cssi/SciSciGPT-SciSciNet huggingface dataset:
Thematic Issue "Apoptosis-like cell death programs in yeasts".

A brewing storm: making the case for yeast suicide In this issue we present a series of papers that arose from presentations at the Second International Meeting on Yeast Apoptosis held during September 2003 in Smolenice, Slovak Republic. This is a relatively new field, and the very question of whether or not yeasts have physiologically-relevant cell death programs still warrants healthy skepticism. It is an established fact that metazoan cells, under many different circumstances, orchestrate the timing and mechanisms of their own – and their neighbors – demise. The adaptive advantage of programmed cell death during animal development and organ maintenance is obvious. Less obvious are the possible adaptive advantages of apoptotic-like cell death programs to yeasts (see [1]). But this is mostly beside the point, since why a cell phenomenon occurs is not the purview of the molecular biologist. Knowing why tigers have stripes, or why cells die, provides useful information, but this type of knowledge is not a prerequisite to research, especially since the methods employed by molecular biologists are suitable only for addressing the what and how. As demonstrated by the contributions to this issue, the case for genetic programs of cell death in yeasts is becoming too strong to ignore. Most would now agree that the continued study of cell death programs in yeasts has important ramifications for biomedical, agricultural, and industrial concerns. The most striking evidence for the existence of cell death programs are genes that act directly to guarantee death, which, when mutated, allow the organism to survive longer under specified conditions. The best-characterized – but not the only – suicide gene in Saccharomyces cerevisiae is the metacaspase YCA1/MCA1 [2,3], which promotes a death process bearing phenotypic markers typically associated with mammalian apoptosis (reviewed in [4]). Metacaspases are a class of caspase-like cysteine proteases that occur in yeasts, plants, a protist, and that has close relatives in bacteria [5]. Importantly, Suarez et al. [6] recently have described a metacaspase-dependent programmed cell death process that is essential for embryogenesis in the plant Arabidopsis. A challenge to the yeast field is the continued development of rigorous morphological and biochemical criteria that confidently distinguish chaotic necrotic deaths from more orderly genetic programs of apoptotic-like or autophagic-like cell deaths. In conclusion, the study of genetic programs of cell death in yeast is in its infancy. Having taken its first steps, this field is poised to both expand and consolidate its discoveries. We hope that the contributions to this special issue will excite the interest of young and established researchers, and, in the best tradition of basic research, speed the discovery of totally unexpected and groundbreaking results.
Rational design of double-negative metamaterials consisting of 3D arrays of two different non-metallic spheres arranged on a simple tetragonal lattice

Non-metallic, low-loss double-negative (DNG) metamaterials can be formed by three-dimensional (3D) arrays of two different non-metallic spheres arranged on a simple tetragonal lattice. Such DNG metamaterials have recently been found to provide DNG bandwidths of 10% through 3D arrays of two different dielectric spheres, and of 18% through 3D arrays of dielectric and magnetic spheres. However, a method of rational design of these DNG metamaterials has not yet been presented. This paper develops a design procedure based on the theoretical description of traveling waves supported by the 3D arrays. Analytical calculations of k-β (dispersion) diagram and effective constitutive parameters of several DNG metamaterials designed using this rule are presented.
New tests for null hypothesis of non unity ratio of proportions.

Testing for noninferiority and equivalence between an experimental therapy and a standard therapy in terms of the ratio of binomial proportions is considered. New tests based on the Fieller–Hinkley distribution of the ratio of random variables are proposed. Restricted maximum likelihood estimates of the null variances are used to derive the tests. Sample size determination is discussed. The proposed test procedure is extended to multiple tables. The tests are applied to numerical examples.
Gassmann's equation and fluid‐saturation effects on seismic velocities

Gassmann’s (1951) equations commonly are used to predict velocity changes resulting from different porefluid saturations. However, the input parameters are often crudely estimated, and the resulting estimates of fluid effects can be unrealistic. In rocks, parameters such as porosity, density, and velocity are not independent, and values must be kept consistent and constrained. Otherwise, estimating fluid substitution can result in substantial errors. We recast the Gassmann’s relations in terms of a porosity-dependent normalized modulus Kn and the fluid sensitivity in terms of a simplified gain function G. General Voigt-Reuss bounds and critical porosity limits constrain the equations and provide upper and lower bounds of the fluid-saturation effect on bulk modulus. The “D” functions are simplified modulus-porosity relations that are based on empirical porosity-velocity trends. These functions are applicable to fluid-substitution calculations and add important constraints on the results. More importantly, the simplified Gassmann’s relations provide better physical insight into the significance of each parameter. The estimated moduli remain physical, the calculations are more stable, and the results are more realistic.
Electromechanical considerations in developing low-voltage RF MEMS switches

This paper reports on the design, fabrication, and testing of a low-actuation voltage Microelectromechanical systems (MEMS) switch for high-frequency applications. The mechanical design of low spring-constant folded-suspension beams is presented first, and switches using these beams are demonstrated with measured actuation voltages of as low as 6 V. Furthermore, common nonidealities such as residual in-plane and gradient stress, as well as down-state stiction problems are addressed, and possible solutions are discussed. Finally, both experimental and theoretical data for the dynamic behavior of these devices are presented. The results of this paper clearly underline the need of an integrated design approach for the development of ultra low-voltage RF MEMS switches.
Colon and Rectum

We often forget that colorectal carcinoma is the most common kind of visceral cancer in America and very much a disease of the elderly. It is more common than lung, breast, or prostate cancer. As shown in Fig. 6.1, the incidence at age 50–54 is 51.5 per 100,000 per year, more than doubling every decade until it is 451.1 at age 80–84. Colorectal cancer is equally common in men and women.
Heavy metal binding capacity (HMBC) of municipal solid waste landfill leachates.

