cssi/SciSciGPT-SciSciNet huggingface dataset:
Exosomes as therapeutics: The implications of molecular composition and exosomal heterogeneity

Harnessing exosomes as therapeutic drug delivery vehicles requires a better understanding of exosomal composition and their mode of action. A full appreciation of all the exosomal components (proteins, lipids, and RNA content) will be important for the design of effective exosome-based or exosome-mimicking drug carriers. In this review we describe the presence of rarely studied, non-coding RNAs that exist in high numbers in exosomes. We discuss the implications of the molecular composition and heterogeneity of exosomes on their biological and therapeutic effects. Finally, we highlight outstanding questions with regard to RNA loading into exosomes, analytical methods to sort exosomes and their sub-populations, and the effects of exosomal proteins and lipids on recipient cells. Investigations into these facets of exosome biology will further advance the field, could lead to the clinical translation of exosome-based therapeutics, and aid in the reverse-engineering of synthetic exosomes. Although synthetic exosomes are still an underexplored area, they could offer researchers a way to manufacture exosomes with highly defined structure, composition, and function.
Properties of CVD Diamond and its Application for Field Emitters

Diamond possesses the potential for application as a field emitter cathode because of its negative electron affinity. In order to fabricate diamond field emitter devices, the developments of electrical properties and structures of diamond are required.In terms of the development of electrical properties, conduction mechanism of boron-doped homoepitaxial diamond was investigated by means of Hall measurements and infrared-visble spectroscopy. Diamond films with various boron concentrations were grown by the microwave plasma-assisted CVD method. It is shown that owing to the strong interactions between the hole and the optical phonon, the conduction mechanism changes from a valence-band conduction to an impurity-band conduction in a sample with a carrier concentration of more than 1018 cm-3 at room temperature. This impurity-band conduction can be used as a source of electrons for a field emission.In terms of the development of device structures, reactive ion etching (RIE) of synthetic Ib diamond and CVD diamond films in O2 and CF4 has been investigated. The large etch rate of up to 2.8μm/hr and etch rate ratios of 15-20 for diamond (100)/Al were obtained at CF4/O2 = 10-20%. Numerous columnar structures of approximately 300 nm length and 10 nm width have been made by etching CVD polycrystalline diamond films in O2 plasma. The structures made the diamond film “porous”. A comparative study of field emission characteristics has been made for as-grown diamond films and porous diamond films. The average turn-on field was in the range of 2-3 V/μm for porous diamond films and 6-8 V/μm for as-grown diamond films.
Megavolt Bioron and Arsenic Implantation into Silicon

Formation of buried p-type and n-type layers in (100) silicon has been accomplished by implanting with 4 MeV boron and 11 MeV arsenic ions respectively. The projected range (Rp) of 4 MeV boron is 5.2 microns with a straggle (ΔRp) of.2 microns. The 11 MeV arsenic implant has a Rp of 4.37 microns with a ΔRp of.37 microns. The 4 MeV boron implant was carried out to a dose of l×1015/ cm2 while the 11 MeV arsenic implant dose was 1.9×1015/ cm2. For both dopants the target holder could be cooled with either liquid nitrogen (LN) or flowing room temperature water (RT). Buried amorphous regions are seen by cross sectional transmission electron microscopy (XTEM) for both boron and arsenic when LN cooling is used. Arsenic shows a buried amorphous region for the RT case as well. The extent of the buried amorphous regions are compared with the energy deposited into nuclear stopping as determined by computer simulation. Threshold levels are determined for the creation of these buried amorphous regions. The boron samples were annealed for 30 minutes at 900°C in a nitrogen ambient, and XTEM shows no residual damage for both cooling conditions. The arsenic samples underwent a two step annealing procedure; 545°C for 16 hours followed by a 945°C step for 15 minutes. Regions containing dislocation networks are observed by XTEM for both cooling conditions. The 4 MeV implanted boron buried layer was applied to an NMOS process. Transistors fabricated above the p-type buried layer show channel mobility, threshold voltage, and sub-threshold leakage which are indistinguishable from transistors fabricated without the buried layer. Vertical npn bipolar transistors have been fabricated using the 11 MeV arsenic buried layer to form the collector. Electrical characteristics from both these devices indicate that megavolt ion implantation can be applied to silicon for active device geometries.
Synthesis, Spectroscopy, and Electrochemistry of (α-Diimine)M(CO)3Br, M = Mn, Re, Complexes: Ligands Isoelectronic to Bipyridyl Show Differences in CO2 Reduction.

The synthesis and characterization of new Mn(I)- and Re(I)-centered organometallic complexes fashioned with 1,4-diazabutadiene (DAB) ligands is reported. Ten compounds of the type fac-(α-diimine)M(CO)3Br (M = Mn, Re) were obtained in moderate to excellent yield (35–80%) and high purity from the coordination of the five ligands with M(CO)5Br in refluxing ethanol. Despite the electronic similarity of DAB to 2,2′-bipyridyl, the complexes described herein were poor mediators of electrochemical CO2 conversion to CO, but provide insight into the role of redox-active ligands in catalysis. Additional characterization of the one-electron reduced rhenium compounds, relevant intermediates in CO2 reduction, by EPR and single-crystal X-ray analysis is described.
The performance effect of early versus late carbohydrate feedings during prolonged exercise.

