cssi/SciSciGPT-SciSciNet huggingface dataset:
Immune modulation of T-cell and NK (natural killer) cell activities by TEXs (tumour-derived exosomes)

Body fluids of cancer patients contain TEXs (tumour-derived exosomes). Tumours release large quantities of TEXs, and the protein content of exosome or MV (microvesicle) fractions isolated from patients’ sera is high. TEXs down-regulate functions of immune cells, thus promoting tumour progression. We isolated TEXs from tumour cell supernatants and sera of patients with solid tumours or AML (acute myelogenous leukaemia). The molecular profile of TEXs was distinct from that of circulating exosomes derived from normal cells. TEXs were co-incubated with activated T-cells, conventional CD4 + CD25 neg T-cells or CD56 + CD16 + NK (natural killer) cells respectively. TEXs down-regulated CD3ζ and JAK3 (Janus kinase 3) expression in primary activated T-cells and mediated Fas/FasL (Fas ligand)-driven apoptosis of CD8 + T-cells. TEXs promoted CD4 + CD25 neg T-cell proliferation and their conversion into CD4 + CD25 hi FOXP3 + (FOXP3 is forkhead box P3) Treg cells (regulatory T-cells), which also expressed IL-10 (interleukin 10), TGFβ1 (transforming growth factor β1), CTLA-4 (cytotoxic T-lymphocyte antigen 4), GrB (granzyme B)/perforin and effectively mediated suppression. Neutralizing antibodies specific for TGFβ1 and/or IL-10 inhibited the ability of TEXs to expand Treg cells. TEXs obtained at diagnosis from AML patients’ sera were positive for blast-associated markers CD33, CD34, CD117 and TGFβ1, and they decreased cytotoxic activity of NK cells isolated from NC (normal control) donors, induced Smad phosphorylation and down-regulated NKG2D receptor expression. Correlations between the TEX molecular profile or TEX protein levels and clinical data in cancer patients suggest that TEX-mediated effects on immune cells are prognostically important. In contrast with exosomes released by normal cells, TEXs have immunosuppressive properties and are involved in regulating peripheral tolerance in patients with cancer.
Closing ranks in vehicle formations based on rigidity

In this paper, a systematic way of maintaining rigidity in case of vehicle removals in formations for coordinating mobile autonomous vehicles with limited communication/sensing links is presented. The main concern is the minimal rearrangement of links in such a way that the links that have not been removed are preserved as they are, and the minimum number of new links are created in the formation to maintain rigidity. The problem is solved by the tools used in the Henneberg method. This method gives us provably rigid formations with the minimum number of links. The proposed framework meets this challenge for removed vehicles with any number of links in both 2 and 3-space. The same problem is also considered for the minimal Delaunay edge formations, which is a special class of the formations created by the Henneberg method with some geometrical properties.
COMPLEMENTARY ROLES OF MICROTUBULES AND MICROFILAMENTS IN THE LUNG FIBROBLAST-MEDIATED CONTRACTION OF COLLAGEN GELS: DYNAMICS AND THE INFLUENCE OF CELL DENSITY

Fibroblasts are important cellular components in wound healing, scar formation, and fibrotic disorders; and the fibroblast-populated collagen-gel (FPCG) model allows examination of fibroblast behavior in an in vitro three-dimensional environment similar to that in vivo. Contraction of free-floating FPCGs depends on an active and dynamic cytoskeleton, and the contraction dynamics are highly influenced by cell density. We investigated mechanistic differences between high- and low-cell density FPCG contraction by evaluating contraction dynamics in detail, using specific cytoskeletal disruptors. Collagen gels were seeded with human lung fibroblasts at either high (HD) or low (LD) density, and incubated with or without cytoskeletal disruptors colchicine (microtubules) or cytochalasin D (microfilaments). Gel area was measured daily. FPCG contraction curves were essentially sigmoidal, featuring an initial period of no contraction (lag phase), followed by a period of rapid contraction (log phase). Contraction curves of HD-FPCGs were distinct from those of LD-FPCGs. For example, HD-FPCGs had a negligible lag phase (compared with 3 d for LD-FPCGs) and exhibited a higher rate of log-phase contraction. Both colchicine and cytochalasin dose-dependently inhibited contraction but specifically affected different phases of contraction in HD- and LD-FPCGs; and colchicine inhibited LD-FPCGs much more than HD-FPCGs. The data indicate that LD- and HD-FPCGs contract through different primary mechanisms. Microtubules and microfilaments are both complementarily and dynamically involved in the contraction of FPCGs, and cell density influences primary cytoskeletal mechanisms. These results provide valuable information about fibroblast behavior in healing and fibrosis, and may suggest novel treatment options.
One approach to microprocessor implementation of 4800 b/s data modem for telephone channels

