gebhart/patrepeval huggingface dataset:
Active specific immunotherapy in patients with melanoma. A clinical trial with mouse antiidiotypic monoclonal antibodies elicited with syngeneic anti-high-molecular-weight-melanoma-associated antigen monoclonal antibodies. (1990)

In two clinical trials the mouse antiidiotypic monoclonal antibody (MAb) MF11-30, which bears the internal image of human high-molecular-weight-melanoma-associated antigen (HMW-MAA) was administered by subcutaneous route without adjuvants to patients with stage IV malignant melanoma on day 0, 7, and 28. Additional injections were administered if anti-antiidiotypic antibodies were not found or their titer decreased. In the first phase I trial with 16 patients the initial dose was 0.5 mg per injection and escalated to 4 mg per injection. Neither toxicity nor allergic reactions were observed despite the development of anti-mouse Ig antibodies. Minor responses were observed in three patients. In a second clinical trial MAb MF11-30 was administered to 21 patients at a dose of 2 mg per injection, since this dose had been shown in the initial study to be effective in inducing anti-antiidiotypic antibodies. Two patients were inevaluable; in the remaining 19 patients, the average duration of treatment was 34 wk. In this trial as well, neither toxicity nor allergic reactions were observed. 17 of the 19 immunized patients increased the levels of anti-mouse Ig antibodies and 16 developed antibodies that inhibit the binding of antiidiotypic MAb MF11-30 to the immunizing anti-HMW-MAA MAb 225.28. One patient increased the level of anti-HMW-MAA antibodies. One patient achieved a complete remission with disappearance of multiple abdominal lymph nodes for a duration of 95 wk. Minor responses were observed in three patients. These results suggest that mouse antiidiotypic MAb that bear the internal image of HMW-MAA may be useful reagents to implement active specific immunotherapy in patients with melanoma.
Detection of ERBB2 (HER2) Gene Amplification Events in Cell-Free DNA and Response to Anti-HER2 Agents in a Large Asian Cancer Patient Cohort (2019)

Background: HER2 antagonists have marked activity and are approved in the first-line for HER2 overexpressing breast and gastric (GC) cancers. Recent studies show that ERBB2 (HER2) gene amplification and overexpression may also be actionable in other tumor types. Inter- and intratumoral heterogeneity in HER2 status, however, poses a significant challenge in identifying patients that may benefit from HER2-targeted therapies. ERBB2 amplification as identified by circulating cell-free (cfDNA), which circumvents tissue heterogeneity issues, is emerging as a robust biomarker predictive of response to anti-HER2 agents. Here, the prevalence of ERBB2 alterations detectable by next-generation sequencing (NGS) of cfDNA was evaluated in a large cohort of Asian patients with advanced solid tumors. Methods: Results were queried for consecutive patients (n=469) tested by a comprehensive 73-gene cfDNA NGS assay (Guardant360) between November 2015 and June 2018. Patients with ERBB2 gene alterations including copy number amplifications (CNA), single nucleotide variants (SNV), and insertion-deletions (indel) were identified. Results: ERBB2 alterations were detected in 52 patients (11.1%); ERBB2 SNV, CNA, and indel were found in 27 (5.8%), 27 (5.8%), and 10 (2.1%) patients, respectively. ERBB2 amplification was most frequently identified in GC (21.4%; 6/28), CRC (11.1%; 5/45), lung (4%; 9/226), and breast (3.2%; 1/31) cancer patients. It was often mutually exclusive with other oncogenic drivers in GC (80%; 4/5) and CRC (50%; 2/4). High level ERBB2 copy number (CN) gains were observed in both GC and CRC (median CN 8.4 and 19.2, respectively). We further report two cases of advanced GC patients, one treatment naïve and the other having failed 4 lines of therapy, whose ERBB2 CNA was identified by cfDNA and derived clinical benefit from initiation of HER2-based therapies. Conclusion: Our data indicate that ERBB2 amplification is a common event in solid tumors among Asian cancer patients. Higher ERBB2 incidence and CN were observed in GC and CRC patients in the absence of other oncogenic alterations, underscoring its likely role as the driver alteration in those settings. Finally, we show the potential of comprehensive cfDNA testing in identifying patients who are most likely to benefit from HER2-targeted therapies.
Robust Speaker-Adaptive HMM-Based Text-to-Speech Synthesis (2009)

