the role of these symptoms as the key driver of presentation from the patient's perspective has not been described. Our objective was to survey a large, retrospective VS cohort to document the patient-reported principal initial symptom, and self-reported tumor size, and to study trends in VS patient presentation. Methods Patients diagnosed with VS at our tertiary referral center and belonging to the Acoustic Neuroma Association (ANA) answered a questionnaire between 2015 and 2017. Demographic data, self-reported tumor size, and symptomatology were analyzed. Results 1,304 patients completed the questionnaire. Tumors were diagnosed from 1966 to 2017 at a mean 51.8 years (range: 8–86 years); 66% were female, and 1.1% had confirmed neurofibromatosis type 2 (NF2). Tumor size was reported using a 6-point scale: 0 to 1 cm (22.9%), 1 to 2 cm (28.7%), 2 to 3 cm (20.5%), 3 to 4 cm (10%), greater than 4 cm (7.2%), and unknown (10.6%). Hearing loss was the most common symptom that led to diagnosis (51.5%), followed by dizziness (17%), tinnitus (11.2%), and incidental diagnosis (10.2%); a fraction that has increased significantly in the last decade (p = 0.022). Larger tumors and NF2 were significantly associated with young age (p Conclusion Our large-scale questionnaire-driven review of 1,304 patients confirms that VS presentations are stereotypical, with most individuals recalling hearing loss, dizziness, or tinnitus as their chief complaint. Many tumors were incidentally diagnosed; an expanding population, attributable to increased access to magnetic resonance imaging (MRI). Large tumors were significantly more prevalent among younger patients at diagnosis, excluding NF2 patients, suggesting a more aggressive tumor biology that remains incompletely understood.
Nicolas de Condorcet and the First Intelligence Explosion Hypothesis

The intelligence explosion hypothesis (for example, a technological singularity) is roughly the hypothesis that accelerating knowledge or technological growth radically changes humanity. While 20th-century figures are commonly credited as the first discoverers of the hypothesis, I assert that Nicolas de Condorcet, the 18th-century mathematician, is the earliest to (1) mathematically model an intelligence explosion, and (2) present an accelerating historical worldview, and (3) make intelligence explosion predictions that were restated centuries later. Condorcet provides insights on how ontology and social choice can help resolve value alignment.
Distance Education Strategies to Support Practica in Rural Settings

Personnel preparation programs in special education at the preservice and inservice levels have made extensive use of distance education program models to offer teacher education and staff developm...
Israel on Trial: How International Law is Being Misused to Delegitimize the State of Israel, by Matthijs de Blois and Andrew Tucker: Soest, the Netherlands: The Hague Initiative for International Cooperation, 2018. 500 pp., $29.95 paperback

International Court of Justice (ICJ) Judge Nabil Elaraby, in his separate opinion appended to the ICJ’s 2004 advisory opinion in Legal Consequences of the Construction of a Wall in the Occupied Pal...
Evaluating shear and normal force with the use of an instrumented transtibial socket: A case study

Abstract Patients with transtibial amputation experience ulcers on their residual limb. The loading between the device and underlying material plays a role in loads transmitted to the skin. The objective was to evaluate normal and shear forces at the socket/liner interface during walking. A 53 year old male (85.45 kg and 177.8 cm) with a transtibial amputation participated in this case study. A transtibial prosthesis was instrumented with a load cell to measure normal and shear forces at the socket interface. Three conditions were evaluated during walking: gel liner, additional three ply sock and a hole in the gel liner. Shear and normal forces were highest with the addition of a three ply. Longitudinal shear stresses ranged from 0.4–7.66 kPa, transverse shear stresses ranged from 0.01–7.79 kPa and normal stresses ranged from 2.7–61.9 kPa. Increased shear and normal forces can cause a significant decrease in blood perfusion, linked to an increased risk of ulcer formation. Experimental force results are also important for future work involving finite element modeling of the skin/liner/device interface.
Segmentation of carotid arterial walls using neural networks.

