cssi/SciSciGPT-SciSciNet huggingface dataset:
Integration and excision by the large serine recombinase φRv1 integrase

The Mycobacterium tuberculosis prophage-like element phiRv1 encodes a site-specific recombination system utilizing an integrase of the serine recombinase family. Recombination occurs between a putative attP site and the host chromosome, but is unusual in that the attB site lies within a redundant repetitive element (REP13E12) of which there are seven copies in the M. tuberculosis genome; four of these elements contain attB sites suitable for phiRv1 integration in vivo. Although the mechanism of directional control of large serine integrases is poorly understood, a recombination directionality factor (RDF) has been identified that is required for phiRv1 integrase-mediated excisive recombination in vivo. Here we describe defined in vitro recombination reactions for both phiRv1 integrase-mediated integration and excision and show that the phiRv1 RDF is not only required for excision but inhibits integrative recombination; neither reaction requires DNA supercoiling, host factors, or high-energy cofactors. Integration, excision and excise-mediated inhibition of integration require simple substrates sites, indicating that the control of directionality does not involve the manipulation of higher-order protein-DNA architectures as described for the tyrosine integrases.
Analysis and simulation of distortion in folding and interpolating A/D converters

A method for analyzing distortion in a complementary metal-oxide-semiconductor (CMOS) analog-to-digital (A/D) converter with continuous-time folding and interpolation is presented. Distortion resulting from limited bandwidth at the output of the folders, interpolation at the output of the folders, and comparator offset are considered. Simulation results are presented for a range of architectural configurations, and means of extending the method to include the effect of other nonidealities are considered. The present analysis can be used to estimate distortion in A/D converters employing continuous-time folding and aid in the decision of whether to incorporate a track-and-hold circuit at the input of the converter.
Unsupervised wrinkle detection in reflectance confocal microscopy images of the human skin

Reflectance confocal microscopy (RCM) is a non-invasive and in-vivo imaging modality, which can take images from different depths of the human skin. A challenging problem is to detect a clinically important subsurface section of the skin, the Dermis/Epidermis junction, in RCM images. This is a tough problem because of the huge variation of texture and intensity features across both intersubject and intrasubject tissues. On the other hand, there's almost no wrinkle-free part of the skin. This well-known phenomenon can be used as a histological clue for guessing the probability of being Dermis or Epidermis in the neighboring regions. In this paper, we develop a two-step wrinkle detector for RCM images. By analyzing the results on different RCM images, we conclude it has high sensitivity and specificity, but a relatively lower Jaccard index.
Reduced hamstring strength increases anterior cruciate ligament loading during anticipated sidestep cutting

Abstract Background Dynamic knee stability is considered a critical factor in reducing anterior cruciate ligament loads. While the relationships between hamstring force production and anterior cruciate ligament loading are well known in vitro, the influence of hamstring strength to anterior cruciate ligament loading during athletic maneuvers remains unknown. Therefore, the purpose of this study was to determine the influence of hamstring strength on anterior cruciate ligament loading during anticipated sidestep cut. Methods Seventeen recreationally active females were recruited to perform sidestep cutting maneuvers pre/post an acute hamstring strength reduction protocol. Kinematics and kinetics were calculated during the cut and a musculoskeletal model was used to estimate muscle, joint, and anterior cruciate ligament loads. Dependent t-tests were conducted to investigate differences between the two cutting conditions. Findings Anterior cruciate ligament loading increased by 36% due to reduced hamstring strength. This was mostly due to a 44% increase in sagittal plane loading and a 24% increase in frontal plane loading. Post strength reduction sidestep cuts were also performed with decreased anterior tibiofemoral shear force, an outcome that would theoretically reduce anterior cruciate ligament loading. However, the overall decrease in hamstring force production coupled with a more axial hamstring line of action yielded a net increase in anterior cruciate ligament loading. Interpretation These results suggest that decreased hamstring strength significantly increases anterior cruciate ligament loading during anticipated sidestep cutting. Additionally, these results support the premise that preseason screening programs should monitor hamstring strength to identify female athletes with potential deficits and increased injury risk.
Micropillar Arrays for High Sensitivity Sensors

In this paper, we report on a new micropillar sensor array that is stretchable, flexible, and has high sensitivity in the tactile sensing regime (<10 kPa). The sensor array is capable of detecting deformation modes other than pressure such as shear and planar extension. The capacitance-type sensor is fabricated using soft nanolithography whereby the micropillars are individually electroded using a sputtering technique. Buckled gold electrodes are used in this study to enable large sensor stretches up to 55%. Three micropillar aspect ratios were considered in this work (1:1, 1:2, 1:3). Here we present the highest reported sensitivity [0.8 kPa-1] of a capacitance type flexible/stretchable sensor. Our results show that this sensor is also able to detect very low pressures down to 5.4 Pa, which is in the range of ultra-low detection pressures recently reported. Finally, the microstructured sensor array naturally lends itself to the development of pixel-type pressure sensors. We present preliminary results for a 25 pixel array.
Pegboard: a framework for developing mobile applications