Abstract This research describes the use of a toxicity assay for the identification of metal toxicity, bioavailability and heavy metal binding capacity (HMBC) of municipal solid waste (MSW) landfill leachates. MetPLATE, an assay specific for heavy metal toxicity, was used to determine the HMBC of MSW leachates collected from 14 sites in Florida, with a wide range of chemical and physical characteristics. The leachates displayed a low toxicity which was attributed to the site-specific parameters, including, high concentrations of both organic and inorganic ligands. The HMBC test was undertaken to measure the effect of these site-specific parameters on metal toxicity. The potential for MSW leachate to bind and, thus, detoxify heavy metals was investigated with copper, zinc, and mercury. The HMBC values obtained ranged from 3 to 115, 5 to 93 and 4 to 101 for HMBC-Cu+2, HMBC-Zn+2, and HMBC-Hg2, respectively. Additionally, the high strength leachates displayed the highest binding capacities, although the landfills sampled represented a wide range of characteristics. For comparison, the HMBC values reported with local lake water, Lake Alice and Lake Beverly, and a wastewater treatment plant effluent were all below 3. A partial fractionation of MSW leachate samples from sites 1, 5 and 8, was conducted to further investigate the influence of selected site-specific physico-chemical parameters on metal binding. The fractionation revealed that the HMBC of the leachate samples was heavily influenced by the concentration of solids, organics and hardness.
Modeling the inhibition of dissolved H2 on propionate fermentation and methanogenesis in wetland sediments

Abstract The complex interactions between hydrogen (H 2 ) and methane (CH 4 ) dynamics in wetland sediments are studied here with laboratory measurements supported by a methanogenesis model that includes interactions with H 2 . Results from a series of 24-day incubation experiments producing CH 4 from wetland sediment slurries with different carbon-compound amendments and under different H 2 headspace partial pressures are presented. A simple model was formulated and calibrated to these experimental data, accounting for the interactions between propionate fermenters and H 2 . This methanogenesis model is based on Michaelis–Menten and Monod kinetics with propionate as the only root exudate. While the biological interactions of CH 4 production of the model were based on and calibrated with the results of the batch experiments, the model was expanded to simulate the effects of other well-studied processes than control methanogenesis in wetlands and rice paddies: sulfate reduction, plant-mediated gas volatilization, and the presence or absence of a gas phase in sediments into which H 2 can partition. These common physical and microbial processes generally reduce the negative effects of the H 2 inhibition of propionate degradation in many scenarios, but there may still be some important situations where the inhibition of propionate degradation by H 2 may have significant controls over CH 4 production. More important, processes that aid in reducing the H 2 inhibition of propionate degradation, like plant induced venting, will result in less CH 4 production by hydrogenotrophic methanogens, which should be taken into account in established model formulations.
Stereotype threat reduces false recognition when older adults are forewarned

Exposing older adults to ageing stereotypes can reduce their memory for studied information--a phenomenon attributed to stereotype threat--but little is known about stereotype effects on false memory. Here, we assessed ageing stereotype effects on the Deese-Roediger-McDermott false memory illusion. Older adults studied lists of semantically associated words, and then read a passage about age-related memory decline (threat condition) or an age-neutral passage (control condition). They then took a surprise memory test with a warning to avoid false recognition of non-studied associates. Relative to the control condition, activating stereotype threat reduced the recognition of both studied and non-studied words, implicating a conservative criterion shift for associated test words. These results indicate that stereotype threat can reduce false memory, and they help to clarify mixed results from prior ageing research. Consistent with the regulatory focus hypothesis, threat motivates older adults to respond more conservatively when error-prevention is emphasised at retrieval.
Marktevolution und Wettbewerbsstrategie

Im vierten Kapitel haben wir ausfuhrlich Marktwachstumsraten erortert und gezeigt, wie der Erfolg einer Geschaftseinheit durch die Charakteristika des Marktes, in dem sie operiert, beeinflust wird. In diesem Kapitel wollen wir diese Diskussion vertiefen und untersuchen, wie sich die Marktevolution auf die Art des Wettbewerbs, die Unternehmensstrategien und den Erfolg auswirkt.
Third Ventricular Glioblastoma Multiforme: Case Report and Literature Review

