cssi/SciSciGPT-SciSciNet huggingface dataset:
Broadly neutralizing anti-HIV antibodies prevent HIV infection of mucosal tissue ex vivo

Broadly neutralizing monoclonal antibodies (nAbs) specific for HIV are being investigated for use in HIV prevention. Due to their ability to inhibit HIV attachment to and entry into target cells, nAbs may be suitable for use as topical HIV microbicides. As such, they would present an alternative intervention for individuals who may not benefit from using antiretroviral-based products for HIV prevention. We theorize that nAbs can inhibit viral transmission through mucosal tissue, thus reducing the incidence of HIV infection. The efficacy of the PG9, PG16, VRC01, and 4E10 antibodies was evaluated in an ex vivo human model of mucosal HIV transmission. nAbs reduced HIV transmission, causing 1.5- to 2-log10 reductions in HIV replication in ectocervical tissues and ≈3-log10 reductions in HIV replication in colonic tissues over 21 days. These antibodies demonstrated greater potency in colonic tissues, with a 50-fold higher dose being required to reduce transmission in ectocervical tissues. Importantly, nAbs retained their potency and reduced viral transmission in the presence of whole semen. No changes in tissue viability or immune activation were observed in colonic or ectocervical tissue after nAb exposure. Our data suggest that topically applied nAbs are safe and effective against HIV infection of mucosal tissue and support further development of nAbs as a topical microbicide that could be used for anal as well as vaginal protection.
Embracing The Future: What Can Accounting Graduates Expect?

This article informs accounting educators and graduates about key issues in the accounting profession of today, which has entered a new age, and accounting educators and advisors, old and new, must be informed about future prospects for students and make students aware of what they can expect as accounting graduates. Passing this knowledge to students early on provides them with advanced understanding of what the future holds for accounting professionals and will allow students to better embrace their future once they graduate. This article emphasizes supply and demand, hiring and salary practices, and potential job opportunities for the accounting graduate. Information on the various certifications available for accountants and the interview process is included as well. The final section within the article offers insight into the future of the accounting profession. With this paper, educators and advisors gain knowledge to assist accounting students with their future career search process. Students will still need assistance to help them navigate the new environment that they are about to enter, but a clearer understanding of what to expect provides a better foundation on which to build a successful career.
A ‘tile’ tale: Hierarchical self-assembly of DNA lattices

Abstract DNA has been used as a material for the construction of complex nanostructures. Branched DNA molecules can be glued together by sticky end cohesion, providing a route to dictate hierarchical self-assembly of one-, two- and three-dimensional periodic lattices. DNA tiles provide site-specific attachment sites, and can lead to spatially positioned arrays of nanoparticles or macromolecules with nanometer-scale precision. This review discusses the origin and use of various DNA tiles in constructing higher order DNA lattices that can be used as scaffolds for hosting external guests. In addition, the development of DNA origami tiles and arrays is also discussed.
The Validity of Disease-Specific Quality of Life Attributions Among Adults with Multiple Chronic Conditions

Background : A crucial assumption underlying all disease-specific quality of life (QOL) measures, that patients can validly differentiate a specific disease in the presence of multiple chronic conditions , has not been tested using multiple methods. Our objective was to evaluate the convergent and discriminant validity of QOL attributions to specific diseases among adults with multiple chronic conditions (MCC). Methods : Adults age 18 and older (N=4,480) sampled from eight pre-identified condition groups (asthma, COPD, angina/MI with angina, congestive heart failure, diabetes, chronic kidney disease, osteoarthritis, rheumatoid arthritis) completed an Internet survey. Comorbid conditions were determined using a 35-condition checklist. Product-moment correlations were analyzed separately by pre-identified condition group using the multitrait-multimethod of construct validation, where traits were defined by 9-26 conditions and each condition was measured by two methods: disease severity rating and Disease-specific Quality of Life Impact Scale (QDIS) global rating. A third method (symptom or clinical marker) was available for the eight pre-identified conditions. Convergent validity was supported when correlations among different methods of measuring the same condition (trait) were substantial (râ‰¥ 0.40). Discriminant validity was supported when correlations between the same and different methods of measuring different conditions were significantly lower than corresponding convergent correlations. Results : In support of convergent validity, 22 of 24 convergent correlations were substantial (r=0.38-0.84, median=0.53). In support of discriminant validity, 833 of 924 tests (90.2%) yielded significantly higher convergent than discriminant correlations across the eight pre-identified conditions. Exceptions to this pattern of results were most often observed for comorbid conditions within the same clinical area. Conclusions : Collectively, convergent and discriminant test results support the construct validity of disease-specific QOL impact attributions across MCC within the eight pre-identified conditions. Noteworthy exceptions should be considered when interpreting some specific QOL impact attributions and warrant further study. Pursuit of a summary disease-specific QOL impact score standardized across MCC is recommended.
Multi-Pose and Occluded Facial Landmark Localization Via Sparse Shape Representation

