gebhart/patrepeval huggingface dataset:
Data from Concurrent Definitive Immunoradiotherapy for Patients with Stage III–IV Head and Neck Cancer and Cisplatin Contraindication (2023)

&lt;div&gt;AbstractPurpose:&lt;p&gt;Although cisplatin plus radiotherapy is a standard treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC), cisplatin contraindication is common. Radiation elicits and promotes tumor-directed immune stimulation, which may potentiate anti–PD-1 therapy. We provide the first efficacy report of combined pembrolizumab and definitive radiotherapy in LA-HNSCC.&lt;/p&gt;Patients and Methods:&lt;p&gt;This single-arm, multi-institution, phase II study (NCT02609503) enrolled 29 cisplatin-ineligible patients. Patients received radiotherapy concurrently with three cycles of pembrolizumab 200 mg every 3 weeks followed by three adjuvant cycles. The primary endpoint was a progression-free survival (PFS) of ≥16 months. Correlative studies included peripheral blood flow cytometry and Luminex cytokine profiling.&lt;/p&gt;Results:&lt;p&gt;Reasons for cisplatin ineligibility included otopathy (69.0%), nephropathy (20.7%), and neuropathy (6.9%). With median follow-up of 21 months, estimated 24-month PFS and overall survival rates were 71% (95% confidence interval, 49%–84%) and 75% (51%–88%). The primary PFS endpoint has exceeded the hypothesis and its median has not been reached. Toxicities were typical of radiotherapy; however, high rates of grade 3/4 lymphopenia (58.6%) were observed. Flow cytometry revealed a relative decline in CD4 T cells and B cells, but not CD8 T cells. Upon treatment, frequencies of transitional B cells and tissue-like memory B cells increased, while resting memory B cells decreased. Patients with progression had greater percentages of baseline naïve B cells and fewer marginal zone B cells.&lt;/p&gt;Conclusions:&lt;p&gt;Pembrolizumab and radiotherapy is efficacious in LA-HNSCC and should be evaluated in a randomized trial. The observed changes in B-cell markers deserve further study both as potential biomarkers and as therapeutic targets.&lt;/p&gt;&lt;/div&gt;
A formal synthesis of (.+-.)-ibogamine (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA formal synthesis of (.+-.)-ibogamineJohn W. Huffman, Giovindaswamy Shanmugasundaram, Reuben Sawdaye, Panolil C. Raveendranath, and Ranjit C. DesaiCite this: J. Org. Chem. 1985, 50, 9, 1460–1464Publication Date (Print):May 1, 1985Publication History Published online1 May 2002Published inissue 1 May 1985https://pubs.acs.org/doi/10.1021/jo00209a019https://doi.org/10.1021/jo00209a019research-articleACS PublicationsRequest reuse permissionsArticle Views644Altmetric-Citations16LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Effects of oestradiol and tamoxifen on VEGF, soluble VEGFR-1, and VEGFR-2 in breast cancer and endothelial cells (2005)

Angiogenesis is regulated by the balance between pro- and antiangiogenic factors. Vascular endothelial growth factor (VEGF), acting via the receptors VEGFR-1 and VEGFR-2, is a key mediator of tumour angiogenesis. The soluble form of the VEGF receptor-1 (sVEGFR-1) is an important negative regulator of VEGF-mediated angiogenesis. The majority of breast cancers are oestrogen dependent, but it is not fully understood how oestrogen and the antioestrogen, tamoxifen, affect the balance of angiogenic factors. Angiogenesis is a result of the interplay between cancer and endothelial cells, and sex steroids may exert effects on both cell types. In this study we show that oestradiol decreased secreted sVEGFR-1, increased secreted VEGF, and decreased the ratio of sVEGFR-1/VEGF in MCF-7 human breast cancer cells. The addition of tamoxifen opposed these effects. Moreover, human umbilical vein endothelial cells (HUVEC) incubated with supernatants from oestradiol-treated MCF-7 cells exhibited higher VEGFR-2 levels than controls. In vivo, MCF-7 tumours from oestradiol+tamoxifen-treated nude mice exhibited decreased tumour vasculature. Our results suggest that tamoxifen and oestradiol exert dual effects on the angiogenic environment in breast cancer by regulating cancer cell-secreted angiogenic ligands such as VEGF and sVEGFR-1 and by affecting VEGFR-2 expression of endothelial cells.
The Japanese Cipher Machines (2006)

