cssi/SciSciGPT-SciSciNet huggingface dataset:
Photodynamic Therapy Mediated by Nontoxic Core–Shell Nanoparticles Synergizes with Immune Checkpoint Blockade To Elicit Antitumor Immunity and Antimetastatic Effect on Breast Cancer

An effective, nontoxic, tumor-specific immunotherapy is the ultimate goal in the battle against cancer, especially the metastatic disease. Checkpoint blockade-based immunotherapies have been shown to be extraordinarily effective but benefit only the minority of patients whose tumors have been pre-infiltrated by T cells. Here, we show that Zn-pyrophosphate (ZnP) nanoparticles loaded with the photosensitizer pyrolipid (ZnP@pyro) can kill tumor cells upon irradiation with light directly by inducing apoptosis and/or necrosis and indirectly by disrupting tumor vasculature and increasing tumor immunogenicity. Furthermore, immunogenic ZnP@pyro photodynamic therapy (PDT) treatment sensitizes tumors to checkpoint inhibition mediated by a PD-L1 antibody, not only eradicating the primary 4T1 breast tumor but also significantly preventing metastasis to the lung. The abscopal effects on both 4T1 and TUBO bilateral syngeneic mouse models further demonstrate that ZnP@pyro PDT treatment combined with anti-PD-L1 results i...
Upper Gastrointestinal Tract Mass and Respiratory Failure in a Newborn

Upper gastrointestinal tract mass and respiratory failure in a newborn ### Prenatal History: ### Birth History and Presentation: Fig 1. ### Case Progression: The infant was switched to high-frequency jet ventilation on postnatal day three. Her respiratory condition improved, …
Information Is Power: Women as Information Providers to the President’s Budgeting Men; A History of the Bureau of the Budget Library, 1940-1970

Quietly tucked within the elite agency exercising the president’s power of the purse was a little-known in-house library. Given that information is power, the women of the library of the US Bureau of the Budget collected, cataloged and disseminated information to the bureau’s male budgeteers. This article traces the history of the budget bureau’s library, which has been largely overlooked in the literature, including the extended career of its chief administrator, Ruth Fine, who headed it from 1940 to 1972. Starting her career during the era of the “spinster librarian” and anti-Semitism in the professions, she rose to have a long-time management career as the Bureau’s library director.
Bartell and the Expansion of Facilitated Exchanges

The Tax Court recently granted section 1031 nonrecognition to a title-parking reverse improvements exchange. The transaction occurred before the publication of Rev. Proc. 2000-27, so it was a non-safe-harbor arrangement, and it would have failed to satisfy the safe harbor because the facilitator held title for more than the 180 days allowed for in the safe harbor. The ruling surprised many section 1031 practitioners because it did not consider whether the facilitator had the benefits and burdens of the replacement property while it held title to it. Despite the presence of facts that indicated the exchanger acquired the benefits and burdens at the time the facilitator took title to the replacement property, the Tax Court applied a formalistic view of tax ownership to hold that the facilitator was the tax owner because it was hired to facilitate the exchange and held legal title to the property. This case becomes another in a long line of cases that have applied a formalistic view of tax law to section 1031 exchanges. Even though the ruling surprised many members of the section 1031 industry, it does reflect the Tax Court’s interpretation of the tax ownership in the section 1031 context.
Evolutionary Analysis of Snf1-Related Protein Kinase2 (SnRK2) and Calcium Sensor (SCS) Gene Lineages, and Dimerization of Rice Homologs, Suggest Deep Biochemical Conservation across Angiosperms

Members of the sucrose non-fermenting related kinase Group2 (SnRK2) subclasses are implicated in both direct and indirect abscisic acid (ABA) response pathways. We have used phylogenetic, biochemical, and transient in vivo approaches to examine interactions between Triticum tauschii protein kinase 1 (TtPK1) and an interacting protein, Oryza sativa SnRK2-calcium sensor (OsSCS1). Given that TtPK1 has 100% identity with its rice ortholog, osmotic stress/ABA-activated protein kinase (OsSAPK2), we hypothesized that the SCS and TtPK1 interactions are present in both wheat and rice. Here, we show that SnRK2s are clearly divided into four pan-angiosperm clades with those in the traditionally defined Subclass II encompassing two distinct clades (OsSAPK1/2 and OsSAPK3), although OsSAPK3 lacks an Arabidopsis ortholog. We also show that SCSs are distinct from a second lineage, that we term SCSsister, and while both clades pre-date land plants, the SCSsister clade lacks Poales representatives. Our Y2H assays revealed that the removal of the OsSCS1 C-terminal region along with its N-terminal EF-hand abolished its interaction with the kinase. Using transient in planta bimolecular fluorescence complementation experiments, we demonstrate that TtPK1/OsSCS1 dimerization co-localizes with DAPI-stained nuclei and with FM4-64-stained membranes. Finally, OsSCS1- and OsSAPK2-hybridizing transcripts co-accumulate in shoots/coleoptile of drying seedlings, consistent with up-regulated kinase transcripts of PKABA1 and TtPK1. Our studies suggest that interactions between homologs of the SnRK2 and SCS lineages are broadly conserved across angiosperms and offer new directions for investigations of related proteins.
Ocular Motor Abnormalities and Congenital Facial Weakness (S47.005)

