cssi/SciSciGPT-SciSciNet huggingface dataset:
Hydrophobicity and sorption of chlorophenolates to lipid membranes

Abstract We have studied sorption of ionized species of chlorophenols and pentahalophenols to lipid membranes using egg-phosphatidylcholine (egg-PC) vesicles and measuring their zeta-potential as a function of aqueous concentration of the phenolates. The zeta-potential isotherms can be understood in terms of a sorption model that is a combination of the Gouy-Chapman model of the electrical double layer at the membrane-water interface and the Langmuir model for sorption. Two intrinsic sorption parameters were determined: the linear partition coefficient, β m , which relates the membrane surface density of the phenolates to their aqueous concentration and the area of the adsorption site, P s . The linear partition coefficient is the measure of the affinity of phenolates to the lipid membrane. It depends strongly on the molecular structure: 2,6-dichlorophenolate β im =(0.45±0.08)×10 −7 m; 3,5-dichlorophenolate β m =(0.22±0.02)×10 m; 2,4,6-trichlorophenolate β m =(0.63±0.06)×10 −6 m; 2,4,5-trichlorophenolate β m =(0.11±0.01)×10 −5 m; 2,3,5,6-tetrachlorophenolate β m =(0.56±0.07)×10 −5 m; 2,3,4,5-tetrachlorophenolate β m =(0.55±0.06)×10 −5 m; pentachlorophenolate β m =0.34±0.05)×10 −4 m; pentachorophenolate β m =(1.00±0.13)×10 −7 m and pentabromophenolate β m =(0.19±0.04)×10 −3 m. P s was found to be independent of phenolate structure, P s = 3.3±0.1 nm 2 . The membrane affinity of chlorophenolates was compared with the octanol-water partition coefficients of un-ionized chlorophenols. It was shown that the free energy of transfer of chlorophenolates from water into the lipid membrane can be divided into non-electrostatic and electrostatic contributions. The no-nelectrostatic contribution corresponds to the hydrophobicity parameter α=−3.94±0.0.08 kcal per nm 2 of molecular surface area. The electrostatic contribution contains a term inversely proportional to the molecular radius of the phenolate ion which has the physical meaning of the work of transfer of the phenolate ion from water into the membrane. The polarity of the sorption region of egg-PC membranes is given in terms of the dielectric constant and was estimated to be 12.4 (range 10.5–13.4).
Abstract Syntax for Variable Binders: An Overview

A large variety of computing systems, such as compilers, interpreters, static analyzers, and theorem provers, need to manipulate syntactic objects like programs, types, formulas, and proofs. A common characteristic of these syntactic objects is that they contain variable binders, such as quantifiers, formal parameters, and blocks. It is a common observation that representing such binders using only first-order expressions is problematic since the notions of bound variable names, free and bound occurrences, equality up to alpha-conversion, substitution, etc., are not addressed naturally by the structure of first-order terms (labeled trees). This overview describes a higher-level and more declarative approach to representing syntax within such computational systems. In particular, we shall focus on a representation of syntax called higher-order abstract syntax and on a more primitive version of that representation called λ-tree syntax.
A multilayered ceramic (MLC) interface design for 125+MHz performance wafer probing (of SRAMs)

A design is presented using a multilayered ceramic (MLC) substrate as the basis for the wafer-tester interface. A 27*27 matrix of pads on 225 mu m centers is contacted; this design replaces a hand-wire interface between the wafer probe and tester performance board. Significant reductions in signal crosstalk and power supply noise are realized. >
Left thalamic hemorrhage with dysphasia: a report of five cases.

Abstract A specific type of “thalamic speech” is being recognized with increasing frequency. Paucity of spontaneous speech, fading vocal volume, anomia, perseveration, and neologisms, with intact comprehension and word repetition, characterize the speech disorder associated with thalamic lesions. Nine cases of left thalamic hemorrhage and speech disturbance have been reported previously. This report details the speech, neurological, and neuroradiological findings in five additional cases of thalamic hemorrhage with dysphasia.
Transient Viral DNA Replication and Repression of Viral Transcription Are Supported by the C-Terminal Domain of the Bovine Papillomavirus Type 1 E1 Protein

The bovine papillomavirus type 1 E1 protein is important for viral DNA replication and transcriptional repression. It has been proposed that the full-length E1 protein consists of a small N-terminal and a larger C-terminal domain. In this study, it is shown that an E1 polypeptide containing residues 132 to 605 (which represents the C-terminal domain) is able to support transient viral DNA replication, although at a level lower than that supported by the wild-type protein. This domain can also repress E2-mediated transactivation from the P89 promoter as well as the wild-type E1 protein can.
Testing the Cognitive Interview with Professional Interviewers: Enhancing Recall of Specific Details of Recurring Events

Summary Laboratory research and field research have reliably shown that the cognitive interview (CI) enhances eyewitness recall in comparison with standard interview protocols in a criminal investigation context. To address some of the major criticisms of the existing CI literature, the current experiment compared the CI with the Federal Law Enforcement Training Center's five-step interview protocol in an intelligence-gathering context using experienced interviewers and adult interviewees. The CI elicited significantly more event-relevant information from the interviewees than the five-step model, the standard training offered at Federal Law Enforcement Training Center. Copyright © 2014 John Wiley & Sons, Ltd.
Imperfect squeezing flow viscosimetry for commercial refried beans / Viscosimetría de extensión biaxial imperfecta de frijoles refritos