Tool support for mobile application development can significantly improve programmer productivity and software quality. Pegboard is a novel tooling framework that extends the Eclipse integrated development environment to support the development of mobile distributed applications. Its extensible design supports multiple application models and the orchestration of external tooling components throughout the development cycle. In this paper we describe Pegboard's architecture and implementation, and show how it improves the development experience through organization, visualization, simplification and guidance. We also discuss insights gained from interviewing software developers, including early users of Pegboard.
Antisocial Behavioral Syndromes and Additional Psychiatric Comorbidity in Posttraumatic Stress Disorder Among U.S. Adults: Results From Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions

BACKGROUND: Despite the relatively high prevalence of antisocial personality disorder (ASPD) in individuals with posttraumatic stress disorder (PTSD), associations of ASPD with clinical presentation of PTSD, including additional comorbidity, have not been investigated. OBJECTIVE: To present nationally representative findings on associations of DSM-IV ASPD versus syndromal adult antisocial behavior without conduct disorder before age 15 with additional psychiatric disorders among U.S. adults with PTSD. METHOD: Face-to-face interviews using the Alcohol Use Disorder and Associated Disabilities Interview Schedule- DSM-IV version in the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions (n = 34,653). RESULTS: After adjustment for sociodemographics and additional comorbidity, both antisocial syndromes were significantly associated with bipolar I, attention-deficit/hyperactivity, substance use, and paranoid, schizoid, histrionic, and obsessive-compulsive personality disorders among respondents with PTSD. Odds of major depressive and generalized anxiety disorders were significantly reduced among men with ASPD. CONCLUSIONS: Interventions targeting PTSD may require attention to co-occurring antisociality and additional comorbidity.
Bizarre pulmonary roentgenographic manifestations in heart disease.

Abstract We have presented four cases of chronic heart disease manifesting rather unusual and interesting chest roentgenographic findings. The nature of the chest findings was such that the exact diagnosis by x-ray examination was not made initially, and only the subsequent course in three of the cases and autopsy findings in the fourth case established the true nature of the changes noted.
Design and fabrication of 2D fast electrothermal micromirrors with large scan range and small center shift

We report an elliptical micromirror actuated by a curved electrothermal multimorph that bends and twists upon controlled Joule heating. The mirror plate is elliptical with 92 µm major axis and 142 µm minor axis. The micromirror has an optical scan angle of 22° at 0.37 V applied voltage or 9 mW power input. Mirror-center shift produced by multimorph bending and twisting compensate each other and is only 14.5 µm at an optical scan angle of 22°. The curved actuator shape maximizes chip-area utilization and ensures a high resonant frequency. The first three resonant modes are at 3.9 kHz, 8.6 kHz and 17 kHz. Two-dimensional (2D) optical scanning is demonstrated using the second and third resonant modes.
Distinguished Address: The Near-Term Outlook for Fiscal Policy

Remarks delivered at the December 1999 conference "Fiscal Policy in an Era of Surpluses: Economic and Financial Implications", sponsored by the Federal Reserve Bank of New York.
Two-photon-like microscopy with orders-of-magnitude lower illumination intensity via two-step fluorescence

We describe two-step fluorescence microscopy, a new approach to non-linear imaging based on positive reversible photoswitchable fluorescent probes. The protein Padron approximates ideal two-step fluorescent behaviour: it equilibrates to an inactive state, converts to an active state under blue light, and blue light also excites this active state to fluoresce. Both activation and excitation are linear processes, but the total fluorescent signal is quadratic, proportional to the square of the illumination dose. Here, we use Padron's quadratic non-linearity to demonstrate the principle of two-step microscopy, similar in principle to two-photon microscopy but with orders-of-magnitude better cross-section. As with two-photon, quadratic non-linearity from two-step fluorescence improves resolution and reduces unwanted out-of-focus excitation, and is compatible with structured illumination microscopy. We also show two-step and two-photon imaging can be combined to give quartic non-linearity, further improving imaging in challenging samples. With further improvements, two-step fluorophores could replace conventional fluorophores for many imaging applications.
Concentration of highly potent erythropoietic activity from urine of anemic patients.

Summary1) Some patients with aplastic anemia had exceptionally high levels of erythropoietic activity in plasma. The urine of these patients was assayed, and in some it was equally as potent as the plasma. As little as 1 ml daily for 14 days of untreated urine from such a patient produced a significant polycythemia in normal adult rats. When a concentrate of such urine, prepared by ultrafiltration, was injected at a dose equivalent to 30 ml daily for 14 days into normal adult rats, a polycythemia was produced which exceeded that resulting from exposure to a simulated altitude of 15.000 feet for the same period of time. 2) The high potency of such urine has allowed its assay in normal rats. This finding, together with the easy availability of urine and the efficiency of ultrafiltration as a method for preparing concentrates of urinary erythropoietic activity, should allow for a more rapid investigation of the chemistry and biology of this factor.
Abstract P6-09-09: A second-generation proteasome inhibitor (SGPI) inhibits proliferation of triple negative breast cancer cells to a greater extent than doxorubicin while decreasing IL-6/NF-kB pathway inflammatory activity:

