cssi/SciSciGPT-SciSciNet huggingface dataset:
A look inside the diabetic brain: Contributors to diabetes-induced brain aging

Central nervous system (CNS) complications resulting from diabetes is a problem that is gaining more acceptance and attention. Recent evidence suggests morphological, electrophysiological and cognitive changes, often observed in the hippocampus, in diabetic individuals. Many of the CNS changes observed in diabetic patients and animal models of diabetes are reminiscent of the changes seen in normal aging. The central commonalities between diabetes-induced and age-related CNS changes have led to the theory of advanced brain aging in diabetic patients. This review summarizes the findings of the literature as they relate to the relationship between diabetes and dementia and discusses some of the potential contributors to diabetes-induced CNS impairments.
Projectile Identification and Impact Point Prediction

This paper presents a multiple model procedure to estimate the state of a ballistic object in the atmosphere and identify it using radar measurements for the purpose of impact point prediction (IPP). A key aspect of the projectile identification is the identification of the mode of stabilization used, i.e., fin stabilization or spin stabilization. Measurements are taken during the first part of its trajectory up to apogee, and the final state estimate obtained by the multiple model estimator is then predicted to its impact point on Earth. For each model a different extended Kalman filter (EKF) is used for state estimation, and the model likelihoods are then used to identify the projectile. It is shown from simulations carried out on three fin-stabilized projectile trajectories (mortars of different caliber) and a spin-stabilized (howitzer) projectile trajectory that the projectile can be identified with a high probability and also that the impact point is predicted to a high degree of accuracy and with a consistent covariance. It is also shown that accurate modeling of the gyroscopic effect caused by the spinning of the howitzer projectiles is critical for IPP accuracy in the case of spin-stabilized projectiles. The key in the design of the multiple model filter (MMF) is the choice of the models, which based on the characteristics of the different projectile trajectories, have different state dimensions. A choice has to be made between too few state components, which leads to poor accuracy/consistency, and too many state components, in which case the accuracy and discrimination ability suffers because of too much uncertainty in the model.
A novel approach for constant rate delivery of highly soluble bioactives from a simple monolithic system

A novel monolithic drug delivery system for highly water-soluble bioactive agents to follow pH-independent zero-order kinetics is described. The system utilizes a hydrophilic gel-based swellable polymeric material (polyethylene oxide), a model drug (metoprolol tartrate, 100% water soluble at 25 degrees C) and different electrolytes, such as sodium carbonate and/or pentasodium tripolyphosphate. Based on the induction of in situ intra-gel chemical reactions between different ionic species, drug and polymer, a heterogeneous structure manifested as 'peripheral boundary stiffening,' is accomplished. The consequence of these interactions essentially include the development of gradient-controlled matrix swelling as elucidated through textural profiling, which may contribute to inhibition of drug solubility and its outward diffusion. Analysis of textural profiles and photomicroscopy distinctly provides information on the disposition of peripheral boundary densification for the electrolyte-containing matrices. Electrolytic conductivity measurements performed with the simultaneous analysis of matrix swelling showed that sodium carbonate forms a highly reactive matrix within the first 3 h of medium penetration. On the other hand, larger molecules such as pentasodium tripolyphosphate maintain a constant conductivity level, which may be related to its lower solubility and diffusion in comparison to sodium carbonate. Based on model fitting and statistical analysis, it is shown that drug release kinetics were adequately described by M(t)/M(infinity)=k(0)t, with zero-order release rate constant k(0) of 0.054 h(-1). This novel approach in formulation development could potentially be used for constant rate delivery of highly soluble bioactive agents over an extended period for specific biopharmaceutical needs.
Delay fault testing and silicon debug using scan chains

This paper describes a novel technique to reuse the existing scanpaths in a chip for delay fault testing and silicon debug. Efficient test and debug techniques for VLSI chips are indispensable in Deep Submicron technologies. A systematic debug scheme is also necessary in order to reduce time-to-market. Due to stringent timing requirements of modern chips, test and debug schemes have to be tailored for detection and debug of functional defects as well as delay faults quickly and efficiently. The proposed technique facilitates an efficient scheme for detecting and debugging delay faults and has minimal area and power overhead.
Causes of proteolytic degradation of secreted recombinant proteins produced in methylotrophic yeast Pichia pastoris: Case study with recombinant ovine interferon‐τ

It was observed that during fermentative production of recombinant ovine interferon-tau (r-oIFN-tau) in Pichia pastoris, a secreted recombinant protein, the protein was degraded increasingly after 48 h of induction and the rate of degradation increased towards the end of fermentation at 72 h, when the fermentation was stopped. Proteases, whose primary source was the vacuoles, was found in increasing levels in the cytoplasm and in the fermentation broth after 48 h of induction and reached maximal values when the batch was completed at 72 h. Protease levels at various cell fractions as well as in the culture supernatant were lower when glycerol was used as the carbon source instead of methanol. It can be concluded that methanol metabolism along with cell lysis towards the end of fermentation contributes to increased proteolytic activity and eventual degradation of recombinant protein.
Escherichia coli serogroup O107/O117 lipopolysaccharide binds and neutralizes Shiga toxin 2.

