cssi/SciSciGPT-SciSciNet huggingface dataset:
Evaluation of the Polymerase Chain Reaction for Diagnosis of Lassa Virus Infection

We evaluated the polymerase chain reaction (PCR) and hybridization procedures for diagnosis of Lassa fever. Primers were derived from a region of the small RNA segment of Lassa virus coding for the glycoprotein. Serum samples stored for a 14-year period from patients in Sierra Leone, West Africa were examined retrospectively. Blinded samples were then tested prospectively. Eighty-eight virus isolation-negative control sera were negative by PCR and hybridization. In the retrospective study, virus was isolated from 51 of 98 specimens from patients with Lassa fever, and 33 of these were positive for Lassa virus RNA by PCR, and 42 by PCR and hybridization. Fifteen were positive by PCR and hybridization but isolation-negative, and nine were positive by isolation but PCR/hybridization-negative. Thirty-two were negative by all methods (sensitivity by PCR/hybridization compared with virus isolation 0.82, specificity 0.68). In a prospective blinded study of 195 patient sera, 51 were positive by PCR and virus isolation, and 24 were PCR positive but virus isolation-negative (sensitivity 0.66, specificity 0.71). After hybridization, 66 virus isolation-positive sera were positive. The sensitivity was 0.86 and the specificity was 0.59, and the probability of false-positive results compared with virus isolation was 32%, (chi 2 = 21.9, by McNemar's test). Since some specimens may not have contained viable virus, we re-analyzed the data of individual patients using laboratory-confirmed case definitions for Lassa fever. All specimens from patients in whom Lassa fever was excluded by serologic tests were negative by PCR/hybridization.(ABSTRACT TRUNCATED AT 250 WORDS)
Practical authentication in large-scale internet applications

Internet applications have experienced a rapid and massive growth in popularity in the last decade. For example, today many Web and Voice over IP (VoIP) applications rely on large and highly-distributed infrastructures to process requests from millions of users in a timely manner. Due to their unprecedented requirements, these large-scale Internet applications have often sacrificed security for other goals such as performance, scalability and availability. As a result, these applications have typically preferred weaker but more efficient security mechanisms in their infrastructures. Authentication mechanisms, a security layer required by most Internet applications, are an example of this trend. Mechanisms such as Digest authentication, HTTP Cookies, HTML form-based authentication and SSL/TLS server authentication are widely deployed regardless of their known weaknesses. However, as recent incidents have demonstrated, due to the increasing importance of large-scale Internet applications, powerful adversaries are now targeting and exploiting the weaknesses in these authentication mechanisms. While more robust authentication mechanisms have been proposed, most of them fail to address the specific requirements and threat model of large-scale Internet applications and, as a result, they have not been widely deployed. In this dissertation we demonstrate that by taking into account the specific requirements and threat model of large-scale Internet applications we can design authentication protocols for such applications that are not only more robust but also have low impact on performance, scalability and existing infrastructure. In particular, we show that there is no inherent conflict between stronger authentication and other system goals. This dissertation makes four major contributions. First, through an extensive experimental study, we demonstrate how even a simple authentication mechanism such as SIP Digest authentication can significantly impact the performance and scalability of a carrier-scale VoIP infrastructure. Second, we propose Proxychain, a SIP authentication protocol that not only provides better security guarantees than Digest authentication but also improved performance and scalability for highly-distributed VoIP environments. Third, we develop One-Time Cookies (OTC), a more secure alternative to the use of HTTP cookies as session authentication tokens. OTC is inherently robust against session hijacking attacks while preserving the efficiency and statelessness benefits of cookies. Fourth, we present Direct Validation of SSL/TLS Certificates (DVCert), a practical mechanism that offers more robust validation of SSL/TLS server certificates without requiring external third-parties or additional infrastructure. By providing stronger server authentication, DVCert effectively reduces the risk of man-in-the-middle attacks against SSL/TLS connections. In so doing, we provide robust and practical authentication mechanisms that can improve the overall security of large-scale VoIP and Web applications.
N.C. Innocence Inquiry Commission's First Decade: Impressive Successes and Lessons Learned

This article examines the North Carolina Innocence Inquiry Commission in its first decade of operation. The Commission, which was created in 2006 by the North Carolina legislature, is unique in the nation for its structure and charge to investigate and find cases of factual innocence among convicted felons. This article examines the seven cases handled by the Commission where innocence has been found. In them, nine men have been freed, each after serving decades in prison, in murder and rape cases that the evidence developed by the Commission showed they did not commit. The Commission has demonstrated that its general inquisitorial model with broad access to evidence, investigative tenacity and accumulated expertise, and neutrality provide important benefits in finding and documenting evidence of innocence. These seven cases provide fascinating examples of mistakes in the initial investigation and dogged tunnel vision that focused on finding incriminating evidence to convict the incorrectly selected prime suspect(s). They exhibit an abundance of false statements by informers and erroneous tips by reward seekers, erroneous forensic evidence, false confessions, and mistaken eyewitness identifications. The Commission has enjoyed cooperation from law enforcement and prosecutors, but it has also had to overcome resistance by officials defending earlier flawed investigations and prosecutions. In these seven cases, the process succeeded.The examination of these cases and the Commission’s processes show an important and successful new model for rectifying the systemic errors that produce wrongful convictions and evade correction through ordinary adversarial procedures. The Commission’s successes and the lessons learned from its operation deserve examination by other jurisdictions dealing with the persistent failures of our criminal justice system to avoid convicting and incarcerating defendants who are factually innocent.
Pervasive, yet idiosyncratic, epistatic pleiotropy during adaptation in a behaviourally complex microbe