Background Glioblastoma multiforme (GBM) typically presents in the supratentorial white matter, commonly within the centrum semiovale as a ring-enhancing lesion with areas of necrosis. An atypical presentation of this lesion, both anatomically as well as radiographically, is significant and must be part of the differential for a neoplasm in this anatomical location. Case Description We present a case of a 62-year-old woman with headaches, increasing somnolence, and cognitive decline for several weeks. Magnetic resonance imaging demonstrated mild left ventricular dilatation with a well-marginated, homo- geneous, and nonhemorrhagic lesion located at the ceiling of the third ventricle within the junction of the septum pellucidum and fornix, without exhibiting the typical radiographic features of hemorrhage or necrosis. Final pathology reports confirmed the diagnosis of GBM. Conclusion This case report describes an unusual location for the most common primary brain neoplasm. Moreover, this case identifies the origin of a GBM related to the paracentral ventricular structures infiltrating the body of the fornix and leaves of the septum pellucidum. To our knowledge this report is the first reported case of a GBM found in this anatomical location with an entirely atypical radiographic presentation.
Statistical Thermodynamics in Chemical Kinetics

The dog-flea model illustrates an equilibrium distribution with the maximal states. If all fleas are on dog A, each might jump to dog B with some characteristic time. Independent jumps by fleas in either direction eventually lead to an equilibrium state. Even then, random jumps create a dynamic equilibrium. Even though fleas continue to jump between dogs, the 50–50 distribution is stable. Fleas continue to jump and although the system can fluctuate from this equilibrium, the 50–50 equilibrium is observed predominantly. For equal energy isomers, an initial state of only A isomers leads, in time, to the 50–50 A–B distribution.
Exploring the Relationship Between Octane Sensitivity and Heat-of-Vaporization

The latent heat-of-vaporization (HoV) of blends of biofuel and hydrocarbon components into gasolines has recently experienced expanded interest because of the potential for increased HoV to increase fuel knock resistance in direct-injection (DI) engines. Several studies have been conducted, with some studies identifying an additional anti-knock benefit from HoV and others failing to arrive at the same conclusion. Consideration of these studies holistically shows that they can be grouped according to the level of fuel octane sensitivity variation within their fuel matrices. When comparing fuels of different octane sensitivity significant additional anti-knock benefits associated with HoV are sometimes observed. Studies that fix the octane sensitivity find that HoV does not produce additional anti-knock benefit. New studies were performed at ORNL and NREL to further investigate the relationship between HoV and octane sensitivity. Three fuels were formulated for the ORNL study with matched RON and octane sensitivity, but with differing HoV. Experiments with these fuels in a 1.6-liter GTDI engine showed that the fuels exhibited very similar combustion phasing under knock-limited spark advance (KLSA) conditions. Fuels having a range of RON, octane sensitivity, and HoV were tested at NREL in a single-cylinder GDI engine under conditions where octane sensitivity has littlemore » effect on knock resistance. KLSA was found to be well correlated with RON. These results reinforce the concept that HoV anti-knock effects can be viewed as a contributor to octane sensitivity. From this viewpoint, HoV effects manifest themselves as increases in octane sensitivity.« less
MapReduce programming and cost-based optimization?: crossing this chasm with starfish

MapReduce has emerged as a viable competitor to database systems in big data analytics. MapReduce programs are being written for a wide variety of application domains including business data processing, text analysis, natural language processing, Web graph and social network analysis, and computational science. However, MapReduce systems lack a feature that has been key to the historical success of database systems, namely, cost-based optimization. A major challenge here is that, to the MapReduce system, a program consists of black-box map and reduce functions written in some programming language like C++, Java, Python, or Ruby.Starfish is a self-tuning system for big data analytics that includes, to our knowledge, the first Cost-based Optimizer for simple to arbitrarily complex MapReduce programs. Starfish also includes a Profiler to collect detailed statistical information from unmodified MapReduce programs, and a What-if Engine for fine-grained cost estimation. This demonstration will present the profiling, what-if analysis, and cost-based optimization of MapReduce programs in Starfish. We will show how (nonexpert) users can employ the Starfish Visualizer to (a) get a deep understanding of a MapReduce program's behavior during execution, (b) ask hypothetical questions on how the program's behavior will change when parameter settings, cluster resources, or input data properties change, and (c) ultimately optimize the program.
Family Purchase Decision Making and the Process of Adjustment

Research from social psychology, sociology, and marketing suggests the importance of the process of adjustment in family purchase decision making. Further empirical support is provided by a cross-s...
Measuring Exocytosis Rate Using Corrected Fluorescence Recovery After Photoconversion

Exocytosis plays crucial roles in regulating the distribution and function of plasma membrane (PM) and extracellular matrix proteins. However, measuring the exocytosis rate of a specific protein by conventional methods is very difficult because of exocytosis-independent trafficking such as endocytosis, which also affects membrane protein distribution. Here, we describe a novel method, corrected fluorescence recovery after photoconversion, in which exocytosis-dependent and -independent trafficking events are measured simultaneously to accurately determine exocytosis rate. In this method, the protein-of-interest is tagged with Dendra2, a green-to-red photoconvertible fluorescent protein. Following the photoconversion of PM-localized Dendra2, both the recovery of the green signal and the changes in the photoconverted red signal are measured, and the rate of exocytosis is calculated from the changing rates of these two signals.
Atlantoaxial Rotatory Fixation after Ventriculoperitoneal Shunting