The microprocessor-based implementation of data modems has been attracting a great deal of scientific interest in the past decade. It is a kind of an interdisciplinary field where both information theory and microprocessor engineering strongly interact. A number of different microprocessor-based modems are avavilable on the market. For most of the modems with speeds above 2400 b/s it is common that implementation is based on the bit-slice processor. In case of speeds above 2400 b/s, it is considered that slow and cheap MOS microprocessors (e.g., Intel 8085) can be used only at the cost of simplifications in the algorithms for signal demodulation and detection, i.e., at the cost of decreased performance. This paper, however, describes the MOS microprocessor-based implementation of the 4800 b/s modem which was achieved without deterioration of modem performance.
WHAT ADOLESCENTS THINK THEY KNOW ABOUT NUTRITION AFFECTS WHAT THEY FEEL ABOUT NUTRITION AND WHAT THEY EAT

The purpose of this study was to determine if a child s nutritional beliefs influence their attitudes about certain foods, if these attitudes affect their intention to eat those foods, and if those intentions actually affect the child s eating patterns. The nutritional values of schoolchildren were investigated by conducting a survey of volunteers from grades 7 through 12. The survey offered a list of several foods and a list of adjectives from which students were to choose the one that best represented their attitudes towards a food or food group. The survey also posed questions regarding several other matters related to nutrition further allowing measurement of the student s knowledge of nutrition. Results were based on a survey from an audience that was 65 % female and 35 % male, with a majority of the feedback from grades 10 through 12. The responses were analyzed using simple regression and analysis of variance. The findings showed no significant difference by grade for nutritional beliefs, attitudes, intentions, or behaviors, nor was a distinction found among beliefs, attitudes, or intentions for gender. A considerable difference in eating behavior based on gender was noted. The female participants missed meals more ofen. Further results revealed that 60% of the students received information regarding nutrition from school, 62 % feel that they know “some ’’ about nutrition, and 61 ‘7% would like to increase their knowledge of nutrition. The study shows that children’s beliefs about nutrition are positively related to their attitudes about certain foods and these attitudes ’ Peter Bordi is an Assistant Professor of Hospitality Management; David Cranage is an Assistant Professor of Hospitality Marketing and Constance Cole is a Graduate Research Assistant.
Does physiologic breakdown mask significant pathology in endometrial biopsies? A retrospective case-control study.

Abstract Context.—Adequacy criteria for endometrial biopsy samples do not exist. Objective.—To assess the sensitivity of endometrial sampling for detecting neoplasia in the setting of extensive glandular and stromal breakdown. Design.—Retrospective case-control study. Surgical pathology records between 1996 and 2005 at Beth Israel Deaconess Medical Center (Boston, Mass) were searched for endometrial samples with diagnoses containing the key words “menstrual” or “extensive breakdown.” Hospital records for these women were parsed for demographics, clinical indications, and follow-up with rebiopsy within 6 months. Age cutoffs enriched the population for women at higher risk for carcinoma. A control group, consisting of 2 age-matched control patients for each test patient, was also studied; each control patient had an endometrial sample taken within a 6-month period and was not diagnosed with extensive breakdown, menstrual endometrium, or neoplasia on initial sampling. Results.—Fifty-four cases were identifie...
Effects of Communication Skills Training on Parents and Young Adolescents From Extreme Family Types

PROBLEM. What were the effects of a communication skills training intervention among a sample of young adolescents and parents who scored in the “extreme” range of the Circumplex Model of Family Systems? METHODS. Thirty-seven young adolescents and a parent (intervention group) participated in communication skills training 2 hours/week for 6 weeks. Their responses on measures of satisfaction with the family system and perceptions of communication were compared with those of 47 young adolescents and a parent who scored in the extreme range but did not participate in the training (control group). FINDINGS. Fathers and young adolescents demonstrated no change as a result of the program. Mothers who participated in skills training perceived communication with their young adolescent as more open than control mothers, but became increasingly dissatisfied with the family system.
What is the Problem with Experts

The phenomenon of expertise produces two problems for liberal democratic theory: the first is whether it creates inequalities that undermine citizen rule or make it a sham; the second is whether th...
PRUNER: algorithms for finding monad patterns in DNA sequences

We present new algorithms for discovering monad patterns in DNA sequences. Monad patterns are of the form (l,d)-k, where l is the length of the pattern, d is the maximum number of mismatches allowed, and k is the minimum number of times the pattern is repeated in the given sample. The time-complexity of some of the best known algorithms to date is O(nt/sup 2/l/sup d/|/spl Sigma/|/sup d/2/), where t is the number of input sequences, and n is the length of each input sequence. The first algorithm that we present takes O(n/sup 2/t/sup 2/l/sup d/2/|/spl Sigma/|/sup d/2/) and space O(ntl/sup d/2/|/spl Sigma/|/sup d/2/), and the second algorithm takes O(n/sup 3/t/sup 3/l/sup d/2/|/spl Sigma/|/sup d/2/ time using O(l/sup d/2/|/spl Sigma/|/sup d/2/) space. In practice, our algorithms have much better performance provided the d/l ratio is small.
Names of Our Lives

