Miracle-dz/UniFAR-FTUs huggingface dataset:
Crystal growth and structure of L-methionine L-methioninium hydrogen maleate—a new NLO material

Abstract A new organic nonlinear optical (NLO) crystal from the amino acid family, viz., L-methionine L-methioninium hydrogen maleate (LMMM), has been grown by slow evaporation method from aqueous solution. Bulk crystals were grown using submerged seed solution method. The structure was elucidated using the single crystal x-ray diffraction data. The compound crystallized in the space group P21 and the unit cell contains a protonated L-methioninium cation and a zwitterionic methionine residue plus a maleate anion. The backbone conformation angles Ψ1 and Ψ2 are in cis and trans configurations for both the methionine and methioninium residues, respectively. Amino and carboxyl groups of the methioninium and methionine residues are connected through N–H…O hydrogen bonds leading to a ring R22(10) motif.
D-serine added to clozapine for the treatment of schizophrenia.

OBJECTIVE D-Serine is a full agonist at the glycine site on the N-methyl-D-aspartate (NMDA) receptor. Previous administration of D-serine to schizophrenic patients taking nonclozapine antipsychotics improved positive, negative, and cognitive symptoms, whereas the partial agonist D-cycloserine improved negative symptoms of patients taking conventional antipsychotics but worsened symptoms in clozapine-treated patients. To study the difference between full and partial agonists at the NMDA receptor glycine site, the clinical effects of adding D-serine to clozapine were assessed. METHOD In a 6-week double-blind trial, 20 schizophrenic patients received placebo or D-serine (30 mg/kg per day) in addition to clozapine. Clinical efficacy, side effects, and serum levels of D-serine were determined every other week. RESULTS The patients exhibited no improvement with D-serine, nor did their symptoms worsen, as previously reported with D-cycloserine. CONCLUSIONS The results suggest either that clozapine may have an agonistic effect on the NMDA system or that clozapine-treated patients do not respond to D-serine.
Towards an Unconscious Neurotherapy for Common

​ Can evolutionarily ‘hardwired’ fear responses, e.g. for spiders and snakes, be reprogramed unconsciously in the human brain? Currently, exposure therapy is amongst the most effective treatments for anxiety disorders​1​, but this intervention is subjectively aversive to patients, and rates of premature attrition from treatment have been reported to be as high as 70%​2​. Here we introduce a novel method to bypass the subjective unpleasantness in conscious exposure, by directly pairing monetary reward with unconscious occurrences of decoded representations of naturally feared objects in the brain. The typical way to identify multivoxel functional magnetic resonance imaging (fMRI) representations for feared objects involves repeated presentations of the relevant images explicitly to subjects. However, for our potential treatment method to be effective in actual clinical settings, we need to decode fear representations ​without​ triggering excessively aversive reactions which may cause patients to dropout from treatments prematurely. Here we overcome this challenge by capitalizing on recent advancements in fMRI decoding techniques:​ ​We employed a method called hyperalignment​3,4​ to infer the relevant representations of feared objects for a designated participant based on data from other ‘surrogate’ participants. This way the procedure completely bypasses the need for the conscious encountering of feared objects. We demonstrate that our method can lead to reliable reductions in physiological fear responses measured by skin conductance as well as amygdala hemodynamic activity. Not only do these results raise the intriguing possibility that naturally occurring fear can be ‘re-programmed’ outside of conscious awareness, importantly they also created the rare opportunity for a psychological intervention of this nature to be tested rigorously in a double-blind placebo-controlled fashion. This may pave the way for a novel treatment method, combining the appealing rationale and proven efficacy of conventional psychotherapy with the rigor and leverage of clinical neuroscience. 2 . CC-BY-NC-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi. org/10.1101/170183 doi: bioRxiv preprint first posted online Jul. 30, 2017;
Pathophysiological Role of Vascular Smooth Muscle Alkaline Phosphatase in Medial Artery Calcification