Ventriculoperitoneal (VP) shunting is a common neurosurgical procedure in the pediatric population. Atlantoaxial rotatory fixation (AARF) is not uncommon in this same group. We present the first reported case of AARF following a VP shunt procedure. A 10-year-old boy, with hydrocephalus and a left temporal arachnoid cyst since birth, underwent a revision of his VP and cystoperitoneal shunts. A second operation was performed 2 days later to optimize catheter placement. Postoperative neck pain was attributed to tunneling of the subcutaneous catheter. 2 months after surgery, the child had minimal neck discomfort but maintained his head in a "cock-robin" position. Plain radiographs and computed tomographic (CT) images confirmed AARF. The child was admitted and placed in halo traction. After 3 days of traction, analgesics, sedation, and muscle relaxants, anatomic re-alignment of the C1-C2 vertebral complex was confirmed on CT scan. Following 3 months of immobilization in a halo-vest apparatus, the halo was removed. At 8-year follow-up, the clinical examination is normal and repeat imaging studies remain normal. Due to surgical positioning, and postoperative signs attributed to normal postoperative pain, an AARF was not initially recognized. This case represents the first time that AARF has been reported following a VP shunt procedure.
Coping With Chronic Stress by Unhealthy Behaviors: A Re-Evaluation Among Older Adults by Race/Ethnicity.

Objective: To assess the role of unhealthy behaviors in the relationship between chronic stress and significant depressive symptoms by race/ethnicity among older adults. Method: Participant data from the 2006 to 2008 Health and Retirement Study were analyzed. Unhealthy behaviors included current smoking, excessive/binge drinking, and obesity. Chronic stress was defined by nine previously used factors. The eight-item Center for Epidemiologic Studies Depression (CES-D) Scale measured depressive symptoms, where ≥4 symptoms defined significant. Multivariable logistic regression assessed the effects of chronic stress and unhealthy behaviors in 2006 on depressive symptoms in 2008. Results: A higher chronic stress index score predicted depressive symptoms in 2008 among African Americans, Latinos, and Whites (adjusted odds ratio [aOR] = 1.78, 95% confidence interval [CI] = [1.48, 2.15]; aOR = 1.54, 95% CI = [1.15, 2.05]; and aOR = 1.40, 95% CI = [1.26, 1.56], respectively). Unhealthy behaviors moderated this rela...
Spontaneous death of Echinococcus multilocularis: cases diagnosed serologically (by Em2 ELISA) and clinical significance.

Abstract Nine cases of asymptomatic alveolar hydatid disease (AHD) of the liver were diagnosed in 1985 among Eskimos from the endemic region of western Alaska. The patients were identified by screening with the enzyme-linked immunosorbent assay, using purified Echinococcus multilocularis antigen (Em2 ELISA). Five patients, and one diagnosed earlier (1979), were found to have lesions in which the larval E. multilocularis had died spontaneously at an early stage of infection. Viability was assessed histologically; by the avidinbiotin immunohistochemical method; and in vivo through intraperitoneal inoculation of membranes of the larval cestode into red-backed voles, Clethrionomys rutilus. The results were in agreement with the clinical impression, based on findings by computerized tomography and ultrasound scanning, and on the macroscopic appearance of the lesions, that the cestode was dead. Spontaneous death of E. multilocularis in humans has not been previously reported. The findings show that the Em2 ELISA may be positive in patients having lesions of AHD in which the etiologic agent is no longer viable.
The clerkship in public health: a positive experience.

Cornell University Medical College’s required third-year clerkship in public health offers a unique educational experience well received by faculty and students. Within a two-week period, a combination of field trips, seminars, lectures, required reading, and a research paper enables students to gain familiarity with a broad range of issues by placing them in situations exposing them to relevant problems and solutions. Nearly all students find some aspect of either the field trips or seminars provocative. Some are motivated to plan follow-up electives. A similar course using local resources could be offered elsewhere.
Is there a Home Run Derby Curse

Abstract This chapter analyzes the aggregate performance of Home Run Derby competitors’ performance both before and after the Home Run Derby for the time period 1999–2013. Regression to the mean suggests that in general, those players with outstanding performances in the first half of the season will regress to the mean. The findings here are consistent with regression to the mean, and the mean performance along four key analytics is statistically significantly worse for the competitors. However, the winners’ mean performance both before and after the Home Run Derby are not statistically significantly different. Thus, the results are consistent with previous research, but the results also find so-called “winner and loser” effects in Major League Baseball.
Prospective Comparison of Plain Abdominal Radiography with Conventional and Digital Renal Tomography in Assessing Renal Extracorporeal Shock Wave Lithotripsy Patients

