julilili42/papers huggingface dataset:
A century of experiments and experiences
2009-03-17

In the last 2000 years, life expectancy has increased from 25 years to about 80 years. The changing worldwide age demographics have led to an inordinate increase of proximal femur fractures (in addition to other fractures). Approximately 150.000 inhabitants of Germany over 65 years of age suffer from fractures at the hip joint requiring acute surgery every year. Besides the difficulties involved in treating such fractures adequately as well as the increase in the number of cases we are now seeing makes it a tremendous challenge to provide the highest quality of surgical care. Frequent concomitant and complicating conditions in hip fracture patients include advanced age, pronounced osteoporosis and multiple morbidity. Fracture type and subsequent selection of stabilization method and implant are only some of the factors that relate to outcomes and complications. In addition to technical considerations, there is enormous economic impact and a requirement for coordination of peri-operative and post-operative care given in order to improve the rate of successful results (Fig. 1.1).
Operative procedure
2009-03-17

The osteosynthetic supply potentials with the DMS are not restricted to the traditional indicative areas in the pertrochanteric region. Within the framework of the standard indications, all intertrochanteric femur fractures (type 31 A 1.1-3 and 32 A 2.1-3) can be ideally treated by means of the DMS. After the application of the supporting screw, the valgisation angle can be adjusted to the required angular degree according to the specific requirements of each patient with an intact lateral corticalis by the means of an adjustable worm gear. Thus additional infractions and fractures in the trochanteric or subtrochanteric area can be avoided.
Introduction
2009-03-17

The history of non-locking implants in fracture treatment began in 1944. It was the year when the mother of the engineer Ernst Pohl (1876–1962) died after having suffered a proximal femur fracture which was treated conservatively over several weeks by traction and immobilization. From this moment the instrument maker Pohl worked to construct an implant which could allow stable fracture fixation, early mobilization and the best conditions for fracture healing in a rapid time frame. He is given credit for having developed the first non-locking connection between an intramedullary force carrier (lag screw) and a lateral anchoring plate (barrel plate) (Fig. 1).
Closing remarks
2009-03-17

Since the first implantation of a Dynamic Martin Screw (DMS) on the 15th of November 1992 (70 years old female with a combined inter- and subtrochanteric femur fracture) the implant has started its worldwide success.
Subtrochanteric femur and proximal femur shaft fractures
2009-03-17

Subtrochanteric femur fractures and proximal femur shaft fractures are severe injuries. They are considered as problematical fractures at the lower extremity. Subtrochanteric femoral fractures and proximal femoral shaft fractures occur more rarely in comparison with pertrochanteric femoral fractures. Nevertheless they lead quicker to life-threatening situations because they can be accompanied by rapid blood loss within a short time and other complications.
Post‐Golgi Traffic in Plants
2009-03-18

Secretory and endocytic traffic through the post‐Golgi endomembrane system regulates the abundance of plasma‐membrane proteins such as receptors, transporters and ion channels, modulating the ability of a cell to communicate with its neighbours and to adapt to a changing environment. The major post‐Golgi compartments are numerous and appear to be similar to their counterparts in animals. However, endosomes are rather ill defined morphologically but seem to be involved in specific trafficking pathways. Many plasma‐membrane proteins cycle constitutively via endosomal compartments. The trans ‐Golgi network (TGN) appears to be an early endosome where secretory and endocytic traffic meet. Endocytosed proteins that are to be degraded are targeted to the vacuole via the multivesiculate prevacuolar compartment (PVC) whereas cycling proteins pass through recycling endosomes. The trafficking machinery involves the same classes of proteins as in other eukaryotes. However, there are modifications that match the specifics of post‐Golgi traffic in plants. Although plants lack epithelia, some plasma‐membrane proteins are located on specific faces of the cell which reflects polarized traffic and influences the physiological performance of the tissue. Plants also differentiate highly polarized tip‐growing cells in which post‐Golgi traffic is adapted to very high rates of targeted exocytosis, endocytosis and recycling.
Molecular karyotyping of patients with unexplained mental retardation by SNP arrays: A multicenter study
2009-03-18

