cssi/SciSciGPT-SciSciNet huggingface dataset:
A review of avelumab in locally advanced and metastatic bladder cancer

Urothelial carcinoma remains a devastating disease with a poor prognosis. Though immune therapy with Bacillus Calmette-Guerin (BCG) has been used for localized bladder cancer for years, only immune-checkpoint blockade with antiprogrammed cell-death 1 (anti-PD-1) and antiprogrammed cell-death ligand 1 (anti-PD-L1) inhibitors have demonstrated improvement in survival of patients with metastatic disease. Anti-PD-L1 antibody, avelumab, was recently given United States Food and Drug Administration (FDA) accelerated approval for the treatment of recurrent/metastatic urothelial carcinoma after failure of first-line chemotherapy, marking the fifth immune checkpoint inhibitor to be given FDA approval for the treatment of metastatic urothelial cancer. The following manuscript will review avelumab, its pharmacology, and the clinical experience that has led to its approval, as well as future plans for clinical development of avelumab for the treatment or urothelial cancer.
Hypoxia tolerance of giant axon-mediated escape jetting in California market squid (Doryteuthis opalescens)

ABSTRACT Squids display a wide range of swimming behaviors, including powerful escape jets mediated by the giant axon system. For California market squid (Doryteuthis opalescens), maintaining essential behaviors like the escape response during environmental variations poses a major challenge as this species often encounters intrusions of cold, hypoxic offshore waters in its coastal spawning habitats. To explore the effects of hypoxia on locomotion and the underlying neural mechanisms, we made in vivo recordings of giant axon activity and simultaneous pressure inside the mantle cavity during escape jets in squid exposed to acute progressive hypoxia followed by return to normal dissolved oxygen (DO) concentration (normoxia). Compared with those in normoxia (>8 mg l−1 DO), escape jets were unchanged in moderate hypoxia (4 and 2 mg l−1 DO), but giant axon activity and associated mantle contractions significantly decreased while neuromuscular latency increased under severe hypoxia (0.5 mg l−1 DO). Animals that survived exposure to severe hypoxia reliably produced escape jets under such conditions and fully recovered as more oxygen became available. The reduction in neuromuscular output under hypoxia suggests that market squid may suppress metabolic activity to maintain sufficient behavioral output, a common strategy in many hypoxia-tolerant species. The ability to recover from the deleterious effects of hypoxia suggests that this species is well adapted to cope with coastal hypoxic events that commonly occur in Monterey Bay, unless these events become more severe in the future as climate change progresses.
Genomic Sequencing for Infants and Children in Intensive Care Units

We highlight the evolving clinical application of genomic sequencing in caring for critically ill infants and children in the intensive care unit. As turnaround times for genetic sequencing continue to decrease, the application of this technology in caring for critically ill infants and children has correspondingly increased. Not only are clinicians now using genetic sequencing to make formal diagnoses in medically complex patients, but they are also using this information to inform recommendations regarding potential treatments and anticipate patient outcomes. Importantly, its application not only stands to impact clinical care, but may also streamline health care utilization. Genomic sequencing is a powerful technology with clear clinical application in the neonatal and pediatric ICU settings. In addition to aiding in the diagnostic evaluation of critically ill children with suspected monogenic disorders, it has a clear impact on clinical decision-making and can improve family-centered care.
SEQUENCES OF SV40 DNA

We have determined nucleotide sequences of large regions of SV40 DNA including those spanning the 3′ ends and 5′ ends of “early” and “late” mRNA and the region in which DNA replication begins. The sequences indicate that several percent of the viral genome is untranslated. These untranslated regions contain curious features such as a region of partial homology between the 3′ sequences of SV40 and the 3′ terminal sequences reported for rabbit hemoglobin B chain mRNA, symmetric sequences at or near the origin of DNA replication, and some prominent repeats, including an identical repeat of 21 nucleotides near the origin of DNA replication. Stretches of 6 or more deoxyadenylic acids in the DNA appear to be preferentially located on the strand whose transcript is not represented in stable mRNA and occur near the 3′ and 5′ ends of both “early” and “late” mRNA.
A Paging Training Program for a Fourth-Year Internship Readiness Course.

Introduction New medical interns face a steep learning curve as they must manage complex medical scenarios, many of which they have only seen before in a classroom setting. To ameliorate these chal...
Influence factors analysis of ionized field characteristics of Zhangbei ±500kV flexible direct current transmission lines

The ionized field should be controlled in order to insure the environmental friendliness of high voltage direct current (HVDC) transmission lines. Different with traditional HVDC transmission lines, the metal return lines is first employed in Zhangbei ±500kV flexible HVDC lines. In this paper, the characteristics of ionized field with and without metal return lines are calculated on the basis of numerical method with Deutsch’s assumption. The influence factors, i.e. roughness coefficient, distance between metal return line and height of the metal return line, are analysed in detail. The results show that the metal return lines will have a shield effect on the ionized field on the ground. The distribution of ionized field is nearly independent on the height of metal return line. The shielding effect of the metal return line mainly contributes to the projection position of the metal return line. The presented results can give instructions for the design and control of the ionized field level of flexible HVDC lines with metal return lines.
The Role of Prāṇa in Sāṃkhya Discipline for Freedom

