cssi/SciSciGPT-SciSciNet huggingface dataset:
Scaling Chemosensory Epithelia

Both shrews (Order Insectivora) and mice (Order Rodentia) are considered macrosmatic species. Because Insectivores possess many plesiomorphic traits, and chemoreception is thought to be one of these plesiomorphic traits, chemoreception often is considered the sense that most characterizes them. Alternatively, many rodents are thought to have well developed chemosensory systems, perhaps as a derived character. Using similar sized short-tailed shrews and white-footed mice we measured and compared the volume of chemosensory epithelia (combined olfactory and vomeronasal epithelia) and density of cells within the epithelia, as a measure of number of chemosensory neurons. Although shrews have more elaborately scrolled turbinates, mice have proportionately greater chemosensory epithelial volumes than shrews, but the density of cells within the epithelia was not significantly different. This suggests that mice have more chemosensory cells than similar sized shrews and may have a higher chemosensory performance (able to detect smaller quantities of odor or a greater range of odors), perhaps as an adaptation so living in a more socially complex atmosphere replete with a greater range of odors. We speculate about whether having more chemosensory cells necessarily translates into a higher chemosensory performance.
Multiple actin-based motor genes in Dictyostelium.

Abstract Dictyostelium cells, devoid of conventional myosin, display a variety of motile activities, consistent with the presence of other molecular motors. The Dictyostelium genome was probed at low stringency with a gene fragment containing the conserved conventional myosin head domain sequences to identify other actin-based motors that may play a role in the observed motility of these mutant cells. One gene (abmA) has been characterized and encodes a polypeptide of approximately 135 kDa with a head region homologous to other myosin head sequences and a tail region that is not predicted to form either an alpha-helical structure of coiled-coil interactions. Comparisons of the amino acid sequences of the tail regions of abmA, Dictyostelium myosin I, and Acanthamoeba myosins IB and IL reveal an area of sequence similarity in the amino terminal half of the tail that may be a membrane-binding domain. The abmA gene, however, does not contain an unusual Gly, Pro, Ala stretch typical of many of the previously described myosin Is. Two additional genes (abmB and abmC) were identified using this approach and also found to contain sequences that encode proteins with typical conserved myosin head sequences. The abm genes may be part of a large family of actin-based motors that play various roles in diverse aspects of cellular motility.
Investigating Student Motivation and Performance in Electrical Engineering and Its Subdisciplines

Factors influencing choice of major in electrical engineering and later curricular and professional choices are investigated. Studies include both quantitative and qualitative analyses via student transcripts, surveys, and focus groups. Student motivation for choosing an electrical engineering major and later subdiscipline in the field is interpreted through expectancy-value theory, where primary factors of strong perceived value of future professional opportunities and strong influence of course instructors are identified. Performances in select required electrical engineering courses appear to serve as predictors for student choice of subdiscipline emphasis. In contrast, participation in student professional activities does not show statistically significant correlations with subdiscipline. Curricular and professional choices appear to be explained by expectancy-value theory with inclusion of socializers. The findings suggest that early and integrative exposure of all electrical engineering technical areas, including high-quality teaching, may provide an optimal basis for students to make future decisions on academic path and participation in professional activities.
Polarization, Inequality, and the State Legislatures

While legislative polarization at the national level has been carefully examined and largely explained, the causes of polarization in state legislatures have been more elusive. Studies examining factors such as gerrymandering and party primaries as possible explanations have found largely undetectable or at best very modest relationships between these variables and levels of polarization. This paper provides an explanation of state legislative polarization based on socio-economic and demographic factors within the states. Economics and demographics have long played a significant role in understanding party choice, vote choice, the decision to abstain or vote, and support for various policies. Because of this we explore if these factors also influence polarization of state legislatures. Utilizing the Shorr-McCarty polarization data for state legislatures, which provides the differences between the mean Democratic and Republican legislator scores, and controlling for important economic and demographic factors, we explain a significant amount of the polarization existing in state legislatures. These findings present a fascinating look into not only the root causes of polarization in state legislatures, but also point to some fundamental differences in politics and ideology at the state and national levels.
An Innovative Instrumented Projectile for Dynamic Testing and Material Characterization

Measuring impact-induced contact force history is critically important to understanding the nature of impact events and the associated damage processes of materials/structures involved in the impact. In order to investigate the impact-induced contact force history involved in free impacts, such as ballistic impact and high-speed crash, this study developed an innovative instrumented projectile. Both instrumented projectiles with and without an innovative geometry were constructed, tested and compared. An independent optical method was also used to justify the measurements from the innovative instrumented projectile. Experimental results confirmed the effectiveness and accuracy of the innovative instrumented projectile in measuring impact-induced force history.
Moving Beyond Active-Site Detection: MixMD Applied to Allosteric Systems