Background Automated, accurate, objective, and quantitative medical image segmentation has remained a challenging goal in computer science since its inception. This study applies the technique of convolutional neural networks (CNNs) to the task of segmenting carotid arteries to aid in the assessment of pathology. Aim To investigate CNN's utility as an ancillary tool for researchers who require accurate segmentation of carotid vessels. Methods An expert reader delineated vessel wall boundaries on 4422 axial T2-weighted magnetic resonance images of bilateral carotid arteries from 189 subjects with clinically evident atherosclerotic disease. A portion of this dataset was used to train two CNNs (one to segment the vessel lumen and the other to segment the vessel wall) with the remaining portion used to test the algorithm's efficacy by comparing CNN segmented images with those of an expert reader. Results Overall quantitative assessment between automated and manual segmentations was determined by computing the DICE coefficient for each pair of segmented images in the test dataset for each CNN applied. The average DICE coefficient for the test dataset (CNN segmentations compared to expert's segmentations) was 0.96 for the lumen and 0.87 for the vessel wall. Pearson correlation values and the intra-class correlation coefficient (ICC) were computed for the lumen (Pearson = 0.98, ICC = 0.98) and vessel wall (Pearson = 0.88, ICC = 0.86) segmentations. Bland-Altman plots of area measurements for the CNN and expert readers indicate good agreement with a mean bias of 1%-8%. Conclusion Although the technique produces reasonable results that are on par with expert human assessments, our application requires human supervision and monitoring to ensure consistent results. We intend to deploy this algorithm as part of a software platform to lessen researchers' workload to more quickly obtain reliable results.
Effect of greeting and departure interactions on the development of increased separation-related behaviors in newly adopted adult dogs

Abstract Canine separation anxiety is a common problem behavior with little known about the factors that lead to its development. This study investigated whether high arousal/excited departures and greetings with a dog may lead to the development of increased frequency of separation-related behavior in newly adopted dogs. In experiment 1, we exposed two groups of dogs to a series of either high or low arousal human experimenter interactions. We hypothesized there would be an increase in activity, vocalizations, and time in proximity to door for the dogs in the high arousal condition compared with the low arousal condition, when left alone, and that these behaviors would increase across 10 sessions. Our results did not show this, indicating high arousal departures and arrivals may not play a role in the development of increased separation-related behavior. In experiment 2, we used a survey to ask owners of dogs with, and without, canine separation anxiety about their arousal levels during arrivals and departures at home with their pet dog. We hypothesized dogs with reported canine separation anxiety would have been exposed to higher arousal levels during departures and arrivals. Our results showed a small difference between the groups, in the opposite direction of our hypothesis, where the dogs with reported canine separation anxiety were exposed to slightly lower arousal levels than dogs without, but the difference was small. From both experiment 1 and 2, our results indicate that high excitement and playful levels of owners during departures and arrivals is not associated with the development of increased separation-related behavior in newly adopted dogs. It is important to make the distinction, however, that low arousal departures and arrivals are a well-documented treatment for separation-related behavior, and our results only reflect that these arousal levels do not appear to play a causal role in the development of an increased frequency of them.
Autonomy and Manipulation: Refining the Argument Against Persuasive Advertising

Critics of persuasive advertising argue that it undermines the autonomy of consumers by manipulating their desires in morally problematic ways. My aim is this paper is to refine that argument by employing a conception of autonomy that is not at odds with certain forms of manipulation. I argue that the charge of manipulation is not sufficient for condemning persuasive advertising. On my view, manipulation of an agent’s desires through advertising is justifiable in cases where the agent accepts (or would accept) the process through which the desires were developed. I show how the standard manipulation objection proves too much as it would also condemn cases of that kind. I argue that this distinction is especially important when we consider the implications of “new media.” In addition to increasing vulnerability to manipulation, new media have considerable impacts on well-being. By siding with the traditional autonomy argument, we would be compelled to take an implausible stand against all forms of manipulation through advertising, but I suggest that only a proper subset of those cases are morally problematic. This conclusion opens up a space for persuasive advertising that is permissible while nevertheless condemning cases that violate consumers’ autonomy.
Point-mass sensitivity of gravimetric satellites

Abstract Frequency-domain expressions are found for gradiometer and satellite-to-satellite tracking measurements of a point source on the surface of the Earth. The maximum signal-to-noise ratio as a function of noise in the measurement apparatus is computed, and from that the minimum detectable point mass is inferred. A point mass of magnitude M 3 = 100 Gt gives a signal-to-noise ratio of 3 when a GOCE-like gradiometer passes directly over the mass. On the satellite-to-satellite tracking mission GRACE-FO M 3 = 1.3 Gt for the microwave instrument and M 3 = 0.5 Gt for the laser ranging interferometer. The sensitivity of future GRACE-like missions with different orbital parameters and improved accelerometer sensitivity is explored, and the optimum spacecraft separation for detecting point-like sources is found. The future-mission benefit of improving the accelerometer sensitivity for measurement of non-gravitational disturbances is shown by the resulting reduction of M 3 , to as small as 7 Mt for 500 km orbital altitude and optimized satellite separation of 900 km.
Where Do We Stand Today on Racial and Ethnic Health Disparities? An Analysis of Primary Total Hip Arthroplasty From a 2011-2017 National Database.

