gebhart/patrepeval huggingface dataset:
[Role of hormonal profile in adjusting therapy for prostate cancer]. (2008)

Changes in testosterone, prolactin and estradiol levels were evaluated vis-a-vis outcome and different patterns of androgen suppression--continuous androgen blockade or intermittent therapy--for prostate cancer patients. There was a significant difference between pre- (3.4 +/- 0.5 mM/l) and post- (1.0 +/- 0.3 mM/l) treatment levels of testosterone in cases of tumor progression and that in patients with positive response--(9.1 +/- 0.6 mM/l) and (4.3 +/- 0.4 mM/l), respectively. Relatively low levels of testosterone involved tumor progression. Prolactin level was significantly higher in patients with multiple distant metastases--(18.6 +/- 1.2 microg/l) and isolated foci--(9.5 +/- 0.8 microg/l) while tumor progression was associated with enhancing correlation with PSA concentration. It was established that prolactin level can be used as a criterion for resumption or discontinuation of intermittent therapy. Estradiol dynamics was similar to that of prolactin. The difference between pre- (172.9 +/- 9.8 pM/l) and post- (246.5 +/- 12.8 pM/l) treatment levels of estradiol in cases of tumor progression was significantly higher than that in patients with positive response (85.0 +/- 3.8 pM/l) and (76.9 +/- 4.4 pM/l), respectively.
miR-221 and miR-222 Expression Affects the Proliferation Potential of Human Prostate Carcinoma Cell Lines by Targeting p27Kip1 (2007)

MicroRNAs are short regulatory RNAs that negatively modulate protein expression at a post-transcriptional level and are deeply involved in the pathogenesis of several types of cancers. Here we show that miR-221 and miR-222, encoded in tandem on chromosome X, are overexpressed in the PC3 cellular model of aggressive prostate carcinoma, as compared with LNCaP and 22Rv1 cell line models of slowly growing carcinomas. In all cell lines tested, we show an inverse relationship between the expression of miR-221 and miR-222 and the cell cycle inhibitor p27(Kip1). We recognize two target sites for the microRNAs in the 3' untranslated region of p27 mRNA, and we show that miR-221/222 ectopic overexpression directly results in p27 down-regulation in LNCaP cells. In those cells, we demonstrate that the ectopic overexpression of miR-221/222 strongly affects their growth potential by inducing a G(1) to S shift in the cell cycle and is sufficient to induce a powerful enhancement of their colony-forming potential in soft agar. Consistently, miR-221 and miR-222 knock-down through antisense LNA oligonucleotides increases p27(Kip1) in PC3 cells and strongly reduces their clonogenicity in vitro. Our results suggest that miR-221/222 can be regarded as a new family of oncogenes, directly targeting the tumor suppressor p27(Kip1), and that their overexpression might be one of the factors contributing to the oncogenesis and progression of prostate carcinoma through p27(Kip1) down-regulation.
Cytokines and Growth Factors in the Pathogenesis of AIDS‐Associated Kaposi's Sarcoma (1992)

In the past, the study of KS pathogenesis has been hampered by the lack of in vitro and in vivo experimental systems. Recently, the establishment of long-term cultures of KS spindle cells and the development of animal models have allowed a variety of studies on the pathobiology of the disease. The results from these studies, reviewed herein, indicate that KS is a cytokine-mediated disease and that inflammatory and angiogenic cytokines and the HIV-1 Tat protein cooperate in its induction and progression in HIV-1-infected individuals.
Therapeutic efficacy of an oral nucleoside analog of remdesivir against SARS-CoV-2 pathogenesis in mice (2021)

