Black Bars Research Articles

Black hole interactions at large D: brane blobology

In the large dimension (D) limit, Einstein’s equation reduces to an effective theory on the horizon surface, drastically simplifying the black hole analysis. Especially, the effective theory on the black brane has been successful in describing the non-linear dynamics not only of black branes, but also of compact black objects which are encoded as solitary Gaussian-shaped lumps, blobs. For a rigidly rotating ansatz, in addition to axisymmetric deformed branches, various non-axisymmetric solutions have been found, such as black bars, which only stay stationary in the large D limit.In this article, we demonstrate the blob approximation has a wider range of applicability by formulating the interaction between blobs and subsequent dynamics. We identify that this interaction occurs via thin necks connecting blobs. Especially, black strings are well captured in this approximation sufficiently away from the perturbative regime. Highly deformed black dumbbells and ripples are also found to be tractable in the approximation. By defining the local quantities, the effective force acting on distant blobs are evaluated as well. These results reveal that the large D effective theory is capable of describing not only individual black holes but also the gravitational interactions between them, as a full dynamical theory of interactive blobs, which we call brane blobology.

Co-revolving topological defects in a nematic liquid crystal

A patterned surface defect of strength m = +1 and its associated disclination lines can decompose into a pair of surface defects and disclination lines of strength m = +1/2. For a negative dielectric anisotropy liquid crystal subjected to an applied ac electric field E, these half-integer defects are observed to wobble azimuthally for E > than some threshold field and, for sufficiently large fields, to co-revolve antipodally around a central point approximately midway between the two defects. This behavior is elucidated experimentally as a function of applied field strength E and frequency ν, where the threshold field for full co-revolution scales as ν1/2. Concurrently, nematic electrohydrodynamic instabilities were investigated. A complete field vs. frequency "phase diagram" compellingly suggests that the induced fluctuations and eventual co-revolutions of the ordinarily static defects are coupled strongly to-and driven by-the presence of the hydrodynamic instability. The observed behaviour suggests a Lehmann-like mechanism that drives the co-revolution.

1027. Long-Term Efficacy, Safety, and Durability of Ibalizumab-Based Regimens in Subgroup of TMB-202 Participants

BackgroundThird line antiretroviral regimens have been associated with suboptimal virologic suppression, due to drug cross-resistance and regimen complexity. Yet, in treatment-experienced (TE) HIV patients, ART durability is essential for preventing further resistance and decreasing HIV-associated morbidity and mortality. Ibalizumab (IBA), the first long-acting, post-attachment inhibitor approved to treat multi-drug resistant (MDR) HIV, may support regimen durability given its directly observed administration. We analyzed the safety, efficacy, and durability of response in 12 patients who started IBA in a Phase 2b study.MethodsIn TMB-202, 113 patients with MDR HIV received either 2000 mg IBA every 4 weeks (n=54) or 800 mg IBA every 2 weeks (n=59) for 24 weeks with an optimized background regimen (OBR). Of 96 patients who completed TMB-202, 56 transferred into an investigator-sponsored investigational new drug protocol and 12 later moved onto an expanded access protocol, TMB-311, where efficacy and safety were monitored until IBA was commercially available (approval 2018).ResultsBaseline median viral load (VL) and CD4 count for the 12 patients were 4.4 log10 copies/mL (c/mL) and 135 cells/mL, respectively. The median duration of HIV infection was 22 years (range 18-25). At the completion of TMB-202 11/12 achieved virologic suppression (VL < 200 c/mL) and 8/12 had VL < 50 c/mL. All 12 patients were suppressed (VL < 50 c/mL) at their last TMB-311 visit. Patients gained an average of 99 CD4 cells/mL relative to baseline. There were no treatment-emergent adverse events (TEAE) or therapy discontinuations related to IBA during follow-up. Two patients died from unrelated causes. Overall, the 12 patients remained on IBA for an average of 8.9 years (range 8-9.5), during which 8/12 did not require addition of new ARVs to their OBR to maintain suppression.Figure 1: duration of ibalizumab-based regimen is displayed for the 12 patients. Grey bars represent patients with no addition of new ARVs to OBR. Black bars represent patients with an addition to OBR. Asterisks represent addition of ritonavir only. ConclusionData from 12 patients who received IBA for an average of 9 years validate the long-term efficacy and safety of IBA in TE patients. Importantly, for most patients, the durability of virologic response was maintained with minimal adjustments to the OBR. Altogether, these data demonstrate the contribution of IBA towards durable viral suppression in TE HIV patients with limited therapeutic options.Disclosures William Towner, MD, Dynavax (Research Grant or Support)Gilead (Grant/Research Support)Merck (Research Grant or Support)Tai Med (Research Grant or Support)ViiV (Research Grant or Support) Edwin DeJesus, MD, Gilead Sciences (Advisor or Review Panel member) Colleen McGary, PhD, Theratechnologies (Employee) Mohammed Zogheib, PharmD, MPH, Theratechnologies (Employee) Steven Weinheimer, PhD, TaiMed Biologics USA (Employee) Pedro Mesquita, PhD, Theratechnologies, Inc. (Employee)

