cssi/SciSciGPT-SciSciNet huggingface dataset:
A bush, not a tree: The extraordinary diversity of cold-water basal foraminiferans extends to warm-water environments

Foraminiferal species distribution and richness have traditionally been assessed through examination of the shells (tests) built by most of the described species, but molecular surveys indicate that this approach likely underestimates true foraminiferal diversity. We use a series of targeted DNA-based surveys and focused morphological searches to document the diversity of allogromiid foraminiferans, which have less distinctive tests, at selected locations along the U.S. eastern seaboard. These sites, although well studied by previous foraminiferal researchers, have not been reported to host large numbers or diverse assemblages of allogromiids. Both survey methods revealed the presence of many new allogromiid taxa and documented striking differences in the allogromiid assemblages between the three locations. The assemblage at a given site as determined by morphological criteria also differed substantially from that determined by molecular surveys. Combined with information from other locales, our data strongly suggest that allogromiid diversity is underestimated; indeed, allogromiids may actually dominate many benthic foraminiferal assemblages. This finding has significant implications for benthic trophodynamics and for the reconstruction of paleoenvironments because the morphological inconspicuousness and taphonomic fragility of allogromiid foraminiferans may lead to underestimates of total foraminiferal diversity and abundance.
Writer’s cramp as a presentation of L-2-hydroxyglutaric aciduria

L-2-hydroxyglutaric aciduria (L2HGA) is a neurometabolic disorder characterized by macrocephaly, seizures, progressive mental retardation, pyramidal signs, ataxia and tremor. Dystonia is an under-recognized feature of this entity in the literature. We report two siblings with L2HGA, one of whom presented with writer's cramp followed by dystonia of the other hand. An elevated plasma lysine, highly elevated urine 2-hydroxyglutaric acid, and MRI with characteristic findings (leukoencephalopathy of bilateral subcortical white matter sparing central white matter) suggested the diagnosis, which was confirmed by genetic testing.
Probability-Based Bridge Network Performance Evaluation

This paper presents a comprehensive mathematical model for evaluating the overall performance of a bridge network based on probability analyses of network connectivity, user satisfaction, and structural reliability of the critical bridges in the network. A bridge network consists of all nodes of interest in a geographical region. These nodes of interest are connected to each other through multiple paths. The network performance evaluation in terms of connectivity is formulated by using an event tree technique. The network performance measure of user satisfaction deals with traffic demand and capacity of each link in the network. Moreover, the shortest paths in terms of total traffic costs are identified by network optimization algorithms for each pair of the origin and destination nodes of interest under the specified traffic demands. Using this information, the minimum-weight spanning tree (MST) that consists of the identified shortest paths is constructed. The bridges associated with MST are defined as the critical bridges in the network. The network performance in terms of structural reliability of the critical bridges can be computed from system reliabilities of the critical bridges by using a series-parallel system model. Finally, by combining the above three criteria, a single numerical measure is proposed to evaluate the overall performance of the bridge network. This novel approach is illustrated on a group of fourteen existing bridges with different reliability profiles located in Colorado. This study provides the basis of a network-level bridge management system where lifetime reliability and life-cycle costs are the key considerations for optimal bridge maintenance strategies.
Preconditioning indefinite systems arising from mixed finite element discretization of second-order elliptic problems

We discuss certain preconditioning techniques for solving indefinite linear systems of equations arising from mixed finite element discretizations of elliptic equations of second order. The techniques are based on various approximations of the mass matrix, say, by simply lumping it to be diagonal or by constructing a diagonal matrix assembled of properly scaled lumped element mass matrices. We outline two possible alternatives for preconditioning. One can precondition the original (indefinite) system by some indefinite matrix and hence use either a stationary iterative method or a generalized conjugate gradient type method. Alternatively as in the particular case of rectangular Raviart-Thomas elements, which we consider, one can perform iterations in a subspace, eliminating the velocity unknowns and then considering the corresponding reduced system which is elliptic. So we can use the ordinary preconditioned conjugate gradient method and any known preconditioner (of optimal order, for example, like the multigrid method) for the corresponding finite element discretization of the elliptic problem. Numerical experiments for some of the proposed iterative methods are presented.
α-Helix formation by peptides of defined sequence

Abstract The factors controlling α-helix formation in water by peptides of defined sequence are beginning to be understood. The field is close to the point where the extent of helix formation can be predicted for peptides of any sequence. Our own approach to the problem, and the main results obtained by following this approach, are summarized below. The chief reason for studying α-helix formation by peptides is to understand precisely and in detail one part of the protein folding problem. Questions about peptide helix formation can be answered at a fundamental level, in terms of the physico-chemical mechanisms involved.
Aspects of blood pressure, lipid, and glycemic treatment.