The COVID-19 pandemic remains uncontrolled despite the rapid rollout of safe and effective SARS-CoV-2 vaccines, underscoring the need to develop highly effective antivirals. In the setting of waning immunity from infection and vaccination, breakthrough infections are becoming increasingly common and treatment options remain limited. Additionally, the emergence of SARS-CoV-2 variants of concern with their potential to escape therapeutic monoclonal antibodies emphasizes the need to develop second-generation oral antivirals targeting highly conserved viral proteins that can be rapidly deployed to outpatients. Here, we demonstrate the in vitro antiviral activity and in vivo therapeutic efficacy of GS-621763, an orally bioavailable prodrug of GS-441524, the parental nucleoside of remdesivir, which targets the highly conserved RNA-dependent RNA polymerase. GS-621763 exhibited significant antiviral activity in lung cell lines and two different human primary lung cell culture systems. The dose-proportional pharmacokinetic profile observed after oral administration of GS-621763 translated to dose-dependent antiviral activity in mice infected with SARS-CoV-2. Therapeutic GS-621763 significantly reduced viral load, lung pathology, and improved pulmonary function in COVID-19 mouse model. A direct comparison of GS-621763 with molnupiravir, an oral nucleoside analog antiviral currently in human clinical trial, proved both drugs to be similarly efficacious. These data demonstrate that therapy with oral prodrugs of remdesivir can significantly improve outcomes in SARS-CoV-2 infected mice. Thus, GS-621763 supports the exploration of GS-441524 oral prodrugs for the treatment of COVID-19 in humans.
Inhibition of BET bromodomain-dependent XIAP and FLIP expression sensitizes KRAS-mutated NSCLC to pro-apoptotic agents (2016)

Non-small cell lung cancer (NSCLC) has the highest incidence of cancer-related death worldwide and a high medical need for more effective therapies. Small-molecule inhibitors of the bromodomain and extra terminal domain (BET) family such as JQ1, I-BET762 and OTX-015 are active in a wide range of different cancer types, including lung cancer. Although their activity on oncogene expression such as c-Myc has been addressed in many studies, the effects of BET inhibition on the apoptotic pathway remain largely unknown. Here we evaluated the activity of BET bromodomain inhibitors on cell cycle distribution and on components of the apoptosis response. Using a panel of 12 KRAS-mutated NSCLC models, we found that cell lines responsive to BET inhibitors underwent apoptosis and reduced their S-phase population, concomitant with downregulation of c-Myc expression. Conversely, ectopic c-Myc overexpression rescued the anti-proliferative effect of JQ1. In the H1373 xenograft model, treatment with JQ1 significantly reduced tumor growth and downregulated the expression of c-Myc. The effects of BET inhibition on the expression of 370 genes involved in apoptosis were compared in sensitive and resistant cells and we found the expression of the two key apoptosis regulators FLIP and XIAP to be highly BET dependent. Consistent with this, combination treatment of JQ1 with the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or the pro-apoptotic chemotherapeutic agent cisplatin enhanced induction of apoptosis in both BET inhibitor sensitive and resistant cells. Further we showed that combination of JQ1 with cisplatin led to significantly improved anti-tumor efficacy in A549 tumor-bearing mice. Altogether, these results show that the identification of BET-dependent genes provides guidance for the choice of drug combinations in cancer treatment. They also demonstrate that BET inhibition primes NSCLC cells for induction of apoptosis and that a combination with pro-apoptotic compounds represents a valuable strategy to overcome treatment resistance.
2.0 W CW, diffraction-limited tapered amplifier with diode injection (1992)

A tapered amplifier 1.5 mm in length and with a taper angle of 5.7° emitted 2.0 W CW into a diffraction-limited pattern when injected with 25 mW incident power from a singlemode laser diode.
InnerView hardware debugger : a logic analysis tool for the Virtual Wires emulation system (1995)

The Virtual Wires system is an FPGA-based logic emulator which allows a user to thoroughly test a design before fabrication. It runs at hardware speeds thus making it preferable to a software simulator which is relatively slow. The problem, however, is that one can only use the inputs and outputs of this system to determine its correct functionality. This makes the debugging process extremely difficult. I have developed the InnerView Hardware Debugger which is a logic analysis tool for the Virtual Wires Emulator. Through the readback capability of the Xilinx FPGAs, I extract the state of the emulation and send it back to the host. The ability to know the current state of the internal logic of each FPGA allows a user to debug his/her design with much greater facility than in the case where only the I/O is available. In addition, InnerView provides flexible triggering capabilities, as well as the ability to run the design for a given number of clock cycles and then return the state infor...
Stability of HF-etched Si(100) surfaces in oxygen ambient (2001)