Two new species of loaches from the Irrawaddy River basin, Chin State, Myanmar (Teleostei: Cypriniformes: Nemacheilidae).

Schistura falamensis, a new species of nemacheilid loach, is described from the main channel of the Manipur River in the Irrawaddy River basin, Chin State, western Myanmar. It differs from other congeners of the genus Schistura by a combination of the following characters: 5-8 vertical bars on body; indistinct bars in front of dorsal-fin origin; bars on posterior part of body regular, twice as wide as interspace; black caudal basal bar dissociated, short, not reaching ventral extremity; males with suborbital flap; lateral line complete; and processus dentiformis weak. Schistura altuscauda is a new species described from the Htin stream, Mindat Town, Chin State, Myanmar. It can be distinguished from other congeners by a combination of the following characters: high caudal peduncle (14.0-20.3% SL), strong processus dentiformis on upper jaw; 7-19 bars on flank of body, bars in front of dorsal fin obviously thinner than those behind, sometimes fused in front of dorsal fin; lateral line complete; males with prominent suborbital flap; and pelvic lobe present.

A new species of dartfish of the genus Ptereleotris (Teleostei: Gobiidae) from the East Coast of India.

Ptereleotris cyanops n. sp. is described from five specimens collected in trawl landings at Chennai, Tamil Nadu, East Coast of India. The new species is unusual among congeners in possessing a wide interdorsal space, its width 2.5-3.2% in SL. The new species resembles P. microlepis in general morphology and coloration, but is readily distinguished from it in lacking a black bar at base of pectoral fin, in having a slightly truncate caudal fin with the 5th and 13th branched rays prolonged as filaments (vs. emarginated caudal fin with absence of any caudal filaments), and in having the second dorsal and anal fin not elevated anteriorly (vs. elevated). Ptereleotris cyanops differs from caudal filaments bearing congeners viz., P. arabica and P. hanae, by the absence of chin barbel (vs. present in both); in having a longer pelvic fin (17.7-18.8 vs. 13.1-15.5% SL in P. arabica), and more anal rays (27 vs. 22-25 in P. hanae).

S0392 Spastic Esophageal Changes Detected on Functional Lumen Imaging Probe Topography Are Associated With Lower Acid Exposure in Patients With Suspected Gastroesophageal Reflux Disease

