Discovery of novel isatin-based sulfonamides with potent and selective inhibition of the tumor-associated carbonic anhydrase isoforms IX and XII

A series of 2/3/4-[(2-oxo-1,2-dihydro-3H-indol-3-ylidene)amino]benzenesulfonamides, obtained from substituted isatins and 2-, 3- or 4-aminobenzenesulfonamide, showed low nanomolar inhibitory activity against the tumor associated carbonic anhydrases IX and XII

Manüel Kontrollü Elektrik Direnç Nokta Kaynak Makinesinde Pnömatik Kontrolün Geliştirilmesi

Bu çalışmada; tarım makineleri imalatında kullanılan, manüel kontrollü elektrik direnç nokta kaynak makinesi, yeniden revize edilerek otomasyona uygun hale getirilmiştir. Sistemin dönüştürülmesinde pnömatik devre elemanlarından yararlanılmıştır. Sistemde istenilen basınç ve kaynak periyodu ayarlanabilmektedir. Revize edilen makine ile 2 mm kalınlığındaki St37 sac malzemeden hazırlanan test parçaları, 6 bar basınçta, 4 sn'lik kaynak periyodunda ve 8 kVA görünür güç uygulanarak birleştirilmiştir. İkinci uygulamada ise aynı özelliklerdeki test parçalan tecrübeli bir kaynak teknisyeni tarafından manüel olarak birleştirilmiştir. Araştırmada her iki uygulama için, kaynak bölgesine çekme-makaslama testleri ve soyulma direnci testleri yapılarak karşılaştırılmıştır. Sonuçlar incelendiğinde makinenin istenilen şekilde çalıştığı saptanmıştır. Sistem de uygulanan akım, gerilim ve kaynak basıncı sabit tutulduğu için gerçekleştirilen birleştirmelerde ölçülen çekme-makaslama ve çekme-soyulma dirençlerinde büyük farklılıklar ölçülmemiştir. Kaynak yöntemi, çekme-makaslama ve çekme-soyulma dirençleri arasındaki ilişki önemli bulunmuştur. Anahtar kelimeler: Elektrik direnç nokta kaynağı, pnömatik, kaynak bölgesi, çekme-soyulma testi, basınçIn this research; manual electrical resistance spot welding machine which is used in manufacturing of agricultural machineries fit to automation by revised. Pneumatic cylinder and valve were used in the modification process from mechanical control to automation. System can be adjusted for a determined welding pressure and time. St37 sheet iron in 2 mm thickness were connected under the condition of 6 bar pressure, 4 sec. welding period and 8 kVA apparent power established by electrode in modified welding machine. Second test was realized by an experienced welder for same test conditions. Both for research applications, the tensile-shear and peel resistance tests applied on the weld zone and the tests results compared. According to the results; it is determined that the modified welding machine worked well for adjusted conditions. There are no big differences for measured tensile strength and tensile peel resistance because applied current, voltage, and pressure were constant during the welding in the tests. Relationships between welding methods and tensile shear and tensile peel resistance was found significan

Zeta potential-viscosity relationship in kaolinite slurry in the presence of dispersants

AKÜ-BAPK / 042.MUH.03Kaolinite is a widely used additive for industrial applications. Hence, the properties of kaolinite affect the quality of the final materials. The fact that kaolinite is a heterogeneous mineral with dual charges has to be taken into account. In this study, the zeta potentials and the apparent viscosities of kaolinite suspensions in water in the presence of three dispersants; sodium silicate, sodium tripolyphosphate and sodium-polyacrylate at pH values of 4, 7 and 10 were determined. Diagrams of zeta potentials (ZPs) and viscosity as a function of dispersant concentration all show minima. The concentrations at which minima of these two properties appear do not coincide, except for those mineral dispersants at high pH values. The results are explained in terms of the spatial distribution of charges on basal and edge surfaces of kaolinite plates in acidic, neutral, and basic media.AKÜ-BAPK / 042.MUH.0

The extremo-?±-carbonic anhydrase (CA) from Sulfurihydrogenibium azorense the fastest CA known is highly activated by amino acids and amines

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Open saccharin-based secondary sulfonamides as potent and selective inhibitors of cancer-related carbonic anhydrase IX and XII isoforms

A large number of novel secondary sulfonamides based on the open saccharin scaffold were synthesized and evaluated as selective inhibitors of four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). They were obtained by reductive ring opening of the newly synthesized N-alkylated saccharin derivatives and were shown to be inactive against the two cytosolic off-target hCA I and II (Kis &gt; 10 µM). Interestingly, these compounds inhibited hCA IX in the low nanomolar range with Kis ranging between 20 and 298 nM and were extremely potent inhibitors of hCA XII isoenzyme (Kis ranging between 4.3 and 432 nM). Since hCA IX and XII are the cancer-related isoforms recently validated as drug targets, these results represent an important goal in the development of new anticancer candidates. Finally, a computational approach has been performed to better correlate the biological data to the binding mode of these inhibitors.</p

Carbonic anhydrase inhibitors targeting metabolism and tumor microenvironment

The tumor microenvironment is crucial for the growth of cancer cells, triggering particular biochemical and physiological changes, which frequently influence the outcome of anticancer therapies. The biochemical rationale behind many of these phenomena resides in the activation of transcription factors such as hypoxia-inducible factor 1 and 2 (HIF-1/2). In turn, the HIF pathway activates a number of genes including those involved in glucose metabolism, angiogenesis, and pH regulation. Several carbonic anhydrase (CA, EC 4.2.1.1) isoforms, such as CA IX and XII, actively participate in these processes and were validated as antitumor/antimetastatic drug targets. Here, we review the field of CA inhibitors (CAIs), which selectively inhibit the cancer-associated CA isoforms. Particular focus was on the identification of lead compounds and various inhibitor classes, and the measurement of CA inhibitory on-/off-target effects. In addition, the preclinical data that resulted in the identification of SLC-0111, a sulfonamide in Phase Ib/II clinical trials for the treatment of hypoxic, advanced solid tumors, are detailed