Abstract Background Little is known about the persistence of health disparities in joint arthroplasty. The objective of this study was to update our knowledge on the state of racial and ethnic disparities in total hip arthroplasty (THA). Methods Patients undergoing primary, elective THA using the 2011-2017 American College of Surgeons National Surgical Quality Improvement Program were retrospectively reviewed. Five minority groups (non-Hispanic black or African American, Hispanic or Latino, Asian, American Indian or Alaska Native, and Native Hawaiian or Pacific Islander) were compared with non-Hispanic whites. The primary outcomes were in the differences in demographic characteristics, comorbidities, perioperative characteristics, THA utilization, length of stay (LOS), and 30-day adverse events (mortality, readmission, reoperation, and complications). Results A total of 155,870 patients were identified with racial and ethnic data available on 134,961 (86.6%) of them. Non-Hispanic white patients comprised 74.5% of all THA procedures. Except for Asians, all minority groups were more likely to be younger, have a higher body mass index, and smoke tobacco (P 2 days. Blacks were more likely to develop surgical or medical complications (odds ratio [OR]: 1.21 and 1.2, respectively), whereas Hispanics or Latinos were more likely to develop surgical complications (OR: 1.28). American Indians or Alaska Natives were more likely to undergo reoperations (OR: 1.91). Conclusions Health disparities persist among minority groups with respect to comorbidities, THA utilization, LOS, and complications. Blacks and Hispanics or Latinos appear to be the most impacted by these disparities.
Plantarflexor Torque and Work is Positively Correlated with Medial Gastrocnemius Fascicle Length in Healthy Young Adults

Ankle kinetics are critical for ambulatory function in elite athletes, the elderly, and many patient populations. Despite the robust findings linking plantarflexor muscle structure to gross function with these populations, the link between plantarflexor fascicle length and ankle kinetics has not been established in the literature. In this study, we determined the relationship between muscle structure and peak torque and total work produced by the plantarflexors during maximal effort contractions. We measured resting fascicle length and pennation angle of the medial gastrocnemius using ultrasound in healthy adult subjects (n=12). Subjects performed contractions on a dynamometer during isokinetic and isometric conditions. Longer fascicles were positively correlated with higher peak torque and total work (R2 > 0.41, p 0.296, p < 0.067). None of these correlations were significant in isometric conditions. This provides experimental evidence demonstrating the link between plantarflexor muscle structure and ankle kinetics in healthy young adults which has hitherto not been experimentally demonstrated in existing literature.
ECGAug: A novel method of generating augmented annotated electrocardiogram QRST complexes and rhythm strips.

Abstract Applications of neural networks (NNs) in medicine have increased dramatically in recent years. In order to train a NN that performs ECG segmentation, it can be very time consuming, or even completely prohibitive, to manually annotate fiducial points on enough QRST complexes to reach a high level of performance. Existing methods for time series data augmentation risk creating non-physiological ECG signals that may hamper NN training, and are unable to provide accurate fiducial point locations in the augmented data. We therefore developed ECGAug, a new method which generates an augmented training set of QRST signals (single beats or rhythm strips) with accurate fiducial point annotations. Our algorithm recombines a library of existing, annotated QRS complexes and T waves in physiologic ways, and then performs additional physiological transformations to generate a set of new annotated QRST complexes or rhythm strips to be used for NN training or validation of ECG annotation algorithms. In experiments where we trained NNs to annotate QRST complexes with a limited training dataset, QRST complexes added to the training dataset by ECGAug significantly improved NN performance. We present the ECGAug process, demonstrate its efficacy, and provide links for downloading the open source ECGAug software.
La normalización del proceso penal extrajudicial (c. 1720): Análisis, crítica, propuestas