OBJECTIVE: To characterize ocular motor defects with congenital facial weakness. BACKGROUND: The classic condition of ocular motor deficits and facial weakness is Mobius syndrome, attributed to abducens and facial nerve involvement. Reports of facial weakness with oculomotor dysfunction or accommodative esotropia due to genetic mutations (TUBB3 and HOXB1, respectively), have recently broadened the clinical spectrum. DESIGN/METHODS: We report ocular motor findings in 39 patients with congenital facial weakness. RESULTS: We examined 39 patients (age range 2-64, 25 females), 36 with bilateral and 3 with unilateral facial weakness. Two had isolated bilateral abduction defects. The most common pattern (n=16) was bilateral horizontal gaze paresis (BHGP) with spared vertical range. Ten patients had BHGP plus vertical involvement, 4 with impaired elevation and depression and 6 with impaired elevation only. Nine patients had full motility range; 2 with a large esotropia. One patient had isolated unilateral limited adduction and one could not be characterized. Two patients had bilateral ptosis – one with diffuse ophthalmoplegia and one with spared vertical eye movements. No patient had pupillary involvement. Twenty-nine patients performed pursuit, saccade, and optokinetic nystagmus testing. Of particular importance was the absence of vertical optokinetic nystagmus in 19 patients, even when vertical range of motion was unaffected. Twenty-three patients had not undergone strabismus surgery. Of these, 15 had normal alignment. By history and exam, 59% had tongue abnormalities, 51% imbalance, and 26% cognitive impairment. Mirror movements, seizures, and psychiatric abnormalities occurred, but were less common. CONCLUSIONS: A range of ocular motor abnormalities and other deficits may occur with congenital facial weakness. The most common pattern of BHGP suggests involvement of motoneurons and interneurons in the abducens nuclei. Characterization of the patterns of ocular motor deficits in congenital facial weakness may assist continued advancement in identification of the genetic defects underlying these disorders. Supported by: Mobius Syndrome Foundation. Disclosure: Dr. Rucker has nothing to disclose. Mr. Webb has received research support from the Mobius Syndrome Foundation. Dr. Frempong has nothing to disclose. Dr. Jabs has received research support from the Mobius Syndrome Foundation.
An analysis of dielectric properties of synthetic ballast water at frequencies ranging from 300 to 3000 MHz.

Ballast water presents an important vector for introduction of aquatic invasive species in the coastal waters around the world. Currently there are no established technologies proven to completely eliminate this problem due to the particularities of the ballasting and de-ballasting operations (extremely large volumes of water, efficiency at destroying macro and micro organisms, environmental issues associated with chemical treatments). Continuous microwave heating presents a potential solution to this problem, but the design of suitable applicators depends on the dielectric properties of the ballast water to be processed. The study presented in this paper is focused on the dielectric properties (dielectric constant-e’; dielectric loss-e”) of synthetic ballast water inoculated with four organisms at seven different temperatures in the frequency range of300 to 3000 MHz. The dielectric properties of the mixtures were determined using a network analyzer and a dielectric probe kit using the open-ended coaxial ...
A review of the synthesis of reduced defect density InxGa1−xN for all indium compositions

Abstract A review of metal rich and nitrogen rich (N-rich), low-temperature grown In x Ga 1−x N is provided, focusing on two low-temperature approaches that have resulted in non-phase separated In x Ga 1−x N. The metal modulated epitaxy (MME) and N-rich, low temperature approaches to the reduction of defects in In x Ga 1−x N are described and are capable of growing In x Ga 1−x N throughout the miscibility gap. MME films remain smooth at all thicknesses but show device quality material primarily for x 0.6. Low temperature, N-rich grown films show a critical thickness extend well beyond the theoretical values and results in slower relaxation through the 0.2 x Ga 1−x N substrates are necessary to increase design freedom, as well as improve optoelectronic device performance. Initial results with films up to 800 nm are shown to display evidence of defect annihilation which could be promising for future thick optoelectronic templates and thick devices.
Maternal Vaccination With a Monocomponent Pertussis Toxoid Vaccine Is Sufficient to Protect Infants in a Baboon Model of Whooping Cough.

Background Bordetella pertussis is a human pathogen responsible for serious respiratory illness. The disease is most severe in infants too young to be vaccinated with most hospitalizations and deaths occurring within this age group. The Advisory Committee on Immunization Practices recommended immunization of pregnant women to protect infants from birth until their first vaccination at 6-8 weeks of age. We previously demonstrated that maternal vaccination with licensed acellular pertussis vaccines protected newborn baboons from disease. We hypothesized that protection was due to toxin-neutralizing, maternal anti-pertussis toxin antibodies and predicted that maternal vaccination with a pertussis toxoid (PTx)-only vaccine would protect newborns from disease. Methods Infant baboons born to unvaccinated mothers or mothers vaccinated with a PTx-only vaccine were challenged with B. pertussis at 5 weeks of age and followed for infection and signs of disease. Results Although all challenged infants were heavily colonized, the infant baboons born to mothers vaccinated with PTx-only vaccine were free from clinical disease following exposure to B. pertussis. In contrast, disease was observed in infants born to unvaccinated mothers. Conclusions Our results demonstrated that maternal vaccination with a PTx-only vaccine is sufficient to protect newborn baboons from disease following exposure to pertussis.
Use of the Wearable Cardioverter Defibrillator as a Bridge to Implantable Cardioverter Defibrillator