In situ multiple internal reflection infrared absorption spectroscopy of H-passivated silicon surfaces in controlled oxygen environments reveals that direct oxygen incorporation into the surface Si–Si bonds occurs without surface hydrogen removal, in the temperature range of 550–590 K for 1–20 mTorr O2 pressures. The kinetics of the O2 insertion process display overall effective activation energies of 1.6 to 1.7 eV and prefactors controlled primarily by Si–H steric hindrance for O2 to access Si–Si backbonds.
Personal Area Networks: Near-field intrabody communication (1996)

As electronic devices become smaller, lower in power requirements, and less expensive, we have begun to adorn our bodies with personal information and communication appliances. Such devices include cellular phones, personal digital assistants (PDAs), pocket video games, and pagers. Currently there is no method for these devices to share data. Networking these devices can reduce functional I/O redundancies and allow new conveniences and services. The concept of Personal Area Networks (PANs) is presented to demonstrate how electronic devices on and near the human body can exchange digital information by capacitively coupling picoamp currents through the body. A low-frequency carrier (less than 1 megahertz) is used so no energy is propagated, minimizing remote eavesdropping and interference by neighboring PANs. A prototype pan system allows users to exchange electronic business cards by shaking hands.
Therapeutic interchange of cefazolin with metronidazole for cefoxitin (1992)

The effects on patient outcome and drug therapy costs of a therapeutic interchange program using a cefazolin and metronidazole combination in place of cefoxitin were studied. A therapeutic interchange program was initiated in which the pharmacy department automatically replaced orders for cefoxitin with orders for a cefazolin and metronidazole combination. Data were compared for 100 consecutive patients who received cefoxitin before initiation of the program and the first 100 patients who received cefazolin and metronidazole as part of the program. The impact of the program on therapeutic efficacy, adverse effects associated with therapy, and drug therapy costs was assessed. The two patient groups were similar in age, gender, and white blood cell count. The failure rates for treatment or prophylaxis of infection did not significantly differ between the groups. Duration of therapy and incidence of adverse effects did not significantly differ between the groups. The average cost saving was +72 per patient for treatment with cefazolin and metronidazole instead of cefoxitin. A program for therapeutic interchange of cefazolin and metronidazole in place of cefoxitin demonstrated equivalent efficacy and adverse effects, as well as considerable cost savings.
The Immunogenicity of Human Adipose‐Derived Cells: Temporal Changes In Vitro (2006)

Regenerative medical techniques will require an abundant source of human adult stem cells that can be readily available at the point of care. The ability to use unmatched allogeneic stem cells will help achieve this goal. Since adipose tissue represents an untapped reservoir of human cells, we have compared the immunogenic properties of freshly isolated, collagenase-digested human adipose tissue-derived stromal vascular fraction cells (SVFs) relative to passaged, plastic-adherent adipose-derived stem cells (ASCs). Parallel studies have shown that adherence to plastic and subsequent expansion of human adipose-derived cells selects for a relatively homogeneous cell population based on immunophenotype. Consistent with these findings, the presence of hematopoietic-associated markers (CD11a, CD14, CD45, CD86, and histocompatible locus antigen-DR [HLA-DR]) detected on the heterogeneous SVF cell population decreased upon subsequent passage of the ASCs. In mixed lymphocyte reactions (MLRs), SVFs, and early passage ASCs stimulated proliferation by allogeneic responder T cells. In contrast, the ASCs beyond passage P1 failed to elicit a response from T cells. Indeed, late passage ASCs actually suppressed the MLR response. Although these results support the feasibility of allogeneic human ASC transplantation, confirmatory in vivo animal studies will be required.
Adhesion protein YadA of Yersinia species mediates binding of bacteria to fibronectin (1992)