Classical Sāṃkhya has usually been interpreted as an intellectualist school. Its presumed method for the attainment of liberation is essentially characterized by rational inquiry into reality, which involves the intellectual understanding of the distinction between two principles: the conscious and the material. Some have argued that this liberating process is not only theoretical, but that it entails yogic practice, or that it is the natural outcome of existential forces that tend toward freedom. However, recent studies in Sāṃkhya involving detailed analysis of an anonymous commentary of the Sāṃkhyakārikā, the Yuktidīpikā, suggest a more complex picture. The external functions of the five vital winds (prāṇas) in relation to the sources of action (karmayonis) and dispositions of being (bhāvas) seem to play an important role in the liberating path. In this paper, I review the relation between bhāvas, karmayonis, and the five prāṇas by considering the social, moral, and interpersonal aspects of the five vital winds as described in the Yuktidīpikā. It will be shown how the external functions of prāṇa are related to the moral cultivation of vitality, leading to the enactment and manifestation of dispositions of being (bhāvas) that bring about the realization of oneself as a knower in the ethical engagement with others. It is this unique way of understanding prāṇa in the Yuktidīpikā that makes the Sāṃkhya path for liberation something more than a theoretical cognitive method or a spontaneous and predetermined realization of one’s self.
What Is the 30-Day Mortality Burden After Elective Total Hip Arthroplasty? An Analysis of 194,062 Patients

Abstract Background This study aims to answer the following questions regarding elective total hip arthroplasty (THA): What is (1) the overall 30-day mortality rate; (2) the mortality rate when stratified by age, comorbidities, and preoperative diagnosis; and (3) the distribution of patient demographics, comorbidities, and preoperative diagnoses between the mortality and mortality-free cohorts? Methods The American College of Surgeons National Surgical Quality Improvement Program database was reviewed for all patients undergoing elective primary THA (2011-2018). A total of 194,062 patients were categorized based on the incidence of 30-day mortality (mortality: n = 206 vs mortality-free: n = 193,856). Patient demographics, comorbidities, and preoperative diagnosis (osteoarthritis [OA] vs non-OA) were recorded. Age category, American Society of Anesthesiologists (ASA) score, and modified Charlson Comorbidity Index (CCI) scores were normalized per 1000 and stratified by preoperative diagnosis. Results The 30-day mortality rate was 0.11%. The percentage of deaths per age group (normalized per 1000) was 0% (18-29 years), 0% (30-39 years), 0.049% (40-49 years), 0.052%(50-59 years), 0.071% (60-69 years), 0.133% (70-79 years), and 0.352% (80-89 years). The percentage of deaths per ASA score was 0% (ASA I), 0.035% (ASA II), 0.174% (ASA III), and 1.008% (ASA IV). The percentage of deaths per CCI score was 0.09% (CCI = 0), 0.23% (CCI = 1), 0.74% (CCI = 2), 3.21% (CCI = 3), 4.76% (CCI = 4), and 0.57% (CCI ≥ 5). Non-OA diagnoses were significantly more frequent in the mortality cohort (16.0% vs 7.6%; P Conclusion The risk of mortality was highest in patients aged 80-89, patients of ASA class IV, patients with a CCI score of 4, and patients with a non-OA diagnosis. The overall rate of death was higher in the non-OA cohort compared to the OA cohort. Level of Evidence III.
Role of dipA and pilD in Francisella tularensis Susceptibility to Resazurin

The phenoxazine dye resazurin exhibits bactericidal activity against the Gram-negative pathogens Francisella tularensis and Neisseria gonorrhoeae. One resazurin derivative, resorufin pentyl ether, significantly reduces vaginal colonization by Neisseria gonorrhoeae in a mouse model of infection. The narrow spectrum of bacteria susceptible to resazurin and its derivatives suggests these compounds have a novel mode of action. To identify potential targets of resazurin and mechanisms of resistance, we isolated mutants of F. tularensis subsp. holarctica live vaccine strain (LVS) exhibiting reduced susceptibility to resazurin and performed whole genome sequencing. The genes pilD (FTL_0959) and dipA (FTL_1306) were mutated in half of the 46 resazurin-resistant (RZR) strains sequenced. Complementation of select RZR LVS isolates with wild-type dipA or pilD partially restored sensitivity to resazurin. To further characterize the role of dipA and pilD in resazurin susceptibility, a dipA deletion mutant, ΔdipA, and pilD disruption mutant, FTL_0959d, were generated. Both mutants were less sensitive to killing by resazurin compared to wild-type LVS with phenotypes similar to the spontaneous resazurin-resistant mutants. This study identified a novel role for two genes dipA and pilD in F. tularensis susceptibility to resazurin.
Analysis of six tonB gene homologs in Bacteroides fragilis revealed that tonB3 is essential for survival in experimental intestinal colonization and intra-abdominal infection.

