cssi/SciSciGPT-SciSciNet huggingface dataset:
Sialic Acid Induced Conformational Ensemble Shifts in the Hemagglutinin-Neuraminidase Protein of the Newcastle Disease Virus

Newcastle disease virus (NDV) belongs to the family of enveloped paramyxoviruses that cause many diseases in humans and farm animals. NDV is of serious concern to poultry, and infects over 200 species of birds. To gain entry into host cells, NDV uses a concerted action of two of its membrane proteins: the Hemagglutinin-Neuraminidase (HN) protein, and the fusion protein (F). HN binds to sialic acids expressed on the host surface, and this binding causes HN to activate F, which, in turn, mediates NDV-host membrane fusion. However, the mechanism of long-distance (> 2 nm) allosteric coupling between HN's sialic acid (receptor) binding domains (RBDs) and F-activating domain (FAD) is unknown. Understanding this signaling process has been challenging because HN belongs to the category of proteins like GPCRs and PDZ domains where receptor-induced structural changes are of the order of thermal fluctuations. To gain insight, we carry out multiple all-atom molecular dynamics simulations of HN in its monomer/dimeric forms as well as in its apo and sialic acid bound states. We consider also both optical isomers of sialic acid — the α-anomer that is expressed on host surfaces and the β-anomer that is preferred over the α-anomer in solution, but which does not induce HN to activate F. We find that while the two anomers induce similar RBD-RBD reorientations, they produce strikingly different conformational ensemble shifts within individual RBDs, suggesting that allosteric signaling must involve the RBD-FAD interface. Further analysis yields a cluster of residues proximal to both RBD-FAD and RBD-RBD interfaces whose conformational ensembles are shifted by α-sialic acid. Together, these results suggest that allosteric coupling between RBD and FAD involves a complex pathway comprising of multiple inter-domain interfaces.
XSIM Final Report: Modelling the Past and Future of Identity Management for Scientific Collaborations

US Dept of Energy Next-Generation Networks for Science (NGNS) program Grant No. DE-FG02-12ER26111
Computer security

Computer security has hit the mainstream. This paper is a high-level treatment of computer security, its concepts and terminology, and some pointers about where to go for more information.
THE GENETIC STRUCTURE OF A GYNODIOECIOUS PLANT: NUCLEAR AND CYTOPLASMIC GENES.

Sex expression in gynodioecious plants is often determined by an interaction between biparentally and maternally inherited genes. Their relative rates of gene flow should be considered when modeling the evolution of the sex ratio in structured populations. In order to understand patterns of gene flow in Silene vulgaris, a gynodioecious plant, genetic structure was estimated from biparentally inherited genetic markers (allozymes) and a maternally inherited marker (chloroplast DNA) using Wright's Fst . Based on data from 16 local populations, chloroplast DNA showed considerably more genetic structure than did allozymes (Fst values of 0.62 and 0.22, respectively). This suggests that the rate of gene flow is about three times greater for nuclear genes.
Effects of delayed placement on intestinal characteristics in turkey poults

To determine the effects of delayed access to feed on intestinal villus development, bacterial translocation, and salmonella attachment potential in turkey poults, poults were given ad libitum access to water and feed immediately after hatch (FED) or were delayed access to water and feed for 48 h (DLY). In experiment 1, FED poults were heavier until 5 d postfeeding at which time villi were 50 microm longer and 6.8 microm wider, crypts were 5.9 microm deeper, and there were more goblet cells per villus than in the DLY poults. The DLY poults also had reduced numbers of proliferating enterocytes in the villus and higher apoptotic labeling at 1, 2, and 5 d postfeeding. In experiment 2, DLY poults had higher numbers of aerobic bacteria in the ileal digesta and ileal tissue when compared with the FED poults at 1 d postfeeding. To study salmonella attachment potential to the ileum, a segment of the ileum was inoculated with a salmonella culture, incubated for 1 h at 37 degrees C, and flushed; the tissue was homogenized, and numbers of remaining salmonella were enumerated. No differences in salmonella attachment potential were noted between FED and DLY poults. In conclusion, early access to ad libitum feed in poults stimulated growth and development of small intestinal villi and their absorptive surfaces, whereas delayed access to feed resulted in delayed enterocyte proliferation and greater enterocyte apoptosis during the first week posthatch as well as greater numbers of aerobic bacteria associated with the small intestine shortly after hatch.
Total cardiac by-pass utilizing continuous perfusion from reservoir of oxygenated blood.