This paper describes a speaker-adaptive HMM-based speech synthesis system. The new system, called ldquoHTS-2007,rdquo employs speaker adaptation (CSMAPLR+MAP), feature-space adaptive training, mixed-gender modeling, and full-covariance modeling using CSMAPLR transforms, in addition to several other techniques that have proved effective in our previous systems. Subjective evaluation results show that the new system generates significantly better quality synthetic speech than speaker-dependent approaches with realistic amounts of speech data, and that it bears comparison with speaker-dependent approaches even when large amounts of speech data are available. In addition, a comparison study with several speech synthesis techniques shows the new system is very robust: It is able to build voices from less-than-ideal speech data and synthesize good-quality speech even for out-of-domain sentences.
Percutaneous Pericardial Instrumentation for Endo-Epicardial Mapping of Previously Failed Ablations (2003)

Failure of endocardial ablation could reflect the presence of an epicardial arrhythmia substrate. Epicardial instrumentation and ablation appeared feasible and safe and provided an alternative strategy for the treatment of patients with a variety of arrhythmias. This was particularly true for VT, including patients without structural heart disease.
A simulation based study of on-demand routing protocols for ad hoc wireless networks (2002)

Ad hoc networks are wireless, mobile networks that can be set up anywhere and anytime without the aid of any established infrastructure or centralized administration. Because of the limited range of each host's wireless transmission, to communicate with hosts outside its transmission range, a host needs to enlist the aid of its nearby hosts in forwarding packets to the destination. However, since there is no stationary infrastructure such as base stations, each host has to act as a router for itself. A routing protocol for ad hoc networks is executed on every host and is therefore subject to the limit of the resources at each mobile host. A good routing protocol should minimize the computing load on the host as well as the traffic overhead on the network. Therefore, a number of routing protocols have been proposed for ad hoc wireless networks. We focus upon on-demand schemes. We study and compare the performance of the following three routing protocols AODV, CBRP and DSR. A variety of workload and scenarios, as characterized by mobility, load and size of the ad hoc network were simulated. Our results indicate that despite its improvement in reducing route request packets, CBRP has a higher overhead than DSR because of its periodic hello messages while AODV's end-to-end packet delay is the shortest when compared to DSR and CBRP.
Drugging the Cancer Chaperone HSP90 (2007)

The molecular chaperone HSP90 has emerged as an exciting target for cancer treatment. We review the potential advantages of HSP90 inhibitors, particularly the simultaneous combinatorial depletion of multiple oncogenic "client" proteins, leading to blockade of many cancer-causing pathways and the antagonism of all of the hallmark pathological traits of malignancy. Cancer selectivity is achieved by exploiting cancer "dependencies," including oncogene addiction and the stressed state of malignant cells. The multiple downstream effects of HSP90 inhibitors should make the development of resistance more difficult than with agents having more restricted effects. We review the various classes of HSP90 inhibitor that have been developed, including the natural products geldanamycin and radicicol and also the purine scaffold and pyrazole/isoxazole class of synthetic small molecule inhibitors. A first-in-class HSP90 drug, the geldanamycin analog 17-AAG, has provided proof of concept for HSP90 inhibition in patients at well tolerated doses and therapeutic activity has been seen. Other inhibitors show promise in preclinical and clinical development. Opportunities and challenges for HSP90 inhibitors are discussed, including use in combination with other agents. Most of the current HSP90 inhibitors act by blocking the essential nucleotide binding and ATPase activity required for chaperone function. Potential new approaches are discussed, for example, interference with cochaperone binding and function in the superchaperone complex. Biomarkers for use with HSP90 inhibitors are described. We stress how basic and translational research has been mutually beneficial and indicate future directions to enhance our understanding of molecular chaperones and their exploitation in cancer and other diseases.
[Treatment of extensive deep burn of scalp with full-thickness necrosis of calvarial bone]. (1995)

From 1990 to 1993 eight patients suffering from extensive deep burn of scalp with full-thickness necrosis of calvarial bone were treated. The intra-cranial damage following electrical injury or prolonged contact with heat source, and the extent of skull necrosis were delineated by CT and bone scanning. Primary coverage of the exposed calvarial bone using musculo-cutaneous flap or free skin flap was done, leaving the necrosed skull in situ to serve as a scaffold of "creeping substitution" for bone regeneration. Primary healing of the wound was achieved in four cases. Three cases required an average of 2.6 times of curettage or excision of the infected bone. None of the cases required a late reconstruction of the skull in this group.
Adalimumab for the treatment of fistulas in patients with Crohn’s disease (2009)