The imperfect squeezing flow patterns of almost intact canned fat free and vegetarian refried beans of two national brands were determined using all Teflon and grooved metal sensors. The force versus height curves were remarkably reproducible and characteristic of the products and brands irrespec tive of the upper plate's diameter and the sensor's finish. Both types of product had a very high degree of plasticity but those of one brand were more sensitive to the deformation rate. The consis tency of the corresponding products of the two brands could be compared in terms of an apparent stress at a predetermined height (1.5 and 2.5 mm), and their yield stress in terms of an apparent residual stress, or percent force drop, after a given time (60 and 120 s). At a deformation rate of 6 mm/min the apparent stress at a height of 1.5 mm was in the order of 9-11 or 15-19 kPa for the fat free products and 14-15 versus 18-20 kPa for the vegetarian products. After 120 s of relaxation, the stress decayed to about 30 to 60% of its initial level depending on the product and brand. The re sidual stress level was generally higher when determined with the grooved metal sensors. The prod ucts with relatively higher stresses at a given height also showed a relatively slower relaxation pat tern suggesting that consistency and apparent yield stress may be related rather than independent properties of refried beans.
Action on the Surface: Entomopathogenic Fungi versus the Insect Cuticle

Infections mediated by broad host range entomopathogenic fungi represent seminal observations that led to one of the first germ theories of disease and are a classic example of a co-evolutionary arms race between a pathogen and target hosts. These fungi are able to parasitize susceptible hosts via direct penetration of the cuticle with the initial and potentially determining interaction occurring between the fungal spore and the insect epicuticle. Entomogenous fungi have evolved mechanisms for adhesion and recognition of host surface cues that help direct an adaptive response that includes the production of: (a) hydrolytic, assimilatory, and/or detoxifying enzymes including lipase/esterases, catalases, cytochrome P450s, proteases, and chitinases; (b) specialized infectious structures, e.g., appressoria or penetrant tubes; and (c) secondary and other metabolites that facilitate infection. Aside from immune responses, insects have evolved a number of mechanisms to keep pathogens at bay that include: (a) the production of (epi) cuticular antimicrobial lipids, proteins, and metabolites; (b) shedding of the cuticle during development; and (c) behavioral-environmental adaptations such as induced fever, burrowing, and grooming, as well as potentially enlisting the help of other microbes, all intended to stop the pathogen before it can breach the cuticle. Virulence and host-defense can be considered to be under constant reciprocal selective pressure, and the action on the surface likely contributes to phenomena such as strain variation, host range, and the increased virulence often noted once a (low) virulent strain is “passaged” through an insect host. Since the cuticle represents the first point of contact and barrier between the fungus and the insect, the “action on the surface” may represent the defining interactions that ultimately can lead either to successful mycosis by the pathogen or successful defense by the host. Knowledge concerning the molecular mechanisms underlying this interaction can shed light on the ecology and evolution of virulence and can be used for rational design strategies at increasing the effectiveness of entomopathogenic fungi for pest control in field applications.
Estrogen Sulfotransferase: Intracrinology Meets Metabolic Diseases

Over the past two decades, the female hormone 17β-estradiol (estrogen) has emerged as an important contributor to energy homeostasis in both males and females. Early clinical evidence involved the observation that men lacking estrogen synthesis secondary to mutations in aromatase—the enzyme that converts androgen to estrogen—or men harboring estrogen resistance secondary to mutation of the estrogen receptor (ER)α, develop visceral obesity, insulin resistance, and/or glucose intolerance (1,2). As an experimental confirmation, it was observed that elimination of the aromatase or ERα genes in male and female mice produced the same metabolic syndrome as in humans (3,4). Thus, it is reasonable to assume that although men have lower circulating estrogen concentrations than premenopausal women, aromatization of circulating androgen to estrogen in target metabolic tissues equilibrates cellular estrogen concentrations, and ER activation is critical in both sexes in promoting fuel homeostasis (5). This is consistent with the paradigm that estrogen functions as a circulating hormone in premenopausal women. Conversely, in men and in postmenopausal women—in whom estrogen concentrations are low—estradiol does not function as a hormone; instead, it is synthesized in extragonadal sites such as breast, brain, bone, and fat where it acts locally as a paracrine or intracrine factor (6). Thus, in men and in postmenopausal women, the driver of estrogen action is not circulating estrogens; rather, it depends on estrogen biosynthesis from a circulating source of androgenic precursors such as testosterone. A logical consequence …
Characterization of Paenibacillus larvae bacteriophages and their genomic relationships to firmicute bacteriophages

