cssi/SciSciGPT-SciSciNet huggingface dataset:
Force suppression and the crossbridge cycle in swine carotid artery

Cyclic nucleotides can relax arterial smooth muscle without reductions in crossbridge phosphorylation, a process termed force suppression. There are two potential mechanisms for force suppression: 1) phosphorylated crossbridges binding to thin filaments could be inhibited or 2) the attachment of thin filaments to anchoring structures could be disrupted. These mechanisms were evaluated by comparing histamine-stimulated swine arterial smooth muscle with and without forskolin-induced force suppression and with and without latrunculin-A-induced actin filament disruption. At matched force, force suppression was associated with higher crossbridge phosphorylation and shortening velocity at low loads when compared with tissues without force suppression. Shortening velocity at high loads, noise temperature, hysteresivity, and stiffness did not differ with and without force suppression. These data suggest that crossbridge phosphorylation regulates the crossbridge cycle during force suppression. Actin disruption with latrunculin-A was associated with higher crossbridge phosphorylation when compared with tissues without actin disruption. Shortening velocity, noise temperature, hysteresivity, and stiffness did not differ with and without actin disruption. These data suggest that actin disruption interferes with regulation of crossbridge cycling by crossbridge phosphorylation. Stiffness was linearly dependent on stress, suggesting that the force per attached crossbridge was not altered with force suppression or actin disruption. These data suggest a difference in the mechanical characteristics observed during force suppression and actin disruption, implying that force suppression does not mechanistically involve actin disruption. These data are most consistent with a model where force suppression involves the inhibition of phosphorylated crossbridge binding to thin filaments.
Application of space lidar to the remote sensing of clouds and aerosols

Clouds and aerosols have important influences on the climate and remote sensing from space is required to assess their effects on a global scale. Current capabilities to observe clouds and aerosols using passive satellite sensors are limited, however. The Lidar In-space Technology Experiment, flown on the space shuttle in September 1994, demonstrated the application of space lidar to the study of clouds and aerosols. Lidar technology has now matured to a point where satellite lidars are feasible. Space lidar will provide new measurement capabilities and provide improved detection and characterization of the role of aerosol and cloud in global climate.
Joint classifier and feature optimization for cancer diagnosis using gene expression data

Recent research has demonstrated quite convincingly that accurate cancer diagnosis can be achieved by constructing classifiers that are designed to compare the gene expression profile of a tissue of unknown cancer status to a database of stored expression profiles from tissues of known cancer status. This paper introduces the JCFO, a novel algorithm that uses a sparse Bayesian approach to jointly identify both the optimal nonlinear classifier for diagnosis and the optimal set of genes on which to base that diagnosis. We show that the diagnostic classification accuracy of the proposed algorithm is superior to a number of current state-of-the-art methods in a full leave-one-out cross-validation study of two widely used benchmark datasets. In addition to its superior classification accuracy, the algorithm is designed to automatically identify a small subset of genes (typically around twenty in our experiments) that are capable of providing complete discriminatory information for diagnosis. Focusing attention on a small subset of genes is not only useful because it produces a classifier with good generalization capacity, but also because this set of genes may provide insights into the mechanisms responsible for the disease itself. A number of the genes identified by the JCFO in our experiments are already in use as clinical markers for cancer diagnosis; some of the remaining genes may be excellent candidates for further clinical investigation. If it is possible to identify a small set of genes that is indeed capable of providing complete discrimination, inexpensive diagnostic assays might be widely deployable in clinical settings.
Identification of an endo-β-1,4-d-Xylanase from Magnaporthe grisea by Gene Knockout Analysis, Purification, and Heterologous Expression

Magnaporthe grisea (Hebert) Barr (anamorph, Pyricularia oryzae Cav. or Pyricularia grisea) is the causal agent of the devastating rice blast disease (31). M. grisea primarily infects rice but also infects other Poaceae such as wheat and barley. There have been extensive studies of the cellular and molecular basis underlying M. grisea-plant interactions, particularly of the signal transduction pathways leading to early events of fungal infection (for a review, see reference 31). The recent publication of the M. grisea genome sequence is a cornerstone upon which the molecular interactions between a major crop killer and its plant hosts may be elucidated (9). Also, the ongoing accumulation and increased accessibility of large numbers of expressed sequence tags (ESTs) is greatly expediting the identification of individual proteins and the elucidation of gene expression profiles acquired under various environmental and culture conditions (14, 22, 23). We now describe the identification of an endoglycanase gene from a pool of ESTs of M. grisea grown on rice cell walls (RCWs) as its carbon source. The primary walls of plant cells (6) are pivotal battlegrounds between microbial pathogens and their plant hosts (8, 13, 19, 32-34, 38). Microbial pathogens secrete an array of cell wall-degrading enzymes (CWDEs) capable of depolymerizing the noncellulosic polysaccharides of primary cell walls (2, 10, 11, 18, 19, 37). For example, the recently published M. grisea genome sequence unveiled the possible presence of as many as 20 xylanase genes, which encode six glycoside hydrolase family 10 (GH10), five GH11, and nine GH43 members (reference 9 and unpublished genome-mining data of this laboratory). This high level of redundancy is an indication that xylanase activity is essential for the vitality of M. grisea, either saprophytically or pathogenetically or both. We previously described the purification, cloning, and gene knockout analyses of two endo-β-1,4-d-xylanases (EC 3.2.1.8) secreted by M. grisea (35, 37). We also provided evidence of the presence of at least three other xylanases encoded by M. grisea (37). PCR using degenerated oligonucleotide primers also allowed amplification and cloning of three putative xylanase genes, XYL-3, XYL-4, and XYL-5 (GenBank accession numbers {"type":"entrez-nucleotide","attrs":{"text":"AY144348","term_id":"24496242","term_text":"AY144348"}}AY144348 to 144350) (manuscript in preparation). We now show that one of the M. grisea ESTs encodes a hitherto-undiscovered family GH10 endo-β-1,4-d-xylanase that also possesses a class III (fungal) carbohydrate-binding domain (fCBD) (13, 20, 27).
The Clinical Challenge of Predicting and Preventing Sudden Cardiac Death Immediately after Myocardial Infarction

