cssi/SciSciGPT-SciSciNet huggingface dataset:
Inhibition of ER stress and unfolding protein response pathways causes skeletal muscle wasting during cancer cachexia

Cachexia is a devastating syndrome that causes morbidity and mortality in a large number of patients with cancer. However, the mechanisms of cancer cachexia remain poorly understood. Accumulation of misfolded proteins in the endoplasmic reticulum (ER) causes stress. The ER responds to this stress through activating certain pathways commonly known as the unfolding protein response (UPR). The main function of UPR is to restore homeostasis, but excessive or prolonged activation of UPR can lead to pathologic conditions. In this study, we examined the role of ER stress and UPR in regulation of skeletal muscle mass in naive conditions and during cancer cachexia. Our results demonstrate that multiple markers of ER stress are highly activated in skeletal muscle of Lewis lung carcinoma (LLC) and Apc(Min/+) mouse models of cancer cachexia. Treatment of mice with 4-phenylbutyrate (4-PBA), a chemical chaperon and a potent inhibitor of ER stress, significantly reduced skeletal muscle strength and mass in both control and LLC-bearing mice. Blocking the UPR also increased the proportion of fast-type fibers in soleus muscle of both control and LLC-bearing mice. Inhibition of UPR reduced the activity of Akt/mTOR pathway and increased the expression of the components of the ubiquitin-proteasome system and autophagy in LLC-bearing mice. Moreover, we found that the inhibition of UPR causes severe atrophy in cultured myotubes. Our study provides initial evidence that ER stress and UPR pathways are essential for maintaining skeletal muscle mass and strength and for protection against cancer cachexia.-Bohnert, K. R., Gallot, Y. S., Sato, S., Xiong, G., Hindi, S. M., Kumar, A. Inhibition of ER stress and unfolding protein response pathways causes skeletal muscle wasting during cancer cachexia.
Patient selection for stroke thrombectomy Is CT head good enough

Six randomized controlled trials have established the substantial benefit of mechanical thrombectomy for acute ischemic stroke patients presenting with large vessel occlusive disease.1–6 Enrolling patients with large clinical deficit in the setting of small completed infarct and rapid, complete, or near complete recanalization, and treatment with the most recent generation of thrombectomy devices, contributed to this success. Efforts to generalize the results of these trials beyond select, experienced centers have focused attention on workflow and developing consensus on patient selection. Optimizing outcomes requires identifying patients most likely to improve and those most likely harmed with reperfusion. Imaging played a central role in selecting patients for these studies but the choice of imaging measures varied among studies. Some designs relied heavily on CT perfusion, multiphase CT angiography, or a combination of modalities, but all endeavored to identify the core (irreversibly infarcted brain), the penumbra (tissue at risk), or both.
Waging War on Recidivism Among Justice-Involved Veterans: An Impact Evaluation of a Large Urban Veterans Treatment Court

Problem solving courts have increasingly been adopted by jurisdictions around the country as an alternative to traditional criminal court models of justice. Veterans treatment courts (VTCs) are a type of problem-solving court being established all over the country in response to an increased number of justice-involved veterans with the return of military personnel from the Wars in the Middle East. Despite their rapid expansion, there is a dearth of research evaluating the impact of VTCs on recidivism. The current study conducted an impact evaluation regarding recidivism among participants of a large urban VTC program. Findings from descriptive and multivariate analysis reveal positive results for VTC participants, especially graduates, in comparison with the control group. Implications are discussed in context of three areas: (a) current criminal justice policy and practice implications for VTCs, (b) findings from research on other more established problem-solving courts (i.e., drug courts), and (c) resea...
Antinociceptive effects of the 6-O-sulfate ester of morphine in normal and diabetic rats: Comparative role of mu- and delta-opioid receptors.

Abstract This study determined the antinociceptive effects of morphine and morphine-6-O-sulfate (M6S) in both normal and diabetic rats, and evaluated the comparative role of mu-opioid receptors (mu-ORs) and delta-opioid receptors (delta-ORs) in the antinociceptive action of these opioids. In vitro characterization of mu-OR and delta-OR-mediated signaling by M6S and morphine in stably transfected Chinese hamster ovary (CHO-K1) cells showed that M6S exhibited a 6-fold higher affinity for delta-ORs and modulated G-protein and adenylyl cyclase activity via delta-ORs more potently than morphine. Interestingly, while morphine acted as a full agonist at delta-ORs in both functional assays examined, M6S exhibited either partial or full agonist activity for modulation of G-protein or adenylyl cyclase activity, respectively. Molecular docking studies indicated that M6S but not morphine binds equally well at the ligand binding site of both mu- and delta-ORs. In vivo analgesic effects of M6S and morphine in both normal and streptozotocin-induced diabetic Sprague-Dawley rats utilizing the hot water tail flick latency test showed that M6S produced more potent antinociception than morphine in both normal rats and diabetic rats. This difference in potency was abrogated following antagonism of delta- but not mu- or kappa (kappa-ORs) opioid receptors. During 9 days of chronic treatment, tolerance developed to morphine-treated but not to M6S-treated rats. Rats that developed tolerance to morphine still remained responsive to M6S. Collectively, this study demonstrates that M6S is a potent and efficacious mu/delta opioid analgesic with a delayed tolerance profile when compared to morphine in both normal and diabetic rats. Perspective: This study demonstrates that M6S acts at both mu- and delta-ORs, and adds to the growing evidence that the use of mixed mu/delta opioid agonists in pain treatment may have clinical benefit.
Comment on Narayan. Type 2 Diabetes: Why We Are Winning the Battle but Losing the War? 2015 Kelly West Award Lecture. Diabetes Care 2016;39:653-663.