Genomic microarrays have been implemented in the diagnosis of patients with unexplained mental retardation. This method, although revolutionizing cytogenetics, is still limited to the detection of rare de novo copy number variants (CNVs). Genome-wide single nucleotide polymorphism (SNP) microarrays provide high-resolution genotype as well as CNV information in a single experiment. We hypothesize that the widespread use of these microarray platforms can be exploited to greatly improve our understanding of the genetic causes of mental retardation and many other common disorders, while already providing a robust platform for routine diagnostics. Here we report a detailed validation of Affymetrix 500k SNP microarrays for the detection of CNVs associated to mental retardation. After this validation we applied the same platform in a multicenter study to test a total of 120 patients with unexplained mental retardation and their parents. Rare de novo CNVs were identified in 15% of cases, showing the importance of this approach in daily clinical practice. In addition, much more genomic variation was observed in these patients as well as their parents. We provide all of these data for the scientific community to jointly enhance our understanding of these genomic variants and their potential role in this common disorder.
Pelvic-Organ Prolapse and Uterine Inversion
2009-03-18

A 68-year-old woman presented with dull, persistent abdominal pain, the sensation of a foreign body in the pelvis, difficulty voiding, and vaginal discharge. The symptoms had developed over many years, after two uncomplicated, spontaneous deliveries; at the time of presentation, the symptoms had become unbearable. Physical examination revealed a normal abdomen without a mass; on external inspection of the vulva, the pelvic organs were visibly prolapsed. The prolapsed structure, 30 cm in length, consisted of the vagina (arrow) and the inverted endometrium (asterisk). Repositioning was successfully performed manually in the clinic. The patient underwent vaginal hysterectomy and surgical repair of . . .
SNCA variants are associated with increased risk for multiple system atrophy
2009-03-19

Abstract To test whether the synucleinopathies Parkinson's disease and multiple system atrophy (MSA) share a common genetic etiology, we performed a candidate single nucleotide polymorphism (SNP) association study of the 384 most associated SNPs in a genome‐wide association study of Parkinson's disease in 413 MSA cases and 3,974 control subjects. The 10 most significant SNPs were then replicated in additional 108 MSA cases and 537 controls. SNPs at the SNCA locus were significantly associated with risk for increased risk for the development of MSA (combined p = 5.5 × 10 12 ; odds ratio 6.2). Ann Neurol 2009;65:610–614
DISCOVERY OF VERY HIGH ENERGY γ-RAY EMISSION FROM CENTAURUS A WITH H.E.S.S.
2009-03-19

We report the discovery of faint very high energy (VHE; E &gt; 100 GeV) γ-ray emission from the radio galaxy Centaurus A in observations performed with the High Energy Stereoscopic System (H.E.S.S.) experiment, an imaging atmospheric Cherenkov telescope array consisting of four telescopes located in Namibia. Centaurus A has been observed for more than 120 hr. A signal with a statistical significance of 5.0σ is detected from the region including the radio core and the inner kpc jets. The integral flux above an energy threshold of ~250 GeV is measured to be 0.8% of the flux of the Crab Nebula (apparent luminosity: L(&gt;250 GeV) ≈2.6 × 1039 erg s–1, adopting a distance of 3.8 Mpc). The spectrum can be described by a power law with a photon index of 2.7 ± 0.5stat ± 0.2sys. No significant flux variability is detected in the data set. However, the low flux only allows detection of variability on the timescale of days to flux increments above a factor of ~15-20 (3σ and 4σ, respectively). The discovery of VHE γ-ray emission from Centaurus A reveals particle acceleration in the source to &gt;TeV energies and, together with M 87, establishes radio galaxies as a class of VHE emitters
Cutting Edge: A2B Adenosine Receptor Signaling Provides Potent Protection during Intestinal Ischemia/Reperfusion Injury
2009-03-19

Abstract Gastrointestinal ischemia/reperfusion (IR) injury significantly contributes to the morbidity and mortality of critical illness. In this study, we hypothesized a protective role for extracellular adenosine signaling in intestinal IR injury. Initial profiling studies of mucosal scrapings following murine IR demonstrated selective induction of the A2B adenosine receptor (A2BAR) transcript. Moreover, gene-targeted mice for the A2BAR showed more profound intestinal IR injury compared with controls. In contrast, A2AAR−/− mice exhibited no differences in intestinal injury compared with littermate controls. In addition, selective inhibition of the A2BAR resulted in enhanced intestinal inflammation and injury during IR. Furthermore, A2BAR agonist treatment (BAY 60-6583) protected from intestinal injury, inflammation, and permeability dysfunction in wild-type mice, whereas the therapeutic effects of BAY 60-6583 were abolished following targeted A2BAR gene deletion. Taken together, these studies demonstrate the A2BAR as a novel therapeutic target for protection during gastrointestinal IR injury.
Modulation of TGF‐β activity by latent TGF‐β‐binding protein 1 in human malignant glioma cells
2009-03-19