Mixed-solvent molecular dynamics (MixMD) is a hotspot-mapping technique that relies on molecular dynamics simulations of proteins in binary solvent mixtures. Previous work on MixMD has established the technique’s effectiveness in capturing binding sites of small organic compounds. In this work, we show that MixMD can identify both competitive and allosteric sites on proteins. The MixMD approach embraces full protein flexibility and allows competition between solvent probes and water. Sites preferentially mapped by probe molecules are more likely to be binding hotspots. There are two important requirements for the identification of ligand-binding hotspots: (1) hotspots must be mapped at very high signal-to-noise ratio and (2) the hotspots must be mapped by multiple probe types. We have developed our mapping protocol around acetonitrile, isopropanol, and pyrimidine as probe solvents because they allowed us to capture hydrophilic, hydrophobic, hydrogen-bonding, and aromatic interactions. Charged probes were ...
Quantifying the therapeutic requirements and potential for combination therapy to prevent bacterial coinfection during influenza

Secondary bacterial infections (SBIs) exacerbate influenza-associated disease and mortality. Antimicrobial agents can reduce the severity of SBIs, but many have limited efficacy or cause adverse effects. Thus, new treatment strategies are needed. Kinetic models describing the infection process can help determine optimal therapeutic targets, the time scale on which a drug will be most effective, and how infection dynamics will change under therapy. To understand how different therapies perturb the dynamics of influenza infection and bacterial coinfection and to quantify the benefit of increasing a drug’s efficacy or targeting a different infection process, I analyzed data from mice treated with an antiviral, an antibiotic, or an immune modulatory agent with kinetic models. The results suggest that antivirals targeting the viral life cycle are most efficacious in the first 2 days of infection, potentially because of an improved immune response, and that increasing the clearance of infected cells is important for treatment later in the infection. For a coinfection, immunotherapy could control low bacterial loads with as little as 20 % efficacy, but more effective drugs would be necessary for high bacterial loads. Antibiotics targeting bacterial replication and administered 10 h after infection would require 100 % efficacy, which could be reduced to 40 % with prophylaxis. Combining immunotherapy with antibiotics could substantially increase treatment success. Taken together, the results suggest when and why some therapies fail, determine the efficacy needed for successful treatment, identify potential immune effects, and show how the regulation of underlying mechanisms can be used to design new therapeutic strategies.
Cyberculture and the Digital Divide

Digital divide has created a segmentation of new media users. On the one hand, you have tech-savvy gurus (mostly millennials and college-aged individuals) who can navigate, create, upload, and download with ease materials that are on the cyberspace. On the other hand, there are significant number of users of cell phones, smartphones, tablets, laptops, PCs, and Macs (seniors, disabled, nontech literates) that rely on external help to effectively communicate on their gadgets. This situation has widened the gap especially in Africa where attempts at narrowing the digital divide gap has been undertaken by stakeholders including the government and private sectors. But that effort has not yielded enough dividends because citizens in the rural part of the continent and those not fortunate to be trained by any new media technology still lack behind, and when you have citizens offline using traditional forms of communication and netizens online using social media communication there is bound to be a disconnect.
AMD3100 and G-CSF Synergize To Promote Repopulating Stem Cell Mobilization in Fanca −/− and Fancc −/− Mice.

Fanconi Anemia (FA) is an autosomal recessive DNA repair disorder clinically characterized by congenital abnormalities, progressive bone marrow (BM) failure and a propensity for malignancies. It is advantageous to bank FA patients’ cells for autologous treatment of pancytopenia, transplantation following chemotherapy or future gene therapy trials. Because the amount of cells able to be collected by BM harvesting is limited and the process is often problematic in children, mobilization of stem cells into the circulation would be an ideal means of collecting repopulating hematopoietic stem and progenitor cells (HSPC). Traditional mobilization protocols utilizing granulocyte colony-stimulating factor (G-CSF) as a mobilizing agent result in poor yields of phenotypic HSPC in FA patients. We have shown that analogous to the human patients with FA, administration of recombinant G-CSF is not sufficient to effectively mobilize myeloid progenitors from the BM of Fancc −/− mice (Broxmeyer et al, JEM, 2005). Antagonists to chemokine receptors, together with G-CSF, can enhance mobilization of murine wild type (WT) HSPC. AMD3100 is a selective antagonist of CXCR4, which is thought to function in the retention of HSPC in the BM. We hypothesized that the combination of AMD3100 and G-CSF would enhance mobilization of HSPC in Fanca −/− and Fancc −/− mice. Peripheral blood was collected to assess the number of myeloid progenitors and HSPC repopulating ability. Myeloid progenitor numbers were assessed using progenitor assays. Either G-CSF or AMD3100 alone resulted in poor mobilization of hematopoietic progenitors. In contrast, administration of AMD3100 and G-CSF together increased the number of colonies of myeloid progenitors up to 18 fold above that of either G-CSF or AMD3100 alone in both Fanca −/− and Fancc −/− mice. The stem cell activity of mobilized peripheral blood cells was evaluated using competitive repopulation assays, in which a common pool of isogenic ‘competitor cells’ and ‘test cells’ from mice of different genotypes or treatment conditions are co-transplanted. Fanca −/− and Fancc −/− cells mobilized with both G-CSF and AMD3100 yielded a 3–4 fold increase in peripheral blood chimerism as compared to the cells mobilized with G-CSF or AMD3100 alone. The latter mice also had a decreased survival. Phenotypic analysis of the peripheral blood of primary recipients confirmed the engraftment of multi-lineage test cells. Transplantation of chimeric bone marrow into secondary recipients maintained the test cell chimerism, confirming that long-term repopulating cells were mobilized. Collectively, these data from two FA murine models demonstrate that the AMD3100 and G-CSF protocol is an effective strategy to mobilize FA deficient repopulating HSPC. This has potential implications for more efficient banking of FA patients’ HSPC for future use or for use in gene transfer protocols.
Religious Liberty or Religious License? Legal Schizophrenia and the Case against Exemptions

