大脑半球胶质瘤切除术中锥体束移位的初步研究

目的 探索大脑半球胶质瘤切除术中锥体束的移位情况及解决方法.方法 选择术前影像学诊断为额、颞、岛叶胶质瘤的患者63例,手术采用仰卧位下额颞入路,术前及术中应用MRI弥散张量成像技术进行扫描,并进行锥体束的追踪描计,对比术前及术中锥体束的位置.结果 锥体束在前后方向上18例发生向前移位,移位距离从0.9 mm至11.4 mm,42例发生向后移位,移位距离从1.7 mm至10.4 mm,3例无移位;锥体束在左右方向上31例发生向外移位,移位距离从1.5 mm至11.2 mm,30例发生向内,移位距离从1.3 mm至8.1 mm,2例无移位.结论锥体束的移位的方向和距离具有不可预测性,最佳解决方案是通过术中影像及神经导航的实时更新并予以保护.     

发作期宽频脑电技术精确定位致痫灶

癫痫外科术前评估的目的就是尽可能地找到或无限接近于致痫灶(epileptogenic zone,EZ),然而致病灶却是一个理论上的概念,手术切除的是否为真正的致痫灶,目前还只能靠术后随访患者能否获得完全的临床缓解来予以证实.所以,在癫痫外科的术前评估中我们会尽量用由发作期脑电、发作期SPECT、fMRI和肌电图等手段确定的发作起始区(seizure-onset zone,SOZ)来无限接近致痫灶[1].     

MRI of frozen tissue demonstrates a phase shift

While temperature mapping is desired during cryosurgery for prostate cancer treatment, an effective approach for this purpose is still needed. We have demonstrated a phase shift with temperature in our in vivo canine experiments and ex vivo tissue sample experiments within the frozen tissue. The phase shift is much larger (～0.7 °/°C with an echo time of 0.1 ms at 0.5 T) in magnitude than that predicted by conventional proton resonant frequency shift (0.008 °/°C). It shows little dependence on the echo times used and thus is not due to a frequency change, although frequency‐dependent phase shift has been observed near the frozen tissue. This phase shift varies monotonically with temperature within the frozen tissue and therefore may be potentially used as a novel temperature mapping approach in cryoablation applications. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.     

Geospatial revolution and remote sensing LiDAR in Mesoamerican archaeology

The application of light detection and ranging (LiDAR), a laser-based remote-sensing technology that is capable of penetrating overlying vegetation and forest canopies, is generating a fundamental shift in Mesoamerican archaeology and has the potential to transform research in forested areas world-wide. Much as radiocarbon dating that half a century ago moved archaeology forward by grounding archaeological remains in time, LiDAR is proving to be a catalyst for an improved spatial understanding of the past. With LiDAR, ancient societies can be contextualized within a fully defined landscape. Interpretations about the scale and organization of densely forested sites no longer are constrained by sample size, as they were when mapping required laborious on-ground survey. The ability to articulate ancient landscapes fully permits a better understanding of the complexity of ancient Mesoamerican urbanism and also aids in modern conservation efforts. The importance of this geospatial innovation is demonstrated with newly acquired LiDAR data from the archaeological sites of Caracol, Cayo, Belize and Angamuco, Michoacán, Mexico. These data illustrate the potential of technology to act as a catalytic enabler of rapid transformational change in archaeological research and interpretation and also underscore the value of on-the-ground archaeological investigation in validating and contextualizing results.     

Effect of pre-donation fluid intake on fluid shift from interstitial to intravascular compartment in blood donors

Background

Fluid shifts from interstitial to intravascular space during blood donation helps in compensating the lost blood volume. We aimed to determine the volume of fluid shift following donation in donors with and without pre-donation fluid intake.

Giant exciton-enhanced shift currents and direct current conduction with subbandgap photo excitations produced by many-electron interactions

Shift current is a direct current generated from nonlinear light–matter interaction in a noncentrosymmetric crystal and is considered a promising candidate for next-generation photovoltaic devices. The mechanism for shift currents in real materials is, however, still not well understood, especially if electron–hole interactions are included. Here, we employ a first-principles interacting Green’s-function approach on the Keldysh contour with real-time propagation to study photocurrents generated by nonlinear optical processes under continuous wave illumination in real materials. We demonstrate a strong direct current shift current at subbandgap excitation frequencies in monolayer GeS due to strongly bound excitons, as well as a giant excitonic enhancement in the shift current coefficients at above bandgap photon frequencies. Our results suggest that atomically thin two-dimensional materials may be promising building blocks for next-generation shift current devices.