The purpose of this study was to determine how the timing of isoenergetic carbohydrate feedings during prolonged cycling affects performance in a subsequent 10-km cycling time trial. Recreationally trained male cyclists (n = 8; age, 34.5 ± 8.3 years; mass, 80.0 ± 6.3 kg; body fat, 16.0% ± 3.8%, peak oxygen uptake, 4.54 ± 0.42 L·min−1) completed 4 experimental trials consisting of cycling continuously for 2 h at 62.4% ± 1.9% of peak oxygen uptake, followed immediately by a self-paced 10-km time trial. The 4 conditions included no carbohydrate ingestion (PP), early carbohydrate ingestion (CP), late carbohydrate ingestion (PC), or carbohydrate ingestion throughout (CC). Blood samples were obtained at 0, 60, and 120 min of cycling as well as at the conclusion of the time trial. The 10-km time trial time to completion was faster in trials CC (17.70 ± 0.52 min) and PC (17.60 ± 0.62 min) as compared with trial PP (18.13 ± 0.52 min, p = 0.028 and p = 0.007, respectively) while trial CP (17.85 ± 0.58 min, p = 0.17...
Comprehensive Molecular Characterization of Salivary Duct Carcinoma Reveals Actionable Targets and Similarity to Apocrine Breast Cancer

Purpose Salivary duct carcinoma (SDC) is an aggressive salivary malignancy which is resistant to chemotherapy and has high mortality rates. We investigated the molecular landscape of SDC, focusing on genetic alterations and gene expression profiles. Experimental Design We performed whole-exome sequencing, RNA sequencing and immunohistochemical analyses in 16 SDC tumors, and examined selected alterations via targeted sequencing of 410 genes in a second cohort of 15 SDCs. Results SDCs harbored a higher mutational burden than many other salivary carcinomas (1.7 mutations/megabase). The most frequent genetic alterations were mutations in TP53 (55%), HRAS (23%), PIK3CA (23%), and amplification of ERBB2 (35%). Most (74%) tumors had alterations in either MAP kinase (BRAF/HRAS/NF1) genes or ERBB2. Potentially targetable alterations based on supportive clinical evidence were present in 61% of tumors. Androgen receptor (AR) was overexpressed in 75%; several potential resistance mechanisms to androgen deprivation therapy (ADT) were identified, including the AR-V7 splice variant (present in 50%, often at low ratios compared to full length AR) and FOXA1 mutations (10%). Consensus clustering and pathway analyses in transcriptome data revealed striking similarities between SDC and molecular apocrine breast cancer. Conclusions This study illuminates the landscape of genetic alterations and gene expression programs in SDC, identifying numerous molecular targets and potential determinants of response to AR antagonism. This has relevance for emerging clinical studies of ADT and other targeted therapies in SDC. The similarities between SDC and apocrine breast cancer indicate that clinical data in breast cancer may generate useful hypotheses for SDC.
On Parfit's Personal Identity

Parfit's theory of personal identity plays an important role in the area of the philosophy of mind.But the Wiggins case that Parfit takes use of in his discussion can not commendably support his own idea.The Wiggins case produces a monstrous hypothesis: the possibility of divided self.In this case,Parfit is confronted with a difficult problem: when the two parts become merged,how can the previous two separated individuals be preserved? If Jack and Jill are combined into one person,how can they exist in the new identical person Lack/Jill? It is not possible to make two persons merged into a new physical man,so there is no reason to believe they can exist in this new person for a moment.Personal identity is a serious question which should not be dealt with at will simply.
Interleukin-10 inhibits proinflammatory activation of endothelium in response to Borrelia burgdorferi or lipopolysaccharide but not interleukin-1β or tumor necrosis factor α

Interleukin (IL)-10 is generally regarded as an anti-inflammatory cytokine, since it acts on a variety of cell types to suppress production of proinflammatory mediators. In inflammation, endothelial cells (EC) play a crucial role in recruiting leukocytes to sites of injury or infection. In this study, the actions of IL-10 on human umbilical vein EC were investigated. IL-10 reduced migration of monocytes and T lymphocytes across endothelium stimulated by lipopolysaccharide and decreased endothelial production of chemokines in response to lipopolysaccharide and Borrelia burgdorferi, the agent of Lyme disease. However, IL-10 did not affect these responses when EC were activated by the host proinflammatory cytokines IL-1β or tumor necrosis factor a. Moreover, IL-10 did not prevent up-regulation of the adhesion molecules E-selectin and intercellular adhesion molecule-1 by EC exposed to any of these activating agents. IL-10 therefore inhibits proinflammatory activation of EC in a manner that is selective with respect to stimulus and effector response. J. Leukoc. Biol. 72: 503-511; 2002.
Bending without Breaking: Making Software More Flexible

In this talk we discuss the problem of simultaneously refining mutually interdependent classes and object types. We discuss possible solutions using existing static type systems that include parametric polymorphism. A statically type-safe solution is presented that involves the introduction of type groups, a construct that can be understood as a generalization of the MyType construct introduced in a statically type-safe way in languages like PolyTOIL [3] and LOOM [2].
Uniform integration of gold nanoparticles in PDMS microfluidics with 3D micromixing

