Miracle-dz/UniFAR-FTUs huggingface dataset:
The Emerging Role of Targeted Therapy and Immunotherapy in the Management of Brain Metastases in Non-Small Cell Lung Cancer

Lung cancer is the worldwide leading cause of cancer-related mortality in men and second leading in women. Brain metastases (BM) account for 10% of non-small cell lung cancer (NSCLC) patients at initial presentation, with another 25–40% developing BM during the course of their disease. In the last decade, the field of precision oncology has led to the discovery of a multitude of heterogenous molecular abnormalities within NSCLC as well as the development of tyrosine kinase inhibitors that target them. In this review, the focus will be on targeted therapy and immunotherapy that show efficacy in BM rather than conventional treatment for multiple BM (such as surgical resection, WBRT, or stereotactic radiosurgery).
Structure of catalase determined by MicroED

MicroED is a recently developed method that uses electron diffraction for structure determination from very small three-dimensional crystals of biological material. Previously we used a series of still diffraction patterns to determine the structure of lysozyme at 2.9 Å resolution with MicroED (Shi et al., 2013). Here we present the structure of bovine liver catalase determined from a single crystal at 3.2 Å resolution by MicroED. The data were collected by continuous rotation of the sample under constant exposure and were processed and refined using standard programs for X-ray crystallography. The ability of MicroED to determine the structure of bovine liver catalase, a protein that has long resisted atomic analysis by traditional electron crystallography, demonstrates the potential of this method for structure determination. DOI: http://dx.doi. org/10.7554/eLife.03600. 001
Factors influencing the identification of major genes in a complex disease genome scan

A two‐stage linkage strategy was employed to identify major genes for a simulated complex disease via a genome scan. The importance of several approaches for improving the ability to locate major genes has been illustrated. These approaches are: adjusting for covariates, ascertaining through multiple affected family members, increasing the sample size, and using multipoint linkage analysis. © 1997 Wiley‐Liss, Inc.
Transcription-associated recombination is independent of XRCC2 and mechanistically separate from homology-directed DNA double-strand break repair

It has previously been shown that transcription greatly enhances recombination in mammalian cells. However, the proteins involved in catalysing this process and the recombination pathways involved in transcription-associated recombination (TAR) are still unknown. It is well established that both the BRCA2 protein and the RAD51 paralog protein XRCC2 are required for homologous recombination. Here, we show that the BRCA2 protein is also required for TAR, while the XRCC2 protein is not involved. Expression of the XRCC2 gene in XRCC2 mutated irs1 cells restores the defect in homologous recombination repair of an I-SceI-induced DNA double-strand break, while TAR is unaffected. Interestingly, the XRCC2-deficient irs1 cells are also proficient in recombination induced at slowed replication forks, suggesting that TAR is mechanistically linked with this recombination pathway. In conclusion, we show that TAR depends on BRCA2 but is independent of XRCC2, and that this recombination pathway is separate from that used to repair a two-ended DNA double-strand break.
Uniformly Moving Dislocations

An expression is derived for the displacements in an isotropic elastic medium which contains an edge dislocation moving with uniform velocity c. When c=0 the solution reduces to that given by Burgers for a stationary edge dislocation. The energy density in the medium becomes infinite as c approaches c2, the velocity of shear waves in the medium; this velocity therefore sets a limit beyond which the dislocation cannot be accelerated by applied stresses. The atomic structure of the medium is next partly taken into account, following the method already used by Peierls and Nabarro for the stationary dislocation. The solution found in this way differs from the one in which the atomic structure is neglected only within a region of width ζ which extends not more than a few atomic distances from the centre. ζ varies with c and vanishes when c=cr, the velocity of Rayleigh waves. It becomes negative when cr< c<c2. Thus cr rather than c2 appears to be the limiting velocity when the atomic nature of the medium is taken into account. Since cr similar, equals 0.9c2 the difference is not of much importance. The same method applied to a screw dislocation gives, in the purely elastic case, the expression already derived by Frank. The corresponding Peierls-Nabarro calculation shows that the width ζ is proportional to (1 - c2/c22)½. This "relativistic" behaviour is analogous to Frenkel and Kontorowa's results for their one-dimensional dislocation model.
Alternatives to stabilization scenarios