Medial vascular calcification (MVC) is a pathological phenomenon that causes vascular stiffening and can lead to heart failure; it is common to a variety of conditions, including aging, chronic kidney disease, diabetes, obesity, and a variety of rare genetic diseases. These conditions share the common feature of tissue‐nonspecific alkaline phosphatase (TNAP) upregulation in the vasculature. To evaluate the role of TNAP in MVC, we developed a mouse model that overexpresses human TNAP in vascular smooth muscle cells in an X‐linked manner. Hemizygous overexpressor male mice (Tagln‐Cre+/–; HprtALPL/Y or TNAP‐OE) show extensive vascular calcification, high blood pressure, and cardiac hypertrophy, and have a median age of death of 44 days, whereas the cardiovascular phenotype is much less pronounced and life expectancy is longer in heterozygous (Tagln‐Cre+/–; HprtALPL/−) female TNAP‐OE mice. Gene expression analysis showed upregulation of osteoblast and chondrocyte markers and decreased expression of vascular smooth muscle markers in the aortas of TNAP‐OE mice. Through medicinal chemistry efforts, we developed inhibitors of TNAP with drug‐like pharmacokinetic characteristics. TNAP‐OE mice were treated with the prototypical TNAP inhibitor SBI‐425 or vehicle to evaluate the feasibility of TNAP inhibition in vivo. Treatment with this inhibitor significantly reduced aortic calcification and cardiac hypertrophy, and extended lifespan over vehicle‐treated controls, in the absence of secondary effects on the skeleton. This study shows that TNAP in the vasculature contributes to the pathology of MVC and that it is a druggable target. © 2015 American Society for Bone and Mineral Research.
Cell Cycle , Cell Death , and Senescence TLE 1 Is an Anoikis Regulator and Is Downregulated by Bit 1 in Breast Cancer Cells

TLE1 is a Groucho-related transcriptional repressor protein that exerts survival and antiapoptotic function in several cellular systems and has been implicated in the pathogenesis of cancer. In the present study, we found that TLE1 is a regulator of anoikis in normal mammary epithelial and breast carcinoma cells. The induction of apoptosis following loss of cell attachment to the extracellular matrix (anoikis) in untransformed mammary epithelial MCF10A cells was associated with significant downregulation of TLE1 expression. Forced expression of exogenous TLE1 in these cells promoted resistance to anoikis. In breast cancer cells, TLE1 expression was significantly upregulated following detachment from the extracellular matrix. Genetic manipulation of TLE1 expression via overexpression and downregulation approaches indicated that TLE1 promotes the anoikis resistance and anchorage-independent growth of breast carcinoma cells. Mechanistically, we show that TLE1 inhibits the Bit1 anoikis pathway by reducing the formation of the proapoptotic Bit1-AES complex in part through sequestration of AES in the nucleus. The mitochondrial release of Bit1 during anoikis as well as exogenous expression of the cytoplasmic localized Bit1 or its cell death domain induced cytoplasmic translocation and degradation of nuclear TLE1 protein. These findings indicate a novel role for TLE1 in the maintenance of anoikis resistance in breast cancer cells. This conclusion is supported by an immunohistochemical analysis of a breast cancer tissue array illustrating that TLE1 is selectively upregulated in invasive breast tumors relative to noninvasive ductal carcinoma in situ and normal mammary epithelial tissues. Mol Cancer Res; 10(11); 1–14. 2012 AACR.
Self-managed groups: Fitting self-management approaches into classroom systems.

Examines the factors limiting the use of classroom self-management interventions. Self-management approaches that contribute to its inappropriateness and impracticality; Review peer tutoring as a strategy with self-management features in classroom use; Combination of student choice and student management with interdependent group reward contingencies; Reciprocal peer teaching.
Analysis of IMP3 expression in prostate adenocarcinomas.