The AB5 toxin Shiga toxin 2 (Stx2) has been implicated as a major virulence factor of Escherichia coli O157:H7 and other Shiga toxin-producing E. coli strains in the progression of intestinal disease to more severe systemic complications. Here, we demonstrate that supernatant from a normal E. coli isolate, FI-29, neutralizes the effect of Stx2, but not the related Stx1, on Vero cells. Biochemical characterization of the neutralizing activity identified the lipopolysaccharide (LPS) of FI-29, a serogroup O107/O117 strain, as the toxin-neutralizing component. LPSs from FI-29 as well as from type strains E. coli O107 and E. coli O117 were able bind Stx2 but not Stx1, indicating that the mechanism of toxin neutralization may involve inhibition of the interaction between Stx2 and the Gb3 receptor on Vero cells.
Serine proteases from two cell types target different components of a complex that governs regulated intramembrane proteolysis of pro‐σK during Bacillus subtilis development

Upon starvation Bacillus subtilis undergoes a developmental process involving creation of two cell types, the mother cell and forespore. A signal in the form of a serine protease, SpoIVB, is secreted from the forespore and leads to regulated intramembrane proteolysis (RIP) of pro-σK, releasing active σK into the mother cell. RIP of pro-σK is carried out by a membrane-embedded metalloprotease, SpoIVFB, which is inactive when bound by BofA and SpoIVFA. We have investigated the mechanism by which this complex is activated. By expressing components of the signalling pathway in Escherichia coli, we reconstructed complete inhibition of pro-σK RIP by BofA and SpoIVFA, and found that SpoIVB serine protease activity could partially restore RIP, apparently by targeting SpoIVFA. Pulse-chase experiments demonstrated that SpoIVFA synthesized early during B. subtilis sporulation is lost in a SpoIVB-dependent fashion, coincident with the onset of pro-σK RIP, supporting the idea that SpoIVB targets SpoIVFA to trigger RIP of pro-σK. Loss of BofA depended not only on SpoIVB, but also on CtpB, a serine protease secreted from the mother cell. CtpB appeared to cleave BofA near its C-terminus upon coexpression in E. coli, and purified CtpB degraded BofA. We propose that RIP of pro-σK involves a three-step proteolytic cascade in which SpoIVB first cleaves SpoIVFA, CtpB then cleaves BofA and finally SpoIVFB cleaves pro-σK.
Incremental Effects of Concurrent Pharmacotherapeutic Regimens for Heart Failure on Hospitalizations and Costs

BACKGROUNDInappropriate medication use in patients with heart failure (HF) presents challenges in providing optimal, evidence-based care.OBJECTIVETo evaluate the incremental differences of concurrent and persistent use of angiotensin-converting enzyme (ACE) inhibitors, β-blockers, loop diuretics, and digoxin on the one-year, all-cause risk of hospitalization and total healthcare costs associated with treatment of HF in patients enrolled in a managed care organization within the US.METHODSA retrospective database analysis was conducted spanning from January 1, 1997, to December 31, 1999. Multivariate regression methods were used to examine the association between treatment regimens and hospitalizations or costs after controlling for patient demographics and risk factors.RESULTSOf the 1903 patients meeting inclusion criteria, 32.3% (n = 615) received none of the 4 HF agents studied and were associated with a 2.5 times greater risk (p ≤ 0.001) of hospitalization and 43.6% higher (p ≤ 0.001) total costs compa...
Synergistic integration of dynamic cache reconfiguration and code compression in embedded systems

Optimization techniques are widely used in embedded systems design to improve overall area, performance and energy requirements. Dynamic cache reconfiguration is very effective to reduce energy consumption of cache subsystems which accounts for about half of the total energy consumption in embedded systems. Various studies have shown that code compression can significantly reduce memory requirements, and may improve performance in many scenarios. In this paper, we study the challenges and associated opportunities in integrating dynamic cache reconfiguration with code compression to retain the advantages of both approaches. Experimental results demonstrate that synergistic combination of cache reconfiguration and code compression can significantly reduce both energy consumption (65% on average) and memory requirements while drastically improve the overall performance (up to 75%) compared to dynamic cache reconfiguration alone.
How Are Sovereign Ratings Assigned

This chapter describes the rating process and emphasizes that CRAs have always used an analyst-driven approach to assign sovereign ratings.
Sequel to Liebowitz's Comment on the Oberholzer-Gee and Strumpf Paper on Filesharing

Through a stroke of luck, a referee report in the review process at the JPE has been positively identified as the Oberholzer-Gee/Strumpf (O/S) response to my earlier comment. Regardless of the response's provenance, what counts is whether it solidly refuted my comment. This 'sequel' analyzes the O/S response. The O/S response only deals with four of the nine points discussed in my comment, leaving the five remaining critiques unchallenged. The conclusion of my review is that the O/S response fails as a defense of these four points and contains many of the same types of errors that marred their original paper. This sequel also discusses the history of this dispute including O/S' various reasons for not making their data available. Finally, this sequel provides full documentation on the JPE's decision not to publish the comment.
What Is Backlog Is Prologue: A Measurement of Archival Processing