This is the fourth of a series of articles reviewing presentations at the 63rd annual scientific session of the American Diabetes Association, held in New Orleans, Louisiana, June 2003. William Cushman described the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial), which had a total of 33,357 hypertensive participants, 36% of whom had diabetes, making it the largest study of blood pressure treatment in diabetes (1). Interestingly, 60% of the population studied satisfied criteria for the metabolic syndrome. In both the diabetic and nondiabetic subgroups, there was no difference in coronary heart disease (CHD) events or mortality between patients randomized to chlorthalidone, amlodipine, and lisinopril. Congestive heart failure (CHF) was less common with chlorthalidone than with the other agents. For those with fasting glucose <126 mg/dl at baseline, the mean glucose was 93 mg/dl at baseline, with levels increasing to 104 mg/dl with chlorthalidone, 103 mg/dl with amlodipine, and 101 mg/dl with lisinopril at 4 years. Similarly, diabetes incidence was highest with chlorthalidone at 11.6 vs. 9.8% with amlodipine and 8.1% with lisinopril. Including those persons who developed diabetes, and those with fasting glucose ≥126 mg/dl who had unrecognized diabetes, 39, 40, and 39% of persons in the three groups actually had diabetes. In each group, 4% had impaired fasting glucose (IFG) at levels of 110–125 mg/dl. The diabetic participants had 36% CVD prevalence, as opposed to 62% of the IFG and nondiabetic groups, based on the differing entry criteria for those with and without diabetes. Initial fasting glucose levels were 169, 116, and 91 mg/dl in the respective groups. Lisinopril did not lower systolic blood pressure as effectively as the two other agents, although it affected diastolic blood pressure similarly. Among persons with diabetes, at 2 years fasting blood glucose decreased 3 and 2 mg/dl with amlodipine …
The undescended testis.

Cryptorchidism represents a common condition affecting male infants that has significant clinical implications, including infertility and testicular malignancy. The precise developmental mechanisms leading to cryptorchidism are poorly understood; however, abnormalities in both functional anatomic and hormonal factors during embryogenesis and testicular descent are implicated. Although surgical intervention is ultimately required, there is a defined role for diagnostic imaging in patient evaluation—particularly in the setting of a nonpalpable undescended testis. Consultation among urologists, pediatric surgeons, and radiologists is paramount to optimize patient care.
Decadal Variations in Climate Associated with the North Atlantic Oscillation

Large changes in the wintertime atmospheric circulation have occurred over the past two decades over the ocean basins of the Northern Hemisphere, and these changes have had a profound effect on regional distributions of surface temperature and precipitation. The changes over the North Pacific have been well documented and have contributed to increases in temperatures across Alaska and much of western North America and to decreases in sea surface temperatures over the central North Pacific. The variations over the North Atlantic are related to changes in the North Atlantic Oscillation (NAO). Over the past 130 years, the NAO has exhibited considerable variability at quasi-biennial and quasi-decadal time scales, and the latter have become especially pronounced the second half of this century. Since 1980, the NAO has tended to remain in one extreme phase and has accounted for a substantial part of the observed wintertime surface warming over Europe and downstream over Eurasia and cooling in the northwest Atlantic. Anomalies in precipitation, including dry wintertime conditions over southern Europe and the Mediterranean and wetter-than-normal conditions over northern Europe and Scandinavia since 1980, are also linked to the behavior of the NAO. Changes in the monthly mean flow over the Atlantic are accompanied by a northward shift in the storm tracks and associated synoptic eddy activity, and these changes help to reinforce and maintain the anomalous mean circulation in the upper troposphere. It is important that studies of trends in local climate records, such as those from high elevation sites, recognize the presence of strong regional patterns of change associated with phenomena like the NAO.
Efficacy of azilsartan medoxomil with chlorthalidone in hypertension

Azilsartan medoxomil (AZL) is the most recently approved angiotensin receptor blocker (ARB) for treating patients with hypertension. A fixed-dose combination product with AZL and the thiazide-like diuretic chlorthalidone (CLD) is now available to treat individuals who require additional blood pressure lowering. For this review, a literature search was conducted using MEDLINE and the keywords and MeSH terms azilsartan, azilsartan medoxomil, chlorthalidone, thiazide, blood pressure and hypertension. References for retrieved articles were also scanned for relevant citations. No language restrictions were used. AZL is structurally related to candesartan and has been shown to provide more potent angiotensin receptor antagonism versus other ARBs. CLD is a thiazide-like diuretic with a longer half-life and greater blood pressure lowering efficacy than hydrochlorothiazide. The combination of AZL plus CLD has superior efficacy to other ARBs alone or in combination with hydrochlorothiazide based on extensive evaluation in clinical trials. This superior efficacy is not offset by a large imbalance in clinically important adverse events.
Two-dimensional vibrational-electronic spectroscopy

