cssi/SciSciGPT-SciSciNet huggingface dataset:
Pharmacoeconomic impact of up-front use of plerixafor for autologous stem cell mobilization in patients with multiple myeloma.

Abstract Background aims Stem cell collection can be a major component of overall cost of autologous stem cell transplantation (ASCT). Plerixafor is an effective agent for mobilization; however, it is often reserved for salvage therapy because of its high cost. We present data on the pharmacoeconomic impact of the use of plerixafor as an up-front mobilization in patients with multiple myeloma (MM). Methods Patients with MM who underwent ASCT between January 2008 and April 2011 at the Mount Sinai Medical Center were reviewed retrospectively. In April 2010, practice changes were instituted for patients with MM to delay initiation of granulocyte-colony-stimulating factor (G-CSF) support from day 0 to day +5 and to add plerixafor to G-CSF as an up-front autologous mobilization. Targets of collection were 5–10 × 10 6 CD34 + cells/kg. Results Of 50 adults with MM who underwent ASCT, 25 received plerixafor/filgrastim and 25 received G-CSF alone as an up-front mobilization. Compared with the control, plerixafor mobilization yielded higher CD34 + cell content (16.1 versus 8.4 × 10 6 CD34 + cells/kg; P = 0.0007) and required fewer sessions of apheresis (1.9 versus 3.1; P = 0.0001). In the plerixafor group, the mean number of plerixafor doses required per patient was 1.8. Although the overall cost of medications was higher in the plerixafor group, the cost for blood products and overall cost of hospitalization were similar between the two groups. Conclusions Up-front use of plerixafor is an effective mobilization strategy in patients with MM and does not have a substantial pharmacoeconomic impact in overall cost of hospitalization combined with the apheresis procedure.
“That was my occupation”: Oral narrative, performance, and black feminist thought

Black feminist thought supports the interdependence of what are called “theories of the flesh” and “specialized knowledge.” Theories of the flesh reflect the distinctive interpretations of the world carved out of the material realities of a group's life experiences. Specialized knowledge infuses elements and themes of black women's culture and traditions with critical interventionist thinking to provide black women with new tools of resistance. The oral narrative of Mrs. Alma Kapper, who worked as a domestic and sharecropper in the black belt of Mississippi, is illuminated through the joining of black feminist thought and the performance paradigm. As a result, black feminist thought and the performance paradigm augment each other as analytical constructs in unveiling the many ways people “lettered” and “unlettered” theorize themselves.
Liquid oxide phase sintering of molybdenum and tungsten

Abstract In the hydrogen sintering of Mo and W at about 1700°C, compacts containing minor amounts of TiO2 combined with UO2 or ThO2 will permit the sintered density to approach theoretical. The combination of these oxides appears to result in a phase which is liquid at the sintering temperature, and wets Mo and W.
Computational evaluation for the mechanical behavior of U10Mo fuel mini plates subject to thermal cycling

Abstract Mechanical behavior of the monolithic mini-plates during a post-fabrication furnace annealing was investigated. Monolithic fuel is a proposed fuel form to accomplish higher uranium densities in the reactor core and thermal cycling is a standard performance evaluation procedure for these fuel elements. To evaluate the mechanical performance of the plate under a thermal loading, a thermo-mechanical finite element simulation was performed. All three stages of the thermal cycling process were considered: (1) heating of a newly fabricated plate to 500 °C, (2) holding at a constant temperature of 500 °C for 60 min, and finally (3) cooling the plate to room temperature. Fabrication induced residual stress fields were implemented as the initial state for the thermal cycle model. It was shown that the fuel foil remains in the elastic regime during the entire process, while the cladding material exhibits additional plasticity. In particular, simulations have revealed the existence of a critical temperature at which the net stress fields on the fuel foils change directions. This stress reversal occurs between 400 and 450 °C which matches the experimental blister temperature of irradiated plates. It was shown that the fuel foil would be in fully tensile state above this transition temperature, facilitating the initiation of blisters. Long transverse edges and the regions around the corners of the fuel foil were identified as possible blister locations. The results have implied that a higher post-fabrication compressive stress field of the foil yields higher threshold temperatures; however, each thermal cycle would progressively relieve compressive stresses of the foil. Comparison with experiments has shown agreement, thus substantiated the capability of the model.
Privacy technologies as political issues: consumption as mobilization

Privacy technologies, particularly anonymous e-mail and value transfer systems, become commonplace not merely by consumer adoption. The networked nature of these systems requires organizational and institutional adoption. In most such cases, institutions decide the parameters of new consumer services, then market those services, giving consumers, at best, veto power over the shape of those services. In the case of privacy technologies, the interests of privacy-preferring individuals are often directly opposed to the interests of organizations which collect personal information, either as a line of profit or as a regulatory requirement. Therefore consumers are unlikely to be offered privacy technologies even to veto them. Privacy activists are left with the question of how to organize consumer demand to influence the planning and development of these systems.
Modern Trunnions Are More Flexible: A Mechanical Analysis of THA Taper Designs