INTRODUCTION: Hypercontractile and spastic motility changes are hypothesized to be an esophageal response to gastroesophageal reflux disease (GERD). The functional lumen imaging probe (FLIP) measures distension induced esophageal contractility. We aim to compare symptoms, acid exposure, and reflux events as related to esophageal motility pattern on FLIP in patients with presumed GERD. METHODS: We prospectively collected data on all patients who underwent FLIP and BravoTM placement during upper endoscopy for evaluation of proton-pump inhibitor (PPI) refractory symptoms presumed to be related to GERD between January 2019 and March 2020. A total of 23 patients were included. Patients with a history of anti-reflux surgery, primary symptoms of dysphagia or a diagnosis of achalasia were excluded. Patients were characterized based on FLIP motility criteria as having either 1) Normal or diminished contractility or 2) Spastic contractility (if FLIP showed esophagogastric junction outflow obstruction or repetitive retrograde contractions). Total and maximal single-day acid exposure % and number of reflux events were compared. Presence of heartburn as the reported primary symptom and GERD questionnaire (GERDQ) scores were also compared. Mann-Whitney test was used to compare continuous variables; Fisher’s exact test was used to compare categorical variables. RESULTS: Normal/diminished and spastic contractility were noted in 14 (61%) and 9 (39%) respectively. Maximal single-day acid exposure % time (4.5% vs 9.2%, P value: 0.02), average acid exposure % time (2.7% vs 6.8%, P value: 0.02) and number of reflux events (24 vs 47.5 events, P value: 0.04) were lower in the spastic contractility group (Figure 1). GERDQ score was 7.5 in the spastic motility group vs 10 in the normal/diminished motility group (P value: 0.8). Seven out of 14 (50%) of the normal/diminished motility group had heartburn in comparison to only 1 out of 9 (11%) in the spastic motility group (P value: 0.08) (Table 1). The most common symptoms in the spastic motility group were non-cardiac chest pain and laryngeal symptoms. CONCLUSION: Spastic motility findings are detected on FLIP in a high proportion of patients with PPI-refractory esophageal symptoms in the absence of dysphagia. Spastic motility on FLIP is associated with less measured acid exposure and a different symptom profile with less heartburn. Studies evaluating resolution of spastic changes and symptoms over time with PPI therapy could confirm this group as a GERD-spectrum entity.Table 1.: Patient characteristicsFigure 1.: BravoTM metrics and Gastroesophageal reflux disease questionnaire (GERDQ) score results in the normal/diminished motility and spastic motility groups are shown. Maximal single-day acid exposure % time and number of reflux events are shown. Group median values are displayed as black bars.

Evaluation of surface roughness and bond-slip behavior of new textured epoxy-coated reinforcing bars

Epoxy-coated reinforcing bars are widely used in bridge decks to mitigate the corrosion of reinforcing steel. Research and practical experience both showed that the smooth epoxy coating significantly reduces the bond between concrete and reinforcing steel, which often results in the early development of transverse cracks in bridge decks. To solve this problem, the Illinois Department of Transportation (IDOT) proposed a new type of textured epoxy-coated (TEC) reinforcing bars with applied roughness to improve the bond between concrete and steel while providing corrosion protection. This study investigates the surface roughness of six different types of TEC bars and how it impacts the bar’s bond-slip behavior with concrete. First, the surface roughness of the TEC bars is compared with that of uncoated black bars (BLK) using 2-D parameters Ra, Rz, and 3-D parameters Sa and Sz. Second, direct pull-out tests are conducted on concrete specimens with embedded 1) BLK, 2) smooth epoxy-coated (SEC), and 3) all six TEC bars to compare their bond characteristics. Finally, a 3-D finite element model is developed and calibrated to simulate the bond-slip behavior of TEC bars embedded in concrete. The results show that the average surface roughness of TEC bars is 3–4 times that of the uncoated bars. Further, TEC bars generally exhibit higher slip resistance than the uncoated and smooth epoxy-coated bars.

Underrepresentation of Racial Minorities in Breast Surgery Literature: A Call for Increased Diversity and Inclusion.