Paenibacillus larvae is a Firmicute bacterium that causes American Foulbrood, a lethal disease in honeybees and is a major source of global agricultural losses. Although P. larvae phages were isolated prior to 2013, no full genome sequences of P. larvae bacteriophages were published or analyzed. This report includes an in-depth analysis of the structure, genomes, and relatedness of P. larvae myoviruses Abouo, Davis, Emery, Jimmer1, Jimmer2, and siphovirus phiIBB_Pl23 to each other and to other known phages. P. larvae phages Abouo, Davies, Emery, Jimmer1, and Jimmer2 are myoviruses with ~50 kbp genomes. The six P. larvae phages form three distinct groups by dotplot analysis. An annotated linear genome map of these six phages displays important identifiable genes and demonstrates the relationship between phages. Sixty phage assembly or structural protein genes and 133 regulatory or other non-structural protein genes were identifiable among the six P. larvae phages. Jimmer1, Jimmer2, and Davies formed stable lysogens resistant to superinfection by genetically similar phages. The correlation between tape measure protein gene length and phage tail length allowed identification of co-isolated phages Emery and Abouo in electron micrographs. A Phamerator database was assembled with the P. larvae phage genomes and 107 genomes of Firmicute-infecting phages, including 71 Bacillus phages. Phamerator identified conserved domains in 1,501 of 6,181 phamilies (only 24.3%) encoded by genes in the database and revealed that P. larvae phage genomes shared at least one phamily with 72 of the 107 other phages. The phamily relationship of large terminase proteins was used to indicate putative DNA packaging strategies. Analyses from CoreGenes, Phamerator, and electron micrograph measurements indicated Jimmer1, Jimmer2, Abouo and Davies were related to phages phiC2, EJ-1, KC5a, and AQ113, which are small-genome myoviruses that infect Streptococcus, Lactobacillus, and Clostridium, respectively. This paper represents the first comparison of phage genomes in the Paenibacillus genus and the first organization of P. larvae phages based on sequence and structure. This analysis provides an important contribution to the field of bacteriophage genomics by serving as a foundation on which to build an understanding of the natural predators of P. larvae.
Lymphedematous verrucous changes simulating squamous cell carcinoma in long-standing hidradenitis suppurativa

Background Hidradenitis suppurativa (HS) is a relatively common condition marked by abscesses, sinus tracts, and scarring in intertriginous regions of the body. Lymphedema is an under-recognized consequence of chronic inflammation in the setting HS. Methods We report five cases of patients with lymphedema resulting from long-standing HS; the patients were seen either in a specialty HS clinic or general dermatology clinic at our institution. Biopsies for histologic analysis were performed on four of the five patients reported here. Results Changes of lymphedema may be manifested diffusely as widespread plaques or focally as verrucous papules and nodules. The latter may be difficult to distinguish clinically from squamous cell carcinoma, another complication of chronic HS. Histopathologic features of lymphedema include dilated lymphatic channels, diffuse edema, verrucous epidermal hyperplasia, mixed inflammation, and dermal fibrosis. Conclusion Lymphedema associated with chronic HS, which we also term “verrucous lymphostasis,” encompasses a spectrum of clinical and histopathologic findings. Squamous cell carcinoma may mimic focal presentations of lymphedema, and biopsy may be necessary to distinguish the two.
Electrical Properties of Boron Nitride Matrix Composites: I, Analysis of McLachlan Equation and Modeling of the Conductivity of Boron Nitride–Boron Carbide and Boron Nitride–Silicon Carbide Composites

The McLachlan equation, which incorporates both effective medium models and percolation, was used to predict the volume fraction-conductivity relationships of insulator-conductor composites, and results were compared with experimental data. Two composite systems were investigated (BN-B 4 C and BN-SiC). Both systems are anisotropic, because of the orientation of BN platelets perpendicular to the hot-pressing direction. For BN-B 4 C composites, with increasing B 4 C content, the ac and dc conductivities are relatively constant to ∼40% B 4 C (the critical volume fraction). At this composition, the conductivity suddenly increases to a value closer to that of B 4 C and then resumes a gradual increase. Little difference is seen for measurements made perpendicular or parallel to the hot-pressing direction, i.e., perpendicular or parallel to the BN platelets. Similar results are found for the BN-SiC composites, except that the critical volume fraction is ∼20% SiC in this case. The experimental curves are in good agreement with those predicted by the McLachlan equation. The parameters s and t of the McLachlan equation relate to the morphology of the phases present in the microstructure. The critical volume fraction relates to the connectivity of the phases in the composites.
Renormalization Group Analysis of Grand Unified Theories in Curved Space-time

We consider a class of grand unified theories (GUT's) based on the Georgi-Glashow model in curved spacetime. We are particularly concerned with the coupling constants involving the curvature. These include the cosmological and gravitational constants, as well as coupling constants appearing in terms quadratic in the curvature and in terms which link the Higgs bosons to the scalar curvature. For asymptotically free theories, we use the renormalization group to obtain expressions for these effective coupling constants at high curvature (between the GUT and Planck scales). We discuss the role of the effective coupling constants in the gravitational field equations. These results may be of importance for cosmology.
Are perceived neighborhood hazards a barrier to physical activity in children