Identifiers are an essential component of online communication. My research focuses on the ways that social, technical and policy factors affect people's behavior with online identifiers. For example, my research demonstrates that people separate both business and professional roles by communicating with separate identifiers. People may have different identifiers for technical reasons, such as difficulties in configuring settings. In addition, corporate security policies place restrictions on people's communications which influences the way people manage identifiers. I conducted a series of in-depth interviews with two groups sampled from different populations.
A perfluorinated anion exchange membrane with a 1,4-dimethylpiperazinium cation

A perfluorinated anion exchange membrane with a 1,4-dimethylpiperazinium cation demonstrated better hydroxide ion conductivity and three-fold reduction in water uptake compared to a hydrocarbon AEM with the same cation. The perfluorinated AEM was stable over 30 days in 2 M KOH at 60 °C and demonstrated good fuel cell performance.
Engineering botulinum neurotoxin to extend therapeutic intervention

Clostridium botulinum neurotoxins (BoNTs) are effective therapeutics for a variety of neurological disorders, such as strabismus, blepharospam, hemificial spasm, and cervical dystonia, because of the toxin's tropism for neurons and specific cleavage of neuronal soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptors (SNARE) proteins. Modifying BoNT to bind nonneuronal cells has been attempted to extend therapeutic applications. However, prerequisite to develop nonneuronal therapies requires the retargeting the catalytic activity of BoNTs to nonneuronal SNARE isoforms. Here, we reported the engineering of a BoNT derivative that cleaves SNAP23, a nonneuronal SNARE protein. SNAP23 mediates vesicle-plasma membrane fusion processes, including secretion of airway mucus, antibody, insulin, gastric acids, and ions. This mutated BoNT/E light chain LC/E(K(224)D) showed extended substrate specificity to cleave SNAP23, and the natural substrate, SNAP25, but not SNAP29 or SNAP47. Upon direct protein delivery into cultured human epithelial cells, LC/E(K(224)D) cleaved endogenous SNAP23, which inhibited secretion of mucin and IL-8. These studies show the feasibility of genetically modifying LCs to target a nonneuronal SNARE protein that extends therapeutic potential for treatment of human hypersecretion diseases.
DUS An Efficient, Effective Sampling Method

Dollar unit sampling (DUS) is a statistical sampling method which is easy to understand and simple to apply on audit engagements. This article gives guidance on preliminary determinations that must be made in order to use DUS. It also illustrates how to figure sample size and select the sample members. Techniques to use in evaluating the results of DUS tests are provided. Finally, there is a discussion of factor to consider in deciding if DUS is the most appropriate sample method in a particular audit situation.
An Evaluation of Streaming Algorithms for Distinct Counting Over a Sliding Window

Counting the number of distinct elements in a data stream (``distinct counting'') is a fundamental aggregation task in database query processing, query optimization and network monitoring. On a stream of elements, it is commonly needed to compute an aggregate over only the most recent elements, leading to the problem of distinct counting over a ``sliding window'' of the stream. We present a detailed experimental study of the performance of different algorithms for distinct counting over a sliding window. We observe that the performance of an algorithm depends on the basic method used, as well as aspects such as the hash function, the mix of query and updates, and the method used to boost accuracy. We compare the performance of prominent algorithms, and evaluate the influence of these factors, leading to practical recommendations for implementation. To the best of our knowledge, this is the first detailed experimental study of distinct counting over a sliding window.
GPU register file virtualization

To support massive number of parallel thread contexts, Graphics Processing Units (GPUs) use a huge register file, which is responsible for a large fraction of GPU's total power and area. The conventional belief is that a large register file is inevitable for accommodating more parallel thread contexts, and technology scaling makes it feasible to incorporate ever increasing size of register file. In this paper, we demonstrate that the register file size need not be large to accommodate more threads context. We first characterize the useful lifetime of a register and show that register lifetimes vary drastically across various registers that are allocated to a kernel. While some registers are alive for the entire duration of the kernel execution, some registers have a short lifespan. We propose GPU register file virtualization that allows multiple warps to share physical registers. Since warps may be scheduled for execution at different points in time, we propose to proactively release dead registers from one warp and re-allocate them to a different warp that may occur later in time, thereby reducing the needless demand for physical registers. By using register virtualization, we shrink the architected register space to a smaller physical register space. By under-provisioning the physical register file to be smaller than the architected register file we reduce dynamic and static power consumption. We then develop a new register throttling mechanism to run applications that exceed the size of the under-provisioned register file without any deadlock. Our evaluation shows that even after halving the architected register file size using our proposed GPU register file virtualization applications run successfully with negligible performance overhead.
Modulation of rat skeletal muscle microvascular O2 pressure via KATP channel inhibition following the onset of contractions.