Studies attempting to constrain climate sensitivity, or equilibrium surface warming in response to a doubling of atmospheric carbon dioxide, by comparing models with observations report a wide range of distributions, particularly regarding the upper bound. There is, by contrast, a considerable consensus surrounding the transient climate response, in large part because it is directly related to observed warming attributable to greenhouse gases. We argue that scenarios which can exploit this consensus may be preferable to stabilization scenarios for practical policy‐making purposes. The difficulty of ruling out a high equilibrium warming response to elevated carbon dioxide levels may provide an opportunity for reassessment of the stabilization scenario as the centerpiece of climate policy in favour of scenarios that are more directly constrained by the transient response.
Geodetic precession or dragging of inertial frames?

In metric theories of gravity the principle of general covariance allows one to describe phenomena by means of any convenient choice of coordinate system. In this paper it is shown that in an appropriately chosen coordinate system, geodetic precession of a gyroscope orbiting a spherically symmetric, spinning mass can be recast as a Lense-Thirring frame-dragging effect without invoking spatial curvature. The origin of this reference frame moves around the source but the frame axes point in fixed directions. The drag can be interpreted to arise from the orbital angular momentum of the source around the origin of the reference frame. In this reference frame the effects of geodetic precession and Lense-Thirring drag due to intrinsic angular momentum of the source have the same origin, namely, gravitomagnetism.
Complete Genome Sequence of the Dehalorespiring Bacterium Desulfitobacterium hafniense Y51 and Comparison withDehalococcoides ethenogenes 195

ABSTRACT Desulfitobacterium strains have the ability to dechlorinate halogenated compounds under anaerobic conditions by dehalorespiration. The complete genome of the tetrachloroethene (PCE)-dechlorinating strain Desulfitobacterium hafniense Y51 is a 5,727,534-bp circular chromosome harboring 5,060 predicted protein coding sequences. This genome contains only two reductive dehalogenase genes, a lower number than reported in most other dehalorespiring strains. More than 50 members of the dimethyl sulfoxide reductase superfamily and 30 paralogs of the flavoprotein subunit of the fumarate reductase are encoded as well. A remarkable feature of the genome is the large number of O-demethylase paralogs, which allow utilization of lignin-derived phenyl methyl ethers as electron donors. The large genome reveals a more versatile microorganism that can utilize a larger set of specialized electron donors and acceptors than previously thought. This is in sharp contrast to the PCE-dechlorinating strain Dehalococcoides ethenogenes 195, which has a relatively small genome with a narrow metabolic repertoire. A genomic comparison of these two very different strains allowed us to narrow down the potential candidates implicated in the dechlorination process. Our results provide further impetus to the use of desulfitobacteria as tools for bioremediation.
Manufacturing and characterization of magnetorheological fluids

Magnetorheological (MR) fluids are stable suspensions of magnetic particles in a carrying fluid exhibiting controllable rheological behavior in the presence of a magnetic field. Magnetorheological effect represents a reversible increase, due to an external magnetic field, of effective viscosity. MR fluids and devices have the potential to revolutionize the design of hydraulic systems, actuators, valves, active shock and vibration dampers, and other components used in mechanical systems. MR fluids that are currently available suffer from high initial viscosity values and low stability. Hence, there is a compelling need to optimize the MR fluid manufacturing process to produce optimum MR fluid characteristics. The present study proposes to manufacture an optimum composition of a MR fluid in terms of its quality and properties. A high-speed bead mill blending machine is used to manufacture the fluid. Characterization studies are conducted to evaluate the produced fluid.
Lyapunov Function-Based Current Controller to Control Active and Reactive Power Flow From a Renewable Energy Source to a Generalized Three-Phase Microgrid System