The integration of gold nanoparticles (AuNPs) on the surface of polydimethylsiloxane (PDMS) microfluidics for biosensing applications is a challenging task. In this paper we address this issue by integration of pre-synthesized AuNPs (in a microreactor) into a microfluidic system. This method explored the affinity of AuNPs toward the PDMS surface so that the pre-synthesized particles will be adsorbed onto the channel walls. AuNPs were synthesized inside a microreactor before integration. In order to improve the size uniformity of the synthesized AuNPs and also to provide full mixing of reactants, a 3D-micromixer was designed, fabricated and then integrated with the microreactor in a single platform. SEM and UV/Vis spectroscopy were used to characterize the AuNPs on the PDMS surface.
Solution rectification of slider-crank mechanisms with transmission angle control

Abstract Transmission angle control is well studied for both crank rocker and Grashof crank slider mechanisms. However, non-Grashof slider-crank mechanisms have received less attention. For these mechanisms, the fully rotatable crank constraint is removed increasing the complexity of the problem. Furthermore, methods of linkage synthesis by optimization are becoming more prevalent. When optimizing a mechanism, it is important to prevent the evaluation of non-constructible and undesirable linkages. Presented here is a method of solution rectification by means of transmission angle control for slider-crank mechanisms which can be used to parameterize a problem to prevent the evaluation of invalid linkages. The solution is kept general to include fully rotatable crank slider mechanisms as well. The solution considers both crank driven and slider driven mechanisms as well as a reversible driver mechanism. An example is provided to demonstrate the method. It will be shown that by defining a transmission angle, valid linkages can be generated preventing the evaluation of invalid solutions.
Pathways between physical activity and quality of life in African-American breast cancer survivors

Introduction Several studies have indicated that the relationship between physical activity and quality of life is not directed but mediated through various pathways. The purpose of this study was to assess the role of cancer-related fatigue, disability, and functional status as potential mediators in African-American breast cancer survivors.
Pulmonary Embolism Incidence Is Increasing with Increasing Use of CT Scans.

Pulmonary embolism (PE) is a major cause of morbidity in hospitalized patients, yet few data exist on PE incidence and characteristics among hospitalized patients. If those at greatest risk were able to be identified, early prevention might improve health outcomes. We, therefore, analyzed statewide discharge data from all hospitals in Pennsylvania on patients with PE, 1997-2001, collected by the Pennsylvania Health Care Cost Containment Council (PHC4) for clinical factors, Atlas severity of illness scores, and trends associated with PE. All non-pregnant Pennsylvania residents hospitalized for PE with the following ICD-9 PE-specific diagnostic codes were included in the analyses: 415.11 and 415.19. Diagnostic procedures were determined on the dataset by revenue codes, specifically for x-ray, chest x-ray, arteriography, nuclear medicine, and CT scan (including spiral CT). Total PE discharges were enumerated by age, race, and sex by year. The analysis was refined to exclude second or later admissions for PE. No subject identifiers or linkage codes were recorded or linked to the dataset. Severity of illness was determined by MediQual Atlas Admission Severity Categories and was analyzed for trends of malignancy, trauma, surgery, and fractures. The incidence of PE discharges among Pennsylvania residents increased from 47 to 63 per 100,000, a mean increase of 0.004% per year, p<0.001. Factors associated with greater PE incidence over the period included African American race (mean 0.031% per year higher than Caucasian), age ≥70 years (mean 0.007% higher than age <70 years), and female gender (0.013% higher than males), all p<0.001. During the same period, the proportion of PE patients undergoing CT scan increased from 19.21% to 41.36%, while rates for other procedure/revenue codes showed no proportionate increase. In a multivariate logistic regression model controlling for age, gender, race, and cancer, there was an increased likelihood over the 5-year period of having a CT scan, OR = 1.30, p<0.001. Comparing 1999 and before with 2000 and after, there was a significant decrease in the two highest Atlas severity of illness categories (49.4% to 37.7%) and a significant increase in the three lowest categories (50.6% to 62.3%), p<0.001, a trend that persisted after controlling for age, gender, and race. During the same period, the proportion of in-hospital deaths among PE patients decreased from 12.8% (1999 and before) to 11.1% (2000 and after), p<0.001. There was no proportionate increase in cancer, CHF, trauma, or fractures over the same period, which persisted after controlling for age, race, and gender. In conclusion, increasing rates of PE in hospitalized patients in Pennsylvania have occurred in parallel with increasing rates of CT scan (including spiral CT) procedures and were accompanied by lower severity of illness scores and lower mortality rates. Further studies will be required to determine the relationship of these factors to the increasing incidence of PE. ![Figure][1] PE incidence in Hospitalized Patients in PA [1]: pending:yes
Vascular Flora of the Deep Fork National Wildlife Refuge, Okmulgee County, Oklahoma

ABSTRACT The Deep Fork National Wildlife Refuge (3,925 ha) is located in east-central Oklahoma. We report 584 taxa of vascular plants (565 species and 19 infraspecific taxa), 349 genera, and 106 families. The largest families were the Poaceae (with 84 taxa), Asteraceae (73 taxa), and Fabaceae (45 taxa). Eighty introduced taxa and 13 taxa tracked by the Oklahoma Natural Heritage Inventory were encountered.
Use of platinum-based neoadjuvant chemotherapy (NACT) in patients (pts) with hormone receptor-positive breast cancer.

