gebhart/patrepeval huggingface dataset:
CD40-mediated activation of Ig-Cγ1- and Ig-Cε germ-line promoters involves multiple TRAF family proteins (1999)

CD40 plays a critical role in immunoglobulin (Ig) class switching in B cells, but the molecular events involved remain poorly understood. Using CD40 mutants with impairments in their ability to bind selected TNF receptor-associated factor (TRAF) family proteins, we observed that CD40-mediated transcriptional induction of the germ-line Ig-Cgamma1- and Ig-Cepsilon promoters was markedly reduced by mutations that prevent TRAF2, TRAF3, TRAF5 or TRAF6 binding. Moreover, co-expression of trans-dominant inhibitory forms of TRAF2, 3, 5 or 6 with wild-type CD40 also suppressed induction of these promoters. Overexpression of TRAF2 or TRAF6 was sufficient to induce transcription of the C(H) promoters through an NF-kappaB-dependent mechanism. In contrast, TRAF3 and TRAF5 failed to induce these promoters, implying a more indirect role for these TRAF family members. Altogether, the results demonstrate a non-redundant role for multiple TRAF in the signal transduction pathways by which CD40 induces transcription of germ-line C(H) promoters. Since C(H) germ-line transcription represents an obligatory step in Ig class switching in B cells, these findings suggest that interference with the functions of any of these TRAF might provide a means of preventing class switching for therapeutic purposes.
How Hardware Evolution is Driving Software Systems (2019)

Computing Systems are undergoing a multitude of interesting changes: from the platforms (cloud, appliances) to the workloads, data types, and operations (big data, machine learning). Many of these changes are driven or being tackled through innovation in hardware even to the point of having fully specialized designs for particular applications. In this talk I will review some of the most important changes happening in hardware and discuss how they affect system design as well as the opportunities they create. I will focus on data processing with an emphasis on streams and event based systems but also discuss applications in other areas. I will also briefly discuss how these trends are likely to result in a very different form of IT, and consequently of Computer Science, from the one we know today.
Leveraging Evolutionary Algorithms for Feasible Hexapod Locomotion Across Uneven Terrain (2022)

Optimizing gait stability for legged robots is a difficult problem. Even on level surfaces, effectively traversing across different textures (e.g., carpet) rests on dynamically tuning parameters in multidimensional space. Inspired by biology, evolutionary algorithms (EA) remain an attractive solution for feasibly implementing robotic locomotion with both energetic economy and rapid parameter convergence. Here, we leveraged this class of algorithms to evolve a stable hexapod gait controller capable of traversing uneven terrain and obstacles. Gait parameters were evolved in a rigid body dynamics simulation on an 8 x 3 meter obstacle course comprised of random step field, linear obstacles and inclined surfaces. Using a fitness function that jointly optimized locomotion velocity and stability, we found that multiple successful gait parameter evolutions yielded specialized functionality for each leg. Specific gait parameters were identified as critical to developing a rough terrain gait.
On Conditions for Uniqueness in Sparse Phase Retrieval (2013)

The phase retrieval problem has a long history and is an important problem in many areas of optics. Theoretical understanding of phase retrieval is still limited and fundamental questions such as uniqueness and stability of the recovered solution are not yet fully understood. This paper provides several additions to the theoretical understanding of sparse phase retrieval. In particular we show that if the measurement ensemble can be chosen freely, as few as 4k-1 phaseless measurements suffice to guarantee uniqueness of a k-sparse M-dimensional real solution. We also prove that 2(k^2-k+1) Fourier magnitude measurements are sufficient under rather general conditions.
A Modified System for the Synthesis of Enantioenriched N‐Arylamines through Copper‐Catalyzed Hydroamination (2018)