In his Kelly West Award Lecture, Narayan suggested that the pathogenesis of type 2 diabetes may be fundamentally different in high-risk populations who vary dramatically in degree of adiposity (1). For example, he raised the possibility that type 2 diabetes was due to “poor insulin secretion” in thin individuals (Asian Indians), whereas the culprit was “poor insulin action” in overweight/obese individuals (Pima Indians). This suggestion does not seem to acknowledge the published evidence from our group and others of the significant differences in degree of insulin resistance that exist among various …
PREPARATION AND EVALUATION OF A MICROBIOLOGICAL GROWTH MEDIUM FORMULATED FROM CATFISH WASTE PEPTONE

A water-soluble, heat-stable peptone was extracted-from enzymatically digested channel catfish (Ictalurus punctatus) heads and skins. Proximate analyses showed that the peptone was composed of 89.02% protein (Kjeldahl N × 6.25), 10.42% ash and 0.44% fat. The peptone contains all amino acids demonstrated to be present in concentrations of greater than 1.0% in six other commercially available microbiological peptones used for comparative purposes in the study. Total cell mass production on catfish and test peptone media by microorganisms representing 13 genera was measured. Catfish peptone supported luxuriant growth of the test organisms and an accumulative average of dry cell mass weights produced by the organisms revealed that the catfish peptone ranked third out of the seven peptones tested. This new peptone offers the clinical and industrial microbiologist a potentially valuable ingredient for formulation of growth and fermentation media.
FE Evaluation of Reinforced Concrete Bridge Decks with Glass-FRP Composite Bars

In order to resolve the steel corrosion problem in bridge decks, glass fiber reinforced polymer (GFRP) has been recommended as a substitute to the conventional steel reinforcement in bridge decks. However, the use of GFRP bars in bridge decks is still limited by several concerns, including the long-term durability of GFRP bars in the concrete under sustained loadings. Literature review showed that the tensile strength reduction of the GFRP bar should be governed by the sustained stress level in the GFRP bar. In this regard, a GFRP reinforced concrete deck was simulated in this paper, aiming to investigate the sustained stress levels in the GFRP bars through three dimensional finite element (FE) modeling. Per AASHTO LRFD specifications, one lane loaded and two lane loaded cases were examined to identify the maximum tensile strains in the internal GFRP bars subjected to dead loads and HL-93 design loadings. The FE results showed that the maximum tensile stresses in GFRP bars under service loads were less than 1% of the GFRP design strength, which implied that the GFRP bars could have excellent long-term performance in real concrete bridge decks.
Opaque: an oblivious and encrypted distributed analytics platform

Many systems run rich analytics on sensitive data in the cloud, but are prone to data breaches. Hardware enclaves promise data confidentiality and secure execution of arbitrary computation, yet still suffer from access pattern leakage. We propose Opaque, a distributed data analytics platform supporting a wide range of queries while providing strong security guarantees. Opaque introduces new distributed oblivious relational operators that hide access patterns, and new query planning techniques to optimize these new operators. Opaque is implemented on Spark SQL with few changes to the underlying system. Opaque provides data encryption, authentication and computation verification with a performance ranging from 52% faster to 3.3x slower as compared to vanilla Spark SQL; obliviousness comes with a 1.6-46x overhead. Opaque provides an improvement of three orders of magnitude over state-of-the-art oblivious protocols, and our query optimization techniques improve performance by 2-5x.
A phase I/II trial of the combination of romidepsin and lenalidomide in patients with relapsed/refractory lymphoma and myeloma: Phase I results.

8582 Background: Epigenetic manipulation and immunomodulation are therapeutic strategies in hematologic malignancies. Romidepsin (Romi), a histone deacetylase inhibitor, and lenalidomide (Len), an ...
Design of an Energy-Efficient Accelerator for Training of Convolutional Neural Networks using Frequency-Domain Computation

Convolutional neural networks (CNNs) require high computation and memory demand for training. This paper presents the design of a frequency-domain accelerator for energy-efficient CNN training. With Fourier representations of parameters, we replace convolutions with simpler pointwise multiplications. To eliminate the Fourier transforms at every layer, we train the network entirely in the frequency domain using approximate frequency-domain nonlinear operations. We further reduce computation and memory requirements using sinc interpolation and Hermitian symmetry. The accelerator is designed and synthesized in 28nm CMOS, as well as prototyped in an FPGA. The simulation results show that the proposed accelerator significantly reduces training time and energy for a target recognition accuracy.
Accuracy of Diagnostic Imaging Modalities for Classifying Pediatric Eyes as Papilledema Versus Pseudopapilledema