Summary1. A simple method permitting total bypass of the heart and lungs for the performance of intracardiac surgical operations is described. 2. This method utilizes continuous perfusion of the recipient's (patient's) arterial system from a reservoir of oxygenated blood. An equivalent quantity of venous blood is removed from the recipient's superior and inferior cavae. 3. A pump is utilized to control this exchange between the recipient and the arterial and venous reservoirs. 4. Arterial blood for the reservoir was obtained from a donor animal used as an oxygenator independent of the perfusion system. This was done by collecting arterial blood from the donor's femoral artery into a heparin glucose solution while stored venous blood was infused into his femoral vein at an equal rate. Ordinarily 2,000 to 3,500 cc of arterial blood was collected from a single donor dog in this fashion. 5. The optimum dose of heparin to prevent clotting in the arterial blood collected for this purpose was 25 to 32 mg/liter o...
The Protection of Indigenous Rights in the Inter-American System

Inter-American System Indigenous Rights American Declaration on the Rights of Indigenous Peoples.
The investigation and analysis of the residents basic health condition after the earthquake in Majing Town of Shifang

Objective To known the residents basic health condition after the earthquake in Majing Town of Shifang city(county level) so that to make the scientific measures in order to avoid the big plague.Methods Unifying serial number for each administrative village's villages by the cluster sampling and the random principle,getting the first village which investigates at random,extracting investigated villages according to the number each other 4,sampling 4 villages from each administrative village,for the villages to carry on the investigations of the residence questionnaire.Results The families which were investigated,67.1% families could use the chlorine disinfectant to disinfect the water for life,76.8% families could do this every day above 1 time.The families those had the cooked food was 82.8% of investigated families.1335 households residents were inquired,84.0% lived in tents;65.2% the tent families environment was neat;99.1% families took measures against mosquitoes;64.2% household families dry restrooms are 5 meters distance to the family water well;92.3% families had not achieved detoxification processes to the domestic animals excrement;The mouse epidemic hemorrhagic fever virus was negative.90% the houses and the restroom were disinfected in each village;to all the investigated families,121 household family members had fallen ill.20.7% people who were investigated asked for the requests of preventing diseases.Conclusion There are the important roles to protect people from diseases.What the local party committees,governments and medical departments did had built the good foundation to avoid the big plague after the earthquake.
CASE ANALYSIS ON HYDROCARBON ALTERNATIVE GAS MISCIBLE FLOODING IN PUBEI OIL FIELD

The oil field in China with the method of development by miscible flooding is scare, to sum up the experiences, this paper analyses the developments of Pubei oil field which is the first sand oil reservoir to perform hydrocarbon miscible flooding in China. It has integrated, good connecting formation with undeveloped cracking system and permeability of 110.5×10~(-3)μm~2. It is a typical volatile oil reservoir. The minimum miscible pressure (MMP) is 33MPa. The Injected gas is the by-produced gas in the oilfield. The results of core flooding experiments showed that oil recovery by primary gas injection is higher than primary water injection. To chose one best method, the field was developed by primary water injection at east and primary gas injection at west, keeping formation pressure at 35MPa. At early exploration time, there were seven injection wells and eight production wells. Now, there are nine production wells and two gas injection wells, seven water injection wells. The velocity of oil production is 44t/d, gas injection is 14.55×10~4m~3/d, water injection is 144m~3/d. It has developed for three years till October 2001; the oil recovery is 19.05%, the synthetic water saturation is 3%. There are certain increases of GOR in some production well but no obvious gas breakout. Primary water injection well cannot change to gas injection since gas cannot be injected after water injection, so cannot perform GAW in east area. This paper introduces general geometry character, basic experimental study, exploration performance, and existing problem of the reservoir and gives some proposals, which is helpful in exploration the similar oil reservoir by miscible flooding.
The NIH Consensus Development Program. The evolution of guidelines.

The U.S. National Institutes of Health (NIH) Consensus Development Program (CDP) Guidelines have undergone some modifications over the program's 18-year history. They have never been published in archival form. This article reviews the evolution of the NIH CDP Guidelines and then presents the complete 1995 version.
Heat Pulses in Alkali Halides at Low Temperatures

Further studies of the propagation of heat pulses, similar to those previously reported for quartz and sapphire,1 have been made on several alkali halides. These include NaCl, KCl, KBr, and KI. The objective was to determine the nature of the heat-pulse propagation in high-purity crystals at temperatures near that at which the thermal conductivity is a maximum. It is at such temperatures that observation of “second sound” in insulating crystalline media,2 if it occurs, is most likely to be observed. Since superconducting film thermal detectors are used, this temperature must be compatible with the operating temperature of the detector used (approx. 8.0°K). This condition is approximately met by several of the alkali halides. At lower temperatures, energy transport should be by direct rectilinear propagation at the acoustic velocity if the defect and boundary scattering rates are sufficiently slow.
Halothane (fluothane) anaesthesia for paediatric cardiac surqery

Light halothane anaesthesia was administered to 200 children during cardiac surgery. The principle advantages of halothane, when compared to other inhalation anaesthetics, was its lack of flammability. The children tolerated the agent very well if low concentrations were employed, but frequently developed alarming signs of cardiac depression with high concentrations of halothane.
COCOON: Ein Objekt-Datenbankrahmensystem

Die Evolutionsproblematik soll in diesem Buch anhand eines konkreten Objekt-Datenbanksystems exemplarisch untersucht werden. Dazu wird COCOON eingesetzt, ein ODBS, das im Zusammenhang mit dieser Arbeit entwickelt wurde und sich damit als Rahmenwerk fur die weiteren Betrachtungen besonders auszeichnet.
Quantum Monte Carlo calculations of electromagnetic moments and transitions in A<=10 nuclei with two-body chiEFT currents