Despite many advances in treatment of myocardial infarction (MI) with percutaneous coronary intervention (PCI) and pharmacologic therapies, mortality immediately after MI remains high in patients with impaired left ventricular function. One of the greatest challenges facing the contemporary cardiologist is predicting and preventing sudden cardiac death (SCD) immediately after MI. Unfortunately, the trials assessing the role of the implantable cardioverter defibrillator (ICD) in patients at high risk for SCD immediately post MI have failed to show survival benefit. Current clinical guidelines restrict ICD implants to patients at least 40 days after MI with continued left ventricular dysfunction while on optimal medical therapy. It is evident that additional research is needed to identify strategies to prevent SCD and improve survival immediately after MI. In the meantime, clinicians should optimize and individualize therapy in the immediate post MI patient while carefully considering the risk of SCD and the competing risk of mortality from other causes.
Imprecise excision of the Caenorhabditis elegans transposon Tc1 creates functional 5' splice sites.

Abstract Imprecise excision of the Caenorhabditis elegans transposon Tc1 from a specific site of insertion within the unc-54 myosin heavy chain gene generates either wild-type or partial phenotypic revertants. Wild-type revertants and one class of partial revertants contain insertions of four nucleotides in the unc-54 third exon (Tc1 "footprints"). Such revertants express large amounts of functional unc-54 myosin despite having what would appear to be frameshifting insertions in the unc-54 third exon. We demonstrate that these Tc1 footprints act as efficient 5' splice sites for removal of the unc-54 third intron. Splicing of these new 5' splice sites to the normal third intron splice acceptor removes the Tc1 footprint from the mature mRNA and restores the normal translational reading frame. Partial revertant unc-54(r661), which contains a single nucleotide substitution relative to the wild-type gene, is spliced similarly, except that the use of its new 5' splice site creates a frameshift in the mature mRNA rather than removing one. In all of these revertants, two alternative 5' splice sites are available to remove intron 3. We determined the relative efficiency with which each alternative 5' splice site is used by stabilizing frameshifted mRNAs with smg(-) genetic backgrounds. In all cases, the upstream member of the two alternative sites is used preferentially (> 75% utilization). This may reflect an inherent preference of the splicing machinery for the upstream member of two closely spaced 5' splice sites. Creation of new 5' splice sites may be a general characteristic of Tc1 insertion and excision events.
Puberty in Developmentally Delayed or Physically Challenged Patients

Puberty is a time of both physical and psychological changes where patients have increasing special needs regarding sexual education, prevention of sexual abuse, and prevention of pregnancy and sexually transmitted infections. Patients with both cognitive and physical disabilities need the same reproductive health care as women without disabilities but may also need specialized care depending on the underlying disability.
Want Better Business Theories? Maybe Karl Popper Has the Answer

Sumantra Ghoshal, in his recent Academy of Management Learning & Education article, argued that management theories currently taught in MBA programs are the causal factor in triggering (a), the rec...
Investigation of Non-adiabatic Molecular Dynamics with Attosecond Transient Absorption

We investigate superexcited molecules with attosecond transient absorption. Spectral lineshape evolution helps resolve the autoionization and predissociation dynamics. Strong-field control is explored and the symmetry of electronic states is found to play an important role.
The Human Liver Fatty Acid Binding Protein T94A Variant Alters the Structure, Stability, and Interaction with Fibrates