The opportunistic, anaerobic pathogen and commensal of the human large intestinal tract, Bacteroides fragilis strain 638R, contains six predicted TonB proteins, termed TonB1-6, four ExbBs orthologs, ExbB1-4, and five ExbDs orthologs, ExbD1-5. The inner membrane TonB/ExbB/ExbD complex harvests energy from the proton motive force (Δp) and the TonB C-terminal domain interacts with and transduces energy to outer membrane TonB-dependent transporters (TBDTs). However, TonB's role in activating nearly one hundred TBDTs for nutrient acquisition in B. fragilis during intestinal colonization and extraintestinal infection has not been established. In this study, we show that growth was abolished in the ΔtonB3 mutant when heme, vitamin B12, Fe(III)-ferrichrome, starch, mucin-glycans, or N-linked glycans were used as a substrate for growth in vitro. Genetic complementation of the ΔtonB3 mutant with the tonB3 gene restored growth on these substrates. The ΔtonB1, ΔtonB2, ΔtonB4, ΔtonB5, and ΔtonB6 single mutants did not show a growth defect. This indicates that there was no functional compensation for the lack of TonB3, and it demonstrates that TonB3, alone, drives the TBDTs involved in the transport of essential nutrients. The ΔtonB3 mutant had a severe growth defect in a mouse model of intestinal colonization compared to the parent strain. This intestinal growth defect was enhanced in the ΔtonB3 ΔtonB6 double mutant strain which completely lost its ability to colonize the mouse intestinal tract compared to the parent strain. The ΔtonB1, ΔtonB2, ΔtonB4, and ΔtonB5 mutants did not significantly affect intestinal colonization. Moreover, the survival of the ΔtonB3 mutant strain was completely eradicated in a rat model of intra-abdominal infection. Taken together, these findings show that TonB3 was essential for survival in vivo. The genetic organization of tonB1, tonB2, tonB4, tonB5, and tonB6 gene orthologs indicates that they may interact with periplasmic and nonreceptor outer membrane proteins, but the physiological relevance of this has not been defined. Because anaerobic fermentation metabolism yields a lower Δp than aerobic respiration and B. fragilis has a reduced redox state in its periplasmic space - in contrast to an oxidative environment in aerobes - it remains to be determined if the diverse system of TonB/ExbB/ExbD orthologs encoded by B. fragilis have an increased sensitivity to PMF (relative to aerobic bacteria) to allow for the harvesting of energy under anaerobic conditions.
Phase Reversal in OHC Response at High Sound Intensities

Kiang and his associates (e.g. Kiang, 1984) discovered an enigmatic phase shift of about 180° occurring in responses of auditory-nerve fibers at high sound intensities. One of us has demonstrated with the help of an electrical-network model that the phase shift can result from a nonlinear mechanical coupling between the tectorial membrane and the organ of Corti (Zwislocki, 1986). The associated distortion pattern produced by the model is essentially the same as found by Kiang’s group.
Subtyping for f-bounded quantifiers and equirecursive types

Equirecursive types consider a recursive type to be equal to its unrolling and have no explicit term-level coercions to change a term's type from the former to the latter or vice versa. This equality makes deciding type equality and subtyping more difficult than the other approach--isorecursive types , in which the types are not equal, but isomorphic, witnessed by explicit term-level coercions. Previous work has built intuition, rules, and polynomial-time decision procedures for equirecursive types for first-order type systems. Some work has been done for type systems with parametric polymorphism, but that work is incomplete (see below). This chapter will give an intuitive theory of equirecursive types for second-order type systems, sound and complete rules, and a decision procedure for subtyping.
A diagnosability metric for parametric path delay faults

Published research on delay fault testing has largely focused on generating a minimal set of test vector pairs to detect as many delay faults in a circuit as possible. Little regard has been paid to the diagnosability of delay faults in the quest for generating tests which can simultaneously detect a delay fault on many paths, one loses the ability to determine which paths caused a chip failure. In an earlier work [1996] we presented a framework to detect which paths are likely to have caused a chip failure for a set of delay fault tests, and to find the associated likely fabrication process parameter variations. Here, we quantify the diagnosability of a path delay fault for a test, and develop a methodology based on the diagnosis framework presented earlier to determine the diagnosability of each path delay fault detected by a given test set. Furthermore, we apply this approach to find the diagnosability of robust path delay faults for the ISCAS'89 benchmark circuits.
Prenatal treatment of congenital adrenal hyperplasia: author differs with technical report.

To the Editor. In the recent report from the American Academy of Pediatrics on congenital adrenal hyperplasia,1 the authors make an inappropriate conclusion about prenatal treatment of congenital adrenal hyperplasia (CAH) with dexamethasone, namely that “spontaneous abortion, fetal demise during late pregnancy, intrauterine growth retardation, liver steatosis, hydrocephalus, agenesis of the corpus callosum, and hypospadias with unilateral cryptorchidism occur occasionally.” In fact, these are rare events mostly in isolated cases. The reason for these unwarranted conclusions is that they are based on an incomplete review of the literature. Indeed, large studies have shown that the frequency of spontaneous abortion and fetal demise is no different in prenatally treated and untreated groups.2–4 Furthermore, in 1 report the occurrence of liver steatosis in the study by Lajic and co-workers2 in 1 unaffected girl who did not receive full-term treatment with dexamethasone was attributed by the author to an adenovirus. In the same study, hydrocephalus and agenesis of the corpus callosum occurred in 1 male infant treated for only 7 weeks, and hypospadias and cryptorchidism occurred in 1 boy treated for only 7 weeks. In the Scandinavian study reporting these events, the authors stated that they could not attribute with certainty these complications to dexamethasone treatment. There have been only 3 incidences of intrauterine growth retardation, all of which had recovery in postnatal life.5,6 Haan's case report6 of a successful prenatal treatment states that the relationship between growth …
The Role of the Fourth Pillar in the Redesign of Social Security

