cssi/SciSciGPT-SciSciNet huggingface dataset:
Success of Targeting Rationale in Deep Brain Stimulation for Parkinson’s Disease (P5.380)

Objective: To characterize the success of our rationale for deep brain stimulation (DBS) target selection in patients with Parkinson’s disease (PD). Background: Subthalamic nucleus (STN) and globus pallidus interna (GPi) DBS are established therapies for advanced PD with motor complications (MC; i.e., motor fluctuations, dyskinesia) but there are no evidence-based guidelines for target selection. Design/methods: A retrospective chart review of PD patients with STN or GPi DBS placement from 1/2010-12/2013 was performed. Inclusion criteria included pre-operative assessments, consensus team review, and post-operative DBS optimization completed at our center. PD-specific variables, indication for DBS, rationale for targeting, stimulation side effects, medications, and time to optimization of DBS settings were recorded. Motor and neuropsychological outcomes were estimated on a -3 (disabling) to +3 (resolved) scale. Results: 34/58 patients were included (16 STN, 18 GPi). DBS was most commonly performed due to MC. Target selection was based on: refractory tremor (n=8) and MC (n=9) for STN, and dystonia (n=8), cognitive impairment (n=6), and gait disorder (n=5) for GPi. The two groups had similar baseline age, disease duration, and off motor score at implantation. More STN patients had tremor-dominant PD (p=0.0002). GPi patients had worse MC, postural stability, and more dystonia (p 2). However, individual patients experienced worsening in various domains. The major features informing target selection were much improved, except cognitive impairment (unchanged). Conclusions: Baseline group differences reflect biases in target selection, but these strategies were generally successful. However, symptom change after DBS varies among individuals, suggesting that personalization of DBS may not be achieved by clinical assessment alone. Disclosure: Dr. Farcas has nothing to disclose. Dr. Jimenez Shahed has received personal compensation for activities with Teva as a consultant. Dr. Jimenez Shahed has received research support from Avid Radiopharmaceutical, Inc., Acadia Pharmaceuticals, US World Meds, and Biotie.
Cutting Edge: Chromatin Accessibility Programs CD8 T Cell Memory

CD8 T cell memory is characterized by rapid recall of effector function, increased proliferation, and reduced activation requirements. Despite the extensive functional characterization, the molecular mechanisms that facilitate these enhanced properties are not well characterized. In this study, the assay for transposase-accessible chromatin sequencing was employed to map the cis-regulatory elements in CD8 T cells responding to acute and chronic lymphocytic choriomeningitis virus infections. Integration of chromatin accessibility profiles with gene expression data identified unique regulatory modules that were enriched for distinct combinations of transcription factor-binding motifs. Memory CD8 T cells displayed a chromatin accessibility structure that was absent from other acute and exhausted cells types and included key effector and proliferative genes. Stimulation of memory cells revealed enhanced transcription of "memory-primed" genes compared with naive cells. Thus, memory CD8 T cells display a preprogrammed chromatin accessibility profile and maintain a molecular history of cis-element usage, thereby reducing the steps necessary to revive effector functions.
‘Studies have shown that …’ how to read a statistical study

Summary This article provides some background for a classroom discussion of statistical research studies. The history of cigarettes and warning labels in the USA is reviewed here in order to demonstrate the challenges of statistical research and communication.
Results of thermo-magnetic analysis of Cretaceous deposits of the Lagich section (Vandam tectonic zone, South slope of the Greater Caucasus, Azerbaijan)

The magnetic study of a tuffbreccia, tuffaceous sandstone, clay rocks, chalky clays, marls and silicides of Cretaceous deposits (the Albian Age, the Cenomanian Age and Turonian — Cognacian Age) the Lagich section of the Vandam tectonic zone of Greater Caucasus (Azerbaijan) has been carried out. For thermomagnetic analysis the magnetic parameter of saturation remanence J rs is used. The magnetic and mineralogical structure of carriers of natural remanent magnetization is determined by the shape of curves and by blocking temperature T b of the studied samples. As a result of the analysis of curves of demagnetization of J rs it has been established that the main carriers of natural remanent magnetization of the studied samples in the Lagich section are magnetite and hematite. On several samples during thermodemagnetization of J rs the curves have displayed the presence of pyrrhotite (greygit). But on mineralogical researches of department of "Analytical center" of Institute of Geology of National Academy of Sciences of Azerbaijdan presence of pyrrhotite (greygit) in the studied samples hasn't been revealed. In Cretaceous deposits (the Albian Age, the Cenomanian Age and Turonian—Congnacian Age) however availability of magnetite and hematite are checked out by department of "Analytical center" in the Lagich section
Identification of eleven novel HLA alleles by sequence based typing (SBT): A∗02:557, A∗11:01:64, B∗40:299, B∗53:37, C∗01:98 N, C∗02:14:02, C∗04:195, C∗08:110, C∗08:111, DRB1∗03:110, DRB∗13:184