Background : Proteasome inhibitors limit tumor growth by lowering the capacity of cancer cells to degrade pro-apoptotic signals. Given the success of proteasome inhibitors as a treatment for multiple myeloma, this class of drugs has been investigated as a possible treatment for other malignancies with poor prognoses, such as metastatic triple negative breast cancer (TNBC). Doxorubicin (DOX), is the current standard of treatment for TNBC but it has a very toxic side effect profile. Furthermore, it has been shown that the pro-inflammatory markers IL-6/NF-kB plays a critical role in angiogenesis, anti-apoptosis, metastasis and hematogenous spread of tumor cells, and is elevated at baseline in TNBC and increases further with DOX treatment. Recent studies with SGPI on myeloma patients have reported that only 2-5% patients exhibited side effects as compared to the 25% heart failure seen with DOX, a more tolerable side-effect profile. However, in a recent clinical trial, Bortezomib (BOR), a first-generation proteasome inhibitor, showed limited activity in metastatic breast cancer when used as single agent. SGPI differs from BOR in its structure and its activity on the proteasome complex. Therefore, we studied the effect of SGPI on proliferation and inflammation in the triple negative breast cancer cell line MDA-MB-231. Method : MDA-MB-231 cells were treated with known D50 concentrations of DOX, SGPI, and BOR alone and in combination for 24 hours. Cells were then incubated in complete medium for another 24 hours. The viability of each group was analyzed by quantitating cell proliferation (MTT assay). The inflammatory markers IL-6 and NF-kB were measured by ELISA and lentiviral signal assay. Results : DOX (2 uM) decreased TNBC proliferation by 40% while SGPI (10nM) and the combined regimen decreased it by over 70%. BOR (5 nM) was less efficacious than DOX or SGPI. Although the combination showed no appreciable synergism, the large proliferation difference between the treatments suggests that SGPI has a greater anti-tumor activity than DOX at a D50 concentration. The DOX/BOR combination also showed no synergism. SGPI halved baseline IL-6 levels and reduced DOX-stimulated levels 6-fold. Similar results were seen with NF-kB. BOR also lowered inflammation but to a lesser extent. Conclusion: SGPI is more efficacious than either DOX or BOR in inhibiting TNBC proliferation in vitro, perhaps as a result of a reduced IL-6/NF-kB pathway pro-inflammatory response, which represents a potential improvement in the toxicity profile of existing chemotherapy. These preliminary results indicate that SGPI might reduce angiogenesis and metastasis. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-09-09.
Serious juvenile offenders who have experienced emerging adulthood: Substance use and recidivism

Using data from the California Youth Authority, this article examines whether or not specific substance use differentially predicts recidivism for individual offense-type among a group of serious juvenile offenders who have experienced emerging adulthood. The results of the logistic regression analysis indicate that users of specific substances have a higher overall likelihood of receipt of a subsequent arrest for different offense-types when compared to other substances. Specifically, among the 524 serious juvenile offenders analyzed, one demographic, one social bond, and two substance use measures were significant indicators of an offender being arrested during the seven-year follow-up period. The social bond measure of full-time employment and substance use measure of using mind-altering drugs were significant indicators of receipt of an arrest for a non-violent offense, while being non-white and reported use of uppers/downers were significant predictors of arrest(s) for violent and both non-violent and violent offenses. Policy implications, limitations, and directions for future research are discussed. Language: en
Radiologic-Pathologic Discordance and Outcome After MRI-Guided Vacuum-Assisted Biopsy

OBJECTIVE. The purpose of this study was to determine the rate, characteristics, and outcomes of discordant MRI-guided vacuum-assisted biopsy (VAB) in women with suspected breast cancer. MATERIALS AND METHODS. This retrospective study reviewed 1314 MRI-guided VABs performed in 1211 women between 2007 and 2013 and yielded 25 discordant results in 24 women. MRI characteristics; BI-RADS assessments; whether the lesion was missed, partially sampled, or excised at biopsy; and biopsy and surgical pathology results were reviewed. Statistical analyses were performed using Fisher exact and Mann-Whitney U tests. RESULTS. Among 1314 lesions that underwent MRI-guided VAB, 25 results were discordant (1.9%; 95% CI, 1.2–2.8%), and nine lesions with discordant results (36.0%, 95% CI, 18.5–56.9%) were malignant at surgical excision (three invasive ductal carcinoma and six ductal carcinoma in situ). There was no significant association between malignancy and lesion type, size, enhancement pattern, BI-RADS assessment, or cl...
Determining Gender by Raman Spectroscopy of a Bloodstain

The development of novel methods for forensic science is a constantly growing area of modern analytical chemistry. Raman spectroscopy is one of a few analytical techniques capable of nondestructive and nearly instantaneous analysis of a wide variety of forensic evidence, including body fluid stains, at the scene of a crime. In this proof-of-concept study, Raman microspectroscopy was utilized for gender identification based on dry bloodstains. Raman spectra were acquired in mapping mode from multiple spots on a bloodstain to account for intrinsic sample heterogeneity. The obtained Raman spectroscopic data showed highly similar spectroscopic features for female and male blood samples. Nevertheless, support vector machines (SVM) and artificial neuron network (ANN) statistical methods applied to the spectroscopic data allowed for differentiating between male and female bloodstains with high confidence. More specifically, the statistical approach based on a genetic algorithm (GA) coupled with an ANN classifica...
Primary percutaneous coronary intervention: the deception of delay.