Purpose To identify the most accurate diagnostic imaging modality for classifying pediatric eyes as papilledema (PE) or pseudopapilledema (PPE). Design Prospective observational study. Subjects Nineteen children between the ages of 5 and 18 years were recruited. Five children (10 eyes) with PE, 11 children (19 eyes) with PPE owing to suspected buried optic disc drusen (ODD), and 3 children (6 eyes) with PPE owing to superficial ODD were included. Methods All subjects underwent imaging with B-scan ultrasonography, fundus photography, autofluorescence, fluorescein angiography (FA), optical coherence tomography (OCT) of the retinal nerve fiber layer (RNFL), and volumetric OCT scans through the optic nerve head with standard spectral-domain (SD OCT) and enhanced depth imaging (EDI OCT) settings. Images were read by 3 masked neuro-ophthalmologists, and the final image interpretation was based on 2 of 3 reads. Image interpretations were compared with clinical diagnosis to calculate accuracy and misinterpretation rates of each imaging modality. Main Outcome Measures Accuracy of each imaging technique for classifying eyes as PE or PPE, and misinterpretation rates of each imaging modality for PE and PPE. Results Fluorescein angiography had the highest accuracy (97%, 34 of 35 eyes, 95% confidence interval 92%–100%) for classifying an eye as PE or PPE. FA of eyes with PE showed leakage of the optic nerve, whereas eyes with suspected buried ODD demonstrated no hyperfluorescence, and eyes with superficial ODD showed nodular staining. Other modalities had substantial likelihood (30%–70%) of misinterpretation of PE as PPE. Conclusions The best imaging technique for correctly classifying pediatric eyes as PPE or PE is FA. Other imaging modalities, if used in isolation, are more likely to lead to misinterpretation of PE as PPE, which could potentially result in failure to identify a life-threatening disorder causing elevated intracranial pressure and papilledema.
Risk Evaluation in Sewage Treatment Plant Design

A mathematical model is developed to predict, for any particular consecutive-day period, the probability of having less than any specified dissolved oxygen concentration downstream from a waste wat...
Noninfectious and Nonmalignant Complications of Anti-TNF Therapy

Anti-TNF therapies are commonly used in the treatment of moderate to severe inflammatory bowel disease. The noninfectious and nonmalignant complications of anti-TNF therapy include infusion or injection site reactions, psoriasiform and eczematous eruptions, lupus-like reaction, hepatotoxicity, demyelination, and heart failure. Infusion/injection site and dermatologic reactions often can be managed with supportive care without discontinuation of the anti-TNF. Early recognition and management of these complications is important to initiate supportive care if indicated, to minimize symptoms, and to transition to other therapies if necessary. This chapter focuses on the clinical presentation, pathophysiology, diagnostic evaluation, and management of the noninfectious and nonmalignant complications of anti-TNF therapy.
Patterns of adverse childhood experiences and substance use among young adults: A latent class analysis.

Abstract Introduction Adverse childhood experiences (ACEs) have been strongly linked with subsequent substance use. The aim of this study was to investigate how different patterns of ACEs influence substance use in young adulthood. Methods Using a community sample of young individuals (N = 336; ages 18–25), we performed latent class analyses (LCA) to identify homogenous groups of young people with similar patterns of ACEs. Exposure to ACEs incorporates 13 childhood adversities including childhood maltreatment, household dysfunction, and community violence. Multiple linear and logistic regression models were used in an effort to examine the associations between ACEs classes and four young adult outcomes such as alcohol-related problems, current tobacco use, drug dependence symptoms, and psychological distress. Results LCA identified four heterogeneous classes of young people distinguished by different patterns of ACEs exposure: Low ACEs (56%), Household Dysfunction/Community Violence (14%), Emotional ACEs (14%), and High/Multiple ACEs (16%). Multiple regression analyses found that compared to those in the Low ACEs class, young adults in the High/Multiple ACEs class reported more alcohol-related problems, current tobacco use, and psychological symptoms, controlling for sociodemographic characteristics and common risk factors for substance use such as peer substance use. Conclusions Our findings confirm that for many young people, ACEs occur as multiple rather than single experiences. The results of this research suggest that exposure to poly-victimization during childhood is particularly related to substance use during young adulthood.
Quantifying the similarity of topological domains across normal and cancer human cell types.