OBJECTIVE Prostate cancer is the second most common cause of male cancer deaths after lung cancer in developed countries. The prognostic factors currently identified for prostate carcinoma include preoperative serum PSA, TNM staging system, histological grade and surgical margin status and are composed of the clinically most important and useful parameters. However, all the markers studied have not been applied in clinical practice. The oncofetal protein Insulin-Like Growth Factor II has been demonstrated to be associated with aggressive tumor behavior in many organs including urothelial tumors and renal cell carcinoma. Our aim was to investigate the expression status of Insulin-Like Growth Factor II in benign prostate glands, high grade PIN and prostate adenocarcinoma, and to determine the role of Insulin-Like Growth Factor II in pathogenesis of prostate adenocarcinoma. MATERIAL AND METHOD A total of 70 prostate adenocarcinoma cases accompanied by high grade PIN and benign prostate glands were evaluated by immunohistochemistry for the expression of Insulin-Like Growth Factor II. RESULTS Insulin-Like Growth Factor II expression was not seen in any of the 70 prostate adenocarcinoma and high grade PIN cases and benign prostate glands. CONCLUSION Although the number of our cases was limited, our results suggested that Insulin-Like Growth Factor II protein expression was not included in the pathogenesis of the prostate adenocarcinomas and Insulin-Like Growth Factor II expression status cannot be used for diagnosis of prostate adenocarcinomas.
Hybrid alphagamma polypeptides: structural characterization of a C12/C10 helix with alternating hydrogen-bond polarity.

The insertion of the higher homologues of the \alpha-amino acids, specifically \beta, \gamma, and \delta residues, into a peptide sequences results in hybrid structures with novel hydrogen-bonding possibilities. [1] Research in this area of hybrid polypeptides has been stimulated by the observation of novel helical structures in \beta oligopeptides in which the hydrogen-bond polarities are reversed. For example, the 12 helix $(2.5_{12}$ or $2.5_1-P)$ in a $(\beta)_n$ sequence maintains the same directionality $(C=O(i)^{. }NH(i+3))$ as the canonical $3_{10}$ helixin an $(\alpha)_n$ sequence[2] and may be formally considered as an expanded version of the latter. By contrast, the 14 helix $(3_{14}$ or $3_1-M)$ in a $(\beta)_n$ sequence possesses a reversed hydrogen-bond polarity $(NH(i)^{. }C=O(i+2))$. [3] Initial crystallographic results with hybrid \alpha\beta and \alpha\gamma sequences suggest that the expanded analogues of the $3_{10}$ helix, namely, the $C_{11}$ $(\alpha\beta)$ and $C_{12}$ $(\alpha\gamma)$ helices, can indeed be observed in short peptides. [4] Calculations suggest that helices with alternating hydrogen-bond polarities may indeed be stable structures in hybrid sequences. [1c,d] In this Communication, we report the $C_{12}/C_{10}$ mixed hydrogen-bonding pattern in the crystal structure of the tetrapeptide Boc-Leu-Gpn-Leu-Aib-OMe (1; Boc: tertbutoxycarbonyl; Gpn: 1-(aminomethyl)cyclohexaneacetic acid (gabapentin); Aib: aminoisobutyric acid), which was serendipitously obtained during the synthesis of longer hybrid sequences. This novel helical conformation can be generalized as an $(\alpha\gamma)_n$ sequence. The sequence contains the stereochemically constrained \gamma residue gabapentin, which is an achiral \beta,\beta-disubstituted \gamma-amino acid. The presence of gem-dialkyl substituents on the $C\beta$ atom limits the torsion angles about the $C{\gamma}-C{\beta}$ $(\theta_1)$ and $C{\beta}-C{\alpha}$ $(\theta_2)$ bonds to approximately $\pm 60^o$. [5]
Rafts defined: a report on the Keystone symposium on lipid rafts and cell function Published, JLR Papers in Press, April 27, 2006.

The recent Keystone Symposium on Lipid Rafts and Cell Function (March 23–28, 2006 in Steamboat Springs, CO) brought together biophysicists, biochemists, and cell biologists to discuss the structure and function of lipid rafts. What emerged from the meeting was a consensus definition of a membrane raft: “Membrane rafts are small (10–200 nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched domains that compartmentalize cellular processes. Small rafts can sometimes be stabilized to form larger platforms through protein-protein and protein-lipid interactions. ” This definition helps to clarify current thinking in a field that has been plagued by the heterogeneous and sometimes ephemeral nature of its subject.
Immunotherapy compliance: comparison of subcutaneous versus sublingual immunotherapy