Primary percutaneous coronary intervention (PCI) has become the predominant reperfusion strategy for ST-segment elevation myocardial infarction (STEMI) throughout western healthcare systems. Recent estimates in the United States suggest that primary PCI is used in 85% of all STEMI cases that undergo
Gender comparisons of social work faculty using H-Index scores

The objective of this study is to determine the role of gender and faculty rank in explaining variance in individual research impact and productivity for social work doctoral faculty. Research impact and productivity were assessed with the H-Index, which is a widely used citation index measure that assesses the quality and quantity of published research articles. We compared the individual H-Index scores for all doctoral level social work faculty from doctoral programs in the United States (N = 1699). Differences in H-Index means were assessed between genders at each tenure-track faculty rank, and between faculty ranks for each gender. Both gender and faculty rank were associated with differences in scholarly impact and productivity. Although men had higher H-Index scores than women in all faculty ranks, the gender gap was the greatest between men and women at the Full Professor level. The gender gap was least pronounced at the Associate Professor level, where women's H-Index scores were closer to those of men. Results support previous studies in which women in the social sciences have lower H-Index scores than men. The diminished gap between men and women at the Associate Professor level may suggest that women get promoted to Full Professor less frequently than men at comparable career milestones. While the results of this study are consistent with the argument that women face unique barriers to academic promotion and other forms of academic success in social work, these results do not explain any specific barriers that may cause the gender gap.
Strong Landau-quantization effects in high-magnetic-field superconductivity of a two-dimensional multiple-band metal near the Lifshitz transition

We investigate the onset of superconductivity in a magnetic field for a clean two-dimensional multiple-band superconductor in the vicinity of the Lifshitz transition when one of the bands is very shallow. Due to the small number of carriers in this band, the quasiclassical Werthamer-Helfand approximation breaks down and Landau quantization has to be taken into account. We found that the transition temperature ${T}_{C2}(H)$ has giant oscillations and is resonantly enhanced at the magnetic fields corresponding to the matching of the chemical potential with the Landau levels in the shallow band. This enhancement is especially pronounced for the lowest Landau level. As a consequence, the reentrant superconducting regions in the temperature-field phase diagram emerge at low temperatures near the magnetic fields at which the shallow-band Landau levels cross the chemical potential. The specific behavior depends on the relative strength of the intraband and interband pairing interactions and the reentrance is most pronounced in the purely interband coupling scenario. The reentrant behavior is suppressed by the Zeeman spin splitting in the shallow band; the separated regions disappear already for very small spin-splitting factors. On the other hand, the reentrance is restored in the resonance cases when the spin-splitting energy exactly matches the separation between the Landau levels. The predicted behavior may be realized in the gate-tuned FeSe monolayer.
SP and KLF Transcription Factors in Digestive Physiology and Diseases

Specificity proteins (SPs) and Kruppel-like factors (KLFs) belong to the family of transcription factors that contain conserved zinc finger domains involved in binding to target DNA sequences. Many of these proteins are expressed in different tissues and have distinct tissue-specific activities and functions. Studies have shown that SPs and KLFs regulate not only physiological processes such as growth, development, differentiation, proliferation, and embryogenesis, but pathogenesis of many diseases, including cancer and inflammatory disorders. Consistently, these proteins have been shown to regulate normal functions and pathobiology in the digestive system. We review recent findings on the tissue- and organ-specific functions of SPs and KLFs in the digestive system including the oral cavity, esophagus, stomach, small and large intestines, pancreas, and liver. We provide a list of agents under development to target these proteins.
Disparities in care for HIV patients with lung cancer.

e17566 Background: HIV patients with lung cancer appear to have an increased incidence and an overall shorter survival than HIV negative patients. Issues such as compliance with established guidelines, second and third line therapies and molecular testing have not been investigated thoroughly. Methods: We conducted a retrospective review at our institution from 2002-2013 analyzing patients with lung cancer and HIV. Frequency of molecular testing, second and third line therapy, CD4 count, HIV viral load, and survival data were included. Results: Eighteen patients were included for analysis. The median age at diagnosis was 49. Only one patient received EGFR testing; none received ALK testing. Second line and third line therapies were not offered to any patients with stage IV cancers. 64% of the patients with stage III or IV were either not treated or received palliative radiation only. 50% were immune suppressed with CD4 count 15,000 at time of lung cancer diagnosis. The media...
PDI Inhibition Blocks Thrombin Generation in Humans By Interfering with Platelet Factor V Activation