e11038 Background: NACT is used for the treatment of locally advanced breast cancer. Evaluation of breast cancer subtypes and their responses to specific chemotherapy regimens is important. Methods...
A Measurement Technique for Infrared Emissivity of Epoxy-Based Microwave Absorbing Materials

Infrared (IR) emissivity is a critical parameter for modeling and predicting heat transfer by radiation. Microwave absorbing materials, having a high emissivity in the microwave spectrum, are crucial in a wide array of applications, such as electromagnetic interference mitigation, stealth technology, and microwave remote sensing and radiometer calibration. Accurate knowledge of the thermal properties of these materials is necessary for efficient design and optimization of these types of systems. Typical microwave absorbing materials consist of a dielectric epoxy material impregnated with a lossy material, such as iron or carbon. We study a novel cryogenically compatible epoxy-based absorber material that has been loaded with varying concentrations of carbonyl iron powder (CIP). We study six materials with CIP concentrations of 0%, 5%, 10%, 20%, 30%, and 50% by tap volume. We use a commercial IR camera with sensitivity in the range 7.5– $13~\mu \text{m}$ to measure the radiance of the samples and a waterbath IR blackbody at ten temperatures between about 19 °C and 45 °C. A linear Deming fitting is performed, considering uncertainties in both the measured parameters, and the slope of the linear fit is shown to be the IR emissivity, averaged over the spectral response of the camera. The emissivity ranges between 0.868 and 0.757, decreasing monotonically as a function of iron carbonyl concentration between 0% and 50%. The uncertainty of the emissivity determination method is derived and presented. The uncertainty of the presented method is shown to be no larger than 3.3% for all measured samples.
Professional behavior and the optometric profession.

Background Optometry has been recognized as a profession within the United States, both legally and socially, for the better part of the past century. Historically, there have been expectations placed on the behavior of individuals within the professions that would not generally be placed on the general business person. These expectations have existed to protect the clients or patients of professionals from incompetence, uncaring, or selfish excesses. Behavior of an exceptional nature is expected of professionals because of the unusual vulnerability of clients and patients to unprofessional conduct. Doctors of Optometry, as members of the optometric profession, have professional standards placed on their behavior. Methods A search of the literature was conducted to discover the historical and current bases for setting standards for professional behavior. Results The literature search reinforces the rationale for the optometric professions long-standing practice of setting standards for professional conduct. Conclusions Individual Doctors of Optometry will find that the trust resulting from high standards of professional conduct bring many positive benefits to the doctor-patient relationship. The rewards that come to both the doctor and patient from these trusting relationships make the practice of optometry truly an exceptional experience.
The Vibrational Dynamics of Hydrogen Bonded Molecular Complexes at the State-to-State Level

In recent years our understanding of the vibrational predissociation dynamics of weakly bound molecular complexes has improved greatly owing to both the experimental and theoretical advances that have been made in this area. We are now in the very fortunate position where both theory and experiment often can be brought to bare on the same system. The developments made in our laboratory involve the use of the opto-thermal detection technique to measure the infrared spectra and state-to-state dissociation rates for a number of these complexes. In the present report we examine the affects of molecular orientation on the rate of vibrational relaxation. This is done by measuring the predissociation lifetimes associated with several vibrational modes of different isomeric forms of a binary complex. The vibrational relaxation rates are found to be highly anisotropic and several interesting correlations can be made between this data and the collisional relaxation results already available in the literature.
The Presence of Parents at Juveniles’ Interrogations

What law or legal process could best protect juveniles from making uninformed or involuntary decisions about their rights in interrogation? Courts have addressed three general approaches to this problem.
Exploring the relationship between authoritarianism and attitudes toward unions

This study examines the relationship between authoritarianism and attitudes toward unionism. The present study, using a sample of undergraduate business majors, finds a significant and positive correlation between authoritarianism and anti-union attitudes. This suggests that attitudes toward unions are, to some extent, rooted not in simple economic rationality, rather in rigid and dogmatic thought patterns. The implications for labor/management relations, and for successful programs of employee involvement are discussed.
Effects of health insurance coverage on household financial portfolio: Evidence from the Affordable Care Act

Abstract This article examines the effects of the health insurance coverage mandate for dependents on household financial portfolio decisions by focusing on the Affordable Care Act of 2010. Using the Survey of Income and Program Participation data, the author finds that the dependent coverage mandate significantly increased (decreased) the share of stocks (bonds and other interest-accruing assets) by 2.5 (1.3 and 1.1) percentage points for households having both parental employer-sponsored health insurance and dependent children aged 19 to 25 years.
Postoperative Pulmonary Complications Following Brain Tumor Resection: A National Database Analysis