Automatic facial landmark localization is a challenging problem for real world images because of face pose variations and occlusions. This paper proposes a unified framework to robustly locate facial landmarks under different poses and occlusions. Instead of explicitly modeling the statistical point distribution, we use a sparse linear combination to approximate the observed shape, and hence alleviate the multi-pose problem. In addition, we use the sparsity constraint to handle outliers caused by occlusions. We also model the initial misalignment and use convex optimization techniques to solve them simultaneously and efficiently. We evaluated the proposed method extensively on both synthetic and real data. The experimental results are promising on handling pose variations and occlusions.
In-Situ Measurement and Prediction of Hearing Aid Outcomes Using Mobile Phones

Audiologists have devised a battery of clinical tests to measure auditory abilities. While these tests can help determine the candidacy of patients for amplification intervention, they do not accurately predict the degree to which a patient would benefit from using a hearing aid (i.e., The hearing aid outcome). Measuring hearing aid outcomes in the real-world is challenging as it not only depends on a patient's auditory abilities, but also on auditory contexts that include characteristics of the listening activity, social context, and acoustic environment. This paper explores the problem of creating predictive models for hearing aid outcomes that incorporate information about auditory abilities, hearing-aid features, and auditory contexts. Our models are built on a dataset collected using a mobile phone application that measures auditory contexts and hearing aid outcomes using Ecological Momentary Assessments. The use of a mobile application allowed us to collect fine-grained hearing aid outcome measures in different auditory contexts. The dataset includes 5671 surveys from 34 patients collected over two years. Our analysis focuses on identifying the features necessary for predicting hearing aid outcomes in different clinical scenarios. Most importantly, we show that models that only included measures of auditory ability as features are cannot predict the hearing aid outcome of a patient with accuracy better than chance. Incorporating information about auditory contexts increases the prediction accuracy to 68%. More excitingly, accuracies as high as 90% can be achieved when a small amount of training data is collected from a patient in-situ. These results suggest that audiologists could prescribe a mobile phone application at the time of dispensing the hearing aid in order to accurately predict a patient's likelihood of becoming a successful and satisfied hearing aid user.
On Myopic Strategies for Discrete Time Market with Serial Correlation

Optimal investment problem is studied for discrete time market models with serial correlations. It is found sufficient conditions that ensure that the optimal strategy is myopic for the case of power or log utility function. The possibility of discrete time approximation of optimal continuous time strategies for diffusion market is analyzed.
The electron micrography of plant virus-antibody mixtures.

SummaryShadowed electron micrographs of mixtures of purified southern bean mosaic and bushy stunt viruses with their specific antisera show their spherical elementary bodies aggregated into microflocs in which the particle-separations seem to be about twice their normal values. More detailed electron micrographic study of these systems is underway.
A Multiple Objective Nurse Scheduling Model

Abstract The authors present a model for the nurse scheduling problem which works in two phases. In the first phase, the nurses are assigned their day-on/day-off pattern for the two-week scheduling horizon by a goal programming model which allows for consideration of the multiple conflicting objectives inherent in scheduling a nursing staff. The second phase makes specific shift assignments through the use of a heuristic procedure. The two-phase approach results in considerable reductions in problem size, thus reducing the solution effort. Extensions to the basic model are also examined.
Surface Coordination Chemistry of YBa2Cu3O7-δ

The surface coordination chemistry of the cuprate superconductor, YBa2Cu3O7-δ has been extensively surveyed using cyclic voltammetry in conjunction with a series of redox-active ferrocenyl containing adsorbate molecules. Evidence supporting the adsorption of molecules with primary alkylamine, secondary alkylamine, tertiary alkylamine, arylamine, thiol, disulfide, and selenol functionalities is reported. Cyclic voltammetry, atomic force microscopy, scanning electron microscopy, X-ray powder diffraction and resistivity vs temperature measurements were utilized to evaluate the influence of the modification conditions on the bulk and surface properties of the high-Tc superconductor. The spontaneous adsorption of redox-active alkylamines, arylamines, and thiols onto the surfaces of cuprate materials has been shown to produce stable and robust monolayer films with no apparent damage to the bulk properties of the underlying superconductors. Of the molecules studied thus far, primary alkylamines have been determi...
Cloning, expression, purification and preliminary X-­ray crystallographic studies of Escherichia coli Hsp100 nucleotide-binding domain 2 (NBD2)

Escherichia coli Hsp100 ClpB has been identified recently as playing critical roles in multi-chaperone systems. ClpB binds and disaggregates denatured polypeptides by employing ATP hydrolysis and allows other molecular chaperones such as Hsp70 DnaK and Hsp40 DnaJ to refold the non-native polypeptides. ClpB contains two nucleotide-binding domains (NBD1 and NBD2) in its primary sequence. Walker A and Walker B motifs exist in both nucleotide-binding domains. Therefore, ClpB belongs to the large ATPase family known as ATPase associated with various cellular activities (AAA). The mechanisms by which NBD1 and NBD2 function to support the ClpB molecular-chaperone activity are currently unknown. To investigate how NBD2 participates in ClpB function to disaggregate denatured proteins, ClpB NBD2 has been cloned and crystallized. The ClpB NBD2 crystals diffract X-rays to 2.5 A using synchrotron X-ray sources. The crystals belong to space group P212121, with unit-cell parameters a = 99.57, b = 149.34, c = 164.69 A.
An 18th Century Plan for Business Education