Accurate HLA typing and matched donor selection is essential for graft outcome in patients receiving a stem cell transplant. Misidentification of new alleles can result in graft failure or acute graft vs. host disease. This study identifies eleven novel HLA alleles at class I and class II loci. Method Unusual or potentially novel HLA alleles were detected during sequence specific oligonucleotide (SSO) intermediate resolution typing. Characterization of novel alleles was performed by sequence based typing (SBT) using group specific and locus specific primers. Results Eleven novel HLA sequences were identified and characterized in 14 individuals, including HLA-A∗11:01:64 in a patient and a haploidentical sibling, C∗04:195 in a patient and a fully matched sibling, and DRB1∗03:110 in two haploidentical sibling donors. Nine of the eleven novel HLA alleles resulted in an amino acid substitution. The null allele C∗01:98 N resulted in a premature stop codon in exon 2. Six out of the eleven novel alleles have nucleotide/amino acid changes in exon 4 and the rest in exon 2. Table 1 shows the differences of nucleotides and amino acids between these novel alleles and their most homologous allele and the location of the changes. Discussion Identification and characterization of novel HLA alleles is important for the selection of appropriate stem cell transplant donors aimed at improving graft outcome and patient survival. Download : Download full-size image
Patient and cycle characteristics predicting high pregnancy rates with single-embryo transfer: an analysis of the Society for Assisted Reproductive Technology outcomes between 2004 and 2013

Objective To analyze factors associated with high live birth rate and low multiple birth rate in fresh and frozen–thawed assisted reproductive technology (ART) cycles. Design Retrospective cohort analysis. Setting Not applicable. Patient(s) The study population included 181,523 women undergoing in vitro fertilization with autologous fresh first cycles, 27,033 with fresh first oocyte donor cycles, 37,658 with fresh second cycles, and 35,446 with frozen–thawed second cycles. Intervention(s) None. Main Outcome Measure(s) Live birth rate and multiple birth rate after single-embryo transfer (SET) and double embryo transfer (DET) were measured, in addition to cycle characteristics. Result(s) In patients with favorable prognostic factors, including younger maternal age, transfer of a blastocyst, and additional embryos cryopreserved, the gain in the live birth rate from SET to DET was approximately 10%–15%; however, the multiple birth rate increased from approximately 2% to greater than 49% in both autologous and donor fresh and frozen–thawed transfer cycles. Conclusion(s) This study reports a 10%–15% reduction in live birth rate and a 47% decrement in multiple birth rate with SET compared with DET in the setting of favorable patient prognostic factors. Our findings present an opportunity to increase the rate of SET across the United States and thereby reduce the multiple birth rate and its associated poor perinatal outcomes with assisted reproductive technology pregnancies.
Carbon nano-structured neural probes show promise for magnetic resonance imaging applications

Objective. Previous animal studies have demonstrated that carbon nanotube (CNT) electrodes provide several advantages of preferential cell growth and better signal-to-noise ratio (SNR) when interfacing with brain neural tissue. This work explores another advantage of CNT electrodes, namely their MRI compatibility. MRI-compatible neural electrodes that do not produce image artifacts will allow simultaneous co-located functional MRI and neural signal recordings, which will help improve our understanding of the brain. Approach. Prototype CNT electrodes on polyimide substrates are fabricated and tested in vitro and in vivo in rat brain at 9.4 T. To understand the results of the in vitro and in vivo studies, a simulation model based on numerical computation of the magnetic field around a two-dimensional object in a tissue substrate is developed. Main Results. The prototype electrodes are found to introduce negligible image artifacts in structural and functional imaging sequences in vitro and in vivo. Simulation results confirm that CNT prototype electrodes produce less magnetic field distortion than traditional metallic electrodes due to a combination of both superior material properties and geometry. By using CNT films, image artifacts can be nearly eliminated at magnetic fields of strength up to 9.4 T. At the same time, the high surface area of a CNT film provides high charge transfer and enables neural local field potential recordings with an equal or better SNR than traditional electrodes. Significance. CNT film electrodes can be used for simultaneous MRI and electrophysiology in animal models to investigate fundamental neuroscience questions and clinically relevant topics such as epilepsy.
Sand, Bricks, and Seeds: School Change Strategies and Readiness for Reform

In this chapter Robert Slavin argues against a prevailing orthodoxy by maintaining that differences between schools in terms of “effectiveness” are less important than what and how a school teaches. Slavin contends that there are fewer highly effective, in his terms “seed” schools than others suppose, and by the same token a similary fewer number of “sand” or highly ineffective schools. Most schools he claims are “brick” schools, in so far as they are amenable to reform by the introduction of prepared curriculum and instructional packages. In a similar vein Slavin argues that of the three main types of innovation — organisation development, single curricular innovations or comprehensive reform models — it is only the latter that holds any promise for positively affecting student achievement in a majority of schools. Slavin concludes by proposing a series of policy implications that involve the funding and implementation of well-specified (“brick”) models of school improvement.
Ribozyme crevices and catalysis.

