gebhart/patrepeval huggingface dataset:
Blocking TIM-3 in Treatment-refractory Advanced Solid Tumors: A Phase Ia/b Study of LY3321367 with or without an Anti-PD-L1 Antibody (2021)

LY3321367 exhibited acceptable safety profile with favorable pharmacokinetics/pharmacodynamics but only modest antitumor activity. The therapeutic relevance of TIM-3 blockade requires further investigation.
Role of Apoptosis in Wound Healing and Apoptosis Alterations in Microgravity (2021)

Functioning as the outermost self-renewing protective layer of the human organism, skin protects against a multitude of harmful biological and physical stimuli. Consisting of ectodermal, mesenchymal, and neural crest-derived cell lineages, tissue homeostasis, and signal transduction are finely tuned through the interplay of various pathways. A health problem of astronauts in space is skin deterioration. Until today, wound healing has not been considered as a severe health concern for crew members. This can change with deep space exploration missions and commercial spaceflights together with space tourism. Albeit the molecular process of wound healing is not fully elucidated yet, there have been established significant conceptual gains and new scientific methods. Apoptosis, e.g., programmed cell death, enables orchestrated development and cell removal in wounded or infected tissue. Experimental designs utilizing microgravity allow new insights into the role of apoptosis in wound healing. Furthermore, impaired wound healing in unloading conditions would depict a significant challenge in human-crewed exploration space missions. In this review, we provide an overview of alterations in the behavior of cutaneous cell lineages under microgravity in regard to the impact of apoptosis in wound healing. We discuss the current knowledge about wound healing in space and simulated microgravity with respect to apoptosis and available therapeutic strategies.
NMR nomenclature. Nuclear spin properties and conventions for chemical shifts(IUPAC Recommendations 2001) (2001)

Abstract A unified scale is recommended for reporting the NMR chemical shifts of all nuclei relative to the 1 H resonance of tetramethylsilane (TMS). The unified scale is designed to provide a precise ratio, Ξ , of the resonance frequency of a given nuclide to that of the primary reference, the 1H resonance of TMS in dilute solution (volume fraction, φ &lt; 1%) in chloroform. Referencing procedures are discussed, including matters of practical application of the unified scale. Special attention is paid to recommended reference samples, and values of Ξ for secondary references on the unified scale are listed, many of which are the results of new measurements. Some earlier recommendations relating to the reporting of chemical shifts are endorsed. The chemical shift, δ , is redefined to avoid previous ambiguities but to leave practical usage unchanged. Relations between the unified scale and recently published recommendations for referencing in aqueous solutions (for specific use in biochemical work) are discussed, as well as the special effects of working in the solid state with magic-angle spinning. In all, nine new recommendations relating to chemical shifts are made. Standardized nuclear spin data are also presented in tabular form for the stable (and some unstable) isotopes of all elements with nonzero quantum numbers. The information given includes quantum numbers, isotopic abundances, magnetic moments, magnetogyric ratios and receptivities, together with quadrupole moments and line-width factors where appropriate.
Supplementary Figure 3C-D from Engineered Thio-Trastuzumab-DM1 Conjugate with an Improved Therapeutic Index to Target Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer (2023)

Supplementary Figure 3C-D from Engineered Thio-Trastuzumab-DM1 Conjugate with an Improved Therapeutic Index to Target Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer
Evaluation of Waste Concrete Road Materials for Use in Oyster Aquaculture (2013)

The Maryland State Highway Administration (SHA) intends to increase the use of recycled materials and to use products in an environmentally responsible manner. As roads and bridges are resurfaced, old concrete is removed and is usually discarded. It would be in the best interest of SHA, in support of its sustainability initiatives, that these materials be recycled and repurposed for alternative uses. One such potential use is to condition portions of the Chesapeake Bay bottom to support spat-on-shell aquaculture projects. For recycled concrete aggregate (RCA) to be used within the aquatic setting of the Chesapeake Bay, its chemical behavior under saturated conditions must be understood to avoid potential adverse impacts to the bay's aquatic ecosystem. The primary objective of this study was to determine the suitability of recycled concrete as conditioning material for on-bottom oyster aquaculture in the Chesapeake Bay. The results of this project showed that using RCA as a base material for oyster reefs did not adversely affect oyster spat growth and survival, or the surrounding environment. There was no statistical difference between shell and RCA on the growth, survivorship, average length, or recruitment of young oysters. Initial pH was slightly higher for the RCA than the oyster shell control, but pH stabilized to around 7.6 to 7.8 for all treatments after seven days. Based on the findings of this study, the recommendation is to initiate a second phase study that places RCA on test plots in the Chesapeake Bay to validate the laboratory tests in-situ.
Antiviral Activity of Shiga Toxin Requires Enzymatic Activity and Is Associated with Increased Permeability of the Target Cells (2002)

