cssi/SciSciGPT-SciSciNet huggingface dataset:
Glycolysis Inhibition Induces Functional and Metabolic Exhaustion of CD4+ T Cells in Type 1 Diabetes.

In Type 1 Diabetes (T1D), CD4+ T cells initiate autoimmune attack of pancreatic islet β cells. Importantly, bioenergetic programs dictate T cell function, with specific pathways required for progression through the T cell lifecycle. During activation, CD4+ T cells undergo metabolic reprogramming to the less efficient aerobic glycolysis, similarly to highly proliferative cancer cells. In an effort to limit tumor growth in cancer, use of glycolytic inhibitors have been successfully employed in preclinical and clinical studies. This strategy has also been utilized to suppress T cell responses in autoimmune diseases like Systemic Lupus Erythematosus (SLE), Multiple Sclerosis (MS), and Rheumatoid Arthritis (RA). However, modulating T cell metabolism in the context of T1D has remained an understudied therapeutic opportunity. In this study, we utilized the small molecule PFK15, a competitive inhibitor of the rate limiting glycolysis enzyme 6-phosphofructo-2-kinase/fructose-2,6- biphosphatase 3 (PFKFB3). Our results confirmed PFK15 inhibited glycolysis utilization by diabetogenic CD4+ T cells and reduced T cell responses to β cell antigen in vitro. In an adoptive transfer model of T1D, PFK15 treatment delayed diabetes onset, with 57% of animals remaining euglycemic at the end of the study period. Protection was due to induction of a hyporesponsive T cell phenotype, characterized by increased and sustained expression of the checkpoint molecules PD-1 and LAG-3 and downstream functional and metabolic exhaustion. Glycolysis inhibition terminally exhausted diabetogenic CD4+ T cells, which was irreversible through restimulation or checkpoint blockade in vitro and in vivo. In sum, our results demonstrate a novel therapeutic strategy to control aberrant T cell responses by exploiting the metabolic reprogramming of these cells during T1D. Moreover, the data presented here highlight a key role for nutrient availability in fueling T cell function and has implications in our understanding of T cell biology in chronic infection, cancer, and autoimmunity.
Rapid upregulation of fibroblast growth factor receptor 1 (flg) by rat photoreceptor cells after injury.

PURPOSE. To determine the mechanism by which basic fibroblast growth factor (bFGF) exerts its neuroprotective effects on degenerating or injured photoreceptors. METHODS. Confocal immunofluorescence microscopy was used to identify sites of bFGF and FGF receptor 1 (FGFR1) expression after focal injury or experimental retinal detachment in adult rats. FGFR1 expression was analyzed immunohistochemically and at the transcription level in single photoreceptor cells, after reverse transcription (RT), using the polymerase chain reaction (PCR). Real time quantitative RT-PCR was used to measure changes in FGFR1 mRNA levels in the retina in response to injury or detachment. RESULTS. Confocal immunofluorescence observations showed that FGFR1 immunoreactivity in the rat retina is concentrated primarily in the perinuclear cytoplasm of photoreceptor cell bodies. Reverse transcription of total RNA derived from dissociated rat photoreceptor cells, followed by amplification of FGFR1 cDNA using the PCR rified the presence of FGFR1 transcripts in normal rat photoreceptor cells; in contrast, no evidence of bFGF transcription was detected. Collectively, these results provide compelling evidence for FGFR1 gene expression by rat photoreceptors in situ. Within hours after experimental retinal detachment or focal injury, there is a twofold increase in FGFR 1 immunoreactivity in the outer nuclear layer that persists for at least 7 days; a similar increase in bFGF immunoreactivity in the interphotoreceptor matrix is also apparent. This increase in FGFRI protein levels after detachment and injury also was confirmed by western blot analysis. Real time quantitative RT-PCR analyses revealed that a rapid upregulation of FGFR1 mRNA occurred within 12 hours after retinal injury/detachment, but then declined to near baseline levels by 24 hours. CONCLUSIONS. This body of evidence strongly suggests that the photoreceptor rescue effect elicited by retinal injury as well as by injection of exogenous bFGF is mediated, at least in part, by upregulation of the FGFR1 by the photoreceptor cells.
Abstract MP01: Physical Activity and Incident Cardiovascular Disease in Women: Is the Relation Influenced by Level of Global Cardiovascular Risk?