Background There is renewed concern surrounding the potential for corrosion at the modular head-neck junction to cause early failure in contemporary THAs. Although taper corrosion involves a complex interplay of many factors, a previous study suggested that a decrease in flexural rigidity of the femoral trunnion may be associated with an increased likelihood of corrosion at retrieval.
The nature of crystallinity of α-crystallin preparation of bovine lenses

Abstract α-crystallin prepared by isoelectric precipitation yielded well-defined powder diagrams in X-ray diffraction. The reflections could be indexed as coming from a hexagonal primitive unit cell with the dimension of a = b = 8·17 A, c = 7·52 A and γ = 120°. The real unit cell is probably a multiple of this. From the preparation two dialyzable components were obtained. These small molecular weight phosphopeptides (1200 and 2000 daltons respectively) themselves yielded crystalline X-ray diffraction patterns which, however, were different from the patterns obtained with the original preparation. The dialyzed α-crystallin itself was amorphous. Upon recombination of the dialyzed α-crystallin with the dialyzate the original crystalline pattern was again obtained. It is proposed that the phosphopeptide components play a role in the organization of the α-crystallin chains into a well-defined geometrical pattern.
Developing a neurosurgical carotid endarterectomy practice

During the 1984-85 academic year, our neurosurgical service performed 60 carotid endarterectomy (CEA) procedures. By 1989 the annual number of CEAs performed by the neurosurgical service had fallen to six procedures, primarily because of the loss of patient referrals to an aggressive and well-trained vascular surgery group. At that time, an effort was begun to establish a neurosurgical cerebrovascular service and to compete more effectively for patients with extracranial cerebrovascular disease. Protocols for assuring rapid neurosurgical evaluation, improving communications with referring physicians, and developing innovative surgical and perioperative management protocols for CEA patients were instituted. By use of these strategies the annual number of CEAs performed on our neurosurgical service has increased substantially; from six CEAs done in academic year 1988-89 to 107 CEAs done in academic year 1994-95. The number of CEAs will surpass 120 for the present academic year. This presentation reviews the causes of the precipitous decline in the number of CEAs done by our neurosurgical service from 1985-89 and outlines strategies I have found effective for reestablishing neurosurgeons in the care of patients with surgically treatable extracranial cerebrovascular disease.
Using Boolean Queries with a Clustered File Organization.

Various ways of using Boolean queries with a clustered file organization are described. An experiment indicates that such retrieval methods can be effective.
Neural networks versus nonparametric neighbor-based classifiers for semisupervised classification of Landsat Thematic Mapper imagery

Semisupervised classification is one approach to converting multiband optical and infrared imagery into landcover maps. First, a sample of image pixels is extracted and clustered into several classes. The analyst next combines the clusters by hand to create a smaller set of groups that correspond to a useful landcover classification. The remaining image pixels are then assigned to one of the aggregated cluster groups by use of a per-pixel classifier. Since the cluster aggregation process frequently creates groups with multivariate shapes ill suited for parametric classifiers, there has been renewed interest in nonparametric methods for the task. This research reports the results of an experiment conducted on six Landsat Thematic Mapper images to compare the accuracy of pixel assignment performed by four nearest neighbor classifiers and two neural network paradigms in a semisupervised context. In all the experiments, both the neighbor-based classifiers and the neural networks assigned pixels with higher accuracy than the maximum-likelihood approach. There was little substantive difference in accuracy among the neighborhood-based classifiers, but the feedforward network was significantly superior to the probabilistic neural network. The feedforward network classifier generally produced the highest accuracy on all six of the images, but it was not significantly better than the accuracy produced by the best neighbor-based classifier.
Relationship between rheological properties and impact strength in high impact polystyrene

Two batches of a commercially available high-impact polystyrene having different impact strengths were investigated. The steady-shear flow properties, dynamic shear properties, and elongational flow properties of the two were measured. Transmission electron microscopy (TEM) was used to study the microstructure. It is suggested that melt rheology can be a sensitive tool in the characterization of final product properties of rubber-modified polymers: the zero-shear-rate viscosity and the dynamic storage modulus G′, at low frequencies, were experimentally shown to correlate directly with the impact strength, despite the fact that TEM revealed no gross differences in the morphology of the two batches.
Forgetting of verbatim information in discourse

In tree experiments, the causes of forgetting of verbatim information in discourse were investigated. In experiment 1, we tested the view that the surface form of a sentence decays when linguistic elements are integrated into larger discourse structures. Contrary to such a view, the results showed that when text could be integrated, both content and verbatim memory improved. In Experiment 2, we examined the possibility that task instructions could influence the level of memory for exact wording and content. The results showed that although task did influence the amount of verbatim memory, it did not affect memory for content. Experiment 3 was an investigation of the degree to which subjects would spontaneously encode surface information on the basis of the social interactiveness of the sentences. Past research has shown that verbatim memory for insults, jokes, and other personal utterances is quite good. In this experiment, identical sentences were tested in texts that had high versus low interactiveness. Verbatim memory was much higher for the same sentences in the highly interactive context. A pragmatic account of verbatim memory is given to explain how content and instructions influence the encoding of surface form.
A Test of Drive Stimulus Theory Using Saline Stomach Loads