We present ab initio Quantum Monte Carlo calculations of electromagnetic observables of light nuclei based on a many-body nuclear Hamiltonian consisting of the Argonne-v18 and Illioins-7 two- and three-nucleon potentials, respectively. External electromagnetic probes interact with the electromagnetic charge and current distributions of nuclei. Nuclear charge and current operators account for one- and two-bodycontributionsdescribing, respectively,the couplingof photons with individualnucleons, as well as pairs of interacting nucleons. Two-bodyoperatorsare derived from a chiral effective field theory with pions and nucleons including up to two-pion exchange corrections. It is found that two-body contributions can be large and crucial to reach agreement with the experimental data, particularly for selected nuclear magnetic moments and M1 transitions.
Defense contracts: molecular protection in insect-microbe symbioses

Insects cope with environmental threats using a broad array of strategies. A key strategy, widespread among insects but unappreciated until recently, is the use of molecular defenses from symbiotic microbes. Insect-microbe defensive symbioses span the diversity of insect lineages and microbial partners and use molecules ranging from reactive oxygen species to small molecules to protein toxins to defend against predators, parasites, and microbial pathogens. These systems have a strong initial track record as sources of novel biologically active compounds with therapeutic potential. This review surveys the molecular basis for insect-microbe defensive symbioses with a focus on the ecological contexts for defense and on emerging lessons about molecular diversity from bacterial genomes.
How they lost the presidency

ABSTRACTFor the second time in this century and the fifth time in US history, the 2016 presidential popular vote winner was not elected president. One day before the election, the author predicted ...
Metal-Containing Polymers Synthesized via Acyclic Diene Metathesis: Polycarbostannanes

Polycarbostannanes have been successfully synthesized via acyclic diene metathesis chemistry utilizing both a well-defined molybdenum akylidene and an aryloxo tungsten "classical" catalyst system. In the case of the well-defined catalyst, the polymerization proceeds smoothly to produce linear polymer which is characterized by proton, carbon, and tin NMR. Molecular weights of about 16 000 g/mol can be produced. The production of a polycarbostannane via classical metathesis chemistry is just as facile, producing molecular weights comparable to the well-defined system, and in this case, the monomer performs as both the monomer and the cocatalyst species.
The relationship between trauma and weight status among adolescents in eating disorder treatment.

A relationship between trauma and eating disorders in adolescence is well established, though less is known about how different types of trauma, apart from childhood sexual abuse, associate with eating disorders. The purpose of this study is to describe the prevalence of various trauma types in a clinical sample of adolescents presenting at an outpatient eating disorder treatment facility (N = 182). Thirty-five percent of the sample reported experiencing one or more traumatic events during their lifetime. Bullying was the most prevalent type of trauma (10%), followed by significant death/loss (9%), and sexual abuse (8%). Adolescents with any trauma exposure had higher body mass index (BMI), BMI percentile, and percent expected body weight (%EBW) compared to those without any trauma exposure. Specifically, patients who were exposed to bullying and domestic violence reported a significantly higher %EBW than those who were not exposed. On average, adolescents exposed to bullying had a %EBW that was 7 percentage points higher than their non-exposed peers. Patients with bulimia nervosa were more likely to report trauma exposure than those with other eating disorder diagnosis. Providers working with adolescents diagnosed with eating disorders of all weight statuses should consider assessing for past and current trauma, including bullying and exposure to domestic violence. Trauma informed approaches to eating disorder treatment are needed to avoid potentially activating or exacerbating trauma related distress for adolescents in eating disorder treatment.
A Hands-on Approach to Capstone Design and Implementation

Students planning to work in the software industry are best served by exposure to the type of skills necessary to acquire employment in a software developer capacity. One way to prepare students is to teach students the software development life-cycle process utilizing a design and implementation two-course capstone project. This paper describes a successful teaching approach to the capstone project by utilizing a practical hands-on approach.
Polycystic Ovary Syndrome in Active Duty Service Women: A Retrospective Analysis

Introduction Women make up 16.3% of the Department of Defense (DoD) active duty military population. January 2016, the Secretary of the Defense opened all military positions to women, including combat positions. Identifying conditions that may impact health and military readiness are essential to maintaining a fit and ready force. Polycystic ovary syndrome (PCOS) is a condition that has significant health and military readiness implications for active duty service women (ADSW). Some of the common manifestations of PCOS, overweight, obesity, and abnormal menstrual cycles, have a direct impact on the deployment readiness of ADSW, which effects military operations. The prevalence of PCOS in ADSW must be identified to ascertain true numbers in the DoD to appropriately support, treat, and manage this population; therefore, the purpose of this study was to explore the prevalence of PCOS diagnosis, in ADSW. Materials and methods A retrospective analysis of electronic health record data from the Department of Defense Military Health Systems DataMart was conducted for calendar years January 2011 - December 2016, using ICD 9 and 10 codes. ADSW with symptoms and conditions that were present with PCOS but did not have the ICD 9 or 10 code for PCOS were also identified to explore the potential undiagnosed prevalence of PCOS. The diagnosed symptoms and conditions included for analysis were weight gain, obesity, dyslipidemia, glucose intolerance, hypertension, acne, acanthosis nigricans, infertility, and menstrual irregularity. Results There are 11,190 (0.2%) ADSW diagnosed with PCOS, and 9,112 (0.17%) diagnosed with symptoms that meet the profile and characteristics present in PCOS, but have no diagnosis. All branches of service and ranks were represented in these numbers. Conclusions PCOS is present in ADSW. Obtaining an accurate prevalence rate of this condition helps reveal the extent of its presence, helps increase awareness, and identify that there is a population in need of targeted support and interventions to maintain a fit and ready force.
Peripheral Vestibular Organ Degeneration After Temporal Bone Fracture: A Human Otopathology Study.