In this paper, a novel current control technique, implemented in the a-b-c frame, for a three-phase inverter is proposed to control the active and reactive power flow from the renewable energy source to a three-phase generalized microgrid system. The proposed control system not only controls the grid power flow but also reduces the grid current total harmonic distortion in the presence of typical nonlinear loads. The control system shapes the grid current taking into account the grid voltage unbalance, harmonics as well as unbalance in line side inductors. The stability of the control system is ensured by the direct method of Lyapunov. A SRC is also proposed to improve the performance of the current controller by estimating the periodic disturbances of the system. The proposed control system (implemented digitally) provides superior performance over the conventional multiple proportional-integral and proportional-resonant control methods due to the absence of the PARK's transformation blocks as well as phase lock loop requirement in the control structure. A new inverter modeling technique is also presented to take care of unbalances both in grid voltages and line side inductors. Experimental results are provided to show the efficacy of the proposed control system.
A new rail-to-rail comparator with adaptive power control for low power SAR ADCs in biomedical application

In this paper, a new IV rail-to-rail comparator is presented with low noise, high speed and low power consumption. We utilize current mirrors to overcome the kickback noise. A new adaptive power control (APC) technique is also proposed to minimize the power dissipation of the comparator. Moreover, it provides an optimized and stable power dissipation irrelative to process and bias variation. A prototype IV rail-to-rail SAR ADC for biomedical application has been implemented in 0. 18μm TSMC CMOS technology. It consumes 2.86 μW at 250kS/s and the figure of merit is 85.7 fJ/conversion-step. It shows that this work efficiently reduces 52% to 80% power consumption of the dynamic comparator at 500kS/s to 125kS/s.
A trial of unrelated donor marrow transplantation for children with severe sickle cell disease.

Children with sickle cell disease experience organ damage, impaired quality of life, and premature mortality. Allogeneic bone marrow transplant from an HLA-matched sibling can halt disease progression but is limited by donor availability. A Blood and Marrow Transplant Clinical Trials Network (BMT CTN) phase 2 trial conducted from 2008 to 2014 enrolled 30 children aged 4 to 19 years; 29 were eligible for evaluation. The primary objective was 1-year event-free survival (EFS) after HLA allele-matched (at HLA-A, -B, -C, and -DRB1 loci) unrelated donor transplant. The conditioning regimen included alemtuzumab, fludarabine, and melphalan. Graft-versus-host disease (GVHD) prophylaxis included calcineurin inhibitor, short-course methotrexate, and methylprednisolone. Transplant indications included stroke (n = 12), transcranial Doppler velocity >200 cm/s (n = 2), ≥3 vaso-occlusive pain crises per year (n = 12), or ≥2 acute chest syndrome episodes (n = 4) in the 2 years preceding enrollment. Median follow-up was 26 months (range, 12-62 months); graft rejection was 10%. The 1- and 2-year EFS rates were 76% and 69%, respectively. The corresponding rates for overall survival were 86% and 79%. The day 100 incidence rate of grade II-IV acute GVHD was 28%, and the 1-year incidence rate of chronic GVHD was 62%; 38% classified as extensive. There were 7 GVHD-related deaths. A 34% incidence of posterior reversible encephalopathy syndrome was noted in the first 6 months. Although the 1-year EFS met the prespecified target of ≥75%, this regimen cannot be considered sufficiently safe for widespread adoption without modifications to achieve more effective GVHD prophylaxis. The BMT CTN #0601 trial was registered at www.clinicaltrials. gov as #NCT00745420.
Identification of functional sine oculis motifs in the autoregulatory element of its own gene, in the eyeless enhancer and in the signalling gene hedgehog