In this study, the extent of racial diversity in images of breast-related plastic surgery published literature was investigated to better understand disparities that exist in breast surgery. The lack of racial diversity in images of skin color in surgery literature can perpetuate implicit bias and stereotypes. Implicit bias can affect the way patients are evaluated, diagnosed, and treated. The visual aspects of plastic surgery make a lack of diversity in imagery especially impactful on patient care and outcomes. Published medical images and graphics depicting human skin were analyzed across 4 major plastic surgery journals. Up to 4 years were chosen a priori to evaluate from each journal and represented the initial year of color image publication, the year of study initiation (2016), and representative years for a given decade (2000 and 2010). Images and graphics were tabulated, rated by Fitzpatrick scale and categorized into "White" or "non-White." Data were evaluated with pair-wise and linear regression statistics. Of the 2774 images and 353 graphics that met inclusion criteria, only 184 (8.18%) images and 9 graphics (6.34%) depicted non-White skin. Temporal analysis showed that there is an increased diversity of images published since 2010 with 0% of images being non-White before and 7.3% to 10.3% after 2010. International and multi-national authors tended to publish more non-White images. There is insufficient racial diversity visually represented in the breast-related plastic surgery literature with a small degree of progress made towards more equitable imagery over time. Increasing awareness of image content, and the need for equitable visual representation may allow for improved racial diversity in surgical literature.

Entropy production and entropic attractors in black hole fusion and fission

We study how black hole entropy is generated and the role it plays in several highly dynamical processes: the decay of unstable black strings and ultraspinning black holes; the fusion of two rotating black holes; and the subsequent fission of the merged system into two black holes that fly apart (which can occur in dimension D ≥ 6, with a mild violation of cosmic censorship). Our approach uses the effective theory of black holes at D → ∞, but we expect our main conclusions to hold at finite D. Black hole fusion is highly irreversible, while fission, which follows the pattern of the decay of black strings, generates comparatively less entropy. In 2 → 1 → 2 black hole collisions an intermediate, quasi-thermalized state forms that then fissions. This intermediate state erases much of the memory of the initial states and acts as an attractor funneling the evolution of the collision towards a small subset of outgoing parameters, which is narrower the closer the total angular momentum is to the critical value for fission. Entropy maximization provides a very good guide for predicting the final outgoing states. Along our study, we clarify how entropy production and irreversibility appear in the large D effective theory. We also extend the study of the stability of new black hole phases (black bars and dumbbells). Finally, we discuss entropy production through charge diffusion in collisions of charged black holes.

COMPARATIVE ANALYSIS OF STEEL CORROSION RESISTANCE

The objective of the study was to conduct the comparative analysis of steel types corrosion resistance. Three selected steel types were used in the study. The selected types were structural steel, stainless steel, and MMFX steel. The methodology we adopted is that we evaluated the steel parts resistance towards corrosion by doing in-salt spray experiment and the immersion of aqueous solution of sodium chloride. For salt spray test, we used guidelines by ASTM B117. This practice provides a controlled corrosion environment which is used for exposing specimen to salt spray chamber. For immersion test, test specimens are analyzed at regular time interval as the first rust is appeared. For carbon steel, we used three specimen and mostly initial rust appeared in initial 13 to 15 hours. For stainless steel, inter granular corrosion were analyzed. The results show that the first cycle started after about 46 hours; the second cycle started about 1% and the third cycle started with the rage of about 2 to 30%. For MMFX 2 steel, the results show that for MMFX carbon steel, the chloride threshold ratio is about 6 times higher than black bars and more than double of other types. The conclusion of the study is that in big structures like bridges, the MMFX steel should be used.

Variation in the Arrow Loach, Nemacheilus masyae (Cypriniformes: Nemacheilidae), in Mainland Southeast Asia with Description of a New Species

Analyses of morphological and molecular data from recently collected specimens of Nemacheilus from Cambodia, Malaysia, and Thailand indicate that N. pallidus is a junior synonym of N. masyae, and an undescribed species of Nemacheilus occurs in large tributaries of the Mekong River in Thailand. The new species, described herein, is small—with a maximum-known standard length of 28.6 mm—and has a distinctive color pattern of dusky black bars along the side of the body that cross over the back and join the bars on the other side. Molecular phylogenetic analyses suggest that the new species is most closely related to N. masyae , which reaches a much larger size—to 66.2 mm SL—and otherwise is easily distinguished from the new species. The new species is known from the Songkhram and Mun river drainages in Thailand and appears to be restricted to the Khorat Plateau ecoregion of the Mekong River basin. Nemacheilus masyae occurs throughout mainland southeast Asia, including in the Chao Phraya, Mae Klong, Mekong, and coastal drainages of the Malay Peninsula.