AbstractMost publications citing the effectiveness of renal extracorporeal shock wave lithotripsy have used plain abdominal radiography to assess residual calculi after treatment. We compared radiologist sensitivity and specificity in the detection of calculi on plain abdominal radiographs versus conventional film-screen and digital renal tomograms in extracorporeal shock wave lithotripsy patients. Of the patients 50 were imaged before and within 24hours after lithotripsy. Six radiologists evaluated the resultant 300 studies for the presence and location of calculi. The mean sensitivity for digital tomograms was 83% for pre-lithotripsy and post-lithotripsy studies, which was significantly higher than for plain abdominal radiography and conventional tomography after lithotripsy. However, there were significantly more false positive stone diagnoses associated with digital tomogram interpretation. Signal detection analysis verified the over-all superiority of digital tomography for post-extracorporeal shock ...
SU-F-T-179: Fast and Accurate Profile Acquisition for Proton Beam Using Multi-Ion Chamber Arrays

Purpose: Proton beam profile measurement is more time-consuming than photon beam. Due to the energy modulation during proton delivery, chambers have to move step-by-step instead of continuously. Multi-ion chamber arrays are appealing to this task since multiple measurements can be performed at once. However, their utilization suffers from sparse spatial resolution and potential intrinsic volume-averaging effect of the disk-shaped ion chambers. We proposed an approach to measure proton beam profiles accurately and efficiently. Methods: Mevion S250 proton system and IBA Matrixx ion chamber arrays were used in this study. Matrixx has interchamber distance of 7.62 mm, and chamber diameter of 4.5 mm. We measured the same beam profile by moving the Matrixx seven times with 1 mm each time along y axis. All 7 measurements were superimposed to get a “finer” profile with 1 mm spatial resolution. Coarser resolution profiles of 2 mm and 3 mm were also generated by using subsets of measurements. Those profiles were compared to the TPS calculated beam profile. Gamma analysis was performed for 2D dose maps to evaluate the difference to TPS dose plane. Results: Preliminary results showed a large discrepancy between the TPS calculated profile and the single measurement profile with 7.6 mm resolution. A good match could be achieved when the resolution reduced to 3 mm by adding one extra measurement. Gamma analysis for 2D dose map of a 10×10 field showed a passing rate (γ ≤ 1) of 90.6% using a 3% and 3mm criterion for single measurement, which increased to 92.3% for 2-measurement superimposition, and slightly further increased to 92.9% for 7-measurement superimposition. Conclusion: The results indicated that 2 measurements shifted by 3mm using Matrixx generated a smooth proton beam profile with good matching to Eclipse beam profile. We suggest using this 2-measurement approach in clinic for double scattering proton beam profile measurement.
Checkpoint immunotherapy: good for cancer therapy, bad for rheumatic diseases

The goal of harnessing the immune system to fight cancer is not new; it dates back 125 years to when William Coley advocated that the body's response to infection could have anti-tumoural effects.1 However, decades of efforts using vaccines and immune stimulant therapies to harness the immune system to fight tumours have had limited success and at times have been fraught with serious adverse outcomes. Recently, drugs blocking negative immune checkpoint pathways have shown remarkable clinical activity in various solid tumours.2 Several agents targeting two such negative checkpoints, the programmed death-1 (PD-1) pathway (pembrolizumab, nivolumab and atezolizumab) and the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) (ipilimumab) are currently Food and Drug Administration and European Medicines Agency approved. These negative checkpoint pathways play a role in immune tolerance in normal tissues and the activation of these pathways is largely contextual. While these therapies have added immeasurably to the longevity of many patients with malignancies, they have come at a cost with the development of numerous untoward autoimmune inflammatory conditions. The anti-tumour mechanism for checkpoint inhibitor therapies is incompletely understood but clearly relates to the manipulation of T-cell pathways involved in cellular activation and deactivation.2 T-cell homeostasis is a tightly choreographed process whereby naive T cells rapidly proliferate in a logarithmic fashion when effectively activated and then contract following successful defeat of the challenge. CD4 T-cell activation canonically requires two signals: a primary signal ( signal 1 ), mediated by recognition of cognate antigen by the T-cell receptor via presentation by self-major histocompatibility complex class II molecules on the antigen-presenting cell, and a secondary signal ( signal 2 ), mediated by CD28 on the T-cell, binding its ligand partner of the B7 family on the antigen-presenting cell.3 Of vital importance to the host is the integration of deactivating pathways or checkpoints leading to contraction …
High visibility reflective sign sheeting materials: field and computational evaluations of visual performance

Highway signs provide important information to drivers to assist in navigation, to identify potentially hazardous roadway locations, and to remind drivers of safe operating practices. Ensuring that signs have sufficient visibility to the driving public is a key undertaking by transportation agencies. In order to assist in evaluating and comparing different materials for photometric and visual performance, the present study was undertaken to assess the utility of specifying sign sheeting performance in terms of visual performance. As part of this effort, a practical methodology for conducting field measurements of sign luminance along roadways was developed. In addition to describing the methods for an approach to visual performance based specifications, a spreadsheet tool for calculating minimum sign luminance and visibility from different sign sheeting materials was also developed. First published online 20 October 2016
Homeostatic control of metabolic and functional fitness of T reg cells by LKB1 signalling