This study expanded our earlier finding that Shiga toxin type 1 (Stx1) has activity against bovine leukemia virus (BLV) (W. A. Ferens and C. J. Hovde, Infect. Immun. 68:4462-4469, 2000). The Stx molecular motifs required for antiviral activity were identified, and a mechanism of Stx action on virally infected cells is suggested. Using inhibition of BLV-dependent spontaneous lymphocyte proliferation as a measure of antiviral activity, we showed that Stx2 had antiviral activity similar to that of Stx1. Enzymatic and antiviral activities of three StxA1 chain mutants deficient in enzymatic activity or aspects of receptor-mediated cytotoxicity were compared. Using protein synthesis inhibition to measure enzymatic activity, the mutant E167D was 300-fold less catalytically active than wild-type StxA1, was minimally active in antiviral assays, and did not inhibit synthesis of viral proteins. Two StxA1 mutants, A231D-G234E and StxA(1)1 (enzymatically active but unable to kill cells via the classical receptor-mediated route), had undiminished antiviral activity. Although binding of radiolabeled StxA1 to bovine blood cells or to free virus was not detected, flow cytometric analysis showed that the number of BLV-expressing cells were specifically reduced in cultures treated with Stx. These unique and rare lymphocytes were highly permeable to 40- and 70-kDa fluorescent dextrans, indicating that direct absorption of toxins by virus-expressing cells is a potential mechanism of target cell intoxication. These results support the hypothesis that Stx-producing Escherichia coli colonization of the gastrointestinal tract may benefit ruminant hosts by the ability of Stxs to exert antiviral activity.
A practical scheduling algorithm to achieve 100% throughput in input-queued switches (2002)

Input queueing is becoming increasingly used for high-bandwidth switches and routers. In previous work, it was proved that it is possible to achieve 100% throughput for input-queued switches using a combination of virtual output queueing and a scheduling algorithm called LQF However, this is only a theoretical result: LQF is too complex to implement in hardware. We introduce a new algorithm called longest port first (LPF), which is designed to overcome the complexity problems of LQF, and can be implemented in hardware at high speed. By giving preferential service based on queue lengths, we prove that LPF can achieve 100% throughput.
Basal Forebrain Thermoregulatory Mechanism Modulates Auto-Regulated Sleep (2012)

Regulation of body temperature and sleep are two physiological mechanisms that are vital for our survival. Interestingly neural structures implicated in both these functions are common. These areas include the medial preoptic area (POA), the lateral POA, the ventrolateral POA, the median preoptic nucleus, and the medial septum, which form part of the basal forebrain (BF). When given a choice, rats prefer to stay at an ambient temperature of 27°C, though the maximum sleep was observed when they were placed at 30°C. Ambient temperature around 27°C should be considered as the thermoneutral temperature for rats in all sleep studies. At this temperature the diurnal oscillations of sleep and body temperature are properly expressed. The warm sensitive neurons of the POA mediate the increase in sleep at 30°C. Promotion of sleep during the rise in ambient temperature from 27 to 30°C, serve a thermoregulatory function. Autonomous thermoregulatory changes in core body temperature and skin temperature could act as an input signal to modulate neuronal activity in sleep-promoting brain areas. The studies presented here show that the neurons of the BF play a key role in regulating sleep. BF thermoregulatory system is a part of the global homeostatic sleep regulatory mechanism, which is auto-regulated.
Hydrotalcite and an Amorphous Clay Mineral in High-Magnesium Mudstones from the Kozani Basin, Greece (2000)