Although the human liver fatty acid binding protein (L-FABP) T94A variant arises from the most commonly occurring single-nucleotide polymorphism in the entire FABP family, there is a complete lack of understanding regarding the role of this polymorphism in human disease. It has been hypothesized that the T94A substitution results in the complete loss of ligand binding ability and function analogous to that seen with L-FABP gene ablation. This possibility was addressed using the recombinant human wild-type (WT) T94T and T94A variant L-FABP and cultured primary human hepatocytes. Nonconservative replacement of the medium-sized, polar, uncharged T residue with a smaller, nonpolar, aliphatic A residue at position 94 of the human L-FABP significantly increased the L-FABP α-helical structure content at the expense of β-sheet content and concomitantly decreased the thermal stability. T94A did not alter the binding affinities for peroxisome proliferator-activated receptor α (PPARα) agonist ligands (phytanic acid, fenofibrate, and fenofibric acid). While T94A did not alter the impact of phytanic acid and only slightly altered that of fenofibrate on the human L-FABP secondary structure, the active metabolite fenofibric acid altered the T94A secondary structure much more than that of the WT T94T L-FABP. Finally, in cultured primary human hepatocytes, the T94A variant exhibited a significantly reduced extent of fibrate-mediated induction of PPARα-regulated proteins such as L-FABP, FATP5, and PPARα itself. Thus, while the T94A substitution did not alter the affinity of the human L-FABP for PPARα agonist ligands, it significantly altered the human L-FABP structure, stability, and conformational and functional response to fibrate.
Surgical Treatment of Olfactory Neuroblastoma: Major Complication Rates, Progression Free and Overall Survival.

Objective We aimed to compare major complication rates in patients undergoing open versus endoscopic resection of olfactory neuroblastoma (ONB) and to determine the prognostic utility of the Kadish staging and Hyams grading systems with respect to progression-free survival (PFS) and overall survival (OS). Methods It is a retrospective review of experience in treating ONB at a single tertiary care hospital from 1987 through 2015. Major complications were defined as cerebrospinal fluid (CSF) leak, meningitis, osteomyelitis, tracheostomy, and severe neurologic injury. Results Forty-one patients were included. An open approach was used in 34 (83%), endoscopic in 6 (15%), and combined in 1 (2%) case. Rates of major complications by surgical approach were 17% after endoscopic versus 31% after open ( p = 0.65). There was no significant difference in PFS or OS based on Kadish B versus C (PFS, p = 0.28; OS, p = 0.11) or Hyams grade 1 and 2 versus Hyams grade 3 and 4 (PFS, p = 0.53; OS, p = 0.38). Conclusions There was no significant difference in major complications between open and endoscopic approaches for the treatment of ONB. Patient stratification using the Kadish staging and Hyams grading systems did not show significant differences in PFS or OS. Further research is needed to determine if a different staging system would better predict patient outcomes.
Fermentation conditions of penicillinase by Acinetobactercalcoaceticus WM1

Penicillinase production was carried out by submerged fermentation with Acinetobacter calcoaceticus WM1.The effects of carbon source,nitrogen source,metal ion,initial pH,inoculum and temperature on penicillinase synthesis were studied.The optimal fermentation conditions were as followed: the temperature 37℃,the initial pH 7.0,the inoculum 10%,glucose concentration 2%,yeast extract powder 0.3% and magnesian ion concentration 0.01%.Underthese conditions,activities of penicillinase reached 82.72 U/(ml.h).
Advances in the medical management of patients with HIV-1 infection: an overview

New guidelines for the management of patients with HIV-1 infection emphasize early aggressive treatment using multi-drug combination regimens. Accurate assessment of the effectiveness of these treatments and their potential (small as it now seems) to eradicate HIV-1 infection requires testing for viral levels in the blood, and in other compartments that may serve as long-term viral reservoirs, using the most sensitive assays. At present, most of our information regarding triple-drug combination therapies (usually two nucleosides and a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor) has come from the assessment of viral levels in blood. Available results strongly support the virologic superiority of such treatments over monotherapy and two-drug combinations. There are important questions that remain to be answered regarding these highly effective therapies. Questions regarding the durability of these treatments in preventing the evolution of drug resistance can be addressed by using sensitive reverse transcription/polymerase chain reaction assays to assess treatment response. Others, such as how best to treat patients who have failed potent drug therapy, await results from new, large-scale, clinical trials. An important concern with respect to newer antiretroviral therapies is their complexity and thus the increased risk for non-compliance and resultant viral resistance. In addition, longer-term side-effects are increasingly recognized. Programs that enhance compliance with these treatments will increase the probability that they will provide durable suppression of viral replication and arrest the clinical progression of HIV disease.
An In Vivo Gain-of-Function Screen Identifies the Williams-Beuren Syndrome Gene GTF2IRD1 as a Mammary Tumor Promoter.