A numerical analysis of the processing of manuscript and archival materials was undertaken to develop baseline figures for planning and comparison. The time required for different segments of the processing activity was averaged and analyzed for all accessions within a given time period, with size and type introduced as variables. The analysis proved useful in planning staff responsibilities, processor assignments, budgets, and other management data. The feasibility and efficacy of word processing applied to the creation of finding aids was also tested. This survey serves as a starting point for archives searching for a methodology to measure the work of processing within their institutions, as a step towards the standardization needed for self-evaluation, and, perhaps, as a means of furthering cooperation among institutions.
Wafer Bonding for Micro-ElectroMechanical Systems (MEMS)

The wafer bonding technique was originally developed to produce SOI substrates, in which case hydrophilic oxide-to-oxide bonding is involved. Later on it became possible to bond other types of materials including bare (hydrogen terminated) silicon, compound semiconductors and nitride materials. Now wafer bonding is used to produce not only SOI substrates, but high-voltage silicon devices, optical devices, and micro-electromechanical systems. In this paper a review of the various processes for microfabrication of micro-electro-mechanical systems (MEMS) devices will reveal that silicon direct wafer (SDB) bonding combined with techniques such as bulk and surface micromachining, has added advantages for three-dimensional applications. We will report results showing that SDB can be used for the construction of complex structures. Furthermore, we will discuss the advantages of nitride bonding and present examples of practical applications utilizing this technique.
Phenomenology of the utilitarian supersymmetric standard model

Abstract We study the 2010 specific version of the 2002 proposed U ( 1 ) X extension of the supersymmetric standard model, which has no μ term and conserves baryon number and lepton number separately and automatically. We consider in detail the scalar sector as well as the extra Z X gauge boson, and their interactions with the necessary extra color-triplet particles of this model, which behave as leptoquarks. We show how the diphoton excess at 750 GeV, recently observed at the LHC, may be explained within this context. We identify a new fermion dark-matter candidate and discuss its properties. An important byproduct of this study is the discovery of relaxed supersymmetric constraints on the Higgs boson's mass of 125 GeV.
Photosensitization of Single-Crystal ZnO by a Conjugated Polyelectrolyte Designed to Avoid Aggregation

A conjugated polyelectrolyte (CPE) based on a poly(phenylene ethynylene) backbone designed to avoid interchain aggregation was adsorbed onto n-type zinc oxide (0001) single crystals. Photophysical, atomic force microscopy, and photoelectrochemical measurements confirm the absence of aggregation in solution and on ZnO single-crystal surfaces. At high surface coverage on the ZnO surface, individual polymer chains are resolved, and photocurrent efficiency measurements suggest that charge injection occurs with modest efficiency.
Allospecific CD154+ B cells associate with intestine allograft rejection in children.

Background. As a significant determinant of T- and B-cell cooperation, CD 154 has been used to identify allospecific T-cytotoxic memory cells (TcM) for rejection risk assessment with high sensitivity or specificity but not for alloreactive B-cells, especially among recipients predisposed to acute cellular and humoral rejection, that is, children with intestinal transplantation (ITx). Methods. Single blood samples from 32 pediatric ITx after lymphocyte depleting induction therapy were obtained within 30 days of protocol biopsies. Samples were assayed for allospecific CD154 + CD19 + B cells and allospecific CD154 + TcM in 16-hr live-cell mixed leukocyte reaction using multiparametric flow cytometry. Results were expressed as the immunoreactivity index ( IR) or the ratio of donor- to third-party-induced CD154 + B cells or TcM. The rejection threshold IR of B cells was determined by logistic regression, leave-one-out cross-validation, and receiver operating characteristic analyses. Results. Biopsy-proven acute cellular rejection was present in 15 subjects (rejectors) and absent in 17 (nonrejectors). In archived serum samples from 16 of 32 subjects donor-specific anti-HLA antibodies (DSA) were assayed by Luminex bead array. DSA were absent in all 7 nonrejectors but present in 7 of 9 rejectors. The IR of allospecific CD154 + CD19 + B cells more than or equal to 1.351 was associated with rejector status and was present in 13 of 15 rejectors (sensitivity 87%) and absent in 15 of 17 nonrejectors (specificity 88%). Excellent correlations were seen between CD154 + CD19 + B cells and CD154 + TcM (Spearman ρ=0.647, P=0.0001) but could not be tested independently for DSA, which was highly correlated with rejector status and with CD154 + TcM. Conclusions. Allospecific CD154 + CD19 + B cells identify rejection-prone children with ITx and can likely substitute for T-cell alloreactivity in estimating rejection risk in this rare subject population.
Reduction of the Incidence of Hospital Medical Disputes

Objective To reduce the incidence of hospital medical disputes.Method QC group activities.Result The incidence of hospital medical disputes was decreased from 0.2% to 0.09% after the event,which reached the target,improved patient satisfaction,and built a harmonious doctor- patient relationship.
Renal adaptation to dietary phosphate deprivation: role of proximal tubule brush-border membrane fluidity.