Background: The inverse association between physical activity and CVD is well-established and has been shown in persons with and without single CVD risk factors. Nonetheless, it is unknown if physical activity is equally beneficial for prevention of CVD among women with varying levels of global cardiovascular risk. Thus, the purpose of this analysis was to determine whether level of cardiovascular risk, as assessed by the Reynolds Risk Score, modifies the association between physical activity and CVD. Methods and Results: We conducted a prospective analysis among 27,636 women initially healthy women in the Women’s Health Study, followed from 1992 to 2012. Leisure-time physical activity was reported at study entry and updated during follow-up. Participants were divided into 10-year risk groups of Conclusions: In this large prospective cohort of women, global level of cardiovascular risk did not modify the inverse association between physical activity and CVD risk. Thus, women with low as well as high cardiovascular risk can benefit from regular exercise.
The Importance of β‐Alanine for Recognition of the Minor Groove of DNA

It is now well-recognized that there are two global motifs for targeting the minor groove of DNA based on analogs of the N-methylpyrrole-carboxamide ring of the natural product distamycin. There exist 1:1 and 2:1 stoichiometries with quite different rules of recognition and specificity. This ambiguity of sequence targeting depending on stoichiometry raises a serious design issue for the DNA recognition field.
Pathfinding by neuronal growth cones in grasshopper embryos. IV. The effects of ablating the A and P axons upon the behavior of the G growth cone

In the companion paper (Bastiani, M. J., J. A. Raper, and C. S. Goodman (1984) J. Neurosci. 4: 2311–2328), we show that as the G growth cone reaches its choice point and turns anteriorly on the A/P fascicle, its filopodia demonstrate selective affinity for the A/P fascicle as compared to the other approximately 25 longitudinal axon fascicles, and within the A/P fascicle itself, G's filopodia selectively contact the P axons as compared to the A axons. These results support the hypothesis that the A/P fascicle, and, moreover, subsets of axons within it (Ps versus As), are specifically labeled and that the G growth cone is determined to follow a particular labeled pathway. We tested the “labeled pathways” hypothesis by specifically ablating these axons and examining the subsequent behavior of the G growth cone in embryos grown in culture. Ablation of the A and P axons prevents G from growing more than a short distance anteriorly, although the G growth cone is within grasp of many other longitudinal axon fascicles. Ablation of only the P axons has a similar effect; the G growth cone behaves normally if only the A axons are ablated. Transmission electron micrograph semiserial section reconstructions of experimental embryos further indicate that G's growth cone behaves abnormally when the A and P axons, or only the P axons, are ablated. The G growth cone branches extensively in the lateral and ventral neuropil without it or its filopodia showing a high affinity for any other axon fascicle. These results indicate that the G growth cone is able to distinguish the A/P fascicle from the other longitudinal axon fascicles in the developing neuropil. Moreover, the results suggest that within the A/P fascicle the G growth cone is able to distinguish the P axons from the A axons.
SC-CFS: smartcard secured cryptographic file system

Storing information securely is one of the most important roles expected for computer systems, but it is difficult to achieve with current commodity computers. The computers may yield secrets through physical breach, software bug exploitation, or password guessing attack. Even file systems that provide strong security, such as the cryptographic file system, are not perfect against these attacks. We have developed SC-CFS, a file system that encrypts files and takes advantage of a smartcard for per-file key generation. SC-CFS counters password guessing attack, and minimizes the damage caused by physical attack and bug exploitation. The performance of the system is not yet satisfactory, taking 300 ms for accessing a file.
Lumley’s Podt Definition of Large Eddies and a Trio of Numerical Procedures

Lumley’s 1967 Moscow paper provided, for the first time, a completely rational definition of the physically-useful term “Large Eddy,” popular for a half-century. The numerical procedures are based upon his results: 1) PODT (Proper Orthogonal Decomposition Theorem) which extracts the Large Eddy structure of stochastic processes from physical or computer simulation two-point covariances, and 2) LEIM (Large-Eddy Interaction-Model) is a predictive scheme for the dynamical Large Eddies based upon higher order turbulence modelling. Earlier Lumley work (1964) forms the basis for the final member of the triad of numerical procedures: this predicts the global neutral modes of turbulence which have surprising agreement with both structural eigenmodes and those obtained from the dynamical equations. The ultimate goal of improved engineering design tools for turbulence may be near at hand, partly due to the power and storage of “super-” microcomputer workstations finally becoming adequate for the demanding numerics of these procedures.
Unraveling the luminescence signatures of chemical defects in polyethylene

Chemical defects in polyethylene (PE) can deleteriously downgrade its electrical properties and performance. Although these defects usually leave spectroscopic signatures in terms of characteristic luminescence peaks, it is nontrivial to make unambiguous assignments of the peaks to specific defect types. In this work, we go beyond traditional density functional theory calculations to determine intra-defect state transition and charge recombination process derived emission and absorption energies in PE. By calculating the total energy differences of the neutral defect at excited and ground states, the emission energies from intra-defect state transition are obtained, reasonably explaining the photoluminescence peaks in PE. In order to study the luminescence emitted in charge recombination processes, we characterize PE defect levels in terms of thermodynamic and optical charge transition levels that involve total energy calculations of neutral and charged defects. Calculations are performed at several levels of theory including those involving (semi)local and hybrid electron exchange-correlation functionals, and many-body perturbation theory. With these critical elements, the emission energies are computed and further used to clarify and confirm the origins of the observed electroluminescence and thermoluminescence peaks.
Numerical Modeling of Anti-icing Systems and Comparison to Test Results on a NACA 0012 Airfoil

A series of experimental tests were conducted in the NASA Lewis IRT on an electro-thermally heated NACA 0012 airfoil. Quantitative comparisons between the experimental results and those predicted by a computer simulation code were made to assess the validity of a recently developed anti-icing model. An infrared camera was utilized to scan the instantaneous temperature contours of the skin surface. Despite some experimental difficulties, good agreement between the numerical predictions and the experiment results were generally obtained for the surface temperature and the possibility for each runback to freeze. Some recommendations were given for an efficient operation of a thermal anti-icing system.
Intracerebroventricular injection of cerebrospinal fluid (CSF) from a patient with congenital indifference to pain induces analgesia in rats.