Regulatory T cells (Treg cells) have a pivotal role in the establishment and maintenance of immunological self-tolerance and homeostasis. Transcriptional programming of regulatory mechanisms facilitates the functional activation of Treg cells in the prevention of diverse types of inflammatory responses. It remains unclear how Treg cells orchestrate their homeostasis and interplay with environmental signals. Here we show that liver kinase B1 (LKB1) programs the metabolic and functional fitness of Treg cells in the control of immune tolerance and homeostasis. Mice with a Treg-specific deletion of LKB1 developed a fatal inflammatory disease characterized by excessive TH2-type-dominant responses. LKB1 deficiency disrupted Treg cell survival and mitochondrial fitness and metabolism, but also induced aberrant expression of immune regulatory molecules including the negative co-receptor PD-1 and the TNF receptor superfamily proteins GITR and OX40. Unexpectedly, LKB1 function in Treg cells was independent of conventional AMPK signalling or the mTORC1-HIF-1α axis, but contributed to the activation of β-catenin signalling for the control of PD-1 and TNF receptor proteins. Blockade of PD-1 activity reinvigorated the ability of LKB1-deficient Treg cells to suppress TH2 responses and the interplay with dendritic cells primed by thymic stromal lymphopoietin. Thus, Treg cells use LKB1 signalling to coordinate their metabolic and immunological homeostasis and to prevent apoptotic and functional exhaustion, thereby orchestrating the balance between immunity and tolerance.
How Quickly Should You Liquidate Your Vested Stock

I model the optimal behavior of an individual or trustee who decides to liquidate a position in an asset. As his holdings are large, his own sales may have adverse permanent and temporary impact on the realized return. To minimize this effect, a wealthy insider may choose to liquidate slowly. At the optimum, he balances the exposure to the return variance against sale-induced price concessions using a Value-at-Risk-inspired risk-reward function as his decision tool. The prescriptive appeal of the model is demonstrated numerically. For example, I show that a risk-averse individual holding $1 million of his wealth in a stock, subject to 50% volatility and linear temporary impact of $1900, should optimally take 10 days to liquidate.
Impact of Reflex Algorithms on Urine Culture Utilization

Abstract Urine culture is the gold standard for the diagnosis of urinary tract infection (UTI), one of the most common causes of bacterial infection. As such, urine specimens are responsible for a major share of the workload in clinical microbiology laboratories. The inclusion of metrics, such as the catheter-associated UTI (CAUTI) rate, that factor into hospital reimbursements and concerns surrounding the attrition of clinical laboratory personnel have prompted scrutiny of urine culture utilization in many organizations. One strategy to improve urine culture management is the institution of urine reflex algorithms that restrict urine culture to specimens with evidence of inflammation on urinalysis. The high negative predictive value of indicators of pyuria and bacteriuria on urinalysis are useful to rule out UTI and thus the need for culture. Data from several studies support the notion that use of reflex criteria reduces urine culture utilization. However, few studies have examined the impact of reflex algorithms on CAUTI rates and antibiotic use. This article provides an overview of the laboratory diagnosis of urinary tract infections with a focus on the utility of urinalysis and reflex testing algorithms.
Differential Equations with Linear Algebra. By Zbigniew H. Nitecki and Martin M. Guterman/ Introduction to Differential Equations. By Richard K. Miller/ Fundamentals of Differential Equations. By R. Kent Nagle and Edward B. Saff/ Introduction to Differential Equations with Applications. By Fred Brauer and John A. Nohel and Ordinary Differential Equations. By Morris Tenenbaum and Harry Pollard

(1987). Differential Equations with Linear Algebra. By Zbigniew H. Nitecki and Martin M. Guterman/ Introduction to Differential Equations. By Richard K. Miller/ Fundamentals of Differential Equations. By R. Kent Nagle and Edward B. Saff/ Introduction to Differential Equations with Applications. By Fred Brauer and John A. Nohel and Ordinary Differential Equations. By Morris Tenenbaum and Harry Pollard. The American Mathematical Monthly: Vol. 94, No. 10, pp. 1022-1024.
A novel, cell-specific attenuation of a herpes simplex virus type 1 infection in vivo

We have observed a cell-specific attenuation of herpes simplex virus type 1 strain 17syn+ in vivo that was dependent upon the cell type used to grow the virus. Direct corneal infection of rabbits with 17syn+ propagated in Vero cells caused 60% (6 of 10) to develop severe central nervous system (CNS) disease as evidenced by seizures and/or paralysis; all neurologically impaired rabbits died. In contrast, infection of rabbits with 17syn+ propagated in BHK-21 cells induced seizures and was fatal in 10% (1 of 10). The cell-specific attenuation of a 17syn+ occurred after one growth cycle in BHK-21 cells. To determine whether the decreased virulence of the BHK-21 cell-grown virus correlated with a less severe CNS inflammatory reaction, CNS tissues from rabbits infected with 17syn+ grown in Vero and BHK-21 cells were compared. Histopathological analyses revealed no differences in the location or severity of inflammatory lesions from rabbits infected with virus grown in either cell type. Virus-induced corneal disease was less dependent upon the cell type used to propagate the virus as there were no significant differences in the type or severity of observed corneal lesions. Possible explanations based on differences between Vero and BHK-21 cells are discussed.
Auto-Erlebniswelten und Bits im Tank — Multichannel-CRM in der Automobilbranche