With dietary phosphate (Pi) restriction, fluidity of renal proximal tubule brush-border membranes (BBM) and Na-dependent Pi transport (Na-Pi) are increased, suggesting that changes in BBM fluidity are critical for adaptation to Pi restriction. To test this hypothesis, the temporal relationship between Na-Pi transport and changes in BBM fluidity was assessed after Pi deprivation in rats. Renal cortex was obtained from rats fed either a 0.03% (-P) or a 0.6% (+P) Pi diet for 4 h or 7 days, and BBM were prepared. Na-Pi uptake by BBM was measured by use of rapid filtration, and BBM fluidity was assessed by use of the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH). After 4 h on the diets, Na-Pi uptake was 439 +/- 142 (SD) and 984 +/- 184 pmol.mg protein-1.5 s-1 in +P and -P, respectively (P less than 0.01, n, = 8). Na-dependent proline uptake was unchanged. DPH anisotropy and total cholesterol were similar between groups: 0.204 +/- 0.025 and 0.401 +/- 0.047 nmol/mg protein, respectively, in +P and 0.205 +/- 0.015 and 0.392 +/- 0.037 in -P (P greater than 0.05, n = 8-10). After 7 days, Na-Pi uptake was 841 +/- 291 in +P and 2,168 +/- 848 pmol.mg protein-1.5 s-1 in -P, P less than 0.01, n = 8. DPH anisotropy and BBM cholesterol were 0.175 +/- 0.019 and 443 +/- 132 nmol/mg protein, respectively, in +P and 0.162 +/- 0.020 (n = 8) and 341 +/- 128 (n = 3) in -P (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
2007: The Adam Smith Address the Explanatory Power of Monetary Policy Rules

It is an honor to be here today to receive the Adam Smith Award, and it is a pleasure to give the Adam Smith Lecture. Everything I have read about Adam Smith tells me that he was passionate about his research and that his passion spilled over into his lectures. Many years ago,Woodrow Wilson wrote about Smith’s lecture style in his essay, The Old Master. As then Professor Wilson put it, “[Smith] constantly refreshed and rewarded his hearers … by bringing them to those clear streams of practical wisdom and happy illustration which everywhere irrigate his expositions.” You may have heard that Adam Smith would visit my introductory economics lectures at Stanford from time to time, interrupting me and speaking enthusiastically from the heavens. Well, it wasn’t really Adam Smith. It was my own recording of his voice piped through the lecture hall PA system. “Professor Taylor, Professor Taylor” the voice would say in an exasperated tone. “You told your students about economies of scale, and you didn’t even mention my famous story of the pin factory. Well let me tell them about it.” And then the students would listen to him reading out loud his famous, clear, practical story from the Wealth of Nations.
The Basic Brain: Grand Structures

Here I dive into the shallow end of brain study by introducing only those brain structures and functions that are impacted by stress and aging on the one hand, and by the various activities that toughen, on the other. Brain structures needed for the processing of inputs from our sensory systems, and those that operate our muscles will continue to thrive without our immediate attention.
Further evidence of reproductive immaturity among gynecologically young pregnant adolescents

Objective To obtain further information about the reproductive maturity of adolescents who become pregnant soon after menarche. We hypothesized that the length of the follicular phase of the menstrual cycle antedating conception is related inversely to the gynecological age of the adolescent mother at conception. Design Observational clinical study. Setting Pregnant volunteers in a multidisciplinary adolescent-oriented maternity program. Patients Pregnant adolescents with accurate pregnancy dating. Main Outcome Measure We studied the difference between the estimated date of confinement (EDC) computed from the stated last menstrual period (EDC lmp ) and the EDC computed from ultrasound studies (EDC us ) in a group of 66, 12 to 19year olds. A prolonged follicular phase was defined as EDC us −EDC lmp >0 and shortened follicular phase was defined as EDC us −EDC lmp ≤0. Results Pearson correlations revealed a statistically significant inverse relationship between gynecological age and the duration of the follicular phase antedating conception when the follicular phase was prolonged. Within this subgroup of patients EDC us exceeded EDC lmp by 15.6±7.3days when conception occurred within 3years of menarche and 6.2±6.0days when conception occurred ≥3years after menarche. Conclusions Our findings support the hypothesis that some adolescents conceive before establishing a fully mature adult ovulatory pattern.
Racial/ethnic differences in kindergartners' reading and math skills: Parents' knowledge of children's development and home‐based activities as mediators

Despite the growing body of research on parents' beliefs and practices, relatively little is known about the relations between parents' knowledge of children's development, home-based activities, and children's early reading and math skills. This study used data from the Early Childhood Longitudinal Study-Birth Cohort to examine the differences in Asian, Black, Latino, and White children's early reading and math skills at kindergarten entry and whether parents' knowledge of children's development and home-based activities mediate the relation. Parents' knowledge of children's development was assessed when children were 9 months. Home-based activities, including home literacy and enrichment, were assessed when children were preschool age. Asian and White children started kindergarten with significantly higher reading and math scores than Black or Latino children. There also were significant differences across groups in the frequency of engagement in home literacy and enrichment activities. Associations between race/ethnicity and reading/math scores were mediated by parents' knowledge of children's development and home literacy activities. Discussion addresses the importance of parents' knowledge of educationally relevant activities and how to engage in such activities to foster children's reading and math skills and to close racial/ethnic gaps. Highlights This paper examined racial/ethnic difference in children's reading and math skills in kindergarten and explores whether parents' knowledge of children's development and home-based activities mediate the relation between race/ethnicity and children's reading and math skills. By using data from the Early Childhood Longitudinal Study Birth Cohort, this study found that there were systematic racial/ethnic differences in parents' knowledge of children's development, home-based activities, and children's reading and math skills at the start of kindergarten. Parents' knowledge of children's development and home-based activities were found to mediate the association between race/ethnicity and children's reading and math skills for all groups.
Peripheral Nerve Stimulation