Despite significant recent progress in copper-catalyzed enantioselective hydroamination chemistry, the synthesis of chiral N-arylamines, which are frequently found in natural products and pharmaceuticals, has not been realized. Initial experiments with N-arylhydroxylamine ester electrophiles were unsuccessful and, instead, their reduction in the presence of copper hydride (CuH) catalysts was observed. Herein, we report key modifications to our previously reported hydroamination methods that lead to broadly applicable conditions for the enantioselective net addition of secondary anilines across the double bond of styrenes, 1,1-disubstituted olefins, and terminal alkenes. NMR studies suggest that suppression of the undesired reduction pathway is the basis for the dramatic improvements in yield under the reported method.
Clinical Responses to Intramammary Endotoxin Infusion in Dairy Cows Subjected to Feed Restriction (2002)

Nonpregnant, midlactation primiparous Holstein cows were fed ad libitum (n = 12) or at 80% of maintenance energy requirements (n = 12) to determine whether feed restriction influences clinical response to endotoxin-induced mastitis. After 2 wk of ad libitum or restricted feeding, one mammary quarter per cow was infused with 100 microg of endotoxin. Within 3 to 6 h of intramammary infusion, endotoxin increased mean rectal temperature, heart rate, and milk somatic cell count and immunoglobulin (IgG) concentration; and decreased blood leukocyte count and rumen motility in both restricted and ad libitum-fed cows. Mean serum and milk tumor necrosis factor-alpha (TNF-alpha) concentrations showed only modest increases following endotoxin infusion. Restricted fed cows had slightly different acute fever responses and significantly increased heart and respiration rates than ad libitum fed cows. However, feed restriction did not influence mean total leukocyte count, rumen motility, serum TNF-a concentrations or milk IgG and TNF-alpha concentrations. Thus, results of this study suggest that energy balance does not significantly alter clinical symptoms following acute endotoxin-induced mastitis, at least in midlactation cows. As such, negative energy balance may not underlie the increases in severe coliform mastitis commonly observed in periparturient dairy cows.
Evidence for a Direct Action of Cholecalciferol and 25-Hydroxycholecalciferol on the Renal Transport of Phosphate, Sodium, and Calcium (1972)

Acute clearance studies were performed in stable thyroparathyroidectomized dogs to evaluate the possibility of a direct renal action of vitamin D and its biologically active 25-hydroxylated metabolite. Alterations in renal hemodynamics and serum calcium concentration were minimized and attempts at vitamin D depletion were not undertaken. Steady-state volume expansion of modest degree was employed as the control experimental situation so that an effect of the vitamin to enhance phosphate reabsorption would not go undetected because of an already maximal phosphate reabsorptive rate secondary to parathyroidectomy. Under these experimental circumstances, 10,000 U of cholecalciferol and 25-120 U of 25-hydroxycholecalciferol (25-HCC) produced significant depressions in the percentage of filtered phosphate excreted (mean declines of 39 and 47%, respectively), which were not attributable to alterations in renal hemodynamics or to changes in the levels of serum calcium or phosphate. There was an accompanying decline in sodium and calcium excretion; mean percentage excretion rates for sodium fell by 38% with vitamin D and 26% with 25HCC, and for calcium this measurement declined by 46 and 23%, respectively. Furthermore, parathyroid hormone and 25HCC produced antagonistic effects on phosphate excretion. These observations provide the first conclusive evidence for a direct (proximal) tubular action of vitamin D to promote phosphate (as well as sodium and calcium) transport.
The IOERT IntraLine accelerator – the development, current state, and future plans (2016)

Abstract Intraoperative electron radiation therapy (IOERT) is a cancer treatment method that combines oncologic surgery with electron beam radiotherapy. This method can reduce the duration of entire tumor treatment and increase its effectiveness. Moreover, shortening the treatment time significantly reduces the cost and accessibility of the therapy. As a result of interdisciplinary research, an innovative accelerator for IOERT, the IntraLine, was developed. In the course of this work, four patent applications were filed. Today, the work is half way through. In the near future, the device will be optimized. New mechanical design solutions will be developed. Mechanical optimization will significantly reduce the weight of the device. Accelerators control system, which today is in the demo phase, will also be significantly upgraded. This paper describes the stages of the IntraLine accelerator development, its current state and plans for the future R&amp;D work, within the scope of our new Intra-Dose project.
Collaborative information retrieval (2008)