Understanding how multiple mutations interact to jointly impact multiple ecologically important traits is critical for creating a robust picture of organismal fitness and the process of adaptation. However, this is complicated by both environmental heterogeneity and the complexity of genotype-to-phenotype relationships generated by pleiotropy and epistasis. Moreover, little is known about how pleiotropic and epistatic relationships themselves change over evolutionary time. The soil bacterium Myxococcus xanthus employs several distinct social traits across a range of environments. Here, we use an experimental lineage of M. xanthus that evolved a novel form of social motility to address how interactions between epistasis and pleiotropy evolve. Specifically, we test how mutations accumulated during selection on soft agar pleiotropically affect several other social traits (hard agar motility, predation and spore production). Relationships between changes in swarming rate in the selective environment and the four other traits varied greatly over time in both direction and magnitude, both across timescales of the entire evolutionary lineage and individual evolutionary time steps. We also tested how a previously defined epistatic interaction is pleiotropically expressed across these traits. We found that phenotypic effects of this epistatic interaction were highly correlated between soft and hard agar motility, but were uncorrelated between soft agar motility and predation, and inversely correlated between soft agar motility and spore production. Our results show that 'epistatic pleiotropy' varied greatly in magnitude, and often even in sign, across traits and over time, highlighting the necessity of simultaneously considering the interacting complexities of pleiotropy and epistasis when studying the process of adaptation.
Una etnografía de comunidad ante los dilemas económicos.

Valenzuela Garcia, Hugo (2009), Etnografia de un kampung Malayo: pesca, subdesarrollo y multiculturalismo / An thnography of the Impact of Politics and Globalization on the Malaysian Fishing Economy. London and New York: The Edwin and Mellen Press. Prologo de Joaquin Beltran Antolin. “En definitiva, el objetivo de este trabajo es descifrar las causas del aducido ‘problema’ del atraso economico malayo. El medio para llevarlo a cabo es un estudio de caso en profundidad, una etnografia de comunidad que nos permitira, sin embargo, establecer algunas generalizaciones a traves de la comparacion con otras monografias realizadas en la peninsula malaya – en concreto treinta y cinco trabajos etnograficos, de los cuales doce se realizaron en el Estado de Kedah. La descripcion de la cultura malaya y de sus aspectos constitutivos (estructura social, economia, politica y religion) nos posibilitara interrogar el contexto local en relacion al problema de investigacion, revelando asi la verdadera naturaleza del dilema economico malayo y, esperamos, haciendo palmarias las contradicciones del desarrollo inducido implantado en Malaysia.” (Valenzuela, 2009: 21)
Protective effect of intermittent versus chronic calorie restriction on mammary tumor development in relationship to prospective IGF-1 serum concentrations in MMTV-TGF-α mice

B4 Numerous studies indicate that chronic caloric restriction (CCR) provides a protective effect on chemically-induced and spontaneous mammary tumor (MT) development in rodents. Recently, intermittent caloric restriction (ICR) was reported to be more protective than CCR in transgenic mouse models that develop MTs. One growth factor considered to mediate tumorigenesis is IGF-I. Here we compare prospective serum IGF-I levels in relationship to mammary tumorigenesis for these two modes of calorie restriction. > >At 8 wk of age 225 MMTV-TGF-α female mice had ad libitum access to AIN-93M diet. At 10 wk they were assigned to AL (ad libitum AIN-93M diet), ICR (3-wk of 50% caloric restriction of AIN-93M-mod diet with 2x protein, fat, vitamins and minerals followed by 3-wk of 100% AL mice’s consumption of AIN-93M), and CCR (fed a diet to match calorie and nutrient intake for each 6-wk ICR cycle, ~ 75% of AL consumption) groups. Food intakes were determined daily. Body weights, palpation and tumor measurements were done weekly. Mice were followed until MT burden necessitated euthanasia or they reached terminal endpoints of 79 (end of restriction) or 82 (end of refeeding) weeks of age. Serum samples were obtained at euthansia and in cycles 1, 3, 5, 8, and 11 from cohorts corresponding to the 1st, 2nd and 3rd weeks of restriction and refeeding for ICR mice to relate levels of IGF-1 to the appearance of palpable MT. > >Cumulative food intakes for ICR and CCR mice were 24.8% and 22.6% lower, than AL mice (p Body weights fluctuated in response to calorie intake during the study for ICR mice and there was an overall significant difference among the groups. Final body weights, mammary and internal fat pad weights of AL mice were heaviest, followed by CCR and IR-refed mice with similar weights (p>0.05) while ICR-restricted mice weights were the lowest. 68.3% of AL mice developed 1-6 MTs/mouse (grade 1-3), 36.2% of CCR mice had 1-2 MTs/mouse (grade 1-3) and only 8.2% of ICR mice developed 1 MT/mouse (grade 1-2). There were no differences for time to tumor detection and MT weights among the groups. Terminal serum IGF-1 concentration of AL mice was higher (p These results confirm that ICR provides greater protection compared to CCR with respect to prevention of MT development. Additionally, tumor burden and aggressiveness were reduced in ICR mice. The IGF-1 axis appears to be involved in MT development but its specific role in the protective effect of calorie restriction remains to be determined. It is anticipated that ongoing mammary fat pad and MT analyses will provide additional insights into why ICR is superior to CCR with respect to prevention of mammary tumorigenesis. >(Support: NIH CA 101858 and The Hormel Foundation).
Stochastic Buffering for Bundled SWCNT Interconnects Considering Unidimensional Fabrication Variation