Vascular hyperpolarization mediated, in part, by the ATP-sensitive K(+) (KATP) channel contributes to exercise-induced increases in skeletal muscle O2 delivery. We hypothesized that KATP channel inhibition via glibenclamide (GLI) would speed the fall of microvascular O2 driving pressure (PO2mv; set by the O2 delivery-O2 utilization ratio), during muscle contractions. Spinotrapezius muscle PO2mv (phosphorescence quenching) was measured in 12 adult Sprague Dawley rats during 180s of 1-Hz twitch contractions (∼ 6 V) under control and GLI (5mg/kg) conditions. The total mean PO2mv response time was greater with GLI (i.e., slowed; control: 42.0 ± 14.2, GLI: 79.5 ± 14.7s, p 0.05). This indicates that KATP channel inhibition does not speed PO2mv kinetics per se during small muscle mass contraction. However, it does induce a transient mismatch of O2 delivery-O2 utilization, lowers PO2mv, and delays attainment of the contracting steady-state.
Psychometric Evaluation of the Young Children’s Participation and Environment Measure (YC–PEM)

Date Presented 4/18/2015 The Young Children’s Participation and Environment Measure (YC–PEM) is a newly validated proxy questionnaire designed to help occupational therapy researchers build comprehensive and detailed knowledge about young children’s participation and environmental supports and barriers to participation.
Action Recognition and Human Interaction

Recognizing human activities is a fundamental problem in the computer vision community and is a key step toward the automatic understanding of scenes.
A Jewish Approach to Healing

Explicates a notion of well-being from a Jewish perspective based upon a creation paradigm. Notes implications of the understanding for hospital chaplains.
Fundamental symmetries, Dark Sector and Spectroscopy

I will discuss some recent work in these areas involving our group and collaborators. Please see https://budker.uni-mainz.de and http://budker.berkeley.edu for the latest updates.
Epigenetic and genetic burden measures are associated with tumor characteristics in invasive breast carcinoma

The development and progression of invasive breast cancer is characterized by alterations to the genome and epigenome. However, the relationship between breast tumor characteristics, disease subtypes, and patient outcomes with the cumulative burden of these molecular alterations are not well characterized. We determined the average departure of tumor DNA methylation from adjacent normal breast DNA methylation using Illumina 450K methylation data from 700 invasive breast tumors and 90 adjacent normal breast tissues in The Cancer Genome Atlas. From this we generated a novel summary measure of altered DNA methylation, the DNA methylation dysregulation index (MDI), and examined the relation of MDI with tumor characteristics and summary measures that quantify cumulative burden of genetic mutation and copy number alterations. Our analysis revealed that MDI was significantly associated with tumor stage (P = 0.017). Across invasive breast tumor subtypes we observed significant differences in genome-wide DNA MDIs (P = 4.9E-09) and in a fraction of the genome with copy number alterations (FGA) (P = 4.6E-03). Results from a linear regression adjusted for subject age, tumor stage, and estimated tumor purity indicated a positive significant association of MDI with both MCB and FGA (P = 0.036 and P < 2.2E-16). A recursively partitioned mixture model of all 3 somatic alteration burden measures resulted in classes of tumors whose epigenetic and genetic burden profile were associated with the PAM50 subtype and mutations in TP53, PIK3CA, and CDH1. Together, our work presents a novel framework for characterizing the epigenetic burden and adds to the understanding of the aggregate impact of epigenetic and genetic alterations in breast cancer.
Solution of Screw Equation for Inverse Kinematics of 6R Robot Based on Wu's Method

The kinematics model of the 6R serial robot is set up by using screw method,which is under the overall description of rigid body movement,and compared with the traditional D-H method,singularity is avoided when describing in local coordinate. However,solving the inverse kinematics is restricted by the sub-problems algorithm when using screw method. Wu's method is introduced to the process of inverse kinematics,and the algorithm of inverse kinematics is realized by combining the idea of characteristic set with screw method,through the symbolic calculation using mathematics mechanization platform(MMP) and Maple software. Finally,the reliability of the algorithm is illustrated by the calculation of examples. Based on Wu's method,solving the inverse kinematics equation not only inherits the advantage of screw method but also becomes more independent to sub-problems algorithm,which makes the mechanical calculation much easier. The method can be extended to solving the kinematics problems of robot with other configurations(such as parallel mechanism) .
Evaluation of early efficacy of tumor radiation therapy using NIRF imaging

Objective: In order to investigate whether near-infrared fluorescence (NIRF) labeled annexin V could also demonstrate apoptotic cells in small animal model. Methods: Cy5.5-annexin V,a novel NIRF contrast agent was synthesized and characterized. Its binding ability to target apoptotic cells was demonstrated in vitro. MCa-29 tumor cells were inoculated in the hind legs of mice to set up the animal models. The mice were divided into radiation and non-radiation groups. Cy5.5-annexin V was injected into mouse intravenously 6 hours after radiation. The imaging was performed 24 hours after injection. Results: The binding affinity,Kd,to phosphatidylserine(PS) was 2.51nM for the Cy5.5-annexin V and 1.54nM for the unmodi-fied annexin V respectively. The results of flow cytometry and confocal fluorescence microscopy showed Cy5.5-annexin V tar-geted non-viable mouse thymocytes in similar patterns to FITC-annexin V. Fluorescence images of mice with MCa-29 tumor cells demonstrated that the fluorescence intensity in the radiated tumors was higher than that in untreated tumors. Conclusion: Cy5.5-annexin V could be useful in the early evaluation of radiation effect of the tumor.
Explaining Fibrofog: Carbohydrate Cravings Explain More Than Pain and Negative Mood Alone