When continuous wave light is shone on a noncentrosymmetric crystal, a direct current (DC) can arise due to a second-order optical response of the crystal. The origin of this current is interpreted to be related to the “shift” (1–4) of the intracell coordinates of the excited electron. This so-called shift current is proposed as an alternative to the photocurrent generated by traditional semiconductor p–n junctions (i.e., a junction between hole-doped [p-type] and electron-doped [n-type] semiconductors) for photovoltaic applications (5, 6). Unlike conventional photovoltaic devices, shift current is a bulk phenomenon, which does not require a p–n junction to separate the optically generated electron–hole pair for a DC. Moreover, recent studies reveal that the photocarriers in shift current can have long travel distances, which is distinct from the usual drift transport mechanism in traditional solar cells (7, 8) and makes shift current a promising candidate for efficient energy conversion.Despite many investigations over the past decade, a basic understanding of shift currents is far from complete. Most theoretical studies to date rely on the assumption of having noninteracting particles (3–6, 9–11). Given that it is well known that light-induced electron–hole pairs can form bound or resonant excitons (correlated electron–hole states), which dominate and qualitatively change the absorption features of semiconductors, electron–hole interactions or excitons are expected to play a large role in shift currents, especially for reduced dimensional systems. However, it is not straight forward to generalize existing ab initio methods [such as the ab initio GW plus Bethe-Salpeter equation (GW-BSE) approach (12)], used to understand and compute excitonic effects in linear optical absorption, to study nonlinear optical responses. Different model approaches to investigate the effects of many-electron interactions on nonlinear optical responses of materials have been proposed. For instance, a Floquet-based model Hamiltonian formalism showed that excitonic effects enhance nonlinear response (13). In the specific case of second harmonic generation, first-principles approaches have been developed and applied to real materials, for instance, by making an approximation to the full many-body perturbation theory treatment (14, 15) or to the time-dependent density function theory, in which electron interaction effects are taken into account via simplified kernels (16). A real-time formulation based on propagating the time-dependent Schrodinger equation has also been developed (17) and applied to second harmonic generation (18). For shift currents in real materials, only one recent study considered the effects of excitons on the linear optical coefficient that might influence shift currents, but these authors included only the effects of excitons on the electromagnetic field profile in a bulk sample, and the crucial process of shift current generation itself is still treated within an independent-particle picture (11). Thus, there is still no first-principles calculation and understanding of the role of many-electron interactions, particularly those due to excitons, on shift currents.Here, we show from first principles that 1) bound exciton states in the band gap can generate substantial shift currents, and 2) excitonic effects in the electron–hole continuum part of the spectrum can also greatly enhance shift currents due to the enhancement of the optical matrix elements from the coherence of the electron–hole pairs and to interexciton couplings that arose in the nonlinear responses.     

Early acute antibody-mediated rejection of a negative flow crossmatch 3rd kidney transplant with exclusive disparity at HLA-DP

Donor-specific alloantibodies (DSA) to HLA-DP may cause antibody-mediated rejection (AMR), especially in re-transplants. We describe the immunization history of a patient who received 3 kidney transplants; the 3rd kidney was completely matched except at DPA1 and DPB1. Prior to the 3rd transplant, single antigen bead analysis (SAB) showed DSA reactivity against DPA1 shared by the 1st and 3rd donors, but B and T flow crossmatch (FXM) results were negative. Within 11 days the 3rd transplant underwent acute C4d+ AMR which coincided with the presence of complement (C1q)-binding IgG1 DSA against donor DPA1 and DPB1. Using HLAMatchmaker and SAB, we provide evidence that eplet (epitope) spreading on DPA1 and eplet sharing on differing DPB1 alleles of the 1st and 3rd transplants was associated with AMR. Since weak DSA to DPA1/DPB1 may induce acute AMR with negative FXM, donor DPA1/DPB1 high resolution typing should be considered in sensitized patients with DP-directed DSA.     