Abstract Protein disulfide isomerase (PDI) is a ubiquitously expressed oxidoreductase that serves an essential role in protein folding in the endoplasmic reticulum by reshuffling disulfide bonds within nascent proteins. PDI can be released from vascular cells, including platelets, and inhibition or platelet-specific deletion of PDI blocks thrombus formation in vivo. However, the specific function of PDI in thrombus formation is poorly understood. Unlike the role of proteases in blood coagulation, which have been studied in depth, little is known about PDI substrates in the vasculature. Several platelet and endothelial integrins have been identified as putative substrates for PDI, but whether coagulation factors are directly targeted by extracellular PDI has not been established. We now identify platelet factor V as a principal coagulation substrate of extracellular PDI. We developed an unbiased strategy to identify novel substrates of PDI in washed platelets using PDI variants capable of trapping substrates: FLAG-tagged PDI mutants modified by a substitution of arginine or proline for histidine (CGHC → CGRC; CGHC → CGPC) in the catalytic motif of both the a and a’ domains. Whereas the AGHA-PDI variant which has no catalytic activity serves as a control. The CGRC-PDI variant co-precipitated with platelet factor V in a redox-sensitive manner while there was no platelet factor V detected with the AGHA-PDI variant, thus confirming that binding of PDI to platelet-derived factor V occurs through disulfide bond exchange. Platelet factor V associates with multimerin-1 through a disulfide bond. Trapping PDI mutants also bind to multimerin-1 in a reaction requiring disulfide bond exchange. To evaluate the effect of PDI inhibition on the activation of platelet factor V, washed platelets from healthy donors were stimulated with 0.1 U/mL of thrombin in the presence of varying concentrations of isoquercetin (0 to 50 µM), which has previously been shown to inhibit PDI function. We observed a dose-dependent reduction of factor Va following platelet activation despite the fact that isoquercetin did not inhibit platelet release of PF4 or block Xa or thrombin enzymatic activity directly. We next performed a clinical study designed to determine whether oral isoquercetin inhibits thrombin generation in human subjects via its ability to inhibit platelet Va generation. Plasma samples collected from healthy participants before and 4 hours after ingestion of 1000 mg of isoquercetin (N=17). In plasma samples, post-isoquercetin platelet-dependent thrombin generation decreased by 51% compared with pre-ingestion controls (P=0.0004). Furthermore, we observed an overall 26% reduction in FVa in non-FV depleted plasma (P Disclosures Zwicker: Quercegen Pharma: Research Funding.
Climatic Effects of Anthropogenic Trace Gases

Human activities inject several radiatively and photo-chemically active trace gases into the atmosphere. Of these trace gases, CO2 is considered to be the most important one, because of its climatic effects. However, recent photochemical and climate modeling results indicate that anthropogenic sources of trace gases other than CO2 (which include CH4, N2O, CFMs and O3) may contribute as much as 40% of the surface warming to the combined surface warming effects of CO2 and these other gases. Roughly 15% of the total warming is due to the projected increase in tropospheric O3 caused by fossil fuel sources of CO, NO and CH4. These findings may be subject to a large range of uncertainty resulting from: photochemical modeling uncertainties; possible large errors in estimates for the natural sources and sinks for these trace species; and, finally, a big source of uncertainty is the scenarios for future increase in emission rates for these trace species. Hence, the problem, because of its potential importance, should be examined in more detail.
Hedgehog Signaling, Keratin 6 Induction, and Sebaceous Gland Morphogenesis: Implications for Pachyonychia Congenita and Related Conditions

Keratins 6a and b (K6a, K6b) belong to a subset of keratin genes with constitutive expression in epithelial appendages, and inducible expression in additional epithelia, when subjected to environmental challenges or disease. Mutations in K6a or K6b cause a broad spectrum of epithelial lesions that differentially affect nail, hair, and glands in humans. Some lesions reflect a loss of the structural support function shared by K6, other keratins, and intermediate filament proteins. The formation of sebaceous gland-derived epithelial cysts does not fit this paradigm, raising the question of the unique functions of different K6 isoforms in this setting. Here, we exploit a mouse model of constitutively expressed Gli2, a Hedgehog (Hh) signal effector, to show that K6a expression correlates with duct fate in sebaceous glands (SGs). Whether in the setting of Gli2 transgenic mice skin, which develops a prominent SG duct and additional pairs of highly branched SGs, or in wild-type mouse skin, K6a expression consistently coincides with Hh signaling in ductal tissue. Gli2 expression modestly transactivates a K6a promoter-driven reporter in heterologous systems. Our findings thus identify K6 as a marker of duct fate in SGs, partly in response to Hh signaling, with implications for the pathological expansion of SGs that arises in the context of certain keratin-based diseases and related disorders.
Representatives of Each Race: Abolishing Inequalities in Colonial Politics