Two-dimensional vibrational-electronic (2D VE) spectroscopy is a femtosecond Fourier transform (FT) third-order nonlinear technique that creates a link between existing 2D FT spectroscopies in the vibrational and electronic regions of the spectrum. 2D VE spectroscopy enables a direct measurement of infrared (IR) and electronic dipole moment cross terms by utilizing mid-IR pump and optical probe fields that are resonant with vibrational and electronic transitions, respectively, in a sample of interest. We detail this newly developed 2D VE spectroscopy experiment and outline the information contained in a 2D VE spectrum. We then use this technique and its single-pump counterpart (1D VE) to probe the vibrational-electronic couplings between high frequency cyanide stretching vibrations (νCN) and either a ligand-to-metal charge transfer transition ([Fe(III)(CN)6](3-) dissolved in formamide) or a metal-to-metal charge transfer (MMCT) transition ([(CN)5Fe(II)CNRu(III)(NH3)5](-) dissolved in formamide). The 2D VE spectra of both molecules reveal peaks resulting from coupled high- and low-frequency vibrational modes to the charge transfer transition. The time-evolving amplitudes and positions of the peaks in the 2D VE spectra report on coherent and incoherent vibrational energy transfer dynamics among the coupled vibrational modes and the charge transfer transition. The selectivity of 2D VE spectroscopy to vibronic processes is evidenced from the selective coupling of specific νCN modes to the MMCT transition in the mixed valence complex. The lineshapes in 2D VE spectra report on the correlation of the frequency fluctuations between the coupled vibrational and electronic frequencies in the mixed valence complex which has a time scale of 1 ps. The details and results of this study confirm the versatility of 2D VE spectroscopy and its applicability to probe how vibrations modulate charge and energy transfer in a wide range of complex molecular, material, and biological systems.
Thiol–Disulfide Exchange Reactions in the Mammalian Extracellular Environment

Disulfide bonds represent versatile posttranslational modifications whose roles encompass the structure, catalysis, and regulation of protein function. Due to the oxidizing nature of the extracellular environment, disulfide bonds found in secreted proteins were once believed to be inert. This notion has been challenged by the discovery of redox-sensitive disulfides that, once cleaved, can lead to changes in protein activity. These functional disulfides are twisted into unique configurations, leading to high strain and potential energy. In some cases, cleavage of these disulfides can lead to a gain of function in protein activity. Thus, these motifs can be referred to as switches. We describe the couples that control redox in the extracellular environment, examine several examples of proteins with switchable disulfides, and discuss the potential applications of disulfides in molecular biology.
Cell surface antigens during mammalian spermatogenesis.

Publisher Summary The role of the plasma membrane in the regulation of mammalian sperm differentiation remains obscure despite the fact that spermatogenesis offers a unique opportunity for the analysis of both mitotic and meiotic cell proliferation, for the study of cell–cell communication via direct intercellular contact as well as via hormonal interactions, for the investigation of cell differentiation, and for the studies of cell motility. In addition, spermatogenesis provides an advantage that all of these problems may be examined in a single developmental lineage, all of whose constituent cells are well defined morphologically. Mammalian spermatogenesis presents little need for an indirect means of cell identification and is, therefore, ideally suited for detailed experimentation designed to analyze cell growth, cell differentiation, cell movement, and even cell death. The interactions between Sertoli cells and developing male germ cells are dynamic and highly ordered with respect to the timing and spatial arrangements of the successive waves of cellular differentiation. Immunological analysis of purified mouse spermatogenic cells indicates that the mammalian testis exhibits cell surface antigenic determinants that are specific to developing male gametes. By using immunofluorescence, complement-mediated cytotoxicity, and quantitative assays, a variety of antigens are detected that first appear during late pachynema of the first meiotic prophase. These antigens are expressed by all late pachytene primary spermatocytes, round spermatids, and residual bodies in a uniform diffuse fashion on the surface membranes.
The Effects of New York City's Test-Based Promotion Policy

School systems across the nation have recently adopted, or are reportedly considering policies that require students to reach some minimal benchmark on standardized tests in order to be promoted to the next grade. We use a regression discontinuity design to study the effects of New York City’s test-based promotion policy on multiple outcomes up to five years after treatment. Treated students were retained and required to attend summer school prior to the retained year. We find evidence that exposure to the treatment had a statistically significant and substantial positive effect on student math and ELA test scores in the years immediately following the treatment, which dissipate somewhat over time. However, the effect remains statistically significant and substantial several years following treatment. Treated students were absent significantly more days in later grades than were control students. Finally, we find no relationship between the treatment and probability of retention in later grades.
Promoting student engagement in fundamental Java programming classes using a poll software system: faculty poster abstract

Due to the fact that a large amount of material must be taught in a relatively short amount of time, introductory computer programming courses are often frustrating to students [1]. How to improve student comprehension of course content to improve student satisfaction and engagement has a great impact on the likelihood of students' successful school completion [2].
Awareness Displays and Interruptions in Teams

Work life is filled with interruptions, most of which benefit the interrupter more than the one being interrupted. This problem is greatest with remote collaboration, because team members interrupt blindly, without contextual cues about partners' availability. Awareness displays are designed to provide distributed workers with up-to-date status information about their group members. We describe a pair of laboratory experiments conducted to determine whether awareness displays containing information about a remote collaborator's workload aids in timing interruptive communication. Results indicate that such displays can be useful in coordinating communication, but only when the interrupter has motivation to use the display. Our results also indicate that the attentional demand of the awareness displays themselves need to be taken into consideration, because too much detail may distract the person viewing the display from their primary task. In this study, participants spent significantly more time looking at the most detailed-filled displays and these displays harmed their task performance. We conclude that a display with an abstract representation of a collaborator's workload is best; it leads to better timing of interruptions without overwhelming the person viewing the display.
High-temperature oxygen dissolution in liquid zirconium