This paper seeks to demonstrate that religious exemptions are unjustified in theory and corrosive, in practice. By splintering the ultimate sovereignty of a legal system, they fracture its integrity and undermine its ability to fulfill its mission. My analysis proceeds from the function of the legal system – which is the basis of the system’s authority – to show how the practice of granting standing permission for some people to violate generally applicable laws is inimical to that system’s efficacy and an abuse of its authority. The injection of conflicting directives to the officials charged to enforce the law (Go by the law; Go by those people’s consciences) necessarily subjectivizes the use of the government’s coercive power, since those officials have no principled means of deciding between the two directives. The tremendous proliferation of exemptions over the years testifies to the absence of an objective standard for governing this. After establishing the central failings of exemptions, the paper takes up four specific arguments that are frequently offered in their defense: appeals to First Amendment text, the ideal of equality, the ideal of personal liberty, and the profound value of religious identity for many individuals. Careful examination demonstrates that none of these successfully justifies exemptions. Finally, the paper considers the grounds on which differential application of generally sound law might ever be appropriate, finding an important difference between religiously based exemptions and other legitimately exceptional treatment.
Unreasonable Cartesian Doubt

In this paper I argue that Cartesian skepticism about the external world is self-defeating. The Cartesian skeptic holds that we are not justified in believing claims about the external world on the grounds that we cannot rule out the possibility of our being in a radical skeptical scenario. My argument against this position builds upon a critique of Wilson in Analysis, 72(4), 668–673 (2012). Wilson argues that the Cartesian’s skeptical reasoning commits him to mental state skepticism and that this undermines his ability to claim that he is truly skeptical about the external world. I show that Wilson’s argument does not succeed. She is correct that the Cartesian is committed to mental state skepticism. However, she is mistaken in thinking that there is anything incoherent about combining the Cartesian position that one ought to doubt external world claims with doubt about whether one is in fact such a skeptic. I propose an alternative explanation as to why mental state skepticism proves to be the Cartesian’s undoing. I suggest that mental state skepticism leads to epistemic skepticism and that this undermines the Cartesian’s position that belief about the external world is unjustified.
Anastomotic Leak Following Gastric Bypass

Anastomotic leak represents a serious complication of gastric bypass carrying significant morbidity and mortality for the bariatric patient, frequently leading to prolonged hospital stay, additional diagnostic tests, and increased risk for surgical reintervention. Leaks may develop in approximately 5% of patients following gastric bypass as a result of mechanical and/or ischemic factors disrupting the normal healing process of a suture or staple line. This chapter describes the classification and clinical presentation of leaks, as well as the key features for prevention, early diagnosis, and management. Bariatric surgery is an effective therapeutic option for morbid obesity. The prompt identification and management of its related complications are essential to improving clinical practice and surgical outcomes.
A novel low dose fractionation regimen for adjuvant vaginal brachytherapy in early stage endometrioid endometrial cancer

Abstract Purpose To evaluate local control, survival and toxicity in patients with early-stage endometrioid adenocarcinoma of the uterus treated with adjuvant high-dose-rate (HDR) vaginal brachytherapy (VB) alone using a novel low dose regimen. Methods We reviewed records of 414 patients with stage IA to stage II endometrial adenocarcinoma treated with VB alone from 2005 to 2011. Of these, 157 patients with endometrioid histology received 24Gy in 6 fractions of HDR vaginal cylinder brachytherapy and constitute the study population. Dose was prescribed at the cylinder surface and delivered twice weekly in the post-operative setting. Local control and survival rates were calculated by the Kaplan–Meier method. Results All 157 patients completed the prescribed course of VB. Median follow-up time was 22.8months (range, 1.5–76.5). Two patients developed vaginal recurrence, one in the periurethral region below the field and one in the fornix after treatment with a 2.5-cm cylinder. Three patients developed regional recurrence in the para-aortic region. Two patients developed distant metastasis (lung and carcinomatosis). The 2-year rate of vaginal control was 98.6%, locoregional control was 97.9% and disease-free survival was 96.8%. The 2-year overall survival rate was 98.7%. No Grade 2 or higher vaginal, gastrointestinal, genitourinary or skin long-term toxicity was reported for any patient. Conclusion Vaginal brachytherapy alone in early-stage endometrial cancer provides excellent results in terms of locoregional control and disease-free survival. The fractionation scheme of 24Gy in 6 fractions prescribed to the cylinder surface was well-tolerated with minimal late toxicity.
Avoidance of Time-Out From Response-Independent Food Presentation ☆: Effects of Chlordiazepoxide and Buspirone