Social security programs are under intense criticism around the world; increasingly, privatization is proposed as a solution. However, neither the public nor the private approach is problem-free. The choice may not be between public and private approaches but a combination of the two. The paper argues for creating a self-sustaining social security to serve as a stable foundation for some basic level of retirement income. In addition, after pointing out the importance of social security, the paper advocates strengthening the potential of employment as an additional source of income security.
Molecular Diagnosis of Mast Cell Disorders: A Paper from the 2005 William Beaumont Hospital Symposium on Molecular Pathology

Mastocytosis is a disease characterized by pathological mast cell accumulation and activation in tissues. Most patients with mastocytosis exhibit the D816V point mutation in the tyrosine kinase domain of the transmembrane receptor protein Kit, leading to its constitutive activation in bone marrow or lesional skin tissue. Detection of a codon 816 c-kit mutation is included as a minor diagnostic criterion in the World Health Organization's diagnostic criteria for systemic mastocytosis. Determining mutational status of the c-kit gene also has pharmacogenomic implications in patients considered for investigational mast cell cytoreductive therapies. This article reviews diagnostic and therapeutic implications of c-kit mutations as well as other less common molecular abnormalities observed in mast cell disease.
Reduction in delta activity predicted improved negative affect in Major Depressive Disorder

While prior research has demonstrated a paradoxical antidepressant effect of slow-wave disruption (SWD), the specific dimensions of depression affected is still unclear. The current study aimed to extend this research by utilizing a dimensional approach in examining the antidepressant effects of SWD. Of particular interest is the affective dimension, as negative affect in depression is arguably the most salient characteristic of depression. This sample included 16 individuals with depression (10 female) recruited from the community. Participants slept in the lab for three nights (adaptation, baseline night, and SWD) with polysomnography, and completed measures of negative affect and depression severity the following morning. Results show that reduction in delta power was linearly associated with improved negative affect. Comparison of individual change scores revealed that half of the individuals showed improved negative affect, which is comparable to the reported 40–60% antidepressant response rate to sleep deprivation. Results suggest that vulnerability in the sleep homeostatic system may be a contributing individual differences factor in response to slow-wave disruption in depression.
A Cultural Perspective on Health Outcomes of Caregiving Grandparents

ABSTRACT Purpose: Three-generation extended family households still constitute a fairly large proportion of households in China. This study aims to understand intergenerational relationships in Chinese families by examining health outcomes of grandparents that provide caregiving to their grandchildren. Design and Methods: Data are from the Survey on Aging and Intergenerational Relations in Baoding City, China. Multiple regressions are conducted to examine the relationship of caregiving to physical and mental health outcomes of grandparents, after controlling for a number of other factors. Results: Results of multiple regression analysis in this study show that caregiving is positively related to grandparents' physical and mental health status. Results further show that among grandparents providing childcare, those residing with grandchildren have better health outcomes than those who do not live with grandchildren. Implications: Discussion focuses on cultural expectations as well as social support receive...
Two Proteins Form a Heteromeric Bacterial Self-Recognition Complex in Which Variable Subdomains Determine Allele-Restricted Binding

Self- versus nonself-recognition in bacteria has been described recently through genetic analyses in multiple systems; however, understanding of the biochemical properties and mechanisms of recognition-determinant proteins remains limited. Here we extend the molecular and biochemical understanding of two recognition-determinant proteins in bacteria. We have found that a heterotypic complex is formed between two bacterial self-recognition proteins, IdsD and IdsE, the genes of which have been shown to genetically encode the determinants for strain-specific identity in the opportunistic bacterial pathogen Pro- teus mirabilis. This IdsD-IdsE complex forms independently of other P. mirabilis-encoded self-recognition proteins. We have also shown that the binding between IdsD and IdsE is strain- and allele-specific. The specificity for interactions is encoded within a predicted membrane-spanning subdomain within each protein that contains stretches of unique amino acids in each P. mirabilis variant. Finally, we have demonstrated that this in vitro IdsD-IdsE binding interaction correlates to in vivo popula- tion identity, suggesting that the binding interactions between IdsD and IdsE are part of a cellular pathway that underpins self- recognition behavior in P. mirabilis and drives bacterial population sociality. IMPORTANCE Here we demonstrate that two proteins, the genes of which were genetically shown to encode determinants of self- identity in bacteria, bind in vitro in an allele-restricted interaction, suggesting that molecular recognition between these two proteins is a mechanism underpinning self-recognition behaviors in P. mirabilis. Binding specificity in each protein is encapsu- lated in a variable region subdomain that is predicted to span the membrane, suggesting that the interaction occurs in the cell envelope. Furthermore, conversion of binding affinities in vitro correlates with conversion of self-identity in vivo, suggesting that this molecular recognition might help to drive population behaviors.
Utilization of image analysis for the quantification of vascular responses in the chick chorioallantoic membrane.