The enthalpy of oxygen dissolution in liquid zirconium occurring during the combustion of Zr particles is estimated. The analysis presented uses direct experimental measurements of the temperature, size, and composition histories of burning Zr particles. The dissolution enthalpy is limited by the range of 700–830 kJ/mol and is somewhat less than that of Zr oxidation. This enthalpy determines the rate of the heat release during Zr combustion until stoichiometric ZrO2 forms out of the supersaturated Zr/O solution. Stoichiometric ZrO2 is formed near the end of combustion and the additional energy released at that time causes a rapid temperature increase which can trigger a particle explosion.
Modulation of cyclophosphamide-based cytochrome P450 gene therapy using liver P450 inhibitors.

The sensitivity of tumors to cyclophosphamide (CPA) and other anticancer prodrugs can be substantially enhanced by transduction of tumors with a prodrug-activating mammalian cytochrome P 450 (CYP) enzyme in combination with the flavoenzyme P450 reductase. This gene therapy strategy provides for intratumoral prodrug activation, but is also associated with a high level of hepatic prodrug activation, which reduces the extent of intratumoral prodrug activation and contributes to systemic drug toxicity. To address this issue, five P450 inhibitors were tested for their ability to block liver CYP2C-catalyzed CPA activation selectively, i.e., without inhibiting the corresponding intratumoral activation of CPA catalyzed by a transduced CYP2B enzyme. In vitro studies revealed that the P450 inhibitors 1-aminobenzotriazole and DDEP were preferentially inhibitory toward CYP2C-dependent liver microsomal CPA activation, whereas the P450 inhibitor SKF-525A inhibited CYP2C- and CYP2B-dependent CPA activation without P450 form selectivity. By contrast, the P450 inhibitors chloramphenicol and metyrapone preferentially inhibited CYP2B-dependent CPA activation. Rat pharmacokinetic studies confirmed the inhibitory action of these compounds in vivo , with up to a 4-fold decrease in C max and a 7-fold increase in apparent half-life of the activated CPA metabolite, 4-hydroxy-CPA, seen in the case of 1-aminobenzotriazole. Although the rate of hepatic CPA activation could thus be decreased substantially by P450 inhibitor treatment, the net extent of hepatic CPA activation was only modestly decreased, as judged by plasma area-under-the-curve values for 4-hydroxy-CPA. Moreover, P450 inhibitor treatment did not decrease CPA's host toxicity and did not enhance the tumor growth delay response to CPA in rats bearing CYP2B1-transduced gliosarcomas. These findings are discussed in the context of P450-based gene therapy strategies and ongoing efforts to enhance anticancer drug activity by increasing the exposure of P450-expressing tumors to the P450-activated prodrug CPA. Cancer Gene Therapy (2001) 8, 450–458
Retinoblastoma protein-overexpressing HL60 cells resistant to 1,25-dihydroxyvitamin D3 display increased CDK2 and CDK6 activity and shortened G1 phase

Drug resistance that occurs during cancer chemotherapy has been a major problem in controlling neoplastic progression. To study the cellular mechanisms of acquired drug resistance we developed 1,25-dihydroxyvitamin D3 (1,25D3)-resistant sublines of promyelocytic leukemia HL60 cells which have increased proliferation rates (Exp. Cell Res., 224, 312, 1996; Cancer Res., 50, 5513, 1996). We report here that the resistant sublines display varying degrees of shortening of the G1 phase as compared to the parental HL60-G cells. Protein levels of cyclins E, D1, D2 and D3 are elevated in these resistant cell lines, and cyclin D1 is especially high in 40AF cells, which has the shortest G1 length. The protein levels of cyclin-dependent kinase (Cdk)2, Cdk4 and Cdk6 are not altered in the resistant sublines. Both Cdk2 and Cdk6-associated kinase activites are increased in the resistant sublines, but not Cdk4 kinase activity. Protein levels of p27Kip1 are not consistently altered in the resistant sublines as compared to the parental HL60-G cells, but are reduced relative to HL60-G cells arrested by 96 h treatment with 1,25D3. Interestingly, the resistant cell lines constitutively express high levels of retinoblastoma protein (pRb), and pRb is highly phosphorylated, indicating that the G1 cyclin/Cdk complexes in the resistant cells are physiologically active. The results suggest that the increased activity of cyclin D/Cdk6, and perhaps cyclin E/Cdk2, lead to rapid hyperphosphorylation of pRb and consequently a shorter early G1 phase, and that in the resistant cells the increased ratio of cyclin E to p27Kip1 results in activation of Cdk2 and contributes to the abrogation of the 1,25D3-induced block to the S phase entry. Additionally, it is apparent that constitutively increased levels of pRb are compatible with increased rates of cell proliferation.
Analysis of influenza surveillance data in Ningbo city from 2007 to 2011