CSF from a patient with congential indifference to pain was found to produce analgesia in the rat following intracerebroventricular injections. The analgesic effect was attenuated by pretreatment with naloxone suggesting the involvement of hyperactive endogenous opiate mechanisms in this patient.
Aerodynamic Force Required to Detach Bract and Leaf Dust Dispersed on Cotton

A model of the aerodynamic force required to detach dust on cotton is considered on the basis of the crossflow exposure of fibers in an air stream. The model incorporates (a) the probability that a dust particle lies in the concave valley along the fiber axis, (b) the air flow about the particle on the fiber, and (c) the cross-section density of the exposed fiber mass. For respirable bract and leaf dust dispersed on the fiber, the model correctly predicted that particles in the concave valley, <10% of the total mass, are more difficult to detach than are those outside the valley. Double (front and back) crossflow exposure to the air stream is necessary to remove the remainder of the particles adhering to the fiber surface. The mean force required to detach 90% of the bract particles from two grades of cotton is 8.22×104 greater than that due to particle weight alone and 5.40×10−7 smaller than that to break the fiber.
`Enthalpy Titrations' and Thermochemistry in Molten Salts

AUTOMATIC instrumentation for recording ‘thermometric titration’ curves has been described in recent papers1,2 from these laboratories, which represent the first report of a continuous titration procedure successfully carried out in a molten salt solvent. This approach is capable of yielding a wealth of quantitative information on the chemistry of fused salts. Significant thermochemical results, involving the precipitation of silver halides and of silver chromate, are summarized in this communication. A typical titration curve (of chromate with silver), obtained under essentially adiabatic conditions, is illustrated in Fig. 1. Methodologically this is a differential thermometric titration curve, because temperature has been recorded as a function of the amount of titrant. From a phenomenological point of view, however, Fig. 1 represents an ‘enthalpy titration’, the shape of the curve reflecting the heat evolved in the reaction as a function of added silver.
Interrelationships among thiazide diuretics and calcium, magnesium, sodium, and potassium balance in normal and hypertensive man

The benzothiadiazide diuretics are known to cause magnesium and potassium wasting and retention of calcium and uric acid. The effect of magnesium replacement on diuretic-induced changes in sodium, potassium, calcium, and magnesium balance, weight, and blood pressure was studied in 12 normal subjects and 13 hypertensive patients to determine whether oral magnesium would reduce thiazide-induced kaliuresis. The groups differed in their response to diuresis in that the normotensive subjects did not show a fall in blood pressure (despite an equivalent weight loss), returned to a state of sodium balance earlier, and developed a greater net negative potassium balance over 12 days of diuretic therapy. Both groups displayed calcium and uric acid retention and magnesium wasting during diuretic therapy. The addition of oral magnesium replacement during diuretic therapy had no effect on any measured values beyond that seen in subjects who took diuretics without magnesium replacement. Thus, magnesium replacement did not reduce urinary potassium loss. However, urinary calcium losses increased when magnesium was given to subjects who were not receiving diuretics. The data provide the first report that small doses of oral magnesium enhance calcium excretion in hypertensive subjects.
THE STATE OF HEMOGLOBIN IN SICKLED ERYTHROCYTES

Electron microscopic and other evidence have provided support for the hypothesis that the sickling phenomenon is due to the intracellular formation of long slender crystals of reduced sickle hemoglobin. The rapid growth of these crystals causing tenting of the cell membrane is responsible for the bizarre distortion of the erythrocytes and presumably for the disease itself.
Factors associated with women's perceptions of physical activity safety during pregnancy.

Abstract Health benefits of physical activity (PA) during pregnancy have been noted, but women's perceptions of PA safety have been little studied. Objectives To examine associations among PA participation, safety perceptions, and demographic characteristics. Methods Pregnant women were recruited from nine clinics in Grand Rapids, MI (USA) from April to October, 2006. Demographics, participation in moderate and vigorous PA, and perceived safety of both intensities (5-pt Likert scales) were reported. Logistic regression analyses were used to estimate associations. Results Of 342 eligible women, 296 provided complete PA information. Most (88%) participated in some PA and felt moderate PA was safe (89%), but only 36% felt vigorous PA was safe. Feeling unsafe/unsure about moderate PA was associated with non-White race/ethnicity, low education, low income, not participating in moderate PA, and/or not intending to be active during pregnancy. Hispanic ethnicity, low education, nulliparity, and not participating in moderate or vigorous PA were associated with feeling unsafe/unsure about vigorous PA. Conclusions Pregnant women generally feel that moderate PA is safe, but are less certain about vigorous PA. More work is needed to inform pregnant women about the benefits of moderate PA, especially among non-White and low education/income populations.
Managing the Dilemma of Discretion: The European Commission and the Development of EU State Aid Policy

