Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of Cobalt-Labeled Octreotide Analogs for Molecular Imaging and Auger Electron–Based Radionuclide Therapy

The somatostatin receptor, which is overexpressed by many neuroendocrine tumors, is a well-known target for molecular imaging and peptide receptor radionuclide therapy. Recently, 57Co-labeled DOTATOC, an octreotide analog, was shown to have the highest affinity yet found for somatostatin receptor subtype 2. The aim of this study was to evaluate the biologic effects of novel cobalt-labeled octreotide analogs targeting the somatostatin receptor to identify promising candidates for molecular imaging and Auger electron–based radionuclide therapy. Methods: Cobalt-labeled DOTATATE, DOTATOC, and DOTANOC were prepared with 57Co or 58mCo for SPECT or Auger electron–based therapy, respectively. The cellular uptake and intracellular distribution of the radioligands were characterized with the pancreatic tumor cell line AR42J in vitro, including assessment of the therapeutic effects of 58mCo-DOTATATE via DNA double-strand break and proliferation assays. Comparisons with the therapeutic effects of 111In- and 177Lu-DOTATATE were also performed. Tumor uptake and normal tissue uptake were characterized in a subcutaneous pancreatic tumor mouse model. Results: All 3 cobalt-conjugated peptides resulted in time-dependent and receptor-specific uptake, with a high level (≥88%) of cellular internalization in vitro of the total cell-associated radioactivity. The DNA double-strand break yield showed a dose-dependent increase with activity, whereas cell survival showed a dose-dependent decrease. 58mCo-DOTATATE was significantly more efficient in cell killing per cumulated decay than 111In- and 177Lu-DOTATATE. The in vivo pharmacokinetic studies showed a high level of receptor-specific tumor uptake. Conclusion: All cobalt-labeled radioligands showed a high level of receptor-specific uptake both in vitro and in vivo in tumor-bearing mice. Furthermore, 58mCo-DOTATATE showed considerable therapeutic effects in vitro and, thus, could be an effective agent for eradicating disseminated tumor cells and micrometastases.
Significant Differences in Nonmelanoma Skin Cancers of the Upper and Lower Lip

Background Squamous cell carcinomas (SCCs) generally have been reported to be more prevalent on the lips than basal cell carcinomas (BCCs), but in our experience, BCCs of the lips are common, particularly in women. Objectives To determine the tumor characteristics of lip SCCs and BCCs, including tumor type, anatomic location, and size; and to identify the relationship between patient characteristics, including age and sex, and lip tumor characteristics. Methods and Materials Retrospective review of all BCCs and SCCs located on the lip treated between January 1995 and October 2010. Results Of 470 lip nonmelanoma skin cancers (NMSCs) identified, 71.4% were BCCs, and 28.6% were SCCs. Lower lip tumors were predominantly SCCs (79.8%, p < .01), whereas upper lip tumors were predominantly BCCs (85.7%, p < .01). Patients with lower lip tumors were significantly older (68.8 vs 64.7, p = .02) and were largely male (70.8%, p < .01). Patients with SCCs were mostly male (62.2%, p = .02), whereas those with BCCs were predominantly female (68.8%, p < .01). Subgroup analysis showed that upper lip tumors were 98.1% cutaneous or more than 50% cutaneous, whereas 56.3% of lower lip tumors were mucosal or more than 50% mucosal; 87.1% of mucosal tumors were SCCs, whereas 83.6% of cutaneous tumors were BCCs (p < .01). Seventy‐one percent of patients with mucosal tumors were men, whereas 67% of patients with cutaneous only tumors were women (p < .01). Conclusion These data provide evidence of significant differences in patient and tumor characteristics between NMSCs of the upper and lower lips.
Treatment of Akata EBV-Positive Cells with Doxorubicin Causes More EBV Reactivation than Treatment with Etoposide