Objective To understand the epidemiologic characteristics of influenza in Ningbo city and provide the evidence for the control of influenza.Methods Descriptive epidemiological analysis was performed on the data of annual influenza-like cases surveillance and virus isolation/identification in Ningbo from 2007 to 2011.Results According to the data,it showed two epidemic seasons in winter to spring and summer in Ningbo city.The majority of influenza-like illness was distributed in people aged below 15,the percentage of influenza-like illness was above 80%; A total of 82247 cases of influenza-like cases were reported in Ningbo from 2007 to 2011; Throat swab specimens of 6634 patients were collected in influenza-like illness,including 59 seasonal H1N1 virus,244 seasonal H3N2 virus,222 A H1N1 and 102 type B.Conclusion Influenza was prevalent in Ningbo in 2007 and 2009,and the epidemic situation of influenza was relatively stable in Ningbo in 2008,2010 2011.It is important that influenza prevention and control should be publicized among children guardians and educational institutions,improving the awareness rate and the coping skills.
Clinical Responses to Thrombolysis in Acute Ischemic Stroke, and the Importance of the Microvasculature

The development of arterial recanalization strategies using plasminogen activators for treatment of atherothrombotic and thromboembolic cerebral ischemia has exposed events which contribute to the limitation and extension of tissue injury. These include the presence of early ishemic injury, individualization of the potential window for treatment, edema formation, and the mechanisms underlying the hemorrhagic transformation. The appearance of early ischemic injury and the potential window for treatment seem tied to the patency of collateral channels and peculiarities of the microvascular bed of the individual patient. Hemorrhagic transformation, a common accompaniment of focal cerebral ischemia, is related to the time from symptom onset to exposure with the plasminogen activator, persistence of diastolic hypertension, a relative plasminogen activator dose-rate, extensive ischemic injury on CT, anticoagulation, and advanced age. Limited evidence suggests that a threshold of regional cerebral blood flow reduction is significantly associated with symptomatic intracerebral hemorrhage. These contributors suggest a common vascular target. The microvasculature is both a source of cerebral integrity and the target of ischemic injury. Activation of microvascular endothelial cells by ischemia leads to the expression of P-selectin, ICAM-1, and E-selectin which promote PMN leukocyte firm adhesion and transmigration. Obstruction of microvascular flow is a consequence. Activation of platelets, in relationship to PMN leukocytes, and intravascular fibrin formation contribute further to the loss of microvascular patency. Within the myointima of selected microvessels the integrin αvβ3, appears. Constituents of the basal lamina and extracellular matrix, whose loss contributes to hemorrhagic transformation, are affected significantly within the initial 24 hours following ischemic injury. Recently, significant aletrations in cell-matrix interactions between the endothelium and astrocyte end-feet, and their respective matrix partners, have been shown to occur most significantly in the region of severest neuron injury. Interventions which reduce the frequency and severity of these microvascular processes should enhance benefit in acute stroke patients.
Effects of potassium cardioplegia on high-energy phosphate kinetics during circulatory arrest with deep hypothermia in the newborn piglet heart.

The protective effects of hypothermia and potassium-solution cardioplegia on high-energy phosphate levels and intracellular pH were evaluated in the newborn piglet heart by means of in vivo phosphorus nuclear magnetic resonance spectroscopy. All animals underwent cardiopulmonary bypass, cooling to 20° C, 120 minutes of circulatory arrest, rewarming with cardiopulmonary bypass, and 1 hour off extracorporeal support with continuous hemodynamic and nuclear magnetic resonance spectroscopic evaluation. Group I (n = 5) was cooled to 20° C; group II (n = 4) was given a single dose of 20° C cardioplegic solution; group III (n = 7) was given a single dose of 4° C cardioplegic solution; and group IV (n = 4) received 4° C cardioplegic solution every 30 minutes. At end ischemia, adenosine triphosphate, expressed as a percent of control value, was lowest in group I 54% ±6.5% but only slightly greater in group II 66% ± 7.0%. Use of 4° C cardioplegic solution in groups III and IV resulted in a significant decrease in myocardial temperature, 9.9° C versus 17° to 20° C, and significantly higher levels of adenosine triphosphate at end ischemia; with group III levels at 72% ± 6.0% and group IV levels at 73% ±6.0%. Recovery of adenosine triphosphate with reperfusion was not related to the level of adenosine triphosphate at end ischemia and was best in groups I and II, with a recovery level of 95% ±4.0%. In group IV, no recovery of adenosine triphosphate occurred with reperfusion, resulting in a significantly lower level of adenosine triphosphate, 74% ±6.0%, than in groups I and II. Recovery of ventricular function was good for all groups but was best in hearts receiving a single dose of 4° C cardioplegic solution. In this model, multiple doses of cardioplegic solution were not associated with either improved adenosine triphosphate retention during arrest or improved ventricular function after reperfusion, and in fact resulted in a significantly lower level of adenosine triphosphate with reperfusion. The complete recovery of adenosine triphosphate in groups I and II, despite a nearly 50% adenosine triphosphate loss during ischemia, may result from a decrease in the catabolism of the metabolites of adenosine triphosphate consumption in the newborn heart.
Abstract IA13: The LKB1-AMPK pathway reprograms cancer cell metabolism