Motivation Three-dimensional chromosome structure has been increasingly shown to influence various levels of cellular and genomic functions. Through Hi-C data, which maps contact frequency on chromosomes, it has been found that structural elements termed topologically associating domains (TADs) are involved in many regulatory mechanisms. However, we have little understanding of the level of similarity or variability of chromosome structure across cell types and disease states. In this study, we present a method to quantify resemblance and identify structurally similar regions between any two sets of TADs. Results We present an analysis of 23 human Hi-C samples representing various tissue types in normal and cancer cell lines. We quantify global and chromosome-level structural similarity, and compare the relative similarity between cancer and non-cancer cells. We find that cancer cells show higher structural variability around commonly mutated pan-cancer genes than normal cells at these same locations. Availability and implementation Software for the methods and analysis can be found at https://github.com/Kingsford-Group/localtadsim.
“Why Can’t I Find It?” Mining Transparency in Zambia and the Democratic Republic of Congo

This research focuses on foreign intervention in the mining sectors of Zambia and the Democratic Republic of Congo (DRC), concentrating on the transparency of agreements and regulation, or lack thereof, contributing to the longevity of mining practices and the livelihoods of local citizens. The current state of public information regarding natural resource extraction in both countries creates questions about state motives and investors’ economic incentive, with consequences of inequality, human rights offenses, and underdevelopment. Applying Immanuel Wallerstein’s world-systems theory, I describe the economic rationale behind global involvement in the region’s mining operations and identify potential power imbalances. I use commodity statistics, state documentation, and nongovernmental reports to analyze reporting trends on mining operations. Intergovernmental databases with development statistics also contribute to the research. In this study, I argue foreign intervention in underdeveloped, mineral rich countries does not have to be a purely exploitative relationship as emphasized by Wallerstein’s theory, demonstrated through the implementation of international transparency initiatives. These programs, implemented for the benefit of the resource abundant countries like Zambia and the DRC, can increase the accountability of governments and investing companies related to mining activities. Complete reporting on natural resource extraction increases investment values and the development and productivity of the mining industry.
Alternative Nuclear Power Systems

The light water reactor (LWR) has a number of demonstrated virtues — the moderator is inexpensive, the fuel form provides excellent retention of fission products in normal operation, and the reactor operates smoothly and safely. However, the LWR has a few disadvantages. It requires slightly enriched fuel thus, reducing the efficiency of use of natural uranium resources, as a considerable amount of U-235 goes into the tails stream of the isotope separator. The enrichment facilities are costly to build and need significant amounts of energy to operate. When one considers all the possible combinations of nuclear fissile and fertile fuels, the moderators and coolants, and the arrangements of the different materials, the number of different fuel cycles is enormous. In the study labeled Nonproliferation Alternative Systems Assessment Program (NASAP) performed by the U.S. Department of Energy, some 67 different systems are identified, and variants of these would lead into thousands of candidates. The problems of fuel resources and proliferation have led to the exploration of alternative systems that might be preferable to conventional LWR converters from the standpoint of natural resource conservation, economy, safety of the public, and protection against proliferation.
Transacting with Physicians

Pediatric psychologists share the fact they transact with physicians in a variety of settings and endeavors including clinical services, consultation, and research. The importance of our interprofessional collaboration with physicians in medical settings centers around shared patient populations, financial resources, and administrative arrangements. Moreover, given the dominant administrative structures in medical schools and hospitals (Nathan, Lubin, Matarrazo, & Persely, 1979), physicians have a significant impact on the professional deployment and career development of psychologists. For this reason, psychologists’ ability to maintain professional resources and integrity in medical settings in an era of expanding technology and accountability may very well depend upon the efficacy of strategies that are developed to guide professional interactions with physicians. Unfortunately, psychologists in medical settings have not clearly formulated the premises on which their transactions with physicians are based, recognized the difficult realities of such interprofessional exchange, nor developed programmatic strategies to anticipate and/or remedy problematic collaboration.
Introduction of fluid mechanics

A fluid is a substance in which the constituent molecules are free to move relative to each other. Conversely, in a solid, the relative positions of molecules remain essentially fixed under non-destructive conditions of temperature and pressure. While these definitions classify matter into fluids and solids, the fluids subdivide further into liquid and gases.
Effect of Strongly Coupled Vibration-Cavity Polaritons on the Bulk Vibrational States within a Wavelength-Scale Cavity.

A Rabi splitting of 43.0 ± 1.0 cm–1 (95% conf.) was determined for the interaction of the CD3 deformation, the strongest fundamental vibration of the liquid CD3C≡N molecule and fringe modes of a parallel-plate Fabry–Perot cavity containing this liquid. Note that vibration–cavity polaritons are also called dressed states, hybrid or mixed states. Since the experimental configuration has many orders of magnitude more vibrational oscillators than photons, vibrational oscillators not in dressed states far outnumber those in the dressed states. This work is distinguished from related vibration–cavity work by a method to extract the position, width, phase, and intensity of bulk vibrational signals including reconstruction of the position of the fringe without vibrational contributions. It reveals how the bulk vibrational oscillators are changed by interaction within the cavity even though they are not in dressed states. Although the dressed states are obvious targets for manipulation of chemical response, it is ...
COGNITIVE FUNCTION AND DEPRESSION IN PATIENTS WITH FIBROMUSCULAR DYSPLASIA

Although patients with fibromuscular dysplasia (FMD) commonly report symptoms of memory loss, the association of FMD with cognitive function and depression is not known. At a single center, participants with a diagnosis of extracranial or intracranial FMD without a history of stroke were enrolled.
Super resolution projection: leveraging the MEMS speed to double or quadruple the resolution

