471 research outputs found
Surface emissivity retrieval from VIRTIS/VEX data in the Quetzalpetlatl quadrangle on Venus based on the new MSR multi-spectrum retrieval technique
Surface emissivity is difficult and error-prone to retrieve from VIRTIS measurements of Venus’ nightside. A detailed radiative transfer forward model simulation is used to generate synthetic spectra for given atmospheric and surface parameters. The new MSR multi-spectrum retrieval technique is applied to retrieve atmospheric and surface parameters that allow the synthetic spectra to fit the measurements. The incorporation of expected spatial-temporal correlations between parameters describing a selection of contiguous measurements leads to much more reliable parameters, as does the retrieval of surface emissivity of a surface bin as a parameter that is common to measurements that repeatedly cover that bin, thereby neglecting geologic activity.
The method is applied to Quetzalpetlatl quadrangle including the Lada Terra rise and the Quetzalpetlatl corona. This area combines corona-dominated rises, rifted volcanic rises, and large coronae structures. Retrieved emissivity at 1.02 μm is related to regional geologic units
Gestión financiera y su incidencia en la rentabilidad de la Empresa Desarrollo y Consultoría XXI SAC, Distrito Wanchaq, Periodo 2019
En los últimos años un tema bastante debatido en las empresas es la gestión
financiera, la cual es considerada como un instrumento motor para la generación
de renta, presentando ciertas dificultades y falencias, motivo por el cual se ha
desarrollado el presente estudio, con el objetivo de determinar la incidencia de la
gestión financiera en la rentabilidad de la empresa Desarrollo y Consultoría XXI
SAC, distrito de Wanchaq, año 2019, dicho estudio se desarrolló bajo un enfoque
cuantitativo de nivel correlacional, con un diseño no experimental, en el cual
concluyó que la gestión financiera incide en la rentabilidad de la empresa
Desarrollo y Consultoría XXI SAC, distrito de Wanchaq, año 2019, se identificó que
existe incidencia relativa en base a las respuestas de los encuestados quienes
mencionaron que la gestión financiera en la empresa de estudio no es la más
adecuada, presentando falencias, se ha identificado que no se le da la debida
importancia a esta actividad, ello por falta de conocimiento de los directores, así
como por la falta de recursos para desarrollarla, por tal razón no ha presentado
mayor repercusión en la generación de rent
Bevacizumab-Induced Hypertension in Glioblastoma Patients and Its Potential as a Modulator of Treatment Response
Published online: 21 June 2023
OnlinePublGlioblastoma invasion is the primary mechanism responsible for its dismal prognosis and is the direct result of interactions between glioblastoma cells and the tumor vasculature. The dysregulated microvasculature in glioblastoma tumors and vessels co-opted from surrounding brain tissue support rapid tumor growth and are utilized as pathways for invasive cancer cells. Attempts to target the glioblastoma vasculature with antiangiogenic agents (eg, bevacizumab) have nonetheless shown limited and inconsistent efficacy, and the underlying causes of such heterogeneous responses remain unknown. Several studies have identified that patients with glioblastoma who develop hypertension following treatment with bevacizumab show significant improvement in overall survival compared with normotensive nonresponders. Here we review these findings and discuss the potential of hypertension as a biomarker for glioblastoma treatment response in individual patients and the role of hypertension as a modulator of interactions between tumor cells and cells in the perivascular niche. We suggest that a better understanding of the actions of bevacizumab and hypertension at the cellular level will contribute to developing more effective personalized therapies that address glioblastoma tumor cell invasion.Kaitlin G. Scheer, Lisa M. Ebert, Michael S. Samuel, Claudine S. Bonder, Guillermo A. Gome
Asteroid 2008 TC3, not a polymict ureilitic but a polymict C1 chondrite parent body? Survey of 249 Almahata Sitta fragments
