cssi/SciSciGPT-SciSciNet huggingface dataset:
Waiting for lung transplantation: quality of life, mood, caregiving strain and benefit, and social intimacy of spouses.

: Background: The emotional and physical well-being of lung transplant patients is enhanced by the availability and stability of a primary caregiver. Methods: We describe the quality of life (QOL), mood, caregiving strain and benefits, and social intimacy of 73 lung transplant caregivers who completed the QOL Inventory, SF-36 Health Survey, Profile of Mood States, Caregiver Strain Index, Caregiver Benefit Index, and Miller Social Intimacy Scale. Results: Clinically low QOL was reported by 17.8–35.6% of spouses. Relative to a normative sample, spouses reported significantly lower physical (z = 4.01, p < 0.001) and emotional (z = 7.01, p < 0.001) QOL. Over half (56.2%) had clinically elevated caregiving strain. Heightened physical strain (80.8%), inconvenience (79.5%), feeling confined (72.6%), feeling upset that patient has changed so much (69.9%) contributed most to caregiver strain, while discovering inner strength (60.3%), support from others (53.4%), and realizing what is important in life (42.5%) were noted caregiving benefits. Higher caregiving strain was associated with more mood disturbance (r = 0.42, p < 0.001), lower emotional QOL (r = −0.39, p < 0.002), lower social intimacy (r = −0.37, p < 0.002), and longer disease duration (r = 0.55, p < 0.001). Conclusion: Spouses of patients awaiting lung transplantation may experience QOL deficits and high caregiver strain. Interventions to improve QOL and reduce caregiver strain are needed.
Pancreaticoduodenectomy for nonperiampullary primary tumors

introduction This review was performed to evaluate the outcome of patients undergoing pancreaticoduodenectomy (PD) for isolated metastatic or locally advanced nonperiampullary tumors at a single institution over a 13-year period. methods Between 1983 and 1996, patients undergoing PD for metastatic or locally advanced nonperiampullary malignancies were identified. Medical records were reviewed and outcome factors and survival data analyzed. results Eighteen patients were identified. The primary tumor histopathology included colon (n = 7), gastric (n = 4), renal cell (n = 3), lung (n = 2), bladder (n = 1), and melanoma (n = 1). The median length of hospital stay was 15 days (6 to 48) with one perioperative death (5.5%). The median tumor size was 5.5 cm (0.8 to 11.5), and 7 patients had positive peripancreatic lymph nodes. The median survival was 40 months, with a 5-year survival of 35%. conclusions Pancreaticoduodenectomy for nonperiampullary malignancy is infrequently indicated. However, in the absence of widely metastatic disease, PD should be considered for locally advanced tumors or isolated metastatic malignancy
Capture and Visualization of Hydrogen Sulfide by a Fluorescent Probe

Hydrogen sulfide (H2S) has been known as a toxic pollutant for years. However, this molecule has been recently recognized as the third gaseous transmitter (the other two are nitric oxide and carbon monoxide).[1–3] The production of H2S in mammalian systems has been attributed to at least three endogenous enzymes:[4–7] cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfur-transferase (MPST). These enzymes use cysteine or cysteine derivatives as substrates and convert them into H2S within different organs and tissues. In addition to these enzymatic pathways, there are also a range of comparably simple chemical events which may liberate H2S from the intracellular pool of `labile' sulfur, for instance from the `sulfane sulfur' pool (compounds containing sulfur atoms bound only to other sulfur atoms).[8] The production of endogenous H2S and exogenous administration of H2S have been demonstrated to exert protective effects in many pathologies. For example, H2S has been shown to relax vascular smooth muscle, induce vasodilation of isolated blood vessels, and reduce blood pressure. H2S can also inhibit leukocyte adherence in mesenteric microcirculation during vascular inflammation in rats, suggesting H2S is a potent anti-inflammatory molecule. Additionally, it has become evident that H2S is a potent antioxidant and, under chronic conditions, can up-regulate antioxidant defense. Despite the rising interest in H2S research, fundamental questions regarding regulation of its production, its mechanism of action, and its destruction remain. A critical debate in the field involves the biologically relevant levels of H2S as current reports varying over 105-fold concentration range.[9–12] Obviously, accurate and reliable measurement of H2S concentrations in biological samples is needed and can provide useful information to understand the function of H2S. Currently the major methods for H2S detection are colorimetric and electrochemical assays, gas chromatography, and sulfide precipitation.[12–16] These methods often require complicate sample processing. Given the high reactivity of H2S, these methods can yield variable results.[9–12] Fluorescence based assays could be useful in this field due to the high sensitivity and convenience. However, fluorescence method for H2S detection, especially for real-time detection in biological samples, is still very limited so far.[17–19] Here, we report a reaction-based fluorescent turn-on strategy for the detection of H2S.
TIPS: comparison of shunt patency and clinical outcomes between bare stents and expanded polytetrafluoroethylene stent-grafts.