The heterogeneous system architecture which leverages multicore computing paradigm has become increasingly popular. Nevertheless, timing minimization is still a critical design challenge. Buffer insertion for bundled single-walled carbon nanotubes (SWCNTs) is capable of significantly improving circuit timing of signal nets with limited buffer deployment. However, due to the imperfection of fabricating long straight carbon nanotubes, there exist significant variations on the critical CNT geometric parameters such as the diameter and density, which will affect the circuit performance. On the other hand, the prevailing CNT fabrication uses Chemical Vapor Deposition, where the unidimensional spatial correlation manifests strongly. In this work, a unidimensional variation aware stochastic SWCNT interconnects buffering algorithm is developed to handle fabrication variations of CNTs in buffer insertion. To improve its time complexity, a novel importance sampling based timing evaluation technique is proposed considering unidimensional correlations of variations. The simulation results demonstrate that the unidimensional variation aware importance sampling based stochastic SWCNT interconnects buffering algorithm on average saves more than 30 percent buffer area over copper buffering while satisfying timing constraints. In addition, our proposed stochastic algorithm achieves much better performance than the best case design and the worst case design in terms of timing and buffer cost.
An Applied, Combined View of Impulse Shopping

Impulse shopping has been studied and reported on for at least 75 years in the academic press. Yet, there is still no clear or agreed-upon theory for why it occurs or among whom. In this study, a large number of consumers (big data) responded to an “I live for today because tomorrow is so uncertain” statement (a surrogate for impulsive purchasing) through a national US online survey. Demographic differences were used in a grounded theory approach to parse out differences among those reporting. Questionnaire findings were then combined with neural concepts such as relative preference and prospect theory to provide a potential solution to the “who is an impulse” buyer question. Managerial implications for the findings are included in the report.
Cognitive Massive MIMO Relay Networks

The sum rate performance of cognitive multi-user massive multiple-input multiple-output (MIMO) relay networks is investigated. Specifically, a secondary relay network is underlaid in the same cell of a primary multi-user network. Both primary and secondary networks are allowed to share the same frequency spectrum. Hence, the transmit power of the secondary relay network is constrained such that the interference inflicted at the primary network due to the secondary concurrent transmissions does not exceed a predefined interference temperature. Under the aforementioned system set-up, the asymptotic signal-to-interference-plus-noise ratio and achievable sum rate expressions are derived for two specific antenna configurations at the relay, secondary and primary base-stations. Our asymptotic analysis reveals that the secondary relay network can be operated at its peak average transmit power level without degrading the performance of the primary network whenever the numbers of antennas at the relay, secondary and primary base-stations are allowed to grow without bound while keeping fixed ratios among them. Consequently, the asymptotic performance metrics for both primary and secondary networks become independent of the corresponding interference temperature. Furthermore, the intra-cell co-channel interference inflicted at the secondary network due to the primary network and vice-versa can be asymptotically mitigated. Therefore, massive MIMO technology can be exploited for successful deployments of cognitive relay networks with underlay spectrum sharing.
Time-to-Event Ratio to Predict Outcome in Patients with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation?

• The duration of time (from diagnosis) to transplantation (TTT) for patients in first complete remission (CR1), has been used as a surrogate marker for a disease characteristic for patients with acute myeloid leukemia (AML).
Physiological Manifestations of Critical Illness

Critical illness is a condition that may greatly affect the pharmacokinetic behavior of antibiotics. It is characterized by several manifestations that may occur because of different underlying diseases. These manifestations, by altering mainly the volume of distribution (Vd) and the clearance (CL) of a given antibiotic, are expected to cause drug overexposure or underexposure when standard doses of antibiotics are administered to critically ill patients.
Remarks on soundness of proofs

The proof of soundness for many zero-knowledge schemes has been given in an incomplete way. We discuss the consequences.
Core-Mantle Coupling