The wearable cardioverter defibrillator has been shown to be effective in terminating ventricular arrhythmias in patients at risk for sudden cardiac death. There are numerous scenarios in which implant of a permanent implantable cardioverter defibrillator is temporarily contraindicated or not advisable and a wearable cardioverter defibrillator may be beneficial. There are no prospective randomized studies published that provide conclusive guidance toward the use of the wearable cardioverter defibrillator, and thus, patient management needs to be individualized based on the available data.
Design considerations for small scale rotating fluidized beds in static geometry with screens for fine particles

Abstract Design of a small scale rotating fluidized bed (RFB) with diameter of 4–6 cm to fluidize 40–80 μm diameter particles was investigated using computational fluid dynamics (CFD). Simulations explored the impact of the following components on pressure drop and fluidized behavior of the device: particle size, particle density, outer diameter, solids loading, height, number of inlet slots, inlet slot width, angle of inlet slots, chimney diameter, chimney number of slots, chimney slot width, chimney slot angle, and position of the chimney relative to the inlets. Fluidized behavior was evaluated based on a “fluidization quality” metric yielding information about the distribution of particles in the device. Although additional work is required to elucidate design guidelines for small scale RFBs for fine particles, the initial designs evaluated in this work indicate potential for developing a fluidized bed of relatively small diameter, presenting opportunities for process intensification for numerous potential applications.
Vibrational Energy Flow in van der Waals Molecules

We offer here propensity rules which can he used for estimating the lifetimes of vibrationally excited van der Waals molecules and identifying efficient relaxation channels. These propensity rules are based on the reluctance of a molecule to change quantum numbers during a radiationless transition between non-crossing potential surfaces.
Using DRIs for dietary assessment.

Nutrient standards such as the Dietary Reference Intakes (DRIs) may be used to assess diets of both individuals and of population groups. The goal is to estimate the probability of dietary adequacy (or inadequacy) for an individual and the prevalence of dietary adequacy for a group. The DRI that is needed to estimate the probability of dietary adequacy is the estimated average requirement for a nutrient (EAR), as well as an estimate of the standard deviation of the requirement. The probability of adequacy for an individual should be based on usual long-term intake, because the DRIs apply to a person’s usual intake, rather than to intake on only a few days. Due to day-to-day variation in intakes, it is usually necessary to record or observe a person’s intake for a large number of days. For population groups, the prevalence of adequacy can be calculated as the average of each person’s probability of adequacy, and should correspond to the proportion of the population with nutrient intakes exceeding nutrient needs. A short-cut method to estimating the prevalence of adequacy simply calculates the proportion of intakes that are above the EAR. It is not necessary to have usual long-term intake for each person in the group, but a statistical procedure must be used to remove the effect of day-to-day variation from the intake distribution before the prevalence of adequacy within a group is estimated. With the new DRIs, a more informative assessment of both individual and group intakes is possible.
Sedimentary Rocks and the Oceans

Interest in the isotopic composition of strontium in sedimentary rocks is increasing rapidly. Recent work includes dating of argillaceous sedimentary rocks as well as studies of the variation of the 87Sr/86Sr ratios of the oceans in the geologic past. While much progress has been made, many challenging problems remain to be solved. In this chapter we shall examine what has already been done and point out where more progress is still to be made.
Local Anesthetics (LAs) and Cancer Cell Progression: Is There anOncologic Protective Role for LAs in Clinical Practice?

The purpose of this article is to provide a brief review of current literature examining the potential oncologic protective role local anesthetics may provide in the perioperative setting during cancer surgery. Paradoxically, curative surgery for cancer appears to favor the development of recurrences and distant metastasis. The accumulated knowledge about cancer biology and our understanding of the pathophysiological events occurring during the perioperative period have opened several theories on potential mechanisms for this century old observation. In such, cell-mediated immune response, the first line attack against cancer is suppressed during the perioperative period possibly providing circulating tumor cells with a fruitful environment allowing them to escape the immune system to form local recurrence and metastasis. In parallel, surgical stress, acute pain, and inflammatory cytokines released during surgery all directly or indirectly contribute to the immunosuppression state. Current data indicates that surgery itself cannot be regarded as the sole culprit for this paradox, and other factors during the perioperative period such as anesthetic drugs or anesthesia techniques are conceivably involved as well. As an example, volatile anesthetic seem to have negative effects while propofol appears to have protective effects. Opioids were also found to be immunosuppressive and therefore may not represent an ideal choice. Of the drugs used in anesthesia, local anesthetics seem to be the most attractive with regard to cancer surgery. Depending on their mode of administration, local anesthetics have been found in several reports to directly or indirectly blunt the systemic response to surgery, preserve immune function, alter cytokine release, and interfere with cancer cell signaling pathways. They are also analgesic and have anti-inflammatory properties. The former and the latter are sought effects in the perioperative period. However, their impact on recurrence, overall survival and metastasis remains controversial.
POLICY SERIES: NATIONAL FAMILY CAREGIVER SUPPORT PROGRAM: EVALUATION RESULTS AND PRACTICAL APPLICATIONS