OBJECTIVES/HYPOTHESIS Vestibular symptoms are a common sequela of temporal bone fractures (TBFs). The mechanisms of injury to the peripheral vestibular system following TBF, however, are not well described. Herein, we aimed to investigate the histopathology of the peripheral vestibular system in patients who sustained TBFs. STUDY DESIGN Retrospective human specimen analysis. METHODS Specimens from the National Temporal Bone Pathology Registry with (cases) and without (controls) TBFs were evaluated. Specimens were analyzed by light microscopy for vestibular hair cell and/or dendritic degeneration, presence of endolymphatic hydrops, blockage of the endolymphatic duct, and number of Scarpa ganglion cells (ScGCs) in the superior and inferior vestibular nerves. RESULTS Seven temporal bones (TBs) from five individuals with TBFs, and seven TBs from six age-matched individuals without a history of head injury met inclusion and exclusion criteria. All fractures involved the otic capsule. Severe degeneration of the cristae was identified in the semicircular canals in all TBF cases. The utricular and saccular maculae showed mild to severe degeneration in the TBF cases. Vestibular hydrops (n = 2 TBs) and blockage of the endolymphatic duct (n = 3 TBs) were also present in the TBF cases. There was a decrease of 52.6% in the mean total ScGC count in the TBF cases (n = 3 TBs) compared to age-matched controls (n = 7 TBs, P = .015). There was a mean loss of 53% of the ScGCs in the superior vestibular nerve and a mean loss of 52.3% of the ScGCs in the inferior vestibular nerve compared to age-matched controls (P = .033 and P = .021, respectively). CONCLUSIONS In a cohort of patients with TBFs, there were distinct peripheral vestibular changes including reduction of ScGCs. LEVEL OF EVIDENCE NA Laryngoscope, 130:752-760, 2020.
DNA accessibility is not the primary determinant of chromatin-mediated gene regulation

ABSTRACT DNA accessibility is thought to be of major importance in regulating gene expression. We test this hypothesis using a restriction enzyme as a probe of chromatin structure and as a proxy for transcription factors. We measured the digestion rate and the fraction of accessible DNA at all genomic AluI sites in budding yeast and mouse liver nuclei. Hepatocyte DNA is more accessible than yeast DNA, consistent with longer linkers between nucleosomes, and indicating that nucleosome spacing is a major determinant of accessibility. DNA accessibility varies from cell to cell, such that essentially no sites are accessible or inaccessible in every cell. AluI sites in inactive mouse promoters are accessible in some cells, implying that transcription factors could bind without activating the gene. Euchromatin and heterochromatin have very similar accessibilities, suggesting that transcription factors can penetrate heterochromatin. Thus, DNA accessibility is not likely to be the primary determinant of gene regulation.
One-pot selective conversion of lignocellulosic biomass into furfural and co-products using aqueous choline chloride/methyl isobutyl ketone biphasic solvent system.

Abstract This study investigated simultaneous lignocellulose fractionation and conversion in a one-pot reaction using an aqueous choline chloride/methyl isobutyl ketone (ChCl/MIBK) biphasic solvent system. Under the optimized condition (170 °C, 60 min, 0.6 wt% H2SO4, 10.7 wt% solid loading), the biphasic solvent solubilized 96% xylan in raw switchgrass, which was simultaneously converted to furfural with a yield of 84.04%. The biphasic solvent was also able to selectively extract lignin, which had a high purity (93.1%), and uncondensed moieties (i.e., Hibbert’s ketone), as well as decreased molecular weight and polydispersity index. The resultant pulp was enriched with cellulose (73.3%), which can be completely hydrolyzed into glucose within 48 h via enzymatic hydrolysis. Aqueous ChCl was successfully recycled and reused for atleast three cycles with similar performance in switchgrass fractionation. This study demonstrated that aqueous ChCl/MIBK biphasic system was an effective solvent system for co-production of furfural, high quality technical lignin and digestible cellulose for further upgrading.
Oral rehabilitation following fasciocutaneous free-flap reconstruction: A retrospective study.