AbstractObjective: The purpose of the preliminary study was to identify the contributions of various food cravings with the cognitive impairment in fibromyalgia [FMS] known as “Fibrofog”.Methods: Forty-seven, non-diabetic female participants aged 19 and older with FMS completed the Mental Clutter Scale, the Food Craving Inventory, the Profile of Mood States and the Fibromyalgia Impact Questionnaire-Revised.Results: Carbohydrate cravings were found to be a unique correlate of Fibrofog compared to other specific cravings. Results from hierarchal models revealed that carbohydrate cravings independently predicted Fibrofog, albeit modestly, over and above the symptoms of physical impact and mood (even after controlling for BMI).Conclusions: Along with the primary roles of FMS symptom clusters, carbohydrate cravings play a unique role in the cognitive impairment.
Rehabilitation of the cancer patient.

SUMMARY Today, patients who have a diagnosis of cancer often face the same concerns as persons who have other types of chronic illnesses. The effects of the disease, the treatment, or both, may leave patients with residual impairments that necessitate sometimes prolonged periods of rehabilitation. Rehabilitation may be preventive, restorative, supportive, or palliative, depending on the type and stage of the disease and characteristics of the patient. Rehabilitation is most effectively planned and carried out by a team composed of various disciplines, as appropriate, but always with the patient and family as the central members of the team. Patients need to be well-informed about the illness and treatment from an early stage and assisted in learning methods to deal with problems they may face in areas such as coping, independent functioning, sexual functioning, employment, and financial pressures. The physician can provide the most effective care to the patient by being familiar with and involving the wide range of rehabilitation services, community support programs, and necessary resources. Through these services, patients can be helped to lead productive and satisfying lives.
Geometry of manifolds modeled on Hilbert modules

For an associative, unital, and separable C*-algebra A, we describe A-manifolds which are modeled on finitely generate projective modules over A. We discuss the differential calculus, geometric structures such as Lie derivatives, symplectic forms, Hamiltonians, Poisson brackets and differential operators on A-manifolds.
My Pilgrimage in Mission

This personal account chronicles the journey of one expatriate family that tested the viability of the migration evangelism model set forth in 1961 by Mennonite theologian John Howard Yoder. Reflec...
An association between auditory-visual synchrony processing and reading comprehension: Behavioral and electrophysiological evidence

The perceptual system integrates synchronized auditory-visual signals in part to promote individuation of objects in cluttered environments. The processing of auditory-visual synchrony may more generally contribute to cognition by synchronizing internally generated multimodal signals. Reading is a prime example because the ability to synchronize internal phonological and/or lexical processing with visual orthographic processing may facilitate encoding of words and meanings. Consistent with this possibility, developmental and clinical research has suggested a link between reading performance and the ability to compare visual spatial/temporal patterns with auditory temporal patterns. Here, we provide converging behavioral and electrophysiological evidence suggesting that greater behavioral ability to judge auditory-visual synchrony Experiment 1 and greater sensitivity of an electrophysiological marker of auditory-visual synchrony processing Experiment 2 both predict superior reading comprehension performance, accounting for 16% and 25% of the variance, respectively. These results support the idea that the mechanisms that detect auditory-visual synchrony contribute to reading comprehension.
On Shannon capacity and causal estimation

The problem of estimating causal relationships from purely observational data is studied in this paper. We observe samples from a pair of random variables (X,Y) and wish to estimate whether X causes Y or Y causes X. Any joint distribution can be factored as pX,Y = pX pY|X = pY pX|Y and therefore the “causal” direction cannot be inferred from the joint distribution without further assumptions. In this paper, we propose and study the utility of Shannon capacity as a metric for causal directionality estimation. This opens up several open questions and directions for future study.
Imaging Characteristics of Prostate Cancer Patients Who Discontinued Active Surveillance on 3-T Multiparametric Prostate MRI.

OBJECTIVE. Early-stage prostate cancer may be followed with active surveillance to avoid overtreatment. Our institution's active surveillance regimen uses annual MRI in place of serial biopsies, and biopsies are performed only when clinically necessary. The objective of our study was to report the multiparametric MRI characteristics of prostate cancer patients who discontinued active surveillance at our institution after repeat imaging revealed possible evidence of tumor upgrading. MATERIALS AND METHODS. The Department of Urology at Winthrop University Hospital prospectively maintains a database of prostate cancer patients who are monitored with active surveillance. At the time of this study, there were 200 prostate cancer patients being monitored with active surveillance. Of those patients, 114 patients had an initial multiparametric MRI study that was performed before active surveillance started and at least one follow-up multiparametric MRI study that was performed after active surveillance began. The ...
How long bones grow children: Mechanistic paths to variation in human height growth.