Purpose To compare shunt patency and clinical outcomes in two groups of patients who received a transjugular intrahepatic portosystemic shunt (TIPS): one group with bare stents and one with expanded polytetrafluoroethylene stent-grafts. Materials and Methods TIPS were created with bare stents ( n = 41) or stent-grafts ( n = 40). Overall TIPS patency rates were compared between these two groups, as were clinical outcomes in patients with variceal bleeding and those with ascites. Results In the bare stent group, primary shunt patency rates were 63%, 48%, and 24% at 3, 6, and 12 months, respectively. Secondary patency rates were 75% and 62% at 3 and 6 months, respectively. In the stent-graft group, primary patency rates were 94%, 67%, and 38% at 3, 6, and 12 months, respectively. Secondary patency rates were 100% and 92% at 3 and 6 months, respectively. All stent patency rates were higher in the stent-graft group, but only the difference in the 3-month primary patency rate (63% vs 94%) reached significance ( P = .03). In patients with variceal bleeding as well as those with ascites, early and overall clinical success rates were higher in the stent-graft group, but only the 3-month and 12-month differences were statistically significant. Conclusions TIPS created with stent-grafts had better 3-month primary patency rates and better 3-month and 12-month clinical success rates compared with those created with bare stents.
Divergent requirements for fibroblast growth factor signaling in zebrafish maxillary barbel and caudal fin regeneration

The zebrafish maxillary barbel is an integumentary organ containing skin, glands, pigment cells, taste buds, nerves, and endothelial vessels. The maxillary barbel can regenerate (LeClair & Topczewski 2010); however, little is known about its molecular regulation. We have studied fibroblast growth factor (FGF) pathway molecules during barbel regeneration, comparing this system to a well-known regenerating appendage, the zebrafish caudal fin. Multiple FGF ligands (fgf20a, fgf24), receptors (fgfr1-4) and downstream targets (pea3, il17d) are expressed in normal and regenerating barbel tissue, confirming FGF activation. To test if specific FGF pathways were required for barbel regeneration, we performed simultaneous barbel and caudal fin amputations in two temperature-dependent zebrafish lines. Zebrafish homozygous for a point mutation in fgf20a, a factor essential for caudal fin blastema formation, regrew maxillary barbels normally, indicating that the requirement for this ligand is appendage-specific. Global overexpression of a dominant negative FGF receptor, Tg(hsp70l:dn-fgfr1:EGFP)(pd1) completely blocked fin outgrowth but only partially inhibited barbel outgrowth, suggesting reduced requirements for FGFs in barbel tissue. Maxillary barbels expressing dn-fgfr1 regenerated peripheral nerves, dermal connective tissue, endothelial tubes, and a glandular epithelium; in contrast to a recent report in which dn-fgfr1 overexpression blocks pharyngeal taste bud formation in zebrafish larvae (Kapsimali et al. 2011), we observed robust formation of calretinin-positive tastebuds. These are the first experiments to explore the molecular mechanisms of maxillary barbel regeneration. Our results suggest heterogeneous requirements for FGF signaling in the regeneration of different zebrafish appendages (caudal fin versus maxillary barbel) and taste buds of different embryonic origin (pharyngeal endoderm versus barbel ectoderm).
Trametinib (GSK1120212) in the treatment of melanoma.

Introduction: The discovery of somatic mutations in melanoma has advanced our knowledge of the biology of the disease. The mutations, such as those in NRAS, BRAF, GNAQ and GNA11, promote the growth of melanoma cells in most part through the mitogen-activated protein kinase (MAPK) pathway. Understanding the molecular pathways of some of these mutations has resulted in the successful development of selective BRAF inhibitors. Yet, a cure for advanced melanoma is far from reality. Targeting MAPK/ERK kinase (MEK), an essential intermediary kinase protein within the MAPK pathway, may be a promising way to treat patients with BRAF or other genomic mutation. Areas covered: The authors discuss the MAPK pathway in melanoma and review the preclinical and clinical studies of the MEK inhibitor, trametinib, in melanoma. They also discuss the potential of using trametinib in the targeted therapy of advanced melanoma. Expert opinion: Studies have demonstrated the activity of trametinib in BRAF-mutant melanoma, suggesting...
Automatic Node Discovery in CAN (Controller Area Network) Controllers using Reserved Identifier Bits

A new technique for automatic address space configuration in CAN network is proposed in this work. The proposed technique is to use two reserved bits of CAN extended identifier field in the initial address assignment process. These reserved bits can be in one of the following three states: address acquired, address assignment pending and address claim override. An address configuration protocol is proposed based upon these added states and a finite state machine for the protocol is also shown. Real-time behavior of the proposed address space configuration technique can be further validated by a series of parametric simulations using tools like OPNET.
A Stratal OT Analysis of the Sanskrit Nominal Accent Paradigm