Abstract High biological activity of the transforming growth factor (TGF)‐β‐Smad pathway characterizes the malignant phenotype of malignant gliomas and confers poor prognosis to glioma patients. Accordingly, TGF‐β has become a novel target for the experimental treatment of these tumors. TGF‐β is processed by furin‐like proteases (FLP) and secreted from cells in a latent complex with its processed propeptide, the latency‐associated peptide (LAP). Latent TGF‐β‐binding protein 1 (LTBP‐1) covalently binds to this small latent TGF‐β complex (SLC) and regulates its function, presumably via interaction with the extracellular matrix (ECM). We report here that the levels of LTBP‐1 protein in vivo increase with the grade of malignancy in gliomas. LTBP‐1 is associated with the ECM as well as secreted into the medium in cultured malignant glioma cells. The release of LTBP‐1 into the medium is decreased by the inhibition of FLP activity. Gene‐transfer mediated overexpression of LTBP‐1 in glioma cell lines results in an increase inTGF‐β activity. Accordingly, Smad2 phosphorylation as an intracellular marker of TGF‐β activity is enhanced. Conversely, LTBP‐1 gene silencing reduces TGF‐β activity and Smad2 phosphorylation without affecting TGF‐β protein levels. Collectively, we identify LTBP‐1 as an important modulator of TGF‐β activation in glioma cells, which may contribute to the malignant phenotype of these tumors. © 2009 UICC
Study of the accreting pulsar 4U 0115+63 using a bulk and thermal Comptonization model
2009-03-19

Highly magnetized pulsars accreting matter in a binary system are bright\\nsources in the X-ray band (0.1-100 keV). Despite the early comprehension of the\\nbasic emission mechanism, their spectral energy distribution is generally\\ndescribed by phenomenological or simplified models. We propose a study of the\\nspectral emission from the high mass X-ray binary pulsar 4U 0115+634 by means\\nof thermal and bulk Comptonization models based on the physical properties of\\nsuch objects. For this purpose, we analyze the BeppoSAX data in the energy\\nrange 0.7-100 keV of the 1999 giant outburst, 12 days after the maximum. We\\nmodel the spectral energy distribution of the system using a two-component\\ncontinuum. At higher energy, above ~7 keV, the emission is due to thermal and\\nbulk Comptonization of the seed photons produced by cyclotron cooling of the\\naccretion column, and at lower energy, the emission is due to thermal\\nComptonization of a blackbody source in a diffuse halo close to the stellar\\nsurface. From the best fit parameters, we argue that the cyclotron emission is\\nproduced ~1.7 km above the stellar surface, and escapes from the column near\\nits base, where the absorption features are generated by the interaction with\\nthe magnetic field in a surrounding halo. We find that in 4U 0115+634, the\\nobserved spectrum is dominated by reprocessed cyclotron radiation, whereas in\\nother bright sources with stronger magnetic fields such as Her X-1, the\\nspectrum is dominated by reprocessed bremsstrahlung.\\n
Study of the accreting pulsar 4U 0115+63 using a bulk and thermal Comptonization model
2009-03-19

\\n Context. Highly magnetized pulsars accreting matter in a binary system are bright\\n sources in the X-ray band (0.1–100 keV). Despite the early comprehension\\n of the basic emission mechanism, their spectral energy distribution is generally\\n described by phenomenological or simplified models.\\n Aims. We propose a study of the spectral emission from the high mass\\n X-ray binary pulsar 4U 0115+63 by means of thermal and bulk Comptonization models\\n based on the physical properties of such objects.\\n Methods. For this purpose, we analyze the BeppoSAX data in the energy range 0.7–100 keV \\n of the 1999 giant outburst, 12 days after the maximum.\\n\\tWe focus first on the phase averaged emission, and then on the phase resolved\\n spectra, by modeling the system using a two-component continuum.\\n Results. At higher energy, above ~7 keV, the emission is due to thermal and\\n bulk Comptonization of the seed photons produced by cyclotron cooling of\\n the accretion column, and at lower energy, the emission is due to thermal\\n Comptonization of a blackbody source in a diffuse halo close to the stellar\\n surface. Phase resolved analysis establishes that most of the emission in\\n the main peak comes from the column, while the low energy component gives\\n a nearly constant contribution throughout the phase.\\n Conclusions. From the best fit parameters, we argue that the cyclotron emission\\n is produced ~ km above the stellar surface, and escapes from\\n the column near its base, where the absorption features are generated by\\n the interaction with the magnetic field in the halo. We find that in 4U 0115+63 ,\\n the observed spectrum is dominated by reprocessed cyclotron radiation, whereas\\n in other bright sources with stronger magnetic fields such as Her X-1, the spectrum\\n is dominated by reprocessed bremsstrahlung.\\n
Loss of serum response factor in keratinocytes results in hyperproliferative skin disease in mice
2009-03-19