Texas Instruments’ digital mirror device (DMD) uses thousands to millions of individual micromirrors to direct light as a Spatial Light Modulator (SLM). The Tilt-Roll-Pixel (TRP) is currently the smallest DLP Products pixel node at 5.4μm pitch. The small micromirror size, which enables fast switching speed, and precise tilt angles, exploits this speed on a system level to double or quadruple the resolution by using super-resolution projection. Super-resolution projection overlays multiple sub-sampled images, each shifted on the screen by a fraction of a pixel, and as long as the shifting occurs at a rate faster than the critical flicker fusion threshold, the human visual system will act as a temporal low pass filter and naturally integrate all low-resolution SLM images into a single super-resolution result. This paper will discuss the operation of the TRP node, how this node can be operated more quickly, how super-resolution projection works, and how we modified the optical architecture to leverage the switching speed for super-resolution projection.
Risk factors for hemorrhage of brain arteriovenous malformation

Patients with brain arteriovenous malformation (bAVM) are at risk of intracranial hemorrhage (ICH). Overall, bAVM accounts for 25% of hemorrhagic strokes in adults <50 years of age. The treatment of unruptured bAVMs has become controversial, because the natural history of these patients may be less morbid than invasive therapies. Available treatments include observation, surgical resection, endovascular embolization, stereotactic radiosurgery, or combination thereof. Knowing the risk factors for bAVM hemorrhage is crucial for selecting appropriate therapeutic strategies. In this review, we discussed several biological risk factors, which may contribute to bAVM hemorrhage.
A game-theoretic approach for power systems defense against dynamic cyber-attacks

Abstract Technological advancements in today’s electrical grids give rise to new vulnerabilities and increase the potential attack surface for cyber-attacks that can severely affect the resilience of the grid. Cyber-attacks are increasing both in number as well as sophistication and these attacks can be strategically organized in chronological order (dynamic attacks), where they can be instantiated at different time instants. The chronological order of attacks enables us to uncover those attack combinations that can cause severe system damage but this concept remained unexplored due to the lack of dynamic attack models. Motivated by the idea, we consider a game-theoretic approach to design a new attacker-defender model for power systems. Here, the attacker can strategically identify the chronological order in which the critical substations and their protection assemblies can be attacked in order to maximize the overall system damage. However, the defender can intelligently identify the critical substations to protect such that the system damage can be minimized. We apply the developed algorithms to the IEEE-39 and 57 bus systems with finite attacker/defender budgets. Our results show the effectiveness of these models in improving the system resilience under dynamic attacks.
Color Control Functions for Multiprimary Displays—II: Variational Robustness Optimization

In a companion Part I paper, we presented a framework for analyzing robustness of color control functions (CCFs) for multiprimary displays against primary and observer variations and proposed a variational minimization for obtaining robust CCFs. The objective function proposed in the Part I paper combines two nonnegative terms that serve as useful figures of merit for quantitatively characterizing CCFs. The first term measures lack of smoothness of the CCFs and characterizes how well transitions in perceptual color space are preserved in the presence of the primary/observer variations. The second term measures deviation of the CCF, in the vicinity of the gray axis, from a specific axially linear CCF that provides perceptual invariance to the variations along the gray axis. In this paper, using calculus of variations, we develop an algorithm for numerically computing optimal CCFs under the proposed variational formulation. Using the proposed algorithm, we determine optimal CCFs for a several multiprimary display designs and assess and compare their performance against alternative approaches. The variationally optimal CCFs obtained using the proposed approach offer improvements over the alternatives, as assessed visually and via quantitative metrics measuring smoothness and invariance in the presence of primary variations. The relative improvements provided by the proposed CCF increase with increasing number of primaries.
Management of large peripheral nerve defects with autografting.

Abstract Introduction A segmental nerve defect from trauma results in significant loss of function of the extremity, and rarely occurs in isolation. Autografting of the nerve defect is the current gold standard. Methods A review of the recent literature regarding peripheral nerve defects after trauma treated with autograft. Results Identification of the zone of nerve injury is difficult and appropriate resection is critical for good outcomes. Meaningful recovery is more likely with application of excellent technique. Many of the factors affecting outcomes are not modifiable. Conclusion Nerve grafting for segmental nerve injuries continues to be an essential and appropriate treatment.
STAT1 dissociates adipose tissue inflammation from insulin sensitivity in obesity

Abstract Obesity fosters low-grade inflammation in white adipose tissue (WAT) that may contribute to the insulin resistance that characterizes type 2 diabetes mellitus (T2DM). However, the causal relationship of these events remains unclear. The established dominance of signal transducer and activator of transcription 1 (STAT1) function in the immune response suggests an obligate link between inflammation and the co-morbidities of obesity. To this end, we sought to determine how STAT1 activity in white adipocytes affects insulin sensitivity. STAT1 expression in WAT inversely correlated with fasting plasma glucose in both obese mice and humans. Metabolomic and gene expression profiling established STAT1 deletion in adipocytes (STAT1 fKO) enhanced mitochondrial function and accelerated TCA cycle flux coupled with subcutaneous WAT hyperplasia. STAT1 fKO reduced WAT inflammation, but insulin resistance persisted in obese mice. Rather, elimination of type I cytokine interferon gamma (IFNγ) activity enhanced insulin sensitivity in diet-induced obesity. Our findings reveal a permissive mechanism that bridges WAT inflammation to whole-body insulin sensitivity.
Phase I clinical trial of temsirolimus and perifosine for recurrent glioblastoma.