St/mmary.-This study tested the hypothesis that the depression of barpressing following hypertonic NaCl stomach loads is due to their producing unconditioned drive stimuli. Ir was predicted rhar rats given a response-depressing load repeatedly would show less depression on successive occasions as the novel drive stimuli became conditioned to the response. The resulrs did not support this prediction. According to drive stimulus theory responses become conditioned to specific internal stimuli which are produced by particular deprivation conditions. If these internal stimulus conditions are altered, S is less likely to make the response conditioned to them. Estes' (1958) "stimulus-response theory of drive" predicts this by assuming :hat the conditioned stimuli in such a test situation make up a smaller proportion of the total stimuli than they had during prior training. In other words, there are relatively fewer conditioned stimulus elements in the test situation to evoke the response. Such theorizing accounts for satiation effects but also makes the more interesting prediction that as the length of deprivation in a test periad is lolzge~ than in the uaining periods S should also respond less. Supporting this view, Birch, Burnstein, and Clark ( 1958) reported that rats normally fed only zt a specific time each day responded more for food at that time than at shorter or longer deprivation periods. Brown and Belloni ( 1963), however, corrected for a number of deficiencies in the Birch experiment and were unable to replicate [he results. Hatton (1965) used NaCl stomach loads to increase test drive level above that of the training level. Rats were trained to bar-press for water while 23.5-hr. water deprived, then were extinguished after water or hypertonic loads. He obtained an inverted-U function, extinction being more rapid as a function of volume of water load or concenuation of NaCl load. Saline loads which produce more drinking were at the same time more inhibiting to bar-pressing. Since each S received only a single stomach load, Hatton interpreted the depressive effect of NaCl as the result of a change in drive stimuli, conditioned drive stimuli having been replaced by the unconditioned stimuli evoked by the NaC1. Other investigators have reported depressive effects of NaCl loads which might be interpreted in the same manner (e.g., Beck, 1963; Beck & McLean, 1967). In the present experiment rats were given the same response-depressing saline stomach load prior to bar-pressing on 4 different days. It was predicted
Thyroxine derivatives in amniotic fluid

Amniotic fluid protein-bound iodine determinations have been measured in 20euthyroid women in the sixteenth to fortieth week of gestation. The values ranged from 0.7 to 2.2 μg per 100 ml. with a mean of 1.3 μg per 100 ml. T 4 by column values in 11 of the women ranged from 0.7 to 2.0 μg per 100 ml. with a mean of 1.2 μg per 100 ml. Two patients with abnormal thyroid function and one woman who had previously given birth to a child with cretinism were studied. The amniotic fluid protein-bound iodine level in each instance indicated the subsequent thyroid status of the infant. Amniocentesis is a potentially useful procedure in antenatal evaluation of thyroid function.
The Impact of Intravitreal Bevacizumab Therapy on Choroidal Melanoma

Purpose To describe the clinical course and ancillary findings of 3 patients with choroidal melanoma who inadvertently received multiple intravitreal injections of bevacizumab for a presumed diagnosis of choroidal neovascular membrane. Design Observational case series. Methods Three patients with choroidal melanomas who received a series of monthly intravitreal injections of bevacizumab for presumed choroidal neovascularization were evaluated. Clinical, ultrasonographic, and angiographic findings are presented. Histopathologic features are correlated with clinical features in 2 patients who underwent enucleation. Results Lack of benefit in halting tumor progression was observed in all 3 cases. In 2 cases treated with enucleation, there was evidence of bevacizumab-induced gliotic/fibrotic retinal changes. Conclusions We present 3 cases of choroidal melanomas that showed progression while patients received multiple intravitreal injections of bevacizumab. The use of the drug led to the formation of a gliotic/fibrotic membrane that resulted in masking of the underlying tumor and consequently delayed the correct diagnosis.
An Advanced Undergraduate Experiment in 2-D NMR

The concurrent use of one-dimensional (1H-NMR) and two-dimensional (1H-1H-COSY and 1H-1H-Delay-COSY) experiments can unambiguously assign each resonance in a spectrum to a particular proton. We have developed an experiment for the advanced chemistry student that utilizes long-range coupling to assign signals in the spectra of ketopinic acid, borneol, and isoborneol. Prelaboratory discussion of the spectra of camphor, hands-on use of the instrumentation, and determination of molecular stereochemistry are topics visited during the course of this experiment.
Immunogenicity of Induced Pluripotent Stem Cells

iPSC clones, two reprogrammed with three factors (V3-1 and V3-3) and two with four factors (V4-1 and V4-2), were selected for further analysis (Supplementary Fig. 2h). Most implanted B6 ViPSCs failed to form detectable teratomas or formed teratomas that were subsequently immune-rejected with T cell infiltration and massive necrosis (Supplementary Fig. 3a–e). The teratomas that did not undergo apparent regression were also infiltrated with CD4 1 T cells with apparent
PdhR, the pyruvate dehydrogenase repressor, does not regulate lipoic acid synthesis