Summary An attempt has been made to quantify the vascular response in the CAM by using the method of automatic image analysis. In order to obtain a measure for the divergence of preparations with radial capillary growth from unchanged CAM preparations the lengths of radially arranged capillaries were measured, the relative frequency computed and compared with that of radially arranged capillary pieces in normal CAM preparations. The areal difference between both histograms is used as a measure for the grade of neovascularization Investigations performed to test the reproducibility and reliability of this measuring method have given a measuring accuracy of about ± 20 %; this value is comparable with that found by the method of radial vessel counting. The mean values of samples each consisting of 10 preparations obtained by the method of vessel counting and by the automatic measurement correlate quite well (r = 0.97). Angiogenic responses of different grades were produced in the CAM by dropping calf plasma on the CAM surface in amounts between 1 and 10μl. Although the individual values in the single groups vary within a wide range, a dose-response-relationship could be established both by the automatic measurement and by the method of radial vessel counting. Further improvements of the measuring procedure and a shortening of the measuring time from 5–10 min to 1 min or less could make this automatic method very suitable for the quantification of vascular responses in larger experimental series.
A fixed-point theorem of Krasnoselskii

Abstract Krasnoselskii's fixed-point theorem asks for a convex set M and a mapping Pz = Bz + Az such that: 1. (i) Bx + Ay ∈ M for each x , y ∈ M 2. (ii) A is continuous and compact 3. (iii) B is a contraction. Then P has a fixed point. A careful reading of the proof reveals that (i) need only ask that Bx + Ay ∈ M when x = Bx + Ay . The proof also yields a technique for showing that such x is in M .
The Reverse of Social Anxiety Is Not Always the Opposite: The Reverse-Scored Items of the Social Interaction Anxiety Scale Do Not Belong

Although well-used and empirically supported, the Social Interaction Anxiety Scale (SIAS) has a questionable factor structure and includes reverse-scored items with questionable utility. Here, using samples of undergraduates and a sample of clients with social anxiety disorder, we extend previous work that opened the question of whether the reverse-scored items belong on the scale. First, we successfully confirmed the factor structure obtained in previous samples. Second, we found the reverse-scored items to show consistently weaker relationships with a variety of comparison measures. Third, we demonstrated that removing the reverse-scored questions generally helps rather than hinders the psychometric performance of the SIAS total score. Fourth, we found that the reverse-scored items show a strong relationship with the normal personality characteristic of extraversion, suggesting that the reverse-scored items may primarily assess extraversion. Given the above results, we suggest investigators consider performing data analyses using only the straightforwardly worded items of the SIAS.
Competitive concurrent distributed queuing

Distributed queuing is a fundamental problem in distributed computing, arising in a variety of applications. The challenge in designing a distributed queuing algorithm is to minimize message traffic and delay.This paper gives a novel competitive analysis of the Arrow distributed queuing protocol under concurrent access. We analyze the combined latency of r simultaneous requests, and derive a competitive ratio of s · log r, where s is the stretch of a preselected spanning tree in the network.Our analysis employs a novel greedy characterization of the way the Arrow protocol orders concurrent requests, and yields a new lower bound on the quality of the nearest-neighbor heuristic for the Traveling Salesperson Problem.
Conservation of freshwater fishes of Sri Lanka

Abstract Sri Lanka supports a diverse fauna of freshwater fishes, 24% of which are endemic. A survey of the island's streams indicated that a number of the endemic fishes are threatened with extinction and others are depleted due to the interaction of deforestation, urbanization, gem mining, pesticides, exploitation, water diversions, and introductions of exotic species. It is clear that these declines should be halted for ethical, economic, and ecological reasons. Methods proposed to reverse the declines include captive breeding, better watershed management, translocation, and regulation of fisheries, especially that for aquarium fishes. The depauperate Second Peneplain is proposed as a site for translocation of endangered species.
Pulsed-modulated helium-ionization detection☆

Abstract Modifications which enable the helium-ionization detector to operate in a fixed-frequency, pulsed mode have been found to reduce noise and back-ground current levels from those obtained in a direct-current mode. Further modifications have now been completed which enable constant-current, pulsed operation. The result has been an increase in the dynamic range and prevention of discharge of the detector cell when high concentrations are analyzed. The low background current observed in the fixed-frequency mode has been maintained, and the sensitivity has been found to be comparable to d.c. operation. A description of the constant-current system and comparisons of the three modes (fixed-frequency, constant-current, and direct-current) are presented. Application of the pulsed detector to the analysis of organics, separated on an open tubular column, is demonstrated. The sensitivity of the detector is also compared with that of other, conventional ionization detectors.
Interaction between cytokines and ammonia in the mitochondrial permeability transition in cultured astrocytes