On October 7, 2008, the asteroid 2008 TC3 exploded as it entered the Earth’s atmosphere, producing significant dust (in the atmosphere) and delivering thousands of stones in a strewn field in Sudan, collectively known as the Almahata Sitta (AhS) stones. About 600 fragments were officially recovered in 2008 and 2009. Further rocks were collected since the fall event by local people. From these stones, 249 were classified at the Institut für Planetologie in Münster (MS) known as MS‐xxx or MS‐MU‐xxx AhS subsamples. Most of these rocks are ureilitic in origin (168; 67%): 87 coarse‐grained ureilites, 60 fine‐grained ureilites, 15 ureilites with variable texture/mineralogy, four trachyandesites, and two polymict breccias. We identified 81 non‐ureilitic fragments, corresponding to 33% of the recovered samples studied in Münster. These included chondrites, namely 65 enstatite chondrites (43 EL; 22 EH), 11 ordinary chondrites (OC), one carbonaceous chondrite, and one unique R‐like chondrite. Furthermore, three samples represent a unique type of enstatite achondrite. Since all AhS stones must be regarded as individual specimens independent from each other, the number of fresh ureilite and enstatite chondrite falls in our meteorite collections has been increased by several hundred percent. Overall, the samples weigh between <1 and 250 g and have a mean mass of ~15 g. If we consider—almost 15 years after the fall—the mass calculations, observations during and after the asteroid entered the atmosphere, the mineralogy of the C1 stones AhS 91A and AhS 671, and the experimental work on fitting the asteroid spectrum (e.g., Goodrich et al., 2019; Jenniskens et al., 2010; Shaddad et al., 2010), the main portion of the meteoroid was likely made of the fine‐grained (carbonaceous) dust and was mostly lost in the atmosphere. In particular, the fact that C1 materials were found has important implications for interpreting asteroid 2008 TC3's early spectroscopic results. Goodrich et al. (2019) correctly suggested that if scientists had not recovered the “water‐free” samples (e.g., ureilites, enstatites, and OC) from the AhS strewn field, 2008 TC3 would have been assumed to be a carbonaceous chondrite meteoroid. Considering that the dominating mass of the exploding meteoroid consisted of carbonaceous materials, asteroid 2008 TC3 cannot be classified as a polymict ureilite; consequently, we state that the asteroid was a polymict carbonaceous chondrite breccia, specifically a polymict C1 object that may have formed by late accretion at least 50–100 Ma after calcium–aluminum‐rich inclusions
Desmoglein-2 as a cancer modulator: friend or foe?
Desmoglein-2 (DSG2) is a calcium-binding single pass transmembrane glycoprotein and a member of the large cadherin family. Until recently, DSG2 was thought to only function as a cell adhesion protein embedded within desmosome junctions designed to enable cells to better tolerate mechanical stress. However, additional roles for DSG2 outside of desmosomes are continuing to emerge, particularly in cancer. Herein, we review the current literature on DSG2 in cancer and detail its impact on biological functions such as cell adhesion, proliferation, migration, invasion, intracellular signaling, extracellular vesicle release and vasculogenic mimicry. An increased understanding of the diverse repertoire of the biological functions of DSG2 holds promise to exploit this cell surface protein as a potential prognostic biomarker and/or target for better patient outcomes. This review explores the canonical and non-canonical functions of DSG2, as well as the context-dependent impacts of DSG2 in the realm of cancer
Separation of atomic and molecular ions by ion mobility with an RF carpet
Gas-filled stopping cells are used at accelerator laboratories for the
thermalization of high-energy radioactive ion beams. Common challenges of many
stopping cells are a high molecular background of extracted ions and
limitations of extraction efficiency due to space-charge effects. At the FRS
Ion Catcher at GSI, a new technique for removal of ionized molecules prior to
their extraction out of the stopping cell has been developed. This technique
utilizes the RF carpet for the separation of atomic ions from molecular
contaminant ions through their difference in ion mobility. Results from the
successful implementation and test during an experiment with a 600~MeV/u
Xe primary beam are presented. Suppression of molecular contaminants by
three orders of magnitude has been demonstrated. Essentially background-free
measurement conditions with less than of background events within a
mass-to-charge range of 25 u/e have been achieved. The technique can also be
used to reduce the space-charge effects at the extraction nozzle and in the
downstream beamline, thus ensuring high efficiency of ion transport and
highly-accurate measurements under space-charge-free conditions.Comment: 8 pages, 4 figure
Tokenizer Choice For LLM Training: Negligible or Crucial?