Abstract VAN HAAREN, F. AND K. G. ANDERSON. Avoidance of time-out from response- independent food presentation: Effects of chlordiazepoxide and buspirone. PHARMACOL BIOCHEM BEHAV 61 (2) 207–214, 1998.—Five male Wistar rats were exposed to a two- component multiple schedule. In one component, signaled by a tone, food pellets were presented on a random-time 120-s schedule. In the other component, food pellets were presented on a random-time 30-s schedule. Pellets were only presented during a 10-s time-in period that alternated with a 50-s time-out period, unless the subject pressed a lever to postpone time-out presentation by 20 s. Response-independent food pellets were never presented within 2 s of this avoidance response. For most subjects avoidance rates were consistently higher when response-independent food pellets were delivered infrequently than when they were delivered more often. The amount of time spent in time-in varied considerably between subjects but was not consistently related to the frequency of response-independent pellet presentation. Once stable response rates were established subjects were intraperitoneally injected with different doses of chlordiazepoxide (1, 3, 10, 17, or 30 mg/kg) or buspirone (0.1, 0.3, 1.0, 1.7, 3.0, or 4.2 mg/kg). Low doses of chlordiazepoxide either did not affect or slightly increased avoidance response rates, whereas higher doses (10 mg/kg and up) produced a dose-dependent decrease in avoidance responding. The time subjects spent in the presence of stimuli associated with the availability of response-independent food either did not change or increased slightly after the lower doses of chlordiazepoxide, while it decreased dose dependently following the higher doses. Low doses of buspirone increased avoidance rates in subjects first exposed to chlordiazepoxide, but did not alter rates in the remaining subjects. Intermediate doses of buspirone decreased avoidance rates more in the component with the lower frequency of pellet presentation, higher doses further decreased response rates. The amount of time spent in the presence of stimuli associated with pellet presentation was minimally affected by the lower doses of buspirone, but decreased dose dependently following the higher doses. The results of this experiment add further credence to the notion that the behavioral effects of drug administration may depend on nonpharmacological variables including, but not limited to, the nature of the consequent event.
Maximum-Leaf Spanning Trees for Efficient Multi-Robot Recovery with Connectivity Guarantees

This paper presents a self-stabilizing distributed algorithm for the recovery of a large population of robots in a complex environment—that is, to gather them all in a goal location. We assume the robots do not have a map of the environment, but instead use short-range network communications and local sensing to physically route themselves towards the goal location. Since the robot’s motion can disrupt robots network communication and localization in complex environments, we desire an algorithm that can maintain connectivity while preserving efficient operation. Our approach constructs a spanning tree for physical routing, but only allows the leaves of this tree to navigate the goal location. This distributed maximum-leaf spanning tree (DMLST) ensures connectivity, while providing an efficient recovery by allowing the maximum number of robots to be mobile.We present empirical results on the competitive ratio of the DMLST and it is very good, approaching the optimal solution for our communication network. DMLST recovery has been tested in simulation, and implemented on a system of thirteen robots. While a basic recovery fails in all experiments, the DMLST recovery succeeds efficiently in most trials.
Comparative Biochemistry of Chlorophyll-Protein Complexes

The photosynthetic pigments occur in vivo noncovalently bound to protein, forming two functionally and spectrally distinct classes of pigment-protein complexes: the photochemical reaction center and the light-harvesting complexes (Thornber et al. 1978). By using suitable surfactants and standard protein purification techniques, reaction center and the antennae complexes have been independently purified from many photosynthetic organisms (Gingras 1978; Olson, Thomber 1979; Cogdell 1983).
WiSh: Towards a Wireless Shape-aware World using Passive RFIDs

This paper presents WiSh, a solution that makes ordinary surfaces shape-aware, relaying their real-time geometry directly to a user's handheld device. WiSh achieves this using inexpensive, light-weight and battery-free RFID tags attached to these surfaces tracked from a compact single-antenna RFID reader. In doing so, WiSh enables several novel applications: shape-aware clothing that can detect a user's posture, interactive shape-aware toys or even shape-aware bridges that report their structural health. WiSh's core algorithm infers the shape of ordinary surfaces using the wireless channels of signals reflected off RFID tags received at a single-antenna RFID reader. Indeed, locating every RFID tag using a single channel measurement per-tag is challenging, given that neither their 3-D coordinates nor orientation are known a priori. WiSh presents a novel algorithm that models the geometric constraints between the coordinates of the RFID tags based on flexibility of the surface upon which they are mounted. By inferring surface curvature parameters rather than the locations of individual RFID tags, we greatly reduce the number of variables our system needs to compute. Further, WiSh overcomes a variety of system-level challenges stemming from signal multipath, stretching of fabric and modeling large surfaces. We implement WiSh on commodity RFID readers and tags attached to a variety of surfaces and demonstrate mm-accurate shape-tracking across various applications.
Comparison of Asphalt Mixtures Crack Resistance at Intermediate Temperatures using Advanced Test Methods and Theories

