Miracle-dz/UniFAR-FTUs huggingface dataset:
Near infrared fluorescent imaging of choline kinase alpha expression and inhibition in breast tumors

Choline kinase alpha (ChoKα) overexpression is associated with an aggressive tumor phenotype. ChoKα inhibitors induce apoptosis in tumors, however validation of their specificity is difficult in vivo. We report the use of optical imaging to assess ChoKα status in cells and in vivo using JAS239, a carbocyanine-based ChoKα inhibitor with inherent near infrared fluorescence. JAS239 attenuated choline phosphorylation and viability in a panel of human breast cancer cell lines. Antibody blockade prevented cellular retention of JAS239 indicating direct interaction with ChoKα independent of the choline transporters and catabolic choline pathways. In mice bearing orthotopic MCF7 breast xenografts, optical imaging with JAS239 distinguished tumors overexpressing ChoKα from their empty vector counterparts and delineated tumor margins. Pharmacological inhibition of ChoK by the established inhibitor MN58b led to a growth inhibition in 4175-Luc+ tumors that was accompanied by concomitant reduction in JAS239 uptake and decreased total choline metabolite levels as measured using magnetic resonance spectroscopy. At higher therapeutic doses, JAS239 was as effective as MN58b at arresting tumor growth and inducing apoptosis in MDA-MB-231 tumors, significantly reducing tumor choline below baseline levels without observable systemic toxicity. These data introduce a new method to monitor therapeutically effective inhibitors of choline metabolism in breast cancer using a small molecule companion diagnostic.
Cochlear Dead Regions Constrain the Benefit of Combining Acoustic Stimulation With Electric Stimulation

Objective: The aims of this study were to (1) detect the presence and edge frequency (fe) of a cochlear dead region in the ear with residual acoustic hearing for bimodal cochlear implant users, and (2) determine whether amplification based on the presence or absence of a dead region would improve speech understanding and sound quality. Design: Twenty-two listeners with a cochlear implant in one ear and residual acoustic hearing in the nonimplanted ear were tested. Eleven listeners had a cochlear dead region in the acoustic-hearing ear and 11 did not. Dead regions were assessed with the threshold-equalizing noise (TEN) and the sweeping noise, psychophysical tuning curve tests. Speech understanding was assessed with monosyllabic words and the AzBio sentences at +10 dB signal-to-noise ratio. Speech- and music-quality judgments were obtained with the Judgment of Sound Quality questionnaire. Results: Using shifted tips of the psychophysical tuning curve as a basis for diagnosis, the TEN had high sensitivity (0.91) and poor specificity (0.55) for this population. The value of fe was lower when estimated with the sweeping noise, psychophysical tuning curve test than with the TEN test. For the listeners with cochlear dead regions, speech understanding, speech quality and music quality were best when no amplification was applied for frequencies within the dead region. For listeners without dead regions, speech understanding was best with full-bandwidth amplification and was reduced when amplification was not applied when the audiometric threshold exceeded 80 dB HL. Conclusion: The data from this study suggest that, to improve bimodal benefit for listeners who combine electric and acoustic stimulation, audiologists should routinely test for the presence of cochlear dead regions and determine amplification bandwidth accordingly.
Adoptive Transfer of Immunomodulatory M2 Macrophages Prevents Type 1 Diabetes in NOD Mice

Macrophages are multifunctional immune cells that may either drive or modulate disease pathogenesis depending on their activation phenotype. Autoimmune type 1 diabetes (T1D) is a chronic proinflammatory condition characterized by unresolved destruction of pancreatic islets. Adoptive cell transfer of macrophages with immunosuppressive properties represents a novel immunotherapy for treatment of such chronic autoimmune diseases. We used a panel of cytokines and other stimuli to discern the most effective regimen for in vitro induction of immunosuppressive macrophages (M2r) and determined interleukin (IL)-4/IL-10/transforming growth factor-β (TGF-β) to be optimal. M2r cells expressed programmed cell death 1 ligand-2, fragment crystallizable region γ receptor IIb, IL-10, and TGF-β, had a potent deactivating effect on proinflammatory lipopolysaccharide/interferon-γ–stimulated macrophages, and significantly suppressed T-cell proliferation. Clinical therapeutic efficacy was assessed after adoptive transfer in NOD T1D mice, and after a single transfer of M2r macrophages, >80% of treated NOD mice were protected against T1D for at least 3 months, even when transfer was conducted just prior to clinical onset. Fluorescent imaging analyses revealed that adoptively transferred M2r macrophages specifically homed to the inflamed pancreas, promoting β-cell survival. We suggest that M2r macrophage therapy represents a novel intervention that stops ongoing autoimmune T1D and may have relevance in a clinical setting.
Slip Partitioning by Elastoplastic Propagation of Oblique Slip at Depth

Oblique motion along tectonic boundaries is commonly partitioned into slip on faults with different senses of motion. The origin of slip partitioning is important to structural geology, tectonophysics, and earthquake mechanics. Partitioning can be explained by the upward elastoplastic propagation of oblique slip from a fault or shear zone at depth. The strain field ahead of the propagating fault separates into zones of predominantly normal, reverse, and strike-slip faulting. The model successfully predicts the distribution of fault types along parts of the San Andreas and Haiyuan faults.
Reionization Constraints from Five-Year WMAP Data

We study the constraints on reionization from 5 years of WMAP data, parameterizing the evolution of the average fraction of ionized hydrogen with principal components that provide a complete basis for describing the effects of reionization on large-scale E-mode polarization. Using Markov Chain Monte Carlo methods, we find that the resulting model-independent estimate of the total optical depth is nearly twice as well determined as the estimate from 3 year WMAP data, in agreement with simpler analyses that assume instantaneous reionization. The mean value of the optical depth from principal components is slightly larger than the instantaneous value; we find τ = 0.097 ± 0.017 using only large-scale polarization, and τ = 0.101 ± 0.019 when temperature data is included. Scale-invariant ns = 1 spectra are allowed by WMAP for exotic ionization histories with large, sudden changes in the ionized fraction at high redshift, but more realistic models still favor a red spectral tilt. Higher moments of the ionization history show less improvement in the 5 year data than the optical depth. By plotting the distribution of polarization power for models from the MCMC analysis, we show that extracting most of the remaining information about the shape of the reionization history from the CMB requires better measurements of E-mode polarization on scales of ℓ ∼ 10–20. Conversely, the quadrupole and octopole polarization power is already predicted to better than cosmic variance given any allowed ionization history at z < 30 so that more precise measurements will test the ΛCDM paradigm.
Attentional reorienting in response to socially relevant gestures : a neuropsychological investigation

The work presented in this thesis explored the effectiveness and reflexiveness of attentional reorienting in response to different types of socially salient gestures. A traditional target detection paradigm was employed across experiments, allowing for the direct comparison of validity effects in response to eye gaze shifts, human pointing gestures, and symbolic arrows. Previous research has tended to compare the effects of eye gaze shifts and symbolic arrows, so this thesis attempted to ‘bridge the gap’ in the social orienting literature. The effects of these different types of socially relevant stimuli were investigated in three distinct populations. Firstly, we examined whether pointing gestures were as effective as eye gaze shifts in reorienting attention to the impaired hemifield of patients with parietal lobe damage. We then carried out the same set of experiments with a patient displaying an acquired ‘theory of mind’ deficit, to establish the relative social nature of pointing gestures in comparison to gaze. Finally, we assessed the effects in typically developing adults who display a high proportion of autistic traits, to draw inferences about how these cues are attended to in autistic spectrum disorders. We found that pointing gestures hold a similar social relevance as gaze shifts, and produce largely the same attentional reorienting effects in normal observers. Effects are discussed in terms of reflexive visual attention, neuropsychological disorders, and social cognition, with inferences regarding social networks in the brain.
Exploring the potential of audio-tactile messaging for remote interpersonal communication

Shake2Talk is a mobile messaging system that allows users to send sounds and tactile sensations to one another via their mobile phones. Messages are created through gestures and then sent to the receiver's phone where they play upon arrival. This paper reports a study of the Shake2Talk system in use by six couples, and begins to uncover the types of messaging practices that occur, and the values and meanings that users ascribe to these messages.
Alanine aminotransferase is associated with metabolic syndrome independently of insulin resistance.

Background: Few studies have examined the effect of insulin resistance on the association between alanine aminotransferase (ALT) and metabolic syndrome. The association between ALT levels and metabolic syndrome were determined, independently of insulin resistance in Korean populations. Methods and Results: The association between ALT and metabolic syndrome were examined in 28,456 subjects who visited 7 Health Promotion Centers at University Hospitals in Korea from 2006 to 2008. HOMA-IR index was used to represent insulin resistance index. ALT levels were found to be positively associated with metabolic syndrome after adjusting for age, alcohol intake, and smoking status. Furthermore, when additional adjustment was made for insulin resistance, this association between ALT and metabolic syndrome, although slightly attenuated, remained strongly significant. Subjects in the highest ALT quartile were found to have a higher risk of having metabolic syndrome than those in the lowest quartile (odds ratio (OR)=4.45, 95% confidence interval (CI)=3.96-4.99 for men and OR=3.51, 95%CI=2.73-4.52 for women). In addition, the association between ALT level and the risk of metabolic syndrome was significantly higher in the relatively low risk group. Conclusions: ALT levels were found to be significantly associated with metabolic syndrome independently of insulin resistance and with an interaction by age. Further cohort studies are needed to determine the usefulness of ALT levels for predicting the risk of metabolic syndrome. (Circ J 2011; 75: 964-969)
The (true) Stewart platform has 12 configurations

We consider a Stewart platform and show that its forward kinematics has at most 12 solutions. A first geometrical demonstration is provided which uses the concept of circularity and in a second proof we show that this problem is equivalent to find a system of two planar parallel manipulators with each 6 solutions to the forward kinematic problem. A geometrical construction is provided to construct such a system and a Stewart platform with 12 configurations is exhibited. <<ETX>>
Five-Year Follow Up of Thymoglobulin Versus ATGAM Induction in Adult Renal Transplantation

Background. One-year results of a randomized, double-blinded trial of Thymoglobulin versus Atgam for induction therapy in renal transplantation revealed that Thymoglobulin was associated with higher event-free survival (94% vs. 63%), less acute rejection (4% vs. 25%), and better graft survival. This article compares the safety and efficacy of Thymoglobulin versus Atgam induction through 5 years. Methods. Review and analysis of clinic records and electronic databases. Results. At 5 years, event-free survival (73% vs. 33%, P<0.001), graft survival (77% vs. 55%, P=0.047), and freedom from rejection (92% vs. 66%, P=0.007) were higher with Thymoglobulin versus Atgam. No additional cytomegalovirus (CMV) disease occurred after the first year with Thymoglobulin or Atgam (13% vs. 33%, P=0.056). There were two cases of posttransplant lymphoproliferative disorder (PTLD) with the Atgam arm and none with Thymoglobulin. Thymoglobulin was associated with profound lymphopenia at 2 years after transplantation. Conclusions. Thymoglobulin was associated with higher event-free survival, graft survival, and freedom from rejection without increased PTLD or CMV disease at 5 years compared with Atgam. The prolonged and profound lymphopenia may contribute to the long-term results associated with Thymoglobulin.
Linkage studies on chromosome 22 in familial schizophrenia.

As part of a systematic search for a major genetic locus for schizophrenia we have examined chromosome 22 using 14 highly polymorphic markers in 23 disease pedigrees. The markers were distributed at an average distance of 6.6 cM, covering 70-80% of the chromosome. We analyzed the data by the lod score method using five plausible genetic models ranging from dominant to recessive, after testing the power of our sample under the same genetic parameters. The most positive lod score found was 1.51 under a recessive model for the marker D22S278, which is insufficient to conclude linkage. However, an excess of shared alleles in affected siblings (P < .01) was found for both D22S278 and D22S283. For D22S278, the A statistic was equal to the lod score (1.51) and therefore did not provide additional evidence for linkage allowing for heterogeneity, but the Liang statistic was more significant (P = .002). Our results suggest the possibility that the region around D22S278 and D22S283 contains a gene which contributes to the aetiology of schizophrenia.
Relationship of structural magnetic resonance imaging, magnetic resonance perfusion, and other disease factors to neuropsychological outcome in sickle cell disease.

OBJECTIVE To investigate the relationship between neuropsychological functioning and radiographic findings in children with sickle cell disease (SCD) with no history of clinical neurological events. METHODS Thirty-one patients with SCD randomly selected from a regional treatment center underwent neuropsychological and disease severity assessments. Of these, 22 also had structural magnetic resonance imaging and magnetic resonance perfusion studies performed. RESULTS Forty-five percent of the imaged subgroup showed imaging abnormalities that were found to be correlated with disease severity but not neuropsychological level of performance indices. A significant relationship, however, was found between imaging abnormalities and increased variability in neuropsychological performance. CONCLUSIONS These results corroborate the high rate of rheologic and vascular pathology in SCD and underscore the importance of representing neuropsychological functioning in multiple ways.
Improved procedure for bacteriophage typing of Listeria strains and evaluation of new phages

A modified technique in listerial phage typing, termed reversed phage typing procedure, was developed. Ready-to-use typing plates were prepared by preapplication of phage suspensions on tryptose agar plates. The new procedure offers a number of substantial advantages as compared with the conventional method, being much more reliable, efficient, and convenient to use. More than 1,000 strains of Listeria have thus far been typed with the reversed phage typing procedure, employing an extended set of 21 genus-specific bacteriophages. The overall typability of strains was 89.5%.
The blues of P(16)INK(4a): Aberrant promoter methylation and association with colorectal cancer in the Kashmir valley

Hypermethylation of the promoter region of the p16INK4a (p16) gene plays a significant role in the development and progression of colorectal cancer (CRC). The aim of the present study was to establish the role of the methylation status of the p16 gene in 114 CRC cases and to correlate it with the various clinicopathological parameters. Analysis of p16 promoter methylation was performed by methylation-specific PCR. Forty-eight (42.1%) of the CRC cases were found to be methylated for the p16 gene in our population. The methylation status was found to be associated with the gender, lymph node status, tumour stage, smoking status and tumour grade of the CRC patients. p16 plays a pivotal role in tumour development and progression to advanced stages.
VARPU PENNINKILAMPI-KEROLA IMPLICATIONS OF CO-TWIN DEPENDENCE FOR TWINS’ SOCIAL INTERACTIONS, MENTAL HEALTH AND ALCOHOL USE A follow-up study of Finnish twins from adolescence to early adulthood

Background and objective: Relatively few studies have concentrated on the qualities or implications of the relationships between twins and their co-twins. The aim of the present study was to examine co-twin dependence and its impact on twins’ social contacts, leisure-time activities and psycho-emotional well-being. The role of co-twin dependence was also examined as a moderator of genetic and environmental influences on alcohol use in adolescence and in early adulthood. Methods: The present report is based on the Finnish Twin Cohort Study (FinnTwin16), which is a population-based study of five consecutive birth cohorts of Finnish twins born in the years 1975-1979. Baseline assessments were collected through mailed questionnaires during the years 1991-1995, within two months of the twins' sixteenth birthday. The five-year cohort yielded replies from 5563 twin individuals. All respondent twins were sent follow-up questionnaires at ages of 17, 181⁄2, and in early adulthood, when twins were 22-27 years old. Measures: The questionnaires included a survey of health habits and attitudes, a symptom checklist and questions about twins’ relationships with parents, peers and cotwin. Measures used were twins’ self-reports of their own dependence and their co-twin’s dependence at age 16, reports of twins’ leisure-time activities and social contacts, alcohol use, psychological distress and somatic symptoms both in adolescence and in early adulthood. Results: Co-twin dependence is relatively common feature among twins. In the present study 25.6% of twins reported dependence on their co-twin. There were gender and zygosity differences in dependence, females and MZ twins were more likely to report dependence than males and DZ twins. The results also suggested that co-twin dependence can be viewed on one hand as an individual characteristic, but on the other hand as a pattern of dyadic interaction that is mutually regulated and reciprocal. Most of the twins (80.7%) were either concordantly co-twin dependent or concordantly co-twin independent. The associations of co-twin dependence with twins’ social interactions and psycho-emotional characteristics were relatively consistent both in adolescence and in early adulthood. Dependence was related to higher contact frequency and a higher proportion of shared leisure-time activities between twin siblings at the baseline and the follow-up. Additionally co-twin dependence was associated with elevated levels of
Background noise from a natural chorus alters female discrimination of male calls in a Neotropical frog

Many animals communicate in environments with high levels of background noise. Although it is a fundamental prediction of signal detection theory that noise should reduce both detection and discrimination of signals, little is known about these effects in animal communication. Female treefrogs, Hyla ebraccata, in Costa Rica choose mates in large noisy multispecies choruses. We tested gravid females for preferences between computer-synthesized calls with carrier frequencies of 3240 and 2960 Hz (values near the mode and the fifth percentile of the population, respectively) in four levels of background noise from a natural chorus. In the absence of noise (signal/noise ratio >25 dB), females preferred the lower frequency. With moderate signal/noise ratios (6 and 9 dB), they did not discriminate between these frequencies. With low signal/noise ratios (3 dB), females preferred the frequency near the mode for the population. Similar experiments had previously demonstrated that females can detect the presence of a male’s calls with signal/noise ratios of 3 dB or greater. Thus moderate levels of natural background sound reduced a female’s ability to discriminate between males’ calls even when she could detect them. In high levels of background sound, females abandoned discrimination for low-frequency calls and reverted to the task of detecting signals with modal properties for the population. These results justify recent theoretical analyses of the importance of receivers’ errors in the evolution of communication.
DNA Polymorphisms of Genes Involved in Fiber Development in a Selected Set of Cultivated Tetraploid Cotton

The lack of genetic diversity within cultivated upland cotton (Gossypium hirsutum L.) has hindered the construction of genomewide linkage maps and their applications in genetics and breeding. The objective of this investigation was to develop candidate gene markers for fi ber quality and yield on the basis of approximately 90 genes implicated in fi ber development. Polymorphisms using sequence-tagged site (STS) and single nucleotide polymorphism (SNP) markers based on single strand conformation polymorphism (SSCP) and cleaved amplifi ed polymorphism (CAP) were evaluated among three upland and fi ve Pima cotton (G. barbadense L.) genotypes. Of the 90 primer pairs, 75 resulted in polymerase chain reaction amplifi cations, including 11 that yielded polymorphic STS markers. Of the 48 primer pairs that produced polymorphic SSCP markers, 27 yielded interspecifi c polymorphism, while 15 yielded both inter- and intraspecifi c polymorphisms. Six pairs yielded only intraspecifi c polymorphisms. A total of 18 SNPs, including four indels, were identifi ed in seven of the 15 fi ber gene fragments on the basis of direct DNA sequencing, and the average length was 350 bp, with a mean of 1.3 SNPs per fragment. The average rate of SNPs per nucleotide was 0.34%, and 0.31% and 0.41% in coding and noncoding regions, respectively. Eight of the 15 SNPs were interspecifi c and 78% were nucleotide substitutions, with the four indels contributing to interspecifi c polymorphism. Six selected SNPs were confi rmed by restriction enzyme digestion. The high level of SSCP polymorphism observed within a selected set of agronomically improved lines of upland cotton suggests that the use of SSCP will greatly facilitate genomewide mapping in upland cotton.
Lectures on self-avoiding walks

These lecture notes provide a rapid introduction to a number of rigorous results on self-avoiding walks, with emphasis on the critical behaviour. Following an introductory overview of the central problems, an account is given of the Hammersley-Welsh bound on the number of self-avoiding walks and its consequences for the growth rates of bridges and self-avoiding poly- gons. A detailed proof that the connective constant on the hexagonal lattice equals p 2 + p 2 is then provided. The lace expansion for self-avoiding walks is described, and its use in understanding the critical behaviour in dimensions d > 4 is discussed. Functional integral representations of the self-avoiding walk model are discussed and developed, and their use in a renormalisation group analysis in dimension 4 is sketched. Problems and solutions from tutorials are included.