cssi/SciSciGPT-SciSciNet huggingface dataset:
Solithromycin Inhibition of Protein Synthesis and Ribosome Biogenesis in Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae

The continuing increase in antibiotic-resistant microorganisms is driving the search for new antibiotic targets and improved antimicrobial agents. Ketolides are semisynthetic derivatives of macrolide antibiotics, which are effective against certain resistant organisms. Solithromycin (CEM-101) is a novel fluoroketolide with improved antimicrobial effectiveness. This compound binds to the large 50S subunit of the ribosome and inhibits protein biosynthesis. Like other ketolides, it should impair bacterial ribosomal subunit formation. This mechanism of action was examined in strains of Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae. The mean 50% inhibitory concentrations (IC50s) for solithromycin inhibition of cell viability, protein synthesis, and growth rate were 7.5, 40, and 125 ng/ml for Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae, respectively. The net formation of the 50S subunit was reduced in all three organisms, with IC50s similar to those given above. The rates of 50S subunit formation measured by a pulse-chase labeling procedure were reduced by 75% in cells growing at the IC50 of solithromycin. Turnover of 23S rRNA was stimulated by solithromycin as well. Solithromycin was found to be a particularly effective antimicrobial agent, with IC50s comparable to those of telithromycin and significantly better than those of azithromycin and clarithromycin in these three microorganisms.
Lightweight Traffic-Aware Packet Classification for Continuous Operation

Packet classification is primarily used by network devices, such as routers and firewalls, to do additional processing for a specific subset of packets. Such additional processing includes packet filtering, quality of service (QoS), and differentiated services (DiffServ). Most of the existing packet classification algorithms reported in the literature exploits the characteristics of filtering or classifier rules in optimizing their techniques. However, the seminal observation made by Gupta and McKeown [1], [2] that a given packet matches only few rules in the classifier shows promise to another direction that packet classifier’s average performance can be improved by exploiting the locality in the incoming traffic pattern. In this paper, we undertook the investigation of finding the feasibility of exploiting the locality in traffic to improve packet classifier’s average performance. Our lightweight traffic-aware packet classifier reorganizes its internal data structure (rule tree) based on the traffic pattern to reduce the search time for the most frequently visited rules in the rule-set. Unlike existing traffic-adaptive packet classifier requiring a separate, offline reorganization phase, our approach performs reorganization online with little overhead, resulting in higher throughput without compromising the accuracy. Experimental results on our test bed show that our traffic-adaptive packet classifier incurs small number of memory accesses (i.e. less time per packet) in order to classify the packet.
Structural and electron-transfer characteristics of O-, S-, and Se-tethered porphyrin monolayers on Si(100).

Structural and electron-transfer characteristics are reported for two classes of zinc porphyrin monolayers attached to Si(100) surfaces via Si−C bonds. One class, designated ZnP(CH2)n− (n = 2−4), contains an alkyl linker appended to the meso-position of the porphyrin, with the nonlinking substituents being p-tolyl groups. The other, designated ZnPPh(CH2)n− (n = 0−3), contains a phenyl or phenylalkyl linker appended to the meso-position of the porphyrin, with the nonlinking substituents being mesityl groups. Both classes of zinc porphyrin monolayers on Si(100) were examined using Fourier transform infrared spectroscopy and various electrochemical methods. The studies reveal the following: (1) The structural and electron-transfer characteristics of the ZnP(CH2)n− and ZnPPh(CH2)n− monolayers are generally similar to those of monolayers formed from porphyrins with analogous linkers, but anchored with an O, a S, or a Se atom. (2) The ZnP(CH2)n−, ZnPPh−, and ZnPPhCH2− monolayers exhibit lower saturation covera...
Crafting Questions That Address Comprehension Strategies in Content Reading.

This article describes initial attempts by preservice and inservice teachers enrolled in university reading courses to devise questions that encourage students to read content texts strategically. Teachers at both levels tended to confuse questions that encourage the use of comprehension strategies during reading with questions that assess comprehension of what has been read. Despite understanding the aspects of cognition that promote good comprehension, at first these elementary and middle-grade teachers appeared to revert to ingrained questioning models that largely ignored the cognitive components of comprehension. The distinction between the design and functions of these questions must be clear to teachers if they are to be effective in helping students construct meaning from subject matter texts. University classes that provide modeling and practice in crafting and asking strategic questions support content teachers in this important skill.
γ-Synuclein interacts with phospholipase Cβ2 to modulate G protein activation.