Hepatic encephalopathy (HE) is the major neurological complication occurring in patients with acute and chronic liver failure. Elevated levels of blood and brain ammonia are characteristic of HE, and astrocytes are the primary target of ammonia toxicity. In addition to ammonia, recent studies suggest that inflammation and associated cytokines (CKs) also contribute to the pathogenesis of HE. It was previously established that ammonia induces the mitochondrial permeability transition (mPT) in cultured astrocytes. As CKs have been shown to cause mitochondrial dysfunction in other conditions, we examined whether CKs induce the mPT in cultured astrocytes. Cultures treated with tumor necrosis factor-α, interleukin-1β, interleukin-6, and interferon-γ, individually or in a mixture, resulted in the induction of the mPT in a time-dependent manner. Simultaneous treatment of cultures with a mixture of CKs and ammonia showed a marked additive effect on the mPT. As oxidative stress (OS) is known to induce the mPT, so we examined the effect of CKs and ammonia on hemeoxygenase-1 (HO-1) protein expression, a marker of OS. Such treatment displayed a synergistic effect in the upregulation of HO-1. Antioxidants significantly blocked the additive effects on the mPT by CKs and ammonia, suggesting that OS represents a major mechanism in the induction of the mPT. Treatment of cultures with minocycline, an antiinflammatory agent, which is known to inhibit OS, also diminished the additive effects on the mPT caused by CKs and ammonia. Induction of the mPT in astrocytes appears to represent a major pathogenetic factor in HE, in which CKs and ammonia are critically involved.
Absence of H-Y antigen in an XY female with campomelic dysplasia.

We have studied a stillborn infant who had the clinical and radiographic characteristics of campomelic dysplasia. External and internal genitalia were those of a normal female, except for slight enlargement of the clitoris. Microscopic examination of the ovaries revealed some areas resembling immature dysgenetic testicular tissue. Karyotypes from lymphocyte and fibroblast cultures were 46,XY with a structurally normal Y chromosome and no evidence of mosaicism. H-Y antigen was not detected on the fibroblasts in repeated assays using Raji cells as target cells after absorption. The “sexreversal” (chromosomal male→phenotypic female) previously noted in patients with autosomal recessive campomelic dysplasia thus may be mediated through lack of detectable H-Y antigen on the cell surface. It appears that the mutation leading to campomelic dysplasia interferes with normal H-Y antigen expression.
Oligopolistic pricing with heterogeneous consumer search

Abstract A finite number of identical stores sell a homogeneous good to consumers with heterogeneous search costs who search sequentially with perfect recall and without replacement. Consumers' search rules are optimal with respect to the stores' pricing strategies, and consumers must visit a store to obtain information about its actual price. A symmetric Nash equilibrium (SNE) always exists. The model exhibits a variety of equilibrium behaviors between monopoly pricing and marginal-cost pricing. The competitiveness of a market depends crucially on the shape of the search cost distribution, moreso than on the number of competing firms.
Reduction in vulnerability to ventricular fibrillation by bromocriptine, a dopamine agonist

The effect of a dopamine agonist, bromocriptine, on ventricular fibrillation (VF) threshold was studied in anaesthetised dogs. Bromocriptine produced an increase of 50% in VFT. Pretreatment with the dopamine antagonist haloperidol abolished the effects of bromocriptine on VF threshold as did pretreatment with the peripheral dopamine antagonist, domperidone. It is concluded that bromocriptine reduces vulnerability of the nonischaemic canine ventricle to fibrillation. This effect is most probably mediated by peripheral presynaptic stimulation of dopaminergic receptors, thereby inhibiting noradrenaline release.
Impact of age on clinicopathological features and survival of patients with noncardia gastric adenocarcinoma.

Purpose: Gastric cancer often occurs in the elderly but is uncommon in young individuals. Whether young patients have different clinical behaviors and outcomes from those of older patients remain unclear. Materials and Methods: We identified 1,366 cases of newly diagnosed noncardia gastric adenocarcinoma from the Kaiser Permanente Northern California Cancer Registry between 2000 and 2010. We then compared the clinicopathological features and survival among the different age groups. Results: The male : female ratio differed significantly between the younger and older patient groups (0.84 in age 60 years, P<0.01). More younger patients were Hispanic (54% patients <40 years vs. 19% patients ≥70 years, P<0.0001), while more older patients were Caucasian (49% patients ≥70 years vs. 15% patients <40 years; P<0.0001). The diffuse/mixed histological type was more prevalent in younger patients (70% patients <40 years vs. 27% patients ≥70 years; P<0.0001), whereas the intestinal type was more frequent in older patients (71% in patients ≥70 years vs. 30% in patients <40 years; P<0.0001). Poorly differentiated adenocarcinoma was more common in the younger patients (80% in patients <40 years vs. 60% in patients ≥70 years; P=0.016). Survival rates at 1, 2, and 5 years gradually declined with increasing age (overall P=0.0002). Conclusions: Young patients with gastric cancer had more aggressive disease but higher overall survival rates than older patients. Younger Hispanic patients and older Caucasian patients were more likely to be diagnosed with gastric cancer. These differences may be due to biological predisposition and/or environmental exposure.
All-optical logic NOR gate at 40 Gb/s using SOA-based Mach-Zehnder interferometer