Aim: The aim of this study is to retrospectively, observe a consecutive series of patients with segmental mandibulectomy defects reconstructed with fasciocutaneous free flaps and mandibular resection prostheses, and to review treatment concepts for the management of such patients. Settings and Design: Observational study done at Memorial Sloan Kettering Cancer Center, New York, NY, USA. Materials and Methods: Records were reviewed of all patients who had fasciocutaneous free-flap reconstruction and fabrication of mandibular resection prostheses following segmental mandibulectomy between 2000 and 2017 at a tertiary cancer center. Mandibular resection prosthesis fabrication interval data, as well as follow-up interval data, were recorded. Statistical Analysis Used: Descriptive statistics. Results: Twenty-one consecutive patients had mandibular resection prostheses fabricated following segmental mandibulectomy and fasciocutaneous free-flap reconstruction during the study. The median time for mandibular resection prosthesis delivery following surgery was 9 months (range 4–41 months). There was a median of two-follow-up visits (range 0–4) within the first 90 days of mandibular resection prosthesis delivery. Conclusions: Oral rehabilitation with mandibular resection prosthesis following segmental mandibulectomy and fasciocutaneous free-flap reconstruction is an attainable treatment goal for the oncologic patient. Reviewing the proposed course of care is helpful for patient management.
Understanding approaches to measurement and impact of depth of invasion of oral cavity cancers: A survey of American Head and Neck Society Membership.

Abstract Objectives To investigate methods used by head and neck surgeons to pre-operatively measure depth of invasion (DOI) in light of the new staging for oral cavity squamous cell carcinoma (OCSCC). Materials and methods A survey was designed and sent to all American Head and Neck Society (AHNS) members via an email link. The last response was recorded on January 16, 2019. Results We received 185 (13.3%) responses from 184 surgeons and 1 radiation oncologist. The majority of surgeons correctly identified DOI (78.9%) and indicated measuring DOI pre-operatively (86%). The most common methods for measuring DOI were manual palpation (32.5%) and full thickness biopsy (25.2%). In addition, most surgeons (84.7%) reported using a DOI threshold (in mm) as their primary criterion in their decision to pursue a neck dissection in the N0 neck. The most common reported threshold was 4 mm (37.4% of those that reported using DOI), however, the range varied from 2 to >10 mm. Two-thirds of surgeons considered DOI an important indicator for adjuvant therapy. Conclusion DOI is believed to be an important prognostic indicator guiding neck dissection and the need for adjuvant therapy. While most surgeons currently measure DOI pre-operatively, most use subjective methods. Future studies are needed to establish objective pre-operative DOI measurement techniques and to better inform the decision to perform prophylactic neck dissection, given the current majority practice of prophylactic neck dissection for DOI of 4 mm or greater.
Fabrication-tolerant Fourier transform spectrometer on silicon with broad bandwidth and high resolution

We report an advanced Fourier transform spectrometer (FTS) on silicon with significant improvement compared with our previous demonstration in [Nat. Commun.9, 665 (2018)2041-1723]. We retrieve a broadband spectrum (7 THz around 193 THz) with 0.11 THz or sub nm resolution, more than 3 times higher than previously demonstrated [Nat. Commun.9, 665 (2018)2041-1723]. Moreover, it effectively solves the issue of fabrication variation in waveguide width, which is a common issue in silicon photonics. The structure is a balanced Mach–Zehnder interferometer with 10 cm long serpentine waveguides. Quasi-continuous optical path difference between the two arms is induced by changing the effective index of one arm using an integrated heater. The serpentine arms utilize wide multi-mode waveguides at the straight sections to reduce propagation loss and narrow single-mode waveguides at the bending sections to keep the footprint compact and avoid modal crosstalk. The reduction of propagation loss leads to higher spectral efficiency, larger dynamic range, and better signal-to-noise ratio. Also, for the first time to our knowledge, we perform a thorough systematic analysis on how the fabrication variation on the waveguide widths can affect its performance. Additionally, we demonstrate that using wide waveguides efficiently leads to a fabrication-tolerant device. This work could further pave the way towards a mature silicon-based FTS operating with both broad bandwidth (over 60 nm) and high resolution suitable for integration with various mobile platforms.
Multi-panel immunofluorescence analysis of tumor infiltrating lymphocytes in triple negative breast cancer: Evolution of tumor immune profiles and patient prognosis

The evolutionary changes in immune profiles of triple negative breast cancer (TNBC) are not well understood, although it is known that immune checkpoint inhibitors have diminished activity in heavily pre-treated TNBC patients. This study was designed to characterize immune profile changes of longitudinal tumor specimens by studying immune subsets of tumor infiltrating lymphocytes (TILs) in paired primary and metastatic TNBC in a cohort of "poor outcome" (relapsed within 5 years) patients. Immune profiles of TNBCs in a cohort of "good outcome" (no relapse within 5 years) patients were also analyzed. Immune subsets were characterized for CD4, CD8, FOXP3, CD20, CD33, and PD1 using immuno-fluorescence staining in stroma, tumor, and combined stroma and tumor tissue. TIL subsets in "good outcome" versus "poor outcome" patients were also analyzed. Compared with primary, metastatic TNBCs had significantly lower TILs by hematoxylin and eosin (H&E) staining. Stromal TILs (sTILs), but not tumoral TILs (tTILs) had significantly reduced cytotoxic CD8+ T cells (CTLs), PD1+ CTLs, and total PD1+ TILs in metastatic compared with matched primary TNBCs. Higher PD1+ CTLs, PD1+CD4+ helper T cells (PD1+TCONV) and all PD1+ T cells in sTILs, tTILs and total stromal and tumor TILS (s+tTIL) were all associated with better prognosis. In summary, TIL subsets decrease significantly in metastatic TNBCs compared with matched primary. Higher PD1+ TILs are associated with better prognosis in early stage TNBCs. This finding supports the application of immune checkpoint inhibitors early in the treatment of TNBCs.
Epistatic Interplay between Type IV Secretion Effectors Engages the Small GTPase Rab2 in the Brucella Intracellular Cycle