Established in 2000, the National Family Caregiver Support Program (NFCSP) of the Older Americans Act Title III-E is administered by the Administration on Aging within the Administration for Community Living (ACL). The NFCSP supports caregivers through grants to States and Territories for a range of services that assist unpaid family and friend caregivers to care for someone at home for as long as possible. A growing expectation for quality federal programs is a requirement for rigorous evaluation. This session will highlight results of from the first national evaluation of the NFCSP. The first paper sets the stage by describing NFCSP services, participating caregivers, funding levels, and the rationale for the recent process and outcome evaluations. The second paper, focusing on results of the Process Evaluation, highlights program operations based on results of surveys with State Units on Aging, Area Agencies on Aging (AAAs), and Local Service Providers. The third paper presents the experience of Massachusetts, and how NFCSP is integrated with other programs in the state to support family caregivers. The final paper takes a multi-level approach by combining data from the process study and the caregiver outcomes study to look at the association between AAA assessment processes and outcomes of caregivers. To close the session, an expert in federal policy related to unpaid family caregiving will lead discussion about next steps for researchers, practitioners, and policy makers in light of the evaluation results.
Electrophysiological Evidence for Top-Down Lexical Influences on Early Speech Perception:

An unresolved issue in speech perception concerns whether top-down linguistic information influences perceptual responses. We addressed this issue using the event-related-potential technique in two...
Effect of dietary fat and other factors on egg yolk cholesterol: I. The “cholesterol” content of egg yolk as influenced by dietary unsaturated fat and the method of determination

Abstract Studies on the specificity of the method of Zlatkis et al. for the determination of cholesterol indicated that polyunsaturated fatty acids, in eggs from hens fed diets containing large amounts of unsaturated fat, react with the Zlatkis reagent to give a color that interferes with the determination. The apparent cholesterol concentration increased as the unsaturation of the yolk lipids increased. The percentage increase in yolk cholesterol content, measured by the direct Zlatkis method after feeding a diet containing safflower oil at a level of 30% for 3 weeks, was approximately 36%. Upon feeding a diet containing linseed oil at a level of 30%, the increase was 43%. When a modification of the Zlatkis method that included a saponification and extraction procedure was used, the increase in the cholesterol content of eggs from hens fed the diet containing safflower oil was 19%, and the increase was 27% when hens were fed the diet containing linseed oil. The increases in the cholesterol content of the eggs, which paralleled the increases in unsaturation of the yolk lipids, were highly significant even after the removal of the interfering unsaturated fatty acids. Unsaturated carotenoid compounds contributed little to the color development when the modified Zlatkis method was used.
Laparoscopic Left and Sigmoid Colectomy: Options for Colonic and Colorectal Reconstruction

Construction of a safe and healthy anastomosis following a colon or rectal resection is one of the critical steps of the entire operation. There are many options for the type of reconstruction to be performed. All options must include all of the following features: adequate blood supply to the bowel, utilization of healthy bowel, adequate mobilization to avoid tension on the anastomosis, and some form of anastomotic assessment. It is also critical for the surgeon to understand the patient, disease, and surgeon-related factors that impact the creation of a successful anastomosis. Unfortunately, not every anastomosis is straightforward, so surgeons must also be facile with techniques and maneuvers to overcome intraoperative challenges associated with restoring intestinal continuity. This chapter will address many of the technical aspects of the various types of bowel reconstruction, management of intraoperative issues, and will discuss the outcomes of left-sided colon reconstructions.
Prices and Location: A Geographical and Economic Analysis

Government housing projects, not being part of the profit and loss private sector, are able to transcend the market’s tendency to locate people according to income or wealth. This increases transactions costs, reduces social cooperation, creates inefficiency, and undermines incentives to amass wealth (and thus dis-enhances economic development).
Higher body mass index may increase the risk for the development of incisional complications in horses following emergency ventral midline celiotomy