A plain reading of c. 1342 § 1, albeit in its implicit sense, reveals that the judicial process is the ordinary instrument for handling a penal cause, while an extrajudicial or administrative penal process may only be employed when just causes impede a judicial process. Nevertheless, because the formulation of that canon is a result of a compromise in the Code Commission, and also because of the rarity of penal trials in the decades following the promulgation of the CIC, canonical doctrine has yielded much discretion to the Ordinary in selecting the form of penal process, such that the extrajudicial process has come to be considered the “normal” pathway. In any case, it is critical that the judicial nature of the decision concluding the extrajudicial process be born carefully in mind. Moreover, ongoing profound reflection is to be devoted to considering how the extrajudicial process can be a truly just one. It may be optimal for a single penal process to be proposed to the Legislator de iure condendo.
Parasitic Parameter Analysis of High Frequency Transformer for Series Resonant Converter with Experimental Validation

High frequency transformers provide galvanic isolation between the primary and secondary sides of power electronic converters. The parasitic parameters of the HFT affects the converter control parameters especially its resonant frequency (for resonant converters). Most HFT design and optimization methods in literature often ignore the parasitic capacitance during optimization. This paper investigates the impact of the parasitic capacitance and the electromagnetic parameters of two already optimally designed 20kW, 10kHz, 208/208V HFTs (with different design parameters and power densities) used in a DC-DC series resonant converter. An FEA-based simulation of the electrostatic and electromagnetic parameters of the HFTs and experimental measurements are presented. The effects of the parasitic capacitance on series resonant converter's resonant frequency is investigated. The simulation and experimental results show that for series resonant converters, the parasitic capacitance severely affects their resonant frequency values. This effect need to be taken into account during the design and optimization of the HFTs.
Therapeutic effects of equine amniotic membrane suspension on corneal re-epithelialization and haze in a modified lagomorph ex vivo wound healing model.

OBJECTIVE To investigate the therapeutic effects of topical equine amniotic membrane (eAM) suspension following corneal wounding in a controlled experimental setting. PROCEDURES Equine amniotic membrane was collected, gamma irradiated, homogenized for topical suspension preparation, and cryopreserved. Corneoscleral rims harvested from fresh rabbit globes were wounded via keratectomy and were maintained in an air-liquid interface ex vivo corneal culture model. Treatment groups included topical gamma irradiated eAM suspension (n = 20) and a control group (n = 20). Re-epithelialization of the wound was assessed with daily photographic evaluation of area of fluorescein uptake (mm2 ). Corneal wound haze after a 21-day period was assessed by photographic analysis of haze area (mm2 ) and pixel intensity (0-255). Histologic processing of corneal tissue was performed, and protein identification of eAM suspension using Liquid chromatography-mass spectrometry (LC-MS). RESULTS The average day of complete corneal re-epithelialization in controls (5.5 ± 1.1) and topically treated (5.5 ± 0.6) corneas, and rates of reduction in area of fluorescein uptake over time did not significantly differ (p = .44). The corneal wound haze was significantly reduced in mean area by approximately 52% and intensity by 57% in corneas treated with topical eAM suspension (p < .05), compared to controls 21 days following wounding. Protein analysis identified numerous proteins, specifically decorin, dermatopontin, and lumican, which have previously been documented in eAM. CONCLUSIONS Area and intensity of corneal wound haze were significantly reduced in corneas treated with gamma irradiated eAM suspension, which may be due to previously identified therapeutic proteins which promote corneal clarity.
ANKLE1 cleaves mitochondrial DNA and contributes to cancer risk by driving the Warburg effect and apoptosis resistance

Alleles within the chr19p13.1 locus are associated with increased risk of both ovarian and breast cancer and increased expression of the ANKLE1 gene. ANKLE1 is molecularly characterized as an endonuclease that efficiently cuts branched DNA and shuttles between the nucleus and cytoplasm. However, the role of ANKLE1 in mammalian development and homeostasis remains unknown. In normal development ANKLE1 expression is limited to the erythroblast lineage and we found that ANKLE19s role is to cleave the mitochondrial genome during erythropoiesis. We show that ectopic expression of ANKLE1 in breast epithelial-derived cells leads to genome instability and mitochondrial DNA (mtDNA) cleavage. mtDNA degradation then leads to mitophagy and causes a shift from oxidative phosphorylation to glycolysis (Warburg effect). Moreover, mtDNA degradation activates STAT1 and expression of epithelial-mesenchymal transition (EMT) genes. Reduction in mitochondrial content contributes to apoptosis resistance, which may allow precancerous cells to avoid apoptotic checkpoints and proliferate. These findings provide evidence that ANKLE1 is the causal cancer susceptibility gene in the chr19p13.1 locus and describe mechanisms by which higher ANKLE1 expression promotes cancer risk.
Overview on Cluster Analysis