Due to the increased use of recycled materials in pavement, the crack resistance of asphalt mixtures has become a major concern. This study evaluated the crack resistance of asphalt mixtures contai...
Amenorrhea in lung cancer patients.

e20092Background: More than 5,000 premenopausal women are diagnosed (dx’d) with lung cancer annually in the United States. Improvements in treatment are contributing to a growing population of youn...
Ethanol decreases Pseudomonas aeruginosa flagellar motility through a cyclic-di-GMP- and stator-dependent pathway

Pseudomonas aeruginosa frequently encounters microbes that produce bioactive metabolites including ethanol. At concentrations that do not affect growth, we found that ethanol reduces P. aeruginosa motility by 30% in a swim agar assay and this decrease is accompanied by a 2.5-fold increase in levels of cyclic diguanylate (c-di-GMP), a second messenger that represses motility, in planktonic cells. A screen of mutants lacking genes involved in c-di-GMP metabolism identified SadC and GcbA as diguanylate cyclases involved in swim zone reduction by ethanol and ethanol-induced c-di-GMP production. The reduction of swimming in response to ethanol also required the stator set, MotAB, two PilZ-domain proteins (FlgZ and PilZ), PilY1- a proposed surface-sensing protein, and PilMNOP, which comprises the pilus alignment complex and these proteins have been previously implicated in the control of motility on agar surfaces. Microscopic analysis of the fraction of quiescent cells in swim agar showed that ethanol decreased the portion of motile cells in the wild type, but had opposite effects in the {Delta}pilY1, {Delta}pilMNOP, {Delta}motAB, and {Delta}pilZ{Delta}flgZ mutants. Together, these data indicate ethanol induces a regulated change in motility in planktonic cells at concentrations similar to those produced by other microbes. We propose that this ethanol-responsiveness may contribute to the co-localization of P. aeruginosawith ethanol-producing microbes.
Apn2 resolves blocked 3' ends and suppresses Top1-induced mutagenesis at genomic rNMP sites.

Ribonucleoside monophosphates (rNMPs) mis-incorporated during DNA replication are removed by RNase H2-dependent excision repair or by topoisomerase I (Top1)-catalyzed cleavage. The cleavage of rNMPs by Top1 produces 3′ ends harboring terminal adducts, such as 2′,3′-cyclic phosphate or Top1 cleavage complex (Top1cc), and leads to frequent mutagenesis and DNA damage checkpoint induction. We surveyed a range of candidate enzymes from Saccharomyces cerevisiae for potential roles in Top1-dependent genomic rNMP removal. Genetic and biochemical analyses reveal that Apn2 resolves phosphotyrosine–DNA conjugates, terminal 2′,3′-cyclic phosphates, and their hydrolyzed products. APN2 also suppresses 2-base pair (bp) slippage mutagenesis in RNH201-deficient cells. Our results define additional activities of Apn2 in resolving a wide range of 3′ end blocks and identify a role for Apn2 in maintaining genome integrity during rNMP repair. Biochemical and genetic assays show that the nuclease Apn2 removes terminal cyclic phosphates that arise from ribonucleotide incorporation in the genome of budding yeast.
Reactivity and mechanism of α-nucleophile scaffolds as catalytic organophosphate scavengers

Despite their unique benefits imparted by their structure and reactivity, certain α-nucleophile molecules remain underexplored as chemical inactivators for the topical decontamination of reactive organophosphates (OPs). Here, we present a library of thirty α-nucleophile scaffolds, each designed with either a pyridinium aldoxime (PAM) or hydroxamic acid (HA) α-nucleophile core tethered to a polar or charged scaffold for optimized physicochemical properties and reactivity. These library compounds were screened for their abilities to catalyze the hydrolysis of a model OP, paraoxon (POX), in kinetic assays. These screening experiments led to the identification of multiple lead compounds with the ability to inactivate POX two- to four-times more rapidly than Dekon 139—the active ingredient currently used for skin decontamination of OPs. Our mechanistic studies, performed under variable pH and temperature conditions suggested that the differences in the reactivity and activation energy of these compounds are fundamentally attributable to the core nucleophilicity and pKa. Following their screening and mechanistic studies, select lead compounds were further evaluated and demonstrated greater efficacy than Dekon 139 in the topical decontamination of POX in an ex vivo porcine skin model. In addition to OP reactivity, several compounds in the PAM class displayed a dual mode of activity, as they retained the ability to reactivate POX-inhibited acetylcholine esterase (AChE). In summary, this report describes a rationale for the hydrophilic scaffold design of α-nucleophiles, and it offers advanced insights into their chemical reactivity, mechanism, and practical utility as OP decontaminants.
Study of through-space substituent–π interactions using N-phenylimide molecular balances