The serine/threonine kinase LKB1 is a tumor suppressor gene mutated in the familial cancer condition Peutz-Jeghers syndrome, as well as in 30% of non-small cell lung cancer (NSCLC). One of the critical substrates of LKB1 is AMPK, a highly conserved sensor of cellular energy status that restores metabolic homeostasis following stress. Thus LKB1 is a unique energy-state sensitive regulator of growth and metabolic reprogramming via its effects on AMPK. Our laboratory has performed a three-pronged screen to identify novel substrates of AMPK and related kinases that may mediate LKB1 effects on tumor suppression, metabolism, and metastasis. These findings have also spurred examination of whether compounds that activate AMPK may exhibit anti-cancer activities. Notably, the most widely used type 2 diabetes therapeutic in the US and worldwide, metformin, is a mitochondrial OXPHOS inhibitor that activates AMPK. We have therefore examined the potential anti-cancer effects of metformin and compounds against other metabolic targets. Citation Format: Reuben J. Shaw. The LKB1-AMPK pathway reprograms cancer cell metabolism. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr IA13.
Southern Ocean warming delayed by circumpolar upwelling and equatorward transport

Unlike the Arctic, the Southern Ocean has shown little warming. An analysis of observations and numerical simulations suggests that Southern Ocean warming patterns are shaped by meridional overturning more than surface heating.
Seeing the Future of Civilization in the Skies of Quarouble: UFO Encounters and the Problem of Empire in Postwar France

On 10 September 1954, a young metalworker named Marius Dewilde (1921–1996) stepped outside the abandoned railway station house he occupied in Quarouble, France, and encountered an alien world. Even for a man who would later claim to have worked as a traveling circus performer, fought in the resistance, and voyaged around the world in the French merchant marine before his thirty-third birthday, what happened that September night was truly fantastic. Dewilde, who was initially responding to his dog’s furious barking, grabbed his flashlight and headed outside to make sure nothing untoward was afoot. What would prove to be a life-changing experience occurred moments later, when he saw posed on the railroad tracks in front of him a shadowy vessel he first took to be a carelessly placed farmer’s cart, a common occurrence in the area. As he moved to investigate, Dewilde observed two small figures skulking in the shadows. Concluding they were smugglers returning to their contraband — also a frequent sight along the chemin de contrebandiers that passed nearby — he decided to intervene and capture one of them.1 Before he could act, however, a beam of light projected from the vehicle paralyzed him, leaving his senses free to process what was happening even as his body refused to respond. In that instant, Dewilde, an unwitting victim of an otherworldly civilization and their advanced technology, became one of the early focal points for observers — the convinced, the curious and the skeptical — interested in the UFO phenomenon in postwar France.
Correlation of Cobas HPV Testing and Follow-Up Biopsies in Women with Negative Pap Tests

High risk HPV (hrHPV) testing is commonly used as co-testing in cervical cancer screening or as a reflex test in cases with equivocal cytology. Recently the FDA approved the Cobas HPV test as a screening option in women above 25 years. Clinical data regarding the use of Cobas HPV testing in women with negative Pap tests is limited. Utilizing a large series of cases, this study analyzed the correlation of hrHPV tests and histologic biopsies in women with negative Pap tests. INTRODUCTION RESULTS MATERIALS AND METHODS
Imagining Domesticity in Cervantes' Novelas ejemplares and Don Quijote

AbstractThis article discusses the role of the home in both Miguel de Cervantes' Don Quijote and his Novelas ejemplares. The first half of the article addresses the relationship between the idea of wandering and the idea of home, showing that multiple characters understand Don Quijote's vagrancy as the key manifestation of his madness. Moreover, the knight's homelessness connects him to another wandering character: the Morisco Ricote. A historical and textual understanding of home and homelessness thus opens an interpretive space, one that registers Don Quijote's and Ricote's inability to wander as emblematic of the frustrated promise that modernity presented to Spain. Moving on to the Novelas ejemplares, we delineate in El celoso extremeno the identification of the private sphere with patriarchal values of honour, wealth, sexual control and legitimate offspring, and how these are undermined by the representatives of the public sphere. The same is shown to hold in four other stories as well.
STU III operation over 2.4 kbps links

The STU III phones are designed to work over public switched telephone networks and not over a digital link, such as a satellite 2.4-kb/s data link. Two interfaces, the STel 9610 and 9620, which enable two STU III phones to operate over synchronous 2.4 kb/s channels, are described. The STel 9610 STU III digital link interface unit provides an interface to the STU III phone that functions like a central office or PBX interface. It provides loop current, dial tone, ring back, busy signals, and can detect and process dual-tone multifrequency (DTMF) signals. The STel 9620 STU III Telco gateway interface is treated as a normal phone by the public switched network. The applications of these products are discussed. >
A Tyrosine-Serine Phosphorylation Switch in the JAM-A Cytoplasmic Domain Regulates In Vivo Thrombus Growth and Stability,