BACKGROUND Obesity is common in the equine population and it has been associated with increased surgical morbidity and mortality in humans. The effect of increased body mass index (BMI) on the incidence of surgical site infections has not been investigated in horses. OBJECTIVES To determine whether horses with increased body fat, as estimated by BMI, are more likely to develop post-operative complications, particularly incisional complications, following emergency ventral midline celiotomy. STUDY DESIGN Retrospective, multi-institutional clinical study. METHODS Medical records of horses >2 years old presenting with colic that underwent ventral midline celiotomy between January 2010 and September 2018 with follow-up of a minimum of 30 post-operative days were reviewed. Extracted data included signalment, operative details and outcome. BMI was calculated by dividing the patient's weight (kg) by the withers height squared (m2 ). RESULTS In all, 287 horses fit inclusion criteria. Incisional complication prevalence was 23.7%. Horses with incisional complications had a higher BMI (median 203.6 kg/m2 , IQR = 191.5-217.4) compared with those without (median 199.1 kg/m2 , IQR = 184.7-210.2) (P = .03). Multi-variable analysis of the effects of age, sex, breed and presence of metabolic disease on the association between BMI and risk of incisional complications, identified a tendency towards increased risk with a higher BMI, but statistical significance decreased to P = .07. Breed had an association with BMI (P < .01), but not with incisional complication risk. MAIN LIMITATIONS BMI as an estimate of body fat has limitations. Retrospective studies with reliance on owners reporting data and complete medical records is imperfect. When the data were subjected to multi-variable analysis, the trend towards an increased incidence of incisional complications in horses with higher BMI persisted but it was not statistically significant. CONCLUSION Higher BMI may increase the risk for the development of incisional complications in horses following emergency ventral midline celiotomy.
Rapid implementation of a COVID-19 remote patient monitoring program.

OBJECTIVE: The study sought to evaluate early lessons from a remote patient monitoring engagement and education technology solution for patients with coronavirus disease 2019 (COVID-19) symptoms. MATERIALS AND METHODS: A COVID-19-specific remote patient monitoring solution (GetWell Loop) was offered to patients with COVID-19 symptoms. The program engaged patients and provided educational materials and the opportunity to share concerns. Alerts were resolved through a virtual care workforce of providers and medical students. RESULTS: Between March 18 and April 20, 2020, 2255 of 3701 (60.93%) patients with COVID-19 symptoms enrolled, resulting in over 2303 alerts, 4613 messages, 13 hospital admissions, and 91 emergency room visits. A satisfaction survey was given to 300 patient respondents, 74% of whom would be extremely likely to recommend their doctor. DISCUSSION: This program provided a safe and satisfying experience for patients while minimizing COVID-19 exposure and in-person healthcare utilization. CONCLUSIONS: Remote patient monitoring appears to be an effective approach for managing COVID-19 symptoms at home.
The outcome of tuberous sclerosis complex afar surgical treatment

Objective Presenting of 6 cases with tuberous sclerosis complex being surgically treated, to observe the clinical effects after 18-30 months follow-up. Method We retrospectively analyze the clinical data of 6 cases with tuberous sclerosis complex. Different operations had been made based on the pre-operation evaluations, including the semiologies, CT, MRI, VEEG, PET, MEG and regular follow-up (18-30 months) was made. Through the synthetical estimations, in 3 cases the tubers which conducted epilepsy seizure were resected with navigation and the low power heat burn was made;in 2 cases the tubers were resected after subdural electrodes implantation;in 1 case anterior callosotomy was made. Results In the follow-up term,2 cases epilepsy seizured free, 1 case occasionally epilepsy seizured,3 cases the seizure frequencies were reduced. Conclusions The operations are effective to control or reduce the epilepsy seizure which is conducted by tuberous sclerosis complex. Key words: Tuberous sclerosis complex; Epilepsy; Surgical procedures,operative
Mind the Gap: A critical analysis of school ethnography

School ethnography is a relatively young form of scientific inquiry, originally designed to solve social problems in the late twentieth century. As such, there are a series of prevailing issues that plague its use. This analysis searches to pinpoint what these issues are, how they contribute to knowledge gaps in school ethnographies, and the problems of interpretation and application that can arise from them. This will happen through first an evaluation of past ethnographic work and existing critiques to identify the most glaring issues, and then an application of how said issues are relevant to more recent ethnogra­phies. Finally, this paper will conclude with a series of potential solutions that would help to alleviate some of these gaps.
Validating NASA's Airborne Multikilohertz Microlaser Altimeter (Microaltimeter) by Direct Comparison of Data Taken Over Ocean City, Maryland Against an Existing Digital Elevation Model

NASA's Airborne Multikilohertz Microlaser Altimeter (Microaltimeter) is a scanning, photon-counting laser altimeter, which uses a low energy (less than 10 microJuoles), high repetition rate (approximately 10 kHz) laser, transmitting at 532 nm. A 14 cm diameter telescope images the ground return onto a segmented anode photomultiplier, which provides up to 16 range returns for each fire. Multiple engineering flights were made during 2001 and 2002 over the Maryland and Virginia coastal area, all during daylight hours. Post-processing of the data to geolocate the laser footprint and determine the terrain height requires post- detection Poisson filtering techniques to extract the actual ground returns from the noise. Validation of the instrument's ability to produce accurate terrain heights will be accomplished by direct comparison of data taken over Ocean City, Maryland with a Digital Elevation Model (DEM) of the region produced at Ohio State University (OSU) from other laser altimeter and photographic sources. The techniques employed to produce terrain heights from the Microaltimeter ranges will be shown, along with some preliminary comparisons with the OSU DEM.
Cryogenic-Temperature Operation of SPADs in Deep Submicrometer CMOS

We discuss dark count, afterpulsing, and detection efficiency trends from 77K to 300K in SPADs fabricated in standard 90nm CMOS. With 1μs dead time, afterpulses and primary dark counts are traded-off optimally at 120K.
Quantitative Magnetization Transfer Detects Renal Fibrosis in Murine Kidneys With Renal Artery Stenosis.