Substituent–π interactions associated with aromatic stacking interactions were experimentally measured using a small N-phenylimide molecular balance model system. The direct interaction of the substituent (NH2, CH3, OH, F, Br, CF3 and NO2) with an aromatic ring was measured in the absence of the aromatic stacking interactions in solution. The measured substituent–π energies were found to correlate well with the Hammett σm parameter similar to the substituent effects observed in aromatic stacking systems. The persistent electrostatic trends in substituent effects can arise from the direct electrostatic interactions between substituents and opposing π-systems.
Ehlers–Danlos syndrome and other heritable connective tissue disorders that impact pregnancies can be detected using next-generation DNA sequencing

Ehlers-Danlos syndromes (EDS) are a genetically heterogeneous group of inherited connective tissue disorders classified into six major types with a variable collection of findings and different inheritance patterns. Although complications occur in about one-half of pregnancies in women with EDS, the majority can have a good outcome if managed appropriately. Classic EDS is characterized by joint hypermobility, loose skin with poor healing and easy bruising, musculoskeletal problems with chronic pain and at risk for pre-term delivery. In addition, the vascular form of EDS can have cardiac anomalies, aneurysms, gastrointestinal perforation and uterine rupture during pregnancy. Due to overlapping features among the connective tissue disorders, it is difficult to categorize the disorder into specific types without detailed genetic testing which is now available through advanced genomic technology using next-generation DNA sequencing, searching genomic databases and bioinformatics approach. Therefore, obstetrical complications are variable but relate to specific connective tissue disorders requiring an exact diagnosis. There are several dozen genes causing connective tissue disorders that are currently available for testing using next-generation sequencing and bioinformatics to provide pertinent care, treatment and surveillance of the affected pregnant woman but also for her at-risk fetus related to the specific heritable condition.
Optimizing QDs and Other Inorganic Probes for Imaging and Sensing

We describe the design of high affinity metal-coordinating ligands for the effective coating of inorganic nanocrystals. The ligand design exploits the advantages of the nucleophilic addition reaction to introduce several metal-anchors, hydrophilic moieties and specific reactive groups along a poly(isobutylene-alt-maleic anhydride) short chain. Cap exchange with these ligands applied to luminescent quantum dots (QDs) yields homogeneous nanocrystal dispersions that exhibit long term colloidal stability over several biologically-relevant conditions. The introduction of a controllable number of reactive groups allows conjugation of the QDs to biomolecules via bio-orthogonal coupling chemistries including self-assembly of biotinylated QDs with streptavidin-dye, and coupling of azide-functionalized QDs to cyclooctyne-modified transferrin via copper-free click chemistry.
IL-6 Negatively Regulates IL-22Rα Expression on Epidermal Keratinocytes: Implications for Irritant Contact Dermatitis

Irritant Contact Dermatitis (ICD) is characterized by epidermal hyperplasia and inflammatory cytokine release. IL-6 has been shown to be involved in the pathogenesis of ICD; however, the involvement of the IL-22/IL-22Rα axis and its relation to IL-6 in the inflammatory response following irritant exposure are unknown. Using a chemical model of ICD, it was observed that mice with a keratinocyte-specific knockout of IL-6Rα (IL-6RαΔker) presented with increased inflammation and IL-22Rα and IL-22 protein expression relative to WT following irritant exposure, indicating that IL-6Rα deficiency in epidermal keratinocytes leads to the upregulation of IL-22Rα and its ligand during ICD. Furthermore, it was shown that IL-6 negatively regulates the expression of IL-22Rα on epidermal keratinocytes. This effect is functional as the effects of IL-22 on keratinocyte proliferation and differentiation were markedly reduced when keratinocytes were pretreated with IL-6 prior to IL-22 treatment. These results show that IL-6 modulates the IL-22/IL-22Rα axis in the skin and suggest that this occurrence may be associated with the increased epidermal hyperplasia and exacerbated inflammatory response observed in IL-6RαΔker mice during ICD.
Grammatical Violations and Financial Reporting Quality

We examine whether grammatical violations (GVs) in annual financial reports (10-Ks) provide a timely signal of financial reporting quality. To the extent that GVs capture the time, effort, and resources devoted to the preparation of financial filings, we predict that GVs are correlated with the reliability of the accounting numbers. We validate this assumption by documenting that GVs are negatively correlated with empirical measures of (i) the quality of the firm’s internal information environment, (ii) the time that firms have to file their financial statements, and (iii) the strength of the firm’s monitoring over the financial reporting process. Consistent with our prediction, we find that GVs are positively correlated with the likelihood of a restatement and internal control weakness. Overall, we document that GVs can provide a timely, ex ante signal of the reliability of accounting information, and our findings shed light on the relation between the qualitative and quantitative characteristics of financial disclosures.
Multispecies yield and profit when exploitation rates vary spatially including the impact on mortality of ocean acidification on North Pacific crab stocks