Philanthropic whites contributed politically to the Haitian Revolution. Some had an impact at critical junctures, such as when white radicals led various mobilization efforts, including the get-out-the-vote campaigns in 1793 to ratify the civil commissioners’ emancipation decrees. Others had a more subtle effect on the revolution through their continued political presence in Saint-Domingue before and during the Revolution. Despite their contributions, the literature has overlooked the role of colonial whites in Saint-Domingue’s revolution. Historians have focused upon the influence of whites from France, suggesting the politics of race came to the colony from the metropole, overlooking whites—some longtime residents of the colony—who participated in the revolutionary administrations alongside former slaves and men of color to achieve abolition and racial equality.
Dual biozonation scheme (benthic foraminifera and “calcareous” green algae) over the Jurassic–Cretaceous transition. Another plea to revert the system boundary to its historical Orbigny's and Oppel's definition

Abstract The Tithonian–Valanginian interval is subdivided into 5 biozones (zones and subzones) combining mostly large benthic foraminifera and “calcareous” green algae, which are typical of photozoan assemblages from the shallow-water carbonate facies of the Tethysian realm. This dual zonation is calibrated on a sequence stratigraphic framework for the Jura Mountains where earlier findings of ammonites and calpionellids are plotted. The microfossil diversity was low in the Tithonian–early Berriasian times; then it significantly increased over the middle–late Berriasian times before a first extinction event at the Berriasian/Valanginian boundary followed by a second extinction event in the early Valanginian times. The lower/middle Berriasian and the Berriasian/Valanginian boundaries can be traced consistently from West to East through the whole Tethysian realm. By contrast, the upper Tithonian and the lower Berriasian cannot be distinguished. Because the location of the Jurassic/Cretaceous system boundary has been pending a decision of the International Commission on Stratigraphy since 1975, this survey provides one more argument to abandon the early 20th century Kilian's view which placed it at the Tithonian/Berriasian stage boundary, and to return it to the original 19th century Orbigny's and Oppel's view, i.e., back at the Berriasian/Valanginian stage boundary.
A Comparison Study of Vitamin D Deficiency among Older Adults in China and the United States.

Vitamin D deficiency is a common health concern worldwide. We aim to compare the prevalence of vitamin D deficiency among older adults (65+) in China and the United States (US). We used data from the 2011 wave of Chinese Longitudinal Healthy Longevity Survey (CLHLS) in China (n = 2180), and 2011–2014 National Health and Nutrition Examination Survey (NHANES) in the US (n = 2283). Serum 25-hydroxyvitamin D [25(OH)D] was measured and a level of under 30/50 nmol/L was defined as vitamin D severe deficiency/deficiency. Risk factors of vitamin D deficiency were examined by multivariate regression models. We found that the mean 25(OH)D concentration was lower in China than in the US (45.1 vs. 83.5 nmol/L), with Chinese elderly lower than American elderly for every age group. 70.3% in China and 17.4% in the US were considered as vitamin D deficiency (30.6% and 3.4% were considered as severe deficiency). Older age, females, ethnic minorities, higher household income, self-rated “very bad” health, and never drinkers, were statistically significant in predicting lower serum 25(OH)D levels in China. In the US, males, ethnic minorities, lower income, self-rated “very bad” health, physically inactive, overweight, and obese were related to lower serum 25(OH)D levels. Our findings suggest that different interventional strategies are needed to improve vitamin D deficiency and its associated negative health outcomes in China and the US.
Intracranial Langerhans cell Histiocytosis: A review

Abstract Introduction Intracranial Langerhans Cell Histiocytosis (LCH) is a rare disease caused by the proliferation and dissemination of antigen presenting cells in the skin. Few cases have been reported on to date and there is a lack of consensus on the most effective means of diagnosis and treatment of these lesions. This paper will serve as a review of this malady. Methods MeSH database search was performed to include all relevant studies on intracranial LCH. Results A total of 146 studies with 192 patients were included in our review. Men were more commonly affected and the average age of diagnosis was 31.6 and 28.0 in men and women respectively. CT and MRI were the most common imaging modalities. The majority of the case reports performed biopsies and the most common lesion location was the hypothalamus-pituitary axis. All studies used surgical resection, radiotherapy, chemotherapy or combination therapy as means of treatment, with resection plus chemotherapy being the most successful. 74 cases were successful in preventing recurrence. Conclusion LCH rarely affects the brain as primary or secondary focus. Biopsy is required for precise diagnosis and exclusion of other intracranial lesions. There is no standard treatment for LCH of the central nervous system, but this review may serve as a guide to chronicle previous efficacious therapeutics strategies.
Aspirin-triggered 15-epi-lipoxin A4 and novel lipoxin B4 stable analogs inhibit neutrophil-mediated changes in vascular permeability.