Background: We hypothesized that children’s perceptions of more neighborhood hazards would be associated with less physical activity, less aerobic fitness, and a higher body mass index. Objective: To examine the association between a hazardous neighborhood context and physical activity in children. Methods: Fourth-grade students (n=796) of diverse ethnic and economic backgrounds completed measures of neighborhood hazards, self-reported physical activity, physical fitness, height, and weight. Parents (n=518) completed telephone interviews and provided data on their education level and occupation. Results: As expected, children from families of lower socioeconomic status perceived significantly more neighborhood hazards. Contrary to our hypothesis, the perception of more hazards was significantly associated with more reported physical activity. This finding was not explained by school heterogeneity, alteration of the hazards measure, or differences in socioeconomic status. Conclusion: To further examine the relationship between neighborhood hazards and physical activity, we suggest that future studies include assessments of sedentary behavior, parental fear of violence, parental regulation of children’s leisure activities, and cost and quality of available play areas and organized sports. Arch Pediatr Adolesc Med. 2001;155:1143-1148
Probability Angling: A Recreational Fishery Management Strategy

Abstract Probability angling is a recreational fishery management strategy that uses catch assessment data to establish criteria for evaluating personal recreational angling success. Angling groups on two reservoirs on each of two river drainages in the southeastern United States were asked to rate their incompleted trip quality and fishing success as either poor, fair, good or excellent. Trip-quality ratings were not correlated with ratings of fishing success. Total weight and total number of fish caught per incompleted trip were correlated best with fishing-success ratings among eight descriptors of each group's catch. Drainage catches (via pooling catches from two reservoirs) were significantly different regarding total number of fish per angling group, yet anglers did not rate their fishing success differently between drainages. Collectively, fishermen adjusted their success expectations (i.e., mean number of fish caught within each success category) according to intended target and river system fishe...
Functional organization of crayfish abdominal ganglia: II. Sensory afferents and extensor motor neurons

Abdominal ganglia of crayfish contain identifiable neuropils, commissures, longitudinal tracts, and vertical tracts. To determine the functional significance of this ganglionic framework, we backfilled the following types of neurons with cobalt chloride: sensory hair afferents, slow and fast extensor motor neurons, the segmental stretch receptor neurons, and their inhibitory accessory cells. After the cobalt ions were precipitated and intensified, we studied the central projections of the filled neurons within the ganglionic structures. All of the axons of these neurons exit or enter each of the first five abdominal ganglia through the second pair of nerves. Our description of the central projections of the hair afferents is the first in the literature. These afferents innervate the large ventral horseshoe neuropil (HN) in the core of each ganglion. This neuropil is homologous to the insect ventral association centers, which also process sensory information. Furthermore, we discovered that some of the crayfish afferents innervate glomeruli within the HN. The slow and fast extensor motor neurons, the stretch receptor neurons, and the accessory cells branch mostly in the dorsal part of the ganglion. We reinterpret previous identifications of the extensor neurons that were based largely on soma position. Together with our previous descriptions of the flexor motor neurons, these results allow us to relate both rapid tail-flips and slower postural movements to the structure of the segmental ganglia.
Novel Alkylidenating Agents via the α Lithiation of Monoalkyl Group 4 Metal Derivatives: Methylidene-Metal Complexes and Their Active Lithiated Precursors

The interaction of the Group 4 metal chlorides, MCl4, where M = Ti, Zr, Hf, with two equiv. of methyllithium at –78 °C in toluene has led to the corresponding methylidene-metal complex, H2C=MCl2, possibly complexed with LiCl. That this complex was stable to at least –40 °C was demonstrated by adding chemical trapping agents at this temperature: 1) benzophenone was quantitatively converted into 1,1-diphenylethylene when M = Ti or Zr; with the Hf analogue, a 1:3 mixture of 1,1-diphenylethylene and 1,1-diphenylethanol was produced; 2) propiophenone reacted with the methylidene complex to yield 2-phenyl-1-butene, 38 % (M = Ti) or 25 % (M = Zr), with the majority of the propiophenone being recovered (the unreacted ketone is attributed to enolate salt formation competing with the methylidenation); 3) diphenylacetylene reacted with H2C=TiCl2 by cycloaddition in 50 % yield, ultimately to give a 1:1 mixture of α-methyl-cis-stilbene and α-methyl-trans-stilbene; and finally 4) norbornene was polymerized in a ROMP process by either the methylidene-titanium or methylidene-zirconium complex, but the titanium catalyst exhibited higher activity. The stability of such methylidene complexes proved to be highly temperature- and solvent-dependent: 1) the methylidene complex in toluene was no longer detectable by chemical trapping when the reaction mixture was warmed to 0 °C or above; 2) the generation of the methylidene complex in THF was uniformly unsuccessful even at –78 °C or above. From these observations this study concludes that in toluene the free methylidene complex, H2C=MCl2, is not present but rather the agent is still bonded to LiCl. At higher temperatures in toluene or even at –78 °C in THF, the LiCl dissociates from such complexation and the free methylidene dimerizes to [Cl2M–CH2]2, as is known in the case of Cp2Ti=CH2. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Social Capital, Labor Mobility, and Welfare: The Impact of Uniting States