Stratal Optimality Theory posits constraint evaluation at three distinct levels or strata: stem, word and phrase level. This multi-level variation of the original OT model may provide more economical and elegant explanations of problems involving opacity, derived environment effects and paradigmatic effects than other Parallel OT theories that have been developed to address these issues. Alternations of pitch accent placement within the Vedic Sanskrit nominal inflectional and derivational paradigms provide evidence supporting Stratal OT. First, two major accentual patterns surface upon inflection; accent may remain fixed on a stem syllable in all cases or may shift to the inflectional ending in “weak” cases only. Second, for all nominals, the vocative is not accented, except when it appears at the beginning of a phrase; in that case, the accent is always on the initial syllable, regardless of the position of the accent on the stem or other inflected forms. Finally, accentual variation of primary and secondary derived stems and words is seen; accent may remain on the root (or primary stem) or may fall on the derivational ending; in either case, accent remains fixed throughout inflection (i.e., no accent shift). In this analysis, a system of well-grounded morphological, prosodic, identity and alignment constraints are proposed for the stem, word and phrase levels to explain these alternations. It is argued that inflection takes place at the word level while derivation occurs at the stem level. Constraints at the three levels follow a consistent ranking pattern, while remaining relevant to the prosodic and morphological requirements of the specific level. The highest ranked identity constraint at the stem and word levels are substantively identical: MAXIO(Accent)HEAD. Crucially, however, the head is different at each level, with the derivational suffix being the head at the stem (derivational) level, while the stem or root is the head at the word (inflectional) level. This allows for a principled explanation of the various accentual phenomena and, additionally, provides evidence for the operation of distinct stem and word levels. Numerous constraint tableaux are presented; in each case, the winner is the correct surface form. These data indicate that Stratal OT effectively captures the Sanskrit nominal accentual paradigms using a small number of well-grounded constraints. Importantly, it is demonstrated that Parallel OT is unable to generate the correct surface forms for all the relevant alternations without the introduction of exotic and otherwise unnecessary constraints. Further cross-linguistic and theoretical research into the Stratal OT model is needed to establish its universality and superiority to other models.
Predicted Institutional Trades and the Cross-Section of Returns

I investigate whether it is possible to predict the aggregate net trades into a stock by financial institutions and to profitably trade on these predictions. I find that aggregate net trades can be predicted across forecast horizons ranging from 1 quarter to 20 quarters. Predicted institutional trades, defined as the forecasted cumulative net trades of all financial institutions into a stock over the following Q quarters scaled by a stock’s current number of shares outstanding, has a negative relation with returns. The low-high predicted institutional trades portfolio earns an annualized Fama and French alphas of 10.55%.
Reactive objects

Object-oriented, concurrent, and event-based programming models provide a natural framework in which to express the behavior of distributed and embedded software systems. However, contemporary programming languages still base their I/O primitives on a model in which the environment is assumed to be centrally controlled and synchronous, and interactions with the environment carried out through blocking subroutine calls. The gap between this view and the natural asynchrony of the real world has made event-based programming a complex and error-prone activity, despite recent focus on event-based frameworks and middleware. In thin paper we present a consistent model of event-based concurrency, centered around the notion of reactive objects. This model relieves the object-oriented paradigm from the idea of transparent blocking, and naturally enforces reactivity and state consistency We illustrate our point by a program example that offers substantial improvements in size and simplicity over a corresponding Java-based solution.
DNA charge transport: Moving beyond 1D

Abstract Charge transport across novel DNA junctions has been studied for several decades. From early attempts to move charge across DNA double crossover junctions to recent studies on DNA three-way junctions and G4 motifs, it is becoming clear that efficient cross-junction charge migration requires strong base-to-base electronic coupling at the junction, facilitated by favorable pi-stacking. We review recent progress toward the goal of manipulating and controlling charge transport through DNA junctions.
Application of Solution Structure Theorems for Asymmetric Heating in Thin Films

The purpose of this study is to examine thermal wave phenomena in a thin finite film subjected to non-homogeneous boundary conditions. The Cattaneo-Vernotte (C-V) heat conduction model is solved using the superposition principle in conjunction with the solution structure theorems. For comparison purposes, the diffusion model is also solved to demonstrate the flexibility in the technique as well as to show the differences in the results. It is recognized that the solution structure theorems are suitable for homogeneous systems only. However, by performing a functional transformation, the original nonhomogeneous partial differential equation governing the physical problem can be cast into a new form with homogeneous boundary conditions such that it can be solved directly with the solution structure theorems. In this study, details of this process will be examined and explored for achieving solutions in such systems. The methodology provides a convenient technique for the solution of the diffusion and C-V heat conduction equations with non-homogeneous boundary conditions.
A Patterned Conducting Polyaniline Layer on a Non-Conducting Polymer Matrix

Polyaniline is one of the most studied conducting polymers and its properties have been used in many sensor applications including gas sensors and pH sensors. In this work, we present a method that is able to embed a conducting polyaniline film in a desired pattern onto a nonconducting polymer matrix. We have developed an embedded polyaniline film on a polydimethylsiloxane (PDMS) matrix using a cast molding technique. The polyaniline film was grown by electrochemically polymerizing polyaniline from an electrolyte containing sulfuric acid and aniline monomer. A three-electrode cell system was used with a standard Ag/AgCl reference electrode, a gold auxiliary electrode, and a patterned gold working electrode. After the polyaniline film was formed on the patterned working electrode, PDMS was poured atop and cured. Cured PDMS was then debonded along with the polyaniline film embedded on the PDMS layer or block. The gold layer of the working electrode can be patterned using a photolithography steps so that the designed pattern can be transferred by the polyaniline growth on the working electrode. The greenish color of the polyaniline film indicated that the embedded polyaniline was in the conducting state (emeraldine salt form) and the conductivity of the polyaniline has also been verified by applying a DC voltage across the film and measuring the current through the polyaniline layer. The measured conductivity of the PANi layer at room temperature was in the range of 4.5 ~ 4.6 S/m. The advantage of this technique is that the PDMS matrix holds the polyaniline in place while allowing the polyaniline film to undergo reversible doping/dedoping chemistry when electrolyte solution comes into contact with the surface of the film. The developed technology can be used for various chemical sensor applications, for example, a pH sensor or gas sensors where a flexible and all-polymer apparatus is needed.
A data-driven multidimensional visualization technique for process fault detection and diagnosis