Definition, scope, and aims The Earth is not a perfect timekeeper, and the spectrum of the variations in the mantle’s angular velocity b V spans a wide range of frequencies. Of particular interest here are the comparatively large amplitude decadal and semidecadal variations in which changes in length of day, P, of up to 2 ms occur. These would not be explained even if the global circulations of the atmosphere and oceans could be reversed. This is confirmed by a more detailed argument given in our recent review (Roberts and Aurnou, 2012), which will be referred to here as “RA12.” The origin of these length of day (LOD) variations must be sought in the Earth’s core, and Figure 1 suggests that the task is not an easy one. Figure 1b shows dP/dt, derived by differentiating smoothed LOD data from the last half century, with atmospheric, oceanic, and tidal signals removed; semi-decadal time variations are clearly seen with a period tLOD of about 6 years (e.g., Abarca del Rio et al., 2000). Figure 1c shows the implied b Gz as a function of time t, where b Gz is the component parallel to the polar axis Oz of the torque b G exerted by the core on the mantle. This shows that b Gz of nearly 10 Nm is generated. We shall call this the “target torque” and seek its origin. In addition, to the semi-decadal oscillations, larger variations seem to exist having longer periods, one of which is estimated to have a roughly 60 year period (e.g., Roberts et al., 2007). This time scale is reminiscent of the geomagnetic secular variation, and it is natural to seek
The neuro-ophthalmic examination

Abstract The neuro-ophthalmic examination combines ophthalmic and neurologic techniques to assess the patient's vision, pupillary function, ocular motility, eyelids, orbits, fundus appearance, and neurologic status. In most cases, after obtaining the history, the examiner should have already formed an opinion regarding the possible localization and differential diagnosis. The examination then either supports or refutes these initial impressions; examination findings may also prompt consideration of other diagnoses. In this chapter, the major elements of the neuro-ophthalmic examination are reviewed, and in each section, disorders that affect them are mentioned briefly. The neuro-ophthalmic examination in comatose patients is also reviewed. The reader should then refer to the appropriate chapters for more detailed differential diagnoses and discussions of the pathologic disorders.
Alcohol expectancies and distress tolerance: Potential mechanisms in the relationship between posttraumatic stress and alcohol use

Abstract Individual reactions following trauma exposure vary, with up to one-third of survivors developing posttraumatic stress disorder (PTSD; Kessler, Chiu, Demler, & Walters, 2005 ). Individuals exposed to trauma have high rates of co-occurring psychiatric disorders, with alcohol abuse among the most common comorbid conditions ( Kessler et al., 2005 ). One factor that may influence this relationship is alcohol expectancies ( Hruska & Delahanty, 2012 ), where individuals who believe that using alcohol will help reduce negative affect (i.e., positive alcohol expectancies) may be more likely to use and misuse alcohol. Low distress tolerance has also been implicated as a vulnerability for the development PTSD and alcohol use disorders, particularly as it relates to a desire to reduce negative affect. In the current study, the relationship between posttraumatic stress and alcohol use was proposed to be influenced by positive PTSD alcohol expectancies, whereas distress tolerance was hypothesized to be a moderator. Results demonstrated that positive PTSD alcohol expectancies partially mediated the relationship between posttraumatic stress and alcohol use. Post-hoc analyses found a conditional indirect effect for symptoms of negative alterations in cognitions and mood when distress tolerance was high. These results underscore the importance of advancing knowledge on how individual differences impact posttrauma processes.
Velocity and Path Reconstruction of a Moving Object Using a Moving Camera

Integral concurrent learning based observers are developed that use velocity measurements of a monocular camera and pixel coordinates of tracked features to simultaneously estimate the path of a moving monocular camera, the distance to stationary features, as well as the structure and motion of rigid moving objects features in real time. A Lyapunov-based stability analysis is provided to show the structure and motion observer estimation errors for the moving objects globally exponentially converge to an ultimate bound or zero if the object has a constant velocity.
Work by day and sleep by night, do not sleep too little or too much: Effects of sleep duration, time of day and circadian synchrony on flanker-task performance in internet brain-game users from teens to advanced age.

Research elucidating the effects of sleep and circadian rhythm on cognitive performance is advancing, yet many important questions remain. Using flanker-task performance scores from a large internet sample (N = 48,881) with repeated measures of cognitive performance and linked prior-night self-reported sleep duration, we analysed the relationship between sleep duration, time of day of task performance, and chronotype synchrony with performance in participants aged 15-80 years. Results indicate a performance peak at 7 hr habitual sleep duration, and point to a variable effect of deviation from habitual sleep duration depending on users' habitual sleep duration and age. Time-of-day effects were notable for a steady decline in performance up until 01:00 hours-02:00 hours for the group as a whole, which was accounted for by nighttime deterioration on trials requiring inhibitory executive functioning, particularly in older subjects. Analyses did not demonstrate an advantage for playing in synchrony with self-identified chronotype. Results strengthen findings indicating an inverted U-shaped relationship between sleep duration and cognitive performance across a broad spectrum of age groups. These findings underscore the importance of daytime task performance for tasks requiring inhibitory function, especially in elderly people. Findings highlight the utility of large-scale internet data in contributing to sleep and circadian science.
The Geometric Effects of Distributing Constrained Nonconvex Optimization Problems