This chapter provides an overview of cluster analysis. Its main purpose is to introduce the reader to the major concepts underlying this data mining (DM) technique, particularly those that are relevant to the chapter that involves the use of this technique. It also provides an illustrative example of cluster analysis.
Different effects of angiopoietin-2 in different vascular beds: new vessels are most sensitive

In this study, we used double transgenic mice with inducible expression of angiopoietin-2 (Ang2) to investigate the role of Ang2 in the retinal and choroidal circulations and in three models of ocular neovascularization (NV). Mice with induced expression of Ang2 ubiquitously, or specifically in the retina, survived and appeared grossly normal. They also had normal-appearing retinal and choroidal circulations, demonstrating that high levels of Ang2 did not induce regression of mature retinal or choroidal vessels. When Ang2 expression was induced soon after birth, there was increased density of the deep capillary bed on postnatal day (P) 11 that returned to normal by P18, the time that retinal vascular development is usually completed. In mice with ischemic retinopathy, induction of Ang2 during the ischemic period resulted in a significant increase in retinal NV, but induction of Ang2 at a later time point when ischemia (and vascular endothelial growth factor [VEGF]) was less, hastened regression of NV. In triple transgenic mice that coexpressed VEGF and Ang2, the increased expression of Ang2 inhibited VEGF-induced NV in the retina. Increased expression of Ang2 also resulted in regression of choroidal neovascularization. These data suggest that ocular neovascularization, but not mature retinal or choroidal vessels, is sensitive to Ang2; a high Ang2/VEGF ratio promotes regression, while high Ang2 in the setting of hypoxia and/or concomitantly high Ang2 and VEGF stimulate neovascularization.
8 Reversible modification of proteins with thioester-linked fatty acids

Publisher Summary This chapter discusses the present understanding of the mechanisms underlying protein thioacylation and deacylation. The structural requirements for this modification and the intracellular sites where proteins are thioacylated are reviewed in the chapter. The dynamic nature of protein thioacylation dictates that mechanisms exist not only for the addition, but also for the removal of fatty acids from proteins. Significant progress has been made in purifying palmitoyl–protein thioesterase activities and cloning the genes corresponding to these activities, permitting first glimpse of the physiological settings in which protein deacylation is functionally important. The mechanism of fatty acid addition to proteins is controversial. Although several protein acyltransferase activities have been purified to apparent homogeneity, it has not been established that these enzymes mediate protein thioacylation in cells. The chapter discusses the evidence supporting enzymatic versus nonenzymatic mechanisms for the addition of fatty acids to proteins. The properties, localization, and function of palmitoyl–protein thioesterases are discussed in the chapter.
PCRC-based HPF Compilation

This paper describes an ongoing effort supported by ARPA PCRC (Parallel Compiler Runtime Consortium) project. In particular, we discuess the design and implementation of an HPF compilation system based on PCRC runtime. The approaches to issues such as directive analysis and communication detection are discussed in detail. The discussion includes fragments of code generated by the compiler.
A characterization of the problem of new, out-of-vocabulary words in continuous speech recognition and understanding

This thesis is directed toward the characterization of the problem of new, out-of-vocabulary words for continuous-speech recognition and understanding. It is motivated by the belief that this problem is critical to the eventual deployment of the technology, and that a thorough understanding of the problem is necessary before solutions can be proposed. The first goal of this thesis is to demonstrate the magnitude of the problem. By examining a wide variety of speech and text corpora for multiple languages, we show that new words will always occur, even given very large system vocabularies, and that their frequency depends on the type of recognition task. We classify potential new words in terms of their phonological and syntactic characteristics. The second goal of this thesis is to characterize recognizer behavior when new words occur. We demonstrate that not only are new words themselves misrecognized, but their occurrence can cause misrecognition of in-vocabulary words in other parts of an utterance due to contextual effects. To perform our recognition study of new words, we developed an algorithm for efficiently computing word graphs. We show that word graph computation is relatively insensitive to the position of new words within an utterance. Further, we find that word graphs are an effective tool for speech recognition in general, irrespective of the new-word problem. The third and final goal of this thesis is to examine the issues related to learning new words. We examine the ability of the (context-independent) acoustic models, the pronunciation models, and the class n-gram language models of the SUMMIT system to incorporate, or learn, new words; we find the system's learning effective even without additional training. Overall, this thesis offers a broad characterization of the new-word problem, describing in detail the magnitude and dimensions of the problem that must be solved. (Copies available exclusively from MIT Libraries, Rm. 14-0551, Cambridge, MA 02139-4307. Ph. 617-253-5668; Fax 617-253-1690.)
Compiler-Assisted Leakage Energy Reduction for Cache Memories