The goal of the workshop is to bring together researchers interested in various aspects of small-team collaborative search to share ideas, to stimulate research in the area, and to increase the visibility of this emerging area. We expect to identify promising directions for further exploration and to establish collaborative links among research groups.
TMPRSS2:ERG Gene Fusion Predicts Subsequent Detection of Prostate Cancer in Patients With High-Grade Prostatic Intraepithelial Neoplasia (2013)

This study underscores the necessity of more stringent follow-up for men with HGPIN that is also positive for ERG overexpression. Clinicians should consider molecular characterization of HGPIN as a means to improve risk stratification.
Alloying as a method of tuning of interlayer exchange coupling in magnetic multilayers (2006)

Magnetic properties of diluted magnetic semiconductors and magnetic metallic multilayers are investigated by SQUID magnetometry. By doping GaAs with magnetic Mn2+ ions under well defined growth conditions, one obtains a diluted magnetic semiconductor, (Ga,Mn)As, in which the randomly-distributed magnetic ions act as acceptor centers. At high enough dopant and hole concentration a carrier-induced ferromagnetic state results between the magnetic ions. Due to peculiarities of the growth process sizable amounts of donor defects, such as Mn interstitials and As antisites, are also introduced into the GaAs host. The magnetic properties of (Ga,Mn)As are altered by the presence of such defects through the compensation effect of the holes. The Mn interstitials are thermally unstable above a certain threshold temperature and therefore their concentration can be controlled by post-growth annealing. The influence of the interfaces on the magnetic moment of FeNi/V and FeNi/Co superlattices has been studied. A decrease of the `FeNi' magnetic moment at the interfaces is observed for FeNi/V superlattices while in case of FeNi/Co an enhanced magnetic moment is obtained at the interfaces. Changes of the interlayer exchange coupling have been studied in a series of Fe/V(Fe) multilayers in which the V spacer was alloyed with small amounts of Fe. The dynamic magnetic properties of discontinuous metal-insulator multilayers of Ni81Fe19/Al2O3 have been investigated. By varying the thickness of the insulator the system exhibits a superferromagnetic, a 3d spin-glass-like and a superparamagnetic behavior.
Cochlear Implant Outcomes between Patients with Sporadic and Neurofibromatosis Type 2–Associated Vestibular Schwannoma (2023)

Select patients with VS achieve successful hearing rehabilitation with a CI. In this cohort, tumor management strategy significantly influenced CI performance, whereas differences in NF2 status exhibited less effect. Specifically, all patients managed with observation or radiosurgery achieved open-set speech perception, whereas approximately half of people with NF2-related VS and two-thirds of people with sporadic VS achieved this outcome after tumor microsurgery. When disease permits, observation and radiosurgery should be considered in patients who may later pursue a CI.
Wideband LTCC transitions of flip-chip to waveguides/connectors for a highly dense phased array system-in-package at 60 GHz (2017)

This paper presents two types of wideband transitions from a flip-chip interconnect to external v-band rectangular waveguides and surface-mount coaxial connectors, based on LTCC technology. The flip-chip interconnect is directly connected to a multi-level stacked via allowing compact routing of RF signals for a highly dense phased array system-in-package. The signal is guided from striplines into the waveguides using a T-shape launcher and impedance matching is performed by several means including implementing a stub and tapering a near-quarter wavelength embedded waveguide. In the other design, mm-wave signals are directed from a stripline to a surface-mount 1.85 mm v-type connector to provide a compact solution for multiple input/output transceivers. Both types of transitions are fabricated and initial measurement results are presented. Compactness and low loss (0.5 dB) performance along with over 20 % bandwidth from 55 to 67 GHz make the transitions suitable for 60 GHz WiGig applications.
Chromophore Environment Provides Clue to “Kindling Fluorescent Protein” Riddle (2003)