Lipoic acid is a covalently-bound enzyme cofactor required for central metabolism all three domains of life. In the last 20 years the pathway of lipoic acid synthesis and metabolism has been established in Escherichia coli. Expression of the genes of the lipoic acid biosynthesis pathway was believed to be constitutive. However, in 2010 Kaleta and coworkers (BMC Syst. Biol. 4:116) predicted a binding site for the pyruvate dehydrogenase operon repressor, PdhR (referred to lipA site 1) upstream of lipA, the gene encoding lipoic acid synthase and concluded that PdhR regulates lipA transcription. We report in vivo and in vitro evidence that lipA is not controlled by PdhR and that the putative regulatory site deduced by the prior workers is nonfunctional and physiologically irrelevant. E. coli PdhR was purified to homogeneity and used for electrophoretic mobility shift assays. The lipA site 1 of Kaleta and coworkers failed to bind PdhR. The binding detected by these workers is due to another site (lipA site 3) located far upstream of the lipA promoter. Relative to the canonical PdhR binding site lipA site 3 is a half-palindrome and as expected had only weak PdhR binding ability. Manipulation of lipA site 3 to construct a palindrome gave significantly enhanced PdhR binding affinity. The native lipA promoter and the version carrying the artificial lipA3 palindrome were transcriptionally fused to a LacZ reporter gene to directly assay lipA expression. Deletion of pdhR gave no significant change in lipA promoter-driven β-galactosidase activity with either the native or constructed palindrome upstream sequences, indicating that PdhR plays no physiological role in regulation of lipA expression.
Racial Differences in Self-Reported Pain and Function among Individuals with Radiographic Hip and Knee Osteoarthritis: The Johnston County Osteoarthritis Project

Summary Objective This study compared pain and function among African Americans and Caucasian with radiographic hip and/or knee osteoarthritis (OA), controlling for radiographic severity and other patient characteristics. Methods Participants were 1368 individuals (32% African American) from the Johnston County Osteoarthritis Project with only knee OA, only hip OA, and both knee and hip OA. Linear regression models examined racial differences in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total scores and pain and function subscales, adjusting for radiographic severity, age, gender, education, body mass index (BMI), depressive symptoms, and WOMAC pain (last variable in models of function). Results Among those with only knee OA, African Americans had significantly worse mean WOMAC total scores than Caucasian (32.8 vs 24.3, P P Conclusion Among participants with knee OA, racial differences in pain and function may be explained by BMI and depressive symptoms, and racial differences in function may also be largely influenced by pain. Improving management of weight and depressive symptoms may be key steps toward reducing racial disparities in knee OA symptoms.
Analysis of using EMG and mechanical sensors to enhance intent recognition in powered lower limb prostheses

Objective. The purpose of this study was to determine the contribution of electromyography (EMG) data, in combination with a diverse array of mechanical sensors, to locomotion mode intent recognition in transfemoral amputees using powered prostheses. Additionally, we determined the effect of adding time history information using a dynamic Bayesian network (DBN) for both the mechanical and EMG sensors. Approach. EMG signals from the residual limbs of amputees have been proposed to enhance pattern recognition‐based intent recognition systems for powered lower limb prostheses, but mechanical sensors on the prosthesis—such as inertial measurement units, position and velocity sensors, and load cells—may be just as useful. EMG and mechanical sensor data were collected from 8 transfemoral amputees using a powered knee/ankle prosthesis over basic locomotion modes such as walking, slopes and stairs. An offline study was conducted to determine the benefit of different sensor sets for predicting intent. Main results. EMG information was not as accurate alone as mechanical sensor information (p < 0.05) for any classification strategy. However, EMG in combination with the mechanical sensor data did significantly reduce intent recognition errors (p < 0.05) both for transitions between locomotion modes and steady-state locomotion. The sensor time history (DBN) classifier significantly reduced error rates compared to a linear discriminant classifier for steady-state steps, without increasing the transitional error, for both EMG and mechanical sensors. Combining EMG and mechanical sensor data with sensor time history reduced the average transitional error from 18.4% to 12.2% and the average steady-state error from 3.8% to 1.0% when classifying level-ground walking, ramps, and stairs in eight transfemoral amputee subjects. Significance. These results suggest that a neural interface in combination with time history methods for locomotion mode classification can enhance intent recognition performance; this strategy should be considered for future real-time experiments.
Antifilarial Cellular Responses Detected in a Haitian Pediatric Population by Use of a Microblastogenesis Assay

Previous reports have demonstrated age-related shifts in antifilarial humoral immune responses in 6- to 10-year-old Haitian children; the responses consisted of elevated parasite-specific IgG2 and IgG3 in amicrofilaremic children and elevated IgG4 in microfilaremic children. In this study, the cell-mediated immune responses to soluble adult and microfilarial extracts of Brugia pahangi, determined by use of a microblastogenesis assay, were examined. Capillary blood samples were collected by finger prick from 176 Haitian children in an area with endemic Wuchereria bancrofti. Antigen-specific cellular responsiveness varied as a function of infection status but not age or sex; amicrofilaremic children had significantly greater responses to adult antigens than did microfilaremic children. Significant responses were detected in children less than 2 years of age; thus, correlations observed between filarial antigen-specific responses and infection status are established early in life.
Quantum transport and localization in disordered media: Liouville space dynamics with frequency-dependent dephasing