Phospholipase Cβ2 (PLC β2) is activated by G proteins and generates calcium signals in cells. PLCβ2 is absent in normal breast tissue, but is highly expressed in breast tumors where its expression is correlated with the progression and migration of the tumor. This pattern of expression parallels the expression of the breast cancer specific gene protein 1 which is also known as γ-synuclein. The cellular function of γ-synuclein and the role it plays in proliferation are unknown. Here, we determined whether γ-synuclein can interact with PLCβ2 and affect its activity. Using co-immunprecitation and co-immunofluorescence, we find that in both benign and aggressive breast cancer cell lines γ-synuclein and PLCβ2 are associated. In solution, purified γ-synuclein binds to PLCβ2 with high affinity as measured by fluorescence methods. Protease digestion and mass spectrometry studies show that γ-synuclein binds to a site on the C-terminus of PLCβ2 that overlaps with the Gαq binding site. Additionally, γ-synuclein competes for Gαq association, but not for activators that bind to the N-terminus (i.e. Rac1 and Gβγ). Binding of γ-synuclein reduces the catalytic activity of PLCβ2 by mechanism that involves inhibition of product release without affecting membrane interactions. Since activated Gαq binds more strongly to PLCβ2 than γ-synuclein, addition of Gαq(GTPγS) to the γ-synuclein –PLCβ2 complex allows for relief of enzyme inhibition along with concomitant activation. We also find that Gβγ can reverse γ-synuclein inhibition without dissociating the γ-synuclein- PLCβ2- complex. These studies point to a role of γ-synuclein in promoting a more robust G protein activation of PLCβ2.
Access control for a replica management database

Distributed computation systems have become an important tool for scientific simulation, and a similarly distributed replica management system may be employed to increase the locality and availability of storage services. While users of such systems may have low expectations regarding the security and reliability of the computation involved, they expect that committed data sets resulting from complete jobs will be protected against storage faults, accidents and intrusion. We offer a solution to the distributed storage security problem that has no global view on user names or authentication specifics. Access control is handled by a rendition protocol, which is similar to a rendezvous protocol but is driven by the capability of the client user to effect change in the data on the underlying storage. In this paper, we discuss the benefits and liabilities of such a system.
Lower-bound performance estimation for the high-level synthesis scheduling problem

A given behavioral specification can be implemented on a large number of register-transfer level designs. Instead of producing several designs and selecting the best one, synthesis systems may use estimation to reduce the design space. In this paper, we present a new technique for computing a lower-bound completion time for non-pipelined resource-constrained scheduling problem. Given a data flow graph, a set of resources, resource delays and a clock cycle, we derive a lower-bound on the completion time of a schedule. Our technique can handle chaining, multi-cycle operations and pipelined modules. The technique is very fast and experimental results show that it is also very tight. >
Partitioning single-molecule maps into multiple populations: algorithms and probabilistic analysis

Abstract Given a set of m molecules, derived from K homologous clones, we wish to partition these molecules into K populations, each giving rise to distinct ordered restriction maps, thus providing simple means for studying biological variations. With the emergence of single-molecule methods, such as optical mapping, that can create individual ordered restriction maps reliably and with high throughput, it becomes interesting to study the related algorithmic problems. In particular, we provide a complete computational complexity analysis of the “ K -populations” problem along with a probabilistic analysis. We also present some simple polynomial heuristics, while exposing the relations among various error sources that the optical mapping approach may need to cope with. We believe that these results will be of interest to computational biologists in devising better algorithms, to biochemists in understanding the trade-offs among the error sources and finally, to biologists in creating reliable protocols for population study.
Effects of spinal lesions on temporal resolution of cutaneous sensations.

In order to test the possibility that the dorsal columns (DCs) contribute to temporal resolution of tactile stimuli, Macaca speciosa monkeys were trained to discriminate different frequencies of stimulation delivered to the glabrous surface of the left foot. Brief (11-msec) pulses of 550-μm indentation from the skin surface were presented for 1 sec at a standard rate of 10 pulses per second (pps), and subsequent trains of the same duration either were replications of the standard or consisted of a higher (comparison) frequency of up to 35 pps. Correct performance consisted of a lever press in response to the comparison stimulus when it occurred as the second or third train in a trial. Signal detection analysis of response tendencies in the second stimulus interval revealed difference threshold values of 2.8 pps, on the average, for 75% correct responding. Transections of the ipsilateral dorsolateral column or the contralateral anterolateral column or both did not significantly affect discrimination of the...
Electoral competition, factionalism, and persistent party dominance in Botswana

The Botswana Democratic Party (BDP) has maintained a super-majority in the National Assembly for over forty years despite increasingly competitive elections. Several factors contribute to the BDP's continued legislative dominance, including features of the electoral system, fragmentation of the party system, and obstacles to strategic voting behaviour. Factional competition has played a particularly important role. Botswana's political institutions encourage factional competition, and factionalism interacts with the electoral system to hinder consolidation of the party system. Botswana's experience underlines the importance of internal party dynamics and their interaction with features of the electoral and party system in enabling the persistence of legislative dominance in competitive electoral systems.
Hysteresis and Eddy-Current Losses in Iron at Radio Frequencies

After reviewing the bibliography of heat losses per cycle at various frequencies, the author describes a comparison calorimnetic method whereby the losses in the soft iron wire core of a toroid are measured (against a similarly wound toroid without an iron core). The Chaffee gap radio frequency generator is used. Braun tube oscillograms of the cycle are shown, together with experimental data on the iron losses. It is found that the loss per cycle decreases as the frequency increases.
DOMINEERINGNESS AND DOMINANCE: A TRANSACTIONAL VIEW