The broad implementation of precision medicine in cancer is impeded by the lack of a complete inventory of the genes involved in tumorigenesis. We performed in vivo screening of ∼1,000 genes that are associated with signaling for positive roles in breast cancer, using lentiviral expression vectors in primary MMTV-ErbB2 mammary tissue. Gain of function of five genes, including RET, GTF2IRD1, ADORA1, LARS2, and DPP8, significantly promoted mammary tumor growth. We further studied one tumor-promoting gene, the transcription factor GTF2IRD1. The mis-regulation of genes downstream of GTF2IRD1, including TβR2 and BMPR1b, also individually promoted mammary cancer development, and silencing of TβR2 suppressed GTF2IRD1-driven tumor promotion. In addition, GTF2IRD1 is highly expressed in human breast tumors, correlating with high tumor grades and poor prognosis. Our in vivo approach is readily expandable to whole-genome annotation of tumor-promoting genes.
Urachal adenocarcinoma: incidental finding at the time of surgery for ruptured appendicitis.

BACKGROUND The urachus is a vestigial structure between the dome of the bladder and the umbilicus. Tumors may develop from the remnants, most of which are well-differentiated, mucinous adenocarcinomas. Urachal adenocarcinoma is an exceedingly rare type of tumor. METHODS We present a case of a 51-year-old female presenting to our institution with complaints of abdominal pain for 36 hours. The patient was taken to the operating room for an acute appendicitis. Laparoscopy was performed, and gross purulence and appendiceal perforation were noted as well as a mass on the anterior abdominal wall. Based on the location of the mass, we converted to an open midline laparotomy to treat both the perforated appendicitis and to remove the mass. RESULTS Pathology confirmed the diagnosis of perforated appendicitis and a mucinous-producing urachal adenocarcinoma. DISCUSSION Data support both open and laparoscopic approaches for appendicitis. This case, although rare, highlights the importance of laparoscopy in a complete and thorough examination of the abdominal cavity. A standard right lower quadrant incision for an open technique would likely have resulted in omission of this lesion, and the patient would have presented at a more typical late stage of her cancer development with significantly more morbidity.
Glucose Transporter 1 Deficiency and Myoclonic Astatic Epilepsy

Researchers at University of Melbourne, Australia; University of Florence, Italy; and University of Antwerp, Belgium performed genetic analysis on 84 unrelated probands with myoclonic-astatic epilepsy (MAE).
A multi-purpose quality assurance tool for MLC-based IMRT

Intensity modulated radiation therapy (IMRT) has emerged as a maturing clinical technology. More fields are often used in an IMRT treatment than in conventional conformai therapy. Complex intensity distributions in the fields are planned in order to spare critical structures adjacent to the planning target volume (PTV). The complexity of IMRT has led most facilities gaining experience with this new technology to adopt a conservative quality assurance (QA) process. This extensive QA has been a limiting factor to the wide spread use of IMRT. A QA program involves virtually every aspects of treatment planning and delivery, including verification of intensity maps for each field, absolute dose at given points, and the integrity of the hardware and software of the beam delivery systems. In order to verify the patient position, digitally reconstructed radiographs (DRR) in the beam’s eye view (BEV) are computed as references for, checking the setup accuracy and target localization during treatment using portal imaging. In our clinic, a QA protocol, which is similar to the prototype IMRT QA program described by Burman et al, has been implemented.1
Non-Hermitian coupled-mode theory for incoherently pumped exciton-polariton condensates

The generalized Gross-Pitaevskii equation (gGPE) is an effective phenomenological description for the dynamics of incoherently pumped exciton-polariton condensates. However, a brute force numerical simulation of the gGPE provides little physical insight into condensate formation under arbitrary pumping configurations, and is demanding in terms of computational resources. We introduce in this paper a modal description of polariton condensation under incoherent pumping of arbitrary spatial profile, based on eigenmodes of the non-Hermitian generator of the linearized dynamics. A pump-dependent basis is then introduced to formulate a temporal coupled-mode theory that captures condensate dynamics in the presence of all nonlinear interactions. Simulations using a single set of modes for a given pumping and trapping configuration agree very well with a full integration of the gGPE in diverse dynamical regimes, supporting the validity of this modal description, while also providing a speedup in simulation times.
Controllability, Approximations and Stabilization

A wide variety of systems in e.g. engineering or biological applications can be described or modelled by control systems (or controlled differential equations) of the general form \(\dot x = F\left( {x,u} \right)\) where the state a; is a point on a smooth manifold, the control u takes values in a compact interval or another manifold and is integrable as a function of time, and for each fixed value of u the vector field F(·,u) is smooth. One of the main topics in the investigation of such systems is the problem of understanding the local behaviour near an equilibrium point x0, or more generally near a reference trajectory.
Introgression of acylsugar chemistry QTL modifies the composition and structure of acylsugars produced by high-accumulating tomato lines