Patient compliance is critical for successful allergen immunotherapy (AIT). Previous studies suggest that AIT compliance is worse outside of controlled clinical trials, with reported subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) noncompliance at 11% to 50% and 3% to 25%, respectively.
Kafka's Rhetorical Moment

Much of Kafka's fiction exploits language whose performative status is ambiguous–language that Paul de Man calls “rhetorical”–to generate a peculiar and characteristic narrative “space” in which Kafka's stories operate. Speech-act theory helps to clarify the way in which problems arising from language become the central problems that Kafka's characters face. In particular, the distinction between illocutions and perlocutions provides an analytic tool that reveals Kafka's abiding concern with the “gap,” or “aporia,” produced by assertions, requests, commands, and other illocutionary acts that turn out not to assert, request, or command anything the reader or listener can pin down. This tool helps us discover the linguistic sources for the bewilderment and anxiety that characterize Kafka's fictional world.
Characterization of the Arsenate Respiratory Reductase from Shewanella sp. Strain ANA-3

ABSTRACT Microbial arsenate respiration contributes to the mobilization of arsenic from the solid to the soluble phase in various locales worldwide. To begin to predict the extent to which As(V) respiration impacts arsenic geochemical cycling, we characterized the expression and activity of the Shewanella sp. strain ANA-3 arsenate respiratory reductase (ARR), the key enzyme involved in this metabolism. ARR is expressed at the beginning of the exponential phase and persists throughout the stationary phase, at which point it is released from the cell. In intact cells, the enzyme localizes to the periplasm. To purify ARR, a heterologous expression system was developed in Escherichia coli. ARR requires anaerobic conditions and molybdenum for activity. ARR is a heterodimer of ∼131 kDa, composed of one ArrA subunit (∼95 kDa) and one ArrB subunit (∼27 kDa). For ARR to be functional, the two subunits must be expressed together. Elemental analysis of pure protein indicates that one Mo atom, four S atoms associated with a bis-molybdopterin guanine dinucleotide cofactor, and four to five [4Fe-4S] are present per ARR. ARR has an apparent melting temperature of 41°C, a K m of 5 μM, and a V max of 11,111 μmol of As(V) reduced min−1 mg of protein−1 and shows no activity in the presence of alternative electron acceptors such as antimonite, nitrate, selenate, and sulfate. The development of a heterologous overexpression system for ARR will facilitate future structural and/or functional studies of this protein family.
Molecular characterization of the gene encoding an 18-kilodalton small heat shock protein associated with the membrane of Leuconostoc oenos

In Leuconostoc oenos, different stresses such as heat, ethanol, and acid shocks dramatically induce the expression of an 18-kDa small heat shock protein called Lo 18. The corresponding gene (hsp18) was cloned from a genomic library of L. oenos constructed in Escherichia coli. A 2.3-kb DNA fragment carrying the hsp18 gene was sequenced. The hsp18 gene encodes a polypeptide of 148 amino acids with a calculated molecular mass of 16,938 Da. The Lo18 protein has a significant identity with small heat shock proteins of the alpha-crystallin family. The transcriptional start site was determined by primer extension. This experiment allowed us to identify the promoter region exhibiting high similarity to consensus promoter sequences of gram-positive bacteria, as well as E. coli. Northern blot analysis showed that hsp18 consists of a unique transcription unit of 0.6 kb. Moreover, hsp18 expression seemed to be controlled at the transcriptional level. This small heat shock protein was found to be peripherally associated with the membrane of L. oenos.
P2Y receptor‐mediated inhibition of voltage‐dependent Ca2+ channels in rat dorsal root ganglion neurons