asCP, the unique green fluorescent protein-like nonfluorescent chromoprotein from the sea anemone Anemonia sulcata, becomes fluorescent ("kindles") upon green light irradiation, with maximum emission at 595 nm. The kindled protein then relaxes to a nonfluorescent state or can be "quenched" instantly by blue light irradiation. In this work, we used asCP mutants to investigate the mechanism underlying kindling. Using site-directed mutagenesis we showed that amino acids spatially surrounding Tyr(66) in the chromophore are crucial for kindling. We propose a model of the kindling mechanism, in which the key event is chromophore turning or cis-trans isomerization. Using site-directed mutagenesis we also managed to transfer the kindling property to the two other coral chromoproteins. Remarkably, most kindling mutants were capable of both reversible and irreversible kindling. Also, we obtained novel variants that kindled upon blue light irradiation. The diversity of photoactivated fluorescent proteins that can be developed by site-directed mutagenesis is promising for biotechnological needs.
The PATH Experience in Vaccine Development Partnerships with Manufacturers from Emerging Markets (2022)

Partnerships between public sector agencies and emerging market manufacturers, often facilitated by support from foundations and governments, have long been touted as a way to ensure that affordable vaccines are developed and commercialized to address sustainably the public health needs of low- and middle-income countries (LMICs). Technology transfer for vaccines is difficult, however, under any circumstances and, not surprisingly, the success record of such partnerships is mixed. This chapter presents a critical look at how three different partnerships with one private and one state-owned LMIC vaccine manufacturer have succeeded and the pivotal role played by the global health organization PATH. The vaccines include a meningococcal A conjugate (MenAfriVac®), a 10-valent pneumococcal conjugate (PNEUMOSIL®), and a Japanese encephalitis vaccine (CD.JEVAX®). The vaccines differed in development and manufacturing complexities and whether a global or regional market already existed with established competitors. The factors that prompted project initiation and key challenges faced are discussed. The chapter highlights the innovative strategies and approaches taken, what the public sector and local manufacturers brought to the table, the resulting benefits to each, and the evolving roles of funding agencies. Two tables summarize key aspects of each of the partnerships. Future partnerships may benefit from the “lessons learned” in these three successful projects.
Problems and Mitigation Strategies for Developing and Validating Statistical Cyber Defenses (2014)

Abstract : The development and validation of advanced cyber security technology frequently relies on data capturing normal and suspicious activities at various system layers. However, getting access to meaningful data continues to be a major hurdle for innovation in statistical cyber defense research. This paper describes the data challenges encountered during development of the machine learning approach called Behavior-Based Access Control (BBAC), together with mitigation strategies that were instrumental in allowing R&D to proceed. The paper also discusses results from applying a spiral-based agile development process focused on continuous experimental validation of the resulting prototype capabilities.
Fragile histidine triad gene and skin cancer. (2001)

Five years ago the fragile histidine triad (FHIT) gene including the most common fragile site locus of the human genome, FRA3B, was identified. The gene is altered in many types of cancer and several data support the idea that FHIT has to be considered a tumor suppressor. FHIT abnormalities were investigated in some skin tumors. Fifty-seven per cent of Merkel cell carcinomas displayed abnormal FHIT products but the involvement of FHIT in human non-melanoma skin cancer is still unclear. Because the murine Fhit locus is similar to its human homologue and is altered in cancer cell lines, we have established a strain of Fhit-deficient mice. After N-nitrosomethylbenzylamine treatment, the spectrum of tumors developed by the Fhit-deficient mice was similar to those observed in a familial skin cancer condition, the Muir-Torre syndrome, although there is no clear evidence yet for a relationship of FHIT and the human syndrome. Because cancer cells lacking in FHIT are defective in apoptosis, we propose the Fhit-deficient mouse as a model to understand a possible proapoptotic mechanism deficiency in the human syndrome.
Synthesis and evaluation of a monoreactive DOTA derivative for indium-111-based residualizing label to estimate protein pharmacokinetics (2002)