After waiting almost 15 years since the first ribozyme (catalytic RNA molecule) was crystallized, the RNA community finds that such structures are a bit like buses, with two coming at once. One is the high-resolution structure of the hepatitis delta helper virus ribozyme, and the other, at slightly lower resolution, is the group I intron from Tetrahymena thermophila.
Characteristics of the synergistic actions of platelet agonists

Platelets are activated by many different agonists that act synergistically. Since there is a characteristic pattern of responses to each agonist, and since there is a clear distinction between weak and strong agonists, understanding the nature of the synergism and its physiologic significance requires characterization of the pattern of responses to the synergistic action of the various agonists. Shape change, aggregation, and secretion of ATP by human platelets in citrated plasma were analyzed after activation by ADP, epinephrine, arachidonic acid, gamma-thrombin, or collagen, either singly or in pairs. The patterns of responses were characteristic of the agonist in higher concentration relative to its threshold concentration; if neither was clearly higher, the pattern of responses was intermediate between the responses characteristic of each agonist. No combination of weak agonists had the characteristics of a strong agonist. These results help define the extent to which platelet responses can be attributed to the synergistic actions of weak agonists.
A Large Database Analysis of Rates of Aneurysm Screening, Elective Treatment, and Subarachnoid Hemorrhage in Patients With Polycystic Kidney Disease.

BACKGROUND Professional societies provide conflicting guidelines on aneurysm screening in patients with polycystic kidney disease (PKD), and the rate of subarachnoid hemorrhage (SAH) is poorly understood. OBJECTIVE To evaluate screening, elective treatment, and the rate of SAH in patients with known PKD. METHODS We examined longitudinally linked claims data from a large private insurer, identifying screening, elective treatment, aneurysmal subarachnoid hemorrhage (aSAH) and secured aneurysmal SAH (saSAH) in 2004 to 2014 amongst patients with known PKD. RESULTS We identified 20 704 patients diagnosed with PKD. Among patients with an initial PKD diagnosis, 51/446 (15.9%) underwent angiographic screening within 2 yr. Forty aneurysms were treated electively in 48 868 yr at risk in PKD patients (82/100K patient yr, 95% confidence interval [CI] 60-112) vs 24 elective treatments in 349 861 yr at risk in age- and sex-matched controls (7/100K patient yr, 95% CI 5-10, P < .0001). Eleven admissions for aSAH were identified in PKD patients (23/100K patient yr, 95% CI 13-41) and 22 admissions for aSAH in controls (6/100K patient yr, 95% CI 4-10), giving an incidence rate ratio (IRR) of 3.6 (95% CI 1.7-7.4, P < .0001) and a comorbidity-adjusted IRR of 3.1 (95% CI 1.4-6.9). The incidence of saSAH was proportionally even higher in PKD patients than controls, 16 vs 2/100K patient years, IRR 9.5 (95% CI 3.3-27.5, P < .0001). CONCLUSION Screening in PKD is performed only selectively, though resulting rates of elective treatment were over 10× those of controls. Despite screening and treatment, the rate of SAH remains significantly elevated over that of controls.
Selective vulnerability of dorsal raphe-medial prefrontal cortex projection neurons to corticosterone-induced hypofunction.

Glucocorticoid hormones and serotonin (5-HT) are strongly associated with the development and treatment of depression, respectively. Glucocorticoids regulate the function of serotonergic neurons in the dorsal raphe nucleus (DR), which are the major source of 5-HT to the forebrain. DR 5-HT neurons are electrophysiologically heterogeneous, though whether this phenotypic variation aligns with specific brain functions or neuropsychiatric disease states is largely unknown. The goal of this work was to determine if chronic exogenous glucocorticoid administration differentially affects the electrophysiological profile of DR neurons implicated in the regulation of emotion versus visual sensation by comparing properties of cells projecting to medial prefrontal cortex (mPFC) versus lateral geniculate nucleus (LGN). Following retrograde tracer injection into mPFC or LGN, male Sprague-Dawley rats received daily injections of corticosterone (CORT) for 21 days, after which whole-cell patch clamp recordings were made from retrogradely labeled DR neurons. CORT-treatment significantly increased the action potential half-width of LGN-projecting DR neurons, but did not significantly affect the firing frequency or excitatory postsynaptic currents of these cells. CORT-treatment significantly reduced the input resistance, evoked firing frequency, and spontaneous excitatory postsynaptic current frequency of mPFC-projecting DR neurons, indicating a concurrent reduction of both intrinsic excitability and excitatory drive. Our results suggest that the serotonergic regulation of cognitive and emotional networks in the mPFC may be more sensitive to the effects of glucocorticoid excess than visual sensory circuits in the LGN and that reduced 5-HT transmission in the mPFC may underlie the association between glucocorticoid excess and depression.
Sonvilier Pen Company: An Outsourcing Decision