This article examines the role played by the European Commission in the development of the European Union’s (EU) state aid policy. It does so through the prism of a “dilemma” that exists at the nexus of the Commission’s delegated authority to administer EU treaty state aid provisions, the discretion conferred on Commission authorities by the imprecise language in which those provisions are written, and the political and institutional control mechanisms EU member governments use to influence the exercise of that discretion. Examining Commission efforts to manage this dilemma over the history of the EU, we provide evidence to illustrate how the Commission’s approach adapted to shifting economic and political conditions.
Instructional Design for the Future of Undergraduate Journalism Education

In the face of communication changes brought on by technology, journalism curriculum needs restructuring while staying true to its core values. Using an instructional design framework, and a case study, this paper proposes a journalism education based on Esserâ€™s spheres of influence. Current practices and principles are discussed. A literature review and emerging trends shape the proposed curriculum clusters: the business and profession of journalism, communication, and community/society.
Low-distortion slow light using two absorption resonances

We consider group delay and broadening using two strongly absorbing and widely spaced resonances. We derive relations which show that very large pulse bandwidths coupled with large group delays and small broadening can be achieved. Unlike single resonance systems, the dispersive broadening dominates the absorptive broadening which leads to a dramatic increase in the possible group delay. We show that the double resonance systems are excellent candidates for realizing all-optical delay lines. We report on an experiment which achieved up to 50 pulse delays with 40% broadening.
Skin squamous cell cancer: the time is right for greater involvement of the medical oncologist.

Squamous cell cancer (SCC) of the skin is a paradox for the medical oncologist. It is one of the most common malignancies, yet medical oncologists are involved infrequently in the management of most skin SCCs. Most patients with the disease have an excellent prognosis and are treated by a dermatologist, surgeon, or radiation oncologist. There has been no established role for systemic therapy in the adjuvant setting, either alone or with radiation, with the recent exception of the potential use of oral retinoids with preventive intent in selected patients at increased risk for the development of new skin cancers. 1 Historically, the medical oncologist’s role has been relegated largely to the palliative treatment and symptom management of patients with recurrent locoregional or distant disease not amenable to further local treatment measures. Although chemotherapy has limited efficacy in this setting, relatively little attention has been paid to the prospective evaluation of promising new agents in patients with cutaneous SCC. Oncologists have regularly relied on low-quality evidence from the literature, preclinical data, expert opinion, experience with the treatment of SCC from other primary sites such as the aerodigestive tract or cervix, and clinical judgment to assist in chemotherapy drug selection. However, several factors point toward the need for more investigations into the pathogenesis, molecular biology, prevention, developmental therapeutics, and combined-modality therapy of SCC of the skin, as well as a growing awareness of the disease and its management among medical oncologists. Because the incidence of SCC of the skin increases after age 40, 2,3 an aging population of baby boomers will contribute to a further increase in the incidence of the disease. A number of risk factors have been identified that predispose one to developing cutaneous SCC— exposure to sunlight and related ultraviolet radiation is the most important and best characterized risk factor. 3 A prior diagnosis of SCC of the skin is associated with an increased likelihood of subsequent skin cancer, 4 as well as cancer at other sites. 5 Many such factors lend themselves to risk-reduction strategies, so there is a keen interest in preventive interventions, including chemoprevention. 6,7 Skin cancer preventive education warrants broad-based attention across all age groups, 1 and it
Classical Spin-Configuration Stability in the Presence of Competing Exchange Forces

It is pointed out that Yafet-Kittel triangular arrangements are not stable in the cubic spinel. The stability criterion used is that the classical Heisenberg energy should not decrease for small, but otherwise arbitrary, spin-deviations from the configuration of interest. It is found that the Yafet-Kittel-Prince configuration can probably be stabilized by a sufficient tetragonal distortion of the pattern of $B\ensuremath{-}B$ interactions. In addition, the classical ground state is found for the antiferromagnetic body-centered cubic lattice with first, second, and third neighbor antiferromagnetic interactions (with parameters ${J}_{1}$, ${J}_{1}{\ensuremath{\sigma}}_{2}$ and ${J}_{1}{\ensuremath{\sigma}}_{3}$): the spin $\mathrm{S}({\mathrm{R}}_{n})$ at lattice point ${\mathrm{R}}_{n}$ is independent of time, is always parallel to one plane, $P$, and the angle made by $\mathrm{S}({\mathrm{R}}_{n})$ with a fixed line in $P$ is of the form $\mathrm{k}\ifmmode\cdot\else\textperiodcentered\fi{}{\mathrm{R}}_{n}$ for ${\mathrm{R}}_{n}$ a cube corner, and of the form $\mathrm{k}\ifmmode\cdot\else\textperiodcentered\fi{}{\mathrm{R}}_{n}+\ensuremath{\pi}$ for ${\mathrm{R}}_{n}$ a body-center position with the vector k determined by the ${\ensuremath{\sigma}}_{i}$. The neutron diffraction pattern for such a "spiral" configuration (with ${\ensuremath{\sigma}}_{2}\ensuremath{\sim}0.6$, ${\ensuremath{\sigma}}_{3}\ensuremath{\sim}0.1$, for example) bears a close relationship with the unusual pattern obtained by Corliss, Hastings, and Weiss with a single crystal of chromium.
The linkage between magnesium binding and RNA folding.