Intracellular bacterial pathogens remodel cellular functions during their infectious cycle via the coordinated actions of effector molecules delivered through dedicated secretion systems. While the function of many individual effectors is known, how they interact to promote pathogenesis is rarely understood. The zoonotic bacterium Brucella abortus, the causative agent of brucellosis, delivers effector proteins via its VirB type IV secretion system (T4SS) which mediate biogenesis of the endoplasmic reticulum (ER)-derived replicative Brucella-containing vacuole (rBCV). Here, we show that T4SS effectors BspB and RicA display epistatic interactions in Brucella replication. Defects in rBCV biogenesis and Brucella replication caused by deletion of bspB were dependent on the host GTPase Rab2a and suppressed by the deletion of ricA, indicating a role of Rab2-binding effector RicA in these phenotypic defects. Rab2a requirements for rBCV biogenesis and Brucella intracellular replication were abolished upon deletion of both bspB and ricA, demonstrating that the functional interaction of these effectors engages Rab2-dependent transport in the Brucella intracellular cycle. Expression of RicA impaired host secretion and caused Golgi fragmentation. While BspB-mediated changes in ER-to-Golgi transport were independent of RicA and Rab2a, BspB-driven alterations in Golgi vesicular traffic also involved RicA and Rab2a, defining BspB and RicA's functional interplay at the Golgi interface. Altogether, these findings support a model where RicA modulation of Rab2a functions impairs Brucella replication but is compensated by BspB-mediated remodeling of Golgi apparatus-associated vesicular transport, revealing an epistatic interaction between these T4SS effectors.IMPORTANCE Bacterial pathogens with an intracellular lifestyle modulate many host cellular processes to promote their infectious cycle. They do so by delivering effector proteins into host cells via dedicated secretion systems that target specific host functions. While the roles of many individual effectors are known, how their modes of action are coordinated is rarely understood. Here, we show that the zoonotic bacterium Brucella abortus delivers the BspB effector that mitigates the negative effect on bacterial replication that the RicA effector exerts via modulation of the host small GTPase Rab2. These findings provide an example of functional integration between bacterial effectors that promotes proliferation of pathogens.
Mechanistic modeling of CO2 well leakage in a generic abandoned well through a bridge plug cement-casing gap

Abstract Both known and unmapped plugged and abandoned wells are potential leakage pathways for CO2 from geologic carbon sequestration (GCS) sites. Although many abandoned wells have cement bridge plugs installed to prevent leakage, the seal between the cement and the inner casing wall is subject to failure. In this study, we carried out detailed T2Well simulations of cases of sudden non-Darcy flow of CO2 and brine leakage up the gap between a cement plug and the inner steel casing wall that becomes a fully connected flow path during the post-injection period. The goal of our study was two-fold: (1) to understand the dynamics, rates, and the characteristic temporal signals associated with the onset of leakage through various gap-aperture sizes, and (2) to suggest potential monitoring strategies based on the findings. Simulation results show that the leakage of CO2 and brine upward is transient with interesting phase interference behavior. Time-dependent oscillatory flows with varying pressure, temperature, and flow rates of CO2 and brine show strong dependence on gap aperture. Phase-change and decompression lead to very low temperatures at the top of the well for gap apertures larger than 4 mm suggesting that remote thermal monitoring at the ground surface may be an effective way of monitoring even if well locations are not known a priori. Pressure in the well is also indicative of CO2 leakage. The temporal patterns of changing temperature and pressure may be useful diagnostic signals for leakage detection. Finally, these transient leakage signals may provide information on the cause of leakage and/or characteristics of the flow path that could inform effective remediation design and execution approaches.
The Affordable Care Act and Polarization in the United States

We argue that partisan polarization in public support of the Affordable Care Act (ACA) is affected not only by policy design but also by which party makes those decisions. Using an innovative dataset that measures state-level quarterly ACA support from 2009 through the start of the 2016 presidential election, we find that opinions toward the ACA are less polarized in states with misaligned partisan environments where Republican governors support Medicaid expansion. We also find evidence that Republican opposition intensifies when a Democratic governor supports expansion. We do not find consistent evidence of such patterns for governors’ positions on state health insurance exchanges. Our research sheds light on a key aspect of how health policy preferences respond to shifting political contexts in a polarized, federated polity.
Predicting Individualized Joint Kinematics over a Continuous Range of Slopes and Speeds