Peripheral nerve stimulation (PNS) best treats neuropathic pain localized to a specific nerve. Successful treatment of many conditions has been demonstrated: CRPS, headaches, cranial neuralgias, phantom limb pain, cancer pain, chronic pelvic pain, and coccydynia. PNS may be preferred over SCS if the painful area is small or if SCS lead placement will be difficult (e.g., in the patient with scoliosis). Patients must be carefully selected; they should have failed more conservative management. Contraindications included but are not limited to certain severe psychological comorbidities (e.g., substance abuse), severe coagulopathy, and infection, especially if close to the intended implantation site. In all cases, patients must first undergo a trial and show a 50 % reduction in pain or significant improvement in functional status. Targeted nerves include but are not limited to occipital, supraorbital, inguinal, and pudendal sites.
Affordability Challenges to Value-Based Pricing: Mass Diseases, Orphan Diseases, and Cures

Abstract Objectives To analyze how value-based pricing (VBP), which grounds the price paid for pharmaceuticals in their value, can manage "affordability" challenges, defined as drugs that meet cost-effectiveness thresholds but are "unaffordable" within the short-run budget. Methods Three specific contexts are examined, drawing on recent experience. First, an effective new treatment for a chronic, progressive disease, such as hepatitis C, creates a budget spike that is transitory because initial prevalence is high, relative to current incidence. Second, "cures" that potentially provide lifetime benefits may claim abnormally high VBP prices, with high immediate budget impact potentially/partially offset by deferred cost savings. Third, although orphan drugs in principle target rare diseases, in aggregate they pose affordability concerns because of the growing number of orphan indications and increasingly high prices. Results For mass diseases, the transitory budget impact of treating the accumulated patient stock can be managed by stratified rollout that delays treatment of stable patients and prioritizes patients at high risk of deterioration. Delay spreads the budget impact and permits potential savings from launch of competing treatments. For cures, installment payments contingent on outcomes could align payment flows and appropriately shift risk to producers. This approach, however, entails high administrative and incentive costs, especially if applied across multiple payers in the United States. For orphan drugs, the available evidence on research and development trends and returns argues against the need for a higher VBP threshold to incentivize research and development in orphan drugs, given existing statutory benefits under orphan drug legislation.
Decision Making Under Uncertainty

The ultimate goal of data processing is to make appropriate decisions. In this chapter, we analyze how different types of uncertainty affect our decisions. In Sects. 6.1 and 6.2, we consider decision making under interval uncertainty: the usual case of decision making is considered in Sect. 6.1, and the case of decision making in conflict situations is analyzed in Sect. 6.2. In Sect. 6.3, we consider decision making under probabilistic uncertainty and in Sect. 6.4, we consider the case of general uncertainty.
Altered Left-Ventriculoarterial Coupling in Mitral Regurgitation

Twenty-nine control patients and 41 patients with long-term mitral regurgitation were studied, using micromanometer left-ventricular catheters and radionuclide angiography, to test the hypothesis that the low-impedance left atrium obscures an impairment in left-ventriculoarterial coupling and forward left-ventricular pump efficiency in patients with long-term mitral regurgitation. Left-ventriculoarterial coupling relationships were calculated in patients with long-term mitral regurgitation both before mitral valve surgery at baseline and during steady-state vasodilation and at 1 year following successful mitral valve surgery. The data indicate that, although total left-ventricular stroke work is performed efficiently by coupling of the left ventricle to both the arterial and atrial systems, left-ventricular pump efficiency for performing forward left-ventricular stroke work is impaired, despite preservation of normal forward left-ventricular stroke work. This impairment occurs in patients with long-term mitral regurgitation and a normal left-ventricular ejection fraction as the result of impairment of contractility coupled with a normal total arterial elastance. Acute vasodilation did not significantly improve this impairment in leftventriculoarterial coupling and pump efficiency. In contrast, successful mitral valve surgery improves forward left-ventricular stroke work and pump efficiency because of recovery of left-ventricular contractility. One potential mechanism for this reversible impairment of left-ventricular contractility is proposed. In conclusion, left-ventricular pump efficiency for performing forward stroke work is impaired in patients with long-term mitral regurgitation, despite the outward appearance of normal left-ventricular ejection performance manifest by a normal ejection fraction. This probably results from coupling of the left ventricle to both the arterial and atrial systems. Consequently, the clinical implication of these data is that mitral valve surgery, particularly mitral valve repair, should be considered earlier in these patients when left-ventricular contractility is reversible and pump efficiency can be returned to normal.
Bierman et al. Reply

reply to the Comment by C.H.Dasso et al., Phys. Rev. Lett. 78,XXX(1997). A Reply to the Comment by C.H. Dasso and J. Fern{acute a}ndez-Niello. {copyright} {ital 1997} {ital The American Physical Society}
The middle cranial base and cavernous sinus