Objectives Eveleth and Tanner's descriptive documentation of worldwide variability in human growth provided evidence of the interaction between genetics and environment during development that has been foundational to the science of human growth. There remains a need, however, to describe the mechanistic foundations of variability in human height growth patterns. Methods A review of research documenting cellular activities at the endochondral growth plate aims to show how the unique microenvironment and cell functions during the sequential phases of the chondrocyte lifecycle affect long bone elongation, a fundamental source of height growth. Results There are critical junctures within the chondrocytic differentiation cascade at which environmental influences are integrated and have the ability to influence progression to the hypertrophic chondrocyte phase, the primary driver of long bone elongation. Phenotypic differences in height growth patterns reflect variability in amplitude and frequency of discretely timed hypertrophic cellular expansion events, the cellular basis of saltation and stasis growth biology. Conclusions Final height is a summary of the dynamic processes carried out by the growth plate cellular machinery. As these cell-level mechanisms unfold in an individual, time-specific manner, there are many critical points at which a genetic growth program can be enhanced or perturbed. Recognizing both the complexity and fluidity of this adaptive system questions the likelihood of a single, optimal growth pattern and instead identifies a larger bandwidth of saltatory frequencies for “normal” growth. Further inquiry into mechanistic sources of variability acting at critical organizational points of chondrogenesis can provide new opportunities for growth interventions.
Confusing Convergence: How Courts Misunderstand Internet-Delivered Services

This paper will demonstrate that converging information, communications and entertainment (“ICE”) markets and technologies challenge the ability of regulatory agencies and reviewing courts to apply statutory definitions of service such as telecommunications and common carriage. Because carriers offer many services and devices, such as smartphones, a single all-encompassing regulatory classification cannot always apply. The paper recommends that courts recognize the lack of certainty presented by convergence and embrace a developing body of case precedent recognizing that common carriage services do not typically exist on a mutually exclusive basis with other private information services. If courts and regulatory agencies accept the blurring of so-called, bright line service distinctions, jurisdictional and statutory interpretations can occur with greater flexibility leading to greater certainty that both regulatory over-reach and under-reach will not occur. Courts reviewing the regulatory actions of the Federal Communications Commission (“FCC”) and the Federal Trade Commission (“FTC”) have evidenced great difficulty in incorporating the consequence of convergence in their decisions. For example, a recent decision by the Ninth Circuit Court of Appeals questioned whether the FTC has any jurisdiction to sanction deceptive or unfair acts and practices by Internet Service Providers (“ISPs”) if they also operate as common carriers providing telecommunications service. In a convergent world, the FCC and FTC should coordinate and calibrate investigations based on their expertise and whether a venture has engaged in questionable practices in its capacity as a common carrier, telecommunications service provider, or something else. The court refused to approve of such shared jurisdiction so that the FTC could investigate possible misrepresentation about the scope and nature of “unlimited” wireless data service as well as whether and when a wireless carrier could “throttle” the speed of bit transmission when subscribers exceed a monthly usage threshold. The court rejected the view that a wireless carrier could offer subscribers both common carrier and private carrier services, thereby triggering different levels of regulatory oversight from both FCC and FTC. In light of the FCC’s reclassification of broadband data service as common carriage, the court concluded that the FTC had no jurisdiction whatsoever, because it lacked authority to oversee at least one of the many different types of services available to smartphones via wireless carriers. This decision largely eliminates FTC regulatory safeguards for ICE services at the same time the FCC appears reluctant to impose broadband subscriber privacy safeguards. With both regulatory agencies unable or disinclined to address real privacy concerns, the possibility exists that major privacy and cybersecurity concerns will go unprotected absent new thinking about regulatory classifications in a converging, Internet ecosystem.
Theoretical Study of Epoxidation Reactions Relevant to Hydrocarbon Oxidation

Advances in computational modeling tools have allowed for the construction of detailed chemical models of oxidation processes to enhance the understanding of mechanisms and answer questions of interest in diverse fields such as DNA damage, lubricant oxidation, food chemistry, and art conservation. The construction of detailed kinetic models is facilitated by the use of kinetic correlations, such as Evans–Polanyi relationships, where the activation energy, EA, is related linearly to the heat of reaction, ΔHR: EA = E0 + α ΔHR. In this work, we present an Evans–Polanyi relationship based on properties determined from hybrid G4 quantum chemical calculations for an epoxidation reaction of peroxy species. We explore a broader chemical space at a higher level of theory than previous reports, and as a result, the importance of several key structural features, such as alkylhydroperoxy functional groups, that can strongly influence the trends observed was revealed. We suggest a subdivision of the reaction family in...
Cenozoic global cooling and increased seawater Mg/Ca via reduced reverse weathering.