Individuality in clinical gait analysis is often quantified by an individual’s kinematic deviation from the norm, but it is unclear how these deviations generalize across different walking speeds and ground slopes. Understanding individuality across tasks has important implications in the tuning of prosthetic legs, where clinicians have limited time and resources to personalize the kinematic motion of the leg to therapeutically enhance the wearer’s gait. This study seeks to determine an efficient way to predictively model an individual’s kinematics over a continuous range of slopes and speeds given only one personalized task at level ground. We were able to predict the kinematics of able-bodied individuals at a wide variety of conditions that were not specifically tuned. Applied to 10 human subjects, the individualization method reduced the RMSE between the model and subject’s kinematics over all tasks by an average of 2% (max 52%) at the ankle, 27% (max 59%) at the knee, and 45% (max 83%) at the hip. Our results indicate that knowing how an individual subject differs from the average subject at level ground alone is enough information to improve kinematic predictions across all tasks. This research offers a new method for personalizing robotic prosthetic legs over a variety of tasks without the need of an engineer, which could make these complex devices more clinically viable.
Medical Students Screen for Social Determinants of Health: A Service Learning Model to Improve Health Equity

Introduction Medical schools are now required to address health disparities within their curriculum, with a recent emphasis on social determinants of health (SDOH). However, there is scant evidence that incorporating educational experiences around SDOH impacts health equity for patients. The COVID-19 pandemic provided a unique setting to engage students to address SDOH directly with patients. Methods The authors designed a service-learning experience in which medical students conducted a patient needs assessment survey by phone to assess SDOH in the domains of health care access, economic stability, and social cohesion. We drew descriptive statistics from a deidentified Excel database of call outcomes to quantify health care interactions and community resource referrals generated by callers. Results The call outcomes revealed unmet health and social needs among the patient population and generated a substantial number of actions to improve health care access and awareness of community resources. Conclusion The results of this project show that employing medical students to engage with SDOH through action-oriented service learning positively impacts health care access and referrals to community resources. This initiative provides a flexible model to engage medical trainees in addressing health-related social needs that can be applied to a range of clinical settings and learner levels.
Ga-68 Dotatoc versus In-111 Ocreotide.

2038 Aim: This abstract aims to evaluate whether Ga-68 dotatoc is, in fact, a more comprehensive and accurate study for detecting neuroendocrine tumors versus the more familiar method, In-111 octreotide scan. Both radiopharmaceuticals are used to localize, diagnose, and follow patients with neuroendocrine tumors (NETs). NETs are rare tumors found in neuroendocrine cells that can spread throughout the body. If caught in the early stages, NETs may be curable. Overall survival rate usually varies depending on the stage or grade. Ga-68 dotatoc localizes in tumors by receptor binding. It has a half-life of just 68 minutes with an energy of 511 KeV. The typical dose is 4-6 mCi. IV with uptake of approximately 45 minutes to 1 hour. The patient is positioned supine, head first, and imaged skull base to thigh. Ga-68 dotatoc is an extremely useful radiopharmaceutical because of the rapid isotope localization, quick scanning time of 20-25 minutes, and the short half-life. In-111 octreotide has a half-life of 67 hours and an energy of 171 KeV and 245 KeV. The recommended dose of In-111 octreotide is approximately 6 mCi IV. The patient returns 4 hours later for imaging. The first set of whole-body images take approximately 20 - 30 minutes. After these images are acquired, SPECT imaging is often required which takes an additional 20 - 30 minutes. The patient returns in 24 hours for the same set of pictures including SPECT. If high intestinal activity is detected on the first set of images, the patient may be asked to take a mild laxative before they go to bed to reduce interfering activity on the 24-hour images. If high background persists, the patient may need to return for 48-hour imaging and SPECT. Ga-68 dotatoc has many advantages over In-111 octreotide imaging. Ga-68 dotatoc is extremely quick because the patient is injected and imaged within an hour. The complete test is over within 2 hours. With In-111octreotide, localization of the radioisotope is slow, multiple images must be acquired up to 24 and even 48 hours, delaying time to final results and diagnosis. A disadvantage of Ga-68 dotatoc is that it is more expensive. Both Ga-68 dotatoc and In-111 octreotide imaging are clinically useful for detecting neuroendocrine tumors. However, Ga-68-dotatoc, as PET tracer, has been shown to be more accurate with higher sensitivity (96% vs. 86%) and specificity (93% vs 50%) than In-111 octreotide. Subject 1: 57-year-old patient with ileal carcinoid, status post-surgery, radiation therapy for metastases in the breast and left femur, rising serotonin.References: (For Picture) Graham MM, Gu X, Ginader T, Breheny P, Sunderland JJ. 68Ga-DOTATOC Imaging of Neuroendocrine Tumors: A Systematic Review and Metaanalysis. 2017;58(9):1452-1458.
0103 Comparing the performance of two short predictive screeners to assess future development of PTSD and depression: results from a cohort study of seriously injured adults