Abstract With the scaling of technology, leakage energy reduction has become increasingly important for microprocessor design. Being the major consumer of the on-chip transistor budget, it is particularly critical to mitigate cache leakage energy. In contrast to many recent studies that attempt to minimize cache leakage by exploiting architectural-level information, this chapter introduces two compiler-assisted approaches to manage the cache leakage dissipation without significant impact on either performance or the dynamic energy consumption. More specifically, the first approach exploits static and profiling information to detect the sub-bank transitions at the compilation time, which can improve the energy efficiency of the drowsy instruction caches. The second approach exploits the fact that only a small portion of the data caches will be accessed during the loop execution, the compiler can provide hints to place other non-active cache blocks into the low power mode during the loop execution to save the data cache leakage energy. Our experiments on a state-of-the-art VLIW processor indicate that the proposed compiler-based approaches can improve the energy-efficiency of both instruction and data caches effectively.
Twin fluorophore near infrared KRAS peptide nucleic acid molecular beacons

A7 Most pancreas cancer patients die within a year because they are diagnosed at an advanced incurable stage. However, even before an enlarged mass can be seen by MRI or CT, early stage pancreatic intraepithelial neoplasia (PanIN-1) pancreas cells contain high levels of mRNAs copied from hyperactive cancer genes such as KRAS and HER2. However, PanIN-1 does not always progress. Later stage PanIN-3 pancreas cells, which do progress to frank cancer, contain high levels of mRNAs overproduced by activated CCND1 or BRCA2 oncogenes. Specific detection of PanIN-3 would enable resection of ductal pancreas cancer at a survivable stage. We hypothesized that developing pancreas cancer can be imaged externally in live cells and animals by near infrared hybridization fluorescence (NIRF) imaging of overexpressed cancer gene mRNAs basepaired to molecular beacons. We designed a 12 base peptide nucleic acid (PNA) without a hairpin stem. We hypothesized that twin NIR664 fluorophores at the N and C termini could stack upon each other, mutually quenching their fluorescence, unless the PNA were hybridized to a complementary RNA. No quencher chromophore or hairpin stem is required in this case, unlike typical molecular beacons. Incubation of human AsPC1 KRAS G12D+ pancreas cancer cells with NIR664-KRAS G12D PNA-NIR664 for 24 h incubation, followed by 24 h of efflux, yielded bright NIRF images in the AsPC1 cells. Base mismatch, peptide mismatch, and cell mismatch control experiments are necessary before proceeding to animal experiments. This work was supported in part by NCI contract N01 CO27175 and NCI grant U54 CA105008.
Evolutionary Alternatives to Equilibrium Economics: A Suggested Research Agenda

Built on the fictional concept of equilibrium, mainstream economics provides a method of analysis which, when paired with the calculus, enables relatively easy identification of maximum and minimum values. Lacking empirical evidence of its behavioral assumptions, the profession accepts such familiar claims as consumer maximization of utility and business firm maximization of profit or revenue. In place of the relatively static concept of equilibrium, the Veblen-Myrdal notion of circular and cumulative causation (CCC) arguably has greater descriptive capability and more penetrating insight for policy recommendations. This article traces the historical origins of both concepts and argues that CCC offers considerable potential for a broad, dynamic, interdisciplinary, more thorough, and more accurate analytical framework. Specific examples of work that has been done along with suggestions for future applications of this concept are given.
The Effect of Palmitic and Oleic Acids on the Properties and Composition of the Very Low Density Lipoprotein Secreted by the Liver