The recent success of LLMs has been predominantly driven by curating the
training dataset composition, scaling of model architectures and dataset sizes
and advancements in pretraining objectives, leaving tokenizer influence as a
blind spot. Shedding light on this underexplored area, we conduct a
comprehensive study on the influence of tokenizer choice on LLM downstream
performance by training 24 mono- and multilingual LLMs at a 2.6B parameter
scale, ablating different tokenizer algorithms and parameterizations. Our
studies highlight that the tokenizer choice can significantly impact the
model's downstream performance, training and inference costs. In particular, we
find that the common tokenizer evaluation metrics fertility and parity are not
always predictive of model downstream performance, rendering these metrics a
questionable proxy for the model's downstream performance. Furthermore, we show
that multilingual tokenizers trained on the five most frequent European
languages require vocabulary size increases of factor three in comparison to
English. While English-only tokenizers have been applied to the training of
multi-lingual LLMs, we find that this approach results in a severe downstream
performance degradation and additional training costs of up to 68%, due to an
inefficient tokenization vocabulary
Efficacy and safety of immune checkpoint inhibitor rechallenge in individuals with hepatocellular carcinoma
BACKGROUND & AIMS: We investigated the efficacy and safety of immune checkpoint inhibitor (ICI) rechallenge in patients with hepatocellular carcinoma (HCC) who received ICI-based therapies in a previous systemic line.
METHODS: In this international, retrospective multicenter study, patients with HCC who received at least two lines of ICI-based therapies (ICI-1, ICI-2) at 14 institutions were eligible. The main outcomes included best overall response and treatment-related adverse events.
RESULTS: Of 994 ICI-treated patients screened, a total of 58 patients (male, n = 41; 71%) with a mean age of 65.0±9.0 years were included. Median systemic treatment lines of ICI-1 and ICI-2 were 1 (range, 1-4) and 3 (range, 2-9), respectively. ICI-based therapies used at ICI-1 and ICI-2 included ICI alone (ICI-1, n = 26, 45%; ICI-2, n = 4, 7%), dual ICI regimens (n = 1, 2%; n = 12, 21%), or ICI combined with targeted therapies/anti-VEGF (n = 31, 53%; n = 42, 72%). Most patients discontinued ICI-1 due to progression (n = 52, 90%). Objective response rate was 22% at ICI-1 and 26% at ICI-2. Responses at ICI-2 were also seen in patients who had progressive disease as best overall response at ICI-1 (n = 11/21; 52%). Median time-to-progression at ICI-1 and ICI-2 was 5.4 (95% CI 3.0-7.7) months and 5.2 (95% CI 3.3-7.0) months, respectively. Treatment-related adverse events of grade 3-4 at ICI-1 and ICI-2 were observed in 9 (16%) and 10 (17%) patients, respectively.
CONCLUSIONS: ICI rechallenge was safe and resulted in a treatment benefit in a meaningful proportion of patients with HCC. These data provide a rationale for investigating ICI-based regimens in patients who progressed on first-line immunotherapy in prospective trials.
IMPACT AND IMPLICATIONS: Therapeutic sequencing after first-line immune checkpoint inhibitor (ICI)-based therapy for advanced hepatocellular carcinoma (HCC) remains a challenge as no available second-line treatment options have been studied in immunotherapy-pretreated patients. Particularly, the role of ICI rechallenge in patients with HCC is unclear, as data from prospective trials are lacking. We investigated the efficacy and safety of ICI-based regimens in patients with HCC pretreated with immunotherapy in a retrospective, international, multicenter study. Our data provide the rationale for prospective trials investigating the role of ICI-based regimens in patients who have progressed on first-line immunotherapy
Measurement of the Spectroscopy of Orbitally Excited B Mesons at LEP
We measure the masses, decay widths and relative production rate of orbitally
excited B mesons using 1.25 million hadronic Z decays recorded by the L3
detector. B-meson candidates are inclusively reconstructed and combined with
charged pions produced at the primary event vertex. An excess of events above
the expected background in the B\pi mass spectrum in the region 5.6-5.8 GeV is
interpreted as resulting from the decay B_u,d^** -> B^(*)\pi, where B_u,d^**
denotes a mixture of l=1 B-meson states containing a u or a d quark. A fit to
the mass spectrum yields the masses and decay widths of the B_1^* and B_2^*
spin states, as well as the branching fraction for the combination of l=1
states. In addition, evidence is presented for the existence of an excited
B-meson state or mixture of states in the region 5.9-6.0 GeV
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