Abstract A multidimensional visualization technique is described for fault detection and diagnosis of a multivariate process by principal component analysis (PCA) of historical data. The technique uses a parallel coordinate system to visualize data that allows for monitoring of abnormal process events that lead to process faults, enabling the visualization of multiple principal components effectively and facilitating the study of how each principal component varies with respect to time. The principal component and residual space control limits are established for fault detection and the Random Forests machine learning tool is adopted for fault diagnosis. The key features of the methodology are demonstrated through a study of the benchmark Tennessee Eastman process.
Bioluminescence Assisted Switching and Fluorescence Imaging (BASFI)

Forster resonance energy transfer (FRET) and bioluminescence resonance energy transfer (BRET) are two major biophysical techniques for studying nanometer-scale motion dynamics within living cells. ...
Functions which Parametrize Means

(1983). Functions which Parametrize Means. The American Mathematical Monthly: Vol. 90, No. 10, pp. 677-683.
Differential bioavailability of polychlorinated biphenyls associated with environmental particles: Microplastic in comparison to wood, coal and biochar.

Microplastic particles are increasingly being discovered in diverse habitats and a host of species are found to ingest them. Since plastics are known to sorb hydrophobic organic contaminants (HOCs) there is a question of what risk of chemical exposure is posed to aquatic biota from microplastic-associated contaminants. We investigate bioavailability of polychlorinated biphenyls (PCBs) from polypropylene microplastic by measuring solid-water distribution coefficients, gut fluid solubilization, and bioaccumulation using sediment invertebrate worms as a test system. Microplastic-associated PCBs are placed in a differential bioavailability framework by comparing the results to several other natural and anthrogenic particles, including wood, coal, and biochar. PCB distribution coefficients for polypropylene were higher than natural organic materials like wood, but in the range of lipids and sediment organic carbon, and smaller than black carbons like coal and biochars. Gut fluid solubilization potential increased in the order: coal < polypropylene < biochar < wood. Interestingly, lower gut fluid solubilization for polypropylene than biochar infers that gut fluid micelles may have solubilized part of the biochar matrix while bioaccessibility from plastic can be limited by the solubilizing potential of gut fluids dependent on the solid to liquid ratio or renewal of fluids in the gut. Biouptake in worms was lower by 76% when PCBs were associated with polypropylene compared to sediment. The presence of microplastics in sediments had an overall impact of reducing bioavailability and transfer of HOCs to sediment-ingesting organisms. Since the vast majority of sediment and suspended particles in the environment are natural organic and inorganic materials, pollutant transfer through particle ingestion will be dominated by these particles and not microplastics. Therefore, these results support the conclusion that in most cases the transfer of organic pollutants to aquatic organisms from microplastic in the diet is likely a small contribution compared to other natural pathways of exposure.
The N-Glycans Modulate the Binding of ADAMTS13 with von Willebrand Factor.

Abstract ADAMTS13, a circulating multidomain protease consisting a metalloprotease (MP), a disintegrin, a thrombospondin type 1 repeat [TSR], a cysteine rich region, a spacer, 7 additional TSR and 2 CUB domains, is critical for maintaining the homeostasis of von Willebrand factor (VWF). Severe deficiency of the enzyme can lead to VWF-platelet thrombosis in the microcirculation characteristic of thrombotic thrombocytopenic purpura (TTP). Sequence analysis predicts that ADAMTS13 contains 2 and 6 likely N-glycosylation sites respectively at or near the MP and spacer domains, and 2 possible sites in the CUB domains. To investigate the N-glycosylation status and the role of N-glycans in the function of ADAMTS13, we digested plasma derived ADAMTS13 and recombinant ADAMTS13 or its truncated variants with peptide-N-glycosidase F (PNGase F) or endoglycosidase H. SDS PAGE analysis showed that digestion with PNGase F, but not with endo H, decreased the molecular weights of plasma derived ADAMTS13 as well as recombinant ADAMTS13 proteins, including AD7 (residues 1-1427, full-length), AD5 (residues 1-745, MP-TSR#1), AD2 (residues 1-448, MP-TSR#1), AD8 (residues 556-748, spacer-TSR#2) and AD13 (residues 1016-1427, TSR#8-CUB#2), indicating that the MP, spacer and CUB domains were all N-glycosylated as predicted, and contained complex type carbohydrate chains. Enzyme linked immunoassay showed that removal of the N-glycans did not affect the binding of proteases to immobilized VWF multimers or VWF73 peptide. Removal of the N-glycans modestly affected the protease-TTP IgG binding, increasing the Kd by 190% for AD7 and by 50% for AD5. Expression experiments in Lec1 mutant Chinese hamster ovary (CHO) cells with defective GlcNAc-TI activity due to mutations in the Mgat1 gene showed that the resulting high-mannose type AD7 and AD5 variant proteases were secreted normally, showed no difference in VWF cleaving and TTP IgG binding activities, but exhibited increased binding to VWF multimers or VWF73 peptide. In summary, ADAMTS13 are N-glycosylated with complex type oligosaccharides at the MP, spacer and CUB domains. Intracellular conversion from high mannose to complex type glycans modulates the binding of the protease to VWF, suggesting that this process may help prevent depletion of the protease under conditions of high VWF levels in the circulation.
Equational Security Proofs of Oblivious Transfer Protocols