OBJECTIVE There is sparse literature that investigates the adverse effects of postoperative pulmonary complication (PPCs) specifically in postcraniotomy tumor patients. In this study, we describe the rate of PPCs, determine predictive factors, and delineate associations with adverse outcomes. METHODS The National Surgical Quality Improvement Program (2006-2016) database was queried for patients who underwent craniotomy for brain tumors. A total of 28,700 eligible patients were identified. Univariate tests and/or multivariate logistic regression were used to determine predictors of PPC and associations with adverse outcomes. RESULTS A total of 19 predictors of PPC across 14 different categories were identified: age 65-79 years (odds ratio [OR] 1.6; P < 0.001), age ≥80 years (OR 2.3; P < 0.001), male sex (OR 1.3; P < 0.001), operative time ≥360 minutes (OR 4.3; P < 0.001), operative time 300-359 minutes (OR 2.5; P < 0.001), operative time 240-299 minutes (OR 1.8; P < 0.001), operative time 180-239 minutes (OR 1.3; P < 0.001), total functional dependence (OR 3.8; P < 0.001), partial functional dependence (OR 1.7; P < 0.001), insulin-dependent diabetes (OR 1.5; P < 0.001), preoperative dyspnea (OR 1.3; P = 0.01), chronic steroid use (OR 1.4; P < 0.001), chronic obstructive pulmonary disease (OR 1.8; P < 0.001), preoperative leukocytosis (OR 1.4; P < 0.001), anemia (OR 1.2; P < 0.001), American Society of Anesthesiologists (ASA) classification ≥3 (OR 2.0; P < 0.001), emergency case status (OR 2.0; P < 0.001), and infratentorial lesions (OR 1.4; P < 0.001). PPCs were significantly associated with higher reoperation, readmission, and mortality rates as well as longer length of stay (univariate). CONCLUSIONS There are several predictive factors of PPCs in patients that undergo surgical resection of brain tumors, and PPC development is associated with numerous adverse outcomes. It is critically important to understand and, if possible, mitigate controllable circumstances that may reduce morbidity and mortality associated with PPCs.
Indirect Pain Measurement

Measurement of pain severity can be difficult in neonates, infants and patients with dementia or cognitive impairment. In these patients who may not be able to communicate, it is important to use scales that measure behavioral or physiological indicators of pain.
Quantitative analysis of in vivo methionine oxidation of the human proteome

ABSTRACT The oxidation of methionine is an important posttranslational modification of proteins with numerous roles in physiology and pathology. However, the quantitative analysis of methionine oxidation on a proteome-wide scale has been hampered by technical limitations. Methionine is readily oxidized in vitro during sample preparation and analysis. In addition, there is a lack of enrichment protocols for peptides that contain an oxidized methionine residue; making the accurate quantification of methionine oxidation difficult to achieve on a global scale. Herein, we report a methodology to circumvent these issues by isotopically labeling unoxidized methionines with 18O labeled hydrogen peroxide and quantifying the relative ratios of 18O and 16O oxidized methionines. We validate our methodology using artificially oxidized proteomes made to mimic varying degrees of methionine oxidation. Using this method, we identify and quantify a number of novel sites of in vivo methionine oxidation in an unstressed human cell line.
The Effects of a Manualized Group-Psychotherapy Intervention on Client God Images and Attachment to God: A Pilot Study:

The goal of this pilot study was to examine the effects of an 8-week, manualized, outpatient group-psychotherapy intervention on client god images and attachment to God. Participants were 26 adults...
Pool Boiling Coupled with Nanoscale Evaporation Using Buried Nanochannels.

Pool boiling is explicitly coupled with nanoscale evaporation by using buried nanochannels of height ∼728 nm and ∼100 nm to enhance critical heat flux (CHF) by ∼105%. Additional menisci and contact...
An Overview of the Burden of Illness and the Role of Once-Weekly Glucagon-like Peptide-1 Receptor Agonists in the Treatment of Type 2 Diabetes

Type 2 diabetes (T2D) is a debilitating condition and more people are being diagnosed each year. T2D increases patients' risk of developing disabling micro- and macrovascular complications, significantly reduces patients' quality of life, and is a substantial global economic burden. The efficacy and safety of antihyperglycemic therapies have improved over the years and have increased the lifespan for these patients. Consequently, patients are living longer with the condition and the associated comorbidities, but with a lowered quality of life. Therefore, therapies should aim to provide both optimal glycemic control and improve quality of life. Glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy improves glycemic control, reduces body weight, and has a low risk for hypoglycemia. GLP-1 RAs are available as once-daily (OD), twice-daily (BD), or once-weekly (OW) injectable formulations; OW injections may increase patients' satisfaction and improve treatment adherence. In the last decade, concern has been raised about the cardiovascular (CV) safety of antihyperglycemic therapies. Clinical data have been limited on CV outcomes among OW GLP-1 RAs. However, a post hoc analysis of the SUSTAIN-6 trial suggested that semaglutide, the most recently US Food and Drug Administration (FDA)-approved OW GLP-1 RA therapy, may offer cardioprotection, addressing this previously unmet clinical need.
Solution-Based Dosage Forms and Sterile Products

This chapter expands upon the concept of drug solubility and dissolution as it relates to dosage form design. Excipients utilized in solution-based dosage forms and parenteral products are discussed in detail, including solvents, cosolvents, antioxidants, preservatives, complexing agents, and surfactants. Special considerations which must be made for parenteral dosage forms are introduced. Lastly, a review of lyophilization and sterilization techniques is provided.
Feasibility of 3D tracking and adaptation of VMAT based on VMAT-CT