The middle cranial base can be divided into a medial portion, the sellar and the parasellar region, where the pituitary gland and cavernous sinus are located and a lateral portion, containing the middle cranial fossa and the upper surface of the temporal bone (Fig. 1). The focus of this paper is the cavernous sinus and adjacent parts of the middle cranial fossa [22, 23].
Molecular Analysis of Pathogenicity Specific Genes in PseudomonasSyringae Pv. Syringae

Two Tn5 generated non-pathogenic mutants of Pseudomonas syringae pv. syringae strain B728a have been isolated. Both mutants (designated as NPS3136 and NPS3139) grow to the same extent as the parental strain either epiphytically on leaves or intercellularly within the leaf tissue of bean. However, NPS3136 and NPS3139 fail to elicit any disease symptoms on either the pods or leaves of bean cultivars (Phaseolus vulgaris) which are susceptible to wild-type parental strain B728a. These mutants still produce the typical hypersensitive response (HR) shown by the parent strain when infiltrated into the leaves of tobacco. When infiltrated into bean pods, NPS3136 and NPS3139 exhibit a slow necrotic response (3–5 d) that is distinct from the fast HR (20–36 h) show by heterologous (non-pathogenic on bean) P. s. pv syringae strains.
Wildlife Responses to Urbanization: Patterns of Diversity and Community Structure in Built Environments

As the study of biodiversity, the field of community ecology seeks to understand what factors govern the formation and maintenance of multispecies assemblages (i.e., how and why certain species coexist). The structure of communities is described by their diversity—comprised of richness (number of species present) and evenness (the relative abundance of each species)—and interactions among the constituent species. Communities are biotic components within ecosystems, and because cities can be viewed as an ecosystem (albeit one characterized by high-density human habitation and built structure), understanding how wildlife responds to the ever-increasing scope of urban development makes urban-community ecology an important component of contemporary wildlife science.
SliC is a surface-displayed lipoprotein that is required for the anti-lysozyme strategy during Neisseria gonorrhoeae infection

Lysozymes are nearly omnipresent as the first line of immune defense against microbes in animals. They exert bactericidal action through antimicrobial peptide activity and peptidoglycan hydrolysis. Gram-negative bacteria developed several weapons to battle lysozymes, including inhibitors of c-type lysozymes in the MliC/PliC family and the Neisseria adhesin complex protein (ACP). Until the recent discovery of ACP, no proteinaceous lysozyme inhibitors were reported for the genus Neisseria, including the important human pathogen N. gonorrhoeae. Here, we describe a previously unrecognized gonococcal virulence mechanism involving a protein encoded by the open reading frame ngo1063 that acts to counteract c-type Iysozyme and provides a competitive advantage in the murine model of gonorrhea. We named this protein SliC as a surface-exposed lysozyme inhibitor of c-type lysozyme. SliC displays low overall primary sequence similarity to the MliC/PliC inhibitors, but we demonstrate that it has a parallel inhibitory mechanism. Our studies provide the first evidence that bacterial proteinaceous lysozyme inhibitors protect against host lysozyme during infection based on lack of attenuation of the ΔsliC mutant in lysozyme knock-out mice, and that the conserved residues involved in lysozyme inhibition, S83 and K103, are functionally indispensable during infection in wild type mice. Recombinant SliC completely abrogated the lytic activity of human and chicken c-type lysozymes, showing a preference towards human lysozyme with an IC50 of 1.85 μM and calculated KD value of 9.2 ± 1.9 μM. In contrast, mutated SliC bearing S83A and K103A substitutions failed to protect fluorescein-labeled cell-wall from lysozyme-mediated hydrolysis. Further, we present data revealing that SliC is a surface-displayed lipoprotein released in membrane vesicles that is expressed throughout all phases of growth, in conditions relevant to different niches of the human host, and during experimental infection of the murine genital tract. SliC is also highly conserved and expressed by diverse gonococcal isolates as well as N. meningitidis, N. lactamica, and N. weaveri. This study is the first to highlight the importance of an anti-lysozyme strategy to escape the innate immune response during N. gonorrhoeae infection.
A Novel Engineered Small Protein for Positron Emission Tomography Imaging of Human Programmed Death Ligand-1 : Validation in Mouse Models and Human Cancer Tissues