This paper attempts to clarify the conceptualization of interpersonal power dimensions and offers a relational-level definition and measure of dominance. A distinction is made between control movements indicating domineering message behavior and control patterns of dominance. The findings support (1) that domineeringness and dominance are separate control variables, and (2) that different dyadic patterns of satisfaction and interaction style are associated with these two dimensions.
Access to Nursing Home Hospice: Perspectives of Nursing Home and Hospice Administrators

Background and objectives: Hospice improves the quality of end of life care in nursing homes but serves less than 10% of dying residents. For residents to elect hospice, nursing homes must first co...
Grief Counseling and Crisis Intervention in Hospital Trauma Units Counseling Families Affected by Traumatic Brain Injury

The demand for family counselors implementing crisis intervention and grief counseling in hospital trauma units continues to increase. Thus, this article provides a review of the nature of family c...
On isospectral locally symmetric spaces and a theorem of von Neumann

1. Introduction. Call two lattices F1 and F2 in a locally compact group G isospectral if the representations of G on L2(G/FI) and L2(G/F2) are unitarily equivalent. Here we show that isospectral lattices are quite common in semisimple real algebraic groups G. We construct them using a variation of a technique of Sunada [Su]. As a consequence, we obtain new examples of locally symmetric spaces with isospectral Laplacians. In particular, we get such examples with higher rank. Previously, the only higher-rank isospectral manifolds known were locally reducible. These were Vigneras’s examples of quotients of products of hyperbolic spaces I-V]. On the other hand, Brooks found irreducible higher-rank locally symmetric spaces with isospectral potentials i-Br-I. However, the underlying manifolds in his examples happened to be isometric. This was due to Mostow rigidity, since the fundamental groups were isomorphic. In fact, this work was largely motivated by the question of whether the rigidity properties of lattices in higher rank force an isospectral rigidity.
SURVIVAL AND DEVELOPMENT OF IPS PARACONFUSUS LANIER (COLEOPTERA: SCOLYTIDAE) REARED AXENICALLY AND WITH TREE-PATHOGENIC FUNGI VECTORED BY COHABITING DENDROCTONUS SPECIES

Survival and development of Ips paraconfusus Lanier larvae reared individually in intact Pinus ponderosa Laws. phloem without associated fungi and dietary supplements was demonstrated. Survival was reduced.in intact ponderosa pine phloem previously occupied by other larvae or by bluestaining fungi [i.e. Ophiostoma ips (Rumb.) vectored by I. paraconfusus, O. minus (Hedge.) H. & P. Syd. vectored by Dendroctonus brevicomis LeConte, O. clavigerum (Robins.-Jeff. & Davids.) vectored by D. ponderosae Hopkins, and Leptographium terebrantis Barras & Perry vectored by D. valens LeConte] compared with those reared without fungi or symbiotic yeasts. The highest proportion of larvae initiating tunnels and surviving to adult was observed for untreated eggs, and the lowest proportion occurred in the L. terebrantis treatment. Size was reduced and developmental rate was slower for larvae reared without fungi compared with larvae reared with associated fungi.Tunnels excavated by first- and second-instar larvae reared without associated fungi were longer than those excavated by larvae reared with associated fungi. The most frequent larval turnabouts occurred with larvae reared axenically and reared with Ips yeast and O. ips. The fewest occurred with larvae reared with Ips egg niche plugs and from untreated eggs. Females reared free of any fungi or with Penicillium or Aspergillus did not oviposit in surface-sterilized ponderosa pine logs. Naturally eclosed females from ponderosa pine logs in which they developed, laid eggs in these sterilized logs. Potential for a new association among bark beetles and fungi is discussed.
Electrically Tunable Ultra-specific Zinc Oxide Biosensor

Zinc oxide surface states can be utilized for ultra-specific detection of biomolecules. The major challenges in using ZnO for bio-sensing are attaining enhanced sensitivity and specificity. In this study, we explore the functionalization of zinc in ZnO through utilizing the thiol bond. The purpose of this study is to demonstrate that the ZnO based sensor is capable of achieving high specificity in presence of competitive surface binding through the thiol bond. The final goal is to design an ultra-specific biosensor to detect low occurring biomolecules. In this study, we have selected cortisol as a stress marker to demonstrate quantification and detection from synthetic sweat. In order to demonstrate ultra-specificity, we have used two competitive thiol based molecules binding to zinc, a linker Dithiobis succinimidyl propionate (DSP) and reducing agent of DSP, Dithiothreitol (DTT). Electrochemical impedance spectroscopy (EIS) is used to quantify the signal obtained through various ratiometric concentrations of DSP and DTT. To validate the EIS study results, inherent fluorescence studies are done by mapping changes in green emission spectrum of ZnO before and after linker functionalization. The optimal combination in terms of highest signal is identified to be of 25mM DTT and 50mM DSP. This is implemented in the experiments performed to calibrate the cortisol concentration in synthetic sweat. This study demonstrates the detection of cortisol antigen in synthetic sweat present within the physiological levels of 8 ng/mL to 140 ng/mL.
Measurements of scattering and absorption in mammalian cell suspensions