Abstract A unified theory of quantum transport processes and spectral lineshapes in condensed phases in terms of frequency-dependent dephasing rates is developed. The effective dephasing approximation (EDA) provides a self-consistent procedure for calculating the transport properties of a quantum particle in a disordered medium. It is based on mapping the averaged Liouville space propagator into the propagator of a particle moving in an ordered lattice with an effective frequency-dependent dephasing rate. The effective dephasing rate is determined self-consistently. The Liouville equation for the averaged density matrix is isomorphic to a linearized Boltzmann equation, and the effective dephasing rate represents a generalized BGK. strong-collision operator. Applications of the EDA to the Anderson model of static disorder and to a model of dynamical disorder with a finite timescale are presented, and are shown to be in agreement with scaling theories. The frequency-dependent dephasing which determines the transport processes is found to be much more sensitive to quantum localization than the dephasing which enters into the calculation of optical lineshapes and densities of states.
Microprocessors and integrated electronic technology

The microprocessor has made it possible for a standard complex function to be employed in a broad range of applications that extends the applicability of large-scale integration (LSI) to many situations that could not support special chip designs. This in turn has freed the technology from previous restrictions to evolve in directions appropriate for microprocessors and associated LSI functions. The result is that many new variations of cirucit design and process technology have arisen that lead toward more dense and higher performance integrated-circuit structures.
Demonstration of LMMP (lunar mapping and modeling) using amazon's elastic compute cloud

The Lunar Mapping and Modeling Project (LMMP) is currently being built by NASA. The goal is to provide a single point of access to the best state of knowledge of the moon's terrain, rock and crater fields, resource maps, lighting conditions and thermal conditions. The architecture and design employ a variety of technologies, allowing for execution of complex models, the processing of large data sets and the distribution of the information, over the internet, to both authenticated users and the general public. The architecture supports a variety of light-weight clients including a Flash based display, an iPad/iPhone interface and a set of programmatic APIs that allow rich clients to interact with the LMMP system.
Taking the Long View on the Publication Process

As we write this editorial, we have just finished our cosponsoring attendance at the Research in Management Learning & Education (RMLE) Unconference in Copenhagen. The Unconference afforded us an important opportunity to build community with editors from the other three major management education journals—Eugene Sadler-Smith from Management Learning, Ken Brown from Academy of Management Learning & Education, and Vijay Kannan from DSI Journal of Innovative Education—and to move SOTL work in new directions as an academic field. We don’t see it as hyperbole to say that the Unconference was one of the most energizing experiences we have had in any of our JME roles. Participating in an Unconference structure—one that deliberately destabilizes traditional academic meeting hierarchy to foster creative, often unfettered idea generation—led us to consider the process by which ideas and questions ultimately become published journal articles. What we came to realize from this experience is that the scholarly creative endeavor of publication is a much longer, messier, and quite personal process than we had overtly acknowledged prior to the meeting. During the one and one half days of the Unconference, we participated in group discussions with no set agenda or named facilitator that were organically put together, ever-changing, and group member-directed. Following the first morning session, we weren’t at all sure where things were going (a not entirely comfortable place for journal editors!) and had to consciously remind ourselves to “trust the process.” By the end of the Unconference, we were interacting with participants who were
Hotspot Preventing Routing Algorithm for Delay-Sensitive Biomedical Sensor Networks

Networks of implanted biomedical sensor nodes promise to give a new direction to medical research. Implanted biosensor nodes are already being used for various medical applications. The in-vivo sensor nodes collect the desired biometric data and communicate the data wirelessly among themselves and with a base station located outside the body. The sensor nodes are equipped with radio transmitters and receivers and hence produce heat while communicating, leading to a rise in the temperature of the nodes. A high temperature of the in-vivo nodes for a prolonged period might damage the surrounding tissues. So a considerable rise in the temperature of the nodes is not desired. For certain delay-sensitive medical applications a large delay in communicating the sensed information to the base-station might also be fatal. In this paper, we propose hotspot preventing routing (HPR) algorithm that reduces the average packet delivery delay in the network of biomedical sensor nodes while preventing the formation of hotspots. The proposed algorithm performs much better in terms of preventing the formation of hotspots and reducing the average packet delivery delay as compared to the shortest hop routing algorithm and the previously proposed thermal aware routing algorithm (TARA).
IL-2 Simultaneously Expands Foxp3+ T Regulatory and T Effector Cells and Confers Resistance to Severe Tuberculosis (TB): Implicative Treg–T Effector Cooperation in Immunity to TB