Understanding the linkage between Mg(2+) binding and RNA folding requires a proper theoretical model describing the energetics of Mg(2+) binding to the folded and unfolded states of RNA. Our current understanding of Mg(2+) binding to these different RNA states derives from empirical thermodynamic models that depend on a number of unjustified assumptions. We present a rigorous theoretical model describing the linkage between RNA folding and magnesium ion binding. In this model, based on the non-linear Poisson-Boltzmann (NLPB) equation, the stabilization of RNA by Mg(2+) arises from two distinct binding modes, diffuse binding and site binding. Diffusely bound Mg(2+) are described as an ensemble of hydrated ions that are attracted to the negative charge of the RNA. Site-bound Mg(2+) are partially desolvated ions that are attracted to electronegative pockets on the RNA surface. We explore two systems, yeast tRNA(Phe) and a 58-nucleotide rRNA fragment, with different Mg(2+) binding properties. The NLPB equation accurately describes both the stoichiometric and energetic linkage between Mg(2+) binding and RNA folding for both of these systems without requiring any fitted parameters in the calculation. Moreover, the NLPB model presents a well-defined physical description of how Mg(2+) binding helps fold an RNA. For both of the molecules studied here, the relevant unfolded state is a disordered intermediate state (I) that contains stable helical secondary structure without any tertiary contacts. Diffusely bound Mg(2+) interact with these secondary structure elements to stabilize the I state. The secondary structural elements of the I state fold into a compact, native tertiary structure (the N state). Diffuse binding plays a dominant role in stabilizing the N state for both RNAs studied. However, for the rRNA fragment, site-binding to a location with extraordinarily high electrostatic potential is also coupled to folding. Our results suggest that much experimental data measuring the linkage between Mg(2+) binding and RNA folding must be reinterpreted.
Transmission of human immunodeficiency virus to sexual partners of hemophiliacs.

To examine the variables associated with heterosexual transmission of human immunodeficiency virus (HIV) the authors studied 32 couples in their hemophilia center who had steady sexual relationships for periods of more than 1 year. Of the 32 sexual partners of the hemophiliacs 5 (15.6%) were HIV seropositive. All 5 hemophiliacs with HIV transmission to their sexual partners had measurable immunologic deficiencies as shown by their lower median T-helper (CD-4+) lymphocyte count of 172 cells/mm3. The hemophiliacs without transmission had a slightly higher median CD-+ count of 297 cells/mm3 (P=.26). To determine if factors other than the degree of immunologic deficiency in the hemophiliac might contribute to HIV transmission 18 of 32 couples were studied more intensively by confidential coded questionaires. Regular condom use was reported by 9 couples (50%). 2 of 9 women (22%) without condom usage had acquired HIV. 1 of 9 women (11%) using condoms was seropositive; she also reported 8 needlestick injuries while assisting her spouse with clotting factor treatments. Intravenous drug abuse was reported in 2 of 5 couples with HIV transmission. Thus hemophiliacs are at risk for transmitting HIV parenterally as well as venereally. Despite various risk behaviors associated with HIV transmission the prevalence of infection in this cohort of hemophiliacs sexual partners is low and within the range (6.8-22%) reported by others. This study underscores the need for comprehensive education and counseling in what previously appeared to be a homogenous clinic population at risk for transmitting HIV to others. (authors)
The impact of international migration upon the timing of marriage and childbearing.

Experiences of 1500 native-born Australians and 1000 foreign-born immigrants to Australia, surveyed in Melbourne in 1971, reveal that immigration delayed marriage for migrants arriving between age 15 and marriage, and delayed first, second, third and fourth births for immigrants arriving during each birth interval. This migration effect was clearly finite in its influence, affecting only proximate vital events rather than persisting through several successive events. The temporary nature of the migration effect highlights the adaptability of international migrants.
Isolation and Characterization of Mammalian HDAC10, a Novel Histone Deacetylase

Acetylation of histone core particles plays an important role in modulating chromatin structure and gene expression. The acetylation status of the histone tails is determined by two opposing enzymatic activities, histone acetyltransferases and histone deacetylases (HDACs). Here we describe the isolation and characterization of HDAC10, a novel class II histone deacetylase. Molecular cloning and Northern blot analyses reveal that the HDAC10 transcript is widely expressed and subjected to alternative splicing. HDAC10 is both nuclear and cytoplasmic, a feature reminiscent of HDACs 4, 5, and 7. Distinct from other family members, HDAC10 harbors an amino-terminal catalytic domain and a carboxyl pseudo-repeat that shares significant homology with its catalytic domain. Mutational analysis reveals that transcriptional repression by HDAC10 requires its intrinsic histone deacetylase activity. Taken together, HDAC10 represents a distinct HDAC that may play a role in transcription regulation.
Purine nucleoside therapy of low-grade follicular lymphoma