Acylsugars are important insect defense compounds produced at high levels by glandular trichomes of the wild tomato, Solanum pennellii. The ability to produce acylsugars at elevated levels was bred into the tomato line CU071026. This study utilized a marker-assisted backcross approach to individually introgress into CU071026 and to fine map the three quantitative trait loci (QTL) fatty acid 5 (FA5QTL), fatty acid 7 (FA7QTL), and fatty acid 8 (FA8QTL), which were previously associated with changes in acylsugar chemistry. Additional breeding with and fine mapping the previously introgressed QTL, fatty acid 2 (FA2QTL), was also conducted. The effect of these four QTL on acylsugar quality and quantity in the presence of the five introgressions of CU071026 was evaluated. Incorporation of the QTL altered acylsugar chemotype by modulating the length, orientation, and/or relative proportion of fatty acid acyl groups. The resulting quantities of acylsugar produced in most of the new lines were similar to that of CU071026; however, introgression of FA5QTL reduced acylsugar levels. The acylsugar lines containing each QTL were characterized for acylsugar level, trichome abundance, and acylsugar chemistry through gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry. The novel acylsugar chemotype lines created can contribute to elucidation of the mechanism of insect resistance mediated by acylsugars and help with identification of yet-unknown genes contributing to acylsugar synthesis and diversity.
mTOR Inhibition for Relapsed or Refractory Hodgkin Lymphoma: Promising Single Agent Activity with Everolimus (RAD001).

Background: mTOR inhibition has produced responses in mantle cell lymphoma as well as other non-Hodgkin lymphomas. This phase II study tested the oral mTOR inhibitor everolimus (RAD001, Novartis Pharmaceuticals) in simultaneous two-stage phase II lymphoma studies, including one arm involving Hodgkin lymphoma. The goals were to learn the toxicity profile and to assess the anti-tumor response. A total of 17 patients with Hodgkin lymphoma were enrolled in the uncommon arm at completion of enrollment. Methods: Patients (pts) received 10 mg PO daily for each 28 day cycle (up to 12, with a possible extension in responders) and restaged after 2, 6, and 12 cycles. The primary endpoint is the confirmed response rate, including CR, CRu or PR. Results: The median age of the 17 pts with Hodgkin lymphoma was 37 yrs (range: 27–68), with a median of 6 (range, 4–14) prior therapies. Fourteen pts (82.4%) had a prior stem cell transplant (SCT). Pts completed a median of 6 (range, 1–13) cycles of therapy. Fifteen of 17 patients were evaluable for response as of this analysis. The overall response rate was 47% (7/15), all partial responses. Ten patients are continuing on study while 6 have gone off due to disease progression and 1 due to other reasons. Common grade 3 adverse events (AEs) include thrombocytopenia (5 pts), anemia (5 pts) and alkaline phosphatase elevation (1 pts). 1 patient was reported to have grade 4 neutropenia. Conclusions: Oral everolimus has promising activity with acceptable toxicity in Hodgkin lymphoma. These results provide the rationale for additional studies with this novel class of agents and to integrate mTOR inhibitors into salvage treatment regimens for Hodgkin lymphoma.
Early cytoplasmic uncoating is associated with infectivity of HIV-1

After fusion, HIV delivers its conical capsid into the cytoplasm. To release the contained reverse-transcribing viral genome, the capsid must disassemble in a process termed uncoating. Defining the kinetics, dynamics, and cellular location of uncoating of virions leading to infection has been confounded by defective, noninfectious particles and the stochastic minefield blocking access to host DNA. We used live-cell fluorescent imaging of intravirion fluid phase markers to monitor HIV-1 uncoating at the individual particle level. We find that HIV-1 uncoating of particles leading to infection is a cytoplasmic process that occurs ∼30 min postfusion. Most, but not all, of the capsid protein is rapidly shed in tissue culture and primary target cells, independent of entry pathway. Extended time-lapse imaging with less than one virion per cell allows identification of infected cells by Gag-GFP expression and directly links individual particle behavior to infectivity, providing unprecedented insights into the biology of HIV infection.
An Existential Ecofeminism and a Renewed Critical Theory of Nature: An Imagined Dialogue between Simone de Beauvoir and Jürgen Habermas

Simone de Beauvoir has been commonly criticized for separating women from nature and attempting to make women “like men”, as beings that dominate nature. I defend Beauvoir’s existential concept of freedom as a non-sovereign relationship with nature. I then use the existential model constructed from my defense of Beauvoir as a framework with which to critique and engage Jurgen Habermas’ 2001 intervention against liberal eugenics. My critique of Habermas is important because I would like to explore a renewed critical theory of nature from the perspective gained by an existential ecofeminism.
Resilience-based network design under uncertainty

Abstract This paper introduces an approach to quantify resilience for the design of systems that can be described as a network. A key characteristic of resilience is the ability of restoring functionality and performance in response to a disruptive event. Therefore, the restoration behavior is encapsulated via a non-linear function that provides the ability to model at the component level more refined attributes of restoration. In particular, it considers the remaining capacity (absorptive ability), the degree to which capability can be recovered (restoration ability) and the recovery speed. The component restoration functions can then be used to impose a resilience target at a given time as a design constraint. The resilience-based design optimization is then formulated for both deterministic and stochastic cases of a network system. The objective is to have as the design solution a network that incurs the least cost while meeting system resilience constraints. Maximum flow through the network is used as a measure of system performance. Several possible links are examined with regards to flow performance from origin node to a destination node. A probabilistic solution discovery algorithm is combined with stochastic ranking to approach this problem. Two numerical examples are used to illustrate the procedure and the effectiveness of the proposed method.
The 4-N-acyl and 4-N-alkyl gemcitabine analogues with silicon-fluoride-acceptor: Application to 18 F-Radiolabeling