It is generally assumed that a technological or political change resulting in greater labor mobility raises welfare because it allows labor to move to where returns are higher and exploit profit op...
Robot planning with a semantic map

Context is an important factor for domestic service robots to consider when interpreting their environments to perform tasks. In people's homes, rooms are laid out in a specific arrangement to enable comfortable and efficient living; for example, the living room is central to the house, and the dining room is adjacent to the kitchen. The identity of the objects in a room are a strong cue for determining that room's purpose. This paper will present a planner for an autonomous mobile robot system which uses room connectivity topology and object understanding as context for an object search task in a domestic environment.
A High Sensitivity Gamma Ray Imager (HiSGRI) Based on Wavelength-Shifting Fiber Readout of LaBr3 Scintillators

Cerium-doped lanthanum bromide offers increased light yield and peak emission at shorter wavelengths compared to standard inorganic scintillators such as NaI or CsI. As a result, lanthanum bromide scintillators can be used as the basis of large scale hard x-ray/gamma ray imaging systems. By coupling a Ce: LaBr3 scintillator with orthogonal layers of wavelength-shifting fibers viewed by multianode photomultiplier tubes to provide x-y position together with an Anger camera array of large area photomultiplier tubes to measure energy, a detector can be constructed with millimeter-scale position resolution and energy resolution only somewhat less than that obtained with bulk scintillators. We present measurements of the light yields and position resolution achievable with such a system.
Anaerobic Degradation of Cadaver Waste Using an Attached Growth Recycle System

AbstractIn this study, mixed wastes composed of high levels of phenol, formalin, and ethanol emanating from biotechnology and health science laboratories on the Florida Gulf Coast University (FGCU) campus were degraded under anaerobic conditions in a hybrid suspended-attached growth system. Batch experiments were conducted using 80% removal of initial phenol concentrations as an end point. Formalin concentration was used to set the initial feeding constraints. After a stable, low level of phenol and chemical oxygen demand (COD) removal were established, three experimental periods demonstrated the simultaneous removal of 80% of influent COD, 97% removal of formalin, and at least 85% removal of phenol (concentrations of 1,000, 110, and 170 mg·L−1, respectively). A biogas was produced continuously, but was not quantified nor identified because of constraints. Further research is needed to determine mineralization and possible intermediate formation and to prove such a system is a viable option for the on-si...
Neuropsychological Assessment Approaches and Diagnostic Procedures

The purpose of this chapter is twofold. First, we will briefly review three generally accepted approaches to neuropsychological assessment. Second, we will present our transactional assessment approach. This discussion will include evaluation methods for selected functional areas of the central nervous system. The conceptual framework underlying each battery and research with each approach will also be presented.
Combined treatment with MET inhibitors and other therapies in lung cancer.

Molecular targeted therapy has made significant progress in human cancers in the past decade and has become an integral part of modern human cancer treatment. Targeted drugs are now moving closer to be used in tailored therapy with personalized molecular predictive biomarkers assay development to couple with the therapeutics. Much progress has been made in non-small cell lung cancer (NSCLC) using the tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib to target the epidermal growth factor receptor (EGFR) clinically in patients with advanced disease (1). However, the long term efficacy of the TKIs is still inevitably limited, as patients with NSCLC who initially have primary tumor response, always develop acquired resistance against EGFR-TKI monotherapy typically after 6-12 months of treatment (2). Recent research studies to elucidate mechanisms of acquired EGFR TKI resistance identified alternative molecular targets of receptor tyrosine kinases (RTKs) to be responsible, such as AXL (3), as well as MET receptor (4) and its natural ligand hepatocyte growth factor (HGF) (5), as implicated in mediating the tumor escape process.
Antidiabetic characteristics of dehydroepiandrosterone in animal and human studies

Interest in dehydroepiandrosterone (DHEA) as a metabolic factor involved with diabetes in relation to obesity dates back to a study published by Sonka and coworkers1 30 years ago. They reported that no DHEA was detected in the urine of 27 of 32 elderly obese diabetic subjects. This and other studies led Sonka2 to the speculation that DHEA, a 17-ketosteroid produced in the adrenal gland, may have important regulatory functions in the body. Since these early observations were made, ameliorative effects resulting from the administration of DHEA were obtained in numerous studies. Most studies have used mice and rats, but additional work has been presented in dogs, monkeys, rabbits, and humans. An array of effects was attributed to DHEA treatment, including prevention of cancer, aging, obesity, viral diseases, and atherosclerosis.3–6 Following in Sonka’s path there have also been further investigations into the role of DHEA as an antidiabetic agent. My overview of the literature is pertinent to this potential characteristic of DHEA.
Discovery of 2-Indole-acylsulfonamide Myeloid Cell Leukemia 1 (Mcl-1) Inhibitors Using Fragment-Based Methods