Statement of purpose To appraise the ability of two short clinical screeners designed to predict future development of post-injury depression and PTSD in traumatically injured patients. Methods/Approach This study is part of a prospective longitudinal cohort study to improve the health of urban Black men after serious injury. The sample consisted of English-speaking, self-identified Black men at least 18 years old, residing in the Philadelphia metropolitan area, who were hospitalized for an acute traumatic injury. The two screeners used were the Penn Richmond Screener (PRS) and the Posttraumatic Adjustment Screen (PAS). Results A total of 623 participants completed baseline interviews. Over 80% completed the 3-month follow-up interview and had complete data for depression (n = 502) and PTSD (n = 501). Of these, 177 (35.3%) met criteria for depression and 145 (28.8%) for PTSD; 116 participants met criteria for both depression and PTSD (23.2%). Both screeners have similar positive predictive values (PPV) for depression. PAS performs slightly better in PPV for PTSD. Both screeners have high negative predictive values for PTSD and depression, so they will adequately identify individuals who will not develop symptoms. The area under the curve for PTSD and depression in both screeners is similar, so they similarly classify those with and without future risk of symptom development. Conclusion PRS and PAS, developed through different methods and with different populations, show comparable predictive ability within the study population. Thus, mental health outcomes can be predicted in various populations using screeners the clinician values for brevity over the similarity of patient population to the screener’s test population. Significance ACS-COT encourages screening all patients for depression and PTSD risk. Integrating a predictive screener prior to discharge is critical to identifying those at risk and targeting patients who would benefit from post-discharge concurrent screening.
The Ecosystem Approach: New Departures for Land and Water, Foreword

The regulatory strategies of the past have failed to stop the loss of critical habitat, the collapse of commercial fisheries, and steadily diminished species. Despite these failures, some of the most visible and contentious conflicts over environmental protection have led to a potentially promising strategy that we are starting to call "ecosystem management." The hallmarks of an ecosystem approach are first, taking the ecosystem as the unit to be managed and regulated; second, using multiparty negotiations to involve a broader group of stakeholders than is typical of normal regulatory activities; third, integrating an adaptive management element, which addresses the dynamic biological and physical elements of natural systems; and fourth, creating an effort to create new regulatory tools better able to balance public and private rights, such as transferable development rights and "safe harbor" agreements.
Gender Gap in Earnings in Vietnam: Why Do Vietnamese Women Work in Lower Paid Occupations?

Differences in earnings between male and female workers persist in developed and developing countries despite a narrowing of gender gaps in educational attainment over the past half-century. This paper examines the gender wage gap in Vietnam and shows that a nontrivial part of the gap is associated with occupational sorting. The paper considers three explanations for why occupational sorting emerges. First, it explores whether women sort into occupations with better nonmonetary characteristics, such as paid leave and shorter hours. The data from Labor Force Surveys support this hypothesis. Second, it checks if occupational sorting among the adult labor force is driven by social norms about gender roles learned and internalized at an early age. To do so, the paper checks for evidence of sorting in the aspirations of 12-year-old children. Specifically, the analysis simulates what the gender wage gap would be if boys and girls pursued the occupations they aspired to at age 12, and the distribution of salaries remained unchanged. The paper does not find support for the hypothesis that gender norms drive occupational sorting by inducing aspirational sorting at an early age. Finally, for individuals with higher education, the paper checks if occupational sorting occurs during the school-to-work transition, when women face higher barriers in finding a job in their field of study. The analysis does not find evidence to support this last hypothesis. Overall, the findings suggest that in Vietnam gender-specific preferences for nonmonetary job characteristics play a key role in the emergence of occupational sorting.
LONGITUDINAL WAVES IN NONLINEAR VISCOELASTIC RODS UNDER INITIAL AXIAL STRESS.

Longitudianal wave propagation in a semi-infinite rod is considered, where the medium is nonlinear viscoelastic and under constant initial axial stress, i.e., the rod is undergoing axial creep deformation. The deformation gradient is assumed to be infinitesimal, but the deformation itself may be finite. The constitutive law is taken with stress power functions in the elastic, transient creep and steady creep terms. A wave is generated by a step input in velocity or stress at one end of the rod. It is assumed that the initial stress is much greater than the increment of stress generated by the impact and a perturbation technique is employed. Closed form perturbation stress solutions are obtained for five nonlinear viscoelastic models. Numerical examples are given and discussed.
A Biological Model for Controlling Interface Growth and Morphology

Biological systems create proteins that perform tasks more efficiently and precisely than conventional chemicals. For example, many plants and animals produce proteins to control the freezing of water. Biological antifreeze proteins (AFPs) inhibit the solidification process, even below the freezing point. These molecules bond to specific sites at the ice/water interface and are theorized to suppress solidification chemically or geometrically. In this project, we investigated the theoretical and experimental data on AFPs and performed analyses to understand the unique physics of AFPs. The experimental literature was analyzed to determine chemical mechanisms and effects of protein bonding at ice surfaces, specifically thermodynamic freezing point depression, suppression of ice nucleation, decrease in dendrite growth kinetics, solute drag on the moving solid/liquid interface, and stearic pinning of the ice interface. Stearic pinning was found to be the most likely candidate to explain experimental results, including freezing point depression, growth morphologies, and thermal hysteresis. A new stearic pinning model was developed and applied to AFPs, with excellent quantitative results. Understanding biological antifreeze mechanisms could enable important medical and engineering applications, but considerable future work will be necessary.
The Boundary Layer on a Sharp Cone in High-Enthalpy Flow

The boundary layer on a 5 deg. half-angle cone is studied by measurement of the heat flux distribution and by qualitative flow visualisation. In the laminar layer, heat flux levels are higher in air than in nitrogen because of a larger heat release from oxygen recombination at the wall. By varying the specific reservoir enthalpy in air and N2, and from measurements in CO2, it is found that real-gas effects stabilize the boundary layer.