The COO for Sonvilier Pen, an elite manufacturer of high-quality ballpoint and fountain pens, had gotten a proposal to outsource two pen components to Li Manufacturing, a specialist in the molding and production of intricate metals, located in southeastern China. The proposal was intriguing, but there were a number of factors for the COO to consider before making a decision. Excerpt UVA-C-2406 Rev. Nov. 27, 2018 Sonvilier Pen Company: An Outsourcing Decision Sonvilier Pen Company (Sonvilier Pen) was a manufacturer of high-quality writing pens. The company could trace its origins to the early 1900s, when founder Cedric Mettler and his father began producing various writing implements in their small shop in Sonvilier, Switzerland. The Mettler son later immigrated to the United States and soon thereafter opened his own fountain pen company, taking the name of his hometown in respect for the place where he had honed his craft. By the turn of the next century, Sonvilier Pen had become an elite manufacturer of high-quality ballpoint and fountain pens, producing over three million units annually. Its headquarters and manufacturing facilities were located in northern New England. Peter Harwood was the COO for Sonvilier Pen. On his desk was a proposal to outsource two pen components to Li Manufacturing, a specialist in the molding and production of intricate metals, located in southeastern China. Harwood had not initially courted this opportunity. An intermediary US organization had proposed the partnership to Harwood six months earlier. The intermediary was a go-between agent engaged in matching manufacturing partners, billing itself as a full-service custom-manufacturing facilitator. It specialized in first finding appropriate China-based manufacturers for US-based organizations and then providing a full suite of services related to production: engineering, packaging, customs clearing, and quality control, among others. The proposal was intriguing, and left Harwood with a number of factors to consider before he made a decision regarding the offer. Li Manufacturing's location alone brought with it a unique set of challenges Sonvilier Pen would have to face if it were to outsource production. Li Manufacturing's operations were located in one of China's many economic development zones. Moreover, the company had a stellar reputation for quality workmanship and execution and had partnerships with numerous other US manufacturers. All those companies gave Li Manufacturing stellar recommendations. . . .
A Changing View of the Auditory System Obtained from the Ears of Bats

For the past 43 years I have been conducting research on how sensory systems encode and represent features of the external world in the brain. This has been, and continues to be, an exciting and rewarding adventure. Indeed, it is difficult to convey the sense of excitement, really exhilaration, that is part and parcel of discovery, when one sees nature reveal a part of itself for the first time. Now, previously unrelated parts begin to fit into a compelling unity, and the realization of that unity provides new and unique insights into the grand scheme of life. The insights are very personal because no one has ever before seen things quite in those ways.
Congenital eccrine angiomatous hamartoma: Expanding the morphologic presentation and a review of the literature

Eccrine angiomatous hamartoma (EAH) is a rare benign vascular hamartoma characterized histologically by an increased size and number of mature eccrine glands associated with multiple foci of dilated capillaries in the dermis and subcutis. EAH typically presents in children as discrete, solitary nodules, or plaques most commonly located on the extremities. Some cases of EAH have an agminated distribution involving classic locations, or present as solitary lesions in less common locations such as the face, scalp, or trunk. We report the case of congenital EAH in a child with atypical morphological features and pattern of distribution further expanding on the range of presentations classically described.
Decreasing wind speed extrapolation error via domain-specific feature extraction and selection

Abstract. Model uncertainty is a significant challenge in the wind energy industry and can lead to mischaracterization of millions of dollars' worth of wind resource. Machine learning methods, notably deep artificial neural networks (ANNs), are capable of modeling turbulent and chaotic systems and offer a promising tool that can be used to produce high-accuracy wind speed forecasts and extrapolations. This paper quantifies the role of domain knowledge on ANN wind speed extrapolation accuracy using data collected using profiling lidars over three field campaigns. A series of 11 meteorological features are used as ANN inputs and the resulting output accuracy is compared with that of a simple power law extrapolation. It is found that normalized inputs, namely turbulence intensity, normalized current wind speed, and normalized previous wind speed, are the features that most reliably improve ANN accuracy, providing up to a 52 % increase in extrapolation accuracy over the power law predictions. The volume of input data is also deemed important for achieving robust results. One test case is analyzed in-depth using dimensional and non-dimensional features, showing that feature normalization drastically improves network accuracy and robustness for uncommon atmospheric cases.
Coverage Extension with UAV Based on Constrained Uplink and Downlink Phases for Disaster-Resilient Communication Networks

Unmanned aerial vehicles (UAVs) have been considered as a solution to extend coverage for disaster-resilient communication networks in a disaster area when the communication infrastructure which is known as the base station (BS) cannot afford the service as usual. However, when the link between the UAV and the serving BS is constrained, the UAV must keep the appropriate distance for reliable transmission. In addition, the altitude of the UAV may significantly affect the link quality between the UAV and the BS, as well as the link between the UAV and the users/rescuers. In this paper, we analyze the coverage of the disaster-resilient communication network with a UAV for guaranteeing the reliability of all links. We show that the position of UAV can be a function of the BS's and user's elevation angle. The simulation results show that the maximum radius of coverage in the high-rise urban environment can be 5.25 km and 2.46 km for downlink and uplink, respectively. Moreover, this paper can provide a principle for the central emergency operation center (CEOC) to immediately deploy the disaster-resilient communication network.
Textures of the tumour microenvironment