Can training for business actually be provided by schools? If so, what type of training is most effective? Should businessmen be trained as generalists or specialists?Questions such as these are no...
Latent Class Multidimensional Scaling. A Review of Recent Developments in the Marketing and Psychometric Literature

We present a description of current, state-of-the-art methods for per­forming latent class multidimensional scaling (LCMDS). The organizing framework utilized to present these various methods revolves around the types of data collected and the associated spatial representation desired from such approaches. As such, methods for proximity, paired compar­isons, preference, choice, and profile or ratings data are described. A general form of the E-M maximum likelihood estimation procedure typ­ically utilized for the vast majority of these methods is also presented. Finally, the potential application of these methods in marketing, as well as directions for future research, are discussed.
Histopathologic basis of the teratogenic effects of H-1 virus on hamster embryos

Rat virus (RV), an extremely small DNA virus with a diameter of 15 mμ (Dalton, Kilham & Zeigel, 1963), has exhibited a marked ability to proliferate in placental and fetal tissues following intravenous inoculations of pregnant hamsters, the maternal health remaining unaffected. Effects on the fetus, however, have varied with the strains of RV employed. In initial experiments, a strain which had been carried in forty-two passages through suckling hamsters was without apparent effect on hamster fetuses, although present in high titers in both placental and fetal tissues (Ferm & Kilham, 1963). These results encouraged similar studies on other strains of RV, attempting to find some which would proliferate in a similar manner and also induce teratogenic effects. These studies resulted in the finding of the teratogenicity of the H-1 strain of RV (Ferm & Kilham, 1964 a ).
The Incidence and Prevalence of Febrile Seizures

Publisher Summary Nearly every article or text written about febrile seizures contains a statement about febrile seizures being the most common type of seizure in childhood, occurring in 2–5% of children. The prognosis of febrile seizures in the early literature was fairly pessimistic because of the inclusion of symptomatic causes of seizure other than fever and patient selection bias. The consensus that febrile seizures do not constitute a form of epilepsy is an important conceptual advance with relevance to the consideration of febrile seizure incidence and prevalence. A disproportionate number of patients with temporal lobe epilepsy have febrile seizures as young children. According to the International League, febrile seizures are an acute, symptomatic type—that is, a “special,” situation-related—seizure. Febrile seizures are not associated with a structural or developmental anomaly of brain, though the existence of such pathology may enhance the susceptibility to febrile seizures. The majority of febrile seizures occurs between 6 months and 3 years of age, with the peak incidence at about 18 months. The data obtained from epidemiological studies can help in the understanding of the genetics and prognosis of febrile seizures.
Fast Alternating Minimization Algorithms for Dictionary Learning

We present theoretical guarantees for an alternating minimization algorithm for the dictionary learning/sparse coding problem. The dictionary learning problem is to factorize samples $y$ into an appropriate basis (dictionary) $A^*$ times a sparse vector $x^*$. Our algorithm is a simple alternating minimization procedure switching between gradient descent and $\ell_1$ minimization at every step. Dictionary learning and specifically alternating minimization algorithms for dictionary learning are well studied both theoretically and empirically. However, in contrast to previous theoretical analysis for this problem we replace the condition on the operator norm of the true underlying dictionary ($A^*$) with a condition on the matrix infinity norm. This allows us to not only get convergence rates in terms of the error in estimated dictionary in the infinity norm but, also allows us to initialize randomly and converge to the globally optimum. Our guarantees under a reasonable generative model allow for dictionaries with growing operator norms, can handle an arbitrary level of overcompleteness while having sparsity which is information theoretically optimal for incoherent dictionaries. We also present statistical guarantees and present sample complexity guarantees for our algorithm.
Getting into the Game: The Trickster in American Ethnic Fiction

Trickster novels, especially those by Gerald Vizenor and Maxine Hong Kingston, can be used to destabilize and undermine ethnic stereotypes. As many studies show, the trickster him/herself cannot be stable and thus resists the limitations of definition as the embodiment of ambiguity. Both insider and outsider, s/he plays with the whole concept of “sides” so as to erase the distinction between them. The trickster plays the game, including the game of language, in order to break and exploit its rules and thus destabilizes linguistic markers. Kingston and Vizenor use their novels to subvert the rules of the linguistic game and free perception from stereotypic rigidity. Perceptions of race and ethnicity are frequently codified in the form of stereotypes with which we are all familiar. Once established, they, of course, prove remarkably difficult to dismantle however false or misleading they might be with regard to the race or ethnicity in question; and thus they continue to exacerbate the social tensions with which we are equally familiar. Ethnic American literature has frequently addressed this issue; in this essay I intend to look at one narrative strategy which is specifically designed to question, challenge, exploit, and even manipulate perception.
Acute oxygen sensing by the carotid body: a rattlebag of molecular mechanisms.