Background/Aims: EBV has been associated with Burkitt lymphoma (BL). It establishes a latent infection but its reactivation has been observed in patients receiving long-term chemotherapy. The effect of doxorubicin on virus reactivation has been described previously, but the effect of etoposide or cytarabine on EBV reactivation has not been reported in the literature. The aim of this work was to carry out such a study. Methods: Akata EBV-positive cell lines were treated with etoposide, doxorubicin or cytarabine. Viable cells were analyzed by trypan blue, programmed cell death by TUNEL assay, mRNA levels by RT-PCR and cellular or viral proteins by Western blot. Viruses were visualized by electron microscopy. Results: All of the studied drugs caused cell death by apoptosis. Comparing the effect of etoposide and doxorubicin (at their IC50) in the EBV-positive cells, etoposide caused less EBV reactivation than doxorubicin. Cytarabine apparently did not reactivate EBV. Conclusion: When treating Akata EBV-positive cells with the respective IC50 of the following drugs, etoposide induced less EBV reactivation than doxorubicin, and cytarabine apparently did not induce EBV reactivation.
Protein structure comparison using iterated double dynamic programming

A protein structure comparison method is described that allows the generation of large populations of high‐scoring alternate alignments. This was achieved by incorporating a random element into an iterative double dynamic programming algorithm. The maximum scores from repeated comparisons of a pair of structures converged on a value that was taken as the global maximum. This lay 15% over the score obtained from the single fixed (unrandomized) calculation. The effect of the gap penalty was observed through the shift of the alignment populations, characterized by their alignment length and root‐mean‐square deviation (RMSD). The best (lowest RMSD) values found in these populations provided a base‐line against which other methods were compared.
Physical Validation of Microwave Properties of Winter Precipitation Over the Sea of Japan

In order to evaluate variations in the physical properties of winter precipitation over the Sea of Japan, we analyzed the Wakasa Bay Experiment 2003 datasets. The results show that synoptic scale differences in freezing-level height (FLH) were observed between extra-tropical low cases and winter monsoon and upper cold low cases, and that, frozen-particle density and cloud liquid water content (CLWC) observed at the surface showed great variation independent of the precipitation rate, although positive correlation may exist between these two properties. The radiative transfer model (RTM) simulation and the validation using the advanced microwave scanning radiometer on EOS (AMSR-E) and millimeter-wave imaging radiometer brightness temperatures (TBs) indicate that sensitivity to frozen precipitation rate (0-5 mm ldr h-1) was found in 89-GHz polarization-corrected temperature (PCT89), 89-GHz polarization difference (PD89), and 150-GHz TBs and that this sensitivity decreased with FLH due to emission from mixed- and liquid-phase particles. The RTM simulation, however, overestimated the AMSR-E PCT89 depressions for nonzero FLH cases. This indicates that microwave retrieval for winter precipitation requires a priori information about FLH and an efficient mixed-phase-particle model for RTM. The relationship between surface precipitation rate and TBs was also influenced by the observed variation of CLWC. The relationship between PCT89 and PD89 is greatly altered in terms of CLWC. Relationship between AMSR-E PCT89 precipitation sensitivity and CLWC estimated from PCT89 and PD89 was qualitatively consistent with those of the RTM simulations. This suggests that CLWC, another important retrieval parameter, can be estimated from PCT89 and PD89.
Obesity and Its Metabolic Complications: The Role of Adipokines and the Relationship between Obesity, Inflammation, Insulin Resistance, Dyslipidemia and Nonalcoholic Fatty Liver Disease

Accumulating evidence indicates that obesity is closely associated with an increased risk of metabolic diseases such as insulin resistance, type 2 diabetes, dyslipidemia and nonalcoholic fatty liver disease. Obesity results from an imbalance between food intake and energy expenditure, which leads to an excessive accumulation of adipose tissue. Adipose tissue is now recognized not only as a main site of storage of excess energy derived from food intake but also as an endocrine organ. The expansion of adipose tissue produces a number of bioactive substances, known as adipocytokines or adipokines, which trigger chronic low-grade inflammation and interact with a range of processes in many different organs. Although the precise mechanisms are still unclear, dysregulated production or secretion of these adipokines caused by excess adipose tissue and adipose tissue dysfunction can contribute to the development of obesity-related metabolic diseases. In this review, we focus on the role of several adipokines associated with obesity and the potential impact on obesity-related metabolic diseases. Multiple lines evidence provides valuable insights into the roles of adipokines in the development of obesity and its metabolic complications. Further research is still required to fully understand the mechanisms underlying the metabolic actions of a few newly identified adipokines.
Characterization of Microsatellite Markers and Their Application to Genetic Diversity Analysis of Brachypodium sylvaticum var. breviglume from Yunnan, China