Authigenic clay minerals formed on or in the seafloor occur in every type of marine sediment. They are recognized to be a major sink of many elements in the ocean but are difficult to study directly due to dilution by detrital clay minerals. The extremely low dust fluxes and marine sedimentation rates in the South Pacific Gyre (SPG) provide a unique opportunity to examine relatively undiluted authigenic clay. Here, using Mg isotopes and element concentrations combined with multivariate statistical modeling, we fingerprint and quantify the abundance of authigenic clay within SPG sediment. Key reactants include volcanic ash (source of reactive aluminium) and reactive biogenic silica on or shallowly buried within the seafloor. Our results, together with previous studies, suggest that global reorganizations of biogenic silica burial over the Cenozoic reduced marine authigenic clay formation, contributing to the rise in seawater Mg/Ca and decline in atmospheric CO2 over the past 50 million years. Reverse weathering reactions on or in the seafloor are a major sink of many elements and alkalinity in seawater. Here, the authors show how reduced rates of reverse weathering may be responsible for global cooling and increased seawater Mg/Ca over the past 50 million years.
Trends in Breast, Colorectal, and Cervical Cancer Incidence Following the Affordable Care Act: Implications for Cancer Screening.

This observational study uses incidence rates before and after adoption of the Affordable Care Act (ACA) to assess whether adoption of the ACA increased screening for breast, colorectal, and cervical cancer.
Automatic alignment of geographic features in contemporary vector data and historical maps

With large amounts of digital map archives becoming available, the capability to automatically extracting information from historical maps is important for many domains that require long-term geographic data, such as understanding the development of the landscape and human activities. In the previous work, we built a system to automatically recognize geographic features in historical maps using Convolutional Neural Networks (CNN). Our system uses contemporary vector data to automatically label examples of the geographic feature of interest in historical maps as training samples for the CNN model. The alignment between the vector data and geographic features in maps controls if the system can generate representative training samples, which has a significant impact on recognition performance of the system. Due to the large number of training data that the CNN model needs and tens of thousands of maps needed to be processed in an archive, manually aligning the vector data to each map in an archive is not practical. In this paper, we present an algorithm that automatically aligns vector data with geographic features in historical maps. Existing alignment approaches focus on road features and imagery and are difficult to generalize for other geographic features. Our algorithm aligns various types of geographic features in document images with the corresponding vector data. In the experiment, our alignment algorithm increased the correctness and completeness of the extracted railroad and river vector data for about 100% and 20%, respectively. For the performance of feature recognition, the aligned vector data had a 100% improvement on the precision while maintained a similar recall.
Activated heterotrimeric G protein αi subunits inhibit Rap-dependent cell adhesion and promote cell migration.

Our recent work uncovered novel roles for activated Gαi signaling in the regulation of neutrophil polarity and adhesion. GαiGTP-mediated enhancement of neutrophil polarization was dependent on inhibition of cAMP/PKA signaling, whereas reversal of Gβγ-stimulated adhesion was cAMP/PKA independent. To uncover the mechanism for Gαi regulation of adhesion, we analyzed the effects of constitutively active Gαi1(Q204L) expression on adhesion driven by constitutively active Rap1a(G12V) or its downstream effector Radil in neutrophil-like HL-60 cells, or in HT-1080 fibrosarcoma cells. In HT-1080 cells, Rap1a(G12V) or Radil cause an increase in cell spreading and adhesion to fibronectin, which are both reversed by Gαi1(Q204L) but not WT Gαi1. In contrast, Gαi1(Q204L) did not reverse Rap1-GTP–interacting adaptor molecule (RIAM)–dependent increases in cell adhesion. This indicates that adhesion regulation by Gαi-GTP occurs downstream of Rap1a and Radil, but is upstream of components such as integrins and talin that are regulated by both Radil and RIAM. HL-60 neutrophil-like cells expressing Rap1a(G12V) or Radil have an elongated phenotype because of enhanced uropod adhesion as they attempt to migrate on fibronectin. This elongated phenotype driven by Rap1a(G12V) or Radil is reversed by Gαi1(Q204L), but not by WT Gαi1 expression, suggesting that Gαi-GTP also regulates adhesion in immune cells at the level of, or downstream of, Radil. These data identify a novel role of Gαi-GTP in regulation of cell adhesion and migration. Cell migration involves cycles of adhesion and de-adhesion, and we propose that the dynamic spatiotemporal balance between Gβγ-promoted adhesion and Gαi-GTP reversal of adhesion is important for this process.
Role of Renin-Angiotensin-Aldosterone System Inhibition in Autosomal Dominant Polycystic Kidney Disease

Activation of the renin-angiotensin-aldosterone system (RAAS) has been postulated to contribute to hypertension, cyst growth, and decline in kidney function in autosomal dominant polycystic kidney disease (ADPKD). Several observations from the bench and at the bedside support this postulate. Small randomized clinical trials (RCTs) comparing angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB) against other antihypertensive drug classes showed greater reductions in albuminuria and left ventricular mass index (LVMI) with RAAS blockers, but no effect on kidney function decline, though such studies were not powered for the latter. The multicenter, RCTs HALT-PKD Study A (eGFR >60 mL/min) and B (eGFR 20–59 mL/min) compared dual blockade of the RAAS with ACE-I and ARB against ACE-I monotherapy. Results showed no difference in the rate of GFR decline with combination therapy in early (eGFR >60 mL/min/1.73 m2) or late (eGFR 20–59 mL/min/1.73 m2) disease and no effect on TKV growth or LVMI in early disease. The second intervention tested in Study A, treatment to a BP of ≤110/70 mm Hg as compared with 120–130/70–80 mm Hg, was well tolerated and was associated with a 14% reduction in the annual rate of TKV growth, a reduction in LVMI, and a non-significant trend toward a reduction in GFR decline. A large RCT testing RAAS blockers versus other classes of antihypertensive agents or placebo is unlikely. Extrapolating the evidence about RAAS blockers in other forms of kidney disease and given the data showing heightened activity of the RAAS in ADPKD, RAAS blocking agents are recommended as first-line therapy for treating hypertension in ADPKD. It is clear from the HALT-PKD Studies that ACE-I/ARB combination therapy provides no benefit over ACE-I alone and is not routinely recommended, given the potential for hyperkalemia and AKI. ADPKD patients with eGFR ≥60 mlL/min should be treated to a BP ≤110/70 mm Hg for benefits on kidney and cardiac outcomes.
Models to Study Experimental Infarction — Pharmacologic