Wohl kaum eine andere Branche nimmt in Deutschland, aber auch weltweit, eine vergleichbare Vorreiterrolle ein wie die Automobilindustrie. Lean Management, Total Quality Management, Business Process Reengineering oder Supply Chain Management sind Management-Konzepte, die bereits seit den achtziger Jahren in der Branche adaptiert wurden. Parallel dazu fanden Konzentrationsprozesse statt, wie die Fusionen von Daimler Benz mit Chrysler und Mitsubishi sowie Nissan mit Renault zu global prasenten Mega-Unternehmen verdeutlichen. Sowohl die anhaltende Konzentration als auch die zahlreichen Management-Konzepte sind dabei im uberwiegenden Mas dem Streben nach Kosteneffizienz zuzurechnen. Der Automobilbranche kann nach Jahren stetiger Verbesserung der angefuhrten Management-Konzepte zusammenfassend attestiert werden, dass der Grad der Prozessintegration im Inter-Branchenvergleich bereits sehr weit vorangeschritten ist. Allerdings nimmt die organisatorische Ausrichtung noch uberwiegend einen produktgetriebenen Fokus ein. Dies bedeutet, dass samtliche Wertschopfungsprozesse primar an der Herstellung und Vermarktung des Automobils orientiert sind, so dass sich der Wert fur den Kunden einzig und allein aus dem Produkt inharenten Leistungsmerkmalen und dem fur das Produkt zu zahlenden Preis ergibt. Erst langsam vollzieht sich der Wandel von der Produkt- und Technologieorientierung zur Kundenorientierung.
Government Liability Under Section 1983: The Present Is Prologue

Government liability under 42 U.S.C ? 1983, an important federal civil rights statute which created a fourteenth amendment action for damages, is a growth area of litigation.1 Ever since 1978, when the Su preme Court held in Monell v. Department of Social Services2 that local governments are considered persons amenable to suit under section 1983, the amount of litigation dealing with the standards for such liabil ity has been ever increasing, both at the federal district court and court of appeals level and in the Supreme Court. This should not be surprising given the importance for section 1983 plaintiffs of the availability of such deep-pocket defendants for whom, as will be seen, even qualified immunity is not available.3 This article will analyze recent developments concerning government liability under section 1983. It will begin with a brief description of the prior law, then move into a discussion of the current law. The following will be addressed: the status of states as suable persons under section 1983; the official policy or custom requirement for government liabil ity; the two ways in which a government can be held liable under section 1983; the differences among cases dealing with affirmative acts and failures to train or supervise; and government immunities from section 1983 liability. Significant Supreme Court cases will be analyzed, to gether with illustrative circuit court decisions.
Pericytes: The Brain’s Very First Responders?

Infection can negatively impact brain functions. Here, Duan et al. (2018) show that specific PDGFRβ-expressing cell subtypes of the neurovascular unit release the chemokine CCL2 rapidly after systemic infection, leading to increased neural excitability.
Pneumococcal vaccination for welders: Global deployment within a multi-national corporation.

Background Lobar pneumonia is an occupational disease of welders. This is the first report of global deployment of a pneumococcal vaccination program for welders within a multi-national corporation. Methods Global webinars were conducted to introduce the program. Communication packages translated into all location languages were deployed. All employee welders who had not previously been vaccinated were offered a free single dose of pneumococcal polysaccharide vaccine (PPV23) by on-site location medical centers during normal working hours. Numbers of vaccinated welders were reported by each location each month. Results Twelve months after starting the program, 241 of 767 welders have been vaccinated (31%) across six countries. Conclusions Global deployment of pneumococcal vaccination for welders can be successfully undertaken by a multi-national corporation. Adoption of this practice by corporations could reduce the incidence and mortality of pneumonia among welders globally.
Long-Lived 1D Excitons in Bright CdTe Quantum Wires

Time-resolved photoluminescence (PL) intensity decay profiles were recorded for room-temperature ensemble samples of CdTe quantum wires (QWs) with varying PL quantum yields (ΦPL). The PL lifetimes for samples with ΦPL > 4% are nearly an order of magnitude greater than the radiative lifetime of CdTe QDs, ≥200 versus ∼25 ns. The photogenerated electron–hole pairs relax to the lowest exciton state, correlating with the 1Σe and 1Σ3/2h quantum-confinement states, and are bound together as one-dimensional (1D) excitons. These 1D excitons have a thermal distribution of translational kinetic energy along the long, unconfined dimension of the QWs. The extended lifetimes are justified via the constraints imposed by the conservation of wave vector (or momentum) and the large mismatch between the wave vector of the moving 1D excitons and of the photons emitted during radiative relaxation. The long charge-carrier lifetimes and the dimensionality of these high-quality semiconductor QWs offer distinct advantages for use...
A murine ex vivo 3D kidney proximal tubule model predicts clinical drug-induced nephrotoxicity.