Abstract Livers from normal fed male rats were perfused in vitro with equimolar quantities of either palmitic acid or oleic acids, and, after an experimental period of 4 hours, the very low density lipoprotein (VLDL) was isolated from the perfusate by ultracentrifugation in zonal rotors. The VLDL was characterized by rate-zonal mobility, by lipid composition, and by electrophoretic mobility on paper. Approximately 50% more VLDL triglyceride was secreted by the liver when oleate was the substrate than when palmitate was the substrate. The VLDL produced when palmitate was infused was a more dense particle and had a slower rate-zonal mobility under our conditions of zonal ultracentrifugation than did the VLDL produced from oleate. When palmitate was the substrate, the VLDL secreted by the liver was characterized by a single, apparently homogeneous peak in the density gradient in the zonal rotor, whereas the VLDL produced from oleate appeared to consist of at least two components; the lighter component behaved as a "chylomicron-like" particle in its rate-zonal mobility, whereas the heavier component was similar to the VLDL produced from palmitate. Both fractions derived from oleate and the lipoprotein derived from palmitate migrated on paper as a VLDL ("pre-β-lipoprotein"); the lipid composition of the chylomicron-like VLDL secreted by the liver after infusion of oleate was similar to that of the chylomicrons isolated from the perfusate at the beginning of the experiment although the chylomicrons remained at the origin and did not migrate as a VLDL on paper electrophoresis. The less dense VLDL produced from oleate, furthermore, had a lipid composition which differed from that of the VLDL produced from palmitate; the lighter VLDL produced from oleate contained half as much cholesterol and phospholipid per µmole of triglyceride (TG) than either the VLDL produced from palmitate or the heavier VLDL secreted after infusion of oleate. Even though more triglyceride was secreted per gram of liver when oleate was the substrate than when palmitate was infused, the total quantity of cholesterol and phospholipid secreted, respectively, in response to either fatty acid was the same, e.g. twice as much cholesterol and phospholipid was secreted per g of liver per µmole of VLDL triglyceride derived from palmitate than from the lighter lipoprotein produced from oleate. We can conclude from these data that certain physical properties and the lipid composition of the VLDL secreted by the liver were prescribed by infusion of either palmitate or oleate; it remains to be determined whether these observations can be extended to some general relationship describing effects of saturated and unsaturated free fatty acid (FFA) on the hepatic production and properties of the VLDL. The concentration of TG, phospholipid, and cholesterol in the VLDL of serum in vivo, which is the result, in part, of hepatic secretion of VLDL, must also be regulated by the chemical structure of the FFA from which the triglyceride fatty acids are derived.
On the correspondence between quantum and classical variational principles

Abstract Classical variational principles can be deduced from quantum variational principles via formal reparameterization of the latter. It is shown that such reparameterization is possible without invoking any assumptions other than classicality and without appealing to dynamical equations. As examples, first principle variational formulations of classical point-particle and cold-fluid motion are derived from their quantum counterparts for Schrodinger, Pauli, and Klein–Gordon particles.
Thermoelectric properties of Ge doped n-type TixZr1−xNiSn0.975Ge0.025 half-Heusler alloys

Several compositions of the n-type, TixZr1−xNiSn0.975Ge0.025 (x = 0, 0.1, 0.15 and 0.25), half-Heusler (HH) alloys were synthesized by reacting elemental powders at high temperature using induction melting. The resulting ingots were annealed at 900 °C for 2 weeks and mechanically alloyed to achieve fine grain size. X-ray powder diffraction suggested the formation of products with HH structure. However, electron microscopy studies revealed phase separation into Ti-rich and Zr-rich domains for the ingot with x = 0.25. The effect of band gap engineering through isoelectronic substitution of Sn by Ge and mass fluctuation arising from the intermixing of Ti and Zr in the HH structure on the electronic and thermal transport in the temperature range from 300 K to 775 K was investigated. A large reduction in the lattice thermal conductivity (4.9 W K−1 m−1 to 2.7 W K−1 m−1 at 300 K) was observed with increasing Ti concentration. Surprisingly, the thermopower and electrical conductivity for the sample with x = 0.25 simultaneously increase with rising temperature from −120 μV K−1 and 510 S cm−1 at 300 K to −160 μV K−1 and 840 S cm−1 at 775 K. The combination of large reduction in lattice thermal conductivity via mass fluctuation at the Ti/Zr site with optimization of the thermopower and electrical conductivity through Ge substitution at the Sn site significantly improved the figure of merit from 0.05 to 0.48 at 775 K for the sample with x = 0.25.
Minimal-rank ℋ 2 -matrix-based iterative and direct volume integral equation solvers for large-scale scattering analysis