Myeloid cell leukemia-1 (Mcl-1) is a member of the Bcl-2 family of proteins responsible for the regulation of programmed cell death. Amplification of Mcl-1 is a common genetic aberration in human cancer whose overexpression contributes to the evasion of apoptosis and is one of the major resistance mechanisms for many chemotherapies. Mcl-1 mediates its effects primarily through interactions with pro-apoptotic BH3 containing proteins that achieve high affinity for the target by utilizing four hydrophobic pockets in its binding groove. Here we describe the discovery of Mcl-1 inhibitors using fragment-based methods and structure-based design. These novel inhibitors exhibit low nanomolar binding affinities to Mcl-1 and >500-fold selectivity over Bcl-xL. X-ray structures of lead Mcl-1 inhibitors when complexed to Mcl-1 provided detailed information on how these small-molecules bind to the target and were used extensively to guide compound optimization.
Blood In, Buyout: A Property & Economic Approach to Street Gangs

This article offers a fresh analysis of and solution to problems modern American street gangs present. Common wisdom dictates that, since they commit crimes, gangs should be understood and combatted through criminal sanctions. Popular interventions, like gang injunctions, expand that punitive orientation into civil strategies. But, gang criminality is merely a manifestation of a broader property-based disease. Therefore, those strategies will be ineffective and inefficient, as evidenced by the continuing rise in gang membership across the United States. The consensus in gang research is that gangs are not crime syndicates; they are capitalist social institutions creating and operating in alternative markets. Violence and criminality are secondary or tertiary facets of gangs, resulting from the inaccessibility of mainstream markets. Integrating these findings into a unique synthesis of disparate threads of property theory—from Charles A. Reich’s The New Property and Margaret Jane Radin’s Property and Personhood to Cheryl I. Harris’ Whiteness as Property—it is clear that gangs’ primary purpose is to pursue the forms of property central to human identity. That insight frees anti-gang strategies from the strictures imposed by criminal law, but it also complicates the equation by revealing social justice considerations not normally associated with gangs. From that foundation, this article presents a novel idea: Gangs are recreating a traditional market-based property system, so the approach to the problems associated with them should be market-inspired. In the market, actors are paid to induce desired behavior. Therefore, local governments should compensate gang members for nonparticipation in legal (but undesirable) gang activity. The article tests this proposal using Guido Calabresi and A. Douglas Melamed’s framework for allocating and protecting entitlements advanced in Property Rules, Liability Rules, and Inalienability: One View of the Cathedral. That analysis shows that the so-called “paid injunction” is a more effective and efficient approach to curbing the non-criminal activities of gangs that simultaneously advances the social justice concerns revealed by the property law analysis.
A comparison of Giardia microti and Spironucleus muris cysts in the vole: an immunocytochemical, light, and electron microscopic study.

We have shown that cysts of the genus Spironucleus share many common morphological features with Giardia cysts including: 2-4 nuclei, flagellar axonemes, a distinct cyst wall, and they even display the same immunostaining as Giardia cysts when labeled with antibodies specific for Giardia cyst wall. A direct comparison of Spironucleus muris and Giardia microti cysts has revealed that cysts of S. muris are significantly smaller than cysts of G. microti. At the ultrastructural level, the cyst walls are similar in fibrillar appearance, but the width of the S. muris cyst wall is significantly less than that of G. microti. The cysts of S. muris also differ from G. microti in that they contain a striated rootlet fiber, flagellar sheath, and numerous glycogen rosettes. Characteristic features of Giardia include the adhesive disc and median body. Although the cysts of Spironucleus and Giardia are similar in appearance, these unique morphological features can be used to distinguish between the 2 protozoa and should be employed in the detection of Giardia cysts in water samples. Giardiasis is the most common waterborne
Effect of Application Methods and pH Values on Induced Resistance of Pectinases Extract against Scab Disease of Cucumber

Influence of different treatment methods and pH variation of pectinases extract of Penicillium oxalicum on its efficiency of induced resistance to scab caused by Cladosporium cucumerinum in cucumber plants was studied.Among these 4 treatment methods,spray application showed the maximum decrease of disease index of scab and the induced efficiency of two concentrations of pectinases(100 and 200 U/ml) were 56.34% and 64.13%,respectively.Other methods,including hypocotyls injection,root soakage and seed treatment had less induced efficiency. The disease index decreased in pectinases treated leaves,while no difference in disease index was observed between untreated leaves and control leaves.The result indicated the induced efficiency against the disease mainly attributed to local resistance.Repeated applications of pectinases extract enhanced induced efficiency and prolonged the duration of control of the disease.pH variation of pectinases extract showed different effect on induced resistance to cucumber scab.At pH5.5,cucumber plants expressed the highest resistance with induced efficiency of 51.87% and 66.42% respectively at the two concentrations.
Alcohol and pyruvate cardioplegia: Twenty-four-hour in situ preservation of hamster hearts