Southwestern China is abundant in a large species diversity of grasses and Brachypodium sylvaticum var. breviglume is unquestionably appropriate to serve as an ideal model to investigate the adaptation, evolution and diversification of grasses in this region. In this study, a total of 37 microsatellite markers were screened and genetic variation was estimated for 100 individuals from the five natural populations of the species. Our results showed that seven of them were polymorphic for the five studied populations, while the other thirty were monomorphic. These seven SSR loci exhibited a high level of genetic diversity among populations, i.e. allele number varied from 5 to 24, with an average of 13.29; expected heterozygosity (He) ranged from 0.439 to 0.561, with an average of 0.488; percentage of polymorphic loci (PPL) ranged from 85.71% to 100%, with an average of 97. 14%. The FCA and UPGMA analyses revealed that the five populations were divided into three clusters. Our results indicate that these newly characterized SSR markers are useful for the exploration of genetic diversity and evolutionary history of the B. sylvaticum var. breviglume populations in Yunnan, China.
Trajectory analysis for magnetic particle imaging

Recently a new imaging technique called magnetic particle imaging was proposed. The method uses the nonlinear response of magnetic nanoparticles when a time varying magnetic field is applied. Spatial encoding is achieved by moving a field-free point through an object of interest while the field strength in the vicinity of the point is high. A resolution in the submillimeter range is provided even for fast data acquisition sequences. In this paper, a simulation study is performed on different trajectories moving the field-free point through the field of view. The purpose is to provide mandatory information for the design of a magnetic particle imaging scanner. Trajectories are compared with respect to density, speed and image quality when applied in data acquisition. Since simulation of the involved physics is a time demanding task, moreover, an efficient implementation is presented utilizing caching techniques.
A study of 133 Chinese children with mitochondrial respiratory chain complex I deficiency

To investigate the clinical, enzymological and mitochondrial gene profiles of complex I deficiency in Chinese, clinical and laboratory data of the patients (79 boys, 54 girls) were retrospectively assessed. Activities of mitochondrial respiratory chain complexes in peripheral leucocytes were spectrophotometrically measured. The entire mitochondrial DNA (mtDNA) sequence was analyzed in 62 patients. Restriction fragment length polymorphism and gene sequencing analyses were performed in 15 families. Ninety‐one patients had isolated complex I deficiency; 42 had combined deficiencies of complex I and other complexes. The main clinical presentations were neuromuscular disorders (107 patients) and non‐neurological dysfunction (hepatopathy, renal damage and cardiomyopathy; 26 patients). In 32 of 62 patients who underwent mtDNA sequencing, 24 mutations were identified in 15 mitochondrial genes. The 12338T>C, 4833A>G and 14502T>C mutations were found in 12.9%, 11.3% and 4.8% patients, respectively. Seven patients had multiple mutations. Three novel mutations were identified. Chinese patients with complex I deficiency presented heterogeneous phenotypes and genotypes. Twenty‐four mutations were identified in 15 mitochondrial genes in 51.6% patients. mtDNA mutations were more common in isolated complex I deficiency than in combined complex deficiencies. The 12338T>C, 4833A>G and 14502T>C mutations were common.
Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions

OJECTIVE:Steatohepatitis is a morphological pattern of liver injury that may be seen in alcoholic or nonalcoholic liver disease. This pattern may occur with obesity, diabetes, the use of certain drugs, or the cause may be idiopathic. The well-recognized histopathological features of nonalcoholic steatohepatitis (NASH) include hepatocellular steatosis and ballooning, mixed acute and chronic lobular inflammation, and zone 3 perisinusoidal fibrosis. Currently, there are no systems for grading necroinflammatory activity or for staging fibrosis as exist for various other forms of chronic liver disease. The purpose of this study was to develop such a grading and staging system and was based on review of liver biopsies from 51 patients with nonalcoholic steatohepatitis from Saint Louis University Health Sciences Center.METHODS:For determination of grade, 10 histological variables of activity were initially analyzed; an overall impression of mild, moderate, and severe was made and the variables considered to be most significant were used to develop the necroinflammatory grade.RESULTS:The histological lesions considered to be significant were: steatosis, ballooning, and intra-acinar and portal inflammation. A staging score was developed to reflect both location and extent of fibrosis. The fibrosis score was derived from the extent of zone 3 perisinusoidal fibrosis with possible additional portal/periportal fibrosis and architectural remodeling. Fibrosis stages are as follows: Stage 1, zone 3 perisinusoidal fibrosis; Stage 2, as above with portal fibrosis; Stage 3, as above with bridging fibrosis; and Stage 4, cirrhosis.CONCLUSION:We propose a grading and staging system that reflects the unique histological features of nonalcoholic steatohepatitis.
On Brain Oedema

Traumatic brain injury and bacterial meningitis may at a glance appear as two different disease entities. The host reaction, however, to both trauma and infection involves a strong inflammatory response, with the classical symptomology of rubor, tumor, calor, dolor et functio laesa. Tumor, swelling, will increase the volume within the closed cranial vault, and may thereby raise the intracranial pressure to critical levels, affecting cerebral blood flow and oxygenation. In this thesis, brain oedema and its origins are investigated in experimental models of brain trauma and bacterial meningitis, and in patients suffering severe head injury. The studies are focused on fluid therapy, blood-brain barrier permeability changes, and their effects on oedema formation. In study I and II, it was shown that plasma volume expansion with crystalloid compared to colloid fluids resulted in increased cortical brain oedema after brain trauma in rats, and increased intracranial pressure in experimental meningitis in cats. Evidence is given that increased permeability of the blood-brain barrier is a key determinant of tissue water content after the insults. In study III, it was shown that post treatment with prostacyclin in experimental meningitis reduces systemic plasma volume loss, and may diminish the rise in intracranial pressure. In study IV, the effect of statin treatment after brain trauma in rats was investigated. No effect on brain oedema, cortical blood flow, or the transfer constant for a small molecule was detected, but capillary patency was better preserved in the statin group. Statin treatment was associated with increased plasma levels of nitric oxide, and decreased levels of prostacyclin. In study V, post-traumatic permeability changes of the blood-brain barrier in 17 brain trauma patients were quantified using contrast enhanced computerized tomography with multiple scanning during 25 minutes. It was shown that blood to brain transfer for iohexol was increased up to 20-fold in traumatized tissue. The relevance of these results regarding our understanding of the pathophysiology of post-traumatic brain oedema, and the implications for the clinical management of brain trauma patients are discussed. (Less)
4-Methoxybenzamidinium chloride monohydrate

In the cation of the title compound, C8H11N2O+·Cl−·H2O, the C—N bonds of the amidinium group are identical within experiemental error [1.305 (2) and 1.304 (2) Å], and its plane forms a dihedral angle of 25.83 (8)° with the phenyl ring. The ionic components are associated in the crystal into polymeric hydrogen-bonded supramolecular tapes stabilized by N—H+⋯Cl− and N—H+⋯Ow intermolecular hydrogen bonds, and by Ow—H⋯Cl− interactions.
Overcoming the customization bottleneck using example-based MT

We describe MSR-MT, a large-scale hybrid machine translation system under development for several language pairs. This system's ability to acquire its primary translation knowledge automatically by parsing a bilingual corpus of hundreds of thousands of sentence pairs and aligning resulting logical forms demonstrates true promise for overcoming the so-called MT customization bottleneck. Trained on English and Spanish technical prose, a blind evaluation shows that MSR-MT's integration of rule-based parsers, example based processing, and statistical techniques produces translations whose quality exceeds that of uncustomized commercial MT systems in this domain.
Nuclear sequences reveal mid‐range isolation of an imperilled deep‐water coral population