A variety of nonconvex machine learning problems have recently been shown to have benign geometric landscapes, in which there are no spurious local minima and all saddle points are strict saddles at which the Hessian has at least one negative eigenvalue. For such problems, a variety of algorithms can converge to global minimizers. We present a general result relating the geometry of a centralized problem to its distributed extension; our result is new in considering the scenario where the centralized problem obeys a manifold constraint such as when the variables are normalized to the sphere. We show that the first/second-order stationary points of the centralized and distributed problems are one-to-one correspondent, implying that the distributed problem—in spite of its additional variables and constraints—can inherit the benign geometry of its centralized counterpart. We apply this result to show that the distributed matrix eigenvalue problem, multichannel blind deconvolution problem, and dictionary learning problem all enjoy benign geometric landscapes.
Stomping Harm and Reducing Preventable Infections (SHARPI) Rounds - A novel strategy for CLABSI prevention

Background Elimination of central line associated blood stream infections (CLABSI) is a patient safety priority. Our quaternary NICU struggles on our journey to zero harm. Apparent cause analyses identified lapses in bundle compliance, but did not impact CLABSI rates. Objective To utilize SHARPI rounds to discuss bundle compliance, line necessity and accesses at the bedside in order to reduce CLABSI rates. Design/Methods An intra-professional team of physicians, nurses and …
Toughening magnesium with gradient twin meshes

Abstract In the present study, we combine comprehensive site-specific microstructural and mechanical characterization studies to evaluate the toughening effect induced by applying a surface SPEX milling (SSM) approach to commercially-pure Mg. Our results show that the high frequency, multi-directional deformation strain induced by SSM generated gradients in the grain size and orientation with depth from the surface. More importantly, it also resulted in a gradient in the density of twin meshes, which are defined as two or more intersecting arrays of twins, along the sample thickness direction. Tensile tests at room temperature indicate that after SSM, the samples have higher ultimate tensile strengths and two-fold increases in ductility as compared to those of the untreated samples. The effect of the initial texture and SSM parameters on the microstructural evolution and texture randomization were analyzed by electron backscattered diffraction (EBSD). Furthermore, in order to correlate the variation in microstructure with the site-specific mechanical response, TEM and in-situ micropillar compression testing in SEM were performed at various distances from the SSM-treated surface. The results show that twin meshes may be responsible for the activation of more slip systems and higher strain hardening, which result in higher uniform plastic strain.
Correction to: Discrimination Matters: Relations of Perceived Discrimination to Student Mental Health

The first author noticed an error in the description of the referent group for the interaction between student race and discrimination on the outcome of anxiety. The corrected results should read:
Quality of Life Following Stroke: A Qualitative Study Across 30 Years

Much of what we know about stroke is limited to the first 5 years postinjury; however, the effects of having a stroke remain several years, even decades, postinjury, and the impact this has on an i...
Diacetyl exposure disrupts iron homeostasis in animals and cells.

OBJECTIVE Several mechanisms have been proposed for the biological effect of diacetyl. We tested the postulate that animal and cell exposures to diacetyl are associated with a disruption in iron homeostasis. MATERIALS AND METHODS Male, Sprague-Dawley rats were intratracheally-instilled with either distilled water or diacetyl. Seven days after treatment, animals were euthanized and the lungs removed, fixed, and embedded. Sections were cut and stained for iron, collagen, and ferritin. Human epithelial (BEAS-2B) and monocytic (THP-1) cells were exposed in vitro to ferric ammonium citrate (FAC), diacetyl, and both FAC and diacetyl. Cell non-heme iron concentrations and ferritin levels were quantified using inductively coupled plasma optical emission spectroscopy and an immunoassay respectively. RESULTS After exposure of animals to diacetyl, there were airway polypoid lesions which stained positively for both iron and the intracellular storage protein ferritin. Trichrome stain showed a deposition of collagen immediately adjacent to accumulated metal following diacetyl exposure. In in vitro cell exposures, FAC increased non-heme iron concentration but co-incubations of FAC and diacetyl elevated levels to significantly greater values. Levels of ferritin were increased with exposures of BEAS-2B and THP-1 cells to FAC but were similarly greater after co-exposure with FAC and diacetyl. CONCLUSIONS Results of animal and cell studies support a disruption of iron homeostasis by diacetyl. It is proposed that, following internalization, diacetyl complexes intracellular sources of iron. The cell recognizes a loss of its requisite iron to diacetyl and imports greater concentrations of the metal.
Non-redundant requirement for CXCR3 signalling during tumoricidal T-cell trafficking across tumour vascular checkpoints