The molecular underpinnings of the oxygen sensitivity of the carotid body Type I cells are becoming better defined as research begins to identify potential interactions between previously separate theories. Nevertheless, the field of oxygen chemoreception still presents the general observer with a bewildering array of potential signalling pathways by which a fall in oxygen levels might initiate Type I cell activation. The purpose of this brief review is to address five of the current oxygen sensing hypotheses: the lactate-Olfr 78 hypothesis of oxygen chemotransduction; the role mitochondrial ATP and metabolism may have in chemotransduction; the AMP-activated protein kinase hypothesis and its current role in oxygen sensing by the carotid body; reactive oxygen species as key transducers in the oxygen sensing cascade; and the mechanisms by which H2 S, reactive oxygen species and haem oxygenase may integrate to provide a rapid oxygen sensing transduction system. Over the previous 15 years several lines of research into acute hypoxic chemotransduction mechanisms have focused on the integration of mitochondrial and membrane signalling. This review places an emphasis on the subplasmalemmal-mitochondrial microenvironment in Type I cells and how theories of acute oxygen sensing are increasingly dependent on functional interaction within this microenvironment.
MFT Students’ Recount Experiences of Attending Phone and Online Overeaters Anonymous Meetings

The purpose of this study was to explore Marriage and Family Therapy students’ experiences attending Overeaters Anonymous (OA). Utilizing a qualitative survey administered in an addictions course at an institution located in a rural area of the United States, 18 marriage and family therapy (MFT) graduate students reflected on their participation in both online and telephone meetings. In this study, MFT students provided their perspectives regarding the feasible utilization of Overeaters Anonymous in clinical treatment, with an emphasis on the consideration of social support for clients who may reside in rural areas. Three major themes emerged which included (1) enlightenment through exposure; (2) OA as a viable adjunct to therapy; and (3) convenience and comfort. The study addressed recommendations for MFT education, clinical implications, and future research.
Evidence that a Membrane Corticosteroid Receptor is an Opioid-Like Receptor

Survival for animals in the wild frequently depends on responding rapidly and appropriately to life-threatening conditions. These responses typically involve rapid behavioral changes, such as the expression of defensive behaviors, and a suite of physiological changes. Although the physiological changes associated with stress responses are complex, the suite of hormones involved in responding to stressful conditions is relatively conserved among vertebrates.
Verb-First Clauses in Icelandic, Successive Cyclic wh-Movement and Syntactic Binding

In their important 1978 paper, Kayne & Pollock argue that Stylistic Inversion in French provides independent evidence for the successive cyclic movement hypothesis argued for in Chomsky (1977) and references cited there, on the basis of island phenomena. Bresnan (1975) and Grimshaw (1975), on the other hand, show that both in the comparative construction in Modern English and in relative clauses in Chaucerian English, the successive cyclic wh-movement hypothesis runs into trouble and that in these constructions, unbounded deletion should be allowed. Nevertheless, both comparative subdeletion and presumably relativization in Chaucerian English obey the “island” constraints that the successive cyclic wh-movement hypothesis was meant to explain. The same state of affairs obtains in Irish, according to the analysis given in McCloskey (1979), in Kikuyu as argued in Clements (1979), in Old English (Allen (1977)), and Old Icelandic (Maling (1976)).
Detrusor Function with Lesions of the Cauda Equina, with Special Emphasis on the Bladder Neck

AbstractA total of 13 patients with proved lesions of the cauda equina underwent neurourological evaluation. All patients had video urodynamic testing, while 9 underwent a varying combination of pelvic floor electromyography, lumbosacral evoked potentials to tibial nerve stimulation and the sympathetic skin response from the perineum. All patients had detrusor areflexia with varying degrees of bladder neck incompetence.Reports of clinical and experimental studies are discussed in relation to the pathophysiology of bladder neck function following lesions of the pudendal and preganglionic pelvic nerve to explain why there have been conflicting reports in the literature regarding bladder neck function with lesions of the cauda equina. The adaptive changes observed in the experimental animal, consisting of random regeneration of the cholinergic neuroeffective junctions, adrenergic hyperinnervation and an increased sensitivity of the prejunctional inhibitory muscarinic receptors on the adrenergic nerve, may ex...
ERGs and Noise: Detection Probability, Time and Amplitude Errors

The effect of background noise on a waveform is to change it in a manner which to some extent depends upon statistical parameters of the signal and the noise. When the signal-to-noise ratio is low the signal may be masked by the noise so that it is not detected most of the time, that is the probability of detection is close to zero. As the signal-to-noise ratio increases, the probability of detecting the signal increases. This process can be described by a curve of probability of detection as a function of signal-to-noise ratio. Measurements of the amplitude and implicit time of the signal have ranges of errors associated with them which also depend upon the signal-to-noise ratio, tending to be large when the signal-to-noise ratio is low, and decreasing as the signal-to-noise ratio improves. These general concepts can be readily applied to electroretinography measurements, and some model ERG and noise waveforms are described and compared with live recordings. The model system is used to obtain measurements of the probability of detection and of the time and amplitude errors which occur at different signal-to-noise ratios. Some techniques are discussed for estimating these effects in practical cases.
Measurement Based Care in Child Welfare-Involved Children and Youth: Reliability and Validity of the PSC-17