During the past several years a range of spectroscopies, including fluorescence and elastic-scatter spectroscopy, have been investigated for optically based detection of cancer and other tissue pathologies. Both elastic-scatter and fluorescence signals depend, in part, on scattering and absorption properties of the cells in the tissue. Therefore an understanding of the scattering and absorption properties of cells is a necessary prerequisite for understanding and developing these techniques. Cell suspensions provide a simple model with which to begin studying the absorption and scattering properties of cells. In this study we have made preliminary measurements of the scattering and absorption properties of suspensions of mouse mammary carcinoma cells (EMT6) over a broad wavelength range (380 nm to 800 nm).
The Performance of Two Tympanic Thermometers in a Pediatric Emergency Department

In a prospective, unblinded, controlled study, 303 children underwent comparison of rectal (RT) and right-sided tympanic membrane (TMT) temperatures. Digital electronic thermometers were used for RT, while two different infrared detection devices assessed TMT. The performance of TMT devices were compared using correlation with RT, fever detection, and ease of use. Correlation between RT and the two devices was good, r = 0.70 and r = 0.69, with little influence of patient age on performance. Using receiver operating characteristics curves to assess fever screening. Thermoscan@ performed somewhat better than First Temp@. Staff rated the Thermoscan® as significantly easier to use.
Cushing Syndrome Induced by Serial Occipital Nerve Blocks Containing Corticosteroids

A patient with chronic daily headaches developed overt signs of Cushing syndrome during treatment with serial occipital nerve block injections. Investigation demonstrated an exogenous source of corticosteroids as the cause of the Cushing syndrome in this patient, thus, implicating the corticosteroid component of the occipital nerve blocks. To our knowledge, this is the first report of Cushing syndrome caused by occipital nerve blockade. Caution is warranted in employing even usual therapeutic doses of synthetic corticosteroids, particularly in long-acting or depot preparations.
Entire Flexor Carpi Radialis Tendon Harvest for Thumb Carpometacarpal Arthroplasty Alters Wrist Kinetics

Purpose To investigate the clinical outcome of thumb carpometacarpal arthroplasty with entire-thickness flexor carpi radialis (FCR) ligament reconstruction and tendon interposition and to investigate the isokinetic wrist flexion/extension torque and flexion fatigue strength of the surgically treated wrist compared with the nonsurgically treated wrist. Methods Thirty-nine patients with osteoarthritis who had unilateral thumb carpometacarpal arthroplasty with the entire FCR tendon were studied prospectively with a minimum follow-up period of 24 months. Preoperative Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire score, grip, pinch, and postoperative DASH score, grip, pinch, and Biodex (Shirley, NY) isokinetic wrist flexion/extension torques were recorded. The nonsurgically treated extremity served as the control for each patient with unilateral ligament reconstruction and tendon interposition. Peak torque ratios and fatigue were measured for the control and surgically treated extremities with the Biodex. Results Postoperative DASH scores were 12 ± 4 and were improved significantly from preoperative scores of 43 ± 4. The surgically treated extremity showed a significantly lower wrist flexion-to-extension peak torque ratio than the control extremity. The control extremity had 2.5 times greater wrist flexion fatigue resistance than the surgically treated side. After surgery the surgically treated extremity had significantly improved grip strength and thumb–index tip pinch compared with the preoperative status. Conclusions Our data show conclusively that wrist flexion extension torque ratio decreases and wrist flexion fatigue resistance decreases when the entire FCR tendon is harvested even though the final outcome is favorable and uniformly based on traditional DASH, grip, and pinch scores.
The tale of the wandering circumflex

A 53-year-old male underwent coronary catheterization after presenting with recurrent chest pain and non-specific ECG changes. The RCA and LAD were noted to arise from the right sinus of …
Blur identification by residual spectral matching

The estimation of the point spread function (PSF) for blur identification, often a necessary first step in the restoration of real images, method is presented. The PSF estimate is chosen from a collection of candidate PSFs, which may be constructed using a parametric model or from experimental measurements. The PSF estimate is selected to provide the best match between the restoration residual power spectrum and its expected value, derived under the assumption that the candidate PSF is equal to the true PSF. Several distance measures were studied to determine which one provides the best match. The a priori knowledge required is the noise variance and the original image spectrum. The estimation of these statistics is discussed, and the sensitivity of the method to the estimates is examined analytically and by simulations. The method successfully identified blurs in both synthetically and optically blurred images. >
Filmless radiology at the Baltimore VA Medical Center: a 9 year retrospective.