A NEW SPECIES OF Dendrelaphis BOULENGER, 1890 (REPTILIA : COLUBRIDAE) FROM THE WET ZONE OF SRI LANKA WITH A REDESCRIPTION OF Dendrelaphis bifrenalis (BOULENGER, 1890)

Examination of the Dendrelaphis bifrenalis populations on Sri Lanka showed that there are two populations that are morphologically different from each other. One population is distributed only in the wet zone forests (hereafter treated as wet zone population), while the other population occurs widely in the dry zone and intermediate zones (hereafter dry zone population). The type series of D. bifrenalis consist of 3 specimens from which the specimen representing the dry zone population was chosen as lectotype, and the wet zone population is described here as a new species. It clearly differs from D. bifrenalis by having a shorter snout, orbit diameter 103–114% of eye–nostril length (vs 77–95%), and larger eye, orbit diameter 21–23% of head length (vs 17–20%). Furthermore it differs by having a temporal stripe stopping just beyond the neck (vs continues behind neck), the absence of black transverse dorsolateral bars on the anterior 1/4th of body (vs prominent), a narrow and pointed snout (vs broad and flat), a divided nasal (vs single), and a ventrolateral stripe continuing up to the tail (vs stopping at the level of the anal plate). This morphological differentiation is supported by the divergence in the mitochondrial NADH dehydrogenase subunit 4 (ND4) region separating clearly with the divergence of 1.70±0.35%. Also, here we resurrect D. effrenis (Werner, 1909) as a valid species, and D. sinharajensis as a junior synonym of it. The holotype of D. sinharajensis was chosen as the neotype of D. effrenis to stabilize nomenclature, and to make it an objective synonym. The third and fourth known specimens of this rare species are reported. A key of the species of the genus Dendrelaphis in Sri Lanka is provided.

Scientificity of traditional commodity grade of Chinese medicinal materials--taking Lonicerae Japonicae Flos as example

Taking Lonicerae Japonicae Flos as an example, the method of &quot;expert consensus of different regions&quot; was used to screen the representative samples and evaluate their commodity grades. The correlation analysis, hierarchical cluster analysis and partial least squares discriminant analysis(PLS-DA) of &quot;commodity grade-appearance characteristic-component content&quot; were carried out to reveal the scientificity of traditional commodity grade of Chinese medicinal material. By referring to the existing literature and the grade investigation from the sample collection regions, 78 &quot;initial grade&quot; samples were screened out from 118 collected samples. Authoritative experts from four regions(n=4) including Linyi(Shangdong province), Bozhou(Anhui province), Anguo(Hebei province) and Beijing were organized to evaluate their commodity grades, separately. Based on the grade consistency rate(R_i≥70%), 69 &quot;local grade&quot; samples were screened out from the &quot;initial grade&quot; samples. Based on the average grade consistency rate ■ &quot;authoritative grade&quot; samples were screened out from the &quot;local grade&quot; samples, including15 first-grade samples, 9 second-grade samples, 11 third-grade samples and 17 fourth-grade samples. For these &quot;authoritative grade&quot; samples, the main appea-rance characteristics were quantified and the contents of 13 components were determined by ultra performance liquid chromatography(UPLC). Furthermore, the total contents of 6 phenolic acids, 4 flavonoids and 3 iridoids were calculated, respectively. The results of correlation analysis showed that 4 appearance characteristics indices were correlated with the commodity grades: color, rate of yellow bars(including blooming flowers), rate of black heads(including black bars), and rate of stems and leaves(including bud debris). Five component content indices were correlated with the commodity grades: chlorogenic acid, isochlorogenic acid C, sweroside, loganin and the total contents of six phenolic acids. Furthermore, chlorogenic acid, loganin and the total contents of six phenolic acids showed significantly negative correlation with the main appearance characteristics, indicating that the appearance characteristics of Lonicerae Japonicae Flos can reflect its internal quality, and these 3 indices can be used as quality markers(Q-markers). The results of hierarchical cluster analysis showed that the samples of four grades were classified into four categories, and the samples with the same grades and the same categories accounted for 80.8% of the total samples, while the samples with the different grades were obviously classified into different categories. The results of PLS-DA analysis showed that the samples of different grades showed obvious intragroup aggregation and intergroup dispersion. The above results indicated that it was feasible to evaluate the traditional commodity grade of Lonicerae Japonicae Flos by the method of &quot;expert consensus of different regions&quot;. For the evaluation of traditional commodity grade of Chinese medicinal material, the samples should be representative, expert conclusions should have enough consensuses, and grade determination should be authoritative. As the crystallization of clinical experience, traditional commodity grade can scientifically reflect the internal quality of Chinese medicinal material.