Abstract Abstract 3247 Dysregulation of the endogenous negative regulators present within the platelets may aid the thrombotic complications seen in various diseases. How endogenous negative regulators suppress platelet functions is not well understood. We have shown that junctional adhesion molecule A (JAM-A), a member of CTX (Cortical Thymocyte marker of the Xenopus) family is expressed on platelets. To understand the role of JAM-A in thrombosis, we used the Jam-A knockout mouse. We found that Jam-A knockout mice show a prothrombotic phenotype, as assessed by significantly (P Disclosures: No relevant conflicts of interest to declare.
Circulating Estradiol Regulates Brain-Derived Estradiol via Actions at GnRH Receptors to Impact Memory in Ovariectomized Rats

Systemic estradiol treatment enhances hippocampus-dependent memory in ovariectomized rats. Although these enhancements are traditionally thought to be due to circulating estradiol, recent data suggest these changes are brought on by hippocampus-derived estradiol, the synthesis of which depends on gonadotropin-releasing hormone (GnRH) activity. The goal of the current work is to test the hypothesis that peripheral estradiol affects hippocampus-dependent memory through brain-derived estradiol regulated via hippocampal GnRH receptor activity. In the first experiment, intracerebroventricular infusion of letrozole, which prevents the synthesis of estradiol, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory in a radial-maze task. In the second experiment, hippocampal infusion of antide, a long-lasting GnRH receptor antagonist, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory. In the third experiment, hippocampal infusion of GnRH enhanced hippocampus-dependent memory, the effects of which were blocked by letrozole infusion. Results indicate that peripheral estradiol-induced enhancement of cognition is mediated by brain-derived estradiol via hippocampal GnRH receptor activity.
Mental Health Aspects of Responding to Campus Crises

Tragedy can strike a college campus in unpredictable and often horrific ways that may lead to traumatic responses for individuals and the entire campus community. Crises on campus demand an appropriate response to support the community, provide assistance to affected individuals and guide healing efforts.
Assessing indirect measures of abundance and distribution with remote cameras: Simplifying indices of activity at pygmy rabbit burrows

Abstract Estimating abundance or distribution of species that are scarce or difficult to detect is challenging for wildlife biologists. Pygmy rabbits (Brachylagus idahoensis) are secretive, sagebrush (Artemisia spp.) obligates of conservation concern that occupy the Intermountain West, USA. These unique leporids are difficult to monitor; however using remote cameras in conjunction with ranking of burrow activity may help refine sampling techniques for these mammals. We classified and deployed remote cameras at 405 burrows of pygmy rabbits between 2006 and 2010 in six study areas across Utah, USA. We ranked burrows based on the appearance of fecal pellets, as well as the condition of burrow entrances. We also documented the presence of pygmy rabbits and potential competitors and predators of pygmy rabbits at burrows using remote cameras. We used mixed-effects, zero-inflated negative binomial models and AIC model selection to evaluate the relative influences of burrow activity ranking, season, and rate of photographs for potential competitors and predators of pygmy rabbits on photo rates of pygmy rabbits. The top 2 models supported a simplified (active or inactive) burrow classification system and accounted for 45% of AIC weight. Rates of pygmy rabbit photographs were further influenced by meters from habitat edge (β = 0.0008 ± 0.0004, 95% CI = 7.07E-05–0.002), photo rate of cottontail rabbits (β = 0.31 ± 0.11, 95% CI = 0.08–0.53), and were higher during summer than other times of the year (β = 0.38 ± 0.19, 95% CI = 0.01–0.74). Mean number of days to detection of pygmy rabbits at burrow complexes classified as active was four (SE = 0.61), and a two-week sampling period was needed to capture 81% of first detections. Our results refine commonly used ranking criteria of burrow complexes to a 2-level scale (active and inactive), and also emphasize the use of remote cameras as an effective technique for quantifying activity of pygmy rabbits at burrow complexes. Such information can help researchers and land managers more effectively survey this species for conservation and management efforts.
Vaginal Heparan Sulfate Linked to Neutrophil Dysfunction in the Acute Inflammatory Response Associated with Experimental Vulvovaginal Candidiasis.