The transition from conventional film based to filmless operation at the Baltimore VA Medical Center in 1993 was successful and has resulted in a number of clinical and economic benefits. The subsequent integration of the Department of VA hospitals in Maryland into a single network, the VA Maryland Health Care System, resulted in the opportunity to establish a 'virtual' radiology and nuclear medicine department. This integrated department is based upon a wide area network in which outlying medical centers utilize a central HIS/RIS and a central commercial Picture archival and communication system (PACS) as well as a VA 'home grown' image management and communication system, the VISTA imaging system. The creation of this virtual radiology/nuclear medicine department has resulted in additional savings and improvements in clinical care. The benefits of the PACS were made possible, to a large extent, by the high level of integration of the PACS and medical modalities with the hospital information and transcription systems. Our experience suggests that it is absolutely essential to integrate the PACS into the patient's electronic medical record in order to maximize efficiency and clinical effectiveness of the system.
Effect of fractal rough-surface Hurst exponent on speckle in imaging systems

Speckle image contrasts from a fractal rough-surface object are investigated in simulation, where the image surface is conjugate to the object surface. It is observed that the Hurst exponent H of fractal roughness affects speckle contrast and statistics dramatically. For example, a strong rough surface (σh>λ) exhibits Rayleigh statistics over increasing ranges of point spread function widths as H decreases. Conceptual explanations are also presented for effects of H and the coherence factor on speckle in imaging systems.
Use of an interactive teaching program to teach medical workers, about MUMPS programming.

The MUMPS computer language is widely and increasingly used for medical applications. It is useful for medical students and others in the medical environment to have an understanding of such languages that can help them perform their jobs well. The author is therefore making available an interactive teaching program to instruct such people in the MUMPS computer language. Use of the teaching program is reported for 19 novice MUMPS programmers and compared with results for two experienced programmers. Free-text comments by the novices emphasize areas in which they had difficulty. There is a considerable variation in the mean time taken by the novices to answer the questions, and in the number of questions repeated because of erroneous answers. Most novices found the teaching program very helpful. A copy of the Standard MUMPS teaching program and the QUEST driver on which it is based has been sent to 24 institutions, including six in Europe and one in Japan, for further use.Le langage MUMPS est de plus en pl...
Design and construction of tapered cells

Tapered cells are used in E-field probes calibration [1]–[2]. Nevertheless, few studies on tapered cells are found. In this paper, the structure of taper cells is introduced and a theoretical model for characteristic impedance calculation is provided. Based on this model, we constructed a tapered cell. And the model is then verified by the measured characteristic impedances of the tapered cell.
Seasonal suicide attempts and forms of loneliness.

The purpose of this study was to assess the relation of two components of loneliness, present and future loneliness, to seasonality of suicide attempts. The 110 subjects were persons who attempted suicide during 1 mo. of a 12-mo. period. Seasonally the maximum frequencies of occurrence were in spring and winter. The mean scale scores for present and future loneliness were greatest for spring and winter, the peak seasons for the timing of suicide attempts. It was speculated that persons may actually postpone acts of attempted suicide in order to participate and become emotionally involved in important annual ceremonies. This would account for the seasonal pattern in attempted suicide and in specific forms of loneliness.
Predicted secondary structure of the foraminiferal SSU 3' major domain reveals a molecular synapomorphy for granuloreticulosean protists

The small subunit ribosomal RNA genes of foraminiferal protists are the largest and most divergent of any eukaryote. We demonstrate that this foraminiferal sequence alteration represents a substantial modification to the small subunit ribosomal RNA structure, including a large (up to 350 nt) novel helix in a very well-conserved portion of the head domain. This modification dates from the beginning of the foraminiferal radiation and, within modern orders, is partially conserved at the sequence level, suggesting that it is a functional part of the ribosome. The pattern of conservation makes it particularly useful for determining lower-taxon relationships in morphologically ambiguous allogromiid foraminifera.
Cholesterol microcrystals associated with concanavalin A-binding glycoproteins contribute artifactually to nucleating activity assays

Concanavalin A (Con A) affinity chromatography is the standard procedure to separate cholesterol nucleating biliary proteins from lipids and pigment. We observed that even after extensive washing following application of bile, lipid contaminants remain. We have determined the contribution of lipid contamination to cholesterol nucleation and assessed a modified procedure to remove lipids from the column. Human gallbladder bile was spiked with [3H]cholesterol and [14C]phospholipid and applied to two sets of Con A-Sepharose columns. One column was washed in the usual manner with Tris-HCl buffer and the other with buffer containing 10 mM taurocholate prior to eluting bound glycoproteins with alpha-D-methylmannopyranoside. Eluted proteins were added to heated abnormal bile at a final concentration of 250 micrograms/ml to study the effect on cholesterol nucleation. A separate aliquot (20 microliter) of the protein solutions was counted for radioactivity. Cholesterol nucleating activity was less in samples from columns washed with 10 mM taurocholate than in samples from columns not washed with the bile salt. Lipid radioactivity was associated with Con A-binding proteins prepared without taurocholate, but not in those prepared with taurocholate wash. Light microscopy revealed the presence of cholesterol microcrystals and vesicles in some Con A-binding protein preparations prepared without a taurocholate wash. However, pellets from ultracentrifuged Con A preparations prepared without a bile salt wash revealed cholesterol crystals in all samples (n = 6). Washing with taurocholate did not affect recovery of protein mass and appearance of bands on SDS-PAGE gel showed an identical pattern in the two groups. This modified procedure to prepare potential nucleating proteins from gallbladder bile should eliminate erroneous results that may arise due to lipid contamination.
The gastrin-releasing peptide analog bombesin preserves exocrine and endocrine pancreas morphology and function during parenteral nutrition