This chapter contains sections titled: Japanese Signaling Conventions Half-Rotors Components of the RED Machine Cribbing RED Ciphertext Generalized Vowels and Consonants “Climb Mount Itaka” – War! Components of the PURPLE Machine The PURPLE Keys Cribbing PURPLE: Finding the V-Stepper Cribbing PURPLE: Finding the C-Steppers
Deep‐ultraviolet laser ablation electrospray ionization mass spectrometry (2019)

A 193-nm wavelength deep ultraviolet laser was used for ambient laser ablation electrospray ionization mass spectrometry of biological samples. A pulsed ArF excimer laser was used to ablate solid samples, and the resulting plume of the desorbed material merged with charged electrospray droplets to form ions that were detected with a quadrupole time-of-flight mass spectrometer. Solutions containing peptide and protein standards up to 66-kDa molecular weight were deposited on a metal target, dried, and analyzed. No fragmentation was observed from peptides and proteins as well as from the more easily fragmented vitamin B<sub>12</sub> molecule. The mass spectra contained peaks from multiply charged ions that were identical to conventional electrospray. Deep UV laser ablation of tissue allowed detection of lipids from untreated tissue. The mechanism of ionization is postulated to involve absorption of laser energy by a fraction of the analyte molecules that act as a sacrificial matrix or by residual water in the sample.
Effects of hypoxia on density of beta-adrenergic receptors (1981)

Exposure to chronic hypoxia results in a lower resting heart rate and a blunted cardiovascular responsiveness to beta-adrenergic receptor stimulation. Possible effects of acclimatization to high altitude on the binding of [125I]iodohydroxybenzylpindolol to beta-adrenergic receptors on membranes of right and left ventricles of rat heart were determined. Chronic high-altitude exposure led to a decrease in the density of beta-adrenergic receptors in nonhypertrophied left ventricles as well as in hypertrophied right ventricles. The affinity of the receptor for the radioligand was not changed by the exposure to high altitude, suggesting that the properties of the receptor were not affected. Basal and isoproterenol-stimulated adenylate cyclase activities were decreased in membranes prepared from hearts and pulmonary arteries of rats acclimatized to high altitude. The loss of cardiac beta-adrenergic receptors in rats adapted to high altitude was prevented by the chronic coadministration of a low dose of DL-propranolol. The results suggest that changes in beta-adrenergic receptor density may partially explain the hemodynamic adaptation that occurs with chronic hypoxia. These decreases may be due to a loss of functional beta-adrenergic receptors caused by chronically elevated concentrations of circulating neurally released catecholamines.
The Electrochemistry of Iridium Oxide Films in Some Nonaqueous Solvents (1988)

Ir oxide films, grown in aqueous solutions , have been found to exhibit excellent charge capacities, charging and discharging kinetics, and stability in acetonitrile and propylene carbonate with as the supporting electrolyte, while the results in THF also appear to be quite promising. The oxide is electrochromic in all of these media. In order to obtain the optimum response of Ir oxide in nonaqueous solutions, it is important to prevent the drying out of the oxide when transferring it from the aqueous to nonaqueous media. Discharging and charging of the oxide appears to involve Li+ insertion and expulsion from the oxide, respectively. Oxides formed in neutral aqueous solutions have been found to be mechanically more stable than those grown in aqueous or in 50% aqueous . This is supported by SEM evidence of a less cracked and more adherent Ir oxide film when grown in neutral aqueous solutions, as compared to the case in the latter solutions.
Determination of ED50 and ED95 of 0.5% Ropivacaine in Adductor Canal Block to Produce Quadriceps Weakness (2017)