Unveiling the “invisible” druggable conformations of GDP-bound inactive Ras

The prevalent view on whether Ras is druggable has gradually changed in the recent decade with the discovery of effective inhibitors binding to cryptic sites unseen in the native structures. Despite the promising advances, therapeutics development toward higher potency and specificity is challenged by the elusive nature of these binding pockets. Here we derive a conformational ensemble of guanosine diphosphate (GDP)-bound inactive Ras by integrating spin relaxation-validated atomistic simulation with NMR chemical shifts and residual dipolar couplings, which provides a quantitative delineation of the intrinsic dynamics up to the microsecond timescale. The experimentally informed ensemble unequivocally demonstrates the preformation of both surface-exposed and buried cryptic sites in Ras•GDP, advocating design of inhibition by targeting the transient druggable conformers that are invisible to conventional experimental methods. The viability of the ensemble-based rational design has been established by retrospective testing of the ability of the Ras•GDP ensemble to identify known ligands from decoys in virtual screening.

Situated in a central position of the complex intracellular signaling network, Ras proteins play critical roles in regulating cell growth, differentiation, migration and apoptosis through cycling between the guanosine diphosphate (GDP)-bound inactive and guanosine triphosphate (GTP)-bound active forms (1, 2). Aberrant signaling caused by oncogenic mutations in Ras that break this physiological balance can result in uncontrolled cell proliferation and ultimately the development of human malignancies (3, 4). Despite its well-established role in tumorigenesis and the extensive efforts to target this oncoprotein in past decades, clinically approved therapies remain unavailable. One obstacle to the development of anti-Ras drugs lies in the native structures of active and inactive Ras that lack apparently druggable pockets for high-affinity interactions with inhibitory compounds (5–7).Both the active and inactive forms of Ras, however, are inherently flexible, populating rare conformers distinct from the native structures and presenting alternative opportunities for drug discovery (8–11). For example, in GTP-bound active Ras, a major and minor state (termed states 2 and 1, respectively) coexist in solution and exchange on a millisecond timescale, with state 1 showing surface roughness unobserved in the major state (12–18). The direct visibility of state 1 in the one-dimensional ³¹P NMR spectra of active Ras largely facilitated its early discovery and characterization (12, 19). And the available mutants of H-Ras (e.g., T35A), or the homolog M-Ras, which predominantly assume the state 1 conformation, further promoted the atomic-resolution studies of its structure and internal dynamics, as well as the concomitant drug discovery efforts targeting this low-populated conformer (17, 18, 20).In comparison to the intensive studies on active Ras, research on the dynamics of GDP-bound inactive Ras has lagged far behind, presumably due to its high degree of spectral homogeneity with little sign of resonance splitting or exchange broadening at room temperature (21). The previously reported cryptic pockets for covalent and noncovalent inhibitors of Ras•GDP (22–24), which are unseen in the compound-free structure, nevertheless indicate that the inactive form is also structurally plastic. The recent relaxation-based NMR experiments carried out at low temperature successfully captured the intrinsic microsecond timescale motions in Ras•GDP, which map to regions that overlap with those rearranged on the binding of inhibitors (11). However, the structural information of the transiently formed excited state, in the form of chemical shifts, is not available from the relaxation measurements, owing to the fast exchange rate on the chemical shift timescale. Moreover, unlike the case of active Ras, there are no known mutations that can stabilize the excited state of Ras•GDP for investigations using conventional biophysical techniques. Thus far, the sparsely populated conformations of inactive Ras derived from its microsecond dynamics remain poorly understood, precluding structure-based rational drug discovery.To address these challenges, in this work we constructed a solution ensemble of Ras•GDP by integrating atomistic computer simulation with diverse NMR experimental parameters containing complementary information about the intrinsic protein motions on timescales from picoseconds to microseconds. This NMR-based ensemble well covers the slow dynamics as probed by spin relaxation and provides an atomic-resolution delineation of thermally accessible conformations, including those bearing surface or buried pockets similar to the cryptic pockets previously observed in the inhibitor-bound forms. The utility of the Ras•GDP ensemble in the development of inhibitors is demonstrated by ensemble-based virtual screening, which achieves an impressive level of enrichment of known binders.     

Central Nervous System and Ocular Manifestations in Puumala Hantavirus Infection

Puumala hantavirus (PUUV), carried and spread by the bank vole (Myodes glareolus), causes a mild form of hemorrhagic fever with renal syndrome (HFRS) called nephropathia epidemica (NE). Acute high fever, acute kidney injury (AKI), thrombocytopenia, and hematuria are typical features of this syndrome. In addition, headache, blurred vision, insomnia, vertigo, and nausea are commonly associated with the disease. This review explores the mechanisms and presentations of ocular and central nervous system involvement in acute NE.