BACKGROUND Renal fibrosis is a common pathway in tubulointerstitial injury and a major determinant of renal insufficiency. Collagen deposition, a key feature of renal fibrosis, may serve as an imaging biomarker to differentiate scarred from healthy kidneys. PURPOSE To test the feasibility of using quantitative magnetization transfer (qMT), which assesses tissue macromolecule content, to measure renal fibrosis. STUDY TYPE Prospective. ANIMAL MODEL Fifteen 129S1 mice were studied 4 weeks after either sham (n = 7) or unilateral renal artery stenosis (RAS, n = 8) surgeries. FIELD STRENGTH/SEQUENCE Magnetization transfer (MT)-weighted images were acquired at 16.4T using an MT-prepared fast-low-angle-shot sequence. Renal B0, B1, and T1 maps were also acquired, using a dual-echo gradient echo, an actual flip angle, and inversion recovery method, respectively. ASSESSMENT A two-pool model was used to estimate the bound water fraction (f) and other tissue imaging biomarkers. Masson's trichrome staining was subsequently performed ex vivo to evaluate renal fibrosis. STATISTICAL TESTS Comparisons of renal parameters between sham and RAS were performed using independent samples t-tests. Pearson's correlation was conducted to investigate the relationship between renal fibrosis by histology and the qMT-derived bound pool fraction f. RESULTS The two-pool model provided accurate fittings of measured MT signal. The qMT-derived f of RAS kidneys was significantly increased compared to sham in all kidney zones (renal cortex [CO], 7.6 ± 2.4% vs. 4.6 ± 0.6%; outer medulla [OM], 8.2 ± 4.2% vs. 4.2 ± 0.9%; inner medulla [IM] + P, 5.8 ± 1.6% vs. 2.9 ± 0.6%, all P < 0.05). Measured f correlated well with histological fibrosis in all kidney zones (CO, Pearson's correlation coefficient r = 0.95; OM, r = 0.93; IM + P, r = 0.94, all P < 0.05). DATA CONCLUSION The bound pool fraction f can be quantified using qMT at 16.4T in murine kidneys, increases significantly in fibrotic RAS kidneys, and correlates well with fibrosis by histology. Therefore, qMT may constitute a valuable tool for measuring renal fibrosis in RAS. LEVEL OF EVIDENCE 1 TECHNICAL EFFICACY STAGE: 3.
Development and validation of a potent and specific inhibitor for the CLC-2 chloride channel

CLC-2 is a voltage-gated chloride channel that is widely expressed in many mammalian tissues. In the central nervous system (CNS), CLC-2 is expressed in neurons and glia. Studies to define how this channel contributes to normal and pathophysiological function in the CNS have been controversial, in part due to the absence of precise pharmacological tools for modulating CLC-2 activity. Herein, we describe the development and optimization of AK-42, a specific small-molecule inhibitor of CLC-2 with nanomolar potency (IC50 = 17 nM). AK-42 displays unprecedented selectivity (>1000-fold) over CLC-1, the closest CLC-2 homolog, and exhibits no off-target engagement against a panel of 58 common channels, receptors, and transporters expressed in brain tissue. Computational docking, validated by mutagenesis and kinetic studies, indicates that AK-42 binds to an extracellular vestibule above the channel pore. In electrophysiological recordings of mouse CA1 hippocampal pyramidal neurons, AK-42 acutely and reversibly inhibits CLC-2 currents; no effect on current is observed on brain slices taken from CLC-2 knockout mice. These results establish AK-42 as a powerful new tool for investigating CLC-2 neurophysiology.
Kinetic Effects of β,γ-Modified Deoxynucleoside 5'-Triphosphate Analogues on RNA-Catalyzed Polymerization of DNA.

A recently described DNA polymerase ribozyme, obtained by in vitro evolution, provides the opportunity to investigate mechanistic features of RNA catalysis using methods that previously had only been applied to DNA polymerase proteins. Insight can be gained into the transition state of the DNA polymerization reaction by studying the behavior of various β,γ-bridging substituted methylene (CXY; X, Y = H, halo, methyl) or imido (NH) dNTP analogues that differ with regard to the pKa4 of the bisphosphonate or imidodiphosphate leaving group. The apparent rate constant (kpol) of the polymerase ribozyme was determined for analogues of dGTP and dCTP that span a broad range of acidities for the leaving group, ranging from 7.8 for the CF2-bisphosphonate to 11.6 for the CHCH3-bisphosphonate. A Bronsted plot of log(kpol) versus pKa4 of the leaving group demonstrates linear free energy relationships (LFERs) for dihalo-, monohalo-, and non-halogen-substituted analogues of the dNTPs, with negative slopes, as has been observed for DNA polymerase proteins. The unsubstituted dNTPs have a faster catalytic rate than would be predicted from consideration of the linear free energy relationship alone, presumably due to a relatively more favorable interaction of the β,γ-bridging oxygen within the active site. Although the DNA polymerase ribozyme is considerably slower than DNA polymerase proteins, it exhibits a similar LFER fingerprint, suggesting mechanistic commonality pertaining to the buildup of negative charge in the transition state, despite the very different chemical compositions of the two catalysts.
The role of medications in successful aging