Abstract A multi-species size-structured population dynamics model that can account for spatial structure and technical interactions between commercial fisheries was developed and applied to the snow and southern Tanner crab fisheries in the eastern Bering Sea. The model was then used as the basis for forecasts to calculate reference points related to yield and profit under the effects of ocean acidification on snow and southern Tanner crab. Stochastic projections that account for variation about the stock-recruitment relationship were undertaken for a constant F35% harvest strategy, a strategy that sets effort to maximize profit ignoring the effects of environmental variability such as ocean acidification, and the Acceptable Biological Catch control rule, which includes a reduction in fishing mortality rate when stocks are below target levels. Single- and four-area models led to similar fits to abundance and catch data, and provide similar estimates of time-trajectories of mature male biomass. The model is used to compute Maximum Sustainable Yield (MSY) and an upper bound on Maximum Economic Yield (uMEY). The effort levels that achieve MSY and uMEY were sensitive to whether a spatial or non-spatial model was used to calculate reference points and hence how technical interactions among species were accounted for. Dynamic projections based on various management strategies indicated that adopting a uMEY target level of effort leads to some robustness to the effects of ocean acidification, although similar results can be obtained using the Acceptable Biological Catch control rule, which reduces harvest rates as biomass levels decline.
Modeling Repeat DUI Offender Probation Outcomes Using the Wisconsin Risk Need Assessment

This multiyear study of felony driving while intoxicated (DWI) probationers explores the efficacy of the Wisconsin Risk Need Assessment tool along with sociodemographic factors as measures of proba...
Alternate Formulations for the Operational Space Inertia Matrix

The operational space inertia matrix, A, like its joint space counterpart, H, is an inertial quantity which defines the dynamic relationship between certain forces exerted on a manipulator and a corresponding acceleration vector. In the case of the joint space inertia matrix, H, the forces of interest are the actuator joint forces and torques, and the corresponding acceleration is the joint acceleration vector. On the other hand, A relates the spatial vector of forces and moments exerted at the tip or end effector and the spatial acceleration of this same point. Matrix or vector quantities which are defined with respect to the end effector are often said to be in “workspace” or “operational space” coordinates. Hence, A is called the operational space inertia matrix of a manipulator.
Mental Distress in the United States at the Beginning of the COVID-19 Pandemic.

Objectives. To assess the impact of the COVID-19 pandemic on mental distress in US adults.Methods. Participants were 5065 adults from the Understanding America Study, a probability-based Internet panel representative of the US adult population. The main exposure was survey completion date (March 10-16, 2020). The outcome was mental distress measured via the 4-item version of the Patient Health Questionnaire.Results. Among states with 50 or more COVID-19 cases as of March 10, each additional day was significantly associated with an 11% increase in the odds of moving up a category of distress (odds ratio = 1.11; 95% confidence interval = 1.01, 1.21; P = .02). Perceptions about the likelihood of getting infected, death from the virus, and steps taken to avoid infecting others were associated with increased mental distress in the model that included all states. Individuals with higher consumption of alcohol or cannabis or with history of depressive symptoms were at significantly higher risk for mental distress.Conclusions. These data suggest that as the COVID-19 pandemic continues, mental distress may continue to increase and should be regularly monitored. Specific populations are at high risk for mental distress, particularly those with preexisting depressive symptoms.
Acute Cerebellar Ataxia in COVID-19 Infection: A Case Report.

Abstract Background The outbreak of coronavirus disease 2019 (COVID-19) has been widely reported to cause symptoms such as fever, cough, sore throat, fatigue, and shortness of breath. Neurologic complications have not been widely reported without associated respiratory symptoms. These neurologic manifestations have been found mostly in the elderly. There has been no report of ataxia or COVID-19 cerebellitis in the young adult population without associated respiratory symptoms. Case Report Here we report the case of a 30-year-old patient who presented with isolated cerebellar symptoms and was diagnosed with COVID-19 cerebellitis. Why Should an Emergency Physician Be Aware of This? It is important for emergency physicians to know that COVID-19 can have many clinical manifestations and to have a high level of suspicion with acute neurologic symptoms.
Did Holocene climate changes drive West Antarctic grounding line retreat and readvance