This study evaluates whether the psychometric properties of the Pediatric Symptoms Checklist-17 (PSC-17), a common behavioral health measure typically used as a dichotomous screening tool for mental health needs, support its use as a continuous measure for tracking behavioral health over time. A total of 6492 foster parents of children and youth aged 5.5–17 completed the PSC-17. Convergent and discriminant validity was assessed by comparing raw PSC-17 subscale scores with associated outcomes (e.g. psychiatric diagnoses). Long-term test–retest reliability was assessed over 6 months. Scores on the PSC-17 demonstrated good convergent and divergent validity. PSC-17 subscale scores were most strongly associated with analogous diagnoses. Test–retest reliability was moderate, as expected for a time window of this length. This study provides moderate support for the psychometric qualities of the PSC-17 when used with children and youth in the child welfare system as a continuous measure of psychosocial functioning over time.
Perceptions of Vocational Educators and Human Resource/Training and Development Professionals Regarding Skill Dimensions of School-to-Work Transition Programs

The study examined the perceptions of vocational educators and training and development professionals regarding academic, occupational/technical and employability skill dimensions of school-to-work programs for secondary school students in central Ohio. Randomly selected individuals were asked to define levels of student skill mastery prior to beginning a school-to-work program, as well as to determine school-based and work-based responsibility levels for student skill development. Additionally, respondents were asked to ascertain school-based and work-based responsibilities for evaluation of student skill achievement. Results indicated that vocational educators and training and development professionals have varying ranges of agreement regarding responsibilities for skill development and evaluation of students involved in school-to-work programs. Consensus between the two groups is urged if school-to-work initiatives are to be successful.
Characterization of invertebrate cell lines

The usefulness of isozyme patterns for distinguishing 14 lepidopteran and 2 dipteran cell lines was evaluated. The lepidopteran cell lines used in this study represent eight taxonomic families with one family, Noctuidae, having five representatives. Cell extracts were examined for 18 isozymes using a starch gel electrophoretic system. Ten isozymes proved to be suitable because their isozyme patterns permitted the allocation of the cell lines into distinct groups. Furthermore, four isozymes (isocitrate dehydrogenase, malic enzyme, phosphoglucoisomerase, and phosphoglucomutase) were found to be adequate to distinguish the cell lines. The isozyme patterns observed for the two dipteran and one of the lepidopteran cell lines were analogous to the profiles found using the intact insect. Isozyme analyses differentiated the cell lines and may prove useful for identifications of species of origin. The use of this technique as a criterion for identification of invertebrate cell lines is proposed.
Sweating Tennessee Williams: Working Actors in A Streetcar Named Desire and Portrait of a Madonna

This article reads Tennessee Williams’s A Streetcar Named Desire and Portrait of a Madonna by paying closer attention to the playwright’s representations of labour, gender, and especially sweat – a...
Fixation and Processing of the Peripheral Nervous System

Processing of the peripheral nervous system for morphological investigations has unique challenges relative to other organ systems. The sites for sample collection and the endpoints being evaluated will determine the appropriate processing procedures to use. Ultrastructural studies require perfusion fixation with a protein fixative, osmium postfixation of myelin, dehydration, and embedding in a hard resin to allow the cutting of thin sections for transmission electron microscopy. This processing procedure also provides the best resolution for light microscopy but precludes the evaluation of immunohistochemistry and histochemical endpoints. For these endpoints, there are multiple approaches available that include alternate protein fixatives and embedding media that need to be selected based on the specific reagents used for the analysis. This article discusses the factors to consider when selecting a processing procedure and the relative merits and limitations of peripheral nerve processing procedures.
BDNF and endocannabinoids in brain development: neuronal commitment, migration, and synaptogenesis

Abstract Brain derived growth factor (BDNF) and its receptor, Trk B, play major roles in many aspects of brain development. Many reports indicate that BDNF is important in axon specification. It also serves as a survival factor during early development. BDNF can be secreted from both pre- and postsynaptic membranes. When it is taken up by presynaptic axons with its receptor, Trk B, into endosomes, the endosomes are activated to signal. Once BDNF and Trk B reach the cell nucleus, genes involved in development and survival are activated. BDNF plays a key role in specifying column formation in the visual cortex, which is necessary for proper vision to occur. BDNF is also required in both phases of long-term potentiation, which are crucial for memory consolidation. Marijuana and its derivatives contain molecules that function through binding to two G-protein coupled receptors: CB1 and 2. A great quantity of CB1 is expressed in all portions of the brain. These receptors bind to two endocannabinoids (eCBs), amantidine, and 2-arachidonoyl glycerol. Binding of a neurotransmitter to its receptor on the postsynaptic ending of either excitatory or inhibitory neurons triggers the cleavage of a phospholipid to release either amantidine or 2-arachidonoyl glycerol. After eCB binding to its receptor, the presynaptic neuron is inhibited from further neurotransmitter release. eCBs and their receptors, CB1 and 2, play important roles in the specification of neurons during early development. They also serve to guide neurite growth. ECBs and CB1 and 2 are involved in the final specification of synapses. Finally, eCBs and CB1 and 2 function as yin to BDNF and Trk B’s yang. In other words, BDNF release from the postsynaptic terminals triggers neurotransmitter release while eCB release inhibits it.
Riskier Tests of the Validity of the Bifactor Model of Psychopathology