Objective: To evaluate the efficacy of adalimumab in the healing of draining fistulas in patients with active Crohn’s disease (CD). Design: A phase III, multicentre, randomised, double-blind, placebo controlled study with an open-label extension was conducted in 92 sites. Patients: A subgroup of adults with moderate to severely active CD (CD activity index 220–450) for ⩾4 months who had draining fistulas at baseline. Interventions: All patients received initial open-label adalimumab induction therapy (80 mg/40 mg at weeks 0/2). At week 4, all patients were randomly assigned to receive double-blind placebo or adalimumab 40 mg every other week or weekly to week 56 (irrespective of fistula status). Patients completing week 56 of therapy were then eligible to enroll in an open-label extension. Main Outcome Measures: Complete fistula healing/closure (assessed at every visit) was defined as no drainage, either spontaneous or with gentle compression. Results: Of 854 patients enrolled, 117 had draining fistulas at both screening and baseline (70 randomly assigned to adalimumab and 47 to placebo). The mean number of draining fistulas per day was significantly decreased in adalimumab-treated patients compared with placebo-treated patients during the double-blind treatment period. Of all patients with healed fistulas at week 56 (both adalimumab and placebo groups), 90% (28/31) maintained healing following 1 year of open-label adalimumab therapy (observed analysis). Conclusions: In patients with active CD, adalimumab therapy was more effective than placebo for inducing fistula healing. Complete fistula healing was sustained for up to 2 years by most patients in an open-label extension trial. ClinicalTrials.gov Identifier: NCT00077779 and NCT00195715.
Plasma terminal half‐life (2004)

Terminal plasma half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium, and not the time required to eliminate half the administered dose. When the process of absorption is not a limiting factor, half-life is a hybrid parameter controlled by plasma clearance and extent of distribution. In contrast, when the process of absorption is a limiting factor, the terminal half-life reflects rate and extent of absorption and not the elimination process (flip-flop pharmacokinetics). The terminal half-life is especially relevant to multiple dosing regimens, because it controls the degree of drug accumulation, concentration fluctuations and the time taken to reach equilibrium.
A Matter of Degree: Faculty Morale as a Function of Involvement in Institutional Decisions During Times of Financial Distress (1986)

Recent literature suggests that including faculty in institutional governance relates positively with higher faculty morale. This study examined provosts’ and faculty perceptions of morale as related to faculty involvement in decision making during a time of financial stress. The results indicate a direct relationship between morale and the severity of the institutional reduction plan implemented. However, a relationship between faculty participation in the reduction process and faculty morale was not found. Suggestions for institutional decision making strategies are presented.
Direct Access to Ketones from Aldehydes via Rhodium-Catalyzed Cross-Coupling Reaction with Potassium Trifluoro(organo)borates (2004)

A direct cross-coupling reaction of aromatic aldehydes with potassium trifluoro(organo)borates afforded ketones in high yields and under mild conditions in the presence of a rhodium catalyst and acetone. This new reaction, involving a formal aldehyde C-H bond activation, is believed to proceed via a Heck-type mechanism followed by hydride transfer to acetone.
Multilineage Potential Research of Bovine Amniotic Fluid Mesenchymal Stem Cells (2014)

The use of amnion and amniotic fluid (AF) are abundant sources of mesenchymal stem cells (MSCs) that can be harvested at low cost and do not pose ethical conflicts. In human and veterinary research, stem cells derived from these tissues are promising candidates for disease treatment, specifically for their plasticity, their reduced immunogenicity, and high anti-inflammatory potential. This work aimed to obtain and characterize bovine amniotic fluid mesenchymal stem cells (AFMSC). The bovine AF from the amniotic cavity of pregnant gilts in the early stages of gestation (3- and 4-m-old bovine embryos) was collected. AFMSCs exhibit a fibroblastic-like morphology only starting from the fourth passage, being heterogeneous during the primary culture. Immunofluorescence results showed that AFMSCs were positive for β-integrin, CD44, CD73 and CD166, but negative for CD34, CD45. Meanwhile, AFMSCs expressed ES cell markers, such as Oct4, and when appropriately induced, are capable of differentiating into ectodermal and mesodermal lineages. This study reinforces the emerging importance of these cells as ideal tools in veterinary medicine; future studies aimed at a deeper evaluation of their immunological properties will allow a better understanding of their role in cellular therapy.
The roles of the prostaglandin D2receptors DP1and CRTH2 in promoting allergic responses (2007)