We exemplify and evaluate the use of the equational framework of Micciancio and Tessaro (ITCS 2013) by analyzing a number of concrete Oblivious Transfer protocols: a classic OT transformation to increase the message size, and the recent (so called “simplest”) OT protocol in the random oracle model of Chou and Orlandi (Latincrypt 2015), together with some simple variants. Our analysis uncovers subtle timing bugs or shortcomings in both protocols, or the OT definition typically employed when using them. In the case of the OT length extension transformation, we show that the protocol can be formally proved secure using a revised OT definition and a simple protocol modification. In the case of the “simplest” OT protocol, we show that it cannot be proved secure according to either the original or revised OT definition, in the sense that for any candidate simulator (expressible in the equational framework) there is an environment that distinguishes the real from the ideal system.
Hospital Length of Stay Among Patients Receiving Intermittent Versus Prolonged Piperacillin/Tazobactam Infusion in the Intensive Care Units.

Objectives:We sought to evaluate clinical outcomes of intensive care unit (ICU) patients following a hospital-wide initiative of prolonged piperacillin/tazobactam (PIP/TAZ) infusion.Methods:Retrosp...
Double-ionization satellites in the x-ray emission spectrum of Ni metal

We report measurements of the nonresonant x-ray emission spectroscopy (XES) from Ni metal in an energy range spanning the $K\ensuremath{\beta}$ diagram line, valence-to-core emission, and double-ionization (DI) satellites that appear beyond the single-particle Fermi level. We make special use of a laboratory-based x-ray spectrometer capable of both x-ray emission and x-ray absorption measurements to accurately align the XES and x-ray absorption spectra to a common energy scale. The careful alignment of energy scales is requisite for correction of the strong sample absorption of DI fluorescence above the Ni $K$-edge energy. The successful correction of absorption effects allows a determination of the branching ratios for the $[1s3d],[1s3p],[1s2p]$ and $[1s2s]$ satellites with respect to their corresponding diagram lines. We compare our results with other work, finding good agreement with prior experiments and with theoretical calculations in the multiconfiguration Dirac-Fock framework.
Distance Aggregation based Score Fusion for improving person re-identification

Person re-identification is an important problem for automated video-based surveillance. Person re-identification is the problem of identifying a person over multiple cameras with varying viewpoints at different locations and different points of time. The most common directions of research in this domain are feature extraction and distance metric learning. While a number of algorithms have been proposed for solving this problem, the performance of these algorithms is varied and mistakes in detecting the correct person are often encountered. In this paper, we propose a novel framework for aggregating the “distances” between images of different persons that are generated by person re-identification algorithms in order to rank “gallery” images in terms of their “closeness” from a given “probe” image. The Distance Aggregation-based Score Fusion (DASF) framework uses aggregated distances to rank the gallery, and results in improved performance over each individual person re-identification algorithm that is used to obtain distances. Towards this end, we have applied Simulated Annealing, a heuristic algorithm, to find the optimum distances between images using the distances from individual algorithms. The DASF framework is unsupervised and requires no prior information about how each of the individual algorithms works. Our results show significant improvement in performance for commonly used datasets. Performed experiments also indicate that the DASF framework yields better results than the state-of-the-art score fusion algorithms for person reidentification.
Sepsis-Induced Acute Kidney Injury

Abstract Sepsis is broadly defined as the systemic inflammatory response to known or suspected infection. It remains a common cause of both morbidity and mortality in the critical care setting. Injury to multiple organ systems including the kidneys, liver, lungs, and brain is an important consequence of the overwhelming inflammatory response in sepsis. Current estimates indicate that acute kidney injury (AKI) occurs in approximately 60% of septic patients and significantly increases the risk of sepsis-associated mortality. Despite extensive laboratory and clinical study, therapy for sepsis and septic AKI remains limited to supportive measures. The purpose of this article is to review current understanding of the pathophysiology of AKI and sepsis and highlight areas where further work is needed. Important concepts, definitions, epidemiology, and experimental models of sepsis-induced AKI are introduced. The molecular mechanisms underlying sepsis-induced AKI are then extensively reviewed. Finally, we focus on the emerging role of mitochondrial dysfunction in septic AKI and discuss mitochondrial dynamics as a novel therapeutic target in this disease.
The effect of diet, adiposity, and weight loss on the secretion of incretin hormones in cats.