Isolated hamster hearts were first perfused with a normal Krebs-Henseleit medium to demonstrate comparable viability of hearts before perfusing and storing them for 24 hours in one of three solutions. The three solutions were a physiologic saline with pyruvate as the substrate and 4% alcohol to arrest the heart (group 1), a standard cardioplegic solution (group 2), and an alcohol-free physiologic saline with pyruvate as the substrate (group 3). Recovery in terms of rate/pressure product and oxygen consumption after 30 minutes of reperfusion was 81% and 93%, respectively, for group 1, 13% and 32% for group 2, and 70% and 72% for group 3. Percent of physiologic recovery was not related to recovery of adenosine triphosphate. The adenosine triphosphate level returned to approximately 40% control level in all three groups, and in all three groups inorganic phosphate remained approximately 320% over control level after 30 minutes of reperfusion. Phosphocreatine level was significantly higher in groups 1 and 3 than in group 2, as a result of improved oxygen consumption. Intracellular pH, determined by phosphorous 31 nuclear magnetic resonance spectroscopy, was physiologic in groups 1 and 3 but alkaline in group 2. This alkalinity may have been caused by leaky membranes. Pyruvate helped preserve mitochondrial function during depressed oxygen delivery, such as was seen during the 24-hour storage period. Four percent alcohol arrested the heart; combined with pyruvate, it was best for preserving functional recovery. Both pyruvate and pyruvate plus alcohol solutions were better than a standard cardioplegic solution for maintaining functional capability.
2-year-olds use syntax to infer actor intentions in a rational-action paradigm.

Verbs may refer to the means (I bumped into the lamp) or outcome (I broke the lamp) of an action (cf. Rappaport Hovav & Levin, 2010; Talmy, 1985). Do young children expect language to encode this distinction? Children’s imitation patterns suggest that they analyze nonlinguistic events in these terms. When a head-touch is the simplest action available, toddlers include just the outcome, not the means, in their own imitation (Gergely, Bekkering, & Kiraly, 2002). We ask whether syntax influences this inference. An experimenter with her hands occupied made a toy activate with a headtouch, using either Means-focused (I’m daxing to my toy) or Outcome-focused language (I’m daxing my toy). Toddlers then imitated the action. Meansbut not Outcome-focus language encouraged children to include the distinctive headtouch, overriding the standard ‘rational imitation’ effect. This suggests that toddlers’ knowledge of argument structure includes an understanding of a means/outcome divide in verb meaning.
Paul Ehrlich and the Early History of Granulocytes.

Paul Ehrlich's techniques, published between 1879 and 1880, for staining blood films using coal tar dyes, and his method of differential blood cell counting, ended years of speculation regarding the classification of white cells. Acidic and basic dyes had allowed him to recognize eosinophil and basophil granules, respectively, work that was a direct continuation of his discovery of the tissue mast cell described in his doctoral thesis. Ehrlich went on to develop neutral dyes that identified epsilon granules in neutrophils ("cells with polymorphous nuclei"). He also speculated, for the most part correctly, on the formation, function, and fate of blood neutrophils and eosinophils. Before Ehrlich, a number of important observations had been made on white cells and their role in health and disease. Among the most notable were William Hewson's studies of blood and lymph; the early descriptions of leukemia by Alfred Donne, John Hughes Bennett, Rudolf Virchow, and others; as well as seminal observations on inflammation by William Addison, Friedrich von Recklinghausen, and Julius Cohnheim. Eosinophils were almost certainly recognized previously by others. In 1846, Thomas Wharton Jones (1808-1891) described "granule blood-cells" in several species including humans. The term "granule cell" had also been used by Julius Vogel (1814-1880), who had previously observed similar cells in inflammatory exudates. Vogel, in turn, was aware of the work of Gottlieb Gluge (1812-1898), who had observed "compound inflammatory globules" in pus and serum that resembled eosinophils. Almost 20 years before Ehrlich developed his staining methods, Max Johann Schultze (1825-1874) performed functional experiments on fine and coarse granular cells using a warm stage microscopic technique and showed they had amoeboid movement and phagocytic abilities. Despite these earlier observations, it was Ehrlich's use of stains that heralded the modern era of studies of leukocyte biology and pathology.
Plato on the Necessity of Imitation and Habituation for the Cultivation of the Virtues

In his paper “On the old saw that dialogue is a Socratic but not an Aristotelian method of moral education,” Kristjan Kristjansson (2014, p. 33) attempts to “chip away at [the] received wisdom” concerning certain distinctions between Socrates/Plato’s and Aristotle’s ideas on moral education. Kristjansson argues against “the old saw” that it is only Socrates who promotes dialogue as a necessary component of moral education. According to Kristjansson, contrary to received wisdom, Aristotle also promotes dialogue, believing that it is central to the development of certain virtues. I find Kristjansson’s argument persuasive and believe that he has made an important first step in “blur[ring] the boundaries between the two thinkers” (2014, p. 33). This paper aims to blur further the boundary between them by arguing that there is another “old saw” that needs to be dealt with, namely, that it is only Aristotle who believes in the necessity of imitation and habituation in the development of virtues. I argue, contrary to the received wisdom, that Plato is not indifferent to imitation and habituation, but actually sees them as central to moral education. The standard interpretation, popularized among educators by the towering figure of Lawrence Kohlberg (1981, pp. 29–38), holds that Plato considers knowledge to be sufficient for virtuous action and a virtuous life. I argue that this interpretation is false. While Plato believes that knowledge is, at times, an extremely important handmaiden of moral education in the initial stages of an individual’s development, he does not believe that it is sufficient to complete the education. Only imitation and habituation can do that work. One of the aims of this chapter is to make Plato’s position on this clear, and in so doing make clearer the similarity between Plato and Aristotle. There is another aim to this paper, however. It is to show that the fact that Plato does emphasize the role of knowledge in the initial stages of education makes his conception of moral education particularly useful to contemporary educators of secondary students. Indeed, in this respect, Plato’s vision is superior to Aristotle’s insofar as it includes a process by which students who missed the proper imitation and habituation in their youth can develop it later in their lives. Aristotle says that such people are not morally educable (Aristotle 1984, p. 1864; Burnyeat 1980, p. 75; Sherman 1999, p. 237), whereas Plato believes that they are educable, and even provides insights into how to go about educating them.
Sexual function following hysterectomy for endometrial cancer: A five-year follow up investigation.