Prostaglandin D(2) (PGD(2)) is produced by mast cells, Th2 lymphocytes and dendritic cells and has been detected in high concentrations at sites of allergic inflammation. PGD(2) exerts its inflammatory effects through high affinity interactions with the G protein coupled receptors DP(1) and chemoattractant-homologous receptor expressed on Th2 cells (CRTH2, also known as DP(2)). DP(1) and CRTH2 act in concert to promote a number of biological effects associated with the development and maintenance of the allergic response. During the process of allergen sensitization, DP(1) activation may enhance polarization of Th0 cells to Th2 cells by inhibiting production of interleukin 12 by dendritic cells. Upon exposure to allergen in sensitized individuals, activation of DP(1) may contribute to the long lasting blood flow changes in the target organ. CRTH2 is expressed by Th2 lymphocytes, eosinophils and basophils and may mediate the recruitment of these cell types during the late phase allergic response. The role played by CRTH2 in promoting the production of Th2 cytokines and IgE make antagonism of this receptor a particularly attractive approach to the treatment of chronic allergic disease.
Human Toll-like receptor 4 responses toP. gingivalisare regulated by lipid A 1- and 4′-phosphatase activities (2009)

Signal transduction following binding of lipopolysaccharide (LPS) to Toll-like receptor 4 (TLR4) is an essential aspect of host innate immune responses to infection by Gram-negative pathogens. Here, we describe a novel molecular mechanism used by a prevalent human bacterial pathogen to evade and subvert the human innate immune system. We show that the oral pathogen, Porphyromonas gingivalis, uses endogenous lipid A 1- and 4'-phosphatase activities to modify its LPS, creating immunologically silent, non-phosphorylated lipid A. This unique lipid A provides a highly effective mechanism employed by this bacterium to evade TLR4 sensing and to resist killing by cationic antimicrobial peptides. In addition, lipid A 1-phosphatase activity is suppressed by haemin, an important nutrient in the oral cavity. Specifically, P. gingivalis grown in the presence of high haemin produces lipid A that acts as a potent TLR4 antagonist. These results suggest that haemin-dependent regulation of lipid A 1-dephosphorylation can shift P. gingivalis lipid A activity from TLR4 evasive to TLR4 suppressive, potentially altering critical interactions between this bacterium, the local microbial community and the host innate immune system.
Involvement of Alcohol Dehydrogenase, Short-Chain Dehydrogenase/Reductase, Aldehyde Dehydrogenase, and Cytochrome P450 in the Control of Retinoid Signaling by Activation of Retinoic Acid Synthesis (1996)

The effects of vitamin A (retinol) on growth and development are mediated by the active metabolite retinoic acid which controls a nuclear receptor signaling pathway. While elegant work on the retinoic acid receptor family has focused attention upon how the receptor controls this pathway, there now exists a relatively large gap in our understanding of how retinol is activated to form the ligand. During vertebrate embryogenesis and in adult organs retinoic acid is detected in a distinct spatiotemporal pattern, suggesting that it is produced from retinol in a regulated fashion. Enzymes involved in retinol and retinal metabolism are likely candidates for regulators of tissue retinoic acid levels. Members of the alcohol dehydrogenase and short-chain dehydrogenase/reductase enzyme families catalyze the reversible interconversion of retinol and retinal, the rate-limiting step, whereas members of the aldehyde dehydrogenase and cytochrome P450 enzyme families catalyze the irreversible oxidation of retinal to retinoic acid. The identification of enzymes likely to catalyze retinol oxidation in vivo has been particularly controversial, and this is made even more difficult by the reversible nature of this reaction. Taking into account enzymatic properties and coenzyme preferences, a case can be made that class IV alcohol dehydrogenase catalyzes retinol oxidation to provide retinal for retinoic acid synthesis, whereas microsomal retinol dehydrogenase (a short-chain dehydrogenase/reductase) catalyzes the reduction of retinal to retinol to promote retinoid storage. Further studies on these enzyme families will allow this layer of control in the retinoid signaling pathway to be understood.
Restoration of Blood Total Glutathione Status and Lymphocyte Function Following α -Lipoic Acid Supplementation in Patients with HIV Infection (2008)