It can be shown that the matrix structure resulting from a fast multipole method (FMM)-based algorithm is an ℋ2-matrix, but with a full-rank representation for electrically large analysis. We compare the computational complexity of a volume integral equation (VIE) solver having a minimal-rank ℋ2-representation with that of a VIE solver using an FMM-based ℋ2-representation. The former is shown to be strict O(N) in storage and matrix-vector multiplication, and O(NlogN) in inverse irrespective of electric size. Such a complexity has been demonstrated by the analysis of large-scale dielectric scattering problems involving millions of unknowns.
Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis.

It has been > 130 years since the first description of the upper and lower motor neuron disease called amyotropic lateral sclerosis (ALS). Sadly, there has been little change in the long interval over which this disease is diagnosed, or in its poor prognosis. Significant gains have been made, however, in understanding its pathophysiology and in symptomatic care. Disease-causing mutations have been identified and used to create animal models. Other identified mutations may increase susceptibility and cause disease only in a particular environment and at a particular age. A number of ‘downstream’ molecular pathways have been implicated, including transcriptional disturbances, protein aggregation, excitotoxicity, mitochondrial dysfunction, oxidative stress, neuroinflammation, cytoskeletal and axonal transport derangements, growth factor dysregulation and apoptosis. This knowledge has led to an impressive pipeline of candidate therapies that offer hope for finally being able to alter ALS disease progression. ...
Marriage and Finance

This chapter reviews interdisciplinary research concerning the association between marriage and personal finances. The first section of the chapter discusses financial practices within marriage and the financial differences between married couples and other family types. The second section reviews the research on the ability of financial factors to predict marital formation, satisfaction/conflict, and dissolution. The chapter also suggests future research avenues.
Mechanical Properties of Dilated Human Ascending Aorta

Dilation of the ascending aorta, associated with Marfan Syndrome, bicuspid aortic valve, or advanced age, may lead to aortic dissection and rupture. Mathematical models can be used to assess the relative importance of increased wall stresses and decreased strength in these mechanical failures. To obtain needed inputs for such models, mechanical properties of dilated human ascending aorta were measured in vitro. Specimens for opening angle, biaxial elastic, and uniaxial circumferential strength tests were cut from excised tissue obtained from 54 patients (age 18–81 years) undergoing elective aortic graft replacement surgery. Opening angle was significantly greater in patients older than 50 years (262°±76°, n=21) compared to younger patients (202°±70°, n=13 All biaxial elastic specimens n=40 exhibited nonlinear stress-strain behavior. Rapid increases in circumferential and axial stresses occurred at lower strains in the older patient group than in the younger. Mean strength was significantly lower in older patients (1.35±0.37 MPa, n=14) than younger (2.04 ± 0.46 MPa, n=11, age <50 years). These changes in mechanical properties suggest that age may influence the risk of aortic dissection or rupture of dilated ascending aorta. © 2002 Biomedical Engineering Society.
Energy dispersion features in the vicinity of the cusp

Highly energetic particles have been observed by the Polar spacecraft in the vicinity of the cusp. The energy of these particles, which often exceeds 1 MeV, is frequently characterized by dispersion. Emphasis is given to the data obtained by Polar in the time interval March 1996-May 1997. Time-Energy Dispersive (TED) features are observed almost every day in the vicinity of the dayside cusp (and usually multiple times in one day), from 66° to 78° invariant latitude, while no TEDs are detected at latitudes lower than 60° or higher than 84°. In addition, TEDs are observed mostly around the time period between 12:00 and 15:00 MLT, and they can last from a few minutes up to three hours.
Thermal and elastic properties of Cu–Zr–Be bulk metallic glass forming alloys

The compositional dependence of thermal and elastic properties of Cu–Zr–Be ternary bulk metallic glass forming alloys was systematically studied. There exists a linear relationship between the glass transition temperature Tg and the total Zr concentration. G decreases linearly with increasing Zr concentration as well. The results also show that Tg, shear modulus G, and Poisson's ratio nu are very sensitive to changes in compositions. Low Tg, low G, and relatively high nu can be achieved with high Zr and Ti concentration.