The transcription factor serum response factor (SRF) plays a crucial role in the development of several organs. However, its role in the skin has not been explored. Here, we show that keratinocytes in normal human and mouse skin expressed high levels of SRF but that SRF expression was strongly downregulated in the hyperproliferative epidermis of wounded and psoriatic skin. Keratinocyte-specific deletion within the mouse SRF locus during embryonic development caused edema and skin blistering, and all animals died in utero. Postnatal loss of mouse SRF in keratinocytes resulted in the development of psoriasis-like skin lesions. These lesions were characterized by inflammation, hyperproliferation, and abnormal differentiation of keratinocytes as well as by disruption of the actin cytoskeleton. Ultrastructural analysis revealed markedly reduced cell-cell and cell-matrix contacts and loss of cell compaction in all epidermal layers. siRNA-mediated knockdown of SRF in primary human keratinocytes revealed that the cytoskeletal abnormalities and adhesion defects were a direct consequence of the loss of SRF. In contrast, the hyperproliferation observed in vivo was an indirect effect that was most likely a consequence of the inflammation. These results reveal that loss of SRF disrupts epidermal homeostasis and strongly suggest its involvement in the pathogenesis of hyperproliferative skin diseases, including psoriasis.
Automated scaffold selection for enzyme design
2009-03-19

Abstract A major goal of computational protein design is the construction of novel functions on existing protein scaffolds. There the first question is which scaffold is suitable for a specific reaction. Given a set of catalytic residues and their spatial arrangement, one wants to identify a protein scaffold that can host this active site. Here, we present an algorithm called ScaffoldSelection that is able to rapidly search large sets of protein structures for potential attachment sites of an enzymatic motif. The method consists of two steps; it first identifies pairs of backbone positions in pocket‐like regions. Then, it combines these to complete attachment sites using a graph theoretical approach. Identified matches are assessed for their ability to accommodate the substrate or transition state. A representative set of structures from the Protein Data Bank (∼3500) was searched for backbone geometries that support the catalytic residues for 12 chemical reactions. Recapitulation of native active site geometries is used as a benchmark for the performance of the program. The native motif is identified in all 12 test cases, ranking it in the top percentile in 5 out of 12. The algorithm is fast and efficient, although dependent on the complexity of the motif. Comparisons to other methods show that ScaffoldSelection performs equally well in terms of accuracy and far better in terms of speed. Thus, ScaffoldSelection will aid future computational protein design experiments by preselecting protein scaffolds that are suitable for a specific reaction type and the introduction of a predefined amino acid motif. Proteins 2009. © 2009 Wiley‐Liss, Inc.
Advanced Intercross Line Mapping Suggests That Ncf1 (Ean6) Regulates Severity in an Animal Model of Guillain-Barré Syndrome
2009-03-19

Abstract We here present the first genetic fine mapping of experimental autoimmune neuritis (EAN), the animal model of Guillain-Barré syndrome, in a rat advanced intercross line. We identified and refined a total of five quantitative trait loci on rat chromosomes 4, 10, and 12 (RNO4, RNO10, RNO12), showing linkage to splenic IFN-γ secretion and disease severity. All quantitative trait loci were shared with other models of complex inflammatory diseases. The quantitative trait locus showing strongest linkage to clinical disease was Ean6 and spans 4.3 Mb on RNO12, harboring the neutrophil cytosolic factor 1 (Ncf1) among other genes. Polymorphisms in Ncf1, a member of the NADPH oxidase complex, have been associated with disease regulation in experimental arthritis and encephalomyelitis. We therefore tested the Ncf1 pathway by treating rats with a NADPH oxidase complex activator and ameliorated EAN compared the oil-treated control group. By proving the therapeutic effect of stimulating the NADPH oxidase complex, our data strongly suggest the first identification of a gene regulating peripheral nervous system inflammation. Taken together with previous reports, our findings suggest a general role of Ncf1 and oxidative burst in pathogenesis of experimental autoimmune animal models.
Two Distinctive Granite Suites in the Southwestern Bohemian Massif: Reply to F. Finger and M. Rene
2009-03-19