Purpose: To design and evaluate a small engineered protein binder targeting human programmed death-1 ligand (hPD-L1) in vivo for PET imaging in four mouse tumor models, and in situ in human cancer specimens. Experimental Design: The hPD-L1 protein binder, FN3hPD-L1, was engineered using a 12-kDa human fibronectin type-3 domain (FN3) scaffold. The binder9s affinity was assayed in CT26 mouse colon carcinoma cells stably expressing hPD-L1 (CT26/hPD-L1). 64Cu-FN3hPD-L1 was assayed for purity, specific activity, and immunoreactivity. Four groups of NSG mice (n = 3–5/group) were imaged with 64Cu-FN3hPD-L1 PET imaging (1–24 hours postinjection of 3.7 MBq/7 μg of Do-FN3 in 200 μL PBS): Nod SCID Gamma (NSG) mice bearing (i) syngeneic CT26/hPD-L1tumors, (ii) CT26/hPD-L1 tumors blocked (blk) by preinjected nonradioactive FN3hPD-L1 binder, (iii) hPD-L1-negative Raji xenografts, and (iv) MDA-MB-231 xenografts. The FN3hPD-L1 binder staining was evaluated against validated hPD-L1 antibodies by immunostaining in human cancer specimens. Results: FN3hPD-L1 bound hPD-L1 with 1.4 ± 0.3 nmol/L affinity in CT26/hPD-L1 cells. 64Cu-FN3hPD-L1 radiotracer showed >70% yield and >95% purity. 64Cu-FN3hPD-L1 PET imaging of mice bearing CT26/hPD-L1 tumors showed tumor-to-muscle ratios of 5.6 ± 0.9 and 13.1 ± 2.3 at 1 and 4 hours postinjection, respectively. The FN3hPD-L1 binder detected hPD-L1 expression in human tissues with known hPD-L1 expression status based on two validated antibodies. Conclusions: The 64Cu-FN3hPD-L1 radiotracer represents a novel, small, and high-affinity binder for imaging hPD-L1 in tumors. Our data support further exploration and clinical translation of this binder for noninvasive identification of cancer patients who may respond to immune checkpoint blockade therapies.
Acute toxic and genotoxic effects of formalin in Danio rerio (zebrafish)

Formalin is a readily soluble chemical used as a sanitizing agent in the home and hospital. Formaldehyde solutions are routinely used in aquaculture for the prophylaxis and treatment of parasites and fungi, but the adverse effects of their application need to be further investigated. Danio rerio or zebrafish has characteristics favorable to its handling and breeding, and it is highly sensitive to various chemicals, being an ideal experimental model for this type of investigation. Thus, the objective of this study was to verify the toxic and genotoxic effects of formalin and to determine the lethal concentrations of this chemical to support its safe use in disinfection processes. Acute and chronic tests were performed using methods in accordance with international protocols. The genotoxic effect of formalin was evaluated with the micronucleus test using blood samples, which were collected at 96 and 192 h of exposure. The LC50–96h of formalin in D. rerio was 45.73 mg L−1, demonstrating its high resistance compared to other species. Regarding the genotoxic effect, the sublethal concentrations of formalin showed a positive correlation with micronuclei according to the increase in its concentration independent of the time of exposure. The incidence of micronuclei increased with concentration, and the addition of 1 mg L−1 formalin corresponded to an increase of 2.9% in the average number of micronuclei. In other words, formalin at even sublethal concentrations caused genotoxic effects in peripheral blood erythrocytes of D. rerio. Therefore, we recommend further studies and other tests involving this chemical for its use at environmentally safe concentrations.
Applied Resiliency and Suicide Prevention: A Strengths-Based, Risk-Reduction Framework

In this volume, our contributing experts have described the potential application of positive psychological constructs to the prevention of suicide, melding together the two seemingly disparate fields of positive psychology and suicidology. Using a framework of applied resiliency, this new field of Positive Suicidology stands in contrast to traditional deficit-oriented therapeutic and research approaches, with its emphasis on strengths, virtues, and adaptivity. Comprising classic topics such as reasons for living and social support, as well as the modern perspectives of gratitude, forgiveness, and mindfulness, we have posited Positive Suicidology as a new paradigm for suicide prevention and intervention, including as a proactive and preemptive public health strategy. Thematic patterns emerged from our exploration, suggesting that protection from suicide is multi-faceted, involving interpersonal and intrapersonal well-being, but also existential health and temporal balance. Our authors address theoretical and research support for an array of positive psychological factors found to reduce suicide risk, and discuss strategies for their clinical application, including therapies based on future orientation, mindfulness, and meaning-making. Future longitudinal research is needed on these and additional positive psychological factors, such as humor and grit, including in clinical samples, to insure the strengths-based approach we are advocating is efficacious. Overall, Positive Suicidology seems to be a necessary approach to suicide prevention, given that many of its primary constructs are overlooked in traditional therapeutic approaches, despite burgeoning empirical evidence, person-centered appeal, and the potential to improve well-being and prevent suicide.
An Effective Model of Mentorship and Capacity Building: Lessons Learned and Lived Out at a Midwest AANAPISI

This chapter shares the experiences of a Puerto Rican dean of a school of urban education and the experiences of a Korean department chair, both working at a Midwest Asian American Native American Pacific Islander-Serving Institution (AANAPISI). They share stories and experiences which are situated within the context of this AANAPISI as well as the literature on higher education leadership in Minority-Serving Institutions (MSIs). The chapter shares a model of mentorship that builds the capacity of diverse leaders within the School of Urban Education.
Accuracy assessment of MODIS land aerosol optical thickness algorithms using AERONET measurements over North America