The interaction between fibronectin and Yersinia strains was studied. Wild-type Y. enterocolitica strains expressing the virulence-plasmid-encoded adhesion protein YadA adhered strongly to fibronectin-coated coverslips, while their plasmid-cured variants expressed weaker binding. The cloned yadA gene of Y. enterocolitica or Y. pseudotuberculosis conferred fibronectin-binding ability both to Escherichia coli and to Y. psuedotuberculosis strains lacking the YadA protein. The YadA protein did not mediate binding to isolated fragments of fibronectin or to soluble fibronectin.
Differentially constrained mobile robot motion planning in state lattices (2009)

Abstract We present an approach to the problem of differentially constrained mobile robot motion planning in arbitrary cost fields. The approach is based on deterministic search in a specially discretized state space. We compute a set of elementary motions that connects each discrete state value to a set of its reachable neighbors via feasible motions. Thus, this set of motions induces a connected search graph. The motions are carefully designed to terminate at discrete states, whose dimensions include relevant state variables (e.g., position, heading, curvature, and velocity). The discrete states, and thus the motions, repeat at regular intervals, forming a lattice. We ensure that all paths in the graph encode feasible motions via the imposition of continuity constraints on state variables at graph vertices and compliance of the graph edges with a differential equation comprising the vehicle model. The resulting state lattice permits fast full configuration space cost evaluation and collision detection. Experimental results with research prototype rovers demonstrate that the planner allows us to exploit the entire envelope of vehicle maneuverability in rough terrain, while featuring real‐time performance. © 2009 Wiley Periodicals, Inc.
Mass spectroscopy: Mix and match (2001)

Weighing up the options for proteins.
Carbon nanotube electronics (2003)

We briefly review the electronic properties of carbon nanotubes (CNTs) and present results on the fabrication and characteristics of carbon nanotube field-effect transistors (CNTFETs) and simple integrated circuits. A novel approach allowing the catalyst-free synthesis of oriented CNTs is also presented.
A Stable System for the High-Titer Production of Multiply Attenuated Lentiviral Vectors (2000)

Lentiviral vectors open exciting perspectives for the genetic treatment of a wide array of inherited and acquired diseases, owing to their ability to govern the efficient delivery, integration, and long-term expression of transgenes into nondividing cells both in vitro and in vivo. The genomic complexity of HIV, where a whole set of genes encode virulence factors essential for pathogenesis but not required for gene transfer, allowed a major step toward clinical acceptability through the creation of multiply attenuated packaging systems. Until now, however, vector particles could only be produced by transient transfection because no high-output, stable packaging cell line was available that produced the latest generation of HIV-based vectors. Here we describe such a line, based on the doxycycline-repressible expression of HIV-1 Rev/Gag/Pol and of the vesicular stomatitis virus G envelope (VSV G) in 293 human embryonic kidney cells. Upon induction, the LVG clones can produce 1 to 20 HeLa-transducing units per cell per day for about a week, a yield that compares favorably with that of transiently transfected 293T cells. These virions exhibit functional properties similar to those of viruses produced transiently, in particular the ability to transduce nonmitotic targets. This system will facilitate the further development of lentiviral vectors for gene therapy.
Large Enhancements in the Thermoelectric Power Factor of Bulk PbTe at High Temperature by Synergistic Nanostructuring (2008)

Co-nanostructuring of PbTe with two kinds of metallic nanoparticles (Pb and Sb) can significantly increase its power factor at high temperatures (up to 87 % at 700 K; see picture, ZT=figure of merit). The electrical conductivity is dramatically increased at high temperatures without degrading the thermopower. This emergent synergy results only when both Pb and Sb nanocrystals are present. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Orally Bioavailable Potent Soluble Epoxide Hydrolase Inhibitors (2007)