Abstract The coupling of gemcitabine with functionalized carboxylic acids using peptide coupling conditions afforded 4-N-alkanoyl analogues with a terminal alkyne or azido moiety. Reaction of 4-N-tosylgemcitabine with azidoalkyl amine provided 4-N-alkyl gemcitabine with a terminal azido group. Click reaction with silane building blocks afforded 4-N-alkanoyl or 4-N-alkyl gemcitabine analogues suitable for fluorination. RP-HPLC analysis indicated better chemical stability of 4-N-alkyl gemcitabine analogues versus 4-N-alkanoyl analogues in acidic aqueous conditions. The 4-N-alkanoyl gemcitabine analogues showed potent cytostatic activity against L1210 cell line, but cytotoxicity of the 4-N-alkylgemcitabine analogues was low. However, 4-N-alkanoyl and 4-N-alkyl analogues had comparable antiproliferative activities in the HEK293 cells. The 4-N-alkyl analogue with a terminal azide group was shown to be localized inside HEK293 cells by fluorescence microscopy after labelling with Fluor 488-alkyne. The [18F]4-N-alkyl or alkanoyl silane gemcitabine analogues were successfully synthesized using microscale and conventional silane-labeling radiochemical protocols. Preliminary positron-emission tomography (PET) imaging in mice showed the biodistribution of [18F]4-N-alkyl to have initial concentration in the liver, kidneys and GI tract followed by increasing signal in the bone.
Spectrum-based comparison of multivariate complex random signals of unequal lengths

We consider the problem of comparing two complex multivariate random signal realizations of unequal lengths, to ascertain whether they have identical power spectral densities. A binary hypothesis testing approach is formulated and a generalized likelihood ratio test (GLRT) is derived. An asymptotic analytical solution for calculating the test threshold is provided. The results are illustrated via computer simulations. Past work on this problem is limited to either complex or real signals of equal lengths, or to real-valued scalar signals of unequal lengths. The proposed test has applications in diverse areas including user authentication in wireless networks with multiantenna receivers.
Implications of Consumer Heterogeneity with Online and Offline Channels of Distribution

The existing models of search cost and their applications to the internet markets, implicitly assume the consumers in the electronic markets to be essentially the searchers while those in the physical market typically constitute the non-searcher population. This paper departs from this traditional assumption to include a group of searcher and non-searcher in each of the physical and internet markets respectively for a homogenous good. The paper builds on the theoretical framework of Stahl (1989) to show that an increased share of people with internet access creates a positive externality by reducing the expected price in the overall market. However, this is associated with a higher dispersion of prices in the overall market. We also show that the searchers in the internet market on average pays a lower price than the searcher in the offline market. The same result is also found to hold true for the non-searchers in the two markets.
Fear-avoidance beliefs and parental responses to pain in adolescents with chronic pain

BACKGROUND: The fear-avoidance model of chronic pain posits that fear of pain is associated with fear and avoidance of activity, which can lead to deconditioning and persistence of pain and disability. Despite being well supported in adults, little is known about the role of fear-avoidance beliefs regarding physical activity in children. Research has shown that parental protectiveness contributes to activity limitations in children; however, no studies have examined relationships between protectiveness, and fear and avoidance.
The Dermal-Epidermal Basement Membrane Zone in Cutaneous Wound Healing

The formation and repair of the functional extracellular matrix as part of the wound healing process requires coordinate expression of a repertoire of related and unrelated genes, including those encoding matrix proteins and proteolytic and regulatory enzymes. In addition, the formation of a functionally organized basement membrane between the epidermis and the dermis is essential for the integrity of the skin to allow its function as a protective organ. This chapter will highlight the recent progress made in understanding the biochemistry and molecular biology of the cutaneous basement membrane zone.
High Frequency Power Integrity Design Sensitivity to Package Design Rules

Package design rules are traditionally determined by signal integrity reasons. However, these determine the total package inductance and the number of capacitors that can be installed, in turn determining the highest frequency impedance peak in the power delivery network. This paper provides an overview of design rule impact to electrical metrics. Simple equations and simulations based on electromagnetic extractions of representative microprocessor packages are utilized throughout. Based on these guidelines are provided for capacitor spacing and PTH size & placement evaluation as logic block sizes shrink with process node advancement.
Protein and polypeptide hormones as inhibitors

It is becoming increasingly apparent that hormones regulate morphogenetic processes and metabolic reactions through inhibitory mechanisms as well as stimulatory effects. Inhibition by protein and polypeptide hormones and the numerous analogs that have been prepared, was discussed in a recent article (1). The present brief review is concerned with more recent developments in this field, including the role of protein and polypeptide hormones in the control of cell proliferation and differentiation.
On the Reliability of 97% Carbon Content Graphene-based Transmission Lines in Bending Applications and Comparison to Copper and Aluminum Conductors