Purpose Malignant glioma (MG) is the most deadly primary brain cancer. Signaling though the PI3K/AKT/mTOR axis is activated in most MGs and therefore a potential therapeutic target. The mTOR inhibitor temsirolimus and the AKT inhibitor perifosine are each well-tolerated as single agents but with limited activity reclinical data demonstrate synergistic anti-tumor effects from combined treatment. Therefore, we initiated a phase I trial of combined therapy in recurrent MGs to determine safety and a recommended phase II dose. Methods Adults with recurrent MG, Karnofsky Performance Status ≥ 60 were enrolled, with no limit on the number of prior therapies. Temsirolimus dose was escalated using standard 3 + 3 design from 15 mg to 170 mg administered once weekly. Perifosine was fixed as a 600 mg load on day 1 followed by 100 mg nightly (single agent MTD) until dose level 7 when the load increased to 900 mg. Results We treated 35 patients with with glioblastoma (17) or other MGs (18; including nine anaplastic astrocytoma, nine anaplastic oligodendroglioma, one anaplastic oligoastrocytoma, and two low grade astrocytomas with radiographic transformation to MG). We observed five dose-limiting toxicities (DLTs): one at dose level 3 (50mg temsirolimus), then two at dose level 7 expansion (170 mg temsirolimus), and then two more at dose level 6 expansion (170 mg temsirolimus). DLTs included thrombocytopenia (n = 3), intracerebral hemorrhage (n = 1) and lung infection (n = 1). Conclusion Combining the mTOR inhibitor temsirolimus dosed at 115 mg weekly and the AKT inhibitor perifosine dosed at 100 mg daily (following 600 mg load) is tolerable in heavily pretreated adults with recurrent MGs.
Entity-Enriched Neural Models for Clinical Question Answering

We explore state-of-the-art neural models for question answering on electronic medical records and improve their ability to generalize better on previously unseen (paraphrased) questions at test time. We enable this by learning to predict logical forms as an auxiliary task along with the main task of answer span detection. The predicted logical forms also serve as a rationale for the answer. Further, we also incorporate medical entity information in these models via the ERNIE architecture. We train our models on the large-scale emrQA dataset and observe that our multi-task entity-enriched models generalize to paraphrased questions ~5% better than the baseline BERT model.
Robust power grid network design considering EM aging effects for multi-segment wires

Abstract This paper presents a number of power grid network design and optimization techniques that consider the electromigration (EM) effects for multi-segment interconnect wires. First, we consider a new EM immortality constraint due to EM void saturation volume for multi-segment interconnects. It helps reduce conservativeness in the EM-aware on-chip power grid design. Along with the EM nucleation phase immortality constraint, we show that both EM immortality constraints can be naturally integrated into the existing programming based power grid optimization framework. Second, to mitigate the overly conservativeness of the immortality constrained optimization methods, we further explore three strategies: we first size up failed wires to meet one of the immortality conditions subject to the design rules; second, we consider the EM-induced aging effects on power supply networks for a target lifetime, which allows some short-lived wires to fail and optimizes the remaining wires; third, we propose a large change sensitivity-based optimization scheme to perform localized fixing based on recently proposed coupled EM-IR drop analysis method. Numerical results on a number of IBM-format power grid networks demonstrate that the new method can reduce more power grid area compared to the existing EM immortality constrained optimizations. Moreover, the new method is able to optimize power grids with nucleated wires, which would not be possible with the existing methods. Results also show the sensitivity-based localized power girds fixing can fix EM-induced IR drop violations in a few minutes for synthesized power grid networks from ARM core designs.
506 ROLE OF NUCLEAR FACTOR κB IN MELANOMA PROGRESSION.

Although the incidence of melanoma is increasing, we continue to lack a systemic therapy that has been proven to provide a significant survival benefit. Molecular pathways involved in the progression of melanoma may provide new therapeutic targets. Therefore, understanding the molecular basis of melanoma progression is necessary to achieve more effective treatment for this deadly disease. Constitutive activation of the protein nuclear factor κB (NF-κB) can result in overexpression of proinflammatory mediators, leading to organ damage and carcinogenesis. NF-κB, when activated, is translocated to the nucleus, where it binds DNA at certain promoter regions. The goal of this investigation is to question the role NF-κB has in the tumorigenesis of melanoma. One cell line from a noninvasive radial growth phase melanoma lesion and one cell line from an invasive, more aggressive, vertical growth phase lesion were both stained using immunohistochemistry using antibody tagged with fluorescence to NF-κB. The cells were then viewed under a fluorescent microscope. It was seen that the early noninvasive cells had increased uptake in the cytoplasm, whereas the more aggressive, invasive cells had an increased uptake in the nucleus. This indicates that, in the invasive cells, NF-κB is more active. Thus, NF-κB may play a role in the progression of melanoma, allowing cells to gain the capacity to invade and metastasize. Therefore, proteins involved in the NF-κB pathway may be potential targets for novel chemotherapeutic agents.
Case of Limping – A Symptom of Spondylodiscitis in the Toddler