This study was registered at ClinicalTrials.gov, identifier NCT02541552.
With Great Freedom Comes Great Opportunity: Rethinking Resource Allocation for Serverless Functions (2021)

Current serverless offerings give users a limited degree of flexibility for configuring the resources allocated to their function invocations by either coupling memory and CPU resources together or providing no knobs at all. These configuration choices simplify resource allocation decisions on behalf of users, but at the same time, create deployments that are resource inefficient. In this paper, we take a principled approach to the problem of resource allocation for serverless functions, allowing this choice to be made in an automatic way that leads to the best combination of performance and cost. In particular, we systematically explore the opportunities that come with decoupling memory and CPU resource allocations and also enabling the use of different VM types. We find a rich trade-off space between performance and cost. The provider can use this in a number of ways: from exposing all these parameters to the user, to eliciting preferences for performance and cost from users, or by simply offering the same performance with lower cost. This flexibility can also enable the provider to optimize its resource utilization and enable a cost-effective service with predictable performance. Our results show that, by decoupling memory and CPU allocation, there is potential to have up to 40% lower execution cost than the preset coupled configurations that are the norm in current serverless offerings. Similarly, making the correct choice of VM instance type can provide up to 50% better execution time. Furthermore, we demonstrate that providers can utilize different instance types for the same functions to maximize resource utilization while providing performance within 10-20% of the best resource configuration for each respective function.
Giant Bubble Pinch-Off (2006)

Self-similarity has been the paradigmatic picture for the pinch-off of a drop. Here we will show through high-speed imaging and boundary integral simulations that the inverse problem, the pinch-off of an air bubble in water, is not self-similar in a strict sense: A disk is quickly pulled through a water surface, leading to a giant, cylindrical void which after collapse creates an upward and a downward jet. Only in the limiting case of large Froude numbers does the purely inertial scaling h(-logh)(1/4) proportional tau(1/2) for the neck radius h [J. M. Gordillo et al., Phys. Rev. Lett. 95, 194501 (2005)] become visible. For any finite Froude number the collapse is slower, and a second length scale, the curvature of the void, comes into play. Both length scales are found to exhibit power-law scaling in time, but with different exponents depending on the Froude number, signaling the nonuniversality of the bubble pinch-off.
RIS-Enabled and Access-Point-Free Simultaneous Radio Localization and Mapping (2022)

In the upcoming sixth generation (6G) of wireless communication systems, reconfigurable intelligent surfaces~(RISs) are regarded as one of the promising technological enablers, which can provide programmable signal propagation. Therefore, simultaneous radio localization and mapping(SLAM) with RISs appears as an emerging research direction within the 6G ecosystem. In this paper, we propose a novel framework of RIS-enabled radio SLAM for wireless operation without the intervention of access points (APs). We first design the RIS phase profiles leveraging prior information for the user equipment~(UE), such that they uniformly illuminate the angular sector where the UE is probabilistically located. Second, we modify the marginal Poisson multi-Bernoulli SLAM filter and estimate the UE state and landmarks, which enables efficient mapping of the radio propagation environment. Third, we derive the theoretical Cramér-Rao lower bounds on the estimators for the channel parameters and the UE state. We finally evaluate the performance of the proposed method under scenarios with a limited number of transmissions, taking into account the channel coherence time. Our results demonstrate that the RIS enables solving the radio SLAM problem with zero APs, and that the consideration of the Doppler shift contributes to improving the UE speed estimates.
Slow binding inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (1990)