Successful aging includes good health and low levels of disability. To that end, primary prevention is far better than managing subsequent organ damage. When medication is needed to prevent or mana...
The CD8+ T cell landscape of human brain metastases

Abstract Despite improved outcomes with checkpoint blockade immunotherapy, patients with brain metastases have the worst prognosis among patients with metastatic cancer. Immune checkpoint blockade agents target inhibitory receptors, such as PD-1, on exhausted CD8+ T cells to restore their anti-cancer function. Many patients, however, either do not respond or progress after an initial response to immune checkpoint blockade, and distant intracranial failure is common despite excellent options for local treatment of brain metastasis. To develop more effective therapeutic strategies for the treatment of brain metastases, an understanding of the phenotype of brain metastasis-infiltrating CD8+ T cells is essential. Here we performed a detailed characterization of the CD8+ T cells contained in brain metastases. Brain metastases were densely infiltrated by CD8+ T cells; blood contamination of tumor samples was rare. Compared to patient-matched circulating cells, brain metastasis-infiltrating CD8+ T cells had a distinct phenotype characterized by more frequent expression of PD-1, with subpopulations defined by expression of additional co-inhibitory molecules and the residence marker CD69. Single cell RNA-sequencing identified four phenotypic subpopulations within brain metastasis-infiltrating PD-1+ CD8+ T cells. Two of these populations — a terminally-differentiated and a dividing population — were characterized by high expression of co-inhibitory molecules and lacked expression of progenitor markers such as TCF-1. There was significant T cell receptor (TCR) overlap between the terminally-differentiated and dividing populations, suggesting that the dividing cells give rise to the terminally-differentiated cells. There was minimal TCR overlap between these two populations and other brain metastasis-infiltrating PD-1+ CD8+ T cells. T cell clones from brain metastasis-infiltrating CD8+ T cells were rare in circulation, particularly clones from the terminally-differentiated and dividing populations. We systematically identified bystander CD8+ T cells specific for microbial antigens; these cells infiltrated brain metastases and expressed genes shared with exhausted progenitor CD8+ T cells, such as TCF7 and IL7R. We performed spatial transcriptomics on brain metastases and used a novel method to obtain TCR sequences from spatial transcriptomics data. These data revealed distinct niches within the TME defined by their gene expression patterns and cytokine profiles. Terminally-differentiated CD8+ T cells preferentially occupied niches within the tumor parenchyma. Together, our results show that antigen-specificity restricts the spatial localization, phenotypic states, and differentiation pathways available to CD8+ T cells within the brain metastasis TME.
Optimization of single dose VSV-based COVID-19 vaccination in hamsters

The ongoing COVID-19 pandemic has resulted in global effects on human health, economic stability, and social norms. The emergence of viral variants raises concerns about the efficacy of existing vaccines and highlights the continued need the for the development of efficient, fast-acting, and cost-effective vaccines. Here, we demonstrate the immunogenicity and protective efficacy of two vesicular stomatitis virus (VSV)-based vaccines encoding the SARS-CoV-2 spike protein either alone (VSV-SARS2) or in combination with the Ebola virus glycoprotein (VSV-SARS2-EBOV). Intranasally vaccinated hamsters showed an early CD8 + T cell response in the lungs and a greater antigen-specific IgG response, while intramuscularly vaccinated hamsters had an early CD4 + T cell and NK cell response. Intranasal vaccination resulted in protection within 10 days with hamsters not showing clinical signs of pneumonia when challenged with three different SARS-CoV-2 variants. This data demonstrates that VSV-based vaccines are viable single-dose, fast-acting vaccine candidates that are protective from COVID-19.
Protocol for pragmatic randomised trial: integrating electronic health record-based behavioural economic 'nudges' into the electronic health record to reduce preoperative testing for patients undergoing cataract surgery.

Introduction Robust randomised trial data have shown that routine preoperative (pre-op) testing for cataract surgery patients is inappropriate. While guidelines have discouraged testing since 2002, cataract pre-op testing rates have remained unchanged since the 1990s. Given the challenges of reducing low-value care despite strong consensus around the evidence, innovative approaches are needed to promote high-value care. This trial evaluates the impact of an interdisciplinary electronic health record (EHR) intervention that is informed by behavioural economic theory. Methods and analysis This pragmatic randomised trial is being conducted at UCLA Health between June 2021 and June 2022 with a 12-month follow-up period. We are randomising all UCLA Health physicians who perform pre-op visits during the study period to one of the three nudge arms or usual care. These three nudge alerts address (1) patient harm, (2) increased out-of-pocket costs for patients and (3) psychological harm to the patients related to pre-op testing. The nudges are triggered when a physician starts to order a pre-op test. We hypothesise that receipt of a nudge will be associated with reduced pre-op testing. The primary outcome will be the change in the percentage of patients undergoing pre-op testing at 12 months. Secondary outcomes will include the percentage of patients undergoing specific categories of pre-op tests (labs, EKGs, chest X-rays (CXRs)), the efficacy of each nudge, same-day surgery cancellations and cost savings. Ethics and dissemination The study protocol was approved by the institutional review board of the University of California, Los Angeles as well as a nominated Data Safety Monitoring Board. If successful, we will have created a tool that can be disseminated rapidly to EHR vendors across the nation to reduce inappropriate testing for the most common low-risk surgical procedures in the country. Trial registration number ClinicalTrials.gov identifier: NCT04104256.
Embedding Hercule Poirot in networks: addressing inefficiencies in digital forensic investigations