ABSTRACT The paper describes two unusual lithologies that occur in a sequence of Mg-rich lacustrine sediments in northern Greece. The first is a laminated mudstone in which layers composed of magnesian smectite alternate with layers composed of an amorphous clay of similar chemical composition. The second lithology is a thin bed of mudstone in which the only crystalline constituent is hydrotalcite (a magnesium aluminum hydroxide), accompanied by amorphous high-magnesium clay. Hydrotalcite has not previously been recorded from sedimentary rocks except as a product of industrial pollution. The high-magnesium clay is considered to have formed by precipitation from Mg-rich lake water onto volcanic ash particles, whilst the hydrotalcite has filled the molds left by dissolution of volcanic glass within the clay-coated particles.
Comparison of serology and culture for detecting Salmonella infection of 5 to 7 month old swine (1997)

There was a significant direct correlation between the presence of Salmonella in ileocecal lymph nodes and the titer of antibody to Salmonella in meat juice. It was also demonstrated that there is no significant correlation between titer of antibody in serum collected from pigs immediately prior to slaughter and the presence of Salmonella in the feces on the floor of pens. These conclusions suggest that the level of antibody to Salmonella in meat juice can be used to determine whether or not groups of pigs at slaughter contain Salmonella in their ileocecal lymph nodes.
898 Intratumoral administration of NL-201, an alpha-independent IL-2/15 receptor agonist, inhibits the growth of both injected and uninjected tumors in preclinical models (2021)

<h3>Background</h3> NL-201 is a potent, selective, and long-acting computationally designed alpha-independent agonist of the IL-2 and IL-15 receptors that is being developed as an immunotherapy for cancer. Intravenous NL-201 administration is active in numerous pre-clinical tumor models. Here, we report data demonstrating favorable tolerability, pharmacokinetics, and antitumor activity of NL-201 after intratumoral (IT) administration in syngeneic murine tumor models. <h3>Methods</h3> Mice were implanted with syngeneic colorectal tumors in a single tumor (right flank) or bilateral tumor model (right and left flank). Once tumors were established, mice were randomized to receive IT or intravenous (IV) NL-201, or IV vehicle as control. Tumor volumes (mm<sup>3</sup>) and bodyweights were measured twice weekly, and mice were monitored for abnormal clinical signs. Blood samples were collected at pre-specified time points, and serum was analyzed for NL-201 concentration using a ligand-binding assay. Toxicokinetic parameters were determined using a non-compartmental model consistent with the IT and IV routes. Animals were sacrificed if tumor sizes reached 2000 mm<sup>3</sup> or if body weight loss was &gt;20%. In the bilateral tumor models, surviving tumor-free animals from both the IT and IV treatment arms were rechallenged with tumor cells after a washout period to assess antitumor immune responses. <h3>Results</h3> IT NL-201 demonstrated dose-dependent antitumor activity and was well tolerated based on a lack of clinical observations and body weight changes at doses up to 10 µg/mouse. Comparable antitumor activity was observed in mice receiving 3 μg/mouse NL-201 via IV or IT routes, but reduced systemic exposure and better tolerability were observed after IT administration. The estimated absolute bioavailability following 3 µg/mouse IT administration was 19.4%–66.5% of the NL-201 IV exposure. In the bilateral tumor model, IT NL-201 resulted in significant antitumor activity in both the treated and untreated tumors. Surviving animals from both IT and IV groups in which the initial tumors regressed rejected engraftment of the same tumor cell line upon rechallenge. <h3>Conclusions</h3> IT NL-201 administration resulted in dose-dependent antitumor activity in both injected and uninjected tumors while demonstrating markedly reduced systemic exposure and improved tolerability compared to systemic administration at equivalent dose levels. Rechallenged animals failed to develop tumors, demonstrating durable tumor-specific immunity after IT NL-201 treatment. Results of this study support planned clinical investigation of IT NL-201 administration to increase NL-201 concentrations in accessible lesions. <h3>Ethics Approval</h3> This study was approved by the Institutional Animal Care and Use Committee (IACUC) of CrownBio.
ChemInform Abstract: EFFECT OF PRESSURE ON FORMATION OF CAZRO3 BY SOLID‐STATE REACTION BETWEEN CAO AND ZRO2 (1974)

Abstract Die Bildungsgeschwindigkeit von CaZrO 3 in CaO‐ZIOZ‐Diffusionspaaren verändert sich mit dem angelegten Druck.
An endoscopic staining method for detection and operation of early gastric cancer. (1979)