Despite acute inflammation by polymorphonuclear neutrophils (PMNs) during vulvovaginal candidiasis (VVC), clearance of Candida fails to occur. The purpose of this study was to uncover the mechanism of vaginal PMN dysfunction. Designs included assessing PMN migration, proinflammatory mediators, and tissue damage (by analysis of the activity of lactate dehydrogenase [LDH]) in mice susceptible (C3H/HeN-C57BL/6) or resistant (CD-1) to chronic VVC (CVVC-S or CVVC-R) and testing morphology-specific Candida albicans strains under conditions of preinduced PMN migration (CVVC-S mice) or PMN depletion (CVVC-R mice). In vitro designs included evaluation of C. albicans killing by elicited vaginal or peritoneal PMNs in standard or vaginal conditioned medium (VCM). Results showed that despite significant migration of PMNs and high levels of vaginal beta interleukin-1 (IL-1β) and alarmin S100A8, CVVC-S mice failed to reduce vaginal fungal burden irrespective of morphology or whether PMNs were present pre- or postinoculation, and had high LDH levels. In contrast, CVVC-R mice had reduced fungal burden and low LDH levels following PMN recruitment and IL-1β/S100A8 production, but maintained colonization in the absence of PMNs. Elicited vaginal and peritoneal PMNs showed substantial killing activity in standard media or VCM from CVVC-R mice but not in VCM from CVVC-S mice. The inhibitory effect of VCM from CVVC-S mice was unaffected by endogenous or exogenous estrogen and was ablated following depletion/neutralization of Mac-1 ligands using Mac-1+/+ PMNs or recombinant Mac-1. Heparan sulfate (HS) was identified as the putative inhibitor as evidenced by the rescue of PMN killing following heparanase treatment of VCM, as well as by inhibition of killing by purified HS. These results suggest that vaginal HS is linked to PMN dysfunction in CVVC-S mice as a competitive ligand for Mac-1.IMPORTANCE Vaginal candidiasis, caused by Candida albicans, affects a significant number of women worldwide. Despite an acute inflammatory response by neutrophils during infection, the response fails to reduce the organism. Instead, the response is considered a key process underlying the symptoms of vaginitis. Therefore, it is important to determine the mechanism(s) associated with the lack of vaginal neutrophil antifungal activity. The established mouse model of Candida vaginitis was used to uncover the mechanism of neutrophil dysfunction. Results revealed that heparan sulfate present in the vagina of mice susceptible to chronic vaginitis served as a competitive ligand for the receptor (Mac-1) necessary for fungal recognition and neutrophil-mediated killing. This inhibitory function of heparan sulfate, confirmed through several approaches, provides the first evidence to explain the lack of antifungal immune reactivity during vaginal candidiasis. This finding paves the way for design of therapeutic strategies to reduce/eliminate symptomatic vaginal candidiasis and restore quality of life to those affected.
Proximal Junctional Kyphosis Prevention Strategies: A Video Technique Guide

BACKGROUND: Proximal junctional kyphosis (PJK) is a well-recognized complication in patients undergoing posterior instrumented fusion procedures for adult spinal deformity. Strategies that reduce rates of PJK have the potential to improve the safety of these operations and decrease cost by eliminating the need for revision surgery. OBJECTIVE: To present a set of surgical techniques that can decrease rates of PJK in adults undergoing surgery for spinal deformity. METHODS: We summarize the use of vertebroplasty, transverse process hooks, terminal rod contouring, and ligament augmentation as means to reduce rates of PJK. RESULTS: We present PJK prevention strategies and a video technique guide that are safe, technically feasible, and add minimal operative time to these surgical procedures. When applied to appropriate high-risk patients, these techniques have the potential to dramatically reduce rates of PJK, which improves quality of life and decreases the cost associated with this treating adult spinal deformity. CONCLUSION: PJK prevention strategies represent a critical area for improvement in surgery for adult spinal deformity. We present a summary of techniques that are safe, feasible, and add minimal time to the overall procedure. These techniques warrant investigation in a thoughtful, prospective manner, but are supported by existing data and compelling biomechanical rationale. Our hope is that these strategies can be applied, particularly in high-risk patients, to help reduce rates of PJK.
The History of Keratoplasty: A Brief Overview

The histories of keratoprosthesis and corneal allograft (penetrating keratoplasty) are complex and intimately intertwined. Of the two procedures, keratoprosthesis predates penetrating keratoplasty by almost a century and, as such, plays an important role in the development of corneal transplantation. For the contemporary corneal surgeon interested in keratoprosthesis surgery, understanding the historical landmarks of both keratoplasty and prosthokeratoplasty is important to the recognition of the obstacles we face to finding a successful artificial cornea.
An application of the fast gradient method to model predictive control of an atomic force microscope X-Y stage

Random sub-sampling imaging methods in Atomic Force Microscopy require the piezo X-Y stage to track a sequence of step inputs. Control slew-rate limits combined with linear feedback methods have been shown to limit achievable performance in this scenario. Due to its natural ability to account for actuation constraints, we consider the application of Model Predictive Control. By recasting the problem in an incremental form, the arising quadratic program takes a form that can be solved efficiently. Specifically, we solve an input constrained Model Predictive Control problem with 50 states, a control horizon of 12 samples, and a sample frequency of 25 kHz using the Fast Gradient Method. We present experimental results using the method applied to a nano-positioning stage.
Regulation of Bacterial Genes

It is now apparent that the activities of many bacterial genes are regulated by several interlocking control apparatuses that respond to different small molecule effectors. An overview suggests the existence of a hierarchy of controls (Zubay, 1973). For example, the gene cluster known as the lac operon is induced by the presence of lactose. Lactose is also the substrate of the enzyme β-galactosidase, which is encoded by the lac operon. The induction of the lac operon by lactose is brought about by a highly specific control process that does not directly affect the activities of other genes. At a more general level of control, the expression of the lac operon is dependent upon the presence of 3’:5’-cyclic AMP (cAMP). This dependence is characteristic of many genes that encode catabolic enzymes. At an even more general level of control, we find a mechanism that appears to modulate transcription according to the gross rate of translation. The small molecule effector for this control process is probably guanosine tetraphosphate (guano-sine bis-diphosphate, ppGpp). The effect this compound has depends upon the gene — for the lac operon ppGpp is stimulatory.