Abstract Degree of adiposity and dietary macronutrient composition affect incretin hormone secretion in humans and mice, but little is known about their effect in cats. In this study, 7 overweight cats were fed a maintenance diet (MD) for at least 2 wk followed by a reduced calorie diet (RCD), which was lower in fat and higher in carbohydrates and fiber. Cats were fed ad libitum initially, and then, food was restricted to achieve 1%–2% loss of body weight weekly (11 wk). When lean, cats were fed MD for 2 wk. A standardized meal test (SMT) using a third diet was performed after at least 7 d on each diet, before and after weight loss (four SMT's total). Glucose, insulin, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic peptide (GIP) concentrations were measured immediately before and over 6 h after feeding the SMT. Area under the curve (AUC) was compared for GLP-1, GIP, and insulin concentrations using 2-way analysis of variance. Leaner cats had increased GIPAUC compared to obese cats (P = 0.025). There was a trend toward increased GIPAUC on RCD compared to the MD (P = 0.085). There was a moderate negative correlation between body fat percentage and GLP-1AUC (r = −0.45; P = 0.05). There was no effect of diet on GLP-1AUC. In conclusion, degree of adiposity and dietary macronutrient content could be important in determining GIP responses not only acutely but also on a long-term basis. Further investigation of GIP responses in cats should take both diet and degree of adiposity into account.
Leiomyoma of the Prostate: Case Report and Review of the Literature

Leiomyomas can develop in any organ containing smooth muscles. They most commonly occur in the gastrointestinal and the female genital tracts. Leiomyoma of the prostate is a rare, benign tumor. We report 3 cases of rare prostatic leiomyomas. The paucity of literature describing prostatic leiomyoma increases the chance for misdiagnosis. Fewer than 30 cases in the English literature, with none including magnetic resonance imaging, computed tomography (CT), ultrasound, positron emission tomography-CT, and pathological findings together were found. Over the past decade, there has been a shift in the management of prostatic leiomyomas. Prostatectomy was once considered a standard approach for treatment, but now nonsurgical treatment options such as embolization are preferred. Conservative management including surveillance is an option for asymptomatic patients.
Abstract 12203: Fxr1 Regulates Inflammatory mRA Stability and Vascular Disease

Introduction: Vascular smooth muscle cells (VSMC) play a critical role in the etiology and progression of many vascular diseases, and reduction of inflammatory gene expression in VSMC is a rational...
Negative costimulation constrains T cell differentiation

T cell costimulation is a principal mechanism by which T cell activation is regulated, but it remains unclear whether costimulatory pathways also control T cell differentiation. This unresolved question is germane to our understanding of how T cell function is controlled and has therapeutic implications in the context of cancer immunotherapy. Using a mass cytometry based systems approach and murine models we investigated whether negative costimulation regulates T cell differentiation as well as activation. Unsupervised population identification reveals 30 T cell subsets in Ctla-4 −/− and littermate control mice including 6 CD8, 3 T reg , 14 CD4 effector T cell populations. Expectedly, loss of CTLA-4 led to dramatic changes in the relative frequency of CD8 and CD4 T cell subsets. Strikingly, however, loss of CTLA-4 led to the generation of multiple non-canonical T cell populations outside of the normal boundaries of T cell phenotypes, which interestingly, were all in the CD4 T compartment. To determine if the role of negative costimulation in differentiation may be a generalizable phenomenon, we performed similar analyses of Pdcd-1 −/− mice. This profiling revealed that loss of PD-1 leads to a subtle expansion of CD8 T cell phenotypes in addition to changes in the relative frequencies of CD4 and CD8 T cell populations. These observations indicate that CTLA-4 restricts CD4 T cell phenotypes while PD-1 restricts CD8 T cell phenotypes. Consistent with this model, loss of CTLA-4 differentially affects the expression of individual markers in CD4 and CD8 T cells. Together these findings indicate that in addition to attenuating T cell activation, negative costimulation acts to constrain T cell differentiation.
Highly accurate experimentally determined energy levels of H3.

A sub-Doppler rovibrational spectroscopic survey of H3+ has been conducted which included 36 transitions in the ν2 ← 0 fundamental band, 15 transitions in the 2ν22←ν2 hot band, and 7 transitions in the 2ν22←0 overtone band, improving the uncertainties of most transitions by more than an order of magnitude to ∼4 MHz. Combination differences were used to determine relative energy levels and forbidden rotational transitions up to J = 6. A fit of the ground state to an effective Hamiltonian was used to connect ortho and para states, and to determine the absolute energy levels relative to the forbidden (0, 0) state. Ultimately, 62 rovibrational energy levels in the ground, ν2, and 2ν22 states were determined with ∼10 MHz uncertainty. Comparing the experimentally determined energy levels with ab initio calculations revealed an unexpected dependence of the residuals on the quantum number G.
Generalized Jordan Center: A Source Localization Heuristic For Noisy And Incomplete Observations

We consider estimating the source of a spreading process on a directed acyclic graph using noisy and incomplete observations; we believe this is the first work on source estimation under noisy information. Our main contribution is a novel heuristic, the generalized Jordan center (GJC), which is the maximum likelihood estimator of the diffusion source under mild conditions.
Apparatus for Deformation Tests at Intermediate Strain rates — 10−2 to 102 s−1 — and at High Pressure

Few stress-strain data are available at intermediate strain rates (up to 102 s−1) and at confining pressures above 100 kPa. Even though at least three apparatuses work in this regime of strain rate and pressure [1–3], our laboratory’s interest in obtaining equation-of-state data in this regime dictated that we develop a new apparatus.
In vivo Depth Resolved Birefringence Measurement of the Human Retinal Nerve Fiber Layer by Polarization Sensitive OCT