Abstract Background Local computed tomography (CT) reconstruction is achievable with portal images acquired during volumetric-modulated arc therapy (VMAT) delivery and was named as VMAT-CT. However, the application of VMAT-CT is limited because it has limited field of view and no density information. In addition, the new generation of multi-leaf collimator with faster speed and various collimator angles used in patients’ plans could cause more artifacts in VMAT-CT. The goal of this study was to extend VMAT-CT concept, generate complete three-dimensional (3D) CT images, calculate new 3D dose, track and adapt VMAT plan based on updated images and dose. Materials and methods VMAT-CT and planning CT of phantoms were fused by rigid or deformable registration to create VMAT-CT+ images. Trackings based on planning CT, VMAT-CT+, and cone beam CT (CBCT) were compared. When prescription dose was not met for planning target volume (PTV), re-planning was demonstrated on an in-house deformable phantom. Possible uncertainties were also evaluated. Results Tracking based on VMAT-CT+ was accurate and superior to those based on planning CT and CBCT since VMAT-CT+ can detect changes during treatment. PTV coverage in the deformable phantom decreased after deformations but went up and met the prescription goal after re-planning. The impact of uncertainties on dose was minimal. Conclusion 3D tracking and adaptation of VMAT based on VMAT-CT are feasible. Our study has the potential to increase the confidence of beam delivery, catch and remedy errors during VMAT.
Multimodality Imaging of Gastric Pathologic Conditions: A Primer for Radiologists

Understanding the wide spectrum of non–postsurgical gastric pathologic conditions, including neoplastic, infectious and/or inflammatory, and emergent diseases, and their imaging features can help n...
Differentiation of a human monocytic cell line by 1,25-dihydroxyvitamin D3 (calcitriol): a morphologic, phenotypic, and functional analysis

Several recent studies have suggested a role for 1,25-dihydroxyvitamin D3 (calcitriol) in myeloid differentiation. We have examined the effects of calcitriol on the U937 monoblast cell line and found that calcitriol, at near physiologic concentrations, is a potent inhibitor of U937 growth. Moreover, calcitriol induces differentiation to a monocyte-macrophage phenotype marked by enhanced alpha-naphthyl esterase staining. Morphologic changes were attended by de novo induction of the myeloid specific antigen detected by the monoclonal antibody AML-2–23, as well as dramatic increases in Fc receptors for IgG. In addition, calcitriol induced U937 cells to perform phagocytosis and antibody-dependent cellular cytotoxicity. These results indicate the potential activity of calcitriol in myeloid differentiation and additionally suggest a role for calcitriol in monocyte-macrophage activation.
LEGO-Boost: A Merged-Two-Stage Resonant-Switched-Capacitor Converter with High Voltage Conversion Ratio

This paper presents a family of merged-two-stage resonant-switched-capacitor boost converters with a Linear Extendable Group Operated Boost (LEGO-Boost) architecture. In the LEGO-Boost architecture, multiple resonant voltage doubler units are connected in parallel to interface with a high current input source; multiple switched-capacitor units are connected in series to interface with a high voltage output load. The operation of the resonant voltage doubler units and the switched-capacitor units are merged to create mutual advantages: the resonant voltage doubler units are used as current sources to soft-charge the series stacked switched-capacitor units and maintain voltage balancing; the stacked switched-capacitor units are used to multiply the voltage without charge sharing loss and switching loss (achieving soft-switching and soft-charging). All active switches in the LEGO-Boost architecture are configured as ground referenced half-bridge circuits. It offers advantages of high reliability, high scalability and low cost for applications such as grid-interface photovoltaic and fuel cell systems. The effectiveness of the LEGO-Boost architecture is verified by a 20 V-to-240 V 535 W (1:12 voltage conversion ratio) prototype with 94.2% peak efficiency and over 215 W/in3 power density.
Covariance distributions in single particle tracking

Several recent experiments, including our own experiments in the fission yeast, Schizosaccharomyces pombe, have characterized the motions of gene loci within living nuclei by measuring the locus position over time, then proceeding to obtain the statistical properties of this motion. To address the question of whether a population of such single-particle tracks, obtained from many different cells, corresponds to a single mode of diffusion, we derive theoretical equations describing the probability distribution of the displacement covariance, assuming the displacement itself is a zero-mean multivariate Gaussian random variable. We also determine the corresponding theoretical means, variances, and third central moments. Bolstering the theory is good agreement between its predictions and the results obtained for various simulated and measured data sets, including simulated particle trajectories undergoing simple and anomalous diffusion, and the measured trajectories of an optically trapped bead in water, and in a viscoelastic polymer solution. We also show that, for sufficiently long tracks, each covariance distribution in all of these examples is well-described by a skew-normal distribution with mean, variance, and skewness given by the theory. However, for the experimentally measured motion of a gene locus in S. pombe, we find that the first two covariance distributions are wider than predicted, although the third and subsequent covariance distributions are well-described by theory. This observation suggests that the origin of the theory-experiment discrepancy in this case is associated with localization noise, which influences only the first two covariances. Thus, we hypothesized that the discrepancy is caused by locus-to-locus heterogeneity in the localization noise, of independent measurements of the same tagged site. Indeed, simulations implementing heterogeneous localization noise revealed that the excess covariance widths can be largely recreated on the basis of heterogeneous noise. Thus, we conclude that the motion of gene loci in fission yeast is consistent with a single mode of diffusion.
Multiple Mutations in Mycobacterium tuberculosis MmpL3 Increase Resistance to MmpL3 Inhibitors.