T-cell trafficking at vascular sites has emerged as a key step in antitumour immunity. Chemokines are credited with guiding the multistep recruitment of CD8(+) T cells across tumour vessels. However, the multiplicity of chemokines within tumours has obscured the contributions of individual chemokine receptor/chemokine pairs to this process. Moreover, recent studies have challenged whether T cells require chemokine receptor signalling at effector sites. Here we investigate the hierarchy of chemokine receptor requirements during T-cell trafficking to murine and human melanoma. These studies reveal a non-redundant role for Gαi-coupled CXCR3 in stabilizing intravascular adhesion and extravasation of adoptively transferred CD8(+) effectors that is indispensable for therapeutic efficacy. In contrast, functional CCR2 and CCR5 on CD8(+) effectors fail to support trafficking despite the presence of intratumoral cognate chemokines. Taken together, these studies identify CXCR3-mediated trafficking at the tumour vascular interface as a critical checkpoint to effective T-cell-based cancer immunotherapy.
Derivation of an Analytical Solution to a Reaction-Diffusion Model for Autocatalytic Degradation and Erosion in Polymer Microspheres

A mathematical reaction-diffusion model is defined to describe the gradual decomposition of polymer microspheres composed of poly(D,L-lactic-co-glycolic acid) (PLGA) that are used for pharmaceutical drug delivery over extended periods of time. The partial differential equation (PDE) model treats simultaneous first-order generation due to chemical reaction and diffusion of reaction products in spherical geometry to capture the microsphere-size-dependent effects of autocatalysis on PLGA erosion that occurs when the microspheres are exposed to aqueous media such as biological fluids. The model is solved analytically for the concentration of the autocatalytic carboxylic acid end groups of the polymer chains that comprise the microspheres as a function of radial position and time. The analytical solution for the reaction and transport of the autocatalytic chemical species is useful for predicting the conditions under which drug release from PLGA microspheres transitions from diffusion-controlled to erosion-controlled release, for understanding the dynamic coupling between the PLGA degradation and erosion mechanisms, and for designing drug release particles. The model is the first to provide an analytical prediction for the dynamics and spatial heterogeneities of PLGA degradation and erosion within a spherical particle. The analytical solution is applicable to other spherical systems with simultaneous diffusive transport and first-order generation by reaction.
Modification of Essential Histidyl Residues of the β2 Subunit of Tryptophan Synthetase by Photo-oxidation in the Presence of Pyridoxal 5'-Phosphate and l-Serine and by Diethylpyrocarbonate

Photoinactivation of the β2 subunit of tryptophan synthetase is dependent on the presence of the coenzyme, pyridoxal 5′-phosphate, and results in the specific destruction of 1 histidyl residue per β monomer. The rate of photoinactivation is strikingly increased by the addition of a substrate, l -serine. Inactivation of the β2 subunit can also be achieved by the modification of 2 to 3 histidyl residues per monomer with diethylpyrocarbonate. β2 subunit modified by either procedure can still form a complex with pyridoxal 5′-phosphate. The chemically modified β2 subunit can form some Schiff base intermediate between pyridoxal 5′-phosphate and l -serine but appears to be blocked in the further conversion of this intermediate. These results suggest that 1 of the chemically modified histidyl residues may serve a role in the abstraction of the α-proton of l -serine. This suggestion is supported by the finding that the Vmax for the conversion of l -serine to pyruvate is dependent on an ionizing group with a pK of 6.7.
Amniotic-Fluid Phospholipids After Maternal Administration of Dexamethasone

The administration of corticosteroids to pregnant women in premature labor can accelerate fetal lung development and potentially prevent neonatal respiratory distress syndrome (RDS). Controversy exists, however, as to whether amniotic fluid phospholipid indices of lung maturation are influenced by such treatment. Without a suitable test for evaluating the fetal response to corticosteroids, there is no method of recognizing whether and when lung development has been stimulated. In an attempt to resolve this issue, we carried out a study of amniotic fluid phospholipids as part of the National Institutes of Health multicenter trial of prenatal corticosteroids. Amniocenteses were performed before the administration of either steroid hormone or placebo and approximately 1 week after a series of four injections was initiated. Analysis of the ratio of lecithin (phosphatidylcholine) to sphingomyelin (L/S ratio) revealed nearly identical values initially and no significant difference in the posttreatment means when 25 steroid-treated pregnancies were compared to 20 control pregnancies. Although there were significant increases in both groups during the interval between amniocenteses, no statistical difference was found in the extent of change in L/S ratios between the two groups, when pretreatment values were compared with those obtained an average of 1 week later. In addition to evaluating L/S ratios, we performed an assessment of phospholipid concentrations in 17 pregnancies before and after administration of dexamethasone. This revealed no detectable phosphatidylglycerol. There were increases in the absolute concentrations of phosphatidylcholine and disaturated phosphatidylcholine, but these changes were relatively modest in magnitude and could be attributable to either advanced gestational age or dexamethasone. Our results demonstrate that current tests of fetal lung maturity do not provide a routine means for prenatal detection of pulmonary maturational responses to corticosteroids.
EFFECT OF LOAD PLACEMENT ON RIGID PAVEMENT BEHAVIOR