In Drosophila, the sine oculis (so) gene is important for the development of the entire visual system, including Bolwig's organ, compound eyes and ocelli. Together with twin of eyeless, eyeless, eyes absent and dachshund, so belongs to a network of genes that by complex interactions initiate eye development. Although much is known about the genetic interactions of the genes belonging to this retinal determination network, only a few such regulatory interactions have been analysed down to the level of DNA-protein interactions. Previous work in our laboratory identified an eye/ocellus specific enhancer of the sine oculis gene that is directly regulated by eyeless and twin of eyeless. We further characterized this regulatory element and identified a minimal enhancer fragment of so that sets up an autoregulatory feedback loop crucial for proper ocelli development. By systematic analysis of the DNA-binding specificity of so we identified the most important nucleotides for this interaction. Using the emerging consensus sequence for SO-DNA binding we performed a genome-wide search and have thereby been able to identify eyeless as well as the signalling gene hedgehog as putative targets of so. Our results strengthen the general assumption that feedback loops among the genes of the retinal determination network are crucial for proper development of eyes and ocelli.
Motexafin gadolinium: a novel radiosensitizer for brain tumors

For a variety of reasons, the management of brain tumors, both primary and metastatic, remains a considerable challenge. As most systemic therapies do not cross the BBB at therapeutic doses, radiation and surgery have played primary roles in the management of these diseases. Despite significant advances in surgical techniques and radiation delivery, outcomes for most adult brain tumors continue to be poor. In an effort to enhance the effects of radiation in the brain, a variety of radiation sensitizers, including motexafin gadolinium, have been investigated. In the following manuscript, we summarize motexafin gadolinium and its role in brain tumors.
A proof of Mader's conjecture on large clique subdivisions in C4 ‐free graphs

Given any integers s,t⩾2 , we show that there exists some c=c(s,t)>0 such that any Ks,t ‐free graph with average degree d contains a subdivision of a clique with at least cds/2(s−1) vertices. In particular, when s=2, this resolves in a strong sense the conjecture of Mader in 1999 that every C4 ‐free graph has a subdivision of a clique with order linear in the average degree of the original graph. In general, the widely conjectured asymptotic behaviour of the extremal density of Ks,t ‐free graphs suggests our result is tight up to the constant c(s,t) .
Chemokines induce migration and changes in actin polymerization in adult rat brain microglia and a human fetal microglial cell line in vitro

Microglia, the resident macrophages of the central nervous system, are the primary cells to respond to injury in the brain, both in inflammation, e.g., in multiple sclerosis, and trauma. Chemokines are potential mediators of microglial cell recruitment to sites of injury; thus, the ability of microglia to migrate in response to a number of chemokines was assessed. The chemokines monocyte chemoattractant protein 1, macrophage inflammatory protein 1α, macrophage inflammatory protein 1β, RANTES (regulated upon activation normal T cell expressed and secreted), interleukin 8, and IP‐10 (interferon gamma inducible protein‐10), induce migration and changes in the distribution of f‐actin in adult rat microglia and a human microglial cell line, CHME3, in vitro. Both cell types show a significant migration response, above control levels, to all the chemokines tested in a typical dose‐dependent manner. These chemokines also induced a reorganization of the actin cytoskeleton of the cells. This study indicates that chemokines play an important role in the recruitment of microglia to areas of central nervous system inflammation. J. Neurosci. Res. 55: 17–23, 1999. © 1999 Wiley‐Liss, Inc.
Partial Tenon’s capsule resection with adjunctive mitomycin C in Ahmed glaucoma valve implant surgery