We advanced several “riskier tests” of the validity of bifactor models of psychopathology, which included that the general and specific psychopathology factors should be reliable and well represent...
Computing Bottleneck Distance for Multi-parameter Interval Decomposable Persistence Modules

Computation of the interleaving distance between persistence modules is a central task in topological data analysis. For $1$-parameter persistence modules, thanks to the isometry theorem, this can be done by computing the bottleneck distance with known efficient algorithms. The question is open for most $n$-parameter persistence modules, $n>1$, because of the well recognized complications of the indecomposables. Here, we consider a reasonably complicated class called {\em $n$-parameter interval decomposable} modules whose indecomposables may have a description of non-constant complexity. We present a polynomial time algorithm to compute the bottleneck distance for these modules from indecomposables, which bounds the interleaving distance from above, and give another algorithm to compute a new distance called {\em dimension distance} that bounds it from below. An earlier version of this paper considered only the $2$-parameter interval decomposable modules~\cite{DeyCheng18}.
Intergenerational Transmission of Diet-Induced Obesity, Metabolic Imbalance, and Osteoarthritis in Mice

Objective Obesity and osteoarthritis (OA) are 2 major public health issues affecting millions of people worldwide. Whereas parental obesity affects the predisposition to diseases such as cancer or diabetes in children, transgenerational influences on musculoskeletal conditions such as OA are poorly understood. This study was undertaken to assess the intergenerational effects of a parental/grandparental high-fat diet on the metabolic and skeletal phenotype, systemic inflammation, and predisposition to OA in 2 generations of offspring in mice. Methods Metabolic phenotype and predisposition to OA were investigated in the first and second (F1 and F2) generations of offspring (n = 10-16 mice per sex per diet) bred from mice fed a high-fat diet (HFD) or a low-fat control diet. OA was induced by destabilizing the medial meniscus. OA, synovitis, and adipose tissue inflammation were determined histologically, while bone changes were measured using micro-computed tomography. Serum and synovial cytokines were measured by multiplex assay. Results Parental high-fat feeding showed an intergenerational effect, with inheritance of increased weight gain (up to 19% in the F1 generation and 9% in F2), metabolic imbalance, and injury-induced OA in at least 2 generations of mice, despite the fact that the offspring were fed the low-fat diet. Strikingly, both F1 and F2 female mice showed an increased predisposition to injury-induced OA (48% higher predisposition in F1 and 19% in F2 female mice fed the HFD) and developed bone microarchitectural changes that were attributable to parental and grandparental high-fat feeding. Conclusion The results of this study reveal a detrimental effect of parental HFD and obesity on the musculoskeletal integrity of 2 generations of offspring, indicating the importance of further investigation of these effects. An improved understanding of the mechanisms involved in the transmissibility of diet-induced changes through multiple generations may help in the development of future therapies that would target the effects of obesity on OA and related conditions.
Scaling Up: Citizen Science Engagement and Impacts Beyond the Individual

As the application of citizen science expands to address increasingly complex social problems (e.g., community health), there is opportunity to consider higher-order engagement beyond that of individual members of a community. The US Environmental Protection Agency (EPA) is working to foster public engagement in science through Smoke Sense, which is a citizen science research project that aims to reduce the public health burden of wildland fire smoke. Smoke Sense is facilitated by a mobile app that shares information on air quality, smoke, and health, and collects individual reports of smoke exposure and concurrent health symptoms. However, Smoke Sense is also generating interest among organizations that are working in this problem domain at the local, state, national, and tribal levels. The interest in the citizen science project at the organizational level led us to ask: What would motivate members of organizations to engage in a citizen science project like Smoke Sense, and how do they envision that engagement could improve public health? To explore these questions, we collected data through interviews with individuals who were engaged in Smoke Sense through their work at local, state, and tribal environmental and health agencies in the western US. An inductive, thematic analysis suggests that individuals' motivations stem from their experiences and challenges with smoke in their different roles (e.g., personal, professional, and community member). Respondents envisioned leveraging both the app itself and the data generated by individuals in their region to enhance and support their existing outreach and communication efforts related to smoke. Citizen science projects that aim to address issues in complex problem domains should be designed to complement the work of partner organizations.
Oncogenic KRAS engages an RSK1/NF1 complex in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with limited treatment options. Although activating mutations of the KRAS GTPase are the predominant dependency present in >90% of PDAC patients, targeting KRAS mutants directly has been challenging in PDAC. Similarly, strategies targeting known KRAS downstream effectors have had limited clinical success due to feedback mechanisms, alternate pathways and toxicity due to the targeting of normal tissues. Therefore, identifying additional functionally relevant KRAS interactions in PDAC may allow for a better understanding of feedback mechanisms and unveil new potential therapeutic targets. Here, we used proximity labelling to identify protein interactors of active KRAS in PDAC cells. Fusions of wildtype (BirA-KRAS4B), mutant (BirA-KRAS4BG12D) and non-transforming and cytosolic double mutant (BirA-KRAS4BG12D/C185S) KRAS with the BirA biotin ligase were expressed in murine PDAC cells. Mass spectrometry analysis revealed that RSK1 was enriched among proteins that selectively interacted with membrane-bound KRASG12D. RSK1 required the NF1 and SPRED proteins to interact with KRAS-GTP at the membrane. In both murine and human PDAC lines, membrane-targeted RSK1 was tolerated but inhibited cell proliferation following oncogenic KRAS abrogation to reveal a negative feedback role for membrane-localized RSK1 on wild-type KRAS. Inhibition of the wild-type KRAS, which has been previously proposed to suppress KRAS oncogenesis, may partially explain how RSK1 has been identified as a dependency in some KRAS mutant cells and may provide an additional function for NF1 in tumorigenesis.
Intrinsic reward circuit connectivity profiles underlying symptom and quality of life outcomes following antidepressant medication: a report from the iSPOT-D trial