Portland cement concrete pavements are subjected to a variety of loads during their life; however, existing design practices utilize a single so called critical load position for designing pavements. This load is normally the corner or edge load for jointed highway pavements and the interior load for continuously reinforced highway pavements. It is essential that the entire spectrum of loads using the facility be considered. With analytical techniques formerly available, this was difficult; however, at the present time the availability of discrete-element methods makes it possible to consider the effect of a wide range of load sizes, arrangement, and placement on critical stresses and deflections and thus predicted life. This paper presents a study of the sensitivity of pavement behavior as indicated by maximum stress levels and the resulting expected pavement performance relative to the position of the load on the slab. The findings are compared to existing design practice.
The “Dam Talk” of Butler, Tennessee: Tracing the Stability and Change of Historical Memory in Newspaper Coverage

Abstract This analysis followed print newspaper coverage of Butler, Tennessee, to determine the stability and change of historical memory. Utilizing longitudinal analysis, it examines the historical narrative over time using local, regional, and national print coverage. The study determines that historical memory is modified over time in national, regional, and local print outlets, and that media play a pivotal role in the change process. The study concludes that media, particularly local media, often determine source perspective that leads to narrative modifications, thus “changing” memories of the past.
Examining the role of the central melanocortin system in the regulation of adaptive thermogenesis of brown adipose tissu

Previous work from our laboratory has shown that the melanocortin system is required for the acute homeostatic responses to increased dietary fat (Butler et al., 2001). In this study we examine the mechanism underlying the energy expenditure defect observed in melanocortin-4 receptor null (MC4R-/-) mice. Using specific polysynaptic retrograde tracing from interscapular brown adipose tissue (IBA T) coupled with dual labeling immunohistochemistry, we show co-expression of MC4R-green fluorescent proteinimmunoreactivity (MC4R-GFP-IR) and the attenuated pseudorabies virus (PRV)-IR in many hypothalamic and brain stem regions known to play an important role in nonshivering thermogenesis, demonstrating an anatomical link between the central melanocortin system and the sympathetically-mediated regulation of IBA T thermogenic function. Additionally, using both genetic and pharmacological antagonism, we show that intact MC4R signaling is required to appropriately up-regulate UCPl in response to physiological stimuli, such as a high-fat diet and short-term cold exposure. Our results that MC4R-/and agouti related peptide (AGRP)-treated mice on a high-fat diet have a similar increase in their total serum 3,5,3 '-triiodothyronine (T,) levels to wild-type controls also suggests that the MC4R-mediated up-regulation of UCPl in response to a > high-fat diet is independent of the central hypothalamic-pituitary-thyroid (HPT) axis. Our data showing that UCPl is up-regulated normally in MC4R-/mice after longer periods of cold exposure suggests that melanocortin system-mediated non-shivering thermogenesis may be differentially regulated by diet and cold or alternatively that compensatory mechanisms may develop in these animals after long-term cold exposure.
Small-Scale Variations in the 1/4 keV X-Ray Background along the Galactic Plane

Forty-two ROSAT Position Sensitive Proportional Counter pointed observations in the first quadrant (l ~ 4°-26°) of the Galactic plane are mosaicked in order to study the spatial structure of the X-ray-emitting gas in the Local Hot Bubble (LHB). X-ray intensity variations at various angular scales are examined in the 1/4 keV band, and degree-scale variations are detected. In the context of the LHB and the displacement model for the origin of the 1/4 keV band background, the hardness ratio, angular size, and magnitude of the intensity variations suggest that at the ±10% level there is an influence of a clumpy boundary structure superposed upon the emission from the uniformly distributed ~106 K plasma of the LHB interior. The possible origins of such a clumpy boundary structure of the LHB are discussed with Rayleigh-Taylor instabilities and clumping of the cooler interstellar medium at the boundary region being likely candidates.
Removal Reform: A Solution for Federal Question Jurisdiction, Forum Shopping, and Duplicative State-Federal Litigation

Federal court procedural, especially jurisdictional ones, need to be governed by clear, effective, and fair rules. Yet twentieth century doctrines and reforms, even when made in the name of pragmatism, have produced decidedly unpragmatic results: a vague and disputed doctrine of federal question jurisdiction that excludes from federal court many cases where federal law controls the outcome, rules that facilitate forum shopping by plaintiffs and make it impossible to predict in advance what law will apply to decide one’s case, and the stunning waste of a system in which the exact same issues are simultaneously litigated in state and federal courts as part of a “race to judgment.” The status quo is, quite simply, broken. This Article contends that we can ameliorate these concerns by permitting removal to federal court whenever the parties are diverse and whenever the defendant’s answer or plaintiff’s reply shows that a case arises under federal law— rather than artificially limiting our vision to the plaintiff’s well-pleaded complaint. Though modest, these reforms could serve as a tonic to many of the status quo’s most striking irrationalities: the criteria for federal question jurisdiction would be expanded to cover many currently excluded cases that turn on federal law, plaintiffs would lose opportunities to forum shop by pinning unwilling defendants in state courts, and the systemic waste of duplicative and concurrent state-federal litigation could be largely eliminated. By broadly addressing these deeply-rooted problems, this Article aims at improving the clarity, rationality, and essential fairness of the rules that govern our federal courts.
Cooperating search agents explore more than defecting search agents in the Internet information access