In this review, we present recent findings on the dynamic nature of the tumour microenvironment (TME) and how intravital microscopy studies have defined TME components in a spatiotemporal manner. Intravital microscopy has shed light into the nature of the TME, revealing structural details of both tumour cells and other TME co-habitants in vivo, how these cells communicate with each other, and how they are organized in three-dimensional space to orchestrate tumour growth, invasion, dissemination and metastasis. We will review different imaging tools, imaging reporters and fate-mapping strategies that have begun to uncover the complexity of the TME in vivo.
A Role for Sigma Receptors in Stimulant Self-Administration and Addiction

Sigma receptors (σRs) are structurally unique proteins that function intracellularly as chaperones. Historically, σRs have been implicated as modulators of psychomotor stimulant effects and have at times been proposed as potential avenues for modifying stimulant abuse. However, the influence of ligands for σRs on the effects of stimulants, such as cocaine or methamphetamine, in various preclinical procedures related to drug abuse has been varied. The present paper reviews the effects of σR agonists and antagonists in three particularly relevant procedures: stimulant discrimination, place conditioning, and self-administration. The literature to date suggests limited σR involvement in the discriminative-stimulus effects of psychomotor stimulants, either with σR agonists substituting for the stimulant or with σR antagonists blocking stimulant effects. In contrast, studies of place conditioning suggest that administration of σR antagonists or down-regulation of σR protein can block the place conditioning induced by stimulants. Despite place conditioning results, selective σR antagonists are inactive in blocking the self-administration of stimulants. However, compounds binding to the dopamine transporter and blocking σRs can selectively decrease stimulant self-administration. Further, after self-administration of stimulants, σR agonists are self-administered, an effect not seen in subjects without that specific history. These findings suggest that stimulants induce unique changes in σR activity, and once established, the changes induced create redundant, and dopamine independent reinforcement pathways. Concomitant targeting of both dopaminergic pathways and σR proteins produces a selective antagonism of those pathways, suggesting new avenues for combination chemotherapies to specifically combat stimulant abuse.
MULTI-MODALITY APPROACH FOR ARVD TRICUSPID VALVE REPLACEMENT FOR RIGHT HEART FAILURE

Structural changes that occur in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) may predispose to tricuspid regurgitation developing or vice versa in the absence of significant left heart disease. There is little evidence to guide therapy such as tricuspid valve (TV) repair,
Seeing (and Using) the Light: Recent Developments in Bioluminescence Technology.

Bioluminescence has long been used to image biological processes in vivo. This technology features luciferase enzymes and luciferin small molecules that produce visible light. Bioluminescent photons can be detected in tissues and live organisms, enabling sensitive and noninvasive readouts on physiological function. Traditional applications have focused on tracking cells and gene expression patterns, but new probes are pushing the frontiers of what can be visualized. The past few years have also seen the merger of bioluminescence with optogenetic platforms. Luciferase-luciferin reactions can drive light-activatable proteins, ultimately triggering signal transduction and other downstream events. This review highlights these and other recent advances in bioluminescence technology, with an emphasis on tool development. We showcase how new luciferins and engineered luciferases are expanding the scope of optical imaging. We also highlight how bioluminescent systems are being leveraged not just for sensing-but also controlling-biological processes.
Are You Ready: Financial Management, Operating Reserves, and the Immediate Impact of COVID-19 on Nonprofits

Scholars and practitioners have argued that effective financial management, particularly the development of operating reserves, can help nonprofits survive economic shocks. The COVID-19 pandemic, w...
The economical simulation problem

Think of a digital simulation as a computational device for which one must allocate three computational resources for computing: (a) the given inputs, (b) the outputs and (c) each state variable in the dynamics. This paper assigns these computational resources to guarantee a specified bound on response errors. We define the economical simulation problem (ESP) as designing the simulation of a stable linear system and distributing computational resources (wordlength) among the digital devices such that the computational cost (memory) is minimized without violating the required simulation accuracy. This problem is generally not convex because of the scaling constraint. By exploring the special structure of this joint optimization of the choice of the realizations and the computational resources to be applied, and under a scaling assumption, the ESP is converted to a convex problem. Numerical results are given which compare this method with existing approaches.
Abstract #4417: Targeting Notch signaling in colon cancer