The possibility that simultaneous expansion of T regulatory cells (Treg) and T effector cells early postinfection can confer some immunological benefits has not been studied. In this study, we tested the hypothesis that early, simultaneous cytokine expansion of Treg and T effector cells in a tissue infection site can allow these T cell populations to act in concert to control tissue inflammation/damage while containing infection. IL-2 treatments early after Mycobacterium tuberculosis infection of macaques induced simultaneous expansion of CD4(+)CD25(+)Foxp3(+) Treg, CD8(+)CD25(+)Foxp3(+) T cells, and CD4(+) T effector/CD8(+) T effector/Vγ2Vδ2 T effector populations producing anti-M. tuberculosis cytokines IFN-γ and perforin, and conferred resistance to severe TB inflammation and lesions. IL-2-expanded Foxp3(+) Treg readily accumulated in pulmonary compartment, but despite this, rapid pulmonary trafficking/accumulation of IL-2-activated T effector populations still occurred. Such simultaneous recruitments of IL-2-expanded Treg and T effector populations to pulmonary compartment during M. tuberculosis infection correlated with IL-2-induced resistance to TB lesions without causing Treg-associated increases in M. tuberculosis burdens. In vivo depletion of IL-2-expanded CD4(+)Foxp3(+) Treg and CD4(+) T effectors during IL-2 treatment of M. tuberculosis-infected macaques significantly reduced IL-2-induced resistance to TB lesions, suggesting that IL-2-expanded CD4(+) T effector cells and Treg contributed to anti-TB immunity. Thus, IL-2 can simultaneously activate and expand T effector cells and Foxp3(+) Treg populations and confer resistance to severe TB without enhancing M. tuberculosis infection.
Evidence for a role of intrauterine infections in the pathogenesis of cystic ovaries in postpartum dairy cows

Abstract Patterns of uterine microbial recovery and serum concentrations of prostaglandin F2α metabolite (PGFM), cortisol, luteinizing hormone (LH) and progesterone (P4) were determined in normal postpartum dairy cows (n = 12) and in postpartum cows that developed cystic ovaries (n = 12). Palpation per rectum, ultrasound examinations of the reproductive tract and endometrial swab harvest were carried out once every 4 d during the first month postpartum. Daily blood samples were collected during the first 30 d postpartum and every other day until Day 60 postpartum for hormone assay. Bacterial growth densities of cultures of uterine swabs were high in cows that developed cystic ovaries. Cysts were detected between Day 8 and 16 postpartum and persisted for a period of 18.6 ± 9.9 d (range 8 to 41 d), followed by spontaneous regression and ovulations. Serum PGFM and cortisol were elevated for several days prior to detection of cystic ovaries but not prior to first postpartum ovulations. Serum LH concentrations in cystic cows were at basal concentrations prior to discovery of cysts. The results suggest that postpartum intrauterine infections may provoke increased secretion of prostaglandin F2α and cortisol associated with the formation of cystic ovaries in dairy cows.
Cathode Solid Electrolyte Interphase Generation in Lithium-Ion Batteries with Electrolyte Additives

The development of the next generation of lithium ion batteries for EV, HEV or PHEV requires the development of improved electrolytes. It is well known that the reduction potential of the anode in lithium ion batteries is high enough to reduce common electrolytes in lithium ion batteries. During the first few charge cycles, a solid electrolyte interface (SEI) is generated on the surface of the anode which protects the electrolyte from further reduction. The structure and stability of the anode SEI are very important to the performance of the batteries. Modification of the anode SEI has been conducted by the incorporation of film forming additives, including vinylene carbonate (VC), in lithium-ion battery electrolytes. The additives are preferentially reduced on the surface of the anode to form more stable anode SEIs.
Proteasome-Mediated Degradation of p21 via N-Terminal Ubiquitinylation

We examined the mechanism responsible for the degradation of p21, a negative regulator of the cell division cycle. We found that p21 proteolysis requires functional ubiquitin and Nedd8 systems. Ubiquitinylated forms of p21 and p21(K0), a p21 mutant missing all lysines, are detected in vivo and in vitro, showing that the presence of lysines is dispensable for p21 ubiquitinylation. Instead, the free amino group of the N-terminal methionine of p21 is a site for ubiquitinylation in vivo. Although wild-type p21 is more abundantly ubiquitinylated than p21(K0) mutant due to the presence of internal lysine residues, their rates of proteolysis are indistinguishable. These results demonstrate that proteasomal degradation of p21 is regulated by the ubiquitin pathway and suggest that the site of the ubiquitin chain is critical in making p21 a competent substrate for the proteasome.
Fuzzy decision trees: issues and methods

Decision trees are one of the most popular choices for learning and reasoning from feature-based examples. They have undergone a number of alterations to deal with language and measurement uncertainties. We present another modification, aimed at combining symbolic decision trees with approximate reasoning offered by fuzzy representation. The intent is to exploit complementary advantages of both: popularity in applications to learning from examples, high knowledge comprehensibility of decision trees, and the ability to deal with inexact and uncertain information of fuzzy representation. The merger utilizes existing methodologies in both areas to full advantage, but is by no means trivial. In particular, knowledge inferences must be newly defined for the fuzzy tree. We propose a number of alternatives, based on rule-based systems and fuzzy control. We also explore capabilities that the new framework provides. The resulting learning method is most suitable for stationary problems, with both numerical and symbolic features, when the goal is both high knowledge comprehensibility and gradually changing output. We describe the methodology and provide simple illustrations.
Electrostatic hot spot on DNA-binding domains mediates phosphate desolvation and the pre-organization of specificity determinant side chains