ABSTRACT The Mycobacterium tuberculosis protein MmpL3 performs an essential role in cell wall synthesis, since it effects the transport of trehalose monomycolates across the inner membrane. Numerous structurally diverse pharmacophores have been identified as inhibitors of MmpL3 largely based on the identification of resistant isolates with mutations in MmpL3. For some compounds, it is possible there are different primary or secondary targets. Here, we have investigated resistance to the spiral amine class of compounds. Isolation and sequencing of resistant mutants demonstrated that all had mutations in MmpL3. We hypothesized that if additional targets of this pharmacophore existed, then successive rounds to generate resistant isolates might reveal mutations in other loci. Since compounds were still active against resistant isolates, albeit with reduced potency, we isolated resistant mutants in this background at higher concentrations. After a second round of isolation with the spiral amine, we found additional mutations in MmpL3. To increase our chance of finding alternative targets, we ran a third round of isolation using a different molecule scaffold (AU1235, an adamantyl urea). Surprisingly, we obtained further mutations in MmpL3. Multiple mutations in MmpL3 increased the level and spectrum of resistance to different pharmacophores but did not incur a fitness cost in vitro. These results support the hypothesis that MmpL3 is the primary mechanism of resistance and likely target for these pharmacophores. IMPORTANCEMycobacterium tuberculosis is a major global human pathogen, and new drugs and new drug targets are urgently required. Cell wall biosynthesis is a major target of current tuberculosis drugs and of new agents under development. Several new classes of molecules appear to have the same target, MmpL3, which is involved in the export and synthesis of the mycobacterial cell wall. However, there is still debate over whether MmpL3 is the primary or only target for these classes. We wanted to confirm the mechanism of resistance for one series. We identified mutations in MmpL3 which led to resistance to the spiral amine series. High-level resistance to these compounds and two other series was conferred by multiple mutations in the same protein (MmpL3). These mutations did not reduce growth rate in culture. These results support the hypothesis that MmpL3 is the primary mechanism of resistance and likely target for these pharmacophores.
How genetic disease risks can be misestimated across global populations

Background: Accurate assessment of health disparities requires unbiased knowledge of genetic risks in different populations. Unfortunately, most genome-wide association studies use genotyping arrays and European samples. Here, we integrate whole genome sequence data from global populations, results from thousands of GWAS, and extensive computer simulations to identify how genetic disease risks can be misestimated. Results: In contrast to null expectations, we find that risk allele frequencies at known disease loci are significantly different for African populations compared to other continents. Strikingly, ancestral risk alleles are found at 9.51% higher frequency in Africa and derived risk alleles are found at 5.40% lower frequency in Africa. By simulating GWAS with different study populations, we find that non-African cohorts yield disease associations that have biased allele frequencies and that African cohorts yield disease associations that are relatively free of bias. We also find empirical evidence that genotyping arrays and SNP ascertainment bias contribute to continental differences in risk allele frequencies. Because of these causes, polygenic risk scores can be grossly misestimated for individuals of African descent. Importantly, continental differences in risk allele frequencies are only moderately reduced if GWAS use whole genome sequences and hundreds of thousands of cases and controls. Finally, comparisons between uncorrected and corrected genetic risk scores reveal the benefits of considering whether risk alleles are ancestral or derived. Conclusions: Our results imply that caution must be taken when extrapolating GWAS results from one population to predict disease risks in another population.
Establishment, characteristics, and diagnostic uses of cell cultures derived from tissues of exotic species

Methods for the preparation, cultivation, preservation, and maintenance of serially passaged cell cultures derived from different tissues of exotic or threatened animals and certain species of birds are described. The diagnoses of viral pathogens affecting exotic and domestic species were enhanced by the availability of such cell or avian tracheal ring organ cultures to the veterinary diagnostic virology laboratory. Cell cultures from exotic species derived from tissues of bighorn sheep, white-tailed gnu, white-tailed deer, oryx, aoudad sheep, cockatiels, and ring-necked pheasants were developed or obtained by our laboratory. These cell cultures were examined for cellular morphology and growth characteristics at two different temperatures, presence of adventitious agents, and karyotype. Several of the exotic cell lines supported the replication of various viruses associated with avian and mammalian hosts. As comparison, cell cultures of domestic sheep were used. Tracheal ring organ cultures from chickens, turkeys, and pheasants were also assayed for their sensitivity to selected viruses. Cell cultures from exotic species may provide a viable alternative for the detection of viruses from such species which heretofore have been difficult to isolate using cell lines derived from domestic species.
SAVER: Gene expression recovery for UMI-based single cell RNA sequencing