The purpose of this study was to develop an indium-111 (111In)-based residualizing label for estimating the pharmacokinetics of proteins. 1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA), which produced a highly stable and hydrophilic 111In chelate, was selected as the chelating site, and the monoreactive DOTA derivative with a tetrafluorophenyl group as the protein binding site (mDOTA) was designed to avoid cross-linkings of proteins. mDOTA was synthesized with an overall yield of 11%. The stability in murine plasma, the radioactivity retention in the catabolic sites of proteins and the radiochemical yields of 111In-labelled proteins via mDOTA were investigated using human serum albumin (HSA), galactosyl-neoglycoalbumin (NGA) and cytochrome c (cyt c) as model proteins. 111In-labelled HSA via mDOTA was highly stable for 5 days after incubation in murine plasma. Long retention of radioactivity in the catabolic sites was observed after injection of 111In-DOTA-NGA in mice, due to the slow elimination of the radiometabolite from the lysosome. At a chelator concentration of 42.2 microM, 111In-DOTA-cyt c was produced with over 91% radiochemical yield. On the other hand, 111In-DOTA-lysine and 111In-DOTA were obtained with high radiochemical yields at lower chelator concentrations. These findings indicated that mDOTA would be an appropriate 111In-labelling agent for estimating protein pharmacokinetics. These findings also suggested that the introduction of a protein binding site at a position distal from the unmodified DOTA structure would be preferable to preparing 111In-DOTA-labelled proteins with higher specific activity.
Automated contraction detection in electrohysterography during the menstrual cycle (2015)

Interested by a comparative trial on tetracycline concentrations in gallbladder, bile and peritoneum 3 hours after administration, we wanted to know the long-term tissue concentrations, measured towards the end of a 24-hour off-drug interval, as these concentrations are particularly important for a bacteriostatic drug. We found that the tissue concentrations of doxycycline in gallbladder wall, lung, muscle, and thyroid gland were 2 to 3 times higher than those of pyrrolidino-methyltetracycline. The concentrations in the skin, in various sections of the intestinal tract and of the peritoneum, and in the gallbladder content were about the same for both drugs. The implications of these data for therapy are discussed.
Transient introduction of human telomerase mRNA improves hallmarks of progeria cells (2019)

Hutchinson-Gilford progeria syndrome (HGPS) is characterized by accelerated senescence due to a de novo mutation in the LMNA gene. The mutation produces an abnormal lamin A protein called progerin that lacks the splice site necessary to remove a farnesylated domain. Subsequently, progerin accumulates in the nuclear envelope, disrupting nuclear architecture, chromatin organization, and gene expression. These alterations are often associated with rapid telomere erosion and cellular aging. Here, we further characterize the cellular and molecular abnormalities in HGPS cells and report a significant reversal of some of these abnormalities by introduction of in vitro transcribed and purified human telomerase (hTERT) mRNA. There is intra-individual heterogeneity of expression of telomere-associated proteins DNA PKcs/Ku70/Ku80, with low-expressing cells having shorter telomeres. In addition, the loss of the heterochromatin marker H3K9me3 in progeria is associated with accelerated telomere erosion. In HGPS cell lines characterized by short telomeres, transient transfections with hTERT mRNA increase telomere length, increase expression of telomere-associated proteins, increase proliferative capacity and cellular lifespan, and reverse manifestations of cellular senescence as assessed by β-galactosidase expression and secretion of inflammatory cytokines. Unexpectedly, mRNA hTERT also improves nuclear morphology. In combination with the farnesyltransferase inhibitor (FTI) lonafarnib, hTERT mRNA promotes HGPS cell proliferation. Our findings demonstrate transient expression of human telomerase in combination with FTIs could represent an improved therapeutic approach for HGPS.