The Amapá treefrog Boana dentei (Bokermann, 1967): diagnosis and redescription (Hylinae: Cophomantini)

ABSTRACT Many aspects of the Amazonian amphibian fauna are yet understudied. This is the case of the Amapá treefrog, Boana dentei, which was described in the 1960s based on a single female specimen from Serra do Navio, a Brazilian region of lowland Amazonian forests in the easternmost portion of the Guiana Shield. The species has been reported only a few times since its description, and phenotypic data from its type locality still remain unknown. We redescribe this treefrog species, including the first characterisation of the male, life colours, tadpole, vocalisation, and notes on habitat, based on a newly collected series from the type locality. Boana dentei is sexually dimorphic with respect to external morphology and colour patterns. Males are distinguished from females by a smaller snout–vent length, lighter dorsal colouration, bright yellow colour in ventral hindlimbs and palm of hand, and enlarged prepollex. Boana dentei is distinguished from other members of the B. albopunctata group by the snout truncate from above and rounded to vertical in profile, calcar absent on heel, black vertical bars on thigh, and vocal repertoire composed of three types of pulsed notes.

Matching the Directions of Electric Fields from Triboelectric and Ferroelectric Charges in Nanogenerator Devices for Boosted Performance.

SummaryEmbedding additional ferroelectric dipoles in contacting polymer layers is known to enhance the performance of triboelectricnanogenerator (TENG) devices. However, the influence of dipoles formed between the triboelectric surface charges on two contacting ferroelectric films has been ignored in all relevant studies. We demonstrate that proper attention to the alignment of the distinct dipoles present between two contacting surfaces and in composite polymer/BaTiO3 ferroelectric films can lead to up to four times higher energy and power density output compared with cases when dipole arrangement is mismatched. For example, TENG device based on PVAc/BaTiO3 shows energy density increase from 32.4 μJ m−2 to 132.9 μJ m−2 when comparing devices with matched and mismatched dipoles. The presented strategy and understanding of resulting stronger electrostatic induction in the contacting layers enable the development of TENG devices with greatly enhanced properties.

Analysis of HMAX Algorithm on Black Bar Image Dataset

An accurate detection and classification of scenes and objects is essential for interacting with the world, both for living beings and for artificial systems. To reproduce this ability, which is so effective in the animal world, numerous computational models have been proposed, frequently based on bioinspired, computational structures. Among these, Hierarchical Max-pooling (HMAX) is probably one of the most important models. HMAX is a recognition model, mimicking the structures and functions of the primate visual cortex. HMAX has already proven its effectiveness and versatility. Nevertheless, its computational structure presents some criticalities, whose impact on the results has never been systematically assessed. Traditional assessments based on photographs force to choose a specific context; the complexity of images makes it difficult to analyze the computational structure. Here we present a new, general and unspecific assessment of HMAX, introducing the Black Bar Image Dataset, a customizable set of images created to be a universal and flexible model of any ‘real’ image. Results: surprisingly, HMAX demonstrates a notable sensitivity also with a low contrast of luminance. Images containing a wider information pattern enhance the performances. The presence of textures improves performance, but only if the parameterization of the Gabor filter allows its correct encoding. In addition, in complex conditions, HMAX demonstrates good effectiveness in classification. Moreover, the present assessment demonstrates the benefits offered by the Black Bar Image Dataset, its modularity and scalability, for the functional investigations of any computational models.