There is a critical need to better understand the neural basis of antidepressant medication (ADM) response with respect to both symptom alleviation and quality of life (QoL) in major depressive disorder (MDD). Reward neurocircuitry has been implicated in QoL, the neural basis of MDD, and the mechanisms of ADM response. Yet, we do not know whether change in reward neurocircuitry as a function of ADM is associated with change in symptoms and QoL. To address this gap in knowledge, we analyzed data from 128 patients with MDD who participated in the iSPOT-D trial and were assessed with functional neuroimaging pre- and post-ADM treatment (randomized to sertraline, venlafaxine-XR, or escitalopram). 58 matched healthy controls were scanned at the same time points. We quantified functional connectivity (FC) of reward neurocircuitry using nucleus accumbens (NAc) seed regions of interest, and then characterized how changes in FC relate to symptom response (primary outcome) and QoL response (secondary outcome). Symptom responders showed an increase in NAc-dorsal anterior cingulate cortex (ACC) FC relative to non-responders (p < 0.001) which was associated with improvement in physical QoL (p < 0.0003), and a decrease in NAc-inferior parietal lobule FC relative to controls (p < 0.001). QoL response was characterized by increases in FC between NAc-ventral ACC for environmental, NAc-thalamus for physical, and NAc-paracingulate gyrus for social domains (p < 0.001). Symptom responders to sertraline were distinguished by a decrease in NAc-insula FC (p < 0.001) and to venlafaxine-XR by an increase in NAc-inferior temporal gyrus FC (p < 0.005). Findings suggest that change in reward neurocircuitry may underlie differential ADM response profiles with respect to symptoms and QoL in depression.
Costs, Evidence, Context and Values: Journalists' and Policy Experts' Recommendations for U.S. Health Policy Coverage.

Health policy plays a critical role in determining a state’s or nation’s overall population health, and health system change has been a priority for a majority of Americans for at least a decade. N...
PATIENTS WHO ATTEND FORMAL PHYSICAL THERAPY FOR THE ENTIRE DURATION OF RECOVERY AFTER ACLR DEMONSTRATE EXCELLENT FUNCTIONAL OUTCOMES

Background:Limitations in insurance coverage and higher out-of-pocket expenses create challenges for physical therapists rehabilitating pediatric athletes after anterior cruciate ligament reconstru...
Next steps in the early detection of ovarian cancer.

A recent ovarian cancer screening trial found no reduction in mortality, despite increased detection of early stage disease. Here, we discuss these findings and examine next steps to develop more effective approaches for the early detection of ovarian cancer. Bast et al. discuss the early detection of ovarian cancer in the context of the recent UKCTOCS screening trial. The authors suggest potential reasons why the trial failed to achieve a reduction in mortality and outline next steps in the development of biomarkers and imaging modalities to detect ovarian cancer.
Mechanistic Independence of Avian Myeloblastosis Virus DNA Polymerase and Ribonuclease H

Differential inhibition conditions were established for the DNA polymerase and RNase H activities of avian myeloblastosis virus (AMV) with ether-disrupted AMV and a purified enzyme preparation. The RNase H activity of ether-disrupted AMV with (rA) n ·(dT) n and (rA) n ·(dT) 11 as substrates was inhibited 80 to 100% by preincubation with NaF at a final reaction concentration of 27 to 30 mM. Under these conditions, the DNA polymerase activity was inhibited only 0 to 20%. Similar inhibitions were found with exogenous Rous sarcoma virus 35 S and 70 S RNA·DNA hybrid and φX174 DNA·RNA hybrid as substrates. Studies were also performed with a purified enzyme preparation, in which the two activities essentially co-purified. The RNase H activity was inhibited >80% by 150 mM KCl with three different hybrid substrates, whereas the DNA polymerase activity was uninhibited. The DNA polymerase was completely inactivated by heat denaturation at 41 C or by omission of the deoxytriphosphates from the reaction mixture; the RNase H remained active. These differential inhibition conditions were used to compare the size of the DNA product synthesized with and without simultaneous RNase H action and to examine the effect of inhibition of the DNA polymerase on the size of the RNase H products. The size of the products of one activity was not affected by inhibition of the other activity. These results suggest that the AMV DNA polymerase and RNase H are not coupled mechanistically.
Iron Transport in Salmonella typhimurium: Mutants Blocked in the Biosynthesis of Enterobactin