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO Colorectal cancer is the third most frequently diagnosed cancer and the third leading cause of cancer-related deaths in men and women in the United States. The aggressive nature of this disease demands the identification of novel targeted therapies with minimal side effects. The medicinal plant, Withania somnifera , is extensively used in Asian herbal medicines to treat a variety of ailments, including cancer. We identified Withaferin-A (WA), a major bioactive compound in Withania somnifera , exhibits potent anti-cancer effects on colon cancer cells that underscores the necessity of studying the molecular mode of action of WA to clarify its potential clinical merit. Our results suggest that WA inhibits cell proliferation and induces apoptosis in colon cancer cells (SW-480, SW-620 and HCT-116). While dissecting the mechanism of action of WA on colon cancer cells, we found that WA inhibits Notch-1 signaling, which resulted in the downregulation of pAkt and Bcl-2 expression. In addition, inhibition of mTOR signaling by WA resulted in the down regulation of pS6K and p4E-BP1 expression in SW-480, SW-620 and HCT-116 colon cancer cells. We also observed, WA activates caspase-3 and PARP cleavage suggesting that it triggers the pro-apoptotic machinery in colon cancer cells. Interestingly, WA causes a strong mitotic catastrophe by arresting the cells G2/M phase of cell cycle in colon cancer cells. Finally, oral administration of WA resulted in a significant tumor regression of xenografts comprised of highly metastatic colon cancer cells in nude mice. These results suggest that WA can be explored for its anti-cancer activity for the development of targeted chemotherapeutic and/or chemoprevention strategies for colon cancer which possibly would lead to clinical trials to determine the efficacy of WA against colon cancer. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4417.
Protein Translocation Across Membranes

From prokaryotic to eukaryotic cells, the movement of proteins across membranes as well as the integration into membranes is a fundamental process with shared mechanisms. Protein translocation pathways can be viewed as modular systems with basic components. Transported substrates contain targeting information that is decoded by receptors at docking sites. The substrate is then translocated across the membrane generally through a channel. A source of energy is often required and a translocation motor usually mediates translocation through the channel. In this chapter, we will summarize translocation systems in eukaryotic and prokaryotic systems, emphasizing common themes. Our understanding of protein translocation is continuing to grow with the addition of new components to existing systems and the identification of new translocation machines. The reader is encouraged to use this chapter as a starting point for more detailed excursions into scientific literature. Keywords: Molecular Chaperones; Receptor; Signal or Targeting Sequence; Translocase or Translocon; Translocation Channel
GD3 Vaccines for Melanoma: Superior Immunogenicity of Keyhole Limpet Hemocyanin Conjugate Vaccines

Cell surface gangliosides show altered patterns of expression as a consequence of malignant transformation and have therefore been of interest as potential targets for immunotherapy, including vaccine construction. One obstacle has been that some of the gangliosides that are overexpressed in human cancers are poorly immunogenic in humans. A case in point is GD3, a prominent ganglioside of human malignant melanoma. Using an approach that has been effective in the construction of bacterial carbohydrate vaccines, we have succeeded in increasing the immunogenicity of GD3 in the mouse by conjugating the ganglioside with immunogenic carriers. Several conjugation methods were used. The optimal procedure involved ozone cleavage of the double bond of GD3 in the ceramide backbone, introducing an aldehyde group, and coupling to aminolysyl groups of proteins by reductive amination. Conjugates were constructed with a synthetic multiple antigenic peptide expressing repeats of a malarial T-cell epitope, outer membrane proteins of Neisseria meningitidis, cationized bovine serum albumin, keyhole limpet hemocyanin, and polylysine. Mice immunized with these conjugates showed a stronger antibody response to GD3 than mice immunized with unconjugated GD3. The strongest response was observed in mice immunized with the keyhole limpet hemocyanin conjugate of the GD3 aldehyde derivative and the adjuvant QS-21. These mice showed not only a long-lasting high-titer IgM response but also a consistent high-titer IgG response (predominantly IgG1), indicating recruitment of T-cell help, although the titers of IgM and IgG antibodies following booster immunizations were not as high as they are in the response to classical T-cell-dependent antigens. This method is applicable to other gangliosides, and it may be useful in the construction of immunogenic ganglioside vaccines for the immunotherapy of human cancers expressing gangliosides on their cell surface.
The Big Push Déjà Vu

Jeffrey Sachs is the economics profession’s leading advocate of mega-reform. Whether it is stabilization of hyperinflation in Bolivia, shock therapy to leap from Communism to capitalism in Poland and Russia, or a “Big Push” to end world poverty, Sachs’ recommendation throughout his career has been to do it fast, do it big, do it comprehensively, and do it with lots of Western money.
On the Synthesis of Compensators for Non-Overshooting Step Response

A problem of practical and theoretical interest in control is the synthesis of a compensator that results in a closed loop system response with no overshoot. In this short paper we present an approach for synthesizing such compensators for SISO, minimum phase plants. The essential idea of the technique is to appropriately locate the closed loop poles with respect to fixed and added zeros. Admissible pole-zero locations are characterized by two sufficiency theorems.
Breakthroughs in hypothalamic and pituitary research.

Publisher Summary This introductory chapter of the book deals with the breakthroughs in hypothalamic and pituitary research. In the past half century of knowledge, not only of the pituitary but also the hypothalamus, has undergone phenomenal growth and to attempt to grasp its significance. The pituitary and its infundibulum appeared on the horizon, centuries before the hypothalamus came to be known. Galen of Pergamon was the first to recognize their existence and to comment on their function. Many of Galen's studies were based on dissection of the brains of oxen, goats, swine and monkeys ( Macaca inua and Macaca mulatta), in which he described not only the pituitary and the infundibulum but also the 4 chambers (ventricles) of the brain, the fornix, the corpus callosum, the pineal, and the corpora quadrigemina. Among the chambers of the brain were the two lateral ones, which he called the “thalamus” (literally, “bridal chamber”).
The 1992 Polarized Light Source

We describe the Polarized Light Sources used at SLAC during the 1992 runs of the experiments SLD and E142. >
Cultivating Racial Literacy in White, Segregated Settings: Emotions as Site of Ethical Engagement and Inquiry.