The long term survival rate of gastric cancer has been much improved, and the 5-year survival rate in our institute was 42% with a significant difference between 29% in the advanced stage and 94% in the early stage. This result means that gastric cancer must be detected and treated early as possible. However, the diagnosis of early gastric cancer may remain extremely difficult even for an excellent endoscopist. Therefore, in order to clearly recognize early gastric cancer, an endoscopic staining method with methylene blue has been studied. In this method, one capsule of 150 mg methylene blue is swallowed with a small amount of proteinase solution 3 hours before endoscopy. Gastroscopy is performed routinely after this preparation. This procedure was performed on 153 gastric cancers and 137 of them (89.5%) have been successfully dyed in dark blue. In several cases, with this method, the actual borderline between the normal mucosa and the malignant extent was clearly recognized and resection line was decided. Introduction of methylene blue into the stomach could also stain the intestinalized epithelium of the gastric mucosa. Differential diagnosis of the dyed intestinal metaplasia and the dyed carcinoma seems to be very easy, because both gastric lesions have the characteristic dyed patterns. Mechanism of this phenomenon has been considered to be due to an absorption of the dye in the intestinal metaplasia, and in the gastric cancer, many factors may be involved, among which are the infiltration or diffusion of the dye into the cancerous tissue, the absorption from the abnormal epithelium, and the staining of the necrotic tissue.
Association of microRNA-7 and its binding partner CDR1-AS with the prognosis and prediction of 1st-line tamoxifen therapy in breast cancer (2018)

The large number of non-coding RNAs (ncRNAs) and their breadth of functionalities has fuelled many studies on their roles in cancer. We previously linked four microRNAs to breast cancer prognosis. One of these microRNAs, hsa-miR-7, was found to be regulated by another type of ncRNA, the circular non-coding RNA (circRNA) CDR1-AS, which contains multiple hsa-miR-7 binding sites. Based on this finding, we studied the potential clinical value of this circRNA on breast cancer prognosis in a cohort based on a cohort that was previously analysed for hsa-miR-7 and in an adjuvant hormone-naïve cohort for 1<sup>st</sup>-line tamoxifen treatment outcomes, in which we also analysed hsa-miR-7. A negative correlation was observed between hsa-miR-7 and CDR1-AS in both cohorts. Despite associations with various clinical metrics (e.g., tumour grade, tumour size, and relapse location), CDR1-AS was neither prognostic nor predictive of relevant outcomes in our cohorts. However, we did observe stromal CDR1-AS expression, suggesting a possible cell-type specific interaction. Next to the known association of hsa-miR-7 expression with poor prognosis in primary breast cancer, we found that high hsa-miR-7 expression was predictive of an adverse response to tamoxifen therapy and poor progression-free and post-relapse overall survival in patients with recurrent disease.
Mechanical Load of the Lumbar Spine During Forward Bending Motion of the Trunk–A Biomechanical Study (2005)

We found that the increase of the actual spinal load during trunk flexion in healthy individuals consisted of the theoretical spinal load and load generated by the back muscle activities.
Different Tyrosine Autophosphorylation Requirements in Fibroblast Growth Factor Receptor-1 Mediate Urokinase-Type Plasminogen Activator Induction and Mitogenesis (1999)