Purpose: To measure the depth resolved retinal nerve fiber layer (RNFL) birefringence using a new Polarization Sensitive Optical Coherence Tomography (PS-OCT) machine that was developed by the authors [1]. Measurement of RNFL optical birefringence enhances specificity in determining RNFL thickness in structural Optical Coherence Tomography (OCT) images. A decrease in birefringence may also be an early sign of glaucomatous atrophy of the RNFL, and therefore PS-OCT may be particularly helpful in the early diagnosis of glaucoma. Methods: With OCT, cross-sectional structural images of the retina can be made in vivo, allowing determination of the RNFL thickness. From light reflected back from the retina, Scanning Laser Polarimetry (SLP) can measure polarization state changes, which are attributed to the birefringence of the RNFL. We have developed a PS-OCT instrument that combines the depth resolution of OCT with the polarization sensitivity of SLP to image the depth resolved optical birefringence of the human RNFL in vivo. By measuring the OCT interference fringes simultaneously in orthogonal polarization channels, the polarization state of light reflected from a structure within the retina can be determined completely. By modulating the input polarization over two states, the optic axis and birefringence of the RNFL can be uniquely determined. The PS-OCT scan location is co-registered by a video camera during data acquisition. Results: Measurements on one volunteer show that the average double pass phase retardation in the RNFL in near the optic nerve head is equal to 0.29 ± 0.02° / mm. Conclusions: For the first time the depth resolved birefringence of the human retinal nerve fiber layer in vivo was measured using Polarization Sensitive Optical Coherence Tomography. [1] B. Cense, T.C. Chen, B.H. Park, M.C. Pierce, J.F. de Boer, "In vivo depth-resolved birefringence measurements of the human retinal nerve fiber layer by polarization-sensitive optical coherence tomography" Optics Letters 27, 1610 (2002)
A U.S. Court Sends Second Reverse-Payment Case to Trial (Cephalon)

In the Cephalon case, Judge Goldberg (ED Pa) denied defendants' summary judgment motions, sending the second reverse-payment-settlement case to trial. This short article analyzes the judge's decision, in particular addressing the appropriate liability standard under FTC v. Actavis and what constitutes a "large and unjustified" payment.
Feasibility of Tele-Prompt: A tablet-based prompted voiding intervention to support informal caregivers of older adults with urinary incontinence

Urinary incontinence (UI) is a highly prevalent condition, burdening older adults and their informal caregivers. This study explored the development and feasibility of a 6-week evidence-based, educational/skill building program delivered via tablet-personal computer aimed at developing informal caregiver UI knowledge; and enhancing informal caregiver skill set in prompted voiding and toileting strategies. Caregivers also received individualized weekly coaching sessions from a nurse expert. Feasibility and preliminary efficacy were tested in three caregiver/care-recipient dyads. Recruitment of eligible participants through community-based resources was a challenge to feasibility. Most caregivers found the technology acceptable, but adherence to prompted voiding was inconsistent. All caregivers rated the intervention highly, reported improvements in their care-recipient's urine leakage, found access to a UI expert beneficial, and would recommend it to a friend. The results suggest that the tablet-facilitated intervention was feasible and acceptable to informal caregivers and showed promise for improving both caregiver and care recipient outcomes.
Adalimumab induced interstitial lung disease

Tumor necrosis factor inhibitors have been implicated in many pulmonary complications. Before starting these class of drugs latent infection as tuberculosis and preexisting lung disease should be excluded. These agents have been linked to pulmonary nodules, pneumonitis, fibrosis, autoimmune reactions and infection. We report a case of adalimumab induced organizing pneumonia in an old gentleman who was started on the drug for his uncontrolled Psoriasis.
Chapter 97 – Facioscapulohumeral Dystrophy

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common form of muscular dystrophy. Dominantly inherited in most, FSHD is characterized at onset by a restricted distribution of muscle weakness affecting the shoulders and face, and a slow, descending progression. In most patients, FSHD (FSHD1) results from a contraction of a macrosatellite repeat (D4Z4) on chromosome 4q35. Contraction of the repeats results in chromatin relaxation resulting in transcriptional derepression of DUX4, a retrogene, a copy of which is present in each repeat and normally only expressed in the germline. In a minority of patients with phenotypic FSHD (FSHD2), there is chromatin relaxation at the D4Z4 repeats without contraction in repeat number. This chromatin change is the result of mutations in SMCHD1, a gene involved in chromatin regulation. The recent elucidation of a unifying molecular mechanism in FSHD opens the door to understanding disease pathophysiology and the development of targeted treatments.
PET Detection of Cerebral Necrosis Using an Infarct-Avid Agent 2-Deoxy-2-[ 18 F]Fluoro- d -Glucaric Acid (FGA) in a Mouse Model of the Brain Stroke