Low-grade follicular lymphomas, follicular small cleaved and follicular mixed, generally follow an indolent but progressive course. Although available therapies induce responses, continuous relapse occurs. In investigating potential therapeutic regimens, researchers have sought regimens that will result in a postchemotherapy survival plateau rather than a pattern of continuous relapse. The newer, purine analogs, 2'-deoxycoformycin, fludarabine, and 2-chlorodeoxyadenosine have shown activity in the low-grade B-cell lymphomas, especially with the follicular histologic subtype. Response rates in studies of previously untreated patients approach 100%. The newer purine analogs are emerging as an important treatment approach for indolent B-cell lymphomas, but the impact on survival remains to be assessed.
Identification of a human monoclonal natural IgM antibody that recognizes early apoptotic cells and promotes phagocytosis.

Efficient clearance of cells undergoing apoptotic death is crucial for normal tissue homeostasis and for the prevention of autoimmunity. Engulfment of apoptotic cells is finely regulated by a highly redundant system of receptors and bridging molecules. We developed a rapid and efficient method for the identification of human natural IgM antibodies and isolated some natural human monoclonal IgM antibodies specific to the apoptotic cells. Among them, AC34 IgM bound to early apoptotic cells and promoted phagocytosis of apoptotic Jurkat cells by human monocyte-derived macrophage (HMDM). AC34 IgM recognized phosphatidylserine (PS), which means PS might be a possible molecule recognized by AC34 IgM on the surface of apoptotic cells and AC34 IgM might be a possible candidate of bridging molecules between the PS and phagocytes. The sequences of VH and VL of AC34 were almost the same with their germline counterpart. Our experiments suggest a role of natural IgM as an opsonin in the clearance of early apoptotic cells.
Smoking Patterns within a Primary Care Sample of Resettled Bosnian Refugees

The interconnections among smoking status, severity of nicotine related physical dependence (NRPD), posttraumatic stress disorder (PTSD)-related physiological arousal and subjective health were explored within a sample of 66 resettled Bosnian refugees seeking primary healthcare services. Fifty-nine percent (n = 39/66) of the participants reported that they were current smokers and 44% (n = 29/66) indicated that they had smoked prior to the war. Both pre-war smoking and PTSD arousal independently predicted current smoking. In addition, total PTSD arousal and individual symptoms of sleep difficulties, irritability, concentration, and hypervigilance were significantly and positively associated with NRPD. Severity of PTSD arousal and age uniquely predicted NRPD. While poorer subjective health was significantly associated with positive current smoking status, neither poorer subjective health nor severity of PTSD arousal was significantly associated with interest in quitting/reducing smoking. Findings were discussed within the context of culture and stressor-related issues.
Variable range hopping and spin-dependent hopping resistance in magnetic iron oxide films

Abstract Insulating iron oxide films exhibit variable-range-hopping conductance. From 100 K to near room temperature the resistance can be expressed as R=R 0 exp (T 0 /T) p , where p takes values of 0.6–0.7. p is unchanged in an applied field up to 9 T. The magnetoresistance of the films is negative, which increases in magnitude with decreasing temperature. The negative magnetoresistance may originate from the spin-dependent variable-range-hopping in which hopping rate depends on the relative orientation of the spins of the involved sites.
Computer Testing as a Form of Accommodation for English Language Learners

This study compared performance of both English language learners (ELLs) and non-ELL students in Grades 4 and 8 under accommodated and nonaccommodated testing conditions. The accommodations used in this study included a computerized administration of a math test with a pop-up glossary, a customized English dictionary, extra testing time, and small-group testing. Extra time and small-group testing were included only for Grade 4 students. A reading latent composite score was used as a covariate. Results indicated that computer testing was the most effective accommodation in providing valid and accessible assessments for ELL students for both Grades 4 and 8. It is an alternative test item delivery and an easy-to-access gloss of non-math lexicon. This accommodation did not impact the validity of assessments.
The Guide to Community Preventive Services will be influential in academic health centers: education, research and links with practice.

In both clinical medicine and in public health programs services and advice have been built based on individual judgments or professional consensus. There has been a lack of educational commitment a knowledge base and a practice ethic solidly grounded in research and evaluation. The introduction of the Guide to Community Preventive Services which has a clear link with the categories of immunizations counseling services and screening tests is considered to be influential in academic health centers who are engaged in research and evaluation studies. In addition principles and guidelines for community-based research will facilitate real-world tests of ideas and guidelines for community preventive services. Performance standards and cost-effectiveness analyses will be expected by all payers and by policy-makers. Moreover scientific advances especially in the emerging field of public health genetics will be incorporated. Thus academics practitioners and employers should join forces to persuade payers to accept evidence-based convergence of related clinical guidelines. Such initiatives will improve the chances for increased investment in preventive medicine and public health.
Food toxins, ampa receptors, and motor neuron diseases.

Environmental chemicals involved in the etiology of human neurodegenerative disorders are challenging to identify. Described here is research designed to determine the etiology and molecular pathog...
Empowering Head Start African American and Latino Families: Promoting Strengths-Based Parenting Characteristics Through Child Parent Relationship Training—An Evidence-Based Group Parenting Program

With the tendency of low-income African American and Latino children identified at-risk for school readiness and school success compared to their early-childhood counterparts, Head Start personnel are challenged to examine the role of family strengths in the promotion of academic success for these populations. This article provides a rationale for the use of an empirically supported, strengths-based parenting program, Child Parent Relationship Training (CPRT), when working with low-income Head Start African American and Latino families. An examination of the shared objectives of CPRT and key domains within the Head Start Child Outcomes Framework (2003) are also highlighted.
Correction of truncus arteriosus after pulmonary artery banding.

Abstract Correction of truncus arteriosus can be performed in the older child with low mortality. However, many infants are severely symptomatic with increased pulmonary blood flow and require banding of the pulmonary artery at an age when correction has a high mortality. The pulmonary artery band can complicate the usual technique of the subsequent repair. An alternative approach following pulmonary artery banding is to interrupt the pulmonary artery–truncus continuity with a patch from within the truncus and then place the external valved conduit onto the pulmonary artery in an end-to-side manner.
Scalar timing law for interval timing in a plastic network of spiking neurons

In many perceptual tasks there is an observed linear relationship between the magnitude of the estimated variable and the error of the estimate; this is called Weber’s law. Applied to estimates of interval timing this general linear relationship is called the scalar timing law. Under a stronger variant of the law in addition to the standard deviation of the errors increasing linearly with time, the complete distribution of timing estimates scales linearly as well. We have recently developed a model of a plastic network that can represent time through learned temporal dynamics [1]. The temporal representations formed in our network resemble those described experimentally in V1 [2]. Here we train this network to encode various times from several hundred ms to slightly less than 2 sec. We decode this spiking model using a simple population decoding scheme. We show that the standard deviation of reported durations in such a spiking network, scales nearly linearly. We analyze how the slope and intercept of linear fits depend on system parameters such as number of neurons, and network noise levels. Although the error scales linearly with time, the distribution of the decoded times does not scale linearly with the time, and its shape changes. We examine the effect of including an additional source of noise in the decoding process. We show that if an additional source of noise exists in the decoding process, the response distribution can scale nearly linearly as well. We analyze how this additional noise source effect the slope and intercept of the linear fit, and what magnitude of noise is necessary for obtaining linear scaling of the distribution.
A re-examination of exchangeable acidity as extracted by potassium chloride and potassium fluoride.

Abstract In order to better understand some of the factors likely to affect measurements of KC1 extractable acidity, experiments were conducted using synthetic solutions and extracts from a wide range of contrasting soils. The reagents used for measuring exchangeable acidity (i.e., KC1 and KF) were also examined to evaluate the effects of chemical impurities on acidity measurements. Two commonly used titrimetric methods were adapted and tested to determine the accuracy and precision of acidity measurements. The exchangeable acidity of soil extracts was investigated by extraction methods, extractant concentration, and extractant volume. Results from the soil extract experiments indicated that continuous shaking has no significant effect on acidity measurements. Filtration, however, is critical, especially for acidic organic‐rich soils, since aluminum (Al) ions can be lost during centrifugation. Extractant concentration and volume had variable effects on the acidity measurements for individual soils. In gen...
Latinos(as) y la descolonización del imperio estadounidense en el siglo XXI

A pesar de las apariencias, el imperio estadounidense se encuentra en una decadencia acelerada. existen muchas luchas anti-capitalistas, anti-imperialistas y anti-patriarcales al interior de este imperio, invisibles para los pueblos que viven sus consecuencias nefastas en america latina, Africa, asia y el medio oriente. este articulo presenta los dilemas que confronta el imperio estadounidense con respecto al crecimiento de las poblaciones latinas y a las luchas por la descolonizacion desde su interior. en pocas decadas los blancos seran una minoria demografica en los Estados Unidos. Las minorias raciales seran las mayorias; los latinos seran la mayoria de las minorias. el imperio se debate entre nuevas formas de apartheid (neo-apartheid) y la descolonizacion de la supremacia blanca. Por su importancia estrategica, las luchas que se avecinan seran agudas y definitivas para el futuro de toda la humanidad
Rapunzel syndrome causing gastric emphysema and small bowel obstruction

A FOURTEEN-YEAR-OLD GIRL presented with central abdominal pain, associated with multiple episodes of vomiting; the day before admission, she had a normal bowel movement. She had no previous gastric operations or known gastrointestinal motility disorders. Abdominal examination elicited lower abdominal tenderness with guarding, greater on the left. The white cell count was 13,000, and plain abdominal x-ray showed multiple loops of dilated small bowel with air in the rectum. Computed tomography revealed a large amount of material in the stomach with what appeared as gas bubbles within the gastric wall (gastric emphysema [Fig 1]). The distal small bowel contained pieces of the same material with dilated loops proximal to it. A preoperative diagnosis of gastric bezoars causing gastric ischemia and small bowel obstruction was made. At laparotomy there was no evidence of gastric necrosis, nor intraperitoneal infection. The distended stomach contained a giant trichobezoar—filling it like a cast—which was extracted via a gastrotomy (Fig 2). The distal ileum was obstructed by a long cast of trichobezoar (Fig 3) removed through an enterotomy (Fig 4). The postoperative course was uneventful, but the patient was referred for psychiatric counseling.
Model-based fusion of FLIR, color, and ladar

The complementary nature of LADAR, FLIR and color data for Automatic Target Recognition (ATR) is being explored by new algorithms in a three stage recognition system. The stages are initial detection, target class and pose hypothesis generation, and precise model to multisensor coregistration matching. Coregistration globally aligns 3D target models with range, IR and color imagery while simultaneously refining registration parameters between sensors. This model directed approach is expected to improve ATR performance for occluded targets, targets seen at unusual angles, and targets in cluttered settings. Color is used for initial target detection under daylight conditions. Camouflage learned from training examples generalizes across vehicles and distinguishes targets from natural terrain. Target class and pose hypothesis generation will draw upon existing LADAR boundary matching work extended to tolerate more occlusion, clutter and viewpoint variation. New model to multisensor coregistration algorithms appear robust in early tests and are the basis for future coregistration matching. A new interactive 3D visualization environment allows inspection of multisensor data, coregistration, and monitoring of recognition.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
Localized RNAi and Ectopic Gene Expression in the Medicinal Leech

In this video, we show the use of a pneumatic capillary gun for the accurate biolistic delivery of reagents into live tissue. We use the procedure to perturb gene expression patterns in selected segments of leech embryos, leaving the untreated segments as internal controls. The pneumatic capillary gun can be used to reach internal layers of cells at early stages of development without opening the specimen. As a method for localized introduction of substances into living tissues, the biolistic delivery with the gun has several advantages: it is fast, contact-free and non-destructive. In addition, a single capillary gun can be used for independent delivery of different substances. The delivery region can have lateral dimensions of approximately 50-150 microm and extends over approximately 15 microm around the mean penetration depth, which is adjustable between 0 and 50 microm. This delivery has the advantage of being able to target a limited number of cells in a selected location intermediate between single cell knock down by microinjection and systemic knockdown through extracellular injections or by means of genetic approaches. For knocking down or knocking in the expression of the axon guidance molecule Netrin, which is naturally expressed by some central neurons and in the ventral body wall, but not the dorsal domain, we deliver molecules of dsRNA or plasmid-DNA into the body wall and central ganglia. This procedure includes the following steps: (i) preparation of the experimental setup for a specific assay (adjusting the accelerating pressure), (ii) coating the particles with molecules of dsRNA or DNA, (iii) loading the coated particles into the gun, up to two reagents in one assay, (iv) preparing the animals for the particle delivery, (v) delivery of coated particles into the target tissue (body wall or ganglia), and (vi) processing the embryos (immunostaining, immunohistochemistry and neuronal labeling) to visualize the results, usually 2 to 3 days after the delivery. When the particles were coated with netrin dsRNA, they caused clearly visible knock-down of netrin expression that only occurred in cells containing particles (usually, 1-2 particles per cell). Particles coated with a plasmid encoding EGFP induced fluorescence in neuronal cells when they stopped in their nuclei.
Small-molecule inhibition of Wnt signaling through activation of casein kinase 1α

Wnt/β-catenin signaling is critically involved in metazoan development, stem cell maintenance and human disease. Using Xenopus laevis egg extract to screen for compounds that both stabilize Axin and promote β-catenin turnover, we identified an FDA-approved drug, pyrvinium, as a potent inhibitor of Wnt signaling (EC(50) of ∼10 nM). We show pyrvinium binds all casein kinase 1 (CK1) family members in vitro at low nanomolar concentrations and pyrvinium selectively potentiates casein kinase 1α (CK1α) kinase activity. CK1α knockdown abrogates the effects of pyrvinium on the Wnt pathway. In addition to its effects on Axin and β-catenin levels, pyrvinium promotes degradation of Pygopus, a Wnt transcriptional component. Pyrvinium treatment of colon cancer cells with mutation of the gene for adenomatous polyposis coli (APC) or β-catenin inhibits both Wnt signaling and proliferation. Our findings reveal allosteric activation of CK1α as an effective mechanism to inhibit Wnt signaling and highlight a new strategy for targeted therapeutics directed against the Wnt pathway.
On the Equivalence of Upward and Downward Inheritance Reasoners

In this paper, we analyze systematically the downward (property flow) and the upward (individual flow) views of inheritance for different categories of inheritance networks. We observe that both these views assign the same meaning to tree-structured hierarchies, and explain the divergence in the interpretation of more general networks in terms of their expressive power. This simple analysis sheds light on the inherent nature of nonmonotonic inheritance and can form the basis for the design of efficient algorithms for certain classes of queries. In addition, we describe the notion of preferential inheritance to specify additional conflict resolution information that can be integrated smoothly with the upward view of inheritance.