Among the seven tyrosine autophosphorylation sites identified in the intracellular domain of tyrosine kinase fibroblast growth factor receptor-1 (FGFR1), five of them are dispensable for FGFR1-mediated mitogenic signaling. The possibility of dissociating the mitogenic activity of basic FGF (FGF2) from its urokinase-type plasminogen activator (uPA)-inducing capacity both at pharmacological and structural levels prompted us to evaluate the role of these autophosphorylation sites in transducing FGF2-mediated uPA upregulation. To this purpose, L6 myoblasts transfected with either wild-type (wt) or various FGFR1 mutants were evaluated for the capacity to upregulate uPA production by FGF2. uPA was induced in cells transfected with wt-FGFR1, FGFR1-Y463F, -Y585F, -Y730F, -Y766F, or -Y583/585F mutants. In contrast, uPA upregulation was prevented in L6 cells transfected with FGFR1-Y463/583/585/730F mutant (FGFR1-4F) or with FGFR1-Y463/583/585/730/766F mutant (FGFR1-5F) that retained instead a full mitogenic response to FGF2; however, preservation of residue Y730 in FGFR1-Y463/583/585F mutant (FGFR1-3F) and FGFR1-Y463/583/585/766F mutant (FGFR1-4Fbis) allows the receptor to transduce uPA upregulation. Wild-type FGFR1, FGFR1-3F, and FGFR1-4F similarly bind to a 90-kDa tyrosine-phosphorylated protein and activate Shc, extracellular signal-regulated kinase (ERK)2, and JunD after stimulation with FGF2. These data, together with the capacity of the ERK kinase inhibitor PD 098059 to prevent ERK2 activation and uPA upregulation in wt-FGFR1 cells, suggest that signaling through the Ras/Raf-1/ERK kinase/ERK/JunD pathway is necessary but not sufficient for uPA induction in L6 transfectants. Accordingly, FGF2 was able to stimulate ERK1/2 phosphorylation and cell proliferation, but not uPA upregulation, in L6 cells transfected with the FGFR1-Y463/730F mutant, whereas the FGFR1-Y583/585/730F mutant was fully active. We conclude that different tyrosine autophosphorylation requirements in FGFR1 mediate cell proliferation and uPA upregulation induced by FGF2 in L6 cells. In particular, phosphorylation of either Y463 or Y730, dispensable for mitogenic signaling, represents an absolute requirement for FGF2-mediated uPA induction.
ENHANCEMENT OF VEHICLE STABILITY BY CONTROLLING THE FRONT BRAKES AND ENGINE TORQUE (1998)

For the progress of vehicle safety, enhancement of active safety performance is as important as crash safety performance. In emergency situations, it is very difficult for an ordinary driver to stabilize the vehicle because steering, braking, and/or other operations in this situation change the vehicle behavior suddenly. From this point of view, enhancement of vehicle stability is very important for active safety. HONDA has developed an active safety system called VSA (Vehicle Stability Assist) based on expanding the usual active safety system, ABS (Anti-lock Brake System) and TCS (Traction Control System). VSA controls front wheel brakes and engine torque to stabilize the vehicle by comparing yaw rate of the vehicle with the reference value calculated from lateral acceleration and vehicle speed, and the driver's intention estimated from steering angle. For the covering abstract see IRRD E102514.
Stability and intrinsic dissolution of vacuum compression molded amorphous solid dispersions of efavirenz (2022)

In this study, the stability and intrinsic dissolution of vacuum compression molded (VCM) amorphous solid dispersions (ASDs) of efavirenz (EFV) were investigated in relation to its solubility limits in seven polymers determined by the melting point depression (MPD) method. The extrapolated solubility limits of EFV at 22 °C ranged from 3 to 68% (w/w) with PVOH being the only polymer suggesting immiscibility with EFV according to both MPD and Hansen solubility parameters (HSPs). All ASDs with EFV loadings below or close to their calculated solubility limit did not show any signs of crystallization upon conditioning for 7 months at either 22 or 37 °C and 23 or 75% relative humidity. However, all ASDs with EFV loading above the solubility limit crystallized at high humidity, while the ASDs with cellulose derived carrier polymers proved kinetically stable at low humidity over 7 months. While the EFV intrinsic dissolution rates from the VCM ASDs were partly depending on the polymer dissolution rate, no correlation was observed between EFV matrix crystallization and its miscibility in the polymer. Altogether, the observations of the study underline the importance of combining preformulation miscibility determination and dissolution studies to rationally decide on both stability and viability of ASD formulations.
Studies on Dyeing Performance of Novel Acid Azo Dyes and Mordent Acid Azo Dyes Based on 2,4‐Dihydroxybenzophenone (2008)

Novel acid azo and mordent acid azo dyes have been prepared by the coupling of diazo solution of different aminonaphthol sulphonic acids and aromatic amino acids with 2,4‐dihydroxybenzophenone. The resultant dyes were characterized by elemental analysis as well as IR and 1 H NMR spectral studies. The UV‐visible spectral data have also been discussed in terms of structure property relationship. The dyeing assessments of all the dyes were evaluated on wool and silk textile fibers. The dyeing of chrome pretreated wool and silk have also been monitored. The result shows that better hue was obtained on mordented fiber. Results of bactericidal studies of chrome pretreated fibers revealed that the toxicity of mordented dyes against bacteria is fairly good. Dyeing on wool and silk fibers resulted in yellowish pink to reddish brown colourations having excellent light fastness and washing fastness.