In our modern world, the use of conformal surfaces to implement various wireless systems is gaining in popularity. Though many flexible substrates are being developed, the conductive materials are fragile and prone to breakage caused by the repetitive bending at a specific spot. Therefore, understanding the bending on the electromagnetic characteristics of different conductive materials is an important area to study. In this paper, the effect of bending on the top copper, aluminum and graphene-based conductors of microstrip transmission lines is studied. A fixture was developed to experimentally observe the bending characteristics of the different aforementioned TLs. The results in this paper showed that on average, after 57 iterations the aluminum connection failed, and after 74 iterations, the copper connection failed. Then, the fixture conducted 750 iterations on the graphene-based conductors and no failure was observed; showing the additional mechanical benefits of the graphene-based conductors. It was also shown that all the materials agreed on S-parameters in full wave simulations. Graphene-based conductive materials showed its superior reliability on bending applications without compromising the performance on the TL.
Cases of Student Reflection within a Course Using Standards-Based Grading

This Research-To-Practice Category Full Paper is a qualitative study of four students’ reflections on their performance and feedback on assignments in a required first-year engineering course. The intention was to gain a deep understanding of how students engage with a course’s standards-based grading (SBG) system to plan and act via an analysis of their structured reflections. The individual student cases are presented. A cross-case analysis focused on self-ratings compared to performance, actions and connections made to learning objectives, plans and connections made to learning objectives, and other insights is also presented. Implications for the design of SBG systems and accompanying reflections are discussed.
Biomechanical Evaluation of the Accuracy in Radiographic Assessment of Femoral Component Migration Measurement after Total Hip Arthroplasty.

Introduction: Implant subsidence is one criteria utilized to monitor for prosthesis loosening after total hip arthroplasty (THA) with initial implant subsidence assessment often done utilizing plain radiographs. The specific aim of this study was to identify the most reliable references when using plain radiographs to establish an image magnification with the goals being easy to use, inexpensive, reliable, and accurate. Methods: Two femoral stem implants (stem lengths: 127mm, 207mm) were utilized to simulate hemiarthroplasty of the hip with composite femurs. Different combinations of femoral stem distances from the radiographic film (ODD), source-detector differences (SDD), hip rotation, and hip flexion were elected. Standardized anterior-posterior pelvis for each parameter combination setup were taken. Radiographic measurements (head diameter, stem length, stem seating length) were undertaken five times by three examiners. Radiographic image magnification factors were generated from two references (head diameter and stem length). Radiograph measurement reproducibility and stem seating length errors using these magnification factors were evaluated. Results: High level of repeated measurements reliability was found for head diameter (99 ± 0%) and stem length (90 ± 7%) measurements, whereas seating length measurements were less reliable (76 ± 6%). Stem length error using the femoral head magnification factor yielded 11% accuracy. Stem seating length error using both magnification factors were not reliable (< 7% accuracy). All parameters, except SDD, showed significant effect on calibrated measurement error. Conclusions: Current methods of assessing implant subsidence after THA using plain radiographs are inaccurate or reliable. Clinicians should recognize these limitations and be cautious when diagnosing implant stability using plain radiographs alone.
Female Gender Predicts Augmented Immune Infiltration in Lung Adenocarcinoma.

Abstract Introduction Immune infiltration in lung adenocarcinomas (LUADs) has been associated with response to immune checkpoint inhibitors. Clinical features underlying differential responses of patients with LUADs to immunotherapy are not well understood. Here, we analyzed the association between LUAD immune infiltration and clinicopathologic variables. Materials and Methods Intratumoral CD3, CD8, and CD68 cell densities (tumor-associated immune cells [TAICs]) were immunohistochemically assessed in 146 surgically resected LUADs. LUADs were classified into 2 groups, low and high TAICs, based on the median values of cell densities for CD3, CD8, and CD68. Somatic mutation burden and driver gene mutation status were analyzed in a subset of the cases (n = 92). We statistically analyzed the association between the TAIC groups and various clinicopathologic and molecular variables by using the χ2/Fisher and Wilcoxon sum tests and multivariable logistic regression models. Results Patient gender, tumor size, and STK11 mutations were significantly associated with TAIC levels in LUAD. Female patients exhibited significantly elevated TAIC levels (P = .005) compared with male patients. Tumor size was inversely associated with TAIC levels (P = .012). STK11 mutated tumors were associated with lower TAICs (P = .008). Higher TAICs were consistently observed in female patients with LUADs after adjusting for stage, tumor size, and age. Multivariable regression models confirmed female gender as an independent variable associated with TAIC levels in LUAD (P = .0141). Conclusion Immune infiltration in LUADs was significantly higher in female patients, warranting further exploration into the association between this clinical variable and immunotherapeutic response in LUAD.
Memory Forensics Against Ransomware