The mechanism of slow binding inhibition of 3-hydroxy-3-methylglutaryl- coenzyme A reductase by lovastatin, fluindostatin, and related compounds was studied. Several of these compounds, including lovastatin, were found to be slow binding, while other less potent inhibitors were not. From a comparison of kinetic parameters obtained by steady-state measurements and progress curve analysis, it was concluded that the slow binding inhibitors bind by a mechanism which is more accurately described by biphasic binding than by single-step binding. The overall association rates of the slow binding inhibitors range from 1 x 10(6) to 4 x 10(-7) M-1 s-1, and the dissociation rates are in the range of 10(-3) s-1. The structures of slow binding and reversible inhibitors were compared by using molecular modeling methods. From these comparisons, it was proposed that the slow binding and very potent inhibition of, for instance, lovastatin, is not simply a result of binding of a transition state or reaction intermediate analogue. The various lipophilic groups of the inhibitors that do not seem to be related to structural features of the substrate may also play a crucial role in determining the mechanism of binding of HMGR inhibitors.
Latent transcripts of Marek's disease virus are clustered in the short and long repeat regions (1990)

Marek's disease herpesvirus (MDV) induces tumors in chickens, and lymphoblastoid cells derived from such tumors contain the viral genome in a latent state and do not produce infectious virus. Poly(A)+ RNAs extracted from MDV-induced kidney lymphoma cells and from MKT-1 cells, a nonproducing lymphoblastoid cell line derived from a tumor induced by MDV, were electrophoretically separated under denaturing conditions, transferred to a solid substrate, and hybridized with labeled DNA probes representing approximately 95% of the virus genome. These analyses revealed 29 viral RNA transcripts in the kidney lymphoma and 32 viral RNAs in MKT-1 cells. In both instances, the transcripts hybridized to a restricted region comprising approximately 20% of the MDV genome located in the repeats flanking the long and short unique sequences and in the adjacent unique sequences. The sizes of the transcripts derived from kidney lymphoma and MKT-1 cells and the distributions of the homologous regions in the viral genome were very similar. The most abundant transcripts were homologous to the BamHI I2 fragment. The results suggest that expression of the MDV genome in MKT-1 cells closely reflects the expression of the MDV genome in tumors. The gene expression over extended regions of the genome is in concordance with that observed in latent gammaherpesviruses rather than that observed in latent alphaherpesviruses.
Tumor necrosis factor-alpha induces cyclooxygenase-2 expression and prostaglandin release in brain microvessel endothelial cells. (2001)

Primary cultured bovine brain microvessel endothelial cells (BBMECs), were used as an in vitro model of the blood-brain barrier to examine the involvement of eicosanoids in the permeability and cytoskeletal structural changes observed following exposure to tumor necrosis factor-alpha (TNF-alpha). Compared with control monolayers, BBMECs exposed to TNF-alpha formed actin filament tangles and extracellular gaps with a resultant increase in permeability. Both the permeability and cytoskeletal changes observed with TNF-alpha were significantly reduced following pretreatment with NS-398 or indomethacin, inhibitors of cyclooxygenase (COX). Western blot analysis showed that TNF-alpha had no apparent effect on the expression of COX-1, but did induce the expression of COX-2 in the BBMECs. The induction of COX-2 expression occurred within the same time frame (2-4 h following TNF-alpha exposure) as the permeability increases observed with the cytokine. Consistent with the increased expression of COX-2, BBMEC monolayers exposed to TNF-alpha had significantly greater secretion and release of prostaglandin E(2) (PGE(2)) and prostaglandin F(2alpha) (PGF(2alpha)). Furthermore, BBMEC monolayers treated with PGE(2) or PGF(2alpha) showed significant increases in permeability and cytoskeletal structural changes when compared with control monolayers. Together, these results suggest that the TNF-alpha-induced permeability and cytoskeletal structural effects are due, in part, to an induction of the COX-2 system and increased release of prostaglandins in the cerebral microvasculature.
Acquisition of transcranial ultrasonic signals from adult subject’s applications to the detection of brain injury (2004)