Toddlers have difficulty in communicating the location of discomfort. Children who limp and have a stiff spine should be evaluated with plain spine radiographs. Laboratory tests may be normal, with the exception of ESR and CRP. Typically, there is a delay of 2–3 weeks between the onset of symptoms and a diagnosis of spondylodiscitis. In the pre-antibiotic era, these were treated with immobilization alone. Recent studies have shown faster resolution and reduced rates of recurrence with IV antibiotics. Long term, there is typically fibrosis of the disc and even vertebral fusion at the affected level.
Arsenic and an Old Place: Rescuing p53 Mutants in Cancer.

Tumor suppressor p53 lacks conventional drug binding pockets that would facilitate rescue of cancer-driving mutations. In this issue, Chen et al. discover a new role for an old drug, arsenic trioxide, in binding and stabilizing p53. The arsenic atom binds in a conserved, cryptic site and reactivates multiple p53 mutants.
Targeting pre-synaptic tau accumulation: a new strategy to counteract tau-mediated synaptic loss and memory deficits

Synaptic tau accumulation is believed to promote synaptic loss, which contributes to cognitive deficits in Alzheimer's disease and tauopathies. In this issue of Neuron, Largo-Barrientos et al. report that synaptic loss can be mitigated by lowering Synaptogyrin-3, a known mediator of tau binding to synaptic vesicles.
Individualized Degradation Modeling and Prognostics in a Heterogeneous Group via Incorporating Intrinsic Covariate Information

This article focuses on individualized degradation modeling and prognostics for a heterogeneous group, where each individual unit shows a distinct degradation process. Existing degradation models usually treat each unit separately and do not fully utilize the distinct characteristics of each individual. In this study, we propose a generic framework to handle the heterogeneity across units by effectively leveraging the intrinsic covariate information, which is closely related to the unit's degradation process. Specifically, we employ a multivariate Gaussian process (MGP) to nonparametrically establish the relation between the covariate information and degradation process. Through modeling the unit similarities based on the covariates, efficient information transfer among units is enabled for better degradation modeling and prognostics, as the collected degradation signals from one unit can be shared with the entire heterogeneous group. A theoretical justification for the proposed model is also investigated. Simulation studies are presented to evaluate the parameter estimation accuracy and the sensitivity of the proposed method. A case study on the Alzheimer's disease (AD) neuroimaging initiative data set is further conducted, which demonstrates the advantage of the proposed method over existing benchmark approaches.
The CADILLAC risk score accurately identifies patients at low risk for in-hospital mortality and adverse cardiovascular events following ST elevation myocardial infarction.

BACKGROUND The CADILLAC risk score was developed to identify patients at low risk for adverse cardiovascular events following ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI). METHODS We performed a single center retrospective review of STEMI hospitalizations treated with PPCI from 2014 to 2018. Patients were stratified using the CADILLAC risk score into low risk, intermediate risk and high risk groups. Patients presenting with cardiac arrest or cardiogenic shock were excluded from the study. The primary outcome was adverse clinical events during initial hospitalization. Secondary outcomes were adverse clinical events at 30 days and 1 year following index hospitalization. RESULTS The study included 341 patients. Compared to patients with a low CADILLAC score, adverse clinical events were similar in the intermediate risk group during hospitalization (OR 1.23, CI 0.37-4.05, p 0.733) and at 30 days (OR 2.27, CI 0.93-5.56, p 0.0733) while adverse clinical events were significantly elevated in the high risk group during hospitalization (OR 4.75, CI 1.91-11.84, p 0.0008) and at 30 days (OR 8.73, CI 4.02-18.96, p < 0.0001). At 1 year follow-up, compared to the low risk CADILLAC group (9.4% adverse clinical event rate), cumulative adverse clinical events were significantly higher in the intermediate risk group (22.9% event rate, OR 2.86, CI 1.39-5.89, p 0.0044) and in the elevated risk group (58.6% event rate, OR 13.67, CI 6.81-27.43, p < 0.0001). The mortality rate was 0% for patients defined at low risk by CADILLAC score during hospitalization, as well up to 1 year follow up. On receiver operating curve analysis, discrimination of in-hospital adverse clinical events was fair using CADILLAC (C = 0.66, odds ratio 1.18; 95% CI 1.04-1.33; p = 0.0064) with somewhat better discrimination at 30-day follow-up (C = 0.719) and 1-year follow-up (C = 0.715). CONCLUSION Patients defined as low risk by the CADILLAC score following a STEMI were associated with lower mortality and adverse clinical event rates during hospitalization and up to 1 year following STEMI when compared to those with an intermediate or high CADILLAC score.
Inconsistency-Tolerant Reasoning with Classical Logic and Large Databases