We have carefully evaluated the comments of our colleagues F. Finger and M. Rene¤ and we appreciate their interest in our work and the opportunity to further clarify our viewpoints.In our paper (Siebel et al., 2008) we presented detailed geochemical and geochronological analyses of mainly crustal-derived late Variscan granites (328^321 Ma) from the Bavarian Forest, Moldanubian unit, Bohemian Massif.As an important observation, a high Ca^Sr^Y granite suite south of the Pfahl zone was distinguished from a low Ca^Sr^Y granite suite to the north of this zone; this difference is clearly reflected in the Sr and Nd isotopic signatures of the granites (Siebel et al., 2008, fig.8).From these findings we concluded that the Bavarian Forest is made up of two different crustal blocks.We further concluded that the Bavarian Pfahl shear zone represents a terrane boundary within the Moldanubian unit.Our study supports the terrane-based division of the Bavarian Forest into a Bavarian terrane and an Ostrong terrane as originally proposed by Fiala et al. (1995).Finger & Rene¤ (2009) added data from the Weinsberg granite north of the Pfahl zone, from two granites of the Austrian Mu« hl zone (Haibach, Altenberg) and from a flasergranite close to the Pfahl zone near Regen, Bavaria.Their compilation (Finger & Rene¤ , 2009, fig. 1) does not support our classification, leading them to query the validity of the terrane concept.
Pairs of Creatine Kinase Serum Activity
2009-03-19

Background: For patients with an increased risk of developing myopathy with statin treatment, guidelines recommend to measure CK before and 6-12 weeks after initiating statin treatment.Further, in clinical trials of statins, the number of patients experiencing elevated creatine kinase (CK) serum activity is commonly reported as a safety parameter.Usually exceeding the upper limit of normal (ULN) is used as the basis of description to characterize muscular damage potentially caused by statins.Therefore, basic data on both, proportions of patients with specific CK increases, and absolute and relative CK increases, would be helpful to assess potential CK chances in patients.However, no such data are available so far.Methods: CK activity was measured in a group of blood donors (n=40) at two occasions 10 weeks apart.The 95 th percentile of absolute and relative CK increases was selected to separate true from irrelevant changes.A CK difference was defined to be true if a random measurement error of 10% was exceeded.The numbers of subjects with true CK differences were characterised by both measurements being under, crossing, or being above ULN, and twice ULN, respectively.Results: Five percent of subjects (95 th percentile) had an increase of CK more than 139% (men) or 120% (women), respectively, as compared with the first measurement.Five percent of subjects had an absolute difference of at least 94 U/l (men) and 16 U/l (women), respectively.Thirty-one percent of subjects had both CK activities below 2 times the ULN.Six percent of them had the first measurement under and the second above ULN.In three percent, the first measurement was under and the second above 2 times the ULN.In no subject, the first and the second measurement was above 2 times the ULN.Conclusion: It is concluded that CK serum activity substantially varies between two measurements.The present data provide the basis for developing reference ranges of CK activity pairs by simple variables that can be useful for practitioners and trialists.
γ-Secretase Heterogeneity in the Aph1 Subunit: Relevance for Alzheimer’s Disease
2009-03-20

Tactical Target Intramembrane proteolysis by the γ-secretase complex is important during development and in the pathology of Alzheimer's disease. γ-Secretase has usually been considered as a homogeneous activity. Serneels et al. (p. 639 , published online 19 March; see the Perspective by Golde and Kukar ) now show that the Aph1B component of the γ-secretase complex is responsible for the generation of long β-amyloid species involved in Alzheimer's disease. In a mouse model of Alzheimer's disease, full knockout of Aph1B improved disease phenotypes, without the sort of toxicity previously observed when targeting γ-secretase more generally.