Ischemic stroke is a leading cause of disability worldwide. The volume of necrotic core in affected tissue plays a major role in selecting stroke patients for thrombolytic therapy or endovascular thrombectomy. In this study, we investigated a recently reported positron emission tomography (PET) agent 2-deoxy-2-[18F]fluoro-d-glucaric acid (FGA) to determine necrotic core in a model of transient middle cerebral artery occlusion (t-MCAO) in mice. The radiopharmaceutical, FGA, was synthesized by controlled, rapid, and quantitative oxidation of clinical doses of 2-deoxy-2-[18F]fluoro-d-glucose (FDG) in a one-step reaction using a premade kit. Brain stroke was induced in the left cerebral hemisphere of CD-1 mice by occluding the middle cerebral artery for 1 h, and then allowing reperfusion by removing the occlusion. One day post-ictus, perfusion single-photon emission tomography (SPECT) was performed with 99mTc-lableled hexamethylpropyleneamine oxime (HMPAO), followed by PET acquisition with FGA. Plasma and brain tissue homogenates were assayed for markers of inflammation and neurotrophins. The kit-based synthesis was able to convert up to 2.2 GBq of FDG into FGA within 5 min. PET images showed 375 % more accumulation of FGA in the ipsilateral hemisphere than in the contralateral hemisphere. SPECT images showed that the ipsilateral HMPAO accumulation was reduced to 55 % of normal levels; there was a significant negative correlation between the ipsilateral accumulation of FGA and HMAPO (p < 0.05). FGA accumulation in stroke also correlated with IL-6 levels in the ipsilateral hemisphere. There was no change in IL-6 or TNFα in the plasma of stroke mice. Accumulation of FGA correlated well with the perfusion defect and inflammatory injury. As a PET agent, FGA has potential to image infarcted core in the brain stroke injury with high sensitivity, resolution, and specificity.
ppGpp Coordinates Nucleotide and Amino-Acid Synthesis in E. coli During Starvation.

Summary (p)ppGpp is a nucleotide messenger universally produced in bacteria following nutrient starvation. In E. coli, ppGpp inhibits purine nucleotide synthesis by targeting several different enzymes, but the physiological significance of their inhibition is unknown. Here, we report the structural basis of inhibition for one target, Gsk, the inosine-guanosine kinase. Gsk creates an unprecedented, allosteric binding pocket for ppGpp by restructuring terminal sequences, which restrains conformational dynamics necessary for catalysis. Guided by this structure, we generated a chromosomal mutation that abolishes Gsk regulation by ppGpp. This mutant strain accumulates abnormally high levels of purine nucleotides following amino-acid starvation, compromising cellular fitness. We demonstrate that this unrestricted increase in purine nucleotides is detrimental because it severely depletes pRpp and essential, pRpp-derived metabolites, including UTP, histidine, and tryptophan. Thus, our results reveal the significance of ppGpp’s regulation of purine nucleotide synthesis and a critical mechanism by which E. coli coordinates biosynthetic processes during starvation.
Associations Between Tenofovir Diphosphate in Dried Blood Spots, Impaired Physical Function, and Fracture Risk.

Background In this study, we evaluate associations between cumulative antiretroviral adherence/exposure, quantified using tenofovir diphosphate (TFV-DP) in dried blood spots (DBS), and human immunodeficiency virus (HIV)-related aging factors. Methods This is a cross-sectional analysis of younger (ages 18-35) and older (ages ≥60) persons with HIV (PWH) taking TFV disoproxil fumarate. Tenofovir diphosphate concentrations were quantified in DBS. Linear and logistic regression models were used to evaluate associations between TFV-DP and bone mineral density (BMD), physical function, frailty, and falls. Results Forty-five PWH were enrolled (23 younger, 22 older). Every 500 fmol/punch (equivalent to an increase in ~2 doses/week) increase in TFV-DP was associated with decreased hip BMD (-0.021 g/cm2; 95% confidence interval [CI], -0.040 to -0.002; P = .03). Adjusting for total fat mass, every 500 fmol/punch increase in TFV-DP was associated with higher odds of Short Physical Performance Battery impairment (score ≤10; adjusted odds ratio [OR], 1.6; 95% CI, 1.0-2.5; P = .04). Every 500 fmol/punch increase in TFV-DP was associated with slower 400-meter walk time (14.8 seconds; 95% CI, 3.8-25.8; P = .01) and remained significant after adjusting for age, lean body mass, body mass index (BMI), and fat mass (all P ≤ .01). Every 500 fmol/punch increase in TFV-DP was associated with higher odds of reporting a fall in the prior 6 months (OR, 1.8; 95% CI, 1.1-2.8; P = .02); this remained significant after adjusting for age, lean body mass, BMI, and total fat mass (all P Conclusions Higher TFV-DP levels were associated with lower hip BMD, poorer physical function, and greater risk for falls, a concerning combination for increased fracture risk.
Machine Learning-Assisted UAV Operations with the UTM: Requirements, Challenges, and Solutions

Unmanned aerial vehicles (UAVs) are emerging in commercial spaces and will support many applications, such as smart agriculture, dynamic network deployment, network coverage extension, surveillance and security. The unmanned aircraft system (UAS) traffic management (UTM) provides a framework for safe UAV operation by integrating UAV controllers and central data bases through a communications network. This paper discusses the challenges and opportunities for machine learning (ML) for effectively providing critical UTM services. We introduce the four pillars of UTM—operation planning, situational awareness, failure detection and recovery, and remote identification—and discuss the main services, specific opportunities for ML and the ongoing research. We conclude that the multi-faceted operating environment and operational parameters will benefit from collected data and data-driven algorithms, as well as online learning to support new UAV operation situations.