Abstract Objectives We sought to determine a baseline and five-year follow up sexual function score in women undergoing hysterectomy for endometrial cancer. Methods A cross-section of endometrial cancer patients receiving care from 2006 to 2010 was identified. Patients were surveyed during academic year 2011 using the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ). Respondents were re-surveyed in 2016. The PISQ was also administered at a single time point to a control group of urogynecology patients. Statistical analyses were conducted using STATA software, version 13.1. Results 129 endometrial cancer and 63 matched urogynecology patients responded to an initial survey and sufficiently answered the PISQ. There was no statistical difference in BMI, race, diabetes, or smoking history between groups. In 2011, 62.5% of endometrial cancer patients versus 72.6% of urogynecology patients reported sexual activity (p = 0.166). Median PISQ score for these groups was 33 [IQR 29–38] and 32 [IQR 28–37] respectively (p = 0.472). Twenty-nine (22%) endometrial cancer patients sufficiently answered the initial and 5-year follow up PISQ to be included in follow up analysis. Median PISQ score at five years was not significantly different from baseline: 31 [IQR 27–39] versus 33 [IQR 31–38] (p = 0.299). With multivariable modeling, no demographic or clinical characteristics of endometrial cancer patients were independently associated with sexual function (p = NS). Conclusions Sexual function for endometrial cancer patients was not significantly different from women treated for benign disease. Sexual function also remained stable for endometrial cancer patients regardless of time from initial treatment. Further prospective studies are needed to better characterize sexual function in endometrial cancer survivors.
Crouch severity is a poor predictor of elevated oxygen consumption in cerebral palsy

Children with cerebral palsy (CP) expend more energy to walk compared to typically-developing peers. One of the most prevalent gait patterns among children with CP, crouch gait, is often singled out as especially exhausting. The dynamics of crouch gait increase external flexion moments and the demand on extensor muscles. This elevated demand is thought to dramatically increase energy expenditure. However, the impact of crouch severity on energy expenditure has not been investigated among children with CP. We evaluated oxygen consumption and gait kinematics for 573 children with bilateral CP. The average net nondimensional oxygen consumption during gait of the children with CP (0.18±0.06) was 2.9 times that of speed-matched typically-developing peers. Crouch severity was only modestly related to oxygen consumption, with measures of knee flexion angle during gait explaining only 5-20% of the variability in oxygen consumption. While knee moment and muscle activity were moderately to strongly correlated with crouch severity (r2=0.13-0.73), these variables were only weakly correlated with oxygen consumption (r2=0.02-0.04). Thus, although the dynamics of crouch gait increased muscle demand, these effects did not directly result in elevated energy expenditure. In clinical gait analysis, assumptions about an individual's energy expenditure should not be based upon kinematics or kinetics alone. Identifying patient-specific factors that contribute to increased energy expenditure may provide new pathways to improve gait for children with CP.
Evidence of Dietary Improvement and Preventable Costs of Cardiovascular Disease.

We conducted a review to summarize preventable medical costs of cardiovascular disease (CVD) associated with improved diet, as defined by the 2020 Strategic Impact Goal of the American Heart Association. We searched databases of PubMed, Embase, CINAHL and ABI/INFORM to identify population-based studies published from January 1995 to December 2015 on CVD medical costs related to excess intake of salt/sodium or sugar-sweetened beverages, and inadequate intake of fruits and vegetables, fish/fish oils/omega-3 fatty acids, or whole grains/fiber/dietary fiber. Based on the American Heart Association's secondary dietary metrics, we also searched the literature on inadequate intake of nuts and excess intake of processed meat and saturated fat. For each component, we evaluated the CVD cost savings if consumption levels were changed. The cost savings were adjusted into 2013 US dollars. Among 330 studies focusing on diet and economic consequences, 16 studies evaluated CVD costs associated with 1 or more dietary components: salt/sodium (n = 13), fruits and vegetables (n = 1), meat (n = 1), and saturated fat (n = 3). In the United States, reducing individual sodium intake to 2,300 mg/day from the current level could potentially save $1,990.9/person per year for hypertension treatment, based on a simulation study. Increasing consumption of fruits and vegetables from 1.5 cups/day could save $1,568.0/person per year in treatment costs for CVD, based on a cohort study. Potential CVD cost savings associated with diet improvement are substantial. Interventions for reducing sodium intake and increasing fruit and vegetable consumption could be viable means to alleviate the increasing national medical expenditures.