AbstractDrawing on writing from a first-year composition class, this article explores how White students approach racial literacy in a segregated, rural college setting in the United States. I argue for the importance of understanding how emotions inform and propel students’ responses to what I believe needs to be understood as the ethical challenge of racial literacy. White students who defended a color-blind stance of ethical judgment seemed to accept the emotional schooling, the accompanying beliefs, and innocent identities linked to their home communities. In contrast, other White students, adopting a stance of ethical awareness, engaged critically with their emotions so that emotions functioned as a site of ethical inquiry. Rather than defending a stable innocent identity, they began to interrogate an implicated, unstable, racialized identity within the context of their relationships with other Whites. In contrast to research that understands White students’ emotions primarily as a manifestation of r...
FERNANDO VALLEJO: CIUDADANÍA ESTÉTICA Y LA CLAUSURA DE LA LITERATURA MUNDIAL

Este articulo encara deliberaciones actuales sobre la literatura global, desde la perspectiva de la novela urbana colombiana del siglo XX. Explorando la tension entre las historias de las narrativas globales y locales, el autor examina hasta que punto se puede defender que la literatura global y sus apendices socioculturales se prestan a proyectos emancipatorios, y hasta que punto esos apendices simplifican en exceso los espacios de produccion literaria densa. Ubicando la Weltliteratur de Goethe en el contexto de una Colombia esteticamente globalizada, e invocando la relacion particularmente espinosa entre Fernando Vallejo y Gabriel Garcia Marquez como caso de estudio, este articulo avanza que las casas editoriales internacionales y las culturas de la critica crean una ciudadania estetica limitante que sigue siendo dominada por las decisiones de mercadeo de las grandes casas editoriales y el gusto de los publicos lectores, muy alejados del contexto de los bestsellers “perifericos”.
The search and social media workshop at SIGIR 2009

Social applications are the fastest growing segment of the web. They establish new forums for content creation, allow people to connect to each other and share information, and permit novel applications at the intersection of people and information. However, to date, social media has been primarily popular for connecting people, not for finding information. While there has been progress on searching particular kinds of social media, such as blogs, search in others (e.g., Facebook, Myspace, of flickr) are not as well understood. To address these questions, the second workshop on Search and Social Media (SSM 2009) was held at SIGIR 2009 in Boston, MA in July 2009. The main workshop website is available at http://ir.mathcs.emory.edu/SSM2009/. SSM 2009 followed on the highly successful SSM 2008 workshop held at CIKM 2008 in Napa, CA. As in the previous year, the workshop had nearly 50 attendees from academia and industry. The purpose of this workshop was to bring together information retrieval and social media researchers to consider the following questions: How should we search in social media? What are the needs of users, and models of those needs, specific to social media search? What models make the most sense? How does search interact with existing uses of social media? How can social media search complement traditional web search? What new search paradigms for information finding can be facilitated by social media?
The genetics of prion diseases

Prion diseases are a rare group of fatal neurodegenerative disorders of humans and animals that manifest primarily as progressive dementia and ataxia. Unique to these diseases is the prion, a misfolded isoform of the prion protein that can transmit disease from cell to cell or host to host by associating with, and transforming, normal prion protein into the misfolded isoform (the pathogenic scrapie-inducing form). Although the majority of cases occur on a sporadic basis, and rarely result from exposure to prions, such as mad cow disease, 10-15% are attributable to the presence of an autosomal dominant mutation of the prion protein gene (PRNP). Single base pair changes, or the insertion of one or more multiples of a 24 base pair repeat segment, make up the known sequence alterations of PRNP associated with genetic prion disease. The common polymorphic codon 129 of PRNP also plays an important and complex role in risk and phenotype of sporadic and genetic prion disease. This review will focus on the clinical and histopathologic features of the genetic prion diseases. Selected mutations will be highlighted as a way to illustrate general phenotype-genotype correlations.
Pain during transrectal ultrasonography guided prostate biopsy: a randomized prospective trial comparing periprostatic infiltration with lidocaine with the intrarectal instillation of lidocaine-prilocain cream.