Forensic investigations on networks are not scalable in terms of time and money [1]. Those investigations that do occur consume months of attention from the very experts who should be investing in more productive activities, like designing and improving network performance [1]. Given these circumstances, organizations often must select which cases to pursue, ignoring many that could be prosecuted, if time allowed. Recognizing the exponential growth in the number of crimes that employ computers and networks that become subject to digital evidence procedures, researchers and practitioners, alike, have called for embedding forensics-essentially integrating the cognitive skills of a detective into the network [2, 3, 4]. The premise is that the level of effort required to document incidents can thus be reduced, significantly. This paper introduces what technical factors might reflect those detecting skills, leading to solutions that could offset the inefficiencies of current practice.
Virtual interactive presence for real-time, long-distance surgical collaboration during complex microsurgical procedures.

Object The shortage of surgeons compels the development of novel technologies that geographically extend the capabilities of individual surgeons and enhance surgical skills. The authors have developed “Virtual Interactive Presence” (VIP), a platform that allows remote participants to simultaneously view each other's visual field, creating a shared field of view for real-time surgical telecollaboration. Methods The authors demonstrate the capability of VIP to facilitate long-distance telecollaboration during cadaveric dissection. Virtual Interactive Presence consists of local and remote workstations with integrated video capture devices and video displays. Each workstation mutually connects via commercial teleconferencing devices, allowing worldwide point-to-point communication. Software composites the local and remote video feeds, displaying a hybrid perspective to each participant. For demonstration, local and remote VIP stations were situated in Indianapolis, Indiana, and Birmingham, Alabama, respective...
A Secure Plan

Active Networks promise greater flexibility than current networks, but threaten safety and security by virtue of their programmability. In this paper, we describe the design and implementation of a security architecture for the active network PLANet [HMA+99]. Security is obtained with a two-level architecture that combines a functionally restricted packet language, PLAN [HKM+98], with an environment of general-purpose service routines governed by trust management [BFL96]. In particular, we employ a technique which expands or contracts a packet’s service environment based on its level of privilege, termed namespace-based security. As an application of our security architecture, we outline the design and implementation of an active-network firewall. We find that the addition of the firewall imposes an approximately 34% latency overhead and as little as a 6.7% space overhead to incoming packets.
The Others: How Animals Made Us Human

The Others: How Animals Made Us Human. Paul Shepard. Washington, DC: Island Press, 1996. 374 pp.
Radiation characteristics of a 2D periodic slot leaky-wave antenna

The leaky-wave antenna (LWA) under consideration consists of a planar periodic slot array on top of a grounded substrate. The antenna is excited by an infinitesimal horizontal electric dipole. The antenna can produce either a pencil beam at broadside or a scanned conical beam. Increasing the substrate thickness causes the beam to scan towards endfire. The radiation characteristics of a complimentary LWA (using metal patches instead of slots) were discussed in a previous paper (see Zhao, T. et al., IEEE AP-S, vol 3, p.260-3, 2001). For the patch array it was determined that the substrate thickness controls the beam angle, while the patch size determines the beam width. The design principle for determining the substrate thickness is the same for both the slot and patch structures (see Zhao et al., 2001; Jackson, D.R. et al., IEEE Trans. Antennas and Propagation, vol.AP-41, p.344-8, 1993). For the slot array it is shown that the beam width can be controlled by adjusting the slot dimensions. Comparisons between the patch and slot configurations are made.
Morphological and mechanical imaging of Bacillus cereus spore formation at the nanoscale

Summary Bacteria from the genus Bacillus are able to transform into metabolically dormant states called (endo) spores in response to nutrient deprivation and other harsh conditions. These morphologically distinct spores are fascinating constructs, amongst the most durable cells in nature, and have attracted attention owing to their relevance in food-related illnesses and bioterrorism. Observing the course of bacterial spore formation (sporulation) spatially, temporally and mechanically, from the vegetative cell to a mature spore, is critical for a better understanding of this process. Here, we present a fast and versatile strategy for monitoring both the morphological and mechanical changes of Bacillus cereus bacteria at the nanoscale using atomic force microscopy. Through a strategy of imaging and nanomechanical mapping, we show the morphogenesis of the endospore and released mature endospore. Finally, we investigate individual spores to characterizetheirsurfacemechanically.Theprogressioninelasticity coupled with a similarity of characteristic distributions between the incipient endospores and the formed spores show these distinct stages. Taken together, our data demonstrates the power of atomic force microscopy applied in microbiology for probing this important biological process at the single cell scale.