Ransomware leverages the unique knowledge of the cryptographic secrets, such as an encryption key, for ransom extraction. Therefore, acquiring the decryption key via exploitation of weak cryptographic implementations or side-channel attacks allows data restoration without the requirement of ransom payment. In this paper, we examine the effectiveness of physical memory forensics against ransomware to recover raw symmetric and asymmetric keys and demonstrate file decryption against several real-world ransomware. Furthermore, we deploy our own virulent ransomware that are equipped with an effective hybrid cryptosystem to explore the limits of such memory-based side-channel attacks on ransomware. Our results indicate that cryptographic keys can be discovered during encryption in the ransomware process memory for durations long enough to facilitate complete data recovery.
Aldehyde-Functionalized Magnetic Particles to Capture Off-Target Chemotherapeutic Agents.

Drug capture is a promising technique to prevent off-target chemotherapeutic agents from reaching systemic circulation and causing severe side effects. The current work examines the viability of using immobilized aldehydes for drug-capture applications via Schiff base formation between doxorubicin (DOX) and aldehydes. Commercially available pyridoxal-5′-phosphate (VB6) was immobilized on iron oxide nanoparticles (IONPs) to capture DOX from human serum. Leaching of VB6 persisted as a primary issue and thus various aldehydes with anchoring groups such as catechol, silatrane, and phosphonate esters have been studied. The phosphonate group-based anchor was the most stable and used for further capture studies. To improve the hydrophilic nature of the aldehydes, sulfonate-containing aldehydes and polyethylene glycols (PEGs) were investigated. Finally, the optimized functionalized iron oxide particles, PEGylated-IONP, were used to demonstrate doxorubicin capture from human serum at biologically relevant temperature (37 °C), time (30 min), and concentrations (μM). The current study sets the stage for the development of potential compact dimension capture device based on surface-anchorable polymers with aldehyde groups.
Association between tumor mutational burden (TMB) and immune-related adverse events (irAEs) in patients (pts) with metastatic urothelial carcinoma (mUC) during checkpoint immunotherapy.

489Background: Immune checkpoint inhibition (ICI) has greatly improved clinical outcomes for pts with mUC and other cancers. ICI is associated with a class of AEs, deemed irAEs due to immune activa...
Adaptable Resilience Assessment Framework to Evaluate an Impact of a Disruptive Event on Freight Operations

Freight transportation is a major economic backbone of the United States. Ports, as one of the primary components of freight transportation, have experienced significant growth and increased capaci...
EPIDEMIOLOGY IN THE ARMY

Excerpt I. INTRODUCTION The task of safeguarding the health of the American soldier, especially during war, is a responsibility of the entire medical profession of the United States. It has always ...
A new hierarchical architecture for multimedia distribution in integrated services networks

Due to their large bandwidth demand and synchronization requirements, multimedia applications, in general, consume huge buffer sizes which prevent potential customers from using multimedia services. We recognize the problem and propose a hierarchical architecture to reduce the buffer size. The architecture can be applied to both 1-n and n-n applications. We establish the architecture by first determining neighbor sets and then applying a grouping algorithm and renegotiation process. This architecture is also able to meet the synchronization requirements of multimedia applications. We evaluate the performance of the hierarchical architecture through simulation and compare with the direct connection architecture. The result shows that the hierarchical architecture reduces the buffer size significantly without serious penalty on the total bandwidth or introducing extra hot-spots.
Natural gas price elasticities: Variations by region and by sector in the USA

Abstract This article's primary objective is to estimate the own-price and cross-price elasticities of demand for natural gas in the residential, commercial and industrial sectors by DOE region in the USA. A simultaneous-equations model was developed and its reduced form was employed for natural gas consumption demand elasticity estimation in conjuction with the instrumental price variables. Data from 1967 to 1978 were used in the estimation, but the 1973 oil embargo effect was separated with the use of a dummy variable. The demand for natural gas was much more price elastic in the long run than in the short run, and the industrial sector was more less price sensitive than others. However, there were significant interregional and intersectoral variations among the elasticities estimated.
Inconsistent Choices in Lottery Experiments: Evidence from Rwanda

Lottery experiments have been performed in many contexts to test theories of risk aversion and to measure risk preferences. People are typically offered a series of lotteries with increasing expected payoffs and variances. A person with a concave utility function should switch from risky bets to safer bets at some point and never switch back. Switching back implies preferences inconsistent with a concave utility function. Our experiment, conducted with a population of adults in Rwanda, presents respondents with a series of binary-choice lotteries over gains and losses. We observe that 54-55% of subjects made at least one inconsistent choice over gains or losses, and 7-13% made at least two inconsistent choices. This holds for both hypothetical and real lottery payoffs. Inconsistent choices were less common when stakes were higher, and women are more likely to be inconsistent. While risk aversion alone is not correlated with actual economic outcomes, such as membership in savings (tontines) and insurance groups and holding a larger number of bank accounts, inconsistency is.