A number of mutants of Salmonella typhimurium were isolated which are blocked in the biosynthesis of enterobactin, an iron chelator that is secreted by the wild-type bacteria when they are grown on low iron media. One class of these enb mutants accumulates the enterobactin precursor 2,3-dihydroxybenzoic acid, and another class does not accumulate any detectable catechol precursor. The enb mutants grow very well on a glucose-mineral salts medium. Addition of citrate, itself an iron chelator, to the medium drastically inhibits growth unless the medium is supplemented with enterobactin or iron salts. Citrate inhibits iron uptake from the medium by enb mutants; enterobactin counteracts this inhibition and also, by itself, increases iron uptake. Thus, the apparent function of enterobactin is to promote the absorption of iron from the medium by the bacteria. Transduction experiments showed that the genes for enterobactin biosynthesis are closely linked on the S. typhimurium chromosome. It is suggested that they form an operon which is repressed by the presence of iron. S. typhimurium can utilize the iron chelate ferrichrome. (Deferriferrichrome is a cyclic hexapeptide that is produced by some fungi but not by S. typhimurium.) The enb mutants use ferrichrome as an effective growth factor.
Klebsiella ozaenae Septicemia Associated with Hansen's Disease

Two cases of Klebsiella ozaenae septicemia from the National Hansen's Disease Center, Carville, La., are discussed: one fatal and one nonfatal. Although both patients had nasal complications of Hansen's disease (leprosy), the organism was grown initially from spinal fluid, blood, and wound cultures. This report confirms the potential pathogenicity of the K. ozaenae species and its widening disease spectrum.
B. Hayslip Jr. and P. Kaminski (Eds.). Parenting the Custodial Grandparent: Implications for Clinical Practice

A wonderful book has been published to assist primarily professionals dealing with the custodial grandparent and grandchild population. In Parenting the Custodial Grandchild: Implications for Clini...
Nature of the Skin-reactive Principle in Culture Filtrates Prepared from Paracoccidioides brasiliensis

Mycelial and yeast-phase culture filtrates prepared from three strains of Paracoccidioides brasiliensis exhibited equal reactivity in sensitized guinea pigs. Ethyl alcohol-precipitated fractions obtained from the culture filtrates also showed no difference in reactivity between mycelial and yeast phase when tested in sensitized guinea pigs. Chemical analyses of the ethyl alcohol-precipitated fractions revealed the presence of seven aliphatic amino acids in both the mycelial- and yeast-phase products. Glucose, galactose, arabinose, and glucosamine were also detected, but the relative proportions of these sugars were different for the mycelial phase as compared with the yeast phase. Both the mycelial- and yeast-phase ethyl alcohol precipitated fractions contained 2 to 4% nitrogen, but no protein or nucleic acid could be detected. Removal of nitrogen from the ethyl alcohol-precipitated fractions by chloroform extraction resulted in an almost complete loss of skin reactivity, whereas the material recovered from the chloroform, which contained most of the nitrogen, still exhibited almost as much reactivity as was present prior to extraction. A considerable portion of the reducing substances was removed along with the nitrogen by the chloroform extraction, suggesting a strong chemical link between the carbohydrate and the peptide portions of the active moiety. Since no protein was present in the fractions, it was presumed that the active moiety is a glycopeptide.
Metallo-β-lactamase structure and function

β-Lactam antibiotics are the most commonly used antibacterial agents and growing resistance to these drugs is a concern. Metallo-β-lactamases are a diverse set of enzymes that catalyze the hydrolysis of a broad range of β-lactam drugs including carbapenems. This diversity is reflected in the observation that the enzyme mechanisms differ based on whether one or two zincs are bound in the active site that, in turn, is dependent on the subclass of β-lactamase. The dissemination of the genes encoding these enzymes among Gram-negative bacteria has made them an important cause of resistance. In addition, there are currently no clinically available inhibitors to block metallo-β-lactamase action. This review summarizes the numerous studies that have yielded insights into the structure, function, and mechanism of action of these enzymes.
Supporting sustainable technology cluster development: A performance measurement problem

Managers require metrics to measure organizational performance. However, metrics used by organizations that support technology cluster development are poorly understood in the literature. The most frequently referenced indicator for cluster development is regional economic and jobs data. These macro level indicators are not sufficient to measure the performance inside the cluster, leaving champions and policy makers to struggle with ad-hoc trial and error experimentation. The difficulty in defining and developing a performance measurement system is addressed. This paper lays the groundwork for improved approaches towards measuring the performance of technology cluster initiatives.