Prostate biopsy is usually performed without anesthesia. We evaluated the patient’s perception of pain/discomfort experienced during the procedure in terms of the type of anesthesia used: periprostatic infiltration with 2% lidocaine, or intrarectal instillation of lidocaine-prilocain cream. A total of 198 patients were divided into three groups: group 1 (control group, n=40) received sonographic gel intrarectally prior to biopsy, group 2 (n=75) were given intrarectal instillation of lidocaine-prilocain cream, and group 3 (n=80) received periprostatic anesthesia by injecting 10 ml of 2% lidocaine. Pain after each biopsy was assessed using an 11-point linear visual analog pain scale. The mean pain scores were 5.1 in group 1, 4.8 in group 2, and 2.5 in group 3, resulting in a significant difference between group 3 and both groups 1 and 2, but not between groups 1 and 2. The incidence of biopsy-related adverse events did not differ among groups. Transrectal ultrasonographic guided periprostatic anesthesia is superior to intarectal instillation of lidocaine-prilocain cream.
Ion-Exchange Resins: A Retrospective from Industrial and Engineering Chemistry Research

Ion-exchange resins comprise one of the most important scientific developments of the 20th century. Their applicability to water softening, environmental remediation, wastewater treatment, hydrometallurgy, chromatography, biomolecular separations, and catalysis was recognized in numerous publications. The principle of covalently bonding ligands to cross-linked polymer networks became the basis for the area of polymer-supported reagents. The journal Industrial & Engineering Chemistry Research and its predecessors have published some of the most important papers in this field. In celebration of its 100th anniversary, this review provides a retrospective of ion-exchange resins through publications appearing in this journal.
Opioid antagonist effects of dezocine in opioid‐dependent humans

Dezocine is an opioid μ-partial agonist recently approved for use as an analgesic in the United States. This study characterized the relative agonist versus antagonist effects of dezocine in comparison to naloxone (an opioid antagonist), hydromorphone (an opioid μ-agonist), and placebo (saline solution) in opioid-dependent volunteers. In a residential laboratory, six volunteer male opioid abusers maintained on 30 mg/day oral methadone underwent pharmacologic challenges two to three times per week, 20 hours after the last dose of methadone. Challenges consisted of a double-blind intramuscular injection of dezocine (dose range, 7.5 to 60 mg), hydromorphone (5 and 10 mg), naloxone (0.1 and 0.2 mg), or saline solution. Measures included physiologic indexes, self-reports of drug effects, and observer ratings of drug effects. Naloxone and hydromorphone produced characteristic antagonist-like and agonist-like effects, respectively. Dezocine acted as an opioid antagonist, precipitating a withdrawal syndrome only slightly different from that produced by naloxone. Dezocine's antagonist effects were not directly dose related, but peaked at intermediate doses and declined at higher doses. Clinical Pharmacology & Therapeutics (1996) 60, 206–217; doi:
Validation of the in vivo somatic mutation method in the mouse as a prescreen for germinal point mutations

The in-vivo somatic mutation method developed by us in an earlier X-ray experiment was tested for its usefulness in chemical mutagenesis work, specifically in the prescreening for germinal point mutations. In order to explore possible parallelisms, the 7 compounds chosen for study, as well as the genetic markers used, were those with which large-scale specific-locus mutation-rate experiments in germcells had been conducted in the past or were in progress. From 1–3 dose levels were tested for each compound. On day 101/4 after copulation of C57BL females with T males, a single injection of the test compound was administered, and about 2000 offspring altogether were subsequently scored for survival, morphology, and presence of spots of various types. In accordance with our earlier results we found 3 types of spots: white nearmidline ventral spots (WMVS) which probably result from killing of melanocyte precursor cells; spots resulting from misdifferentiation; and the remainder, which probably result from expression of the recessive by one of several mechanisms (RS). Induction of teratogenic effects, which were stage-specific rather than agent-specific, generally paralleled induction of WMVS's. Both are interpreted as resulting from cell killing. Induction of RS's did not always parallel induction of WMVS's, but roughly paralleled relative frequencies of specific-locus mutations induced in spermatogonia by the same compounds. Even though the in vivo somatic-mutation method probably detects genetic changes additional to point mutations, the results indicate that it may be a useful prescreen for germinal specific-locus mutations, provided care is taken to distinguish between the 3 types of spots, only one of which (RS) is indicative of expression of the recessive.
Proton transfer mass spectrometry studies of peroxy radicals

Abstract A laminar flow reactor coupled to a proton transfer mass spectrometer utilizing H3O+·(H2O)n cluster ions is described. Experiments involving the Cl-atom initiated oxidation of organic species (cyclohexane, cyclopentane, ethane, methane) were performed in the flow reactor and detection of the peroxyl radicals and other oxidation products are discussed. The detection sensitivities for the RO2 radicals (R = cyclohexyl, ethyl, and methyl) were estimated. The sensitivities are consistent with a fast rate (coefficient ∼10−9 cm3 molecule−1 s−1) for the proton transfer reaction between many RO2 species and water-proton clusters. The effect of the presence of water vapor in the ion drift region (IDR) on the detection sensitivity for RO2 was investigated. The detection of the methyl and ethyl peroxy radical species was adversely affected by water vapor however, that for the cylcohexyl peroxy radical was much less affected. The cyclohexyl- and cyclopentyl-peroxy radicals were reacted with NO and the products so formed were probed with proton transfer from water molecules. Products identified include a wide array of mono-, di-, and tri-functional species containing peroxyl, alcoholic, carbonyl, nitrate, and peroxynitrate functional groups. These products are shown to be in accord with the current state of knowledge on the oxidation of cyclopentane and cyclohexane.