Abstract. Knowledge of past ice sheet configurations is useful for informing projections of future ice sheet dynamics and for calibrating ice sheet models. The topology of grounding line retreat in the Ross Sea sector of Antarctica has been much debated, but it has generally been assumed that the modern ice sheet is as small as it has been for more than 100 000 years (Conway et al., 1999; Lee et al., 2017; Lowry et al., 2019; McKay et al., 2016; Scherer et al., 1998). Recent findings suggest that the West Antarctic Ice Sheet (WAIS) grounding line retreated beyond its current location earlier in the Holocene and subsequently readvanced to reach its modern position (Bradley et al., 2015; Kingslake et al., 2018). Here, we further constrain the post-LGM (Last Glacial Maximum) grounding line retreat and readvance in the Ross Sea sector using a two-phase model of radiocarbon input and decay in subglacial sediments from six sub-ice sampling locations. In addition, we reinterpret high basal temperature gradients, measured previously at three sites in this region (Engelhardt, 2004), which we explain as resulting from recent ice shelf re-grounding accompanying grounding line readvance. At one location – Whillans Subglacial Lake (SLW) – for which a sediment porewater chemistry profile is known, we estimate the grounding line readvance by simulating ionic diffusion. Collectively, our analyses indicate that the grounding line retreated over SLW 4300 - 2500 + 1500 years ago, and over sites on Whillans Ice Stream (WIS), Kamb Ice Stream (KIS), and Bindschadler Ice Stream (BIS) 4700 - 2300 + 1500 , 1800 - 700 + 2700 , and 1700 - 600 + 2800 years ago, respectively. The grounding line only recently readvanced back over those sites 1100 - 100 + 200 , 1500 - 200 + 500 , 1000 - 300 + 200 , and 800±100 years ago for SLW, WIS, KIS, and BIS, respectively. The timing of grounding line retreat coincided with a warm period in the mid-Holocene to late Holocene. Conversely, grounding line readvance is coincident with cooling climate in the last 1000–2000 years. Our estimates for the timing of grounding line retreat and readvance are also consistent with relatively low carbon-to-nitrogen ratios measured in our subglacial sediment samples (suggesting a marine source of organic matter) and with the lack of grounding zone wedges in front of modern grounding lines. Based on these results, we propose that the Siple Coast grounding line motions in the mid-Holocene to late Holocene were primarily driven by relatively modest changes in regional climate, rather than by ice sheet dynamics and glacioisostatic rebound, as hypothesized previously (Kingslake et al., 2018).
O-GlcNAc: Regulator of Signaling and Epigenetics Linked to X-linked Intellectual Disability.

Cellular identity in multicellular organisms is maintained by characteristic transcriptional networks, nutrient consumption, energy production and metabolite utilization. Integrating these cell-specific programs are epigenetic modifiers, whose activity is often dependent on nutrients and their metabolites to function as substrates and co-factors. Emerging data has highlighted the role of the nutrient-sensing enzyme O-GlcNAc transferase (OGT) as an epigenetic modifier essential in coordinating cellular transcriptional programs and metabolic homeostasis. OGT utilizes the end-product of the hexosamine biosynthetic pathway to modify proteins with O-linked β-D-N-acetylglucosamine (O-GlcNAc). The levels of the modification are held in check by the O-GlcNAcase (OGA). Studies from model organisms and human disease underscore the conserved function these two enzymes of O-GlcNAc cycling play in transcriptional regulation, cellular plasticity and mitochondrial reprogramming. Here, we review these findings and present an integrated view of how O-GlcNAc cycling may contribute to cellular memory and transgenerational inheritance of responses to parental stress. We focus on a rare human genetic disorder where mutant forms of OGT are inherited or acquired de novo. Ongoing analysis of this disorder, OGT- X-linked intellectual disability (OGT-XLID), provides a window into how epigenetic factors linked to O-GlcNAc cycling may influence neurodevelopment.
Analysis of blocking antibodies and lymphocyte subsets in patients with recurrent reproductive failure

This study aimed to explore the relationship between recurrent reproductive failure (RRF) and blocking antibody (BA) and lymphocytes, to explore the difference of immune status between recurrent spontaneous abortion (RSA) and recurrent implantation failure (RIF) patients. We undertook a retrospective analysis of BA and lymphocyte subsets detected by flow cytometry in 720 RRF patients (411 RSA and 309 RIF patients) who were treated at Shanxi Maternal and Child Health Hospital from April 2015 to October 2019. The BA negative rate of RRF patients was 81.80%, which was significantly higher than that of normal women (23.46%) (p < 0.05). There was no significant difference in BA negative rates between RSA and RIF patients. Compared with the normal value, the percentage of CD3+ T lymphocytes and CD3+CD4+ T lymphocytes in RRF patients were 71.1% (65.9-76.0) and 36.8% (32.5-41.9) respectively, which were significantly lower than the normal value (p < 0.05). The percentage of B cells in RSA patients [11.0 (8.8-13.9)] was significantly lower than that in RIF patients [11.9 (9.4-14.8)]. The occurrence of RRF is related to the lack of BA and the change of lymphoid subsets. There are some differences in immune status between RSA and RIF patients.
Characterization of the ABC methionine transporter from Neisseria meningitidis reveals that MetQ is a lipoprotein

NmMetQ is a substrate binding protein (SBP) from Neisseria meningitidis that has been identified as a surface-exposed candidate antigen for meningococcal vaccines. However, this location for NmMetQ challenges the prevailing view that SBPs in Gram-negative bacteria are localized to the periplasmic space to promote interaction with their cognate ABC transporter embedded in the bacterial inner membrane. To address the roles of NmMetQ, we characterized NmMetQ with and without its cognate ABC transporter (NmMetNI). Here, we show that NmMetQ is a lipoprotein (lipo-NmMetQ) that binds multiple methionine analogs and stimulates the ATPase activity of NmMetNI. Using single-particle electron cryo-microscopy, we determined the structures of NmMetNI in the absence and presence of lipo-NmMetQ. Based on our data, we propose that NmMetQ tethers to membranes via a lipid anchor and has dual function/topology, playing a role in NmMetNI-mediated transport at the inner-membrane in addition to moonlighting functions on the bacterial surface.