Aim: To verify if partial intraoperative Tenon’s capsule resection (PTCR) with adjunctive mitomycin C is effective in developing thin, avascular blebs in eyes undergoing Ahmed glaucoma valve insertion, and to assess the efficacy and safety of this procedure. Methods: A multicentre, prospective, alternating case assignment, investigator unmasked, parallel group, comparative interventional study was conducted in four Latin American countries (Argentina, Brazil, Colombia, and Peru). Ahmed glaucoma valve implant insertion with PTCR (group A) and without PCTR (group B) was performed in neovascular glaucomatous eyes without previous surgery. Adjunctive mitomycin C (MMC) was used in both groups. Patients were examined 1 day, 10 days, 1 month, 2 months, 3 months, 6 months, and 1 year following the surgery. Intraocular pressure (IOP) and the appearance of the bleb were evaluated at each examination. Appearance of the bleb was classified at both the 1 month mark and last examinations into one of three groups: flat and vascularised; elevated avascular; or elevated and not avascular. Results: 92 eyes from 92 patients were included in the study. The preoperative mean IOP was 50.0 (SD 10.5) mm Hg in group A and 48.4 (11.7) in group B (p>0.05). Statistically significant IOP reductions were observed at all periods of follow up. 12 months after surgery, the mean IOP was 17.2 (5.0) mm Hg in group A and 18.3 (8.7) mm Hg in group B (p>0.05). A hypertensive phase occurred in 40.0% in group A and in 46.8% in group B (p>0.05). At the 1 month and the final follow up, the blebs in all eyes were considered elevated and not avascular. The success rate (IOP⩽21 mm Hg) at 1 year after surgery was 70.4% in group A and 77.7% in group B (p>0.05). Overall, 74.2% of the patients achieved an IOP ⩽21 mm Hg and 55.2% an IOP⩽17 mm Hg, with or without additional medication administered to lower IOP. The incidence of complications was similar in both groups. Conclusions: In eyes undergoing Ahmed valve implantation for neovascular glaucoma, PCTR with MMC augmentation showed no additional benefits or complications over MMC augmentation alone; no avascular bleb was obtained with this technique. The incidence of a hypertensive phase was lower than reported in previous studies.
Using digital micromirror devices for focusing light through turbid media

The holy grail of biomedical optical imaging is to perform microscopy deep inside living tissue. Unfortunately, biological tissue scatters light, which prevents the formation of a sharp focus. However, recently it was shown that wavefront shaping can be used to focus light through and inside turbid materials. So far, most experiments used liquid crystal devices, which are too slow to match the dynamics of perfused tissue. Since DMD technology is approximately 1000 times faster, it may bring wavefront shaping to in-vivo applications. We will compare analytically the performance of different methods for focusing light through scattering media with an intensity-only light modulator.
Early patterning of the spider embryo: a cluster of mesenchymal cells at the cumulus produces Dpp signals received by germ disc epithelial cells

In early embryogenesis of spiders, the cumulus is characteristically observed as a cellular thickening that arises from the center of the germ disc and moves centrifugally. This cumulus movement breaks the radial symmetry of the germ disc morphology, correlating with the development of the dorsal region of the embryo. Classical experiments on spider embryos have shown that a cumulus has the capacity to induce a secondary axis when transplanted ectopically. In this study, we have examined the house spider, Achaearanea tepidariorum, on the basis of knowledge from Drosophila to characterize the cumulus at the cellular and molecular level. In the cumulus, a cluster of about 10 mesenchymal cells, designated the cumulus mesenchymal (CM) cells, is situated beneath the epithelium, where the CM cells migrate to the rim of the germ disc. Germ disc epithelial cells near the migrating CM cells extend cytoneme-like projections from their basal side onto the surface of the CM cells. Molecular cloning and whole-mount in situ hybridization showed that the CM cells expressed a spider homolog of Drosophila decapentaplegic (dpp), which encodes a secreted protein that functions as a dorsal morphogen in the Drosophila embryo. Furthermore, the spider Dpp signal appeared to induce graded levels of the phosphorylated Mothers against dpp (Mad) protein in the nuclei of germ disc epithelial cells. Adding data from spider homologs of fork head, orthodenticle and caudal, we suggest that, in contrast to the Drosophila embryo, the progressive mesenchymal-epithelial cell interactions involving the Dpp-Mad signaling cascade generate dorsoventral polarity in accordance with the anteroposterior axis formation in the spider embryo. Our findings support the idea that the cumulus plays a central role in the axial pattern formation of the spider embryo.