Stimulation of digestive organs by enteric peptides is lost during total parental nutrition (PN). Here we examine the role of the enteric peptide bombesin (BBS) in stimulation of the exocrine and endocrine pancreas during PN. BBS protects against exocrine pancreas atrophy and dysfunction caused by PN. BBS also augments circulating insulin levels, suggesting an endocrine pancreas phenotype. While no significant changes in gross endocrine pancreas morphology were observed, pancreatic islets isolated from BBS-treated PN mice showed a significantly enhanced insulin secretion response to the glucagon-like peptide-1 (GLP-1) agonist exendin-4, correlating with enhanced GLP-1 receptor expression. BBS itself had no effect on islet function, as reflected in low expression of BBS receptors in islet samples. Intestinal BBS receptor expression was enhanced in PN with BBS, and circulating active GLP-1 levels were significantly enhanced in BBS-treated PN mice. We hypothesized that BBS preserved islet function indirectly, through the enteroendocrine cell-pancreas axis. We confirmed the ability of BBS to directly stimulate intestinal enteroid cells to express the GLP-1 precursor preproglucagon. In conclusion, BBS preserves the exocrine and endocrine pancreas functions during PN; however, the endocrine stimulation is likely indirect, through the enteroendocrine cell-pancreas axis.
Abstract IA25: Autophagy: A potentially druggable resistance mechanism to PI3K/mTOR inhibitors

Inhibition of PI3K/mTOR signaling in cancer cells activates autophagy. Numerous preclinical models have demonstrated therapy-induced autophagy in advanced cancer promotes tumor cell survival and is a targetable resistance mechanism. Clinical trials involving the lysosomal autophagy inhibitor hydroxychloroquine (HCQ) have been launched for patients with refractory malignancies. Currently there are nearly 30 early phase clinical trials involving HCQ for a variety of malignancies in development or actively accruing patients in the United States and abroad. The results of the first 6 HCQ clinical trials (5 in humans, 1 in dogs) that represent the first deliberate attempt to modulate autophagy therapeutically in patients will be presented. This includes a phase I trial of the mTOR inhibitor temsirolimus, and hydroxychloroquine in patients with advanced melanoma which produced a low rate of grade 3-4 toxicities and a 74 % stable disease rate. The development of novel translatable pharmacodynamic assays to characterize autophagy modulation in peripheral blood cells and tumor tissue using electron microscopy, and newer serum-based approaches based on a proteomics discovery effort will be highlighted. Our efforts to synthesize a more potent second generation autophagy inhibitor Lys05, and our plans to move a Lys05 derivative into the clinic will be discussed. Citation Format: Ravi Amaravadi. Autophagy: A potentially druggable resistance mechanism to PI3K/mTOR inhibitors. [abstract]. In: Proceedings of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(7 Suppl):Abstract nr IA25.
Controlling the occlusion of single restorations with CAD/CAM technology.

Abstract Computer-assisted design, computer-assisted machining (CAD/CAM) technology has received considerable clinical and research interest as a means to fabricate all-ceramic restorations. Laboratory CAD/CAM systems recreate occlusal anatomy and functional contacts using accurately articulated casts to minimize the amount of intraoral occlusal adjustment. CAD/CAM systems designed for the chairside do not use articulated casts, and yet fabricate full-contour restorations in a single appointment. Several design techniques are discussed to illustrate the 3 dimensional capability of the CAD program to plan and control occlusal contacts before milling the final restoration.
Positive and negative staircase effect during single twitch and train-of-four stimulation: a laboratory study in dogs

A positive staircase effect is well documented during neuromuscular monitoring. However, the increase in twitch amplitude may not remain stable over time. We compared the staircase phenomenon and twitch stability during single twitch (ST) or train-of-four (TOF) stimulation in anesthetized dogs. Force of contraction was measured in ten dogs. Each thoracic limb was stimulated with ST 0.1 Hz or TOF q 12 s for 25 min (random order). No neuromuscular blockers were administered. Every 5 min, ST and T1 amplitudes were compared within and between groups. Stability of twitch amplitude ( 5 % with TOF. An initial increase in ST amplitude remained stable over the observation period, but the increase in T1 amplitude during TOF was frequently followed by a decay. A stable twitch amplitude (variation <5 % in 5 min) was observed in all dogs with ST after 15 min of stimulation, which was not the case during TOF stimulation. Therefore, it appears at least in dogs, that ST might offer some advantages over T1 for measuring twitch amplitude.
A 10 Gb/s Inductorless AGC Amplifier With 40 dB Linear Variable Gain Control in 0.13 $\upmu \text{m}$ CMOS