A major obstacle towards elucidating the molecular basis of transcriptional regulation is the lack of a detailed understanding of the interplay between non-specific and specific protein–DNA interactions. Based on molecular dynamics simulations of C2H2 zinc fingers (ZFs) and engrailed homeodomain transcription factors (TFs), we show that each of the studied DNA-binding domains has a set of highly constrained side chains in preset configurations ready to form hydrogen bonds with the DNA backbone. Interestingly, those domains that bury their recognition helix into the major groove are found to have an electrostatic hot spot for Cl− ions located on the same binding cavity as the most buried DNA phosphate. The spot is characterized by three protein hydrogen bond donors, often including two basic side chains. If bound, Cl− ions, likely mimicking phosphates, steer side chains that end up forming specific contacts with bases into bound-like conformations. These findings are consistent with a multi-step DNA-binding mechanism in which a pre-organized set of TF side chains assist in the desolvation of phosphates into well defined sites, prompting the re-organization of specificity determining side chains into conformations suitable for the recognition of their cognate sequence.
Regulation of Synaptic Vesicle Recycling by Calcium and Serotonin

Serotonin, a neuromodulator at the crayfish neuromuscular junction, regulates neurotransmission without changing intracellular calcium levels. However, the mechanism of this regulation remains unclear. By analysis of synaptic depression using a depletion model and measurement of vesicle recycling using the styryl dye FM1-43, we show that serotonin increases the number of vesicles available for transmitter release (total synaptic vesicle pool size). This regulation is due either to an increase in the number of vesicles at each release site or to an activation of previously nonsecreting or silent synapses. We also observed that low calcium medium rendered part of the vesicle pool unavailable for release. These results suggest a new mechanism for regulating synaptic transmission.
Antibodies Generated against Conserved Antigens Expressed by Bacteria and Allergen-Bearing Fungi Suppress Airway Disease

There has been a sharp rise in allergic asthma and asthma-related deaths in the developed world, in contrast to many childhood illnesses that have been reduced or eliminated. The hygiene hypothesis proposes that excessively sanitary conditions early in life result in autoimmune and allergic phenomena because of a failure of the immune system to receive proper microbial stimulation during development. We demonstrate that Abs generated against conserved bacterial polysaccharides are reactive with and dampen the immune response against chitin and Aspergillus fumigatus. A reduction in Ag uptake, cell influx, cell activation, and cytokine production occurred in the presence of anti-polysaccharide Abs, resulting in a striking decrease in the severity of allergic airway disease in mice. Overall, our results suggest that Ag exposure--derived from environmental sources, self-antigens, or vaccination--during the neonatal period has dramatic effects on the adult Ab response and modifies the development of allergic airway disease.
Reaction of the CoII-Substrate Radical Pair Catalytic Intermediate in Coenzyme B12-Dependent Ethanolamine Ammonia-Lyase in Frozen Aqueous Solution from 190 to 217 K

The decay kinetics of the aminoethanol-generated CoII-substrate radical pair catalytic intermediate in ethanolamine ammonia-lyase from Salmonella typhimurium have been measured on timescales of <105 s in frozen aqueous solution from 190 to 217 K. X-band continuous-wave electron paramagnetic resonance (EPR) spectroscopy of the disordered samples has been used to continuously monitor the full radical pair EPR spectrum during progress of the decay after temperature step reaction initiation. The decay to a diamagnetic state is complete and no paramagnetic intermediate states are detected. The decay exhibits three kinetic regimes in the measured temperature range, as follows. i), Low temperature range, 190 ≤ T ≤ 207 K: the decay is biexponential with constant fast (0.57 ± 0.04) and slow (0.43 ± 0.04) phase amplitudes. ii), Transition temperature range, 207 < T < 214 K: the amplitude of the slow phase decreases to zero with a compensatory rise in the fast phase amplitude, with increasing temperature. iii), High temperature range, T ≥ 214 K: the decay is monoexponential. The observed first-order rate constants for the monoexponential (kobs,m) and the fast phase of the biexponential decay (kobs,f) adhere to the same linear relation on an lnk versus T−1 (Arrhenius) plot. Thus, kobs,m and kobs,f correspond to the same apparent Arrhenius prefactor and activation energy (logAapp,f (s−1) = 13.0, Ea,app,f = 15.0 kcal/mol), and therefore, a common decay mechanism. We propose that kobs,m and kobs,f represent the native, forward reaction of the substrate through the radical rearrangement step. The slow phase rate constant (kobs,s) for 190 ≤ T ≤ 207 K obeys a different linear Arrhenius relation (logAapp,s (s−1) = 13.9, Ea,app,s = 16.6 kcal/mol). In the transition temperature range, kobs,s displays a super-Arrhenius increase with increasing temperature. The change in Ea,app,s with temperature and the narrow range over which it occurs suggest an origin in a liquid/glass or dynamical transition. A discontinuity in the activation barrier for the chemical reaction is not expected in the transition temperature range. Therefore, the transition arises from a change in the properties of the protein. We propose that a protein dynamical contribution to the reaction, which is present above the transition temperature, is lost below the transition temperature, owing to an increase in the activation energy barrier for protein motions that are coupled to the reaction. For both the fast and slow phases of the low temperature decay, the dynamical transition in protein motions that are obligatorily coupled to the reaction of the CoII-substrate radical pair lies below 190 K.
Entero-endocrine changes after gastric bypass in diabetic and nondiabetic patients: a preliminary study.