Real-world automated reasoning systems must contend with inconsistencies and the vast amount of information stored in relational databases. In this paper, we introduce compilation techniques for inconsistency-tolerant reasoning over the combination of classical logic and a relational database. Our resolution-based algorithms address a quantifier-free, function-free fragment of first-order logic while leveraging off-the-shelf database technology for all data-intensive computation.
Web Delivery of a Monte Carlo Simulation Model: The Base and Yield Analyzer Experience

The provision for producers to update base acres and payment yields in the 2002 farm bill afforded an opportunity to test whether it was feasible to deliver a complex simulation model directly to producers. A Monte Carlo simulation model for assessing the economic impacts of the alternative base and yield options on individual farms was developed and made available to producers via the World Wide Web. The experiences and challenges from this collaborative extension and research effort are described, as well as the issues educators might consider before delivering complex software to a national audience via the Web.
Radiation-Related Orbital Injury: Clinical Manifestations and Considerations for Surgical Repair

Deformity and contracture of ophthalmic soft tissues and the orbital bones which compose the orbital complex may be the result of mechanical, chemical, thermal, and/or radiation injury. While reconstruction is most commonly necessary following traumatic orbital injuries, iatrogenically induced deformities account for a large number of cases as well. Iatrogenic causes range from unavoidable surgically induced deformity resulting from excision of a primary orbital neoplasm or ocular tumor with orbital extension, to contracture resulting from secondary effects of radiation. Radiation-related injury may develop following radiation therapy directed to the globe, orbit, or nasopharynx. Secondary considerations which may exacerbate radiation-induced injury include poor fitting or excessively heavy prostheses in anophthalmic (no globe) patients with orbital volume deficiency, and normal aging changes which may lead to or contribute to socket deformity.
Rethinking Health-Based Environmental Standards

Under the Clean Air Act, the U.S Environmental Protection Agency (EPA) is required to determine the stringency of the National Ambient Air Quality Standards (NAAQS), arguably the most important federal environmental program, without considering the costs of achieving these standards. Instead, it must rely exclusively on health-related criteria. This Article argues that health-based standards, which are one of the principal approaches to setting the stringency of environmental requirements in the United States, exhibit two serious pathologies: the stopping point problem and the inadequacy paradox. The stopping point problem arises because there is no coherent, defensible way for EPA to set the permissible level of pollution based on health considerations alone. Moreover, contrary to the commonly accepted view, the NAAQS have generally been set at levels that are less stringent than those that would result from the application of cost-benefit analysis, giving rise to the inadequacy paradox. We urge a reinterpretation of the Supreme Court’s important decision in Whitman v. American Trucking Associations that would solve the inadequacy paradox and explain how non-welfarist considerations, although they do not avoid the stopping point problem, could justify health-based trumps.
Gene Expression After Transformation in Bacillus subtilis

Abstract Sensitive assays of histidase activity were used to follow the production of this enzyme as directed by a gene newly introduced into cells of Bacillus subtilis by transformation. Histidase activity can be detected in histidase-negative recipient cells within 1 hr after the addition of deoxyribonucleic acid extracted from histidase-positive donors. Enzyme production continues for one to two additional hours and then ceases. Histidase production in the transformed cells is fully sensitive to catabolite repression. Catabolite repression is rapidly established after transformation of recipient cells that are resistant to this form of regulation.
Ultrasonic spray deposition of SiC nanoparticles for laminate metal composite fabrication

Abstract Nanoparticles have been increasingly used in functional and composite materials. One of the challenges, however, has been dispersing and controlling the nanoparticle clusters. In this study, the deposition of SiC nanoparticles via ultrasonic spraying process was investigated for a potential application in synthesis of laminate metal composites. The governing parameters of the ultrasonic spraying process which includes suspension and spraying parameters, and their influence on the deposited structure have been investigated. These parameters determine the driving force that transports the atomized droplets to the substrate, the amount of liquid phase present on the substrate, and its evaporation rate. By controlling these parameters, deposition structures ranging from a few SiC nanoparticles to cluster sizes of 10 μm could be obtained. The potential of using ultrasonic spraying to fabricate laminate composites reinforced at the interfaces with nanoparticles was investigated. Composites with a uniform deposition of SiC at the interface showed better mechanical properties than those with a nonuniform deposition when compared at the same SiC loading.
Overview of energy storage applications

Sandia National Laboratories has been studying energy storage systems since the late 1970s. Sandia's role, as a Department of Energy funded program, is to look ahead at emerging technologies, perform early R&D and identify applications for energy storage systems that offer significant benefit to the nation's electricity providers and users. In order to identify applications of energy storage, a two-phase Opportunities Analysis was conceptualized in FY94. The group of industry experts participating in the study reviewed the requirements for each of the applications identified in Phase I, modified application names, and combined some applications to better reflect the nature of the electricity industry today. Participants of the Phase II analysis used the perceived need for the application across the nation, and the potential technical and economic benefits for utilities as criteria to evaluate the applications.