This work presents an inductorless, 10 Gbps automatic gain control (AGC) circuit including a speed enhanced variable gain amplifier (VGA), a power detector, a comparator, and a novel exponential function generator for extended dB-linear performance. Third-order interleaved feedback technique is utilized in the current steering VGA stage to achieve 10 Gb/s operation without using on-chip inductors. A stagger-tuned switching architecture for CMOS exponential function generation is proposed to achieve a dB-linear gain control range of ${\sim}40\;\text{dB}$ with better than $\pm 1\;\text{dB}$ gain error. The relationship between tuning range and approximation error is analyzed and a novel current ratio generator circuit is proposed to implement the approximation functions in the current domain. The AGC circuit achieves a highest data rate of 10 Gb/s for ${2}^{31}{-}1$ PRBS input, maintaining $360\;\text{mV}_\text{p-p}$ constant differential output with a BER ${ for an input dynamic range of ${\sim}24\;\text{dB}$ (15–240 $\text{mV}_\text{p-p}$ ). Fabricated in IBM 0.13 $\upmu \text{m}$ CMOS technology, the chip draws 50 mW from a 1.2 V power supply (excluding the output buffer) and occupies an active area of $0.4\;\text{mm}^{2}$ .
Developmental defects and mortality rate of fetuses and newborns from multiple pregnancies.

The analysis of 682 newborns indicated that developmental defects accounted for 0.44% of the overall perinatal mortality of twins. The 3.7% higher mortality rate for second twins is frequently due to abnormal presentation and longer time-interval following the birth of the first twin.
CLINICAL ASPECTS ASSOCIATED WITH ADJUSTMENT IN UNUSUAL SLEEPERS

Summay.-Sleep behavior and self-reported adjustment of 93 young adult sleepers were measured. The 34 unusual sleepers (short, long or variable) ddfered in adjusunent from controls. 7 short sleepers reported more intense, worrisome responses than other unusual sleepers and controls. Sleep behavior is measured through a combination of biological rhythms and socially determined patterns. Approximately five percent of the population has an unusual sleep duration pattern which is excessively long (8.5 hr. or more), short (5 hr. or less), or variable (combination of long, short and average). Taub identified an average pattern as 7 to 7.5 hr. Short sleepers have been characterized as efficient, energetic, ambitious, "preprogrammed" nonworriers. Long sleepers have been characterized as nonaggressive, reflective indviduals who are constantly "reprogramming" themselves. The present study involved the identification of adjustment and its concordant cltnical features among usual and average sleepers. It was hypothesized that differences in adjustment would be found among the types of sleepers. Ninety-three protocols were analyzed from a sample of 121 undergraduates with attrition due to incomplete recordings. Of the 93 students 34 were classified as long, short, or variable sleepers using standard criteria. All subjects logged their sleep for two weeks and completed the Rotter Lncomplete Sentence Blank. Separate statement scores and a total score were compared with same age-sex norms; increasing scores reflect greater conflict. The classification of sleepers was 15 long, 7 short, and 12 variable. Twelve protocols selected randomly from the sample of remaining average sleepers were used for a control sample. The index for the short sleepers (M = 141.86) was statistically significantly ddferent from the groups of long (122.42), variable (124.621, and average (128.02; F2,,,=3.38, p < .001). The short sleepers' index score is in the maladjusted range. An index score was computed from the linear (unweighted) addition of responses to questions in four areas (Family, Social and Sexual Relationship, General Attitude, Character Traits); means were subjected to analysis of variance. Statistically significant differences between General and Sleep Attitude areas were noted for unusual sleepers compared to average ones (F,,,,=3.71, p= .001) cf. Table 1.
Enhanced and Retarded Diffusion of Shallow Impurities in Silicon

We have carried out systematic state-of-the-art calculations using density-functional theory, norm-conserving pseudopotentials, and large supercells in order to investigate the diffusion mechanisms of B, P, As, and Sb in Si under both equilibrium and non-equilibrium concentrations of intrinsic point defects. In addition, we have developed a theory for the non-equilibrium concentrations of the relevant diffusing species from which expressions for the activation energies may be derived. In equilibrium, we find that vacancies and self-interstitials mediate the diffusion of B, P, and As with comparable activation energies, but we show from our non-equilibrium diffusion calculations that these impurities have a dominant interstitial component. Sb diffusion, on the other hand, is mediated primarily by vacancies. We also find that the direct exchange mechanism plays only a minor role in all cases.
Re-Evaluating Progression in an Era of Progress: A Review of First- and Second-Line Treatment Options in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer

UNLABELLED : The advent of crizotinib, the first small molecule inhibitor against anaplastic lymphoma kinase (ALK), has led to impressive advances in the care of patients with advanced ALK-rearranged non-small cell lung cancer. The development of second-generation ALK inhibitors, starting with the recent U.S. Food and Drug Administration approval of ceritinib, promises to expand the therapeutic landscape for this cohort of patients. With increasing use of molecularly targeted therapy options, it has been observed that disease progression in patients receiving targeted agents has a heterogeneous biology, manifesting as either oligoprogressive or widely progressive disease, which may require development of innovative treatment strategies. This review discusses the first- and second-generation ALK inhibitors approved or in clinical development, as well as the novel challenges and approaches to disease progression in patients on targeted agents. IMPLICATIONS FOR PRACTICE The identification of driver mutations in non-small cell lung cancer (NSCLC), most prominently epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), has expanded treatment options for a significant cohort of patients. However, the success of targeted agents has brought new challenges, particularly regarding management of progression. Progression manifests heterogeneously, and management of oligoprogression may differ from diffusely progressive disease. Multiple options for treatment at progression exist, and it is becoming evident that selecting the best avenue of care requires understanding the biology and potential drivers of disease progression. This review discusses the array of treatment options available for patients with ALK-positive NSCLC, as well as evaluation and treatment of progressive disease.
Crack Analysis of T23 Steel Tube Welded Joints for 1 000 MW Ultra Supercritical Tower-type Boiler

The macro-inspection and microstructure analysis of cracks for welded joints were investigated,according to the leakage of T23 Steel tube welded joints in a 1 000 MW ultra supercritical tower-type boiler.The result shows that the water-wall tube weld cracks are caused by residual stress and structural binding stress of welded joints.
Bottom-up direct writing approach for controlled fabrication of WS2/MoS2 heterostructure systems

The ability to construct heterostructures that consist of layered transition metal dichalcogenides materials (MX2) in a controlled fashion provides an attractive solution for materials design and device applications. For nanotechnology applications it is important to control the shape, geometry and precise position of the grown heterostructure assemblies on a variety of substrates. In this study, we developed a “direct writing” technique to fabricate arrays of WS2/MoS2 and MoS2/WS2/MoS2 heterostructures at predefined locations on a silicon substrate in a controlled fashion. Water based precursor inks were implemented to ensure the formation of quality heterostructure surfaces which are free of residual polymer contaminants. With this technique we demonstrate an attractive and scalable technology with unique capabilities for precise growth of dissimilar MX2 materials, layered either in a vertical or lateral arrangement.
STRUCTURAL DISTANCES AND INSTITUTIONAL SOCIALISATION

This chapter examines the structure of student social relations within the total institutional context in its relation to external structure and culture. The chapter shows that internal social relations vary in their structure with the relationship, which the student body as a whole has with those who are not students. The category of non-students comprehends those who are not students within the institutional framework such as academic and administrative staff of the university and those who are not students outside the university. These groups represent different degrees of studentness or non-studentness, which regulate the degree of corporateness in student interaction. This can be termed as a situation of “structural opposition” in which those groups which are structurally opposed are conscious of their own special identity. This in turn is related to institutional and sub-group socialization and the way in which this is influenced by structural distances between groups both vertical and horizontal.
Pupil function engineering for enhanced nanoparticle visibility in wide-field interferometric microscopy

Wide-field interferometric microscopy techniques have demonstrated their utility in sensing minute changes in the optical path length as well as visualization of sub-diffraction-limited nanoparticles. In this work, we demonstrate enhanced signal levels for nanoparticle detection by pupil function engineering in wide-field common-path interferometric microscopy. We quantify the improvements in nanoparticle signal achieved by novel optical filtering schemes, benchmark them against theory, and provide physical explanations for the signal enhancements. Our refined common-path interferometric microscopy technique provides an overall ten-fold enhancement in the visibility of low-index, non-resonant polystyrene nanospheres (r∼25 nm), resulting in nearly 8% signal-to-background ratio. Our method can be a highly sensitive, low-cost, label-free, high-throughput platform for accurate detection and characterization of weakly scattering low-index nanoparticles with sizes ranging from several hundred down to a few tens of nanometers, covering nearly the entire size spectrum of biological particles.
A novel approach for secure multi-party secret sharing scheme via Quantum cryptography

Classical secret sharing proposed by Shamir used classical computational power in classical cryptography to achieve secret key sharing, but with the advent of quantum systems, computational power can be overruled. To ensure a secure secret sharing scheme independent of computational power, a scheme independent of computational complexity is needed to achieve security. This paper will provide a protocol dependent on inherent secure nature of quantum cryptography (quantum no cloning theorem and quantum measurement rule). A secure multiparty quantum secret sharing scheme has been proposed to ensure that no one can eavesdrop or extract any share of the secret message via inherent security provided by quantum entanglement swapping and quantum teleportation. Entanglement swapping is a process that allows two non-interacting quantum systems to be entangled. Whereas, Quantum teleportation allows a party to send a qubit to another entangled party without sending the qubit over the channel. Moreover, in order to ensure security against possible active attacks, sender himself will generate and distribute EPR pairs to be used in the scheme. Result will be a secure multiparty QSS scheme which will be secure against internal and external eavesdropping, masquerading and brute-force attacks.