Extracellular ATP has been shown to act at two P2 receptors belonging either to the P2X (ligand-gated cationic channel) or the P2Y (G-protein-coupled receptor) types (Ralevic and Burnstock, 1998). P2X 3 receptors are expressed with considerable selectivity by a subset of sensory neurons in dorsal root ganglia (DRG) and are thought to be involved in pain transmission (Chizh and Illes, 2001). Whereas P2X 3 receptors are situated on small-diameter nonpeptidergic neurons speciﬁcally binding isolectin B 4 and endowed also with capsaicin-sensitive VR1 vanilloid receptors (Guo et al., 2001), P2Y 1 receptors appear to be situated at large-ﬁber mechanosensitive neurons (Nakamura and Stritt-matter, 1996). Opioid analgesics were described as inhibiting Ca 2 (cid:1) currents (I Ca ) in DRG neurons, thereby decreasing the release of the sensory transmitter and interrupting the procession of nociceptive information (Acosta and Lopez, 1999). Since P2Y 1 receptors heter-ologously expressed in rat superior cervical neurons were described to close N-type Ca 2 (cid:1) channels (Filippov et al., 2000), we investigated whether ATP may inhibit the entry of Ca 2 (cid:1) via the cell membrane and the subsequent increase of intracellular Ca 2 (cid:1) in rat DRG neurons. One-day
Energy Scavenging From Low-Frequency Vibrations by Using Frequency Up-Conversion for Wireless Sensor Applications

This paper presents an electromagnetic (EM) vibration-to-electrical power generator for wireless sensors, which can scavenge energy from low-frequency external vibrations. For most wireless applications, the ambient vibration is generally at very low frequencies (1-100 Hz), and traditional scavenging techniques cannot generate enough energy for proper operation. The reported generator up-converts low-frequency environmental vibrations to a higher frequency through a mechanical frequency up-converter using a magnet, and hence provides more efficient energy conversion at low frequencies. Power is generated by means of EM induction using a magnet and coils on top of resonating cantilever beams. The proposed approach has been demonstrated using a macroscale version, which provides 170 nW maximum power and 6 mV maximum voltage. For the microelectromechanical systems (MEMS) version, the expected maximum power and maximum voltage from a single cantilever is 3.97 muW and 76 mV, respectively, in vacuum. Power level can be increased further by using series-connected cantilevers without increasing the overall generator area, which is 4 mm2. This system provides more than an order of magnitude better energy conversion for 10-100 Hz ambient vibration range, compared to a conventional large mass/coil system.
Nimodipine Attenuation of Early Brain Dysfunctions Is Partially Related to its Inverting Acute Vasospasm in a Cisterna Magna Subarachnoid Hemorrhage (SAH) Model in Rats

ABSTRACT Subarachnoid hemorrhage (SAH)-induced brain injury is highly related to neurological deficits and mortality. Regional cerebral blood flow (rCBF) changes and vasoconstriction are two complications that occur soon after SAH experimentally. In this study we investigated the changes in rCBF and vertebro-basilar arterial diameter in a cisterna megna SAH model in Sprague–Dawley rats and intended to explore whether improving early rCBF reduction and cerebral vasospasm could contribute to alleviating blood–brain barrier (BBB) dysfunction. In rats for rCBF, vasospasm and BBB permeability assessments, nimodipine (NDP) or saline was administered intravenously 5 minutes after SAH. rCBF within the first 60 minutes after SAH was measured by laser Doppler flowmetry. BBB permeability indexed by Evans Blue extravasation was assessed 4 hours after SAH. Angiography for the caliber changes of the vertebro-basilar artery were conducted 30 minutes post SAH. Pronounced rCBF reduction and vasospasm were observed soon after SAH, followed by BBB permeability increment. NDP administration could improve rCBF and attenuate vasospasm, followed by the alleviation of BBB permeability. Our results demonstrate that early improvement of cerebral circulation by NDP may contribute to the reduction in brain injury indexed by BBB disruption.
Towards wearable sleep diagnostic systems for point-of-care applications

Current gold standard sleep study systems that record several biophysical parameters during sleep are bulky and are typically located in a medical facility where patient monitoring becomes costly and inefficient. Home-based portable systems solve these problems but are highly inadequate as they record minimal number of biophysical channels due to limited battery life. A survey conducted in the medical community shows the need for wearable systems at point-of-care. Engineering challenges involved in the design of such a low power wearable sleep diagnostic system are explored. A novel wearable system architecture is presented in this paper.