Leukocyte-dependent endothelial cell injury leads to changes in vascular permeability, edema, and further release of chemoattractants.1 The hallmark of reperfusion injury is considered to be diminished barrier function of vascular endothelium. Leukotriene B4 (LTB4)‡ is among the most potent neutrophil stimuli and thus participates in tissue injury via recruiting PMN in pathophysiologic scenarios.2 Lipoxins are trihydroxytetraene-containing eicosanoids that are, among other in vivo sites, also generated within vascular lumen primarily by platelet-leukocyte interactions by pathways that are activated during multicellular responses such as inflammation, atherosclerosis, and thrombosis (as reviewed in Serhan).3 Recently, aspirin was shown to trigger the biosynthesis of a new group of compounds termed 15-epi-LX or aspirin-triggered lipoxins that may contribute to some of the beneficial actions ascribed to aspirin.3 Thus, these two LX branches involving cell-cell interactions within the eicosanoid cascade appear to produce “endogenous stop signals,” whereas the 5-lipoxygenase pathway generates leukotrienes, which are proinflammatory mediators.
Post-hoc physiological waveform extraction from motion estimation in simultaneous multislice (SMS) functional MRI using separate stack processing.

Purpose Motion estimation is an essential step in functional MRI (fMRI) preprocessing. Usually, fMRI processing software packages (eg, FSL and AFNI) automatically estimate motion parameters in order to counteract the effects of motion. However, the time courses of the motion estimation for fMRI data also contain information about physiological processes. Here, we show that respiration and cardiac signals can be extracted from motion estimation at significantly higher bandwidth than is possible with current methods. Method To detect motion at high effective temporal resolution (HighRes), the motion parameters of stacks of simultaneously acquired slices were estimated separately, then combined. This method was validated by extracting physiological motion signals from resting state fMRI (rsfMRI) data (Enhanced Nathan Kline Institute-Rockland Sample) and comparing them to respiration belt and pulse oximeter signals. Results HighRes motion time-courses with an effective sampling rate of 15.5 and 11.4 Hz were extracted from repetition time (TR) = 0.645 and 1.4 s data, respectively. Respiration waveforms were extracted with significantly higher accuracy than the original motion parameters. Even cardiac waveforms could be extracted, despite the fact that the sampling time or TR values were too long to sample cardiac frequencies. Conclusion HighRes motion traces provide insight into the subjects' motion at higher frequencies than can be estimated using standard techniques. In its simplest form, this technique can recover accurate respiration signals and may reveal additional complexity in brain motion.
Metastatic Bladder Cancer and the Use of Cisplatin Chemotherapy

Bladder cancer accounted for 4.6% of all cancer diagnoses and 2.9% of cancer-related deaths in the United States in 2019. The initial evaluation for locally advanced and/or metastatic bladder cancer requires collaboration between specialists in urology, medical oncology, radiation oncology, pathology, and radiology. Although cisplatin-containing regimens are the preferred first-line treatment for metastatic bladder cancer, selecting the patients most likely to benefit from their use has remained a challenge. In fact, as many as 50% of patients are considered cisplatin ineligible after clinical evaluation. Treatment with cisplatin requires careful monitoring and surveillance. Treatment-related toxicities are common, and thorough patient assessment should be conducted at each patient encounter. Periodic surveillance imaging should be obtained at regular intervals to assess for disease response.
Extended Trochanteric Osteotomy in Revision Total Hip Arthroplasty: Contemporary Outcomes of 612 Hips

Background Extended trochanteric osteotomies (ETOs) provide wide femoral and acetabular exposure, give direct access to the femoral medullary canal, and facilitate implant removal and new implant placement during selected revision total hip arthroplasties (THAs). Previous studies are limited by modest patient numbers and limited length of follow-up. The goals of the current study were to assess the union rate, complications, and outcomes of contemporary ETOs performed during revision THAs. Methods From 2003 to 2013, 612 ETOs were performed during revision THAs at 1 institution using 2 techniques: Paprosky (laterally based osteotomy; n = 367) and Wagner (anteriorly based osteotomy; n = 245). The indications for the revision procedures were aseptic loosening (65%), periprosthetic joint infection (18%), periprosthetic fracture (6%), femoral implant fracture (5%), and other (6%). The mean patient age was 69 years, and 57% of the patients were male. The mean number of previous THAs was 1.6. The median duration of follow-up was 5 years (range, 2 to 13 years). Results The mean Harris hip scores increased from 57 preoperatively to 77 at the latest follow-up (p 1 cm occurred in 7% (37) of the 501 hips that had radiographic analysis. Nine hips (2%) had nonunion of the ETO. Intraoperative fracture of the ETO diaphyseal fragment occurred in 22 hips (4%), postoperative fracture of the ETO diaphyseal fragment occurred in 3 hips (0.5%), and postoperative fracture of the greater trochanter occurred in 41 hips (7%). Survivorship at 10 years free of revision for aseptic femoral loosening, free of femoral or acetabular component removal or revision for any reason, and free of reoperation for any reason was 97%, 91%, and 82%, respectively. Conclusions This large series of ETOs shows that the union rate is high and clinically important trochanteric migration is infrequent. The most common complications are fracture of the osteotomy fragment intraoperatively or postoperatively. Level of evidence Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Tuning metal–metal interactions for cooperative small molecule activation