A new drug generally cannot be found without an appropriate animal model to be used for the discovery and development phases. The only exceptions are compounds found to be active as a result of particular clinical experiences. Most of the time such experiences uncover new indications for an old drug. Recent examples of this are studies which tested the hypothesis that use of beta-blocking agents in patients who had a previous myocardial infarction might be beneficial in preventing death.
Vortex Splitting and Shedding Cell Interactions in Wakes Behind Linearly Tapered Cylinders at Low Reynolds Numbers

The large scale or “global” vorticity structure of two-dimensional, non-tapered, bluff bodies at moderate and large Reynolds numbers is dominated by an essentially two-dimensional geometrical structure. However, when the body geometry is three-dimensional and varies in the spanwise direction, three-dimensional vortex dynamics and geometry play an essential role in determining the vortex topology of the global wake structure.
Pericardial Disease Associated with Malignancy

Pericardial effusion is commonly associated with malignancy. The goals of treatment should include optimizing symptom relief, minimizing repeat interventions, and restoring as much functional status as possible. Pericardiocentesis should be the first intervention but has high recurrence rates (30–60%). For patients with recurrence, repeat pericardiocentesis is indicated in those with limited expected lifespans. Extended pericardial drainage decreases recurrence to 10–20%. The addition of sclerosing agents decreases recurrence slightly but creates significant pain and can lead to pericardial constriction and therefore has fallen out of favor. Most patients with symptomatic pericardial disease have a short median survival time due to their underlying disease. In patients with a longer life expectancy, surgical drainage offers the lowest recurrence rate. Surgical approach is based on effusion location and clinical condition. Subxiphoid and thoracoscopic approaches lead to similar outcomes. Thoracotomy should be avoided as it increases morbidity without improving outcomes.
Regulatory Crime: Solutions

On November 14, 2013, Professor Dervan was called to testify before the United States House of Representatives' Committee on the Judiciary Over-Criminalization Task Force. Available here is his written testimony. In his written testimony, Professor Dervan examines the phenomenon of over-criminalization, particularly in the regulatory area, and offers several recommended solutions for Congressional adoption. First, he recommends the adoption of a default rule for mens rea. Second, he recommends the adoption of a default rule applying mens rea to all material elements of an offense. Third, he recommends the codification of the Rule of Lenity. Finally, along with some additional recommendations for consideration, Professor Dervan discusses the role of plea bargaining in the U.S. criminal justice system and encourages the Task Force to more closely examine this issue in the future.
The effect of scoliosis on surface landmarks for lumbar plexus block: a MRI-based retrospective case-control series

Background Degenerative scoliosis (DS) may affect surface landmarks for performance of lumbar plexus (LP) block. We hypothesized the extent of any difference in surface landmarks could be calculated by a formula based on measured degree of DS, body mass index, sex, and age. Methods We retrospectively searched our radiology database until 113 consecutive adult patients with DS were identified with lumbar spine radiographs and magnetic resonance imaging examinations performed. Pertinent surface landmark measurements at the L4 vertebral body level were recorded and compared to 50 controls. Results In patients with severe DS, there is a mean lateral deviation of the needle tip of 1.53 cm (0-3 cm) on the concave side and mean medial deviation of the needle tip of 0.35 cm (0-1.5 cm) on the convex side using typical bony landmarks. We found a significant correlation between body mass index and LP depth with a correlation coefficient ranging between 0.53 and 0.71. We found potential risk of organ injury in two of 13 patients with severe DS using traditional surface landmarks. Conclusions There is a larger degree of lateral deviation of the LP on the concave side of scoliosis compared to medial deviation on the convex side. These deviations remained consistent irrespective of the direction of scoliosis. A review of the imaging studies and preprocedural ultrasound assessment of anatomy should be strongly considered prior to needle puncture. In patients with severe DS, an alternative approach may be considered to avoid the possibility of visceral organ injury.
A phase II study of PD-1 inhibition for the prevention of colon adenomas in patients with Lynch syndrome and a history of partial colectomy.

TPS1587Background: Colon cancers and adenomas that are associated with Lynch syndrome (LS) often display microsatellite instability (MSI), a characteristic that is associated with increased respons...