In the Internet Information Access Problem, information-seeking agents (software or humans) are selfishly rational in obtaining the information sought. From a single agent's perspective, sending out as many queries as possible maximizes the chance of achieving the information sought. However, if every agent does the same, the information servers will be overloaded and most of the search agents won't be able to retrieve the information. Our previous results suggest that when behaviorally similar information-seeking agents cluster together, cooperation is promoted. In these experiments, the ranges of query (i.e., maximum logical distance from the information-seeking agents to potential information severs) is fixed for each search agent; agents only inquire the severs within the distance. The article evolves the range of the access distance. When similar agents (cooperators with cooperators and defectors with defectors), cluster together, cooperators tend to access diversified information sites while defectors tend to access only common information sites, resulting in high congestion. This phenomenon can be seen in human agents as well. When an agent sees too much competition or overuse of resource, it considers alternative choices. For example, when people see a congested highway, they tend to take other routes even if the routes may be longer. A similar phenomena is observed in our experiments. The results of the research can be used to help designing the Internet search agents that are efficient and less burdensome to information servers.
Neurotrophic effects of vascular endothelial growth factor and neurotrophins on cultured major pelvic ganglia.

OBJECTIVE To investigate the feasibility of using a ganglial culture system to screen various growth factors as potential therapeutic agents for pelvic nerve injuries. MATERIALS AND METHODS The major pelvic ganglia (MPG) were isolated from male rats and attached to culture dishes with the aid of Matrigel (Becton Dickinson, Mountain View, CA, USA). Alternatively, the dorso-caudal region (DCR) of MPG, from which the cavernous nerves originate, was dissected and then attached to a Matrigel-coated coverslip. The MPG or DCR was cultured in serum-free medium supplemented with phosphate-buffered saline (PBS, control), 50 ng/mL of vascular endothelial growth factor (VEGF), 20 ng/mL of a neurotrophin (BDNF, NT3, or NT4), or combinations of these growth factors. After 2 days of incubation, the ganglial tissues with their outgrowing nerve fibres were stained for the expression of NADPH-diaphorase, tyrosine hydroxylase (TH) and acetylcholinesterase (AChE). The length and staining intensity of nerve fibres were analysed. RESULTS The outgrowing fibres were significantly longer in MPG treated with any of the four tested growth factors than in PBS-treated MPG. The combination of VEGF and NT3 induced the best fibre growth. Improvements to the culturing conditions allowed a histological examination of the outgrowing fibres for the expression of nitric oxide synthase (NOS), TH and AChE. VEGF and BDNF were equally capable of inducing NOS- and TH-expressing fibres. BDNF was much weaker than VEGF for inducing AChE-expressing fibres. CONCLUSIONS This improved culturing system is potentially useful for screening nerve-regenerating factors; VEGF had neurotrophic effects comparable with BDNF, NT3, or NT4.
Reducing the defect density in {MBE-ZnSe}/{III-V} heterostructures

Abstract The defect densities that are observed in 1 μm ZnSe films grown by molecular beam epitaxy on various III–V buffer layers are compared. Cathodoluminescence (CL) imaging has been used to provide a rapid and non-destructive method of characterizing the defect densities and was found to be in agreement with both etch pit density and transmission electron microscopy characterizations. We also examined the defect density of ZnSe epilayers grown on relaxed buffer layers of (In,Ga)P (lattice-matched to ZnSe) with the phosphide surface capped with eight monolayers of GaAs exhibiting various surface reconstructions. In this manner, the ZnSe GaAs surface chemistry is maintained while simultaneously achieving a lattice-matched buffer layer to ZnSe. Films grown without special nucleation precautions on c(4 × 4)-reconstructed GaAs were typically found to result in defect densities larger than 107 cm−2. Using a Zn pre-exposure on (2 × 4)-reconstructed GaAs, the defect densities were decreased by over an order of magnitude. In this paper, the microstructural and optical properties of ZnSe on phosphide-containing III–V buffer layers will be described and contrasted to the more conventional ZnSe GaAs heterostructure, using atomic force microscopy and CL.
Micro-Tensile Testing of Nanocrystalline Al/Zr Alloys

A novel micro testing machine has been used to perform tensile tests on nanocrystalline Al/Zr microsamples with grain sizes ranging from 10 to 250 nm. The problems associated with testing such small specimens (200 {micro}m x 200 {micro}m in the gage section) were overcome by using a contact-free interferometric strain gage (ISDG) and alignment and low friction loading were assured by use of a linear air bearing. The postulated relationship between yield stress and hardness was investigated and will be discussed. The effect of the microstructure and the grain size of the compacts on their mechanical behavior are also analyzed.