Abstract. The planned simultaneous availability of visible and near-IR observations from the geostationary platforms of Tropospheric Emissions: Monitoring of Pollution (TEMPO) and Geostationary Operational Environmental Satellites (GOES) 16/17 Advanced Base Imager (ABI) will present the opportunity of deriving an accurate aerosol product taking advantage of both ABI's high spatial resolution in the visible range and TEMPO's sensitivity to aerosol absorption in the near-UV range. Because the wavelengths of ABI are similar to those of the Moderate Resolution Imaging Spectroradiometer (MODIS), existing aerosol algorithms of MODIS can be applied to ABI observations. In this work, we evaluate three distinct aerosol algorithms of MODIS deriving aerosol optical thickness (AOT) over land surfaces using visible and near-IR observations. The Dark Target (DT), Deep Blue (DB), and Multiangle Implementation of Atmospheric Correction (MAIAC) algorithms are all applied to the radiance measurements of MODIS on board the Aqua satellite. We have evaluated each algorithm by comparing the satellite-retrieved AOT to space-time collocated ground-based sun photometer measurements of the same parameter at 171 sites of the Aerosol Robotic Network (AERONET) over North America (NA). A spatiotemporal scheme collocating the satellite retrievals with the ground-based measurements was applied consistently to all three retrieval datasets. We find that the statistical performance of all three algorithms is comparable over darker surfaces over eastern NA with the MAIAC algorithm providing relatively better comparison over western NA sites characterized by inhomogeneous elevation and bright surfaces. The higher spatial resolution of the MAIAC product (1 km) allows a substantially larger number of matchups than DB 10 km and DT 10 km (DT 3 km) products by 115 % and 120 % (86 %), respectively, over eastern NA and by 150 % and 220 % (197 %) over western NA. The characterization of the error in AOT for the three aerosol products as a function of bidirectional surface reflectance derived from both MAIAC and an independent MOD09 atmospheric correction shows a systematic positive bias in DT retrievals over brighter surfaces, whereas DB and MAIAC retrievals show no such bias throughout the wide range of surface brightness, with MAIAC offering the lowest spread in errors. The results reported here represent an objective, unbiased evaluation of existing over-land aerosol retrieval algorithms of MODIS. The detailed statistical evaluation of the performance of each of these three algorithms may be used as guidance in the development of inversion schemes to derive aerosol properties from ABI or other MODIS-like sensors.
Time resolved irradiance of an integrating sphere illuminated by a mode-locked optical parametric oscillator

Tunable laser based illumination sources have been adopted by a number of recent hyperspectral instruments for pre-launch spectral radiometric calibration. Some of these sources use mode-locked cavity configurations, which produce a pulse train and create an undesirable fluctuation in the radiometric source at the mode locking frequency. Although typically this frequency is several orders of magnitude higher than the instrument response, care must be taken to ensure the resultant calibration is not biased due to detector or electronic saturation effects. The temporal averaging properties of an integrating sphere can be used to reduce high frequency fluctuations to an acceptable level. In this work, the time resolved output of an integrating sphere coupled with a mode-locked source was measured. A 76 cm diameter sphere with 30 cm output aperture was illuminated using a mode-locked pulse train at 76 MHz, with single pulse durations of 12 ps. The time constant of the sphere was found to be 36 ns, and the resultant temporal averaging of pulses produced a maximum time varying irradiance at the output of 20% of the mean. The form of this time variance is a sawtooth pattern, with a sharp rise during the introduction of each pulse into the sphere followed by a slower decay between pulses. A comparison of instrument calibration data generated with this integrating sphere using both a mode locked source and a continuous wave source is also given. .
Confusion vs Broca Aphasia: A Case Report.

Introduction Broca aphasia presents with impaired expression of spoken and/or written language and is often caused by infarction in the Broca area in the frontal lobe. We present a case of Broca aphasia that was initially interpreted as confusion. Case presentation A 76-year-old woman was brought to the Emergency Department because of confusion and slurred speech that began in the morning. The patient had an extensive history of alcohol abuse, hyperlipidemia, and hypertension and had recently quit drinking 5 days earlier. The patient appeared confused, answering questions with "I don't know," but had no signs of agitation. Magnetic resonance imaging of the brain confirmed a recent infarct involving the left frontal and occipital lobes, coinciding with the Broca area. The patient was able to communicate via writing and eventually made an uneventful recovery of speech. Discussion This case demonstrates a patient without the display of stereotypical signs of stroke, yet that was the underlying condition leading to her aphasia. It is important for clinicians to be aware that a stroke can present with isolated findings such as language deficit or confusion.
Multi-Well Avalanche Selenium Detector for Time-of-Flight PET

For the first time, we propose using amorphous selenium (a-Se) as the photoconductive material for time-of-flight (TOF) PET detectors. One major drawback of a-Se is its poor timing jitter stemming from low carrier mobility due to shallow-traps, a problem that must be circumvented for TOF applications. Thus, we propose using a nanopattern multi-well selenium detector that enables both avalanche multiplication gain and ultrafast charge sensing in one device. We’ve previously shown the capabilities of our avalanche mode multi-well selenium detector, which has a large active area, impact ionization avalanche gain and timing jitter on the order of 100 ps. Using Cramer-Rao Lower Bound analysis in conjunction with experimental measurements, we calculate the lower bound on coincidence time resolution for our selenium photodetector and compare it with that of the current state-of-the-art TOF-PET photodetectors. Our results show that our multi-well selenium detector is a promising candidate to achieve 100 ps coincidence time resolution in TOF-PET using standard-sized scintillator crystals with a photodetector that is cost-effective and uniformly scalable to large area.