Cluster complexes have attracted interest for decades due to their promise of drawing analogies to metallic surfaces and metalloenzyme active sites, but only recently have chemists started to develop ligand scaffolds that are specifically designed to support multinuclear transition metal cores. Such ligands not only hold multiple metal centers in close proximity but also allow for fine-tuning of their electronic structures and surrounding steric environments. This Feature Article highlights ligand designs that allow for cooperative small molecule activation at cluster complexes, with a particular focus on complexes that contain metal–metal bonds. Two useful ligand-design elements have emerged from this work: a degree of geometric flexibility, which allows for novel small molecule activation modes, and the use of redox-active ligands to provide electronic flexibility to the cluster core. The authors have incorporated these factors into a unique class of dinucleating macrocycles (nPDI2). Redox-active fragments in nPDI2 mimic the weak-overlap covalent bonding that is characteristic of M–M interactions, and aliphatic linkers in the ligand backbone provide geometric flexibility, allowing for interconversion between a range of geometries as the dinuclear core responds to the requirements of various small molecule substrates. The union of these design elements appears to be a powerful combination for analogizing critical aspects of heterogeneous and metalloenzyme catalysts.
Harnessing the polyamine transport system to treat BRAF inhibitor-resistant melanoma.

BRAF mutations are present in over half of all melanoma tumors. Although BRAF inhibitors significantly improve survival of patients with metastatic melanoma, recurrences occur within several months. We previously reported that BRAF mutant melanoma cells are more sensitive to a novel arylmethyl-polyamine (AP) compound that exploits their increased polyamine uptake compared to that of BRAF wildtype cells. Using an animal model of BRAF inhibitor-resistant melanoma, we show that co-treatment with the BRAF inhibitor, PLX4720, and AP significantly delays the recurrence of PLX4720-resistant melanoma tumors and decreases tumor-promoting macrophages. Development of BRAF inhibitor-resistance enriches for metastatic cancer stem cells (CSC) and increases tumor-promoting macrophages. In vitro studies demonstrated that CD304+, CXCR4+ spheroid cultures of BRAF mutant melanoma cells are resistant to PLX4720 but are more sensitive to AP compared to monolayer cultures of the same cells. AP significantly inhibited YUMM1.7 melanoma cell invasiveness across a Matrigel-coated filter using the CXCR4 ligand, SDF-1α, as the chemoattractant. AP also blocked the chemotactic effect of SDF-1α on CXCR4+ macrophages and inhibited M2 polarization of macrophages. In melanoma-macrophage co-cultures, AP prevented the PLX4720-induced release of pro-tumorigenic growth factors, such as VEGF, from macrophages and prevented the macrophage rescue of BRAF mutant melanoma cells treated with PLX4720. Our study offers a novel therapy (AP) to treat chemo-resistant melanoma. AP is unique because it targets the polyamine transport system in BRAF inhibitor-resistant CSCs and also blocks CXCR4 signaling in invasive melanoma cells and pro-tumorigenic macrophages.
Effects of cognitive load and type of object on the visual looming bias.

According to the behavioral urgency hypothesis, organisms have evolved various mechanisms that facilitate their survival by focusing attention and resources on approaching danger. One example of such mechanisms is the looming bias—the tendency for an individual to judge an approaching object’s distance as being closer or time-to-collision as being sooner than receding or stationary objects. To date, most research on the looming bias has explored the ways in which human factors and object characteristics influence the strength and direction of the bias. The current study expanded on this field of research in two novels ways by exploring (a) whether cognitive vulnerabilities may influence the strength of the looming bias in the visual domain, and (b) whether the combination of human factors (i.e., cognitive load) and object characteristics (i.e., object threat) interact to create an additive effect on looming bias strength. Findings appear to only partially support the hypotheses that cognitive vulnerabilities can influence looming bias strength in the visual domain, and that factors related to both the individual and the looming object may interact to create a stronger looming bias. These findings help to highlight possible evolutionary advantages of the looming bias and its presence across modalities, as well as add some strength to the claims that the margin of safety theory can be generalized to include psychological factors.
A review of safety considerations for batteries in aircraft with electric propulsion

Modern aircraft designs for “more electric” and “fully electric” aircraft have large battery packs ranging from tens of kWh for urban aviation to hundreds or thousands of kWh for commercial aviation. Such large battery packs require careful consideration of the safety concerns unique to aviation. The most pertinent safety concerns related to batteries can be categorized into two broad areas: exothermic heat related events (thermal issues) and partial or complete loss of safety–critical power supply (functional issues). Degradation during operation of a battery can contribute to capacity fade, increased internal resistance, power fade, and internal short circuits, which lead to the loss of or decrease in propulsive power. When batteries are the primary source of onboard power and energy, it is crucial to be able to estimate their state-of-health in terms of capacity and power capability. Internal short circuits and other sources of excessive heat generation can lead to high temperatures within the cells of a battery pack leading to safety concerns and thermal events. One of the biggest risk factors for batteries used in aviation is the potential for thermal runaway where temperatures reach the flashpoint of one of the cell components, eventually cascading over multiple cells leading to system-wide battery pack failure and a fire hazard. This article reviews the current understanding of the safety concerns related to batteries in the context of urban and regional electric aviation.