Supplementation with alpha-lipoic acid may positively impact patients with HIV and acquired immune deficiency syndrome by restoring blood total glutathione level and improving functional reactivity of lymphocytes to T-cell mitogens.
Free-form shape design using triangulated surfaces (1994)

We present an approach to modeling with truly mutable yet completely controllable free-form surfaces of arbitrary topology. Surfaces may be pinned down at points and along curves, cut up and smoothly welded back together, and faired and reshaped in the large. This style of control is formulated as a constrained shape optimization, with minimization of squared principal curvatures yielding graceful shapes that are free of the parameterization worries accompanying many patch-based approaches. Triangulated point sets are used to approximate these smooth variational surfaces, bridging the gap between patch-based and particle-based representations. Automatic refinement, mesh smoothing, and re-triangulation maintain a good computational mesh as the surface shape evolves, and give sample points and surface features much of the freedom to slide around in the surface that oriented particles enjoy. The resulting surface triangulations are constructed and maintained in real time.
Reconstruction of DNA sequencing by hybridization (2002)

In this paper, a new approach is presented to solve the reconstruction problem of DNA sequencing by hybridization, which realizes the computational part of the SBH experiment. The proposed algorithm accepts both the negative and positive errors. The computational experiments show that the algorithm behaves satisfactorily, especially for the case with k-tuple repetitions and positive errors.
Redox regulation of AP-1: a link between transcription factor signaling and DNA repair. (1996)

The inducible transcription factor, AP-\, is a heterodimeric leucine zipper complex containing the protein products ofthejos andjun protooncogenes. The DNA binding activity of Fos and Jun is regulated in vitro by a posttranslational mechanism involving reduction­ oxidation. Redox regulation is mediated through a conserved cysteine residue located in the DNA binding domain of both proteins. Oxidation or chemical modification of the cysteine has an inhibitory effect on AP-l DNA binding activity. Conversely, reduction of this residue by chemical reducing agents or by a ubiquitous nuclear redox factor (Ref-I), purified and cloned from human cells, stimulates AP-l DNA binding activity. In addition, recombinant Ref-l stimulates the DNA binding activity of several other classes of redox regulated transcription factors. Immunodepletion studies indicate that Ref-l is the major AP-l redox activity in Hela cells. Interestingly, Ref-l is a bifunctional protein; it also possesses an apuriniclapyrimidinic (AlP) endonuclease DNA repair activity. However, the redox and DNA repair activities of Ref-l are physically and biochemically distinguishable. Ref-l may represent a novel component of the signal transduction processes that regulate eukaryotic gene expression in response to cellular stress.
Graphene–Organic Two-Dimensional Charge-Transfer Complexes: Intermolecular Electronic Transitions and Broadband Near-Infrared Photoresponse (2018)

Charge-transfer (CT) complexes with unique intermolecular electronic transitions have attracted broad interest and hold great potential in optoelectronic applications. Here, we report a new family of two-dimensional graphene-organic molecule CT complexes. Density functional theory (DFT) calculation has revealed low-energy CT bands in the near-infrared (NIR) region up to 2000 nm for graphene-TCNQ (tetracyanoquinodimethane), graphene-F4TCNQ (2,3,5,6-Tetrafluoro-tetracyanoquinodimethane) and graphene-TCOQ (tetrachloro-o-benzoquinone) complexes. Raman and electrical measurements have confirmed a partial charge transfer between graphene and the molecules at the ground state. CT excitations have been calculated by DFT and verified by optoelectronic measurements. The graphene–organic CT complexes have shown a broadband photoresponse from the visible to NIR range, attributed to the intermolecular electronic transitions. Further, the photoresponsivity (up to 103 A/W) suggests a high photoelectrical gain arising from the photogating effect at the graphene/molecule interface. At last, the photoresponse property of the graphene–organic CT complexes can be tuned by electrical gating of graphene.