A series of N,N'-disubstituted ureas having a conformationally restricted cis- or trans-1,4-cyclohexane alpha to the urea were prepared and tested as soluble epoxide hydrolase (sEH) inhibitors. This series of compounds showed low nanomolar to picomolar activities against recombinant human sEH. Both isomers showed similar potencies, but the trans isomers were more metabolically stable in human hepatic microsomes. Furthermore, these new potent inhibitors show a greater metabolic stability in vivo than previously described sEH inhibitors. We demonstrated that trans-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy]benzoic acid 13g (t-AUCB, IC50 = 1.3 +/- 0.05 nM) had excellent oral bioavailability (98%, n = 2) and blood area under the curve in dogs and was effective in vivo to treat hypotension in lipopolysaccharide challenged murine models.
Throwing versus walking as indicators of distance perception in similar real and virtual environments (2005)

For humans to effectively interact with their environment, it is important for the visual system to determine the absolute size and distance of objects. Previous experiments performed in full-cue, real-world environments have demonstrated that blind walking to targets serves as an accurate indication of distance perception, up to about 25 m. In contrast, the same task performed in virtual environments (VEs) using head-mounted displays shows significant underestimation in walking. To date, blind walking is the only visually directed action task that has been used to evaluate distance perception in VEs beyond reaching distances. The possible influence of the response measure itself on absolute distance perception in virtual environments is currently an open question. Blind walking involves locomotion and the egocentric updating of the environment with one's own movement. We compared this measure to blind throwing, a task that involves the initiation of a movement directed by vision, but no further interaction within the environment. Both throwing and walking were compressed in the VE but accurate in the real world. We suggest that distance compression found in VEs may be a result of a general perceptual origin rather than specific to the response measure.
Immunoglobulin light chain (IgL) genes in zebrafish: Genomic configurations and inversional rearrangements between (VL–JL–CL) gene clusters (2007)

In mammals, Immunoglobulin light chain (IgL) are localized to two chromosomal regions (designated kappa and lambda). Here we report a genome-wide survey of IgL genes in the zebrafish revealing (V(L)-J(L)-C(L)) clusters spanning 5 separate chromosomes. To elucidate IgL loci present in the zebrafish genome assembly (Zv6), conventional sequence similarity searches and a novel scanning approach based on recombination signal sequence (RSS) motifs were applied. RT-PCR with zebrafish cDNA was used to confirm annotations, evaluate VJ-rearrangement possibilities and show that each chromosomal locus is expressed. In contrast to other vertebrates in which IgL exon usage has been studied, inversional rearrangement between (V(L)-J(L)-C(L)) clusters were found. Inter-cluster rearrangements may convey a selective advantage for editing self-reactive receptors and poise zebrafish by virtue of their extensive numbers of V(L), J(L) and C(L) to have greater potential for immunoglobulin gene shuffling than traditionally studied mice and human models.
Small mammalian animal models of heart disease. (2016)

There is an urgent clinical need to develop new therapeutic approaches for treating cardiovascular disease, but the biology of cardiovascular regeneration is complex. Model systems are required to advance our understanding of the pathogenesis, progression, and mechanisms underlying cardiovascular disease as well as to test therapeutic approaches to regenerate tissue and restore cardiac function following injury. An ideal model system should be inexpensive, easily manipulated, reproducible, physiologically representative of human disease, and ethically sound. The choice of animal model needs to be considered carefully since it affects experimental outcomes and whether findings of the study can be reasonably translated to humans. This review presents a guideline for the commonly used small animal models (mice, rats, rabbits, and cats) used in cardiac research as an effort to standardize the most relevant procedures and obtain translatable and reproducible results.
Role of Fas ligand (CD95L) in immune escape: the tumor cell strikes back (1997)

Several different tumor types have recently been shown to express functional Fas ligand (FasL), which may represent an additional mechanism of tumor escape. However, the in vivo significance of these findings in the context of potent adversaries such as activated CTL or NK cells remains to be fully established. The potential interactions between tumor cells and the host immune response are thus more complex than previously thought; their elucidation will benefit the rational design of cancer immunotherapy strategies.