Rapid advances in massively parallel single cell RNA sequencing (scRNA-seq) is paving the way for high-resolution single cell profiling of biological samples. In most scRNA-seq studies, only a small fraction of the transcripts present in each cell are sequenced. The efficiency, that is, the proportion of transcripts in the cell that are sequenced, can be especially low in highly parallelized experiments where the number of reads allocated for each cell is small. This leads to unreliable quantification of lowly and moderately expressed genes, resulting in extremely sparse data and hindering downstream analysis. To address this challenge, we introduce SAVER (Single-cell Analysis Via Expression Recovery), an expression recovery method for scRNA-seq that borrows information across genes and cells to impute the zeros as well as to improve the expression estimates for all genes. We show, by comparison to RNA fluorescence in situ hybridization (FISH) and by data down-sampling experiments, that SAVER reliably recovers cell-specific gene expression concentrations, cross-cell gene expression distributions, and gene-to-gene and cell-to-cell correlations. This improves the power and accuracy of any downstream analysis involving genes with low to moderate expression.
Non-Stochastic Information Theory

In an effort to develop the foundations for a non-stochastic theory of information, the notion of $\delta$-mutual information between uncertain variables is introduced as a generalization of Nair's non-stochastic information functional. Several properties of this new quantity are illustrated, and used to prove a channel coding theorem in a non-stochastic setting. Namely, it is shown that the largest $\delta$-mutual information between received and transmitted codewords over $\epsilon$-noise channels equals the $(\epsilon, \delta)$-capacity. This notion of capacity generalizes the Kolmogorov $\epsilon$-capacity to packing sets of overlap at most $\delta$, and is a variation of a previous definition proposed by one of the authors. Results are then extended to more general noise models, and to non-stochastic, memoryless, stationary channels. Finally, sufficient conditions are established for the factorization of the $\delta$-mutual information and to obtain a single letter capacity expression. Compared to previous non-stochastic approaches, the presented theory admits the possibility of decoding errors as in Shannon's probabilistic setting, while retaining a worst-case, non-stochastic character.
High incidence of adnexotropism in cytotoxic cutaneous lymphomas.

Background Primary cutaneous gamma-delta T-cell lymphoma (PCγδTCL) and primary cutaneous aggressive epidermotropic T-cell lymphomas (PCAETCL) are rare aggressive cytotoxic cutaneous lymphomas (CyCL) often difficult to diagnose. Histopathologically, PCAETCL and PCγδTCL may resemble mycosis fungoides (MF) and the presence of adnexotropism in CyCL (CyCL) contributes to this diagnostic challenge, especially in the setting of atypical and double-negative phenotypes. Methods In this retrospective study clinical data and histopathological section of 91 patients were analyzed for signs of clinical and histopathological signs adnexotropism. Results Adnexotropism was identified in 48.4% (44/91) of cases, including PCAETCL (40.9%, 18/44), PCγδTCL and cytotoxic cutaneous lymphomas, not otherwise specified (CyCTCL, NOS) (43.2%, 19/44 and 15.9%, 7/44). Comparison between disease-related mortality with Kaplan-Meier survival analysis of non-adnexotropic vs adnexotropic CyCL did not show any significant difference between the two groups (P = 0.8). Clinically they present with patches, plaques, and tumors and commonly with ulceration, but follicular prominence or alopecia are rare. Clinical signs of adnexotropism such as alopecia and hypo- or anhidrosis were rarely seen. Conclusion Adnexotropism is a common finding in CyCL, especially in PCAETCL. Adnexotropic CyCL may be histopathologically difficult to distinguish from folliculotropic mycosis fungoides. A comprehensive IHC panel should be routinely performed in such cases.
Navigating inclusion and legitimacy in campus-community environmental partnerships to advance urban social-ecological resilience

Campus-community partnerships can play a vital role in environmental education by providing universities opportunities to engage diverse communities, but challenges often emerge when research cente...
Rood, Ogden Nicholas 1831–1902

Ogden Nicholas Rood was an American physicist, best known for his work in color theory. He was a descendant of Scottish immigrants arriving in America in the seventeenth century and was born on February 3, 1831, in Danbury, CT. His father was an ordained minister [Rood in Modern chromatics with application to art and industry, Appleton & Co, New York 1879].
Probing Microbiome Genotoxicity: A Stable Colibactin Provides Insight into Structure-Activity Relationships and Facilitates Mechanism of Action Studies.

Colibactin is a genotoxic metabolite produced by commensal-pathogenic members of the human microbiome that possess the clb (aka pks) biosynthetic gene cluster. clb+ bacteria induce tumorigenesis in models of intestinal inflammation and have been causally linked to oncogenesis in humans. While colibactin is believed underlie these effects, it has not been possible to study the molecule directly due to its instability. Herein, we report the synthesis and biological studies of colibactin 742 (4), a stable colibactin derivative. We show that colibactin 742 (4) induces DNA interstrand-cross-links, activation of the Fanconi Anemia DNA repair pathway, and G2/M arrest in a manner similar to clb+E. coli. The linear precursor 9, which mimics the biosynthetic precursor to colibactin, also recapitulates the bacterial phenotype. In the course of this work, we discovered a novel cyclization pathway that was previously undetected in MS-based studies of colibactin, suggesting a refinement to the natural product structure and its mode of DNA binding. Colibactin 742 (4) and its precursor 9 will allow researchers to study colibactin's genotoxic effects independent of the producing organism for the first time.