مدارس المد المتداولة فيما يخص مراتبه ومقاديره في تعليم القراءات وتدريسها

MakaleKıraat ilminde med konusu, detayları ve meselelerinin çeşitliliği ile klâsik dönemden beri ilim adamlarının üzerinde yoğunlaştığı bir konudur. Aslî med miktarı olarak "bir elif" ve ona tekabül eden "iki hareke" takdiri hususunda kurrânın ittifakı oluşmuş, Hadr, Tedvîr ve Tahkîk mertebelerinde de bu ölçünün sabit kaldığı görüşü ağırlık kazanmıştır. Fer'î medlerde ise, yapılan ilâvelerle oluşan mertebe sayılarında, bu ilâvelerin miktarlarında ve bunları ifade etmede kullanılan ıstılahlarda farklı yaklaşımların olduğu görülmektedir. Aslî meddin üzerine ilâve edilen mertebelerin aralarındaki farkı belirtmek için kullanılan "elif" miktarının, edâ ehli dediğimiz yetkin öğreticilerin bir kısmı için "bir hareke", diğer bir kısmı için de "iki hareke" telâffuzu için gereken süreyi ifade ettiği anlaşılmaktadır. Med ölçüleri için kullanılan ilgili teorik tanım ve terimler farklılaşsa bile, örneğin bir "tevassut" uygulamasında "müşâfehe" sistemine dâhil olan okuyucuların tevassut sürelerinde farklılık olmaması öngörülür. Çünkü, herhangi bir med mertebesi için takdir edilen ölçünün ne kadar bir süreye karşılık geleceği hususunda belirleyici olan müşafehedir. Günümüzde Kur'an ve kıraat ilmi eğitim-öğretiminde med ölçülerini ifade ederken kullanılan elif ve hareke ıstılahları bağlamında iki ekol takip edilmektedir. Bunlardan ilkini "Üç Elif Ekolü" diğerini ise "Beş Elif Ekolü" olarak nitelendirmek mümkündür. Med mertebeleri ve ekollerinden bağımsız olarak değerlendirmemiz gereken bu ekollerin usulünü ve kendine ait terminolojisini kavramak, uygulamalarda olası sorunların önünün alınabilmesi için önem arz etmektedir.The subject of stretching (Madd), with its diversity and details, is one of the most important issues on that the scholars of Qirâat focuse. With unanimity of the Qurrâ scholars the amount of stretching of Natural Prolongation (al-Madd al-Tabî’î) is stabilised and it is called “the amount of an alif” which is a meassure corresponding to two vowels. As it is mentioned in the sources it has been conveyed with oral communication as well. This meassure is applied for each methods of the Qur’ân recitation Hadr, Tadwir and Tahqiq. When we look at the works in the areas of Tajwid and Qirâat we see that there is different types of meassurements on extra prolongations added to Natural Prolongation and moreover we see that the concepts used to express them vary. While some mean the amount of time required to pronounce a wovel with “an amount of alif” some others mean the amount of time required to pronounce two vowels. The thing need to be done in a healthy oral system is to have -according to both wievs- the same amount which consept is used. That is why everybody emphasizes the importance of verbal receptives in this context. In expression of prolongation meassures now only two schools are being followed. These are “the school of three alif” and “the school of five alif”.إن باب المد من أهم أصول القراءة التي يعتني بها علماء القراءات لتنوع واختالف مسائله أنَ مقدار المدَاألصليَ محلَ إجماعَبين القراء على مده حركتين وجوبا وهوَماَيعادلَ مقدارَا أللفَ كما ثبتَ بالنصوصَ والتلقي. وهذاَ التقديرَ ثابتَ فيَ كل من مرتبة الحدرَوالتدويرَ والتحقيق. وأما ما يظهر من َخلال َالبحث واَلطالع على المؤل فات في مجال التجويد والقراءات أن هناك محل اختالف بين القراء، وهوَالمصطلحاتَ المستخدمةَ للمدَ الزائدَ و مقاديره. ونجدَ أنَ بعضَ أهلَا ألداء يقوَلَ "مقدار الألف" ويريد به زمن َالنطق بالحركة الواحدة، َوالآخر يريد به زمن النطق بالحركتين. وَأن المشافهة َالسليمة َهيَ التيَتعين المقدارَالزمنيَ العملي للتوسط مثلَا لكالَا لفريقين، ولإلشباعَ كذلكَ رغمَ اختالفهماَفي المقاديرَالنظريةَ والمصطلحاتَال مستخدمةَ لها.َ وألجلَ هذهَ الظاهرة تؤكدَ المصادر إلىَ أهميةَ المشافهةَ إلحكامَ هذهَ المسللة وفي تعليم القراءات وتدريسها اليوم مدرستين للتعبيرعن المصطلحات َالمستخدمة َلمقاديرالمدودَ خاصة، ومعرفة َمنهج كل َمنهما تكتسب أهمية كبيرة لسالمة التدريس، وهما: مدرسة ثالث ألفات، ومدرسةَ خمسَ ألفا