Drug attrition and clinical product withdrawals due to nephrotoxicity remain major challenges for pharmaceutical drug development pipelines. Currently, no reliable high-throughput in vitro screening models are available that provide reliable, predictive toxicology data for clinical nephrotoxicity. Drug screens to predict toxicity and pharmacology assessments are compromised by standard two-dimensional (2D) cell monoculture models. Here we extend a previously reported murine three-dimensional (3D) kidney-derived intact proximal tubule model to provide ex vivo drug toxicity data that reliably compare to clinical experiences and improve nephrotoxicity predictions over current 2D cell assays. Proximal tubule cytotoxicity was monitored by ATP depletion for 12 compounds (acarbose, acetylsalicylic acid, captopril, cimetidine, cidofovir, cisplatin, doxorubicin, gentamicin, polymyxin B, polymyxin B nonapeptide, probenecid and vancomycin) in 3D proximal tubule ex vivo assays. Drug concentration–response curves (1–1000 µM) and IC50, lowest effective concentration (LEC) and AUC values were compared to clinical therapeutic exposure levels (Cmax). The 100-fold Cmax threshold demonstrated best sensitivity (96.9%) and specificity (87.5%) for this assay, with high positive (93.9%) and negative (93.3%) predictive values for nephrotoxicity. IC50 values were superior to LEC. Results also support the model’s capability to predict substrate-inhibitor/competitor interactions, yielding toxicity results similar to those reported in vivo. These 3D proximal tubule-based drug screens provide more reliable nephrotoxicity predictions, and more insight into complex mechanisms implicated in nephrotoxicity than current standard 2D cell assays. This new approach for rapid drug toxicity testing produces more reliable clinical comparisons than current 2D cell culture screening techniques.
Water gas shift reactor modelling and new dimensionless number for thermal management/design of isothermal reactors

Abstract A new simplified modelling approach for using power law kinetics has been presented together with a methodology for modelling internal heat transfer inside the catalyst bed to a heat exchanger steam generator. The model has been validated and shown to be in good agreement with the performance of industrial scale water gas shift reactors. Furthermore, a case study has shown that isothermal shifting is able to reduce the catalyst volume compared to adiabatic shifting, however, a strong dependency upon the cooling density is observed. The here introduced rate optimization number (Ro) which compares the impact of temperature on the thermal driving force to the chemical driving force can help reactor designs to make effective use of the catalyst. For the water-gas-shift reaction, a value of −1 represents the optimum reaction rate. By designing the heat exchanger in the isothermal shift reactor in accordance with the Ro number a reduction of the required catalyst volume from initially 112.1 m3 (adiabatic reference case) to 54.9 m3 was possible; a reduction of 57.5%. The optimization with the Ro number has shown that an adiabatic inlet section is favorable and most of the cooling is needed after the adiabatic inlet length. The ideal temperature profile follows an almost linear temperature increase at the adiabatic inlet followed by an exponential decay along the reactor axis. Moreover, the application of the Ro number has shown to be highly accurate even under severe transport limitations.
Prevalence of denervation in the intrinsic foot muscles in patients with distal predominantly small fiber neuropathy

BACKGROUND We aimed to evaluate the significance of electromyographic findings in the intrinsic foot muscles (IFMs) of patients with skin biopsy proven small fiber neuropathy (SFN). METHODS This was a single-center retrospective analysis of patients who underwent skin biopsy for intra-epidermal nerve fiber density (IENFD) measurement and electrodiagnostic (EDX) study for evaluation of polyneuropathy. RESULTS A total of 1416 patents with normal lower extremity EDX studies proximal to the foot were included. Active denervation was seen in 16.1% of IFMs in patients with skin biopsy proven SFN and 4.1% of patients without SFN (P < .0001). Reinnervation changes without active denervation were observed in 30.4% of SFN patients and 23.8% of patients without SFN (P = .01). IENFD was lower in SFN patients with active denervation in IFMs than without (P < .0001). CONCLUSIONS Evaluation of active denervation in the IFMs can reveal large fiber dysfunction in SFN patients with otherwise normal routine EDX findings.
The shape of things to come: Topological data analysis and biology, from molecules to organisms

Shape is data and data is shape. Biologists are accustomed to thinking about how the shape of biomolecules, cells, tissues, and organisms arise from the effects of genetics, development, and the environment. Less often do we consider that data itself has shape and structure, or that it is possible to measure the shape of data and analyze it. Here, we review applications of topological data analysis (TDA) to biology in a way accessible to biologists and applied mathematicians alike. TDA uses principles from algebraic topology to comprehensively measure shape in data sets. Using a function that relates the similarity of data points to each other, we can monitor the evolution of topological features-connected components, loops, and voids. This evolution, a topological signature, concisely summarizes large, complex data sets. We first provide a TDA primer for biologists before exploring the use of TDA across biological sub-disciplines, spanning structural biology, molecular biology, evolution, and development. We end by comparing and contrasting different TDA approaches and the potential for their use in biology. The vision of TDA, that data are shape and shape is data, will be relevant as biology transitions into a data-driven era where the meaningful interpretation of large data sets is a limiting factor.
Single Flat Lens Enables Extreme Depth of Focus Imaging

With judicious design of a multi-level diffractive lens (MDL), it is possible to drastically enhance the depth of focus by over ∼4 orders of magnitude while maintaining focus for objects that are separated by ∼6m.