In the clinical setting, several technologies (e.g., x-ray CT, MRI, color-duplex ultrasonography) can provide doctors with noninvasive windows through the cranium into the brain. In the field, however, there is a need for a portable device that can noninvasively detect brain injuries at the scene of a trauma, providing first responders with urgent diagnostic information in the critical first hour postincident. Such an instrument should be simple to operate and must supply results that are straightforward to interpret. This work is part of an effort to devise ultrasonic methods that can serve as the operating principle for such a device. In this talk, human studies are described in which backscattered ultrasound data were obtained transcranially from adult volunteers. The ultrasound signals, acquired with single transducers in pulse–echo mode, are interpreted anatomically with the aid of a multilayer model of the propagation path. Through the model, the complex structures of the echo patterns are revealed and the important roles of the scalp and skull layers are made evident. The ultrasound data are further analyzed to assess the suitability of these signals for implementing a tissue characterization approach to the injury detection problem.
[Allogeneic hematopoietic stem cell transplantation for solid tumors in the United States: a review]. (2003)

The field of bone marrow transplantation has undergone dramatic changes over the past few decades. Not only has the terminology changed (e.g., hematopoietic stem-cell transplantation), but the role of allogeneic transplantation has been modified from supportive to immunotherapeutic and the applications have expanded from hematologic malignancies to solid tumors. The development of nonmyeloablative conditioning regimen has greatly increased the number of patients eligible for this kind of treatment. Use of hematopoietic stem-cell transplantation as a form of adoptive immunotherapy in the treatment of cancer depends on advances in tumor immunology, particularly the identification of tumor antigens and mechanisms of immunotherapy. The earliest use of allogeneic transplantation of immunogenic cells for the treatment of solid tumors in the late 1960s and early 1970s produced no definite graft-versus-tumor effects. However, as conventional allogeneic hematopoietic stem-cell transplantation methods for the treatment of hematologic malignancies have matured, these methods have reestablished the foundation for expanding their application to solid tumors. From the first case reports on medulloblastoma and breast cancer to subsequent case series reports on breast cancer and renal cell carcinoma, allogeneic hematopoietic stem-cell transplants have demonstrated graft-versus-tumor effect. At present, the most common solid tumor for which this treatment is used is advanced renal cell carcinoma, but allogeneic hematopoietic stem-cell transplants have proven feasible for other solid tumors as well. Directions for future study include the identification of the definitive tumor antigens involved in the graft-versus-tumor effect and means of selecting those patients who will benefit the most from this form of treatment. This review summarizes the peer-reviewed literature on the use of allogeneic transplantation for solid tumors based on US studies.
Folate status and health: Preventable spina bifida and anencephaly in Europe/Germany (2016)

Objective: Fortification with folic acid has lowered the prevalence of neural tube defects (NTDs) in 70 countries. The absence of this strategy in Europe causes 5000 affected births yearly, while 50% of the cases are preventable. We aimed at investigating the number of NTDs in a representative sample of the European population and estimate the economic burden in Germany.
A fault model for function and delay testing (2001)

Existing gate-level fault models are not well suited to test generation for circuits that contain modules whose logic implementation and timing behavior are unspecified. A high-level fault model called the coupling fault (CF) model is presented which aims to cover both functional and timing faults in an integrated manner. Intuitively, a (single) CF denoted xi|zj exists between input xi and output zj of a module if xi|zj blocks any dynamic effect of xi on zj The set of test vectors CTS <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">xi|zj</sub> that detect xi|zj is represented by the boolean difference of zj with respect to xi. A pair of adjacent vectors in CTS <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">xi|zj</sub> , constitutes a coupling delay test. This article studies the basic properties of coupling faults and test sets, focusing on the relationship between coupling tests and other high-level tests. A coupling test set provides powerjhl, realization-independent coverage of stuck-at faults. Coupling delay tests can detect all robust path delay faults in any realization of afunction.
Pulse compression with highly nonlinear photonic crystal fibers by optimization of input and output chirp parameters up to the third-order (2005)

A commercial photonic crystal fiber is used for pulse compression of sub-nJ laser pulses. Simulations show that optimizing the input chirp of the seed pulse 6 fs compressed pulses can be obtained. Calculations are carried out for sub-ps pulses as well.