An all-optical logic NOR gate operating at 40 Gb/s has been demonstrated using an SOA-based Mach-Zehnder interferometer (MZI). An optical loop mirror is used as a delayed interferometer to reshape the return-to-zero (RZ) NOR sequence from the MZI output port. The performance of the NOR operation is numerically analyzed by solving the rate equation of an SOA. An increase in signal output power enhances the Q factor and extinction ratio. Faster SOAs such as quantum-dot SOAs can achieve higher Q value. The demonstrated technique has potential for optical logic operation at ultrahigh speed
What Is the System in Systemic Reform

policy. State and federal policy is not the only way to pursue improved instruction-The Coalition for Essential Schools, Accelerated Schools, and the New Standards Project all do so largely outside the framework of policy-but systemic reformers have viewed government as their chief vehicle. The leading examples of changed state and national policy include the California and Vermont reforms, Goals 2000, the NSF State Systemic Reform Initiative, and the Kentucky reforms. Systemic reform focuses in two arenas: creating new policy instruments that seem necessary to enact systemic reform, and reducing the inherited tangles of regulation, bureaucracy, proliferating policy, and incoherent governance that would impede reform (Smith & O'Day).1 The new policy instruments are commonly thought to include:
Effects of chronic moderate alcohol consumption and novel environment on heart rate variability in primates (Macaca fascicularis)

The effects of chronic moderate alcohol consumption on cardiac function are not understood. Acute stress may affect cardiac function by shifting autonomic cardiac regulation in favor of the sympathetic nervous system. Although alcohol consumption often increases at times of stress, the interactive effects of stress and chronic moderate alcohol consumption on cardiac regulation have not been studied. The objective was to assess the effects of long-term (1–2 years) moderate (a two-drink/day equivalent, 5 days/week) alcohol consumption on heart rate (HR) variability under normal and acutely stressful conditions in small stable groups of ovariectomized adult cynomolgus monkeys (Macaca fascicularis). Monkeys were trained to voluntarily drink their daily alcohol dose (<30 min), and blood levels were determined an hour later. The animals were acutely stressed by removal from the home cage to a novel environment for 30 min. HR in freely moving subjects was recorded via telemetry in the home cage and the novel environment. Acute stress increased HR, decreased HR variability, and decreased the high frequency component of the power spectrum suggesting reduced parasympathetic cardiac modulation. Chronic moderate alcohol consumption decreased HR variability and the low frequency components of the power spectrum. When stressed, monkeys with a history of chronic moderate alcohol consumption had higher HRs than the controls. HR dynamics in monkeys rapidly respond to acute stress. Chronic moderate alcohol consumption may be deleterious to cardiac function. HR response to stress may be exaggerated when accompanied by a history of chronic moderate alcohol consumption.
Cause and Effect in Apachean Agriculture, Division of Labor, Residence Patterns, and Girls' Puberty Rites

It has been asserted that matrilocal residence among Apacheans is a recent development, resulting from the acquisition of agriculture and a female agricultural division of labor due to Pueblo influence. Yet matrilocal residence is weakly developed among the Pueblos, Pueblo men carry on most of the agriculture, Apacheans who do little or no farming are matrilocal, and Apachean men are very active in cultivation. An alternative explanation for Apachean matrilocal residence is offered.
High-temperature elastic constants of gold single-crystals

Elastic wave velocity measurements in two oriented gold single-crystals have been measured from 270 to 1280 K. The adiabatic elastic constants c11, c2 and c44, deduced from the elastic wave velocities, are in excellent agreement with previous measurements at low temperatures, but exhibit a negative modulus defect at high temperatures. Calculated values of the aggregate elastic properties (shear and Young's moduli) are in excellent agreement with measured values in the same temperature range. The results have been discussed in terms of a simple extension of the harmonic model in which the shift in the frequency spectrum due to volume changes is considered.
How to control self-digestion: transcriptional, post-transcriptional, and post-translational regulation of autophagy

Macroautophagy (hereafter autophagy), literally defined as a type of self-eating, is a dynamic cellular process in which cytoplasm is sequestered within a unique compartment termed the phagophore. Upon completion, the phagophore matures into a double-membrane autophagosome that fuses with the lysosome or vacuole, allowing degradation of the cargo. Nonselective autophagy is primarily a cytoprotective response to various types of stress; however, the process can also be highly selective. Autophagy is involved in various aspects of cell physiology, and its dysregulation is associated with a range of diseases. The regulation of autophagy is complex, and the process must be properly modulated to maintain cellular homeostasis. In this review, we focus on the current state of knowledge concerning transcriptional, post-transcriptional, and post-translational regulation of autophagy in yeast and mammals.
Newer antidotal therapies for pediatric poisonings

Abstract Specific antidotal therapy is essential for the successful management of a limited number of intoxications. Newer antidotes have emerged in the last 10 years that target specific life-threatening poisonings. These newer therapies, including hormones, drug antagonists, enzyme inhibitors, and antibodies against drugs and venoms, illustrate the spectrum of mechanisms by which an antidote can reverse toxicity of a poison. This report focuses on seven newer antidotes: glucagon (β-blocker and calcium channel blocker toxicity), insulin/glucose (calcium-channel blocker toxicity), octreotide (sulfonylurea toxicity), new crotalid antivenom (crotalid snake bit envenomation), antibody therapy for tricyclic antidepressants, fomepizole (ethylene glycol toxicity), and nalmefene (opiod toxicity). The antidotes' mechanisms of action, expected therapeutic actions, indications for use, adverse effects, dosing, and limitations are discussed.
Tone-burst modulated color-center-laser spectroscopy.