Introduction. Alterations in entero-endocrine signaling may play a role in improvements in satiety and glucose tolerance after Roux-en-Y gastric bypass (RYGB). We report our findings of gut hormone secretion in a cohort of diabetic and nondiabetic morbidly obese patients. Materials and methods. Ten morbidly obese subjects who underwent uncomplicated RYGB were studied: 5 were diabetic and 9 were female. Nonfasting plasma levels of glucagon-like peptide-1 (GLP-1), insulin, desacyl ghrelin, active ghrelin, neuropeptide Y (NPY), and gastric inhibitory polypeptide (GIP) were determined preoperatively and 6 months postoperatively. Results. Mean patient age was 42 ± 11 years, and the mean preoperative body mass index was 50 ± 6 kg/m 2 . At 6 months mean BMI fell to 33 ± 5 kg/m 2 (P < 0.0001), and there were no differences between diabetics and nondiabetics with respect to amount of weight loss. In non-diabetics, compared to preoperative levels, there were significant increases in GLP-1 and desacyl-ghrelin in the nondiabetic patients (P = 0.046 and P = 0.016, respectively); no change in plasma insulin, active ghrelin, NPY, or GIP was demonstrated. In contrast, when compared to preoperative levels, there were no significant changes in entero-endocrine hormone levels in the diabetic cohort postoperatively. Conclusions. At 6 months postoperation, RYGB significantly alters the hormone levels for GLP-1 and desacyl-ghrelin in morbidly obese nondiabetic patients. No significant change was noted in a matched cohort of diabetic patients. Weight loss was similar in diabetics and nondiabetics, suggesting that GLP-1 and ghrelin are not the only mechanisms producing weight loss after RYGB.
Gentamicin in Serious Neonatal Infections: Absorption, Excretion, and Clinical Results in 25 Cases

Twenty-five newborn infants with serious infections were treated with gentamicin. Blood and urine were collected to determine the patterns of absorption and excretion. Effective concentrations, with mean peak levels of approximately 3 pLg/ml of serum, were achieved on a dosage schedule of 3 mg/kg every 12 hr. On doses of 2 mg/kg every 12 hr, the levels of gentamicin in serum were inadequate for therapy. Activity equivalent to approximately one-third of the administered dose was recovered in the urine. Infants treated with gentamicin included four with bacteremia, four with meningitis, two with urinary-tract infections, one with an infected wound, and 14 with pneumonia or clinical sepsis. The response to therapy was considered satisfactory in 21, indeterminate in three, and a failure in one newborn with meningitis due to Escherichia coli. No untoward effects of gentamicin were observed. On the basis of these studies, a dosage schedule for gentamicin of 6 mg/kg per day in two doses appears warranted for treatment of severe infections in the newborn.
Potassium Inhibits Cultured Vascular Smooth Muscle Cell Proliferation

Increased dietary K+ increases plasma [K+] and is linked to or associated with reduced mortality from stroke and reduced blood pressure in humans and animals. We hypothesized that physiologic increases in extracellular [K+] ([K]o) directly inhibit cultured vascular smooth muscle cell (VSMC) proliferation. Studies were performed by stimulating quiescent cultured canine coronary artery and A7r5 VSMC with 5% serum at varying [K]o starting on day 0. When plated at 5,200 cells/cm2 A7r5 VSMC counts increased 121% by day 2 and 190% by day 6 in 3 mmol/L [K]o, but only 21% by day 2 and 45% by day 6 in 7 mmol/L [K]o; intermediate [K]o yielded intermediate proliferative rates. Serum caused a four- to fivefold increase in cell counts of cultured canine coronary artery VSMC in 7 days at 2 mmol/L [K]o of 2 mmol/L, and increasing [K]o to 7 mmol/L reduced proliferation by 68%. Uptake of [3H]thymidine by cultured canine coronary artery VSMC was inhibited by 50% between 2 and 7 mmol/L [K]o. Increased [K]o may act by decreasing intracellular Na+ ([Na]i). Exposure to serum for 24 h more than doubles canine coronary artery [Na]i, an effect previously associated with VSMC proliferation, and increased [K]o (from 2 to 7 mmol/L) reduces [Na]i by 74% before and 64% 24 h after serum. We conclude that physiologic increases in [K]o reduce [Na]i and proliferation of cultured VSMC. Similar effects occurring in vivo may help to account for the ability of increased dietary K+ to prevent vascular lesions.