A new livebearing fish of the genus Limia (Cyprinodontiformes: Poeciliidae) from Lake Miragoane, Haiti.

Limia islai, a new species of livebearing fish, is described from Lake Miragoane in south-western Haiti on Hispaniola. The new species has a conspicuous barred pattern consisting of several (4-12) black bars along the body, ray 4p serrae of the gonopodium in males with 10 segments and origin of dorsal fin in females slightly behind the origin of the anal fin. Although the new species colour pattern is similar to that of the humpbacked limia Limia nigrofasciata Regan 1913, L. islai sp. nov. has exclusive morphological features, such as slender body, lack of hump anterior to dorsal fin in males and presence of specific features in the gonopodial suspensory, which allow an unambiguous diagnosis from L. nigrofasciata. L. islai further differs from L. nigrofasciata in reproductive behaviour since L. islai males rely on sneak copulations and gonopodial thrusting, whereas L. nigrofasciata display an elaborate courtship behaviour. The new species is also genetically distinct in both nuclear (Rh, Myh6) and mitochondrial (12S, ND2, D-loop, Cytb) genes from other species in the genus showing reciprocal monophyly. The description of this new Limia species from Lake Miragoane confirms this lake as an important centre of endemism for the genus, with a total of eight endemic species described so far.

Subpixel Motion Detection Using a Commercial Video Camera

Performance metrics for detecting subpixel motion are calculated for a commercial video camera using image difference data processed with three Neyman–Pearson-based algorithms. High-signal-to-noise-ratio data are collected and analyzed for a thin black bar that slowly oscillates against a white background. The position and velocity of the bar are estimated using Fourier-based processing techniques. The probability of detecting subpixel motion as a function of false alarm rate, number of pixels tested, subpixel shift, and detection algorithm are calculated with Monte Carlo simulations using the experimental data. The results characterize the best performance curves for detecting subpixel motion for most commercial video cameras and targets.

A new species of the genus &lt;italic&gt;Sinomicrurus&lt;/italic&gt; (Serpentes: Elapidae) from China and Vietnam

A new species of Sinomicrurus Slowinski, Boundy, and Lawson, 2001 is described herein based on a series of specimens. The new species, Sinomicrurus peinanisp. nov., occurs in southern China and northern Vietnam. Sinomicrurus peinanisp. nov. is distinguished from its congeners by the following combination of characters: (1) 30-35 black cross-bands on body and tail; (2) 13 dorsal scale rows throughout, all smooth; (3) white belly with black cross-bands or irregular spots; (4) broad white transverse bar on top of head with inverted V-shaped anterior margin, white bar wider than anterior black bar; and (5) frontal V-like, 1.3 times as long as wide. In addition, new occurrences of S. houi in Guangxi, China, and Vietnam are discussed.

CRISPR-Cas9 Genome Editing of γ-Globin Promoters in Human Hematopoietic Stem Cells to Induce Erythrocyte Fetal Hemoglobin for Treatment of β-Hemoglobinopathies

Induction of fetal hemoglobin (HbF, α2γ2) via genome editing-mediated disruption of DNA regulatory elements that repress expression of γ-globin genes (HBG1 and HBG2) is a promising therapeutic strategy for b-hemoglobinopathies including sickle cell disease (SCD) and β-thalassemia. Optimal technical approaches and safety profiles are yet to be fully defined. We used CRISPR/Cas9 to target a DNA repressor element near the distal CCAAT box of the HBG1/HBG2 promoters. This region contains a "TGACC" motif recognized by BCL11A, a transcriptional repressor protein that regulates γ-to-β globin switch after birth. Rare germline variants at or near this motif are associated with hereditary persistence of fetal hemoglobin, a benign genetic condition that alleviates the clinical manifestations of co-inherited b-hemoglobinopathies. Previously, we showed that transduction of human CD34+ cells with lentiviral vector encoding Cas9 and guideRNA (gRNA) targeting the HBG1/HBG2 promoter caused induction of HbF in red blood cell (RBC) progeny generated in vitro (Traxler et. al, Nature Medicine v22,2016). Here we present a clinically tractable approach for disrupting the HBG1/HBG2 BCL11A binding site in human hematopoietic stem cells (HSCs). Electroporation of Cas9:gRNA ribonucleoprotein (RNP) complex into healthy or SCD donor CD34+ cells resulted in up to 80% on-target insertion-deletion (indel) mutations and 35% HbF in erythroid progeny generated in vitro. Sixteen to 17 weeks after transplantation of gene edited CD34+ cells into immunodeficient NBSGW mice, up to 75% of donor CD34+ cells in recipient bone marrow contained on-target indels, demonstrating efficient modification of repopulating human HSCs. No differences in CD34+ cell regeneration or differentiation into erythroid, T, B, or myeloid cell lineages were observed between edited and control cells. Moreover, up to 78% of gene edited erythroid cells stained with anti-HbF antibody ("F-cells") compared to 15% in control erythroid cells, suggesting a "pan-cellular" pattern of HbF expression after editing. Strikingly, human donor-derived erythroid cells in recipient bone marrow expressed up to 40% HbF compared to 3% HbF in controls. Although the editing frequencies of HBG1 and HBG2 promoters varied between different donor CD34+ cells, an engineered variant of Cas9 containing 3 nuclear localization sequences (Wu et. al,Nature Medicine v25, 2019) edited repopulating HSCs more efficiently and consistently than conventional Cas9 with two nuclear localization signals. Simultaneous on-target RNP-induced DSBs at both HBG1 and HBG2 can result in the deletion of the intervening 4.9-kb region, leaving a single hybrid gene with HBG2 promoter sequences fused to the downstream HBG1 gene. We detected this deletion in approximately 30% of edited cells, with no associated decline in HbF expression determined by clonal analysis of erythroid colonies. No off-target mutations were detected by targeted sequencing of the 26 top candidate sites identified by CIRCLE-seq, an in vitro genome-scale method for detecting Cas9 activity. Analysis of gene edited human donor cells purified from mouse bone marrow showed no chromosomal rearrangements by G-banding (n=20) or fluorescence in situ hybridization with a probe located distal to the HBG1/HBG2 loci (n=225). Taken together, our studies provide novel and essential preclinical evidence supporting the safety, feasibility, and efficacy of a CRISPR-Cas9 genome editing approach to induce HbF for treating hemoglobinopathies. Figure. Gene editing of the HBG1/HBG2 promoters in HSCs and HbF induction of erythroid progeny in vivo. Plerixafor-mobilized CD34+ cells from an individual with SCD were edited with RNP and transplanted into NBSGW mice, which were analyzed 16-17 weeks later. A. On-target indel frequency before (Pre) and after bone marrow transplantation (BM). The black bars represent a 13-nucleotide deletion associated with human hereditary persistence of fetal hemoglobin. B. Human erythroblasts and reticulocytes derived from RNP-edited and non-edited Control CD34+ donor cells. Scale bar = 10 mm. C. HbF immunostaining control and RNP edited erythroid cells in recipient bone marrow assessed by flow cytometry. D. %HbF protein in hemolysates of control (C) and RNP edited erythroid cells assessed by ion-exchange HPLC. n= 3 biological replicates. **** P &lt; 0.0001. Figure Disclosures Metais: MBIO: Other: St. Jude Children's Research Hospital has an existing exclusive license and ongoing partnership with Mustang Bio for the further clinical development and commercialization of this XSCID gene therapy. Sharma:Doris Duke Foundation: Research Funding; Vertex Pharmaceuticals: Other: Study PI. Weiss:Beam Therapeutics: Consultancy; Rubius INC: Consultancy; GlaxoSmithKline: Consultancy; Cellarity INC: Consultancy; Esperian: Consultancy.