A new modulation technique useful for high-resolution spectroscopy with tunable infrared lasers is described. The high sensitivity of this method is demonstrated by measurements of NO v = 0 → 2 overtone transitions and of transitions in the fundamental band of OH with a color-center laser operating near 2.7 μm.
Collective excitations in the fractional quantum Hall effect of a multicomponent fermion system

We derive the dispersion of the elementary excitations in a two-component integer and fractional quantum Hall effect. We consider the fully polarized ground state and show the existence of both a magnetoroton mode and a low-lying Goldstone mode (GM). For the unpolarized ground state we derive the dispersion for both a density-density mode and a spin-wave mode both going to a finite value at small momentum q. We examine the extension of the charge-density-wave (CDW)-like ground state and fluidlike Laughlin state to multicomponents. We show that the latter has the lowest ground-state energy with a polarized ground state at filling factor ..nu.. = 1, (1/3), and (1/5) and unpolarized at ..nu.. = (2/5). Most important, the CDW predicts a polarized ground state at ..nu.. = (2/5) and would, therefore, show dissipation via the GM channel contrary to the Laughlin-like ground states. We have, therefore, a new experimental possibility for selecting the correct ground state from many of the recent interesting suggestions.
Antibodies Specific for Human Albumin Function as Blocking Antibodies When Attached to Erythrocyte-Bound Albumin

Albumin is shown to be firmly bound to human red blood cells using the techniques of flow cytometry, immunoblotting, and complement fixation. The interactions between antibodies attached to the cell bound albumin and the complement system are examined. Antibodies specific for human serum albumin bind to albumin on erythrocytes and activate both homologous and heterologous complement in the absence of hemolysis. Moreover, treatment of erythrocytes with anti-albumin antibodies renders the cells resistant to classical pathway mediated lysis initiated by a passive lysis system. Thus, erythrocyte-bound anti-albumin antibodies appear to function in a manner similar to "blocking" antibodies described in some bactericidal systems.
Observational constraints on the atmospheres of Uranus and Neptune from new measurements near 10 μm

Uranus was detected at 10.3, 11.6 and 12.5 micrometers approximately 1 micrometer spectral bandpasses, with respective brightness temperatures of 74.0 + 0.9 or -1.1, 67.6 + 0.5 or -0.7, and 65.5 + 0.6 or -0.7 K and the first detection of Neptune at 10.3 micrometers with a brightness temperature of 77.5 + 0.7 or -0.9 K. We also detected Neptune at 11.36 micrometers with 2% spectral resolution at 81.0 + 0.8 or -0.9 K. The 10 micrometers continuous of both Uranus and Neptune may in part be due to reflected solar radiation as well as thermal emission. If all of the observed flux is reflected light, then the maximum geometric albedo of Uranus is 0.115 + or - 0.020, and that of Neptune is 0.229 + or - 0.043. In the context of previous observations in this region, the maximum stratospheric C2H6 mixing ratio is found to be 3 x 10 to the -8 power for Uranus and 3 x 10 to the -6 power for Neptune. A value for the maximum mixing ratio in the stratosphere of Neptune on the order of 1 - 0.004 appears to be consistent with the available data.
Genomewide linkage scan for opioid dependence and related traits.

Risk of opioid dependence is genetically influenced. We recruited a sample of 393 small nuclear families (including 250 full-sib and 46 half-sib pairs), each with at least one individual with opioid dependence. Subjects underwent a detailed evaluation of substance dependence–related traits. As planned a priori to reduce heterogeneity, we used cluster analytic methods to identify opioid dependence–related symptom clusters, which were shown to be heritable. We then completed a genomewide linkage scan (with 409 markers) for the opioid-dependence diagnosis and for the two cluster-defined phenotypes represented by >250 families: the heavy–opioid-use cluster and the non–opioid-use cluster. Further exploratory analyses were completed for the other cluster-defined phenotypes. The statistically strongest results were seen with the cluster-defined traits. For the heavy–opioid-use cluster, we observed a LOD score of 3.06 on chromosome 17 (empirical pointwise P=.0002) for European American (EA) and African American (AA) subjects combined, and, for the non–opioid-use cluster, we observed a LOD score of 3.46 elsewhere on chromosome 17 (empirical pointwise P=.00002, uncorrected for multiple traits studied) for EA subjects only. We also identified a possible linkage (LOD score 2.43) of opioid dependence with chromosome 2 markers for the AA subjects. These results are an initial step in identifying genes for opioid dependence on the basis of a genomewide investigation (i.e., a study not conditioned on prior physiological candidate-gene hypotheses).