The mitochondrial DNA of corals and their anthozoan kin evolves slowly, with substitution rates about two orders of magnitude lower than in typical bilateral animals. This has impeded the delineation of closely related species and isolated populations in corals, compounding problems caused by high morphological plasticity. Here we characterize rates of divergence and levels of variation for three nuclear gene regions, then use these nuclear sequences as markers to test for population structure in Oculina, a taxonomically confused genus of corals. Rates of sequence divergence (obtained by comparison to Solenastrea hyades) were at least five (and sometimes over 10) times faster for the three nuclear markers than for a mitochondrial reference sequence. Nuclear sequence variation was also high within populations, although it tended to decline north of Cape Canaveral. Significant subdivision was evident among samples from 10 locations from between North Carolina and the Florida Panhandle, but neither nominal species designation nor population depth explained much of this variation. Instead, a single population from the unique deep (> 70 m) water reefs at the Oculina Banks off central Florida was a strong genetic outlier: all pairwise measures of subdivision involving this population were greater than those involving all other populations, and multilocus clustering recognized the Oculina Banks as distinct from other populations, despite its close proximity (≤ 36 km) to populations from shallower waters nearby and its location at the centre of the sampled range. Genetic isolation of the Oculina Banks population suggests that focused efforts will be needed to conserve the foundation species of these monotypic reefs and that depth may play a role in isolating marine populations and perhaps facilitating initial steps towards speciation.
Seismic Evidence for Active Underplating Below the Megathrust Earthquake Zone in Japan

Quake Control Large earthquakes occur at the margins of two colliding plates, where one plate subducts beneath the other at a shallow angle. These megathrust earthquakes often cause destructive tsunamis owing to the displacement of large volumes of water at the fault along the plate boundary. Two related studies of the seismic structure of subduction zones attempt to reveal the underlying mechanisms of megathrust earthquakes (see the Perspective by Wang). Kimura et al. (p. 210) compared seismic reflection images and microearthquake locations at the Philippine Sea plate where it subducts obliquely beneath Japan. The locations of repeating microearthquakes correspond to active transfer of material from the subducting plate to the continent—a process only previously assumed from exhumed metamorphic rocks. Dean et al. (p. 207) observe an expansive structure in the sea-floor sediment near the location of the 2004 and 2005 Sumatra earthquakes in Indonesia that suggests sediment properties may influence the magnitude of megathrust ruptures and their subsequent tsunamis. Microearthquakes correlated to seismic data reveal the real-time dynamics of a subduction zone. Determining the structure of subduction zones is important for understanding mechanisms for the generation of interplate phenomena such as megathrust earthquakes. The peeling off of the uppermost part of a subducting slab and accretion to the bottom of an overlying plate (underplating) at deep regions has been inferred from exhumed metamorphic rocks and deep seismic imaging, but direct seismic evidence of this process is lacking. By comparing seismic reflection profiles with microearthquake distributions in central Japan, we show that repeating microearthquakes occur along the bottom interface of the layer peeling off from the subducting Philippine Sea plate. This region coincides with the location of slow-slip events that may serve as signals for monitoring active underplating.
WZB – discussion paper

This paper presents a survey of the entire German CVC-market. As such, it can be considered as an industry report of the CVC-industry in Germany. The goal is, to give an overview of the CVC-market in 2003 and to describe its transformation over time. Based on two datasets from 2000/2001 and 2003/2004, the aspects of change and alteration after the New Economy bust as well as the brake down of the Neuer Markt are particularly accentuated. This is done by focusing on dimensions like strategic goals and their achievement, organizational structures, fund structures, decision making competencies, salaryand incentive structures as well as investment criteria and priorities. The results show that the industry as well as its members/ participants have changed tremendously in some respects, and that they have learned. Particularly the strategic goals, which the parent companies pursue with their CVC-